Ch03-2 Emergency and Critical Care _67ef

01-7 Poisoning
7 Poisoning
Poisoning
SHL Thomas
Comprehensive evaluation of the poisoned patient 132
General approach to the poisoned patient 134
Triage and resuscitation 134
Clinical assessment and investigations 134
Psychiatric assessment 135
General management 135
Poisoning by specific pharmaceutical agents 137
Analgesics 137
Antidepressants 138
Cardiovascular medications 140
Iron 140
Antipsychotic drugs 141
Antidiabetic agents 141
Pharmaceutical agents less commonly taken in poisoning 141
Drugs of misuse 141
Depressants 141
Stimulants and entactogens 143
Hallucinogens 143
Dissociative drugs 144
Volatile substances 144
Body packers and body stuffers 144
Chemicals and pesticides 144
Carbon monoxide 144
Organophosphorus insecticides and nerve agents 145
Carbamate insecticides 146
Paraquat 147
Methanol and ethylene glycol 147
Corrosive substances 147
Aluminium and zinc phosphide 148
Copper sulphate 148
Chemicals less commonly taken in poisoning 148
Chemical warfare agents 149
Environmental poisoning 149
Food-related poisoning 149
Plant poisoning 150
132 • POISONING
Insets (Self-cutting) From Douglas G, Nicol F, Robertson C (eds). Macleod’s Clinical examination, 11th edn. Churchill Livingstone, Elsevier Ltd; 2005.
(Chemical burn) www.firewiki.net. (Needle tracks) www.deep6inc.com. (Pinpoint pupil) http://drugrecognition.com/images. (Injected conjunctiva) http://
knol.google.com.
Movement and muscles
Tone, fasciculations,
myoclonus, tremor,
paralysis, ataxia
Chest
Evidence of aspiration,
bronchoconstriction
Reflexes
Tendon reflexes, plantar
responses, inducible clonus
Eyes
Miosis or mydriasis,
diplopia or strabismus,
lacrimation
Skin
Temperature, cyanosis,
flushing, sweating,
blisters, pressure areas,
piloerection,
evidence of self-harm
Level of consciousness
Presence of seizures,
delirium, agitation
or psychosis
Psychiatric evaluation
Features of psychiatric illness,
mental capacity
Mouth
Dry mouth, excessive salivation
Airway, breathing, circulation
Respiration rate,
oxygen saturation,
pulse, BP,
dysrhythmias
Self-cutting
Needle tracks
Chemical burn
Pinpoint pupil
Injected conjunctiva
Abdomen
Hepatic or epigastric
tenderness, ileus,
palpable bladder
Comprehensive evaluation of the poisoned patient
Taking a history in poisoning
• What toxin(s) have been taken and how much?
• What time were they taken and by what route?
• Has alcohol or any other substance (or substances, including drugs
of misuse) been taken as well?
• Obtain details from witnesses (e.g. family, friends, ambulance
personnel) of the circumstances of the overdose
• Assess immediate suicide risk in those with apparent self-harm (full
psychiatric evaluation when patient has recovered physically)
• Assess capacity to make decisions about accepting or refusing
treatment
• Establish past medical history, drug history and allergies, social and
family history
• Record all information carefully
Comprehensive evaluation of the poisoned patient • 133
Clinical signs of poisoning by pharmaceutical agents and drugs of misuse.
Cerebellar signs
Some anticonvulsants, alcohol
Phenothiazines, haloperidol,
metoclopramide
Extrapyramidal signs
Any CNS depressant drug or agent
(N.B. consider methaemoglobinaemia
caused by dapsone, amyl nitrite etc.)
Cyanosis
Tachycardia or tachyarrhythmias:
tricyclic antidepressants, theophylline,
digoxin, antihistamines
Bradycardia or bradyarrhythmias:
digoxin, β-blockers, calcium channel
blockers, opioids, organophosphates
Heart rate
Needle tracks
Drugs of misuse: opioids etc.
Hyperthermia and sweating:
ecstasy, serotonin re-uptake inhibitors,
salicylates
Hypothermia: any CNS depressant
drug, opioids, chlorpromazine
Small: opioids, clonidine,
organophosphorus compounds
Large: tricyclic antidepressants,
amphetamines, cocaine
Reduced: opioids, benzodiazepines
Increased: salicylates
Paracetamol hepatotoxicity,
renal toxicity
Right upper quadrant /renal angle
tenderness
Epigastric tenderness
NSAIDs, salicylates
Rhabdomyolysis
Amphetamines, caffeine
Hypotension: tricyclic
antidepressants, haloperidol
Hypertension: cocaine,
α-adrenoceptor agonists
Respiratory rate
Pupil size
Body temperature
Blood pressure
Decontamination and enhanced elimination. One of the key aspects in the evaluation of a poisoned patient is deciding if decontamination and/or
enhanced elimination is required.
Blood
Haemodialysis
Haemoperfusion
Kidneys
Urinary alkalinisation
Gastrointestinal tract
Multiple-dose activated charcoal
Enhancing elimination
Direct eye contact
Eye irrigation – remove contact lenses
Wash eyes thoroughly for at least 15
mins with normal saline or water
Remove particles from palpebral
fissures
If pain persists, insert fluorescein
drops and perform slit-lamp
examination for corneal damage
Skin contact (hazardous chemicals/
pesticides)
Remove clothing
Wash with copious amounts of soap
and water
Gastrointestinal decontamination
External decontamination
Gastrointestinal tract
Single-dose oral activated charcoal
Gastric lavage
134 • POISONING
General approach to the
poisoned patient
A general approach is shown on pages 132–133. In many
countries, poisons centres are available to provide advice on
management of suspected poisoning with specific substances.
Information is also available online (p. 150).
Triage and resuscitation
Patients who are seriously poisoned must be identified early so
that appropriate management is not delayed. Triage involves:
• immediately assessing vital signs
• identifying the poison(s) involved and obtaining adequate
information about them
• identifying patients at risk of further attempts at self-harm
and removing any remaining hazards.
Those with possible external contamination with chemical or
environmental toxins should undergo appropriate decontamination
(p. 133). Critically ill patients must be resuscitated (p. 174).
The Glasgow Coma Scale (GCS) is commonly employed to
assess conscious level, although not specifically validated in
poisoning. The AVPU (alert/verbal/painful/unresponsive) scale
is also a rapid and simple method. An electrocardiogram (ECG)
should be performed and cardiac monitoring instituted in all
patients with cardiovascular features or where exposure to
potentially cardiotoxic substances is suspected. Patients who
may need antidotes should be weighed if possible, so that
appropriate weight-related doses can be prescribed.
Substances unlikely to be toxic in humans should be identified
so that inappropriate admission and intervention are avoided
(Box 7.3).
Clinical assessment and investigations
History and examination are described on page 132. Occasionally,
patients may be unaware of or confused about what they have
taken, or may exaggerate (or, less commonly, underestimate) the
size of the overdose, but rarely mislead medical staff deliberately.
In regions of the world where self-poisoning is illegal, patients
may be reticent about giving a history.
Toxic causes of abnormal physical signs are shown on
page 133. The patient may have a cluster of clinical features
(‘toxidrome’) suggestive of poisoning with a particular drug type,
e.g. anticholinergic, serotoninergic (see Box 7.10), stimulant,
sedative, opioid (see Box 7.12) or cholinergic (see Box 7.14)
feature clusters. Poisoning is a common cause of coma, especially
Acute poisoning is common, accounting for about 1% of hospital
admissions in the UK. Common or otherwise important substances
involved are shown in Box 7.1. In developed countries, the
most frequent cause is intentional drug overdose in the context
of self-harm, often involving prescribed or ‘over-the-counter’
medicines. Accidental poisoning is also common, especially
in children and the elderly (Box 7.2). Toxicity also results from
alcohol or recreational substance use, or following occupational
or environmental exposure. Poisoning is a major cause of death
in young adults, but most deaths occur before patients reach
medical attention, and mortality is low (< 1%) in those admitted
to hospital.
In developing countries, the frequency of self-harm is more
difficult to estimate. Because of their widespread availability and
use, household and agricultural products, such as pesticides
and herbicides, are common sources of poisoning and have
a much higher case fatality. In China and South-east Asia,
pesticides account for about 300 000 suicides each year. Snake
bite and other forms of envenomation are also important causes
of morbidity and mortality internationally and are discussed in
Chapter 8.
7.3 Substances of very low toxicity
• Writing/educational materials, e.g. pencil lead, crayons, chalk
• Decorating products, e.g. emulsion paint, wallpaper paste
• Cleaning/bathroom products (except dishwasher tablets and liquid
laundry detergent capsules, which can be corrosive)
• Pharmaceuticals: oral contraceptives, most antibiotics (but not
tetracyclines or antituberculous drugs), vitamins B, C and E,
prednisolone, emollients and other skin creams, baby lotion
• Miscellaneous: plasticine, silica gel, most household plants, plant
food, pet food, soil
7.2 Poisoning in old age
• Aetiology: may result from accidental poisoning (e.g. due to
delirium or dementia) or drug toxicity as a consequence of impaired
renal or hepatic function or drug interaction. Toxic prescription
medicines are more likely to be available.
• Psychiatric illness: self-harm is less common than in younger
adults but more frequently associated with depression and other
psychiatric illness, as well as chronic illness and pain. There is a
higher risk of subsequent suicide.
• Severity of poisoning: increased morbidity and mortality result
from reduced renal and hepatic function, lower functional reserve,
increased sensitivity to sedative agents and frequent comorbidity.
7.1 Important substances involved in poisoning
In the UK
• Analgesics: paracetamol and non-steroidal anti-inflammatory drugs
(NSAIDs)
• Antidepressants: tricyclic antidepressants (TCAs), selective serotonin
re-uptake inhibitors (SSRIs) and lithium
• Cardiovascular agents: β-blockers, calcium channel blockers and
cardiac glycosides
• Drugs of misuse: depressants (e.g. opiates, benzodiazepines),
stimulants and entactogens (e.g. amphetamines, MDMA,
mephedrone, cocaine), hallucinogens (e.g. cannabis, synthetic
cannabinoid receptor agonists, LSD)
• Carbon monoxide
• Alcohol
In South and South-east Asia
• Organophosphorus and carbamate insecticides
• Aluminium and zinc phosphide
• Oleander
• Corrosives
• Snake venoms (Ch. 8)
(LSD = lysergic acid diethylamide; MDMA = 3,4-methylenedioxymethamphetamine, ecstasy)
General approach to the poisoned patient • 135
health professional with appropriate training (p. 1187). This should
occur after they have recovered from poisoning, unless there
is an urgent issue, such as uncertainty about their capacity to
decline medical treatment.
General management
Patients presenting with eye/skin contamination should undergo
local decontamination measures. These are described on
page 133.
Gastrointestinal decontamination
Patients who have ingested potentially life-threatening quantities
of toxins may be considered for gastrointestinal decontamination
if poisoning has been recent (p. 133).
in younger people, but it is important to exclude other potential
causes (p. 194).
Urea, electrolytes and creatinine should be measured in
all patients with suspected systemic poisoning. Arterial blood
gases should be checked in those with significant respiratory or
circulatory compromise, or after poisoning with substances likely to
affect acid–base status (Box 7.4). Calculation of anion and osmolar
gaps may help to inform diagnosis and management (Box 7.5).
Potent oxidising agents may cause methaemoglobinaemia, with
consequent blue discoloration of skin and blood, and reduced
oxygen delivery to the tissues (Fig. 7.1).
For some substances, management may be facilitated by
measurement of the amount of toxin in the blood. Qualitative
urine screens for potential toxins, including near-patient testing
kits, have a limited clinical role.
Psychiatric assessment
Patients presenting with drug overdose in the context of self-harm
should undergo psychiatric evaluation prior to discharge by a
7.5 Anion and osmolar gaps in poisoning
Anion gap
Osmolar gap
Calculation
[Na+ + K+] −
[Cl− + HCO3
−]
[Measured osmolality] −
[(2 × Na) + Urea +
Glucose]1
Reference
range
12–16 mmol/L
< 10
Common toxic
causes of
elevation2
Ethanol
Ethylene glycol
Methanol
Salicylates
Iron
Cyanide
Ethanol
Ethylene glycol
Methanol
1All units should be in mmol/L, except osmolality, which should be in mOsmol/kg.
For non-SI units, the corresponding formula is [Measured osmolality (mOsmol/kg)]
− [(2 × Na (mEq/L)) + Urea/2.8 (mg/dL) + Glucose/18 (mg/dL)]. 2Box 14.19
(p. 365) gives non-toxic causes.
7.4 Causes of acidosis in the poisoned patient
Cause
Normal lactate*
High lactate
Toxic
Salicylates
Methanol
Ethylene glycol
Paraldehyde
Metformin
Iron
Cyanide
Sodium valproate
Carbon monoxide
Other
Renal failure
Ketoacidosis
Severe diarrhoea
Shock
Unless circulatory shock is present, when it will be high in any case.
Fig. 7.1 Methaemoglobinaemia.
Causes
Non-toxic
• Congenital methaemoglobinaemias
Toxic (Oxidising agents)
• Organic nitrites
• Nitrates
• Benzocaine
• Dapsone
• Chloroquine
• Aniline dyes
• Chlorobenzene
• Naphthalene
• Copper sulphate
Consequences
• Haemoglobin–oxygen
dissociation curve is shifted
to the left (see Fig. 23.5)
• Oxygen delivery to tissues
is reduced
• There is apparent ‘cyanosis’
• Breathlessness, fatigue,
headache and chest pain
occur
• Delirium, impaired
consciousness and seizures
may occur in severe cases
Treatment
• Methylthioninium chloride
(‘methylene blue’) 1–2 mg/kg
(intravenous) is given
• Reduces methaemoglobin
(see below)
• Used for symptomatic
patients with severe
methaemoglobinaemia
(e.g. >30%)
• Patients with anaemia or
other comorbidities may
need treatment at lower
concentrations
Cytochrome b5
reductase
NADH
NAD
NADP
NADPH
Methaemoglobin
reductase
Methylthioninium
chloride (reduced)
Methylthioninium
chloride (oxidised)
Methaemoglobin (Fe3+)
Haemoglobin (Fe2+)
136 • POISONING
for most substances and complications are common, especially
pulmonary aspiration. It is contraindicated if strong acids, alkalis
or petroleum distillates have been ingested. Use may be justified
for life-threatening overdoses of those substances that are not
absorbed by activated charcoal (see Box 7.6).
Whole bowel irrigation
This involves the administration of large quantities of osmotically
balanced polyethylene glycol and electrolyte solution (1–2 L/
hr for an adult), usually by a nasogastric tube, until the rectal
effluent is clear. It is occasionally indicated to enhance the
elimination of ingested packets of illicit drugs or slow-release
tablets such as iron and lithium that are not absorbed by
activated charcoal. Contraindications include inadequate
airway protection, haemodynamic instability, gastrointestinal
haemorrhage, obstruction or ileus. Whole bowel irrigation may
precipitate nausea and vomiting, abdominal pain and electrolyte
disturbances.
Urinary alkalinisation
Urinary excretion of weak acids and bases is affected by urinary
pH, which changes the extent to which they are ionised. Highly
ionised molecules pass poorly through lipid membranes and
therefore little tubular reabsorption occurs and urinary excretion is
increased. If the urine is alkalinised (pH > 7.5) by the administration
of sodium bicarbonate (e.g. 1.5 L of 1.26% sodium bicarbonate
over 2 hrs), weak acids (e.g. salicylates, methotrexate) are highly
ionised, resulting in enhanced urinary excretion.
Urinary alkalinisation is currently recommended for patients
with clinically significant salicylate poisoning when the criteria
for haemodialysis are not met (see below). It is also sometimes
used for poisoning with methotrexate. Complications include
alkalaemia, hypokalaemia and occasionally alkalotic tetany
(p. 367). Hypocalcaemia may occur but is rare.
Haemodialysis and haemoperfusion
These techniques can enhance the elimination of poisons that
have a small volume of distribution and a long half-life after
overdose; use is appropriate when poisoning is sufficiently
severe. The toxin must be small enough to cross the dialysis
membrane (haemodialysis) or must bind to activated charcoal
(haemoperfusion) (see Box 7.7). Haemodialysis can also correct
acid–base and metabolic disturbances associated with poisoning
(p. 135).
Lipid emulsion therapy
Lipid emulsion therapy is increasingly used for poisoning
with lipid-soluble agents, such as local anaesthetics, tricyclic
antidepressants, calcium channel blockers and lipid-soluble
β-adrenoceptor antagonists (β-blockers) such as propranolol. It
involves intravenous infusion of 20% lipid emulsion (e.g. Intralipid,
suggested initial dose 1.5 mL/kg, followed by a continued infusion
of 0.25 mL/kg/min until there is clinical improvement). It is thought
that lipid-soluble toxins partition into the intravenous lipid, reducing
target tissue concentrations. The elevated myocardial free fatty
acid concentrations may also have beneficial effects on myocardial
metabolism and performance by counteracting the inhibition of
myocardial fatty acid oxidation produced by some cardiotoxins,
enabling increased adenosine triphosphate (ATP) synthesis and
energy production. Some animal studies have suggested efficacy
and case reports of use in human poisoning have also been
7.7 Poisons effectively eliminated by multiple
doses of activated charcoal, haemodialysis
or haemoperfusion
Multiple doses of activated charcoal
• Carbamazepine
• Dapsone
• Phenobarbital
• Quinine
• Theophylline
Haemodialysis
• Ethylene glycol
• Isopropanol
• Methanol
• Salicylates
• Sodium valproate
• Lithium
Haemoperfusion
• Theophylline
• Phenytoin
• Carbamazepine
• Phenobarbital
• Amobarbital
7.6 Substances poorly adsorbed by
activated charcoal
Medicines
• Iron
• Lithium
Chemicals
• Acids*
• Alkalis*
• Ethanol
• Ethylene glycol
• Mercury
• Methanol
• Petroleum distillates*
*Gastric lavage contraindicated.
Activated charcoal
Given orally as a slurry, activated charcoal absorbs toxins in
the bowel as a result of its large surface area. It can prevent
absorption of an important proportion of the ingested dose of
toxin, but efficacy decreases with time and current guidelines
do not encourage use more than 1 hour after overdose, unless
a sustained-release preparation has been taken or when gastric
emptying may be delayed. Use is ineffective for some toxins
that do not bind to activated charcoal (Box 7.6). In patients
with impaired swallowing or a reduced level of consciousness,
activated charcoal, even via a nasogastric tube, carries a risk of
aspiration pneumonitis, which can be reduced (but not eliminated)
by protecting the airway with a cuffed endotracheal tube.
Multiple doses of oral activated charcoal (50 g 6 times daily
in an adult) may enhance the elimination of some substances at
any time after poisoning (Box 7.7). This interrupts enterohepatic
circulation or reduces the concentration of free drug in the gut
lumen, to the extent that drug diffuses from the blood back into
the bowel to be absorbed on to the charcoal (‘gastrointestinal
dialysis’). A laxative is generally given with the charcoal to reduce
the risk of constipation or intestinal obstruction by charcoal
‘briquette’ formation in the gut lumen.
Evidence suggests that single or multiple doses of activated
charcoal do not improve clinical outcomes after poisoning with
pesticides or oleander.
Gastric aspiration and lavage
Gastric aspiration and/or lavage is very infrequently indicated in
acute poisoning, as it is no more effective than activated charcoal
Poisoning by specific pharmaceutical agents • 137
7.8 Complications of poisoning and their management
Complication
Examples of causative agents
Management
Coma
Sedative agents
Appropriate airway protection and ventilatory support
Oxygen saturation and blood gas monitoring
Pressure area and bladder care
Identification and treatment of aspiration pneumonia
Seizures
NSAIDs
Anticonvulsants
TCAs
Theophylline
Appropriate airway and ventilatory support
IV benzodiazepine (e.g. diazepam 10–20 mg, lorazepam 2–4 mg)
Correction of hypoxia, acid–base and metabolic abnormalities
Acute dystonias
Typical antipsychotics
Metoclopramide
Procyclidine, benzatropine or diazepam
Hypotension
Due to vasodilatation
Vasodilator antihypertensives
Anticholinergic agents
TCAs
IV fluids
Vasopressors (rarely indicated; p. 206)
Due to myocardial suppression
β-blockers
Calcium channel blockers
TCAs
Optimisation of volume status
Inotropic agents (p. 206)
Ventricular tachycardia
Monomorphic, associated with QRS
prolongation
Sodium channel blockers
Correction of electrolyte and acid–base abnormalities and hypoxia
Sodium bicarbonate (e.g. 50 mL 8.4% solution, repeated if necessary)
Torsades de pointes, associated with
QTc prolongation
Anti-arrhythmic drugs (quinidine,
amiodarone, sotalol)
Antimalarials
Organophosphate insecticides
Antipsychotic agents
Antidepressants
Antibiotics (erythromycin)
Correction of electrolyte and acid–base abnormalities and hypoxia
Magnesium sulphate, 2 g IV over 1–2 mins, repeated if necessary
(NSAID = non-steroidal anti-inflammatory drug; TCA = tricyclic antidepressant)
encouraging, with recovery of circulatory collapse reported in
cases where other treatment modalities have been unsuccessful.
No controlled trials of this technique have been performed,
however, and efficacy remains uncertain.
Supportive care
For most poisons, antidotes and methods to accelerate elimination
are inappropriate, unavailable or incompletely effective. Outcome
is dependent on appropriate nursing and supportive care, and
treatment of complications (Box 7.8).
Antidotes
Antidotes are available for some poisons and work by a variety
of mechanisms (Box 7.9). The use of some of these in the
management of specific poisons is described below.
Poisoning by specific
pharmaceutical agents
Analgesics
Paracetamol
Paracetamol (acetaminophen) is the drug most commonly used
in overdose in the UK. Toxicity is caused by an intermediate
reactive metabolite that binds covalently to cellular proteins,
7.9 Specific antidotes used to treat poisoning
Mechanism of action
Examples of
antidote
Poisoning
treated
Glutathione repleters
Acetylcysteine
Methionine
Paracetamol
Receptor antagonists
Naloxone
Opioids
Flumazenil
Benzodiazepines
Atropine
Organophosphorus
compounds
Carbamates
Alcohol dehydrogenase
inhibitors
Fomepizole
Ethanol
Ethylene glycol
Methanol
Chelating agents
Desferrioxamine
Iron
Hydroxocobalamin
Dicobalt edetate
Cyanide
DMSA
Sodium calcium
edetate
Lead
Reducing agents
Methylthioninium
chloride
Organic nitrites
Cholinesterase
reactivators
Pralidoxime
Organophosphorus
compounds
Antibody fragments
Digoxin Fab
fragments
Digoxin
(DMSA = dimercaptosuccinic acid)
138 • POISONING
Salicylates (aspirin)
Clinical features
Salicylate overdose commonly causes nausea, vomiting, sweating,
tinnitus and deafness. Direct stimulation of the respiratory centre
produces hyperventilation and respiratory alkalosis. Peripheral
vasodilatation with bounding pulses and profuse sweating occurs
in moderately severe cases. Serious poisoning is associated with
metabolic acidosis, hypoprothrombinaemia, hyperglycaemia,
hyperpyrexia, renal failure, pulmonary oedema, shock and cerebral
oedema. Agitation, delirium, coma and fits may occur, especially
in children. Toxicity is enhanced by acidosis, which increases
salicylate transfer across the blood–brain barrier.
Management
Activated charcoal should be administered if the patient presents
within 1 hour. Multiple doses may enhance salicylate elimination
but are not routinely recommended.
The plasma salicylate concentration should be measured
at least 2 (symptomatic patients) or 4 hours (asymptomatic
patients) after overdose and repeated in suspected serious
poisoning, as concentrations may continue to rise for several
hours. Clinical status, however, is more important than the
salicylate concentration when assessing severity.
Dehydration should be corrected carefully because of the risk
of pulmonary oedema. Metabolic acidosis should be treated with
intravenous sodium bicarbonate (8.4%), after plasma potassium
has been corrected. Urinary alkalinisation is indicated for adults
with salicylate concentrations above 500 mg/L.
Haemodialysis is very effective for removing salicylate and
correcting associated acid–base and fluid balance abnormalities.
It should be considered when serum concentrations are above
700 mg/L in adults with severe toxic features, or in renal failure,
pulmonary oedema, coma, convulsions or refractory acidosis.
Non-steroidal anti-inflammatory drugs
Clinical features
Overdose of most non-steroidal anti-inflammatory drugs (NSAIDs)
usually causes only minor abdominal discomfort, vomiting and/
or diarrhoea, but convulsions can occur occasionally, especially
with mefenamic acid. Coma, prolonged seizures, apnoea, liver
dysfunction and renal failure may follow substantial overdose but
are rare. Features of toxicity are unlikely to develop in patients
who are asymptomatic more than 6 hours after overdose.
Management
Electrolytes, liver function tests and a full blood count should
be checked in all but the most trivial cases. Activated charcoal
may be given if the patient presents within 1 hour. Symptomatic
treatment for nausea and gastrointestinal irritation may be needed.
Antidepressants
Tricyclic antidepressants
Overdose with tricyclic antidepressants (TCAs) carries a high
morbidity and mortality because of their sodium channel-blocking,
anticholinergic and α-adrenoceptor-blocking effects.
Clinical features
Anticholinergic effects are common (Box 7.10). Severe complications include convulsions, coma and arrhythmias (ventricular
causing cell death. This results in hepatic and occasionally renal
failure. In therapeutic doses, the toxic metabolite is detoxified
in reactions requiring glutathione, but in overdose, glutathione
reserves become exhausted.
Management
Activated charcoal may be used in patients presenting within
1 hour. Antidotes for paracetamol act by replenishing hepatic
glutathione and should be administered to all patients with acute
poisoning and paracetamol concentrations above a ‘treatment line’
provided on paracetamol poisoning nomograms (Fig. 7.2). The
threshold used for these nomograms varies between countries,
however, and local guidance should be followed. Acetylcysteine
given intravenously (or orally in some countries) is highly efficacious
if administered within 8 hours of the overdose. However, efficacy
declines thereafter, so administration should not be delayed
in patients presenting after 8 hours to await a paracetamol
blood concentration result. The antidote can be stopped if the
paracetamol concentration is shown to be below the nomogram
treatment line. Liver and renal function, International Normalised
Ratio (INR) and a venous bicarbonate should also be measured.
Arterial blood gases and lactate should be assessed in patients
with reduced bicarbonate or severe liver function abnormalities;
metabolic acidosis indicates severe poisoning.
Anaphylactoid reactions are the most important adverse
effects of acetylcysteine and are related to dose-related histamine
release. Common features are itching and urticaria, and in severe
cases, bronchospasm and hypotension. Most cases can be
managed by temporary discontinuation of acetylcysteine and
administration of an antihistamine.
An alternative antidote is methionine 2.5 g orally (adult
dose) every 4 hours to a total of four doses, but this may
be less effective, especially after delayed presentation. Liver
transplantation should be considered for paracetamol poisoning
with life-threatening liver failure (p. 856).
If multiple ingestions of paracetamol have taken place over
several hours (‘staggered overdose’) or days (e.g. chronic
therapeutic excess), acetylcysteine may be indicated; specific
treatment recommendations vary between countries.
Fig. 7.2 Paracetamol treatment nomogram (UK). Above the treatment
line, benefits of treatment outweigh risk. Below it, risks of treatment
outweigh benefits.
0 0
10 12
Time since overdose (hr)
Treatment line
14 16 18 20 22 24
Paracetamol concentration (mg/L)
Too early to assess
Poisoning by specific pharmaceutical agents • 139
solution) should be administered and repeated to correct pH.
The correction of the acidosis and the sodium loading that
results may bring about rapid improvement in ECG features and
arrhythmias. Hypoxia and electrolyte abnormalities should also
be corrected. Anti-arrhythmic drugs should only be given on
specialist advice. Prolonged seizures should be treated initially
with intravenous benzodiazepines (see Box 7.8).
Selective serotonin and noradrenaline
re-uptake inhibitors
Selective serotonin re-uptake inhibitor (SSRI) antidepressants
(e.g. fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram,
escitalopram) are increasingly used to treat depression and
are less toxic in overdose than TCAs. The related serotonin–
noradrenaline re-uptake inhibitors (SNRIs), such as venlafaxine
and duloxetine, are also commonly used but are more toxic
than SSRIs in overdose.
Clinical features and management
Overdose of SSRIs may produce nausea and vomiting, tremor,
insomnia and sinus tachycardia. Agitation, drowsiness and
convulsions occur infrequently and may be delayed for several
hours. Serotonin syndrome may occur (see Box 7.10), especially
if SSRIs are taken in combination or with other serotonergic
agents. Cardiac arrhythmias occur infrequently and most patients
require supportive care only. The toxic effects of SNRIs are
similar but tachycardia, hypertension or hypotension and ECG
changes (QRS and QT prolongation) may be more prominent
and hypoglycaemia can also arise.
Lithium
Severe lithium toxicity is uncommon after intentional acute
overdose but is more often encountered in patients taking
therapeutic doses, frequently as a result of interactions with drugs
such as diuretics or NSAIDs. Severe toxicity is more common
after acute overdose in patients already taking chronic therapy
(‘acute on chronic’ poisoning).
Clinical features
Nausea, diarrhoea, polyuria, dizziness and tremor may progress
to muscular weakness, drowsiness, delirium, myoclonus,
fasciculations, choreoathetosis and renal failure. Coma, seizures,
ataxia, cardiac dysrhythmias such as heart block, blood pressure
disturbances and renal failure may occur in severe poisoning.
Management
Activated charcoal is ineffective. Early gastric lavage is of
theoretical benefit, but lithium tablets are likely to remain intact
in the stomach and may be too large for aspiration via a lavage
tube. Whole bowel irrigation is often used after substantial
overdose but efficacy is unproven.
Lithium concentrations should be measured immediately
(symptomatic patients) or after at least 6 hours (asymptomatic
patients) following acute overdose. The usual therapeutic range
is 0.4–1.0 mmol/L. Adequate hydration should be maintained
with intravenous fluids. Seizures should be treated as in Box 7.8.
Haemodialysis should be considered for severe toxicity
associated with high lithium concentrations (e.g. > 4.0 mmol/L
after chronic or ‘acute on chronic’ poisoning, or > 7.5 mmol/L
after acute poisoning). Lithium concentrations are reduced
substantially during dialysis, but rebound increases occur after
discontinuation and multiple sessions are usually required.
tachycardia, ventricular fibrillation and, less commonly, heart
block). Hypotension results from inappropriate vasodilatation or
impaired myocardial contractility. Serious complications appear
more common with dosulepin and amitriptyline.
Management
Activated charcoal should be administered if the patient presents
within 1 hour. A 12-lead ECG should be taken and continuous
cardiac monitoring maintained for at least 6 hours. Prolongation
of the QRS interval (especially if > 0.16 secs) indicates severe
sodium channel blockade and a high risk of arrhythmia (Fig. 7.3).
QT interval prolongation may also occur. Arterial blood gases
should be measured in suspected severe poisoning.
In patients with arrhythmias, significant QRS or QT prolongation
or acidosis, intravenous sodium bicarbonate (50 mL of 8.4%
Fig. 7.3 ECG in severe tricyclic antidepressant poisoning. This rhythm
strip shows a broad QRS complex due to impaired conduction.
II
7.10 Anticholinergic and serotonergic feature clusters
Anticholinergic
Serotonin syndrome
Common causes
Benzodiazepines
Antipsychotics
TCAs
Antihistamines
Scopolamine
Benzatropine
Belladonna
Some plants and
mushrooms (see
Box 7.18)
SSRIs
MAOIs
TCAs
Amphetamines
Tryptamines
Buspirone
Bupropion (especially
in combination)
Clinical features
Cardiovascular
Tachycardia,
hypertension
Tachycardia, hyper- or
hypotension
Central nervous
system
Delirium,
hallucinations,
sedation
Delirium,
hallucinations,
sedation, coma
Muscle
Myoclonus
Shivering, tremor,
myoclonus, raised
creatine kinase
Temperature
Fever
Fever
Eyes
Diplopia, mydriasis
Normal pupil size
Abdomen
Ileus, palpable bladder
Diarrhoea, vomiting
Mouth
Dry
Skin
Flushing, hot, dry
Flushing, sweating
Complications
Seizures
Seizures
Rhabdomyolysis
Renal failure
Metabolic acidosis
Coagulopathies
(MAOI = monoamine oxidase inhibitor; SSRI = selective serotonin re-uptake
inhibitor; TCA = tricyclic antidepressant)
140 • POISONING
Digoxin and oleander
Poisoning with digoxin is usually accidental, arising from
prescription of an excessive dose, impairment of renal function
or drug interactions. In South Asia, deliberate self-poisoning
with yellow oleander (Thevetia peruviana), containing cardiac
glycosides, is common.
Clinical features
Cardiac effects include tachyarrhythmias (either atrial or ventricular)
and bradycardias, with or without atrioventricular block. Ventricular
bigeminy is common and atrial tachycardia with evidence of
atrioventricular block is highly suggestive of the diagnosis. Severe
poisoning is often associated with hyperkalaemia. Non-cardiac
features include delirium, headache, nausea, vomiting, diarrhoea
and (rarely) altered colour vision. Digoxin poisoning can be
confirmed by elevated plasma concentration (usual therapeutic
range 1.3–2.5 mmol/L). After chronic exposure, concentrations
5 mmol/L suggest serious poisoning.
Management
Activated charcoal is commonly administered to patients
presenting soon after acute ingestion, although evidence of benefit
is lacking. Urea, electrolytes and creatinine should be measured,
a 12-lead ECG performed and cardiac monitoring instituted.
Hypoxia, hypokalaemia (sometimes caused by concurrent
diuretic use), hypomagnesaemia and acidosis increase the risk
of arrhythmias and should be corrected. Significant bradycardias
may respond to atropine, although temporary pacing is sometimes
needed. Ventricular arrhythmias may respond to intravenous
magnesium (see Box 7.8). If available, digoxin-specific antibody
fragments should be administered when there are severe refractory
ventricular arrhythmias or bradycardias. These are effective for
both digoxin and yellow oleander poisoning.
Iron
Overdose with iron can cause severe and sometimes fatal
poisoning, with toxicity of individual iron preparations related to
their elemental iron content.
Clinical features
Early features include gastrointestinal disturbance with the
passage of grey or black stools, progressing to hyperglycaemia,
leucocytosis, haematemesis, rectal bleeding, drowsiness,
convulsions, coma, metabolic acidosis and cardiovascular collapse
in severe cases. Early symptoms may improve or resolve within
6–12 hours, but hepatocellular necrosis can develop 12–24 hours
after overdose and occasionally progresses to hepatic failure.
Gastrointestinal strictures are late complications.
Management
Activated charcoal is ineffective but gastric lavage may be
considered in patients presenting soon after substantial overdose,
although efficacy is unknown. Serum iron concentration should
be measured at least 4 hours after overdose or earlier if there are
features of toxicity. Desferrioxamine chelates iron and should be
administered immediately in patients with severe features, without
waiting for serum iron concentrations, as well as symptomatic
patients with high serum iron concentrations (e.g. > 5 mg/L).
Desferrioxamine may cause hypotension, allergic reactions
and occasionally pulmonary oedema. Otherwise, treatment is
supportive and directed at complications.
Cardiovascular medications
Although not common, cardiovascular drug overdose is important
because features of toxicity are often severe.
Beta-blockers
Major features of toxicity are bradycardia and hypotension; heart
block, pulmonary oedema and cardiogenic shock occur in severe
poisoning. Those with additional sodium channel-blocking effects
(e.g. propranolol, acebutolol, carvedilol) may cause seizures,
delirium and coma, while sotalol, which also blocks potassium
channels, may cause QTc prolongation and torsades de pointes
(Box 7.8 and p. 476).
Management
Intravenous fluids may reverse hypotension but care is required
to avoid pulmonary oedema. Bradycardia and hypotension
may respond to high doses of atropine (up to 3 mg in an
adult) or an infusion of isoproterenol. Glucagon (5–10 mg over
10 mins, then 1–5 mg/hr by infusion) counteracts β-blockade by
stimulating intracellular cyclic adenosine monophosphate (cAMP)
production and is now more commonly used. In severe cases,
‘hyperinsulinaemia euglycaemic therapy’ has been used, as
described under calcium channel blockers below. The efficacy
of lipid emulsion therapy in severe poisoning with lipid-soluble
β-blockers, such as propranolol, carvedilol and oxprenolol, is
uncertain.
Calcium channel blockers
L-type calcium channel blockers are highly toxic in overdose.
Dihydropyridines (e.g. nifedipine, amlodipine) cause vasodilatation,
whereas diltiazem and verapamil have predominantly cardiac
effects, including bradycardia and reduced myocardial contractility.
Clinical features
Hypotension due to vasodilatation or myocardial depression
is common and bradycardias and heart block may also
occur, especially with verapamil and diltiazem. Gastrointestinal
disturbances, delirium, metabolic acidosis, hyperglycaemia and
hyperkalaemia may also be present.
Management
Hypotension should be corrected with intravenous fluids, taking
care to avoid pulmonary oedema. Persistent hypotension may
respond to intravenous calcium gluconate (10 mg IV over
5 mins, repeated as required). Isoproterenol and glucagon
may also be useful. Successful use of intravenous insulin with
glucose (10–20% dextrose with insulin initially at 0.5–2.0 U/kg/
hr, increasing to 5–10 U/kg/hr according to clinical response),
so-called ‘hyperinsulinaemia euglycaemic therapy’, has been
reported in patients unresponsive to other strategies. The
mechanism of action remains to be fully elucidated, but in
states of shock myocardial metabolism switches from use of
free fatty acids to glucose. Calcium channel blocker poisoning
is also associated with hypoinsulinaemia and insulin resistance,
impeding glucose uptake by myocytes. High doses of insulin
inhibit lipolysis and increase glucose uptake and the efficiency
of glucose utilisation. Cardiac pacing may be needed for severe
unresponsive bradycardias or heart block. Lipid emulsion therapy
has also been used in severe poisoning with apparent benefit,
although evidence is largely anecdotal.
Drugs of misuse • 141
Arterial blood gases and plasma lactate should be taken
after metformin overdose; acidosis should be corrected with
intravenous sodium bicarbonate (250 mL 1.26% solution or
50 mL 8.4% solution, repeated as necessary). In severe cases,
haemodialysis or haemodiafiltration is used.
Pharmaceutical agents less commonly
taken in poisoning
An overview of the clinical features and management for drugs
less commonly involved in poisoning is provided in Box 7.11.
Drugs of misuse
Drugs of misuse are common causes of toxicity requiring hospital
admission. Management has recently become more complex
because of the emergence of ‘novel psychoactive substances’
(NPS). These are often chemically related to traditional drugs
of misuse, but with structural modifications made to evade
legal control. The constituents of branded NPS products are
often unknown and knowledge about the clinical features and
management of NPS toxicity is limited.
Depressants
These produce CNS depression, including drowsiness, ataxia,
delirium and coma, sometimes with respiratory depression,
airway compromise, aspiration pneumonia and respiratory arrest
Antipsychotic drugs
Antipsychotic drugs (p. 1198) are often prescribed for patients at
high risk of self-harm or suicide and are often taken in overdose.
Clinical features
Anticholinergic features (see Box 7.10) including drowsiness,
tachycardia and hypotension, are common and convulsions may
occur. Acute dystonias, including oculogyric crisis, torticollis and
trismus, may occur after overdose with typical antipsychotics
like haloperidol or chlorpromazine. QT interval prolongation and
torsades de pointes can occur with some typical (e.g. haloperidol)
and atypical (e.g. quetiapine, amisulpride, ziprasidone) agents.
Management
Activated charcoal may be of benefit if given early. Cardiac
monitoring should be undertaken for at least 6 hours. Management
is largely supportive, with treatment directed at complications
(see Box 7.8).
Antidiabetic agents
Overdose is uncommon but toxic effects can be severe.
Clinical features
Sulphonylureas, meglitinides (e.g. nateglinide, repaglinide) and
parenteral insulin cause hypoglycaemia when taken in overdose,
although insulin is non-toxic if ingested by mouth. The duration of
hypoglycaemia depends on the half-life or release characteristics
of the preparation and may be prolonged over several days with
long-acting agents such as glibenclamide, insulin zinc suspension
or insulin glargine.
Features of hypoglycaemia include nausea, agitation, sweating,
aggression, delirium, tachycardia, hypothermia, drowsiness,
convulsions and coma (p. 738). Permanent neurological damage
can occur if hypoglycaemia is prolonged. Hypoglycaemia can
be diagnosed using bedside glucose strips but venous blood
should also be sent for laboratory confirmation.
Metformin is uncommonly associated with hypoglycaemia.
Its major toxic effect is lactic acidosis, which can have a high
mortality, and is particularly common in older patients and
those with renal or hepatic impairment, or when ethanol has
been co-ingested. Other features of metformin overdose are
nausea, vomiting, diarrhoea, abdominal pain, drowsiness, coma,
hypotension and cardiovascular collapse.
There is limited experience of overdose involving
thiazolidinediones (e.g. pioglitazone) and dipeptidyl peptidase
4 (DPP-4) inhibitors (e.g. sitagliptin) but significant hypoglycaemia
is unlikely.
Management
Activated charcoal should be considered for recent substantial
overdose. Venous blood glucose and urea and electrolytes
should be measured and measurement repeated regularly.
Hypoglycaemia should be corrected using oral or intravenous
glucose (50 mL of 50% dextrose); an infusion of 10–20% dextrose
may be required to prevent recurrence. Intramuscular glucagon
can be used as an alternative, especially if intravenous access is
unavailable. Failure to regain consciousness within a few minutes
of normalisation of the blood glucose can indicate that a central
nervous system (CNS) depressant has also been ingested, the
hypoglycaemia has been prolonged, or there is another cause
of coma (e.g. cerebral haemorrhage or oedema).
7.11 Clinical features and specific management of
drugs less commonly involved in poisoning
Substance
Clinical features
Management
Anticonvulsants
Carbamazepine,
phenytoin
Cerebellar signs
Convulsions
Cardiac arrhythmias
Coma
Multiple-dose activated
charcoal (carbamazepine)
Sodium
valproate
Coma
Metabolic acidosis
Haemodialysis for severe
poisoning
Isoniazid
Peripheral
neuropathy
Convulsions
Activated charcoal
IV pyridoxine
Theophylline
Cardiac arrhythmias
Convulsions
Coma
Multiple-dose activated
charcoal
Antimalarial drugs
Chloroquine
Acidosis and
hypokalaemia
Visual loss
Convulsions, coma
ECG changes and
arrhythmias
Correction of pH (but not
potassium)
Monitoring and treatment
of cardiac rhythm
High-dose diazepam with
mechanical ventilation
Quinine
Tremor, tinnitus,
deafness, ataxia,
convulsions, coma
Haemolysis
ECG changes and
arrhythmias
Retinal toxicity
Correction of pH (but not
potassium)
Monitoring and treatment
of cardiac rhythm
Multiple-dose activated
charcoal
No effective treatment
for visual loss
142 • POISONING
experience, often accompanied by heightened sexual arousal.
Physical dependence occurs within a few weeks of regular
high-dose use. Withdrawal can start within 12 hours, causing
intense craving, rhinorrhoea, lacrimation, yawning, perspiration,
shivering, piloerection, vomiting, diarrhoea and abdominal cramps.
Examination reveals tachycardia, hypertension, mydriasis and
facial flushing.
Commonly encountered opioids and clinical features of
poisoning are shown in Box 7.12. Needle tracks may be visible
in intravenous users and there may be drug-related paraphernalia.
Methadone may also cause QTc prolongation and torsades de
pointes. Features of opioid poisoning can be prolonged for up
to 48 hours after use of long-acting agents such as methadone
or oxycodone.
Use of the specific opioid antagonist naloxone (0.4–2 mg IV
in an adult, repeated if necessary) may obviate the need for
intubation, although excessive doses may precipitate acute
withdrawal in chronic opiate users and breakthrough pain in those
receiving opioids for pain management. Repeated doses or an
infusion are often required because the half-life of the antidote
is short compared to that of most opiates, especially those
with prolonged elimination. Patients should be monitored for at
least 6 hours after the last naloxone dose. Rare complications
of naloxone therapy include fits, ventricular arrhythmias and
pulmonary oedema.
(Box 7.12). Other complications of coma include pressure blisters
or sores and rhabdomyolysis. Effects are potentiated by other
CNS depressants, including alcohol.
Essential supportive care is detailed in Box 7.8. Antidotes are
available for some depressants.
Benzodiazepines
Benzodiazepines (e.g. diazepam) and related substances (e.g.
zopiclone) are of low toxicity when taken alone in overdose but
can enhance CNS and respiratory depression when taken with
other sedative agents, including alcohol. They are more hazardous
in the elderly and those with chronic lung or neuromuscular
disease (see Box 7.12).
The specific benzodiazepine antagonist flumazenil (0.5 mg IV,
repeated if needed) increases conscious level in patients with
benzodiazepine overdose, but carries a risk of seizures and is
contraindicated in patients co-ingesting pro-convulsants (e.g.
TCAs) and those with a history of epilepsy.
Opioids
Toxicity may result from misuse of illicit drugs such as heroin
or from intentional or accidental overdose of medicinal opiates.
Intravenous or smoked heroin gives a rapid, intensely pleasurable
7.12 Stimulant, sedative and opioid feature clusters
Stimulant
Sedative hypnotic
Opioid
Common
causes
Amphetamines
MDMA (‘ecstasy’)
Ephedrine
Pseudoephedrine
Cocaine
Cannabis
Phencyclidine
Cathinones (e.g. mephedrone)
Benzylpiperazine
Benzodiazepines
Barbiturates
Ethanol
GHB
Heroin
Morphine
Methadone
Fentanyl and derivatives
Oxycodone
Dihydrocodeine
Codeine
Pethidine
Buprenorphine
Dextropropoxyphene
Tramadol
Clinical features
Respiratory
Tachypnoea
Reduced respiratory rate and ventilation1
Reduced respiratory rate and ventilation
Cardiovascular
Tachycardia, hypertension
Hypotension1
Hypotension, relative bradycardia
Central nervous
system
Restlessness, anxiety, anorexia, insomnia
Delirium, hallucinations, slurred speech
Delirium, hallucinations, slurred speech
Hallucinations
Sedation, coma1
Sedation, coma2
Muscle
Tremor
Ataxia, reduced muscle tone
Ataxia, reduced muscle tone
Temperature
Fever
Hypothermia
Hypothermia
Eyes
Mydriasis
Diplopia, strabismus, nystagmus
Normal pupil size
Miosis
Abdomen
Abdominal pain, diarrhoea
–
Ileus
Mouth
Dry
–
–
Skin
Piloerection
Blisters, pressure sores
Needle tracks2
Complications
Seizures
Myocardial infarction
Dysrhythmias
Rhabdomyolysis
Renal failure
Intracerebral haemorrhage or infarction
Respiratory failure1
Aspiration
Respiratory failure2
Non-cardiogenic pulmonary oedema
Aspiration
1Especially barbiturates. 2IV use.
(GHB = gamma hydroxybutyrate; MDMA = 3,4-methylene-dioxymethamphetamine)
Drugs of misuse • 143
include mephedrone and methylenedioxypyrovalerone. Tolerance
is common, leading regular users to seek ever higher doses.
Toxic features usually appear within a few minutes of use and
last 4–6 hours, or substantially longer after a large overdose.
Sympathomimetic stimulant and serotonergic effects are common
(see Boxes 7.10 and 7.12). Some users develop hyponatraemia as
a result of excessive water-drinking or inappropriate vasopressin
(antidiuretic hormone, ADH) secretion. Muscle rigidity, pain and
bruxism (clenching of the jaw), hyperpyrexia, rhabdomyolysis,
metabolic acidosis, acute renal failure, disseminated intravascular
coagulation, hepatocellular necrosis, acute respiratory distress
syndrome (ARDS) and cardiovascular collapse have all been
described following MDMA use. Cerebral infarction and
haemorrhage have been reported, especially after intravenous
amphetamine use.
Management is supportive and directed at complications
(see Box 7.8).
Hallucinogens
Cannabis
Derived from the dried leaves and flowers of Cannabis sativa,
cannabis produces euphoria, perceptual alterations and
conjunctival injection, followed by enhanced appetite, relaxation
and occasionally hypertension, tachycardia, slurred speech and
ataxia. Effects occur 10–30 minutes after smoking or 1–3 hours
after ingestion, and last 4–8 hours. High doses may produce
anxiety, delirium, hallucinations and psychosis. Psychological
dependence is common, but tolerance and withdrawal symptoms
are unusual. Long-term use is thought to increase the lifetime risk
of psychosis. Serious acute toxicity is uncommon and supportive
treatment is all that is required.
Synthetic cannabinoid receptor agonists
Large numbers of synthetic cannabinoid receptor agonists
(SCRAs), synthetic compounds sometimes referred to collectively
as ‘spice’, are now used as legal alternatives to cannabis; examples
include PB-22, 5F-PB-22, 5F-AKB-48, STS-135, SF-ADB and
MDMB-CHMICA. They are usually sprayed on to a herbal smoking
mix and packaged as smoking products with appealing brand
names. These may contain more than one SCRA and content
may change with time.
The toxic effects of SCRAs differ from those of cannabis,
being generally more marked and including agitation, panic,
delirium, hallucinations, tachycardia, ECG changes, hypertonia,
dyspnoea and vomiting. Coma, respiratory acidosis, seizures,
hypokalaemia and renal dysfunction are also reported. Treatment
of intoxication is supportive.
Tryptamines
These are predominantly 5-hydroxytryptamine (5-HT, serotonin;
especially 5-HT2a) agonists with associated stimulant effects.
Typical clinical features include hallucinations, agitation, delirium,
hypertension, tachycardia, sweating, anxiety and headache.
Serotonin syndrome may occur (see Box 7.10), especially if
tryptamines are used in combination with other serotonergic
agents. Naturally occurring examples are psilocin and psilocybin,
found in ‘magic mushrooms’, and dimethyltryptamine (DMT)
in traditional ayahuasca brews. Synthetic tryptamines, such
as alpha-methyltryptamine (AMT), have been encountered
recently.
Gamma hydroxybutyrate
Gamma hydroxybutyrate (GHB), and the related compounds
gamma butyrolactone (GBL) and 1,4 butanediol are sedative
liquids with psychedelic and body-building effects.
As well as sedative hypnotic features (see Box 7.12), toxicity
may cause nausea, diarrhoea, vertigo, tremor, myoclonus,
extrapyramidal signs, euphoria, bradycardia, convulsions,
metabolic acidosis, hypokalaemia and hyperglycaemia. Coma
usually resolves abruptly within a few hours but occasionally
persists for several days. Dependence may develop in regular
users, who experience severe, prolonged withdrawal effects if
use is discontinued suddenly.
Management is largely supportive. All patients should be
observed for a minimum of 2 hours and until symptoms resolve,
with monitoring of blood pressure, heart rate, respiratory rate
and oxygenation. Withdrawal symptoms may require treatment
with very high doses of benzodiazepine.
Stimulants and entactogens
These are sympathomimetic and serotonergic amines that have
overlapping clinical features, depending on the balance of their
stimulant (see Box 7.12) and serotonergic (see Box 7.10) effects.
As well as traditional drugs such as cocaine, amphetamines
and ecstasy, the group includes many more recently emerging
novel psychoactive substances, including cathinones (e.g.
mephedrone), piperazines (e.g. benzylpiperazine), piperadines
(e.g. ethylphenidate), benzofurans (e.g. 5-aminopropylbenzofuran)
and NBOMe compounds (e.g. 25I-NBOMe).
Cocaine
Cocaine is available as a water-soluble hydrochloride salt powder
suitable for nasal inhalation (‘snorting’), or as insoluble free-base
(‘crack’ cocaine) ‘rocks’ that, unlike the hydrochloride salt,
vaporise at high temperature and can be smoked, giving a more
rapid and intense effect.
Effects appear rapidly after inhalation and especially after
smoking. Sympathomimetic stimulant effects predominate (see
Box 7.12). Serious complications usually occur within 3 hours
of use and include coronary artery spasm, leading to myocardial
ischaemia or infarction, hypotension and ventricular arrhythmias.
Cocaine toxicity should be considered in younger adults presenting
with ischaemic chest pain. Hyperpyrexia, rhabdomyolysis, acute
renal failure and disseminated intravascular coagulation may occur.
A 12-lead ECG and ECG monitoring should be undertaken.
ST segment elevation may occur in the absence of myocardial
infarction and troponin T estimations are the most sensitive and
specific markers of myocardial damage. Benzodiazepines and
intravenous nitrates are useful for managing patients with chest
pain or hypertension. Acidosis should be corrected and physical
cooling measures used for hyperthermia. Beta-blockers may be
contraindicated because of the risk of unopposed α-adrenoceptor
stimulation, but this is debated. Coronary angiography should
be considered in patients with myocardial infarction or acute
coronary syndromes.
Amphetamines and cathinones
Amphetamine-related compounds include amphetamine sulphate
(‘speed’), methylamphetamine (‘crystal meth’) and 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’). Synthetic cathinones
144 • POISONING
ingested. Cocaine, for example, presents a much higher risk than
heroin because of its high toxicity and lack of a specific antidote.
Patients suspected of body packing or stuffing should be
admitted for observation. A careful history taken in private is
important, but for obvious reasons patients may withhold details
of the drugs involved. The mouth, rectum and vagina should
be examined as possible sites for concealed drugs. A urine
toxicology screen performed at intervals may provide evidence
of leakage, although positive results may reflect earlier drug
use. Packages may be visible on plain abdominal films (Fig.
7.4) but ultrasound and computed tomography (CT) are more
sensitive. One of these (preferably CT) should be performed in
all suspected body packers.
Antimotility agents are often used by body packers to prevent
premature passage of packages; it can take several days for
packages to pass spontaneously, during which the carrier is at
risk from package rupture. Whole bowel irrigation is commonly
used to accelerate passage and is continued until all packages
have passed. Surgery may be required when there is mechanical
bowel obstruction or when evolving clinical features suggest
package rupture, especially with cocaine.
Chemicals and pesticides
Carbon monoxide
Carbon monoxide (CO) is a colourless, odourless gas produced
by faulty appliances burning organic fuels. It is also present in
vehicle exhaust fumes and sometimes in smoke from house fires.
It binds with haemoglobin and cytochrome oxidase, reducing
tissue oxygen delivery and inhibiting cellular respiration. CO is
a common cause of death by poisoning and most patients die
before reaching hospital.
Clinical features
Early features include headache, nausea, irritability, weakness
and tachypnoea. The cause of these non-specific features
may not be obvious if the exposure is occult, such as from a
d-Lysergic acid diethylamide
d-Lysergic acid diethylamide (LSD) is a synthetic ergoline usually
ingested as small squares of impregnated absorbent paper
(often printed with a distinctive design) or as ‘microdots’. The
drug causes perceptual effects, such as heightened visual
awareness of colours or distortion of images. Hallucinations may
be pleasurable or terrifying (‘bad trip’). Other features are delirium,
agitation, aggression, dilated pupils, hypertension, pyrexia and
metabolic acidosis. Psychosis may sometimes last several days.
Patients with psychotic reactions or CNS depression should
be observed in hospital, preferably in a quiet, dimly lit room to
minimise external stimulation. A benzodiazepine that can be
used for sedation is required, avoiding antipsychotics if possible,
as they may precipitate cardiovascular collapse or convulsions.
Dissociative drugs
Ketamine, its N-ethyl derivative methoxetamine and phencyclidine
(now rarely encountered) produce a sense of dissociation from
reality, often associated with visual and auditory distortions.
Memory loss, impaired consciousness, agitation, hallucinations,
tremors and numbness may also occur. Long-term ketamine (and
probably methoxetamine) use can cause severe chronic cystitis
with dysuria, frequency, urgency, haematuria and incontinence.
Treatment of intoxication is supportive.
Volatile substances
Inhalation of volatile nitrites (e.g. amyl nitrite, isobutyl nitrite), often
sold in bottles or vials as ‘poppers’, is reported to produce a
feeling of pleasure and warmth, relax the anal sphincter and
prolong orgasm. These potent vasodilators commonly provoke
headache, dizziness, hypotension and tachycardia. They also
oxidise haemoglobin to produce methaemoglobinaemia, with
resulting breathlessness and delirium. Severe cases are treated
with methylthioninium chloride (‘methylene blue’, see Fig 7.1).
Several volatile solvents found in household products, such
as propane, butane, toluene and trichloroethylene, have a mild
euphoriant effect if inhaled. Serious toxic effects can occur,
including reduced level of consciousness, seizures and cardiac
arrhythmias; there is also a risk of asphyxia from some methods
of inhalation.
Nitrous oxide is an anaesthetic gas, but small canisters of it
are sold for the domestic production of whipped cream and the
contents of these can be transferred to balloons for inhalation.
The gas has euphoriant effects (‘laughing gas’), but hazards
include asphyxia from inhalation without oxygen, or vitamin B12
inactivation from chronic use leading to megaloblastic anaemia,
psychosis and other neurological sequelae.
Body packers and body stuffers
Body packers (‘mules’) attempt to smuggle illicit drugs (usually
cocaine, heroin or amphetamines) by ingesting multiple small
packages wrapped in several layers of clingfilm or in condoms.
Body stuffers are those who have ingested unpackaged or poorly
wrapped substances, often to avoid arrest. Both groups are at
risk of severe toxicity if the packages rupture. This is more likely
for body stuffers, who may develop symptoms of poisoning
within 8 hours of ingestion. The risk of poisoning depends on
the quality of the wrapping, and the amount and type of drug
Fig. 7.4 Abdominal X-ray of a body packer showing multiple
drug-filled condoms.
Chemicals and pesticides • 145
complex allows reactivation of the enzyme but, subsequently,
loss of a chemical group from the OP–enzyme complex prevents
further enzyme reactivation. After this process (termed ‘ageing’)
has taken place, new enzyme needs to be synthesised before
function can be restored. The rate of ‘ageing’ is an important
determinant of toxicity and is more rapid with dimethyl (3.7 hrs)
than diethyl (31 hrs) compounds (Box 7.13) and especially rapid
after exposure to nerve agents (soman in particular), which cause
‘ageing’ within minutes.
Clinical features and management
OP poisoning causes an acute cholinergic phase, which may
occasionally be followed by the intermediate syndrome or
organophosphate-induced delayed polyneuropathy (OPIDN).
The onset, severity and duration of poisoning depend on the
route of exposure and agent involved.
faulty domestic appliance. Subsequently, ataxia, nystagmus,
drowsiness and hyper-reflexia may develop, progressing
to coma, convulsions, hypotension, respiratory depression,
cardiovascular collapse and death. Myocardial ischaemia may
result in arrhythmias or myocardial infarction. Cerebral oedema
is common and rhabdomyolysis may cause myoglobinuria and
renal failure. In those who recover from acute toxicity, longer-term
neuropsychiatric effects are common, such as personality change,
memory loss and concentration impairment. Extrapyramidal
effects, urinary or faecal incontinence, and gait disturbance may
also occur. Poisoning during pregnancy may cause fetal hypoxia
and intrauterine death.
Management
Patients should be removed from exposure as soon as possible
and resuscitated as necessary. A high concentration of oxygen
should be administered via a tightly fitting facemask; this reduces
the half-life of carboxyhaemoglobin from 4–6 hours to about
40 minutes. Measurement of carboxyhaemoglobin is useful for
confirming exposure; levels > 20% suggest significant exposure
but do not correlate well with the severity of poisoning, partly
because concentrations fall rapidly after removal of the patient
from exposure, especially if supplemental oxygen has been given.
An ECG should be performed in all patients with acute CO
poisoning, especially those with pre-existing heart disease.
Arterial blood gas analysis should be checked in those with
serious poisoning. Pulse oximetry may provide misleading oxygen
saturations because carboxyhaemoglobin and oxyhaemoglobin
are both measured. Excessive intravenous fluid administration
should be avoided, particularly in the elderly, because of the
risk of pulmonary and cerebral oedema. Convulsions should
be controlled with diazepam.
Hyperbaric oxygen therapy is controversial. At 2.5 atmospheres,
this reduces the half-life of carboxyhaemoglobin to about
20 minutes and increases the amount of oxygen dissolved in
plasma 10-fold, but systematic reviews have not consistently
shown improved clinical outcomes. The logistical difficulties of
transporting sick patients to hyperbaric chambers and managing
them therein are substantial.
Organophosphorus insecticides and
nerve agents
Organophosphorus (OP) compounds (Box 7.13) are widely used
as pesticides, especially in developing countries. Case fatality
following deliberate ingestion is high (5–20%).
Nerve agents, developed for chemical warfare, are derived
from OP insecticides and are much more toxic. They are
commonly classified as G (originally synthesised in Germany)
or V (‘venomous’) agents. The ‘G’ agents, such as tabun, sarin
and soman, are volatile, absorbed by inhalation or via the skin,
and dissipate rapidly after use. ‘V’ agents, such as VX, are
contact poisons unless aerosolised, and contaminate ground
for weeks or months.
The toxicology and management of nerve agent and pesticide
poisoning are similar.
Mechanism of toxicity
OP compounds inactivate acetylcholinesterase (AChE), resulting
in the accumulation of acetylcholine (ACh) in cholinergic synapses
(Fig. 7.5). Initially, spontaneous hydrolysis of the OP–enzyme
7.13 Organophosphorus compounds
Nerve agents
• G agents: sarin, tabun, soman
• V agents: VX,VE
Insecticides
Dimethyl compounds
Diethyl compounds
• Dichlorvos
• Fenthion
• Malathion
• Methamidophos
• Chlorpyrifos
• Diazinon
• Parathion-ethyl
• Quinalphos
Fig. 7.5 Mechanism of toxicity of organophosphorus compounds and
treatment with oxime.
Acetylcholinesterase
enzyme
‘Ageing’: reactivation
not possible
Organophosphate
Enzyme–substrate
complex
Elimination of
‘leaving group’
Reactivation with oxime
Spontaneous
reactivation
AChE–OH + X–P–OR1
O
OR2
AChE–O–X–P–OR1
O
OR2
AChE–O–P–OR1 +
AChE–O–P–OR
O
OR2
OXIME
N–OH
O
O•
AChE–OH + HO–P–OR1
O
OR2
AChE–OH + OXIME
O
OR2
N–P–OR1
XH
146 • POISONING
given rapidly after exposure. Oximes reactivate AChE that has not
undergone ‘ageing’ and are therefore less effective with dimethyl
compounds and nerve agents, especially soman. Oximes may
provoke hypotension, especially if administered rapidly.
Intravenous magnesium sulphate has been reported to increase
survival in animals and in small human studies of OP poisoning;
however, further clinical trial evidence is needed before this can
be recommended routinely.
Ventilatory support should be instituted before the patient
develops respiratory failure. Benzodiazepines may be used
to treat agitation, fasciculations and seizures and for sedation
during mechanical ventilation.
Exposure is confirmed by measurement of plasma or red
blood cell cholinesterase activity but antidote use should not
be delayed pending results. Plasma cholinesterase is reduced
more rapidly but is less specific than red cell cholinesterase.
Values correlate poorly with the severity of clinical features but
are usually < 10% in severe poisoning, 20–50% in moderate
poisoning and > 50% in subclinical poisoning.
The acute cholinergic phase usually lasts 48–72 hours, with
most patients requiring intensive cardiorespiratory support and
monitoring. Cholinergic features may be prolonged over several
weeks with some lipid-soluble agents.
Intermediate syndrome
About 20% of patients with OP poisoning develop weakness that
spreads rapidly from the ocular muscles to those of the head and
neck, proximal limbs and the muscles of respiration, resulting
in ventilatory failure. This ‘intermediate syndrome’ generally
develops 1–4 days after exposure, often after resolution of the
acute cholinergic syndrome, and may last 2–3 weeks. There is
no specific treatment and supportive care is needed, including
maintenance of airway and ventilation.
Organophosphate-induced delayed polyneuropathy
Organophosphate-induced delayed polyneuropathy (OPIDN) is
a rare complication that usually occurs 2–3 weeks after acute
exposure. It is a mixed sensory/motor polyneuropathy, affecting
long myelinated neurons especially, and appears to result from
inhibition of enzymes other than AChE. It is a feature of poisoning
with some OPs such as triorthocresyl phosphate but is less
common with nerve agents. Early clinical features are muscle
cramps followed by numbness and paraesthesiae, proceeding to
flaccid paralysis of the lower and subsequently the upper limbs,
with foot and wrist drop and a high-stepping gait, progressing
to paraplegia. Sensory loss may also be present but is variable.
Initially, tendon reflexes are reduced or lost but mild spasticity
may develop later.
There is no specific therapy for OPIDN. Regular physiotherapy
may limit deformity caused by muscle-wasting. Recovery is
often incomplete and may be limited to the hands and feet,
although substantial functional recovery after 1–2 years may
occur, especially in younger patients.
Carbamate insecticides
Carbamate insecticides such as bendiocarb, carbofuran, carbaryl
and methomyl inhibit a number of tissue esterases, including
AChE. The mechanism, clinical features and management
of toxicity are similar to those of OP compounds. However,
clinical features are usually less severe and of shorter duration,
because the carbamate–AChE complex dissociates quickly, with
a half-life of 30–40 minutes, and does not undergo ageing. Also,
carbamates penetrate the CNS poorly. Intermediate syndrome
Acute cholinergic syndrome
This usually starts within a few minutes of exposure and
nicotinic or muscarinic features may be present (Box 7.14).
Vomiting and profuse diarrhoea are typical following ingestion.
Bronchoconstriction, bronchorrhoea and salivation may cause
severe respiratory compromise. Excess sweating and miosis are
characteristic and the presence of muscular fasciculations strongly
suggests the diagnosis, although this feature is often absent,
even in serious poisoning. Subsequently, generalised flaccid
paralysis may develop and affect respiratory and ocular muscles,
resulting in respiratory failure. Ataxia, coma, convulsions, cardiac
repolarisation abnormalities and torsades de pointes may occur.
Management
The airway should be cleared of excessive secretions, breathing
and circulation assessed, high-flow oxygen administered and
intravenous access obtained. Appropriate external decontamination
is needed (p. 133). Gastric lavage or activated charcoal may be
considered if the patient presents sufficiently early. Seizures
should be treated as described in Box 7.8. The ECG, oxygen
saturation, blood gases, temperature, urea and electrolytes,
amylase and glucose should be monitored closely.
Early use of sufficient doses of atropine is potentially life-saving
in patients with severe toxicity. Atropine reverses ACh-induced
bronchospasm, bronchorrhoea, bradycardia and hypotension.
When the diagnosis is uncertain, a marked increase in heart
rate associated with skin flushing after a 1 mg intravenous dose
makes OP poisoning unlikely. In OP poisoning, atropine (2 mg IV)
should be administered and this dose should be doubled every
5–10 minutes until clinical improvement occurs. Further bolus
doses should be given until secretions are controlled, the skin
is dry, blood pressure is adequate and heart rate is > 80 bpm.
Large doses may be needed, but excessive doses may cause
anticholinergic effects (see Box 7.10).
In severe poisoning requiring atropine, an oxime such as
pralidoxime chloride or obidoxime is generally recommended,
if available, although efficacy is debated. This may reverse or
prevent muscle weakness, convulsions or coma, especially if
7.14 Cholinergic features in poisoning*
Muscarinic
Nicotinic
Respiratory
Bronchorrhoea,
bronchoconstriction
Reduced ventilation
Circulation
Bradycardia, hypotension
Tachycardia,
hypertension
Higher mental
function
Anxiety, delirium, psychosis
Muscle
–
Fasciculation,
paralysis
Temperature
Fever
–
Eyes
Diplopia, miosis, lacrimation
Mydriasis
Abdomen
Vomiting, profuse diarrhoea
–
Mouth
Salivation
–
Skin
Sweating
–
Complications
Coma, seizures, respiratory depression
*Both muscarinic and nicotinic features occur in OP poisoning. Nicotinic features
occur in nicotine poisoning and black widow spider bites. Cholinergic features
are sometimes seen with some mushrooms.
Chemicals and pesticides • 147
and acute tubular necrosis occur because of renal calcium
oxalate precipitation. Hypocalcaemia, hypomagnesaemia and
hyperkalaemia are common.
Methanol poisoning causes headache, delirium and vertigo.
Visual impairment and photophobia develop, associated with optic
disc and retinal oedema and impaired pupil reflexes. Blindness
may be permanent, although some recovery may occur over
several months. Pancreatitis and abnormal liver function have
also been reported.
Management
Urea and electrolytes, chloride, bicarbonate, glucose, calcium,
magnesium, albumin, plasma osmolarity and arterial blood gases
should be measured in all patients with suspected methanol or
ethylene glycol toxicity. The osmolar and anion gaps should be
calculated (see Box 7.5). Initially, poisoning is associated with an
increased osmolar gap, but as toxic metabolites are produced,
an increased anion gap develops, associated with metabolic
acidosis. The diagnosis can be confirmed by measurement of
ethylene glycol or methanol concentrations but assays are not
widely available.
An antidote, ideally fomepizole but otherwise ethanol, should be
administered to all patients with suspected significant exposure
while awaiting the results of laboratory investigations. These
block alcohol dehydrogenase and delay the formation of toxic
metabolites until the parent drug is eliminated in the urine or by
dialysis. The antidote should be continued until ethylene glycol
or methanol concentrations are undetectable. Metabolic acidosis
should be corrected with sodium bicarbonate (e.g. 250 mL of
1.26% solution, repeated as necessary). Convulsions should be
treated with an intravenous benzodiazepine. In ethylene glycol
poisoning, hypocalcaemia should be corrected only if there are
severe ECG features or if seizures occur, as this may increase
calcium oxalate crystal formation. In methanol poisoning, folinic
acid should be administered to enhance the metabolism of the
toxic metabolite, formic acid.
Haemodialysis or haemodiafiltration should be used in severe
poisoning, especially if renal failure is present or there is visual
loss in the context of methanol poisoning. It should be continued
until acute toxic features are no longer present and ethylene
glycol/methanol concentrations are undetectable.
Corrosive substances
Products containing strong acids (e.g. hydrochloric or sulphuric
acid) or alkalis (e.g. sodium hydroxide, calcium carbonate)
may be ingested, accidentally or intentionally, causing
gastrointestinal pain, ulceration and necrosis, with risk of
perforation.
External decontamination (p. 133), if needed, should be
performed after initial resuscitation. Gastric lavage should not be
attempted and neutralising chemicals should not be administered
after large ingestions because of the risk of tissue damage
from heat release. Cardiorespiratory monitoring is necessary
and full blood count, renal function, coagulation and acid–base
status should be assessed. An erect chest X-ray should be
performed if perforation is suspected and may show features
of mediastinitis or gas under the diaphragm. Strong analgesics
should be administered for pain.
Severe abdominal or chest pain, abdominal distension, shock
or acidosis may indicate perforation and should prompt an
urgent CT scan of chest and abdomen and surgical review.
In the absence of perforation, drooling, dysphagia, stridor or
oropharyngeal burns suggest possible severe oesophageal
and OPIDN are not common features of carbamate poisoning.
In spite of this, case fatality can be high for some carbamates,
depending on their formulation.
Atropine may be given intravenously as for OP poisoning
(p. 146). Diazepam may be used to relieve anxiety. The use of
oximes is unnecessary.
Paraquat
Paraquat is a herbicide that is widely used across the world,
although it has been banned in the European Union and some
other countries for several years. It is highly toxic if ingested,
with clinical features including oral burns, vomiting and diarrhoea,
progressing to pneumonitis, pulmonary fibrosis and multi-organ
failure.
Exposure can be confirmed by a urinary dithionite test, while
the plasma paraquat concentration indicates prognosis. There
is no specific antidote but activated charcoal is commonly
administered. Immunosuppression with glucocorticoids and
cyclophosphamide is sometimes used but evidence for benefit is
weak. Irrespective of treatment, death is common and may occur
within 24 hours with substantial poisoning or after 1–2 weeks with
lower doses.
Methanol and ethylene glycol
Ethylene glycol (1,2-ethanediol) is found in antifreeze, brake fluids
and, in lower concentrations, windscreen washes. Methanol is
present in some antifreeze products and commercially available
industrial solvents, and in low concentrations in some screen
washes and methylated spirits. It may also be an adulterant of
illicitly produced alcohol. Both are rapidly absorbed after ingestion.
Methanol and ethylene glycol are not of high intrinsic toxicity but
are converted via alcohol dehydrogenase to toxic metabolites
that are largely responsible for their clinical effects (Fig. 7.6).
Clinical features
Early features of poisoning with either methanol or ethylene glycol
include vomiting, ataxia, drowsiness, dysarthria and nystagmus.
As toxic metabolites are formed, metabolic acidosis, tachypnoea,
coma and seizures may develop.
Toxic effects of ethylene glycol include ophthalmoplegia,
cranial nerve palsies, hyporeflexia and myoclonus. Renal pain
Fig. 7.6 Metabolism of methanol and ethylene glycol.
Ethanol or
fomepizole
Inhibits
Alcohol
dehydrogenase
Ethylene
glycol
Glycoaldehyde
Glycolic acid
Formaldehyde
Formic acid
TOXIC METABOLITES
Glyoxylic acid
Oxalic acid
Methanol
148 • POISONING
vegetable oil to reduce the release of toxic phosphine, but the
benefit is uncertain.
Copper sulphate
This is used as a fungicide. If it is ingested, clinical features of
toxicity include nausea, vomiting, abdominal pain, diarrhoea,
discoloured (blue/green) secretions, corrosive effects on the
gastrointestinal tract, renal or liver failure, methaemoglobinaemia,
haemolysis, rhabdomyolysis, convulsions and coma. Treatment
is as for other corrosive substances (see above) and should
address complications, including use of methylthioninium chloride
for methaemoglobinaemia (see Fig. 7.1). Chelation therapy is
unlikely to be beneficial after acute exposure.
Chemicals less commonly taken
in poisoning
An overview of the clinical features and management for chemicals
less commonly involved in poisoning is provided in Box 7.15.
damage and early endoscopy by an experienced operator should
be considered. Delayed endoscopy (e.g. after several days) may
carry a higher risk of perforation.
Aluminium and zinc phosphide
These rodenticides and fumigants are a common means of
self-poisoning in northern India. The mortality rate for aluminium
phosphide ingestion has been estimated at 60%; zinc phosphide
ingestion appears less toxic, at about 2%. When ingested,
both compounds react with gastric acid to form phosphine, a
potent pulmonary and gastrointestinal toxicant. Clinical features
include severe gastrointestinal disturbances, chest tightness,
cough and breathlessness progressing to ARDS and respiratory
failure, tremor, paraesthesiae, convulsions, coma, tachycardia,
metabolic acidosis, electrolyte disturbances, hypoglycaemia,
myocarditis, liver and renal failure, and leucopenia. Ingestion of
a few tablets can be fatal.
Treatment is supportive and directed at correcting electrolyte
abnormalities and treating complications; there is no specific
antidote. Early gastric lavage is sometimes used, often with
7.15 Clinical features and specific management of chemicals less commonly involved in poisoning
Substance
Clinical features
Management
Lead
e.g. Chronic occupational
exposure, leaded paint, water
contaminated by lead pipes,
use of kohl cosmetics
Abdominal pain
Microcytic anaemia with basophilic stippling
Headache and encephalopathy
Motor neuropathy
Nephrotoxicity
Hypertension
Hypocalcaemia
Prevention of further exposure
Measurement of blood lead concentration, full blood count
and blood film, urea and electrolytes, liver function tests
and calcium
Abdominal X-ray in children to detect pica
Bone X-ray for ‘lead lines’
Chelation therapy with DMSA or sodium calcium edetate
Petroleum distillates
e.g. White spirit, kerosene
Vomiting
Aspiration pneumonitis
Gastric lavage contraindicated
Activated charcoal ineffective
Oxygen and nebulised bronchodilators
Chest X-ray to assess pulmonary effects
Organochlorines
e.g. DDT, lindane, dieldrin,
endosulfan
Nausea, vomiting
Agitation
Fasciculation
Paraesthesiae (face, extremities)
Convulsions
Coma
Respiratory depression
Cardiac arrhythmias
Hyperthermia
Rhabdomyolysis
Pulmonary oedema
Disseminated intravascular coagulation
Activated charcoal (with nasogastric aspiration for liquid
preparations) within 1 hr of ingestion
Cardiac monitoring
Pyrethroid insecticides
e.g. Cypermethrin, permethrin,
imiprothrin
Skin contact: dermatitis, skin paraesthesiae
Eye contact: lacrimation, photophobia and oedema
of the eyelids
Inhalation: dyspnoea, nausea, headaches
Ingestion: epigastric pain, nausea, vomiting,
headache, coma, convulsions, pulmonary oedema
Symptomatic and supportive care
Washing contaminated skin makes irritation worse
Anticoagulant rodenticides
e.g. Brodifacoum, bromadialone
and warfarin
Abnormal bleeding (prolonged)
Monitor INR/prothrombin time
Vitamin K1 by slow IV injection if there is coagulopathy
Fresh frozen plasma or specific clotting factors for bleeding
(DMSA = dimercaptosuccinic acid)
Food-related poisoning • 149
7.16 Chemical warfare agents
Examples
Clinical effects
Antidotes*
Nerve agents
Tabun
Sarin
Soman
VX
See page 145 and
Box 7.13
Atropine
Oximes
(p. 145)
Blistering agents
Nitrogen/sulphur
Mustard
Lewisite
Eyes: watering,
blepharospasm, corneal
ulceration
Skin: erythema, blistering
Respiratory: cough,
hoarseness, dyspnoea,
pneumonitis
None
Choking agents
Chlorine
Phosgene
Eyes: watering,
blepharospasm, corneal
ulceration
Respiratory: cough,
hoarseness, dyspnoea,
pneumonitis
None
Blood agents
Cyanide
Cardiovascular: dizziness,
shock
Respiratory: dyspnoea,
cyanosis
CNS: anxiety, headache,
delirium, convulsions,
coma, fixed dilated pupils
Other: vomiting, lactic
acidosis
Dicobalt edetate
Hydroxocobalamin
*Appropriate resuscitation, decontamination and supportive care are essential
after exposure to all chemical warfare agents. Use appropriate personal
protective equipment.
7.17 Clinical features of chronic arsenic poisoning
Gastrointestinal tract
• Anorexia, vomiting, weight loss, diarrhoea, increased salivation,
metallic taste
Neurological
• Peripheral neuropathy (sensory and motor) with muscle wasting and
fasciculation, ataxia
Skin
• Hyperpigmentation, palmar and plantar keratosis, alopecia, multiple
epitheliomas, Mee’s lines (transverse white lines on fingernails)
Eyes
• Conjunctivitis, corneal necrosis and ulceration
Bone marrow
• Aplastic anaemia
Other
• Low-grade fever, vasospasm and gangrene, jaundice,
hepatomegaly, splenomegaly
Increased risk of malignancy
• Lung, liver, bladder, kidney, larynx and lymphoid system
Chemical warfare agents
Some toxins have been developed for use as chemical warfare
agents. These are summarised in Box 7.16.
Environmental poisoning
Arsenism
Chronic arsenic exposure from drinking water has been reported
in many countries, especially India, Bangladesh, Nepal, Thailand,
Taiwan, China, Mexico and South America, where a large
proportion of the drinking water (ground water) has a high
arsenic content, placing large populations at risk. The World
Health Organisation (WHO) guideline value for arsenic content
in tube well water is 10 μg/L.
Health effects associated with chronic exposure to arsenic in
drinking water are shown in Box 7.17. In exposed individuals,
high concentrations of arsenic are present in bone, hair and
nails. Specific treatments are of no benefit in chronic arsenic
toxicity and recovery from the peripheral neuropathy may never
be complete, so the emphasis should be on prevention.
Fluorosis
Fluoride poisoning can result from exposure to excessive
quantities of fluoride (> 10 ppm) in drinking water, industrial
exposure to fluoride dust or consumption of brick teas. Clinical
features include yellow staining and pitting of permanent teeth,
osteosclerosis, soft tissue calcification, deformities (e.g. kyphosis)
and joint ankylosis. Changes in the bones of the thoracic cage
may lead to rigidity that causes dyspnoea on exertion. Very high
doses of fluoride may cause abdominal pain, nausea, vomiting,
seizures and muscle spasm. In calcium-deficient children,
the toxic effects of fluoride manifest even at marginally high
exposures to fluoride.
In endemic areas, such as Jordan, Turkey, Chile, India,
Bangladesh, China and Tibet, fluorosis is a major public health
problem, especially in communities engaged in physically
strenuous agricultural or industrial activities. Dental fluorosis is
endemic in East Africa and some West African countries.
Food-related poisoning
Paralytic shellfish poisoning
Paralytic shellfish poisoning is caused by consumption of bivalve
molluscs (e.g. mussels, clams, oysters, cockles and scallops)
contaminated with saxitoxins, which are concentrated in the
shellfish as a result of constant filtration of toxic algae during algal
blooms (e.g. ‘red tide’). Symptoms develop within 10–120 minutes
of eating the contaminated shellfish and include gastrointestinal
disturbances, paraesthesia around the mouth or in the extremities,
ataxia, mental state changes and dysphagia. In severe cases,
paralysis and respiratory failure can develop. There is no specific
antidote and treatment is supportive. Most cases resolve over
a few days.
Ciguatera poisoning
Ciguatera toxin and related toxins are produced by dinoflagellate
plankton that adhere to algae and seaweed. These accumulate
in the tropical herbivorous fish that feed on these and in their
larger predators (e.g. snapper, barracuda), especially in the
150 • POISONING
Further information
Books and journal articles
Bateman DN, Jefferson R, Thomas SHL, et al. (eds). Oxford
desk reference: toxicology. Oxford: Oxford University Press;
2014.
Benson BE, Hoppu K, Troutman WG, et al. Position paper update:
gastric lavage for gastrointestinal decontamination. Clin Toxicol
2013; 51:140–146.
Chyka PA, Seger D, Krenzelok EP, et al. Position paper: single-dose
activated charcoal. Clin Toxicol 2005; 43:61–87.
Thompson JP, Watson ID, Thanacoody HK, et al. Guidelines for
laboratory analyses for poisoned patients in the United Kingdom.
Ann Clin Biochem 2014; 51:312–325.
Websites
curriculum.toxicology.wikispaces.net/ Free access to educational
material related to poisoning.
toxbase.org Toxbase, the clinical toxicology database of the UK
National Poisons Information Service. Free for UK health
professionals but registration is required. Access for overseas
users by special arrangement. Low-cost smartphone app
available.
toxnet.nlm.nih.gov US National Library of Medicine’s Toxnet: a
hazardous substances databank, including Toxline for references to
literature on drugs and other chemicals.
who.int/gho/phe/chemical_safety/poisons_centres/en/ World directory
of poisons centres held by the WHO, including interactive map and
contact details.
Pacific and Caribbean. Human exposure occurs through eating
contaminated fish, even if well cooked. Nausea, vomiting,
diarrhoea and abdominal pain develop within a few hours,
followed by paraesthesia, ataxia, blurred vision, ataxia and
tremor. Convulsions and coma can occur, although death is
uncommon. Fatigue and peripheral neuropathy can be long-term
effects. There is no specific treatment. In the South Pacific and
Caribbean, there are approximately 50 000 cases per year, with
a case fatality of 0.1%.
Scombrotoxic fish poisoning
Under poor storage conditions, histidine in scombroid fish
(e.g. tuna, mackerel, bonito, skipjack and the canned dark
meat of sardines) may be converted by bacteria to histamine
and other chemicals. Within minutes of consumption, flushing,
burning, sweating, urticaria, pruritus, headache, colic, nausea
and vomiting, diarrhoea, bronchospasm and hypotension may
occur. Management is with nebulised salbutamol, intravenous
antihistamines and, occasionally, intravenous fluid replacement.
Plant poisoning
A substantial number of plants and fungi are potentially toxic
if consumed, with patterns of poisoning depending on their
geographical distribution. Some toxic examples and the clinical
features of toxicity are shown in Box 7.18.
7.18 Some poisonous plants and fungi, with their clinical effects
Species (common name)
Toxins
Important features of toxicity
Plants
Abrus precatorius (jequirity bean)
Abrin
Gastrointestinal effects, drowsiness, delirium, convulsions, multi-organ
failure
Ricinus communis (castor oil plant)
Ricin
Aconitum napellus (aconite, wolf’s bane,
monkshood)
Aconitum ferox (Indian aconite, bikh)
Aconite
Gastrointestinal effects, paraesthesiae, convulsions, ventricular
tachycardia
Atropa belladonna (deadly nightshade)
Datura stramonium (Jimson weed, thorn apple)
Brugmansia spp. (angel’s trumpet)
Atropine, scopolamine,
hyocyamine
Anticholinergic toxidrome (see Box 7.10)
Colchicum autumnale (autumn crocus)
Colchicine
Gastrointestinal effects, hypotension, cardiogenic shock
Conium maculatum (hemlock)
Toxic nicotinic alkaloids
Hypersalivation, gastrointestinal effects, followed by muscular paralysis
Digitalis purpurea (foxglove)
Nerium oleander (pink oleander)
Thevetia peruviana (yellow oleander)
Cardiac glycosides
Cardiac glycoside toxicity (p. 140)
Laburnum anagyroides (laburnum)
Cytosine
Gastrointestinal effects; convulsions in severe cases
Taxus baccata (yew)
Taxane alkaloids
Hypotension, bradycardia, respiratory depression, convulsions, coma,
arrhythmias
Fungi
Amanita phalloides
(death cap mushroom)
Amatoxins
Gastrointestinal effects, progressing to liver failure
Cortinarius spp.
Orellanine
Gastrointestinal effects, fever, progressing to renal failure
Psilocybe semilanceata
(‘magic mushrooms’)
Psilocybin, psilocin
Hallucinations

02-8 Envenomation
8 Envenomation
Envenomation
J White
Comprehensive evaluation of the envenomed patient 152
Geographical distribution of venomous snakes 153
Bedside tests in the envenomed patient 153
Overview of envenomation 154
Venom 154
Venomous animals 154
Clinical effects 155
General approach to the envenomed patient 156
First aid 156
Assessment and management in hospital 158
Treatment 159
Follow-up 160
Envenomation by specific animals 160
Venomous snakes 160
Scorpions 161
Spiders 161
Paralysis ticks 161
Venomous insects 161
Marine venomous and poisonous animals 162
152 • ENVENOMATION
Comprehensive evaluation of the envenomed patient
Copyright © Julian White.
Cranial nerves
Drooling
Dysarthria
Dysphagia
Upper airway compromise
Mouth, gums
Evidence of bleeding
Increased salivation
Drooling
Chest
Pulmonary oedema
Diminished respiration
Bite/sting site
Pain
Swelling
Bruising
Discoloration
Necrosis
Skin
In addition to (6):
Piloerection
Erythema
Blistering
Infection
Level of consciousness
Confusion
Agitation
Seizures
Eyes
Miosis or mydriasis
Increased lacrimation
Corneal injury (venom spit injury)
Airway, breathing, circulation
Blood pressure
Pulse
Respiration rate
Oxygen saturation
Dysrhythmias
Bilateral mild ptosis
Ptosis and lateral
ophthalmoplegia
Fixed dilated pupils
Chemosis – can indicate
capillary leak syndrome
Local increased sweating
Local bleeding, blistering
Local bleeding
Muscles
Weakness
Tenderness
Pain
Lymph nodes
Tender or enlarged nodes
draining bite/sting area
Abdomen
Intra-abdominal, retroperitoneal
or renal pathology
Reflexes
Decreased or absent reflexes
Bedside tests in the envenomed patient • 153
Geographical distribution of venomous snakes
The geographical location of a snakebite determines the likely animal(s) involved and the nature and risks of the envenomation. Copyright ©
Julian White.
South American
rattlesnake
Crotalus durissus
Indian krait
Bungarus caeruleus
European adder
Vipera aspis
Green pit viper
Trimeresurus gramineus
Russell’s viper
Daboia russelii
Black-necked
spitting cobra
Naja nigricollis
Monacled cobra
Naja kaouthia
Common Indian cobra
Naja naja
Puff adder
Bitis arietans
Saw-scaled viper
Echis carinatus
Examination of urine. Haematuria may indicate
a coagulopathy. Dark urine is suggestive of
myoglobinuria, which is a sign of extensive
rhabdomyolysis. Copyright © Julian White.
Bedside tests in the envenomed patient
Twenty-minute whole-blood clotting test (20WBCT). The presence of coagulopathy is a
key indicator of major envenoming for some species. While full laboratory coagulation studies
may be the ideal, the 20WBCT has emerged as a simple standardised bedside test of
coagulopathy, applicable even in areas with limited health facilities. Copyright © Julian White.
1 Obtain a clean glass container
(test tube or bottle) that is
either new, or has only been
washed with water (not
detergent/soap)
2 Place 2–3 mL venous blood
in the glass container
3 Allow to stand undisturbed
for 20 mins
4 Gently invert/tip the glass
container checking for
presence of a blood clot
4a Clot present = negative test
(no coagulopathy present)
4b Clot absent = positive test
(coagulopathy present)
4a
4b
154 • ENVENOMATION
Venomous animals
There are many animal groups that contain venomous species
(Box 8.2). The epidemiological estimates reflect the importance of
snakes and scorpions as causes of severe or lethal envenomation,
but also the fragmentary nature of the data. For snakes, recent
studies have proposed widely varying estimates of epidemiological
impact, but even the higher estimates may be too low. A recent
Overview of envenomation
Envenomation occurs when a venomous animal injects sufficient
venom by a bite or a sting into a prey item or perceived predator
to cause deleterious local and/or systemic effects. This is defined
as a venom-induced disease (VID). Venomous animals generally
use their venom to acquire and, in some cases, pre-digest prey,
with defensive use a secondary function for many species.
Accidental encounters between venomous animals and humans
are frequent, particularly in the rural tropics, where millions of
cases of venomous bites and stings occur annually. Globally,
an increasing number of exotic venomous animals are kept
privately, so cases of envenoming may present to hospitals
where doctors have insufficient knowledge to manage potentially
complex presentations. Doctors everywhere should thus be
aware of the basic principles of management of envenomation
and how to seek expert support. It is important for doctors to
know what types of venomous animal are likely to occur in their
geographical area (hospital hinterland; p. 153) and the types of
envenoming they may cause.
Venom
Venom is a complex mixture of diverse components (notably
toxins), often with several separate toxins that can cause
adverse effects in humans, and each is potentially capable of
multiple effects (Box 8.1). Venom is produced at considerable
metabolic cost, so is used sparingly; thus only some bites/
stings by venomous animals result in significant envenoming,
the remainder being ‘dry bites’. The concept of dry bites is
important in understanding approaches to first aid and medical
management.
8.2 Venomous animals and human envenoming
Phyla
Principal
venomous
animal groups
Estimated
number of
human
cases/year
Estimated
number of
human
deaths/year
Chordata
Snakes
2.5 million
100 000
Spiny fish
? > 100 000
Close to zero
Stingrays
? > 100 000
? < 10
Arthropoda
Scorpions
1 million
? < 5000
Spiders
? > 100 000
? < 100
Paralysis ticks
? > 1000
? < 10
Insects
? > 1 million
? > 1000*
Mollusca
Cone snails
? < 1000
? < 10
Blue-ringed
octopus
? < 100
? < 10
Coelenterata
Jellyfish
? > 1 million
? < 10
*Social insect stings cause death by anaphylaxis rather than primary venom
toxicity, except for massive multiple sting attacks.
Copyright © Julian White.
Copyright © Julian White.
All venom components have lethal potential.
8.1 Key venom effects
Venom component
Clinical effects
Type of venomous animal
Neurotoxin
Paralytic
Flaccid paralysis
Some snakes
Paralysis ticks
Cone snails
Blue-ringed octopus
Excitatory
Neuroexcitation: autonomic storm, cardiotoxicity,
pulmonary oedema
Some scorpions, spiders, jellyfish (irukandji)
Myotoxins
Systemic or local myolysis
Some snakes
Cardiotoxins
Direct or indirect cardiotoxicity; cardiac collapse, shock
Some snakes, scorpions, spiders and jellyfish (box
jellyfish)
Haemostasis system
toxins
Variation from rapid coagulopathy and bleeding to
thrombosis, deep venous thrombosis and pulmonary
emboli
Many snakes and a few scorpions (Hemiscorpius)
Brazilian caterpillars (Lonomia)
Haemorrhagic toxins
Local vessel damage, fluid extravasation, blistering,
ecchymosis, shock
Mainly some snakes
Nephrotoxins
Renal damage
Some snakes, massed bee and wasp stings
Necrotoxins
Local tissue injury/necrosis, shock
Some snakes, a few scorpions (Hemiscorpius), spiders
(recluse spiders), jellyfish and stingrays
Allergic toxins
Induction of acute allergic response (direct and
indirect)
Almost all venoms but particularly those of social insects
(i.e. bees, wasps, ants)
Overview of envenomation • 155
local effects predominate over systemic, and for some, such
as certain snakes, both are important (p. 152). Some species
commonly cause local necrosis, notably some snakes, brown
recluse spiders, an Iranian scorpion (Hemiscorpius lepturus)
and some stingrays.
General systemic effects
By definition, these are non-specific (Box 8.3). Shock is an
important complication of major local envenoming by some
snake species and, if inadequately treated, can prove lethal,
especially in children.
Specific systemic effects
These are important in both diagnosis and treatment.
• Neurotoxic flaccid paralysis can develop very rapidly,
progressing from mild weakness to full respiratory paralysis
in less than 30 minutes (blue-ringed octopus bite, cone
snail sting), or may develop far more slowly, over hours
(some snakes) to days (paralysis tick). For neurotoxic
snakes, the cranial nerves are usually involved first, with
ptosis a common initial sign, often progressing to partial
and later complete ophthalmoplegia, fixed dilated pupils,
drooling and loss of upper airway protection (p. 152).
From this, paralysis may extend to the limbs, with
weakness and loss of deep tendon reflexes, the neck
(‘broken neck’ sign), then finally respiratory paralysis
affecting the diaphragm.
• Excitatory neurotoxins cause an ‘autonomic storm’, often
with profuse sweating (p. 152), variable cardiac effects and
cardiac failure, sometimes with pulmonary oedema
(notably, Australian funnel web spider bite, some
scorpions such as Indian red scorpion). This type of
envenomation can be rapidly fatal (many scorpions, funnel
web spiders), or may cause distressing symptoms but
constitute a lesser risk of death (widow spiders, banana
spiders).
• Myotoxicity can be localised in the bitten limb, or
systemic, affecting mostly skeletal muscles. It can
initially be silent, then present with generalised muscle
pain, tenderness, myoglobinuria (p. 153) and huge rises
in serum creatine kinase (CK). Secondary renal failure
can precipitate potentially lethal hyperkalaemic
cardiotoxicity.
• Cardiotoxicity is often secondary but symptoms and signs
are non-specific in most cases. For some scorpions,
envenomation can cause direct cardiac effects, including
decreased cardiac output, arrhythmias and pulmonary
oedema.
• Haemostasis system toxins cause a variety of effects,
depending on the type of toxin (Fig. 8.1). Coagulopathy
may present as bruising and bleeding from the bite site
(p. 152), gums and intravenous sites. Surgical interventions
are high-risk in such cases. Other venoms cause
thrombosis, usually presenting as deep venous thrombosis
(DVT), pulmonary embolus or stroke (particularly
Caribbean/Martinique vipers).
• Haemorrhagic toxins cause vascular damage, especially in
the bitten limb, with extravasation of fluid and sometimes
hypotensive shock; this is a problem associated with some
snakebites. The role of these toxins in causing latedeveloping capillary leak syndrome (p. 152), again
comprehensive study in India indicated there are at least 45 000
snakebite-related deaths in that country annually, far above both
government figures and previous estimates. In many areas of
the poor rural tropics, health resources are limited and few
envenoming cases are either seen or recorded within the official
hospital system, compared to the actual community burden of
disease. While fatal cases may gain most attention, long-term
disability from envenomation affects significantly more people
and has a major social and economic cost.
Stings by social insects such as bees and wasps may also
cause lethal anaphylaxis. Other venomous animals may commonly
envenom humans but cause mostly non-lethal effects. A few
animals only rarely envenom humans but have a high potential
for severe or lethal envenoming. These include box jellyfish,
cone snails, blue-ringed octopus, paralysis ticks and Australian
funnel web spiders. Within any given group, particularly snakes,
there may be a wide range of clinical presentations. Some are
described here but for a more detailed discussion of the types
of venomous animal, their venoms and their effects on humans,
see toxinology.com.
Clinical effects
With the exception of dry bites, where no significant toxin effects
occur, venomous bites/stings can result in three broad classes
of effect.
Local effects
These vary from trivial to severe (Box 8.3). There may be minimal
or no local effects with some snakebites (not even pain), yet lethal
systemic envenoming may still be present. For other species,
Copyright © Julian White.
8.3 Local and systemic effects of envenomation
Local effects
• Pain
• Sweating
• Erythema
• Major direct tissue trauma
(e.g. stingray injuries)
• Blistering
• Necrosis
• Swelling
• Bleeding and bruising
Non-specific systemic effects
• Headache
• Nausea
• Vomiting and diarrhoea
• Abdominal pain
• Tachycardia or bradycardia
• Hypertension or
hypotension
• Pulmonary oedema
• Dizziness
• Collapse
• Convulsions
• Shock
• Cardiac arrest
Specific systemic effects
• Neurotoxic flaccid paralysis (descending or ascending)
• Excitatory neurotoxicity (catecholamine storm-like and similar)
• Rhabdomyolysis (systemic or local)
• Coagulopathy (procoagulant/fibrinolytic or anticoagulant or
thrombotic or antiplatelet)
• Cardiotoxicity (decreased/abnormal cardiac function or arrhythmia or
arrest)
• Acute kidney injury (polyuria or oliguria or anuria or isolated elevated
creatinine/urea)
156 • ENVENOMATION
General approach to
the envenomed patient
First aid
First aid can be crucial in determining the outcome for envenomed
patients, yet throughout much of the world inappropriate and
dangerous first aid is often administered.
associated with some snakebites (notably Russell’s viper),
is uncertain.
• Renal damage in envenoming is mostly secondary,
although some species, such as Russell’s vipers, can
cause primary renal damage. The presentation is similar in
both cases, with changes in urine output (polyuria, oliguria
or anuria) or rises in creatinine and urea. In cases with
intravascular haemolysis, secondary renal damage is likely.
The clinical effects of specific animals in different regions
of the world are shown in Boxes 8.4–8.6.
Fig. 8.1 Sites of action of venoms on the haemostasis system. Copyright © Julian White.
Haemorrhagic metalloproteinases and disintegrins
Damage blood vessel wall, cause leakage of blood,
degrade platelet plug response
Direct fibrinolytics
Split fibrinogen, often abnormally, resulting in poor clot
formation and a bleeding tendency
Procoagulants
Activate specific coagulation factors to activate clotting
cascade and promote formation of fibrin clots. Can also
activate fibrinolytic system, resulting in defibrination and
reduced ability to form protective clots
Other haemostasis system toxins
Target various parts of haemostasis, either as activators
(e.g. plasminogen activators), or as inhibitors of coagulation
(e.g. serpin inactivators, platelet aggregation inhibitors)
Clotting
factor pathways
Factor II
Factor IIa
Fibrinogen
Fibrin
8.4 Selected important venomous animals in Asia
Scientific name1
Common name
Clinical effects
Antivenom/antidote/treatment
Indian subcontinent
Bungarus spp. (E)
Kraits
Flaccid paralysis2,3, myolysis4, hyponatraemia5
Indian PV or specific
Naja spp. (E)
Cobras
Flaccid paralysis3, local necrosis/blistering, shock
Indian PV or specific
Ophiophagus hannah (E)
King cobra
Flaccid paralysis3, local necrosis, shock
Indian PV or specific
Echis spp. (Vv)
Saw-scaled vipers
Procoagulant coagulopathy, local necrosis/blistering,
renal failure
Indian PV or specific
Daboia russelii (Vv)
Russell’s viper
Procoagulant coagulopathy, local necrosis/blistering,
myolysis, renal failure, shock, flaccid paralysis2
Indian PV or specific
Hypnale spp. (Vc)
Hump-nosed vipers
Procoagulant coagulopathy, shock, renal failure
Try Indian PV
Trimeresurus6 spp. (Vc)
Green pit vipers
Procoagulant coagulopathy, local necrosis, shock
Indian PV or specific
Hottentotta spp. (Sc)
Indian scorpions
Neuroexcitation, cardiotoxicity
Indian specific AV
Prazosin
East Asia
Bungarus spp. (E)
Kraits
Flaccid paralysis2,3
Specific AV from country
Naja spp. (E)
Cobras (some spitters)
Flaccid paralysis3, local necrosis/blistering, shock
Specific AV from country
Ophiophagus hannah (E)
King cobra
Flaccid paralysis3, local necrosis, shock
King cobra AV
Calloselasma rhodostoma (Vc)
Malayan pit viper
Procoagulant coagulopathy, local necrosis/blistering,
renal failure, shock
Specific AV from country
Daboia siamensis (Vv)
Russell’s viper
Procoagulant coagulopathy, local necrosis/blistering,
renal failure, shock
Specific AV from country
Gloydius spp. (Vc)
Mamushis, pit vipers
Procoagulant coagulopathy, local necrosis/blistering,
shock, renal failure, flaccid paralysis2
Specific AV from country
Trimeresurus6 spp. (Vc)
Green pit vipers, habus
Procoagulant coagulopathy, local necrosis/blistering,
shock
Specific AV from country
1Family names: C = ‘Colubridae’ (mostly ‘non-venomous’; family subject to major taxonomic revisions); E = Elapidae (all venomous); Sc = Scorpionoidea; Vc = Viperidae
Crotalinae (New World and Asian vipers); Vv = Viperidae viperinae (Old World vipers). 2Pre-synaptic. 3Post-synaptic. 4Only reported so far for B. candidus, B. niger and
B. caeruleus. 5Only reported so far for B. multicinctus and B. candidus. 6Genus is subject to major taxonomic change (split into at least eight genera).
(AV = antivenom; PV = polyvalent)
More information is available from WHO-SEARO Guidelines for the management of snake-bites and from toxinology.com.
Copyright © Julian White.
General approach to the envenomed patient • 157
8.5 Selected important venomous animals in the Americas and Australia
Scientific name1
Common name
Clinical effects
Antivenom/antidote/treatment
North America
Crotalus spp. (Vc)
Rattlesnakes
Procoagulant coagulopathy, local necrosis/
blistering (flaccid paralysis2 rare), shock
CroFab AV or Bioclon Antivipmyn AV
Sistrurus spp. (Vc)
Massasaugas
Procoagulant coagulopathy, local necrosis/
blistering, shock
CroFab AV or Bioclon Antivipmyn AV
Agkistrodon spp. (Vc)
Copperheads and moccasins
Procoagulant coagulopathy, local necrosis/
blistering, shock
CroFab AV or Bioclon Antivipmyn AV
Micrurus spp. (E)
Coral snakes
Flaccid paralysis3
Bioclon Coralmyn AV
Latrodectus mactans
Widow spider
Neuroexcitation
MSD Widow spider AV
Centruroides
sculpturatus
Arizona bark scorpion
Neuroexcitation
Bioclon Anascorp AV
Central and South America
Crotalus spp. (Vc)
Rattlesnakes
Flaccid paralysis2, myolysis, procoagulant
coagulopathy, shock, renal failure
Specific AV from country
Bothrops spp. (Vc)
Lancehead vipers
Procoagulant coagulopathy, local necrosis/
blistering, shock, renal failure
Specific AV from country
Bothriechis spp. (Vc)
Eyelash pit vipers
Shock, pain and swelling
Specific AV from country
Lachesis spp. (Vc)
Bushmasters
Procoagulant coagulopathy, shock, renal
failure, local necrosis/blistering
Specific AV from country
Micrurus spp. (E)
Coral snakes
Flaccid paralysis2,3, myolysis, renal failure
Specific AV from country
Tityus serrulatus
Brazilian scorpion
Neuroexcitation, shock
Instituto Butantan scorpion AV
Loxosceles spp.
Recluse spiders
Local necrosis
Instituto Butantan spider AV
Phoneutria nigriventer
Banana spider
Neuroexcitation, shock
Instituto Butantan spider AV
Potamotrygon,
Dasyatis spp.
Freshwater stingrays
Necrosis of bite area, shock, severe pain
and oedema
No available AV; good wound care
Australia
Pseudonaja spp. (E)
Brown snakes
Procoagulant coagulopathy, renal failure,
flaccid paralysis2 (rare)
CSL brown snake AV or PVAV
Notechis spp. (E)
Tiger snakes
Procoagulant coagulopathy, myolysis, flaccid
paralysis2,3, renal failure
CSL tiger snake AV or PVAV
Oxyuranus spp. (E)
Taipans
Procoagulant coagulopathy, flaccid
paralysis2,3, myolysis, renal failure
CSL taipan or PVAV
Acanthophis spp. (E)
Death adders
Flaccid paralysis3
CSL death adder or PVAV
Pseudechis spp.
Black and mulga snakes
Anticoagulant coagulopathy, myolysis, renal
failure
CSL black snake AV or PVAV
Enhydrina schistosa
Sea snakes (all species globally)
Flaccid paralysis and/or myolysis
CSL sea snake AV
Atrax, Hadronyche spp.
Funnel web spiders
Neuroexcitation, shock
CSL funnel web spider AV
Latrodectus hasseltii
Red back spider
Neuroexcitation, pain and sweating
CSL red back spider AV
Chironex fleckeri
Box jellyfish
Neuroexcitation, cardiotoxicity, local necrosis
CSL box jellyfish AV
Synanceia spp.
Stonefish
Severe local pain
CSL stonefish AV
1For family name, see Box 8.4. 2Pre-synaptic. 3Post-synaptic.
(PVAV = polyvalent antivenom)
Copyright © Julian White.
A significant proportion of venom is transported from the bite/
sting site via the lymphatic system, particularly for venoms with
larger molecular weight toxins, such as many snake venoms. It
is recommended that for most forms of envenoming, the patient
should be kept still, the bitten limb immobilised with a splint
and vital systems supported, where required. A patent upper
airway should be specifically ensured and respiratory support
provided, if required. For some animals, notably snakes in certain
regions, the use of a local pressure pad bandage over the bite
site (Myanmar) or a pressure immobilisation bandage (Australia,
New Guinea) is recommended.
Ineffective or dangerous first aid, such as suction devices,
‘cut and suck’, local chemicals, snake stones (stones of some
sort placed over the snakebite) and tourniquets, should not be
used. Tourniquets, in particular, have the potential to cause
catastrophic distal limb injuries in snakebite when applied too
narrowly or too tightly, or left on too long.
Transporting patients
Where possible, transport should be brought to the patient. It
is also vital to obtain medical assessment and intervention at
the earliest opportunity, however, so any delay in transporting
the patient to a medical facility should be avoided. Severely
envenomed patients may develop life-threatening problems,
such as shock or respiratory failure, during transport, so ideally
the transport method used should allow for management of
these problems en route.
In resource-poor environments, simple solutions for
rapid transport have been successfully employed, such as
motorbikes or similar with the patient supported between the
driver in front and another person behind the patient. However,
this method cannot cope with a patient developing airway
compromise or respiratory failure, such as from developing
neurotoxicity.
158 • ENVENOMATION
dilated pupils, absent reflexes, no withdrawal response to painful
stimuli, no movement of limbs, fixed forward gaze with gross
ptosis; p. 152) when, in fact, the patient is conscious.
Assessment for evidence of envenoming
As in other areas of medicine, comprehensive assessment of
a patient bitten/stung by a venomous animal requires a good
history, a careful targeted examination and, where appropriate,
‘laboratory’ testing (though the latter may just consist of simple
bedside tests performed by the doctor; p. 153). Animals that
are unlikely to cause serious envenomation in humans should
be identified so that inappropriate admission and intervention are
avoided. Occasionally, patients may be unaware they have been
bitten/stung and thus provide a misleading history. In regions of
the world where keeping or handling venomous animals is illegal,
patients may be reticent in giving a truthful history. Multiple bites
or stings are more likely to cause major envenoming.
The following key questions should be asked:
• When was the patient exposed to the venomous
bite/sting?
• Was the organism causing it seen and what did it look like
(size, colour)?
• What were the circumstances (on land, in water etc.)?
• Was there more than one bite/sting?
• What first aid was used, when and for how long?
• What symptoms has the patient had (local and systemic)?
• Are there symptoms suggesting systemic envenoming
(paralysis, rhabdomyolysis, coagulopathy etc.)?
Assessment and management in hospital
On arrival at a health station or hospital, there are two immediate
priorities:
• identifying and treating any life-threatening problems (e.g.
circulatory shock, respiratory failure; see Ch. 16)
• determining whether envenoming is present and if that
requires urgent treatment.
Assessment and management of
life-threatening problems
Patients who are seriously envenomed must be identified early
so that appropriate management is not delayed. Critically ill
patients must be resuscitated (p. 202) and this takes precedence
over administration of any antivenom. Clinicians should look
for signs of:
• shock/hypotension
• airway and/or respiratory compromise (likely to be
secondary to flaccid paralysis)
• major bleeding, including internal bleeding (especially
intracranial)
• impending limb compromise from inappropriate first aid
(e.g. a tourniquet) – though beware sudden envenoming
on removal of a tourniquet.
In a patient with severe neurotoxic flaccid paralysis, who is
still able to maintain sufficient respiratory function for survival,
clinical assessment may suggest irretrievable brain injury (fixed
8.6 Selected important venomous animals in Africa and Europe
Scientific name1
Common name
Clinical effects
Antivenom/antidote/treatment
Africa
Naja spp. (E)
Cobras
Non-spitters
Flaccid paralysis3 ± local necrosis/blistering
South African PV or Sanofi Pasteur FavAfrica AV
Spitters
Local necrosis/blistering (flaccid paralysis3
uncommon)
South African PV or Sanofi Pasteur FavAfrica AV
Dendroaspis spp. (E)
Mambas
Mamba neurotoxic flaccid paralysis and muscle
fasciculation, shock, necrosis (uncommon)
South African PV or Sanofi Pasteur FavAfrica AV
Hemachatus
haemachatus (E)
Rinkhals
Flaccid paralysis3, local necrosis, shock
South African PV
Atheris spp. (Vv)
Bush vipers
Procoagulant coagulopathy, shock, pain and
swelling
No available AV (can try South African AV)
Bitis spp. (Vv)
Puff adders etc.
Procoagulant coagulopathy, shock, cardiotoxicity,
local necrosis/blistering
South African PV or Sanofi Pasteur FavAfrica AV
Causus spp. (Vv)
Night adders
Pain and swelling
No available AV
Echis spp. (Vv)
Carpet vipers
Procoagulant coagulopathy, shock, renal failure,
local necrosis/blistering
Specific anti-Echis AV for species/geographical
region or Sanofi Pasteur FavAfrica AV
Cerastes spp. (Vv)
Horned desert vipers
Procoagulant coagulopathy, local necrosis, shock
Specific or polyspecific AV covering Cerastes
from country of origin
Dispholidus typus (C)
Boomslang
Procoagulant coagulopathy, shock
Boomslang AV
Androctonus spp.
North African
scorpions
Neuroexcitation
Specific scorpion AV (Algeria, Tunisia, Sanofi
Pasteur Scorpifav)
Lelurus
quinquestriatus
Yellow scorpion
Neuroexcitation, shock
Specific scorpion AV (Algeria, Tunisia, Sanofi
Pasteur Scorpifav)
Europe
Vipera spp. (Vv)
Vipers and adders
Shock, local necrosis/blistering, procoagulant
coagulopathy (flaccid paralysis2 rare)
ViperaTab AV or Zagreb AV or SanofiPasteur
Viperfav AV
1For family name, see Box 8.4. 2Pre-synaptic. 3Post-synaptic.
More information is available from WHO Guidelines for the prevention and clinical management of snakebite in Africa and from toxinology.com.
Copyright © Julian White.
General approach to the envenomed patient • 159
• Is there any significant past medical history and
medication use?
• Is there a past exposure to antivenom/venom and
allergies?
If patients state that they have been bitten by a particular
species, ensure this information is accurate. Private keepers of
venomous animals may not have accurate knowledge of what they
are keeping, and misidentification of a snake, scorpion or spider
can have dire consequences if the wrong antivenom is used.
An outline of some principal findings on examination of the
envenomed patient is shown on page 152. The patient may
have a cluster of clinical features suggestive of a particular type
of envenoming (see Box 8.1).
Even with dangerously venomous animals, some bites/stings
will be dry bites and will not require antivenom. The time to
onset of first symptoms and signs of envenomation is variable,
depending on both animal and patient factors. It may range
from a matter of minutes post-bite/sting to 24 hours later in
some cases. Therefore, the initial assessment, if normal, must
be repeated multiple times during the first 24 hours. Some types
of envenomation will not cause symptoms or signs at all, or they
may appear very late, long after the optimum time for treatment
has passed. Evidence of envenomation may become apparent
only through laboratory testing.
Laboratory investigations
Specific tests for venom are currently commercially available
only for Australian snakebites but are likely to be developed
for snakebites in other regions. They are not available for other
types of envenomation, where venom concentrations are low.
For snakebite, a screen for envenoming includes full blood count,
coagulation screen, urea and electrolytes, creatinine, CK and
electrocardiogram (ECG). Lung function tests, peripheral oximetry
or arterial blood gases may be indicated in cases with potential
or established respiratory failure. In areas without access to
routine laboratory tests, the 20-minute whole-blood clotting test
(20WBCT) is useful (p. 153).
Treatment
Once a diagnosis of likely envenoming has been made, the next
and urgent decision is whether to give antivenom. Antivenom
may not be the only crucial treatment, however. For a snakebite
by a potentially lethal species such as Russell’s viper, the patient
might have local effects with oedema, blistering, necrosis, and
resultant fluid shifts causing shock, and at the same time have
systemic effects such as intractable vomiting, coagulopathy,
paralysis and secondary renal failure. Specific treatment with
antivenom will be required to reverse the coagulopathy and may
prevent worsening of the paralysis and reduce the vomiting,
but will not greatly affect the local tissue damage or the renal
failure or shock. The latter will require intravenous fluid therapy,
possibly respiratory support, renal dialysis and local wound care,
perhaps including antibiotics.
Each venomous animal will cause a particular pattern of
envenomation, requiring a tailored response. Listing all of these is
beyond the scope of this chapter (see ‘Further information’ below).
Antivenom
Antivenom, sometimes inappropriately labelled as ‘anti-
snake venom’ (ASV), is the most important tool in treating
envenoming. It is made by hyperimmunising an animal, usually
horses, to produce antibodies against venom. Once refined,
these bind to venom toxins and render them inactive or allow
their rapid clearance. Antivenom is available only for certain
venomous animals and cannot reverse all types of envenoming.
With a few exceptions, it should be given intravenously, with
adrenaline (epinephrine) ready in case of anaphylaxis. It should
be used only when clearly indicated, and indications will vary
between venomous animals (Box 8.7). It is critical that the correct
antivenom is used at the appropriate dose. Doses vary widely
between antivenoms. In some situations (such as the Indian
subcontinent), pre-treatment with subcutaneous adrenaline may
reduce the chance of anaphylaxis to antivenom.
Antivenom can sometimes reverse post-synaptic neurotoxic
paralysis (α-bungarotoxin-like neurotoxins) but will not usually
reverse established pre-synaptic paralysis (β-bungarotoxin-like
neurotoxins), so should be given before major paralysis has
occurred (Fig. 8.2). Coagulopathy is best reversed by antivenom,
but even after all venom is neutralised, there may be a delay of
hours before normal coagulation is restored. More antivenom
should not be given because coagulopathy has failed to normalise
fully in the first 1–3 hours (except in very particular circumstances).
Thrombocytopenia may persist for days, despite antivenom. The
role of antivenom in reversing established rhabdomyolysis and
renal failure is uncertain. Antivenom may help limit local tissue
effects or injury in the bitten limb but this is quite variable and
time-dependent. Neuroexcitatory envenoming can respond
very well to antivenom (Australian funnel web spider bites and
Mexican, South American and Indian scorpion stings) but there
is controversy about the effectiveness of antivenom for some
species (some North African and Middle Eastern scorpions).
The role of antivenom in limiting local venom effects, including
necrosis, is also controversial; it is most likely to be effective
when given early.
All patients receiving antivenom are at risk of both early and
late adverse reactions, including anaphylaxis (early; not always
related to immunoglobulin E (IgE)) and serum sickness (late).
Non-antivenom treatments
Anticholinesterases are used as an adjunctive treatment for
post-synaptic paralysis.
Prazosin (an α-adrenoceptor antagonist) is used in the
management of hypertension or pulmonary oedema in scorpion
sting cardiotoxicity, particularly for Indian red scorpion stings,
though antivenom is now the preferred treatment.
8.7 Indications for antivenom
General indications
• Shock/cardiac collapse
• Respiratory compromise
• Rapidly increasing swelling of
the bitten limb
• Active bleeding
• Intractable non-specific
symptoms, including recurrent
vomiting
Specific indications
• Developing paralytic features
(ptosis etc.)
• Developing rhabdomyolysis
• Developing coagulopathy
• Developing renal failure
• Developing neuroexcitatory
envenoming
Copyright © Julian White.
160 • ENVENOMATION
Follow-up
Cases with significant envenomation and those receiving
antivenom should be followed up to ensure any complications
have resolved and to identify any delayed envenoming.
Envenomation by specific animals
Venomous snakes
Venomous snakes represent the single most important cause
of envenomation globally, affecting millions of humans annually
and resulting in large numbers of deaths and patients left with
long-term disability. Of the 3000-plus snake species, more
than 1000 either are venomous or produce oral toxins. The
most important venomous snake families are the Viperidae
(vipers; includes typical vipers (subfamily Viperinae) and pitvipers, with heat-sensing pit organs (subfamily Crotalinae))
and the Elapidae (cobras, kraits, mambas, coral snakes, sea
snakes, Australian snakes). However, there are also dangerous
species among the Atractaspididae (side-fanged burrowing
vipers of Africa and the Middle East) and the non-frontfanged colubrids (NFFC snakes; several families, including the
‘back-fanged’ boomslang and vine snakes of Africa and the
keelbacks of Asia).
A selection of important species is included in Boxes 8.4–8.6.
Clinical features and management
As with other forms of envenoming, the management of snakebite
follows the standard assessment guidelines described previously
(p. 152). The nature of the risks posed will depend on the specific
snake fauna in a given region (p. 153). For example, in the Indian
subcontinent, the major snakebite risks are claimed to come
from the ‘big four’: cobras, kraits, Russell’s viper and saw-scaled
vipers. This list is misleading, though, as it omits other important
snakes, including the hump-nosed vipers, king cobra and green
pit vipers, all of which can cause severe or lethal envenoming
and may not be covered by current Indian antivenoms. Even
for those snakes recognised as causing envenoming, there
may be major geographical variation in venom and features
of envenoming. For Russell’s viper (Daboia spp.), Sri Lankan
specimens can cause rhabdomyolysis and flaccid paralysis, in
addition to classic severe coagulopathy, haemorrhage, local bite
site injury and acute kidney injury (AKI). Indian populations of
the same snake are not associated with either rhabdomyolysis
or paralysis, but in parts of Southern India may cause anterior
pituitary haemorrhage and/or capillary leak syndrome (hypotensive
shock plus vascular leakage resulting in pulmonary oedema).
Capillary leak syndrome is also encountered with populations
of Burmese Russell’s viper (Myanmar), where AKI is especially
common and severe.
Antivenom raised against venom from one population of
these snakes is often poorly effective against bites from snakes
from other regions. Similarly, each of the several species of
saw-scaled vipers (Echis spp.) spread from West Africa across
the Middle East to the Indian subcontinent, including Sri
Lanka, has specific venoms that may not be neutralised by
antivenoms raised against other species in the genus; Indian
antivenoms are ineffective against African species. It follows that,
in managing snakebite envenomation, it is critically important
to choose the appropriate antivenom and to understand that
Antibiotics are not routinely required for most bites/stings,
though a few animals, such as some South American pit vipers
and stingrays, regularly cause significant wound infection or
abscess. Tetanus is a risk in some types of bite or sting, such
as snakebite, but intramuscular toxoid should not be given until
any coagulopathy is reversed.
Mechanical ventilation (p. 202) is vital for established
respiratory paralysis that will not reverse with antivenom and may
be required for prolonged periods (up to several months in
some cases).
Fasciotomy as a treatment for potential compartment syndrome
or severe limb swelling is an overused and often disastrous
surgical intervention in snakebite and is associated with poor
functional outcomes. It should be reserved as a treatment of last
resort and be used only in cases where compartment syndrome
is confirmed by intracompartment pressure measurement and
after first trying limb elevation and antivenom, and ensuring that
any coagulopathy has resolved.
Fig. 8.2 Principal snake venom neurotoxins acting at the
neuromuscular junction (NMJ). The pre-synaptic neurotoxins
(β-bungarotoxin-like) bind to the cell membrane of the terminal axon (1),
form a synaptosome (2) and enter the cell, where they disrupt acetylcholine
(ACh) production (3) and damage intracellular structures, including ion
channels (4). On initial entry, they cause release of excess ACh, followed
by cessation of all ACh release, causing irreversible paralysis until the
cell is repaired (days to weeks later). The post-synaptic neurotoxins
(α-bungarotoxin-like) bind adjacent to the ACh receptor on the external
surface of the muscle end plate and block ACh binding (5), thereby
ceasing neurotransmission. Because this action is external to the cell and
does not cause cell damage, it is potentially a reversible paralysis.
Copyright © Julian White.
Motor
neuron
Acetylcholine
Ca2+
Voltage-gated
calcium
channel
Acetylcholine
receptor
Sodium channels
in clefts amplify
potential change
Depolarisation
of muscle
membrane
β-bungarotoxin
class snake
neurotoxins
Normally,
acetylcholine
packets are
released
following
calcium influx
and cross the
NMJ to
bind to the
ACh receptor
α-bungarotoxin
class snake
neurotoxins
Envenomation by specific animals • 161
Spiders
There are vast numbers and great species diversity of spiders, with
two broad taxonomic groupings: the more ‘primitive’ Mygalomorphs
(several medically important species, especially Australian funnel
web spiders (Atrax, Hadronyche and Illawarra)) and the far more
diverse Araneomorphs (main clinically important species in the
genera Latrodectus (widow spiders), Loxosceles (brown recluse
spiders) and Phoneutria (banana or wandering spiders)).
Clinical features and management
While spiders and spider bites are common, only those genera
noted above commonly cause medically significant effects. In
most cases this is a neuroexcitatory envenoming, sometimes
similar to severe scorpion envenoming (notable from Australian
funnel web spiders), but the recluse spiders cause an often
painless bite that develops into local skin necrosis and sometimes
a systemic illness similar to that caused by the Iranian scorpion,
H. lepturus, and with similar lethal potential.
For most of these spiders, antivenom remains the key treatment
and is life-saving in some cases. Recent studies suggesting
that anti-Latrodectus antivenom is ineffective have not been
confirmed by independent studies and are in contrast to decades
of positive clinical experience.
Paralysis ticks
Most ticks are vectors for disease but a few species in Australia,
North America and parts of Africa can cause flaccid paralysis.
Toxins in the saliva act as potent pre-synaptic neurotoxins that
can cause gradual-onset ascending flaccid paralysis.
There are no antivenoms for tick paralysis. Treatment is based
on removal of all ticks and supportive care, including intubation/
ventilation where required. The paralysis usually resolves by
about 48 hours following removal of all ticks.
Venomous insects
A number of insects are venomous but very few cause significant
envenoming in humans.
Venomous lepidopterans
The Lonomia caterpillars of South America, especially Brazil,
have numerous protective venomous spines that, on contact
with the skin, can discharge a potent procoagulant venom that
can cause a progressive and sometimes fatal consumptive
coagulopathy, with terminal haemorrhagic and/or organ failure
events. Treatment includes use of a Brazilian specific antivenom
and supportive care.
Venomous hymenopterans
Many bees, wasps, hornets and some ants have modified
ovipositors in the abdomen that act as stings, attached to
venom glands. The quantity of venom injected in a single sting
is insufficient to cause significant envenomation, but as many
of these venoms are potently allergenic, it can cause severe
and sometimes fatal anaphylaxis in sensitised persons (p. 75).
Massed stings by hundreds of these insects in a swarm, however,
can cause life-threatening systemic envenoming, often with
intravascular haemolysis, DIC, shock and multi-organ failure.
‘Africanised’ bees are a particular risk for such attacks in South
this may not include every antivenom claiming to cover a
given species.
It is unwise to assume that everything is known about
envenoming by snakes because new clinical information and
syndromes are emerging as more detailed studies are carried
out. For instance, krait bites (Bungarus spp.), long associated
with ‘painless’ bites, later development of devastating flaccid
paralysis and a high mortality rate, are now known to have some
venom diversity. At least some species can cause rhabdomyolysis
and/or severe hyponatraemia, and while bites may be painless,
systemic envenomation can cause severe abdominal pain in at
least some patients. Among cobra bites, the previous division into
‘non-spitting’, neurotoxic species and ‘spitting’, less neurotoxic
species that cause local necrosis is less clear. Non-spitters are
now known to spit in parts of their range (e.g. Naja kaouthia
in West Bengal) and may cause local necrosis in addition to
paralysis. Previously clear diagnostic indicators for envenomation
by particular types of snakes, such as Russell’s vipers and
saw-scaled vipers causing coagulopathy, have also become less
sure, as it is now known that other snakes, such as hump-nosed
vipers (Hypnale spp.) and green pit vipers (Trimeresurus spp.),
found in similar regions, can also cause marked coagulopathy
and yet are often not covered by available antivenoms. The
ability to cause life-threatening coagulopathy, associated with
snakes previously considered harmless, such as the keelbacks
in Asia (Rhabdophis spp.), can further complicate the diagnostic
and management process, as antivenom against these snakes
is currently available only in Japan.
Scorpions
Scorpions are second only to snakes in their venomous impact on
humankind. Most medically important scorpions are in the family
Buthidae and have complex neuroexcitatory venoms with highly
specific ion-channel toxins. Classically, stings by these scorpions
(some key genera listed in Boxes 8.4–8.6) cause moderate to
severe local pain and rapid-onset systemic envenoming with
development of a catecholamine storm-like syndrome as the
toxins target the nervous system. There may be tachycardia or
bradycardia, hyper- or hypotension, profuse sweating, salivation,
cardiac dysfunction and pulmonary oedema. Cardiac collapse
can occur, especially in children. Other clinical features may
vary, depending on the scorpion species.
The Iranian scorpion, Hemiscorpius lepturus (principally southwest Iran), causes a quite different presentation, with an initial
minor sting, followed by progressive development of bite site
or limb necrosis and a potentially lethal systemic envenoming,
characterised by intravascular haemolysis, disseminated
intravascular coagulation (DIC), secondary renal failure and shock.
Clinical features and management
The approach to management varies with species and region.
In Latin America, specific antivenoms are routinely used and
associated with improved outcomes and dramatic falls in mortality
rate. In India, the past reliance on prazosin has been replaced
with use of specific antivenom, again with improved outcomes.
In contrast, in parts of North Africa, past reliance on antivenom
has been replaced with use of cardiac support and arguably
poorer outcomes.
In Iran, H. lepturus stings are treated with antivenom, though
as presentation is often delayed because the sting initially appears
to be minor, the role of late antivenom is unclear.
162 • ENVENOMATION
abdomen or chest are potentially lethal and wounds should be
adequately explored, cleaned and allowed to heal by secondary
intention. For bites by the blue-ringed octopus and stings by
cone snails, rapid-acting venom can cause early cardiovascular
collapse and flaccid paralysis. Supportive care is crucial in
ensuring survival from these potentially lethal and seemingly
trivial local wounds. Sea urchin and venomous starfish wounds
can result in multiple penetrating spines, which cause pain and
act as a nidus for secondary infection, but surgical removal of
spines can be difficult and unrewarding.
Further information
Books and journal articles
Meier J, White J. Handbook of clinical toxicology of animal venoms
and poisons. Boca Raton: CRC Press; 1995.
World Health Organisation, Regional Office for Africa. Guidelines for the
prevention and clinical management of snakebite in Africa; 2010
(afro.who.int).
World Health Organisation, Regional Office for South-East Asia.
Guidelines for the management of snake-bites; 2010 (searo
.who.int).
Websites
toxinology.com Clinical toxinology guide from the University
of Adelaide.
America and now in parts of North America. The giant wasps
and hornets of Asia can similarly cause systemic envenoming
with multiple attacks. Invasive ants, such as Solenopsis spp.,
are colonising new regions and can cause both allergic reactions
and unpleasant local reactions.
Marine venomous and poisonous animals
The marine environment is dominated by animal life, and many
species utilise toxins, either self-produced or taken up from the
environment, to arm themselves for either defence or predation.
Many of these animals can cause adverse effects in humans,
either as a direct venom effect on bites/stings (venomous spiny
fish, sea snakes, stingrays, jellyfish, sea urchins, some starfish,
cone snails, selected octopuses etc.), or through poisoning if
eaten (fugu, ciguatera, scombroid, several types of shellfish
poisoning; p. 149).
For venomous marine animals, there is antivenom available only
for sea snakes, which can cause rhabdomyolysis and/paralytic
neurotoxicity; box jellyfish, which can cause very rapid cardiac
collapse; and stonefish, which cause intense sting-site pain.
In general, marine venoms respond to heat; thus a hot water
immersion or shower (about 45°C) is effective at reducing local
pain, particularly for jellyfish, stinging fish and stingray stings. For
stingray stings, the venom may cause local tissue damage both
through sting trauma and a venom effect; wounds penetrating the

03-9 Environmental medicine
9 Environmental medicine
Environmental medicine
M Byers
Radiation exposure 164
Extremes of temperature 165
High altitude 168
Under water 169
Humanitarian crisis 171
164 • ENVIRONMENTAL MEDICINE
representing 1 J/kg. To take account of different types of radiation
and variations in the sensitivity of various tissues, weighting
factors are used to produce a unit of effective dose, measured
in sieverts (Sv). This value reflects the absorbed dose weighted
for the damaging effects of a particular form of radiation and is
most valuable in evaluating the long-term effects of exposure.
‘Background radiation’ refers to our exposure to naturally
occurring radioactivity (e.g. radon gas and cosmic radiation). This
produces an average annual individual dose of approximately
2.6 mSv per year, although this figure varies according to local
geology.
Effects of radiation exposure
Effects on the individual are classified as either deterministic
or stochastic.
Deterministic effects
Deterministic (threshold) effects occur with increasing severity as
the dose of radiation rises above a threshold level. Tissues with
actively dividing cells, such as bone marrow and gastrointestinal
mucosa, are particularly sensitive to ionising radiation. Lymphocyte
depletion is the most sensitive marker of bone marrow injury, and
after exposure to a fatal dose, marrow aplasia is a common cause
of death. However, gastrointestinal mucosal toxicity may cause
earlier death due to profound diarrhoea, vomiting, dehydration
and sepsis. The gonads are highly radiosensitive and radiation
may result in temporary or permanent sterility. Eye exposure can
lead to cataracts and the skin is susceptible to radiation burns.
Irradiation of the lung may induce acute inflammatory reactions or
pulmonary fibrosis, and irradiation of the central nervous system
may cause permanent neurological deficit. Bone necrosis and
lymphatic fibrosis are characteristic following regional irradiation,
particularly for breast cancer. The thyroid gland is not inherently
sensitive but its ability to concentrate iodine makes it susceptible
to damage after exposure to relatively low doses of radioactive
iodine isotopes, such as those released from Chernobyl.
Stochastic effects
Stochastic (chance) effects occur with increasing probability as
the dose of radiation increases. Carcinogenesis represents a
stochastic effect. With acute exposures, leukaemias may arise
after an interval of around 2–5 years and solid tumours after an
Environmental medicine deals with the interactions between
the environment and human health. While previously concerned
mainly with controlling infectious diseases, the focus at present
is predominantly on the multiple physical, chemical, biological
and social factors that pose risks to human health. As the
environment continually alters, whether through population
growth, economic development or climate change, it plays an
important role in disease causation – one that may increase
over time. This chapter deals principally with acute effects of
environmental hazards on individuals and should be read in
conjunction with the chapters on Poisoning (Ch. 7) and Acute
Medicine and Critical Illness (Ch. 10). Chapter 5 deals with more
general effects of environmental factors on population health.
Radiation exposure
Radiation includes ionising (Fig. 9.1) and non-ionising radiations
(ultraviolet (UV), visible light, laser, infrared and microwave).
While global industrialisation and the generation of fluorocarbons
have raised concerns about loss of the ozone layer, leading to
an increased exposure to UV rays, and disasters such as the
Chernobyl and Fukushima nuclear power station explosions
have demonstrated the harm of ionising radiation, it is important
to remember that it can be harnessed for medical benefit.
Ionising radiation is used in X-rays, computed tomography (CT),
radionuclide scans and radiotherapy, and non-ionising UV for
therapy in skin diseases and laser therapy for diabetic retinopathy.
Types of ionising radiation
These include charged subatomic alpha and beta particles,
uncharged neutrons or high-energy electromagnetic radiations
such as X-rays and gamma rays. When they interact with
atoms, energy is released and the resulting ionisation can lead
to molecular damage. The clinical effects of different forms of
radiation depend on their range in air and tissue penetration
(Fig. 9.1).
Dosage and exposure
The dose of radiation is based on the energy absorbed by a
unit mass of tissue and is measured in grays (Gy), with 1 Gy
Fig. 9.1 Properties of different ionising radiations.
Paper
Range in air
Range in tissue
Few centimetres
No penetration
Few metres
Few millimetres
Kilometres
Passes through
Kilometres
Passes through
Alpha particles
e.g. radium,
uranium
Beta particles
e.g. 14carbon,
90strontium
X-rays/gamma rays
e.g. 131iodine,
99mtechnetium
Neutrons
Aluminium foil
Lead/concrete
Protection
Extremes of temperature • 165
In a cold environment, protective mechanisms include
cutaneous vasoconstriction and shivering; however, any muscle
activity that involves movement may promote heat loss by
increasing convective loss from the skin, and respiratory heat
loss by stimulating ventilation. In a hot environment, sweating
is the main mechanism for increasing heat loss. This usually
occurs when the ambient temperature rises above 32.5°C or
during exercise.
Hypothermia
Hypothermia exists when the body’s normal thermal regulatory
mechanisms are unable to maintain heat in a cold environment
and core temperature falls below 35°C (Fig. 9.2). Moderate
hypothermia occurs below 32°C and severe hypothermia
below 28°C. Other systems define hypothermia on the basis
of symptoms rather than absolute temperature.
While infants are susceptible to hypothermia because of
their poor thermoregulation and high body surface area to
weight ratio, it is the elderly who are at highest risk (Box 9.2).
Hypothyroidism is often a contributory factor in old age, while
interval of about 10–20 years. Thereafter the incidence rises with
time. An individual’s risk of developing cancer depends on the
dose received, the time to accumulate the total dose and the
interval following exposure.
Management of radiation exposure
Exposed people should be removed from ongoing exposure
(‘get inside, stay inside’), and should take off affected clothing
and shower to stop further contamination. If contamination
of food and water supplies may have occurred, only bottled
water and food in sealed containers should be consumed. The
principal problems after large-dose exposures are maintenance
of adequate hydration, control of sepsis and management of
marrow aplasia. Associated injuries such as thermal burns need
specialist management within 48 hours of active resuscitation.
Internal exposure to radioisotopes should be treated with chelating
agents (such as Prussian blue used to chelate 137caesium after
ingestion). White-cell colony stimulation and haematopoietic stem
cell transplantation may need to be considered for marrow aplasia.
Extremes of temperature
Thermoregulation
Body heat is generated by basal metabolic activity and muscle
movement, and lost by conduction (which is more effective
in water than in air), convection, evaporation and radiation
(most important at lower temperatures when other mechanisms
conserve heat) (Box 9.1). Body temperature is controlled in the
hypothalamus, which is directly sensitive to changes in core
temperature and indirectly responds to temperature-sensitive
neurons in the skin. The normal ‘set-point’ of core temperature is
tightly regulated within the range 37 ± 0.5°C, which is necessary
to preserve the normal function of many enzymes and other
metabolic processes. The temperature set-point is increased
in response to infection (p. 218).
Fig. 9.2 Clinical features of abnormal core temperature. The
hypothalamus normally maintains core temperature at 37°C, but this
set-point is altered in, for example, fever (pyrexia, p. 218), and may be lost
in hypothalamic disease (p. 679). In these circumstances, the clinical
picture at a given core temperature may be different.
<37
<35
<32
<28
°C
Definitions
Clinical features
Heat
stroke
Heat
exhaustion
Mild
hypothermia
Severe
hypothermia
Hot and not sweating
Multiple organ failure, confusion,
aggression, shock
Hot and sweating
Headache, weakness, fatigue,
irritability, tachycardia, dehydration
Tachycardia, vasoconstriction
Cold and not shivering
Cold, pale skin
Depressed consciousness
Muscle stiffness
Bradycardia and hypotension
Coma
Dilated, unreactive pupils
Cardiac standstill
Cold and shivering
‘Mumble, stumble, tumble’
Lethargy
Dehydration
Tachypnoea
Moderate
hypothermia
Violent shivering
Slurred speech
Slow, laboured movements
Ataxia, mild confusion
Pale with blue lips
9.1 Thermoregulation: responses to hot and cold
environments
Mechanism
Hot
environment
Cold environment
Heat
production
Basal
metabolic
rate
→
↓ in hypothermia
Muscle
activity
↓ by lethargy
↑ by shivering
↓ in severe
hypothermia
Heat loss
Conduction*
↑ by
vasodilatation
↓ by vasoconstriction
↑↑ in water < 31°C
Convection*
↑ by
vasodilatation
↓ by lethargy
↓ by vasoconstriction
↑ by wind and
movement
Evaporation*
↑↑ by
sweating
↓ by high
humidity
↑ by hyperventilation
Radiation
↑ by
vasodilatation
↓ by vasoconstriction
(but is the major heat
loss in dry cold)
*These losses are dependent on the relative ambient and skin temperatures.
166 • ENVIRONMENTAL MEDICINE
aminotransferase and creatine kinase may be elevated secondary
to muscle damage and the serum amylase is often high due
to subclinical pancreatitis. If the cause of hypothermia is not
obvious, additional investigations for thyroid and pituitary–adrenal
dysfunction (p. 633), hypoglycaemia (p. 725) and the possibility
of drug intoxication (p. 134) should be performed.
Management
Following resuscitation, the objectives of management are
to rewarm the patient in a controlled manner while treating
associated hypoxia (by oxygenation and ventilation if necessary),
fluid and electrolyte disturbance, and cardiovascular abnormalities,
particularly arrhythmias. Careful handling is essential to avoid
precipitating the latter. The method of rewarming is dependent not
on the absolute core temperature, but on haemodynamic stability
and the presence or absence of an effective cardiac output.
Mild hypothermia
Outdoors, continued heat loss is prevented by sheltering the
patient from the cold, replacing wet clothing, covering the head
and insulating him or her from the ground. Once in hospital,
even in the presence of profound hypothermia, if there is an
effective cardiac output then forced-air rewarming, heat packs
placed in axillae and groins and around the abdomen, inhaled
warmed air and correction of fluid and electrolyte disturbances
are usually sufficient. Rewarming rates of 1–2°C per hour are
effective in leading to a gradual and safe return to physiological
normality. Underlying conditions should be treated promptly
(e.g. hypothyroidism with triiodothyronine 10 μg IV 3 times
daily; p. 640).
Severe hypothermia
In the case of severe hypothermia (< 28°C), patients with
cardiopulmonary arrest (non-perfusing rhythm), or those with
cardiac instability (systolic blood pressure < 90 mmHg or
ventricular arrhythmias), the aim is to restore perfusion, and
rapid rewarming at a rate of > 2°C per hour is required. This
is best achieved by cardiopulmonary bypass or extracorporeal
membrane oxygenation (ECMO). If these are unavailable, then
veno–veno haemofiltration, and pleural, peritoneal, thoracic or
bladder lavage with warmed fluids are alternatives. Direct heat
sources, such as hot water or heat pads, should be used with
caution, as these can provoke cardiac arrhythmias or cause
burns. Monitoring of cardiac rhythm and arterial blood gases,
including H+ (pH), is essential. Significant acidosis may require
correction (p. 364).
Cold injury
Freezing cold injury (frostbite)
This represents the direct freezing of body tissues and usually
affects the extremities: in particular, the fingers, toes, ears and
face. Risk factors include smoking, peripheral vascular disease,
dehydration and alcohol consumption. The tissues may become
anaesthetised before freezing and, as a result, the injury often
goes unrecognised at first. Frostbitten tissue is initially pale and
doughy to the touch and insensitive to pain (Fig. 9.4). Once
frozen, the tissue is hard.
Rewarming should not occur until it can be achieved rapidly
in a water bath. Give oxygen and aspirin 300 mg as soon as
possible. Frostbitten extremities should be rewarmed in warm
water at 37–39°C, with antiseptic added. Adequate analgesia
is necessary, as rewarming is very painful. Vasodilators such as
alcohol and other drugs (e.g. phenothiazines) commonly impede
the thermoregulatory response in younger people. More rarely,
hypothermia is secondary to hypothyroidism, glucocorticoid
insufficiency, stroke, hepatic failure or hypoglycaemia.
Hypothermia also occurs in healthy individuals whose
thermoregulatory mechanisms are intact but insufficient to
cope with the intensity of the thermal stress. Typical examples
include immersion in cold water, when core temperature may fall
rapidly (acute hypothermia), exposure to extreme climates such
as during hill walking (subacute hypothermia), and slow-onset
hypothermia, as develops in an immobilised older individual
(subchronic hypothermia). This classification is important, as it
determines the method of rewarming.
Clinical features
Diagnosis is dependent on recognition of the environmental
circumstances and measurement of core (rectal) body temperature.
Clinical features depend on the degree of hypothermia (Fig. 9.2).
In a cold patient, it is very difficult to diagnose death reliably
by clinical means. It has been suggested that, in extreme
environmental conditions, irreversible hypothermia is probably
present if there is asystole (no carotid pulse for 1 min), the
chest and abdomen are rigid, the core temperature is < 13°C
and serum potassium is > 12 mmol/L. However, in general,
resuscitative measures should continue until the core temperature
is normal and only then should a diagnosis of brain death be
considered (p. 211).
Investigations
Blood gases, a full blood count, electrolytes, chest X-ray
and electrocardiogram (ECG) are all essential investigations.
Haemoconcentration and metabolic acidosis are common,
and the ECG may show characteristic J waves, which occur
at the junction of the QRS complex and the ST segment (Fig.
9.3). Cardiac arrhythmias, including ventricular fibrillation, may
occur. Although the arterial oxygen tension may be normal when
measured at room temperature, the arterial PO2 in the blood falls
by 7% for each 1°C fall in core temperature. Serum aspartate
Fig. 9.3 Electrocardiogram showing J waves (arrows) in a
hypothermic patient.
9.2 Thermoregulation in old age
• Age-associated changes: impairments in vasomotor function,
skeletal muscle response and sweating mean that older people
react more slowly to changes in temperature.
• Increased comorbidity: thermoregulatory problems are more likely
in the presence of pathology such as atherosclerosis and
hypothyroidism, and medication such as sedatives and hypnotics.
• Hypothermia: this may arise as a primary event, but more
commonly complicates other acute illness, e.g. pneumonia, stroke
or fracture.
• Ambient temperature: financial pressures and older equipment
may result in inadequate heating during cold weather.
Extremes of temperature • 167
large extent by adequate replacement of salt and water, although
excessive water intake alone should be avoided because of the
risk of dilutional hyponatraemia (p. 357).
A spectrum of illnesses occurs in the heat (see Fig. 9.2). The
cause is usually obvious but the differential diagnosis should be
considered (Box 9.3).
Heat cramps
These painful muscle contractions occur following vigorous
exercise and profuse sweating in hot weather. There is no
elevation of core temperature. The mechanism is considered
to be extracellular sodium depletion as a result of persistent
sweating, exacerbated by replacement of water but not salt.
Symptoms usually respond rapidly to rehydration with oral
rehydration salts or intravenous saline.
Heat syncope
This is similar to a vasovagal faint (p. 181) and is related to
peripheral vasodilatation in hot weather.
Heat exhaustion
Heat exhaustion occurs with prolonged exertion in hot and
humid weather, profuse sweating and inadequate salt and water
replacement. There is an elevation in core (rectal) temperature
to between 37°C and 40°C, leading to the clinical features
shown in Figure 9.2. Blood analyses may show evidence of
dehydration with mild elevation of the blood urea, sodium and
haematocrit. Treatment involves removal of the patient from
the heat, and active evaporative cooling using tepid sprays and
fanning (‘strip–spray–fan’). Fluid losses are replaced with either
oral rehydration mixtures or intravenous isotonic saline. Up to
5 L positive fluid balance may be required in the first 24 hours.
Untreated, heat exhaustion may progress to heat stroke.
Heat stroke
Heat stroke occurs when the core body temperature rises
above 40°C and is a life-threatening condition. The symptoms
of heat exhaustion progress to include headache, nausea and
vomiting. Neurological manifestations include a coarse muscle
tremor and confusion, aggression or loss of consciousness. The
patient’s skin feels very hot, and sweating is often absent due to
failure of thermoregulatory mechanisms. Complications include
hypovolaemic shock, lactic acidosis, disseminated intravascular
coagulation, rhabdomyolysis, hepatic and renal failure, and
pulmonary and cerebral oedema.
Duration of hyperthermia is key to the outcome and immediate
cooling should begin at the scene, before transfer to hospital.
The aim should be to reduce core temperature by > 0.2°C per
minute to approximately 39°C, while avoiding overshooting and
hypothermia. The patient should be resuscitated with evaporative or
convective cooling. Fluid resuscitation with crystalloid intravenous
fluids should be instituted but solutions containing potassium
pentoxifylline (a phosphodiesterase inhibitor) have been shown
to improve tissue survival. Once it has thawed, the injured part
must not be re-exposed to the cold, and should be dressed and
rested. While wound débridement may be necessary, amputations
should be delayed for 60–90 days, as good recovery may occur
over an extended period. As yet, the role of hyperbaric oxygen
in the treatment of frostbite requires further research.
Non-freezing cold injury (trench or immersion foot)
This results from prolonged exposure to cold, damp conditions.
The limb (usually the foot) appears cold, ischaemic and numb,
but there is no freezing of the tissue. On rewarming, the limb
appears mottled and thereafter becomes hyperaemic, swollen
and painful. Recovery may take many months, during which
period there may be chronic pain and sensitivity to cold. The
pathology remains uncertain but probably involves endothelial
injury. Gradual rewarming is associated with less pain than
rapid rewarming. The pain and associated paraesthesia are
difficult to control with conventional analgesia and may require
amitriptyline (50 mg nocte), best instituted early. The patient is
at risk of further damage on subsequent exposure to the cold.
Chilblains
Chilblains are tender, red or purplish skin lesions that occur in
the cold and wet. They are often seen in horse riders, cyclists
and swimmers, and are more common in women than men.
They are short-lived and, although painful, not usually serious.
Heat-related illness
When generation of heat exceeds the body’s capacity for heat
loss, core temperature rises. Non-exertional heat illness (NEHI)
occurs with a high environmental temperature in those with
attenuated thermoregulatory control mechanisms: the elderly,
the young, those with comorbidity or those taking drugs that
affect thermoregulation (particularly phenothiazines, diuretics and
alcohol). Exertional heat illness (EHI), on the other hand, typically
develops in athletes when heat production exceeds the body’s
ability to dissipate it.
Acclimatisation mechanisms to environmental heat include
stimulation of the sweat mechanism with increased sweat volume,
reduced sweat sodium content and secondary hyperaldosteronism
to maintain body sodium balance. The risk of heat-related illness
falls as acclimatisation occurs. Heat illness can be prevented to a
Fig. 9.4 Frostbite in a female Everest sherpa.
9.3 Differential diagnosis in patients with elevated
core body temperature
• Heat illness (heat exhaustion, heat stroke)
• Sepsis, including meningitis
• Malaria
• Drug overdose
• Serotonin syndrome (pp. 139 and 1199)
• Malignant hyperpyrexia
• Thyroid storm (p. 639)
168 • ENVIRONMENTAL MEDICINE
on the shape of the sigmoid oxygen–haemoglobin dissociation
curve (see Fig. 23.5, p. 917) and the ventilatory response.
Acclimatisation to hypoxaemia at high altitude involves a shift
in this dissociation curve (dependent on 2,3-diphosphoglycerate
(2,3-DPG)), erythropoiesis, haemoconcentration, and hyperventilation resulting from hypoxic drive, which is then sustained despite
hypocapnia by restoration of cerebrospinal fluid pH to normal in
prolonged hypoxia. This process takes several days, so travellers
need to plan accordingly.
Illnesses at high altitude
Ascent to altitudes up to 2500 m or travel in a pressurised
aircraft cabin is harmless to healthy people. Above 2500 m
high-altitude illnesses may occur in previously healthy people,
and above 3500 m these become common. Sudden ascent to
altitudes above 6000 m, as experienced by aviators, balloonists
and astronauts, may result in decompression illness with the
same clinical features as seen in divers (see below), or even
loss of consciousness. However, most altitude illness occurs
in travellers and mountaineers.
Acute mountain sickness
Acute mountain sickness (AMS) is a syndrome comprised
principally of headache, together with fatigue, anorexia, nausea
and vomiting, difficulty sleeping or dizziness. Ataxia and peripheral
oedema may be present. The aetiology of AMS is not fully
understood but it is thought that hypoxaemia increases cerebral
blood flow and hence intracranial pressure. Symptoms occur
within 6–12 hours of an ascent and vary in severity from trivial to
completely incapacitating. The incidence in travellers to 3000 m
may be 40–50%, depending on the rate of ascent.
Treatment of mild cases consists of rest and simple analgesia;
symptoms usually resolve after 1–3 days at a stable altitude,
but may recur with further ascent. Occasionally, there is
progression to cerebral oedema. Persistent symptoms indicate
the need to descend but may respond to acetazolamide, a
carbonic anhydrase inhibitor that induces a metabolic acidosis
and stimulates ventilation; acetazolamide may also be used as
prophylaxis if a rapid ascent is planned.
High-altitude cerebral oedema
The cardinal symptoms of high-altitude cerebral oedema
(HACE) are ataxia and altered consciousness. HACE is rare,
life-threatening and usually preceded by AMS. In addition to
features of AMS, the patient suffers confusion, disorientation,
visual disturbance, lethargy and ultimately loss of consciousness.
Papilloedema and retinal haemorrhages are common and focal
neurological signs may be found.
Treatment is directed at improving oxygenation. Descent is
essential and dexamethasone (8 mg immediately and 4 mg 4
times daily) should be given. If descent is impossible, oxygen
therapy in a portable pressurised bag may be helpful.
High-altitude pulmonary oedema
High-altitude pulmonary oedema (HAPE) is a life-threatening
condition that usually occurs in the first 4 days after ascent
above 2500 m. Unlike HACE, HAPE may occur de novo without
the preceding signs of AMS. Presentation is with symptoms
of dry cough, exertional dyspnoea and extreme fatigue. Later,
the cough becomes wet and sputum may be blood-stained.
Tachycardia and tachypnoea occur at rest and crepitations
may often be heard in both lung fields. There may be profound
hypoxaemia, pulmonary hypertension and radiological evidence
should be avoided. Intravenous dextrose may be necessary,
as hypoglycaemia can occur. Appropriate monitoring of fluid
balance, including central venous pressure, is important, as overaggressive fluid replacement may precipitate pulmonary oedema
or further metabolic disturbance. Investigations for complications
include routine haematology and biochemistry, coagulation
screen, hepatic transaminases (aspartate aminotransferase and
alanine aminotransferase), creatine kinase and chest X-ray. Once
emergency treatment is established, heat stroke patients are
best managed in intensive care.
Heat stroke is an emergency with a significant mortality.
However, where temperatures can be reduced to < 40°C within
30 minutes of collapse, death rates can approach zero. Patients
who have had core temperatures of > 40°C should be monitored
carefully for later onset of rhabdomyolysis, renal damage and
other complications before discharge from hospital. Clear advice
to avoid heat and heavy exercise during recovery is important.
High altitude
The physiological effects of high altitude are significant. On
Everest, the barometric pressure of the atmosphere falls from
sea level by approximately 50% at base camp (5400 m) and
approximately 70% at the summit (8848 m). The proportions of
oxygen, nitrogen and carbon dioxide in air do not change with
the fall in pressure but their partial pressure falls in proportion
to barometric pressure (Fig. 9.5). Oxygen tension within the
pulmonary alveoli is further reduced at altitude because the
partial pressure of water vapour is related to body temperature
and not barometric pressure, and so is proportionately greater
at altitude, accounting for only 6% of barometric pressure at
sea level but 19% at 8848 m.
Physiological effects of high altitude
Reduction in oxygen tension results in a fall in arterial oxygen saturation (Fig. 9.5). This varies widely between individuals, depending
Fig. 9.5 Change in inspired oxygen tension and blood oxygen
saturation at altitude. The blue curve shows changes in oxygen
availability at altitude and the red curve shows the typical resultant
changes in arterial oxygen saturation in a healthy person. Oxygen
saturation varies between individuals according to the shape of the
oxygen–haemoglobin dissociation curve and the ventilatory response to
hypoxaemia. (To convert kPa to mmHg, multiply by 7.5.)
Summit
of Everest
(8848 m)
Highest
permanent
habitation
(< 5200 m)
Arterial
oxygen
saturation
Partial
pressure of
inspired oxygen
Partial pressure of oxygen (kPa)
Pressurised
aircraft cabin
(< 2400 m)
Arterial oxygen saturation (%)
Altitude above sea level (m)
Under water • 169
arrhythmia, sickle-cell disease and ischaemic heart disease. Most
airlines decline to carry pregnant women after the 36th week
of gestation. In complicated pregnancies it may be advisable
to avoid air travel at an earlier stage. Patients who have had
recent abdominal surgery, including laparoscopy, should avoid
flying until all intraperitoneal gas is reabsorbed. Divers should
not fly for 24 hours after a dive requiring decompression stops.
Ear and sinus pain due to changes in gas volume are common
but usually mild, although patients with chronic sinusitis and
otitis media may need specialist assessment. A healthy mobile
tympanic membrane visualised during a Valsalva manœuvre
usually suggests a patent Eustachian tube.
On long-haul flights, patients with diabetes mellitus may need
to adjust their insulin or oral hypoglycaemic dosing according to
the timing of in-flight and subsequent meals (p. 750). Advice is
available from Diabetes UK and other websites. Patients should
be able to provide documentary evidence of the need to carry
needles and insulin.
Deep venous thrombosis
Air travellers have an increased risk of venous thrombosis
(p. 975), due to a combination of factors, including loss of venous
emptying because of prolonged immobilisation (lack of muscular
activity) and reduced barometric pressure on the tissues, together
with haemoconcentration as a result of oedema and perhaps a
degree of hypoxia-induced diuresis.
Venous thrombosis can probably be prevented by avoiding
dehydration and excess alcohol, and by exercising muscles during
the flight. Without a clear cost–benefit analysis, prophylaxis with
aspirin or heparin cannot be recommended routinely, but may
be considered in high-risk cases.
Under water
Drowning and near-drowning
Drowning is defined as death due to asphyxiation following
immersion in a fluid, while near-drowning is defined as survival
for longer than 24 hours after suffocation by immersion. Drowning
remains a common cause of accidental death throughout the
world and is particularly common in young children (Box 9.4). In
about 10% of cases, no water enters the lungs and death follows
intense laryngospasm (‘dry’ drowning). Prolonged immersion in
cold water, with or without water inhalation, results in a rapid fall
in core body temperature and hypothermia (p. 165).
Following inhalation of water, there is a rapid onset of ventilation–
perfusion imbalance with hypoxaemia, and the development
of diffuse alveolar oedema. It is not known whether the alveolar
oedema is a result of mechanical stress on the pulmonary
capillaries associated with the high pulmonary arterial pressure,
or an effect of hypoxia on capillary permeability. Reduced arterial
oxygen saturation is not diagnostic but is a marker for disease
progression.
Treatment is directed at reversal of hypoxia with immediate
descent and oxygen administration. Nifedipine (20 mg 4 times
daily) should be given to reduce pulmonary arterial pressure,
and oxygen therapy in a portable pressurised bag should be
used if descent is delayed.
Chronic mountain sickness (Monge’s disease)
This occurs on prolonged exposure to altitude and has been
reported in residents of Colorado, South America and Tibet.
Patients present with headache, poor concentration and other
signs of polycythaemia. The haemoglobin concentration is high
(> 200 g/L) and the haematocrit raised (> 65%). Affected individuals
are cyanosed and often have finger clubbing.
High-altitude retinal haemorrhage
This occurs in over 30% of trekkers at 5000 m. The haemorrhages
are usually asymptomatic and resolve spontaneously. Visual
defects can occur with haemorrhage involving the macula but
there is no specific treatment.
Venous thrombosis
This has been reported at altitudes of > 6000 m. Risk factors
include dehydration, inactivity and the cold. The use of the oral
contraceptive pill at high altitude should be considered carefully,
as this is an additional risk factor.
Refractory cough
A cough at high altitude is common and usually benign. It may be
due to breathing dry, cold air and to increased mouth breathing,
with consequent dry oral mucosa. This may be indistinguishable
from the early signs of HAPE.
Air travel
Commercial aircraft usually cruise at 10 000–12 000 m, with the
cabin pressurised to an equivalent of around 2400 m. At this
altitude, the partial pressure of oxygen is 16 kPa (120 mmHg),
leading to a PaO2 in healthy people of 7.0–8.5 kPa (53–64 mmHg).
Oxygen saturation is also reduced but to a lesser degree (see
Fig. 9.5). Although well tolerated by healthy people, this degree
of hypoxia may be dangerous in patients with respiratory disease.
Advice for patients with respiratory disease
The British Thoracic Society has published guidance on the
management of patients with respiratory disease who want to
fly. Specialist pre-flight assessment is advised for all patients
who have hypoxaemia (oxygen saturation < 95%) at sea level,
and includes spirometry and a hypoxic challenge test with 15%
oxygen (performed in hospital). Air travel may have to be avoided
or undertaken only with inspired oxygen therapy during the flight.
Asthmatic patients should be advised to carry their inhalers in
their hand baggage. Following pneumothorax, flying should
be avoided while air remains in the pleural cavity, but can be
considered after proven resolution or definitive (surgical) treatment.
Advice for other patients
Other circumstances in which patients are more susceptible to
hypoxia require individual assessment. These include cardiac
9.4 Most common causes of drowning by age
Infants/young children
• Domestic baths
• Garden pools
Adolescents
• Swimming pools
• Rivers, sea, etc.
Adults
• Water sports, boating, fishing
• Occupational
Older people
• Domestic baths
170 • ENVIRONMENTAL MEDICINE
Diving-related illness
The underwater environment is extremely hostile. Other than
drowning, most diving illness is related to changes in barometric
pressure and its effect on gas behaviour.
Ambient pressure under water increases by 101 kPa
(1 atmosphere, 1 ata) for every 10 metres of seawater (msw)
or 33 eet of seawater (fsw) depth. As divers descend, the partial
pressures of the gases they are breathing increase (Box 9.5),
and the blood and tissue concentrations of dissolved gases rise
accordingly. Nitrogen is a weak anaesthetic agent, and if the
inspiratory pressure of nitrogen is allowed to increase above
320 kPa (3.2 ata; i.e. a depth of approximately 30 msw), it
produces ‘narcosis’, resulting in impairment of cognitive function
and manual dexterity, not unlike alcohol intoxication. For this
reason, compressed air can be used only for shallow diving.
Oxygen is also toxic at inspired pressures above approximately
40 kPa (0.4 ata; inducing apprehension, muscle twitching,
euphoria, sweating, tinnitus, nausea and vertigo), so 100%
oxygen cannot be used as an alternative. For dives deeper than
approximately 30 msw, mixtures of oxygen with nitrogen and/
or helium are used.
While drowning remains the most common diving-related
cause of death, another important group of disorders usually
present once the diver returns to the surface: decompression
illness (DCI) and barotrauma.
Clinical features
Decompression illness
This includes decompression sickness (DCS) and arterial gas
embolism (AGE). While the vast majority of symptoms of DCI
present within 6 hours of a dive, they can also be provoked by
flying (further decompression), and thus patients may present to
medical services at sites far removed from the dive.
Exposure of individuals to increased partial pressures of
nitrogen results in additional nitrogen being dissolved in body
tissues; the amount dissolved depends on the depth/pressure
and on the duration of the dive. On ascent, the tissues become
supersaturated with nitrogen, and this places the diver at risk
of producing a critical quantity of gas (bubbles) in tissues if the
ascent is too fast. The gas so formed may cause symptoms
locally, peripherally due to bubbles passing through the pulmonary
vascular bed (Box 9.6) or by embolisation elsewhere. Arterial
embolisation may occur if the gas load in the venous system
exceeds the lungs’ abilities to excrete nitrogen, or when bubbles
pass through a patent foramen ovale (present asymptomatically
of diffuse pulmonary oedema. Fresh water is hypotonic and,
although rapidly absorbed across alveolar membranes, impairs
surfactant function, which leads to alveolar collapse and rightto-left shunting of unoxygenated blood. Absorption of large
amounts of hypotonic fluid can result in haemolysis. Salt water
is hypertonic and inhalation provokes alveolar oedema, but the
overall clinical effect is similar to that of freshwater drowning.
Clinical features
Those rescued alive (near-drowning) are often unconscious and
not breathing. Hypoxaemia and metabolic acidosis are inevitable
features. Acute lung injury usually resolves rapidly over 48–
72 hours, unless infection occurs (Fig. 9.6). Complications include
dehydration, hypotension, haemoptysis, rhabdomyolysis, renal
failure and cardiac arrhythmias. A small number of patients, mainly
the more severely ill, progress to develop the acute respiratory
distress syndrome (ARDS; p. 198).
Survival is possible after immersion for up to 30 minutes
in very cold water, as the rapid development of hypothermia
after immersion may be protective, particularly in children.
Long-term outcome depends on the severity of the cerebral
hypoxic injury and is predicted by the duration of immersion,
delay in resuscitation, intensity of acidosis and the presence of
cardiac arrest.
Management
Initial management requires cardiopulmonary resuscitation with
administration of oxygen and maintenance of the circulation
(p. 456). It is important to clear the airway of foreign bodies
and protect the cervical spine. Continuous positive airways
pressure (CPAP; p. 202) should be considered for spontaneously
breathing patients with oxygen saturations of < 94%. Observation
is required for a minimum of 24 hours. Prophylactic antibiotics are
only required if exposure was to obviously contaminated water.
Fig. 9.6 Near-drowning. Chest X-ray of a 39-year-old farmer, 2 weeks
after immersion in a polluted freshwater ditch for 5 min before rescue.
Airspace consolidation and cavities in the left lower lobe reflect secondary
staphylococcal pneumonia and abscess formation.
9.5 Physics of breathing compressed air while diving
in sea water
Depth
Lung
volume
Barometric
pressure
PiO2
PiN2
Surface
100%
101 kPa
(1 ata)
21 kPa
(0.21 ata)
79 kPa
(0.78 ata)
10 m
50%
202 kPa
(2 ata)
42 kPa
(0.42 ata)
159 kPa
(1.58 ata)
20 m
33%
303 kPa
(3 ata)
63 kPa
(0.63 ata)
239 kPa
(2.34 ata)
30 m
25%
404 kPa
(4 ata)
84 kPa
(0.84 ata)
319 kPa
(3.12 ata)
Humanitarian crisis • 171
The majority of patients make a complete recovery with
treatment, although a small but significant proportion are left
with neurological disability.
Humanitarian crisis
Humanitarian crises are common. If the medical profession is
to help, it must understand that the emergency treatment of a
few sick and injured people is not always the priority and that
there is a set of basic needs that must be addressed in order
to do the most for the most.
A humanitarian crisis can take many forms: an environmental
disaster, mass emigration due to drought, conflict or famine, a
disease outbreak or any number of natural or man-made events.
When this event overwhelms the resources of the affected
country’s government, then the international community will
often step in to help. Although a full examination of the subject is
beyond the scope of this book, there are a few basic principles
for managing a humanitarian crisis.
The response is broken down into four phases:
recognition (first week)
emergency response (first month)
consolidation phase (to crisis resolution or crisis
containment)
handover and withdrawal.
Recognition
Recognition of a disaster may be obvious in a sudden event
such as an earthquake or a tidal wave, but less obvious in a
disease outbreak or when it stems from internal conflict. The
recognition phase is for the host nation rather than the international
community, and requests for support will come from the affected
country’s government.
Emergency response
During the emergency phase, responders (whether international,
governmental or the charity sector) will undertake an initial
assessment of need, set objectives, mobilise resources, coordinate
with other agencies and deploy to the crisis in order to deliver
an initial response.
Consolidation phase
The consolidation phase involves matching resources to need,
dealing with the crisis, building resilience, supporting infrastructure
(human and physical) and instituting systems to manage the
ongoing health needs of the population.
Handover and withdrawal
Once the crisis is under control and the country is able to manage
within resources, a phased withdrawal can occur.
Health-care priorities
When the normal infrastructure of a country or area fails, then
populations are at risk, whether they shelter in place or flee,
leading to mass migration. For health-care teams, rather than
logisticians, rescue teams or security forces, there are welldefined priorities, which must be in place (Box 9.7). This must
all occur during the emergency phase and is followed by the
in 25–30% of adults; p. 531). Although DCS and AGE can be
indistinguishable, their early treatment is the same.
Barotrauma
During the ascent phase of a dive, the gas in the diver’s lungs
expands due to the decreasing pressure. The diver must
therefore ascend slowly and breathe regularly; if ascent is
rapid or the diver holds his/her breath, the expanding gas may
cause lung rupture (pulmonary barotrauma). This can result in
pneumomediastinum, pneumothorax or AGE as a result of gas
passing directly into the pulmonary venous system. Other air-filled
body cavities may be subject to barotrauma, including the ear and
sinuses.
Management
The patient is nursed horizontally and airway, breathing and
circulation are assessed. Treatment includes the following:
• High-flow oxygen is given by a tight-fitting mask using a
rebreathing bag. This assists in the washout of excess
inert gas (nitrogen) and may reduce the extent of local
tissue hypoxia resulting from focal embolic injury.
• Fluid replacement (oral or intravenous) corrects the
intravascular fluid loss from endothelial bubble injury and
dehydration associated with immersion. Maintenance of
an adequate peripheral circulation is important for the
excretion of excess dissolved gas.
• Recompression is the definitive therapy. Transfer to a
recompression facility may be by surface or air, provided
that the altitude remains low (< 300 m) and the patient
continues to breathe 100% oxygen. Recompression
reduces the volume of gas within tissues (Boyle’s law),
forces nitrogen back into solution and is followed by
slow decompression, allowing the nitrogen load to be
excreted.
Information required by diving specialists to decide appropriate treatment. See
contact details on page 172.
9.6 Assessment of a patient with
decompression illness
Evolution
• Progressive
• Static
• Relapsing
• Spontaneously improving
Manifestations
• Pain: often large joints, e.g. shoulder (‘the bends’)
• Neurological: any deficit is possible
• Audiovestibular: vertigo, tinnitus, nystagmus; may mimic inner ear
barotrauma
• Pulmonary: chest pain, cough, haemoptysis, dyspnoea; may be due
to arterial gas embolism (AGE)
• Cutaneous: itching, erythematous rash
• Lymphatic: tender lymph nodes, oedema
• Constitutional: headache, fatigue, general malaise
Dive profile
• Depth
• Type of gas used
• Duration of dive
172 • ENVIRONMENTAL MEDICINE
Further information
Websites
altitude.org A website written by doctors with expertise and experience
of expedition and altitude medicine and critical care.
diversalertnetwork.org Advice on the clinical management of diving
illness and emergency assistance services.
emergency.cdc.gov/radiation/ The Centers for Disease Control and
Prevention provides information and links on all forms of radiation
for patients and professionals.
msf.org Information and advice about all aspects of responding to
humanitarian crises around the world.
Telephone numbers
Two organisations can offer national and international advice on
diving emergencies and recompression facilities:
• Within the UK, the National Diving Accident Helpline on
+44 (0)7831 151523 (24 hours).
• Outside the UK, contact the Divers Alert Network
International Emergency Hotline +1-919-684-9111.
implementation of a public health surveillance and reporting
system and the mobilisation of local human resources, and their
training and deployment during the consolidation phase in order
to prepare for handover to the local competent authority and
withdrawal.
9.7 Priorities in a humanitarian crisis
Assessment of population need
Safe water and sanitation
Food and nutrition
Shelter and warmth
Emergency health care
Immunisation of risk groups
Control of communicable diseases
Ongoing health surveillance and reporting
Training and deployment of indigenous health-care
workers
Handover of responsibility to local authorities

04-10 Acute medicine and critical illness
10 Acute medicine and critical illness
Acute medicine and
critical illness
VR Tallentire
MJ MacMahon
Clinical examination in critical care 174
Monitoring 175
Acute medicine 176
The decision to admit to hospital 176
Ambulatory care 176
Presenting problems in acute medicine 176
Chest pain 176
Acute breathlessness 179
Syncope/presyncope 181
Delirium 183
Headache 185
Unilateral leg swelling 186
Identification and assessment of deterioration 188
Early warning scores and the role of the medical emergency team 188
Immediate assessment of the deteriorating patient 188
Selecting the appropriate location for ongoing management 189
Common presentations of deterioration 190
Tachypnoea 190
Hypoxaemia 190
Tachycardia 191
Hypotension 193
Hypertension 193
Decreased conscious level 194
Decreased urine output/deteriorating renal function 195
Disorders causing critical illness 196
Sepsis and the systemic inflammatory response 196
Acute respiratory distress syndrome 198
Acute circulatory failure (cardiogenic shock) 199
Post cardiac arrest 200
Other causes of multi-organ failure 201
Critical care medicine 201
Decisions around intensive care admission 201
Stabilisation and institution of organ support 202
Respiratory support 202
Cardiovascular support 204
Renal support 208
Neurological support 208
Daily clinical management in intensive care 208
Clinical review 208
Sedation and analgesia 209
Delirium in intensive care 209
Weaning from respiratory support 209
Extubation 210
Tracheostomy 210
Nutrition 210
Other essential components of intensive care 210
Complications and outcomes of critical illness 211
Adverse neurological outcomes 211
Other long-term problems 212
The older patient 212
Withdrawal of active treatment and death in intensive care 213
Discharge from intensive care 213
Critical care scoring systems 213
174 • ACUTE MEDICINE AND CRITICAL ILLNESS
Clinical examination in critical care
Airway
Is the airway patent?
Is the end-tidal CO2 trace
normal?
Are there any signs of airway
obstruction?
A
B
Circulation
Is the physiology normal
(heart rate, blood pressure,
peripheral temperature,
lactate, urine output)?
How much support is required
(inotrope,vasopressor)?
C
D
E
Glucose
What is the glucose level?
Is insulin being administered?
G
G
D
Haematology
What are the haemoglobin/
platelet levels?
Are there any signs of
bleeding?
H
Infection
What is the temperature?
Review recent infective
markers and trend
What antibiotics are being
given and what is the
duration of treatment?
I
Enteral/exposure
Feeding regime
Stool frequency
Abdominal tenderness/bowel
sounds present?
Disability
Level of responsiveness
Delirium screen
Pupillary responses
Doses of sedative drugs
F Fluids, electrolytes and
renal system
What is the fluid balance?
Urine volume and colour?
Is there any oedema?
Review the renal biochemistry
and electrolyte levels
Breathing
Is the physiology normal
(SpO2, respiratory rate, tidal
volume)?
What is the level of support?
Are there any abnormal signs
on chest examination?
Review the ventilator settings,
arterial blood gases and
recent chest X-ray
F
E
C
B
A
Monitoring • 175
Bedside physiological data commonly monitored in an intensive care unit setting.
Monitoring
Electrocardiography
Heart rate, rhythm and QRS morphology
Arterial line trace
Size of the area under the curve is proportional to stroke
volume
Narrow peaks suggest low stroke volume as shown here
Oxygen saturation
Saturation of haemoglobin measured by plethysmography
(SpO2). Gives an indication of adequacy of oxygenation,
and the quality of tissue perfusion can also be inferred –
a flat trace suggests poor peripheral perfusion
Central venous pressure trace
A non-specific guide to volume status and right ventricular
function. Increased values in fluid overload and right
ventricular failure
Capnography
Numerical value of end-tidal CO2 (ETCO2) is less than
arterial PCO2 (PaCO2) by a variable amount. Shape of
trace can signify airway displacement/obstruction,
bronchospasm or a low cardiac output (as shown below)
kPa mmHg
Time (secs)
Normal
Steep ‘upstroke’
in early expiration
Bronchospasm
Shallow ‘upstroke’
in early expiration
Partial obstruction/displacement
of airway device
Decreasing cardiac output
Decreasing size of
ETCO2 waveform
No ventilation
(from any cause)
Basic principles
• Uses the different red and infrared
absorption profiles of oxyhaemoglobin
and deoxyhaemoglobin to estimate
arterial oxyhaemoglobin saturation
(SaO2)
• Only pulsatile absorption is
measured
• A poor trace correlates with poor
perfusion
Sources of error
• Carboxyhaemoglobin – absorption profile
is the same as oxyhaemoglobin: falsely
elevated SpO2
• Methaemoglobinaemia – SpO2 will tend
towards 85%
• Ambient light/poor application of probe/
severe tricuspid regurgitation (pulsatile
venous flow): falsely depressed SpO2
• Reduced accuracy below 80% saturation
• Hyperbilirubinaemia does not affect SpO2
Plethysmography (SpO2)
176 • ACUTE MEDICINE AND CRITICAL ILLNESS
is required. The requirement for admission is determined by
many factors, including the severity of illness, the patient’s
physiological reserve, the need for urgent investigations, the nature
of proposed treatments and the patient’s social circumstances.
In many cases, it is clear early in the assessment process that a
patient requires admission. In such cases, a move into a medical
receiving unit – often termed a medical admissions unit (MAU) or
acute medical unit (AMU) – should be facilitated as soon as the
initial assessment has been completed and urgent investigations
and/or treatments have been instigated. In hospitals where
such units do not exist, patients will need to be moved to a
downstream ward once treatment has been commenced and
they have been deemed sufficiently stable. Following the initial
assessment, it may be possible to discharge stable patients
home with a plan for early follow-up (such as a rapid-access
specialist clinic appointment).
Ambulatory care
In some hospitals, it is increasingly possible for patient care to
be coordinated in an ambulatory setting, negating the need for
a patient to remain in hospital overnight. In the context of acute
medicine, ambulatory care can be employed for conditions that
are perceived by either the patient or the referring practitioner as
requiring prompt clinical assessment by a competent decisionmaker with access to appropriate diagnostic resources. The
patient may return on several occasions for investigation,
observation, consultation or treatment. Some presentations,
such as a unilateral swollen leg (p. 186), lend themselves to
this type of management (Box 10.1). If indicated, a Doppler
ultrasound can be arranged, and patients with confirmed deep
vein thromboses can be anticoagulated on an outpatient basis.
Successful ambulatory care requires careful patient selection;
while many patients may cherish the opportunity to sleep at
home, others may find frequent trips to hospital or clinic too
difficult due to frailty, poor mobility or transport difficulties.
Presenting problems in acute medicine
Chest pain
Chest pain is a common symptom in patients presenting to
hospital. The differential diagnosis is wide (Box 10.2), and a
Hospital medicine is becoming ever more specialised and people
are living longer while accruing increasing numbers of chronic
disease diagnoses. Rather than diminishing the role of the
generalist, these factors paradoxically create a need for experts
in the undifferentiated presentation. In the UK such physicians
are known as ‘general physicians’, while in the US they are
referred to as ‘hospitalists’.
Acute illness can present in a large variety of ways, depending
on the nature of the illness, the underlying health of the individual,
and their cultural and religious background. The skills of prompt
diagnosis formation and provision of appropriate treatment rely on
the integration of information from all the available sources, along
with careful consideration of underlying chronic health problems.
Patients who deteriorate while in hospital make up a small
but important cohort. If they are well managed, in-hospital
cardiac arrest rates will be low. This can be achieved through
the combined effects of prompt resuscitation and appropriate
end-of-life decision-making. Early recognition of deterioration by
ward teams and initial management by health-care professionals
operating within a functioning rapid response system are the
central tenets of any system designed to improve the outcomes
of deteriorating ward patients.
Intensive care medicine has developed into a prominent
specialty, central to the safe functioning of a modern acute
hospital. Scientific endeavour has resulted in a much better
understanding of the molecular pathophysiology of processes
such as sepsis and acute respiratory distress syndrome, which
account for much premature death worldwide.
Acute medicine
Acute medicine is the part of general medicine that is concerned
with the immediate and early management of medical patients
who require urgent care. As a specialty, it is closely aligned
with emergency medicine and intensive care medicine, but is
firmly rooted within general medicine. Acute physicians manage
the adult medical take and lead the development of acute care
pathways that aim to reduce variability, improve care and cut
down hospital admissions.
The decision to admit to hospital
Every patient presenting to hospital should be assessed by a
clinician who is able to determine whether or not admission
10.1 Groups of patients who are potentially suitable for ambulatory care
Group
Example(s)
Quality and safety issues
Diagnostic exclusion group
Chest pain – possible myocardial infarction;
breathlessness – possible pulmonary embolism
Even when a specific condition has been excluded, there is still
a need to explain the patient’s symptoms through the diagnostic
process
Low-risk stratification group
Non-variceal upper gastrointestinal bleed with
low Blatchford score (p. 780); communityacquired pneumonia with low CURB-65 score
(p. 583)
Appropriate treatment plans should be in place
Specific procedure group
Replacement of percutaneous endoscopic
gastrostomy (PEG) tube; drainage of pleural
effusion/ascites
The key to implementation is how ambulatory care for this group
of patients can be delivered when they present out of hours
Outpatient group with
supporting infrastructure
Deep vein thrombosis (DVT); cellulitis
These are distinct from the conditions listed above because the
infrastructure required to manage them is quite different
Presenting problems in acute medicine • 177
10.2 Differential diagnosis of chest pain
Central
Cardiac
• Myocardial ischaemia (angina)
• Myocardial infarction
• Myocarditis
• Pericarditis
• Mitral valve prolapse
syndrome
Aortic
• Aortic dissection
• Aortic aneurysm
Oesophageal
• Oesophagitis
• Oesophageal spasm
• Mallory–Weiss syndrome
• Oesophageal perforation
(Boerhaave’s syndrome)
Pulmonary embolus
Mediastinal
• Malignancy
Anxiety/emotion1
Peripheral
Lungs/pleura
• Pulmonary infarct
• Pneumonia
• Pneumothorax
• Malignancy
• Tuberculosis
• Connective tissue disorders
Musculoskeletal2
• Osteoarthritis
• Rib fracture/injury
• Acute vertebral fracture
• Costochondritis (Tietze’s
syndrome)
• Intercostal muscle injury
• Epidemic myalgia (Bornholm
disease)
Neurological
• Prolapsed intervertebral disc
• Herpes zoster
• Thoracic outlet syndrome
1May also cause peripheral chest pain. 2Can sometimes cause central chest pain.
Characteristics
Pleurisy, a sharp or ‘catching’ chest pain aggravated by deep
breathing or coughing, is indicative of respiratory pathology,
particularly pulmonary infection or infarction. However, the pain
associated with myocarditis or pericarditis is often also described
as ‘sharp’ and may ‘catch’ during inspiration, coughing or lying
flat. It typically varies in intensity with movement and the phase
of respiration. A malignant tumour invading the chest wall or
ribs can cause gnawing, continuous local pain. The pain of
myocardial ischaemia is typically dull, constricting, choking or
‘heavy’, and is usually described as squeezing, crushing, burning
or aching. Patients often emphasise that it is a discomfort rather
than a pain. Angina occurs during (not after) exertion and is
promptly relieved (in less than 5 minutes) by rest. It may also be
precipitated or exacerbated by emotion but tends to occur more
readily during exertion, after a large meal or in a cold wind. In
crescendo or unstable angina, similar pain may be precipitated
by minimal exertion or at rest. The increase in venous return or
preload induced by lying down may also be sufficient to provoke
pain in vulnerable patients (decubitus angina). Patients with
reversible airways obstruction, such as asthma, may also describe
exertional chest tightness that is relieved by rest. This may be
difficult to distinguish from myocardial ischaemia. Bronchospasm
may be associated with wheeze, atopy and cough (p. 556).
Musculoskeletal chest pain is variable in site and intensity but
does not usually fall into any of the patterns described above.
The pain may vary with posture or movement of the upper body,
or be associated with a specific movement (bending, stretching,
turning). Many minor soft tissue injuries are related to everyday
activities, such as driving, manual work and sport.
Onset
The pain associated with myocardial infarction (MI) typically takes
several minutes or even longer to develop to its maximal intensity;
similarly, angina builds up gradually in proportion to the intensity
of exertion. Pain that occurs after, rather than during, exertion
is usually musculoskeletal or psychological in origin. The pain
of aortic dissection (severe and ‘tearing’), massive pulmonary
embolism (PE) or pneumothorax is usually very sudden in onset.
Other causes of chest pain tend to develop more gradually, over
hours or even days.
Associated features
The pain of MI, massive PE or aortic dissection is often
accompanied by autonomic disturbance, including sweating,
nausea and vomiting. Some patients describe a feeling of
impending death, referred to as ‘angor animi’. Breathlessness,
due to pulmonary congestion arising from transient ischaemic
left ventricular dysfunction, is often a prominent feature of
myocardial ischemia. Breathlessness may also accompany any
of the respiratory causes of chest pain and can be associated
with cough, wheeze or other respiratory symptoms. Patients
with myocarditis or pericarditis may describe a prodromal viral
illness. Gastrointestinal disorders, such as gastro-oesophageal
reflux or peptic ulceration, may present with chest pain that is
hard to distinguish from myocardial ischaemia; it may even be
precipitated by exercise and be relieved by nitrates. However, it
is usually possible to elicit a history relating chest pain to supine
posture or eating, drinking or oesophageal reflux. The pain of
gastro-oesophageal reflux often radiates to the interscapular region
and dysphagia may be present. Severe chest pain arising after
retching or vomiting, or following oesophageal instrumentation,
should raise the possibility of oesophageal perforation.
detailed history and thorough clinical examination are paramount
to ensure that the subsequent investigative pathway is appropriate.
Presentation
Chest ‘pain’ is clearly a subjective phenomenon and may be
described by patients in a variety of different ways. Whether
the patient describes ‘pain’, ‘discomfort’ or ‘pressure’ in the
chest, there are some key features that must be elicited from
the history.
Site and radiation
Pain secondary to myocardial ischaemia is typically located in the
centre of the chest. It may radiate to the neck, jaw, and upper
or even lower arms. Occasionally, it may be experienced only
at the sites of radiation or in the back. The pain of myocarditis
or pericarditis is characteristically felt retrosternally, to the left of
the sternum, or in the left or right shoulder. The severe pain of
aortic dissection is typically central with radiation through to the
back. Central chest pain may also occur with tumours affecting
the mediastinum, oesophageal disease (p. 791) or disease of the
thoracic aorta (p. 505). Pain situated over the left anterior chest
and radiating laterally is unlikely to be due to cardiac ischaemia
and may have many causes, including pleural or lung disorders,
musculoskeletal problems or anxiety. Rarely, sharp, left-sided
chest pain that is suggestive of a musculoskeletal problem may
be a feature of mitral valve prolapse (p. 520).
178 • ACUTE MEDICINE AND CRITICAL ILLNESS
side. Local tenderness of the chest wall is likely to indicate
musculoskeletal pain but can also be found in pulmonary
infarction.
Subdiaphragmatic inflammatory pathology, such as a liver
abscess, cholecystitis or ascending cholangitis, can mimic
pneumonia by causing fever, pleuritic chest pain and a small
sympathetic pleural effusion, usually on the right. Likewise,
acute pancreatitis can present with thoracic symptoms, and an
amylase or lipase level should be requested where appropriate.
It is imperative that the abdomen is examined routinely in all
patients presenting with pleuritic chest pain.
Initial investigations
Chest X-ray, ECG and biomarkers (e.g. troponin, D-dimer) play a
pivotal role in the evaluation of chest pain. However, indiscriminate
ordering of such investigations may result in diagnostic confusion
and over-investigation. The choice of investigation(s) is intimately
linked to the history and examination findings. A chest X-ray
and 12-lead ECG should be performed in the vast majority of
patients presenting to hospital with chest pain. Pregnancy is not
a contraindication to chest X-ray, but particular consideration
should be given to whether the additional diagnostic information
justifies breast irradiation.
The chest X-ray may confirm the suspected diagnosis,
particularly in the case of pneumonia. Small pneumothoraces
are easily missed, as are rib fractures or small metastatic deposits,
and all should be considered individually during chest X-ray review.
A widened mediastinum suggests acute aortic dissection but a
normal chest X-ray does not exclude the diagnosis. Provided it
has been more than 1 hour since the onset of pain, chest X-ray
in oesophageal rupture may reveal subcutaneous emphysema,
pneumomediastinum or a pleural effusion.
Patients with a history compatible with myocardial ischaemia
require an urgent 12-lead ECG. Acute chest pain with ECG
changes indicating a ST segment elevation myocardial infarction
(STEMI) suggests that the patient is likely to benefit from immediate
reperfusion therapy. Specific information relating to cocaine or
amphetamine use should be sought, particularly in younger
Anxiety-induced chest pain may be associated with
breathlessness (without hypoxaemia), throat tightness, perioral
tingling and other evidence of emotional distress. It is important
to remember, however, that chest pain itself can be an extremely
frightening experience, and so psychological and organic features
often coexist. Anxiety may amplify the effects of organic disease
and a confusing clinical picture may result.
A detailed and clear history is key to narrowing the differential
diagnosis of chest pain. Figure 10.1 shows how certain features
of the history, particularly when combined, can tip the balance
of evidence towards or away from ischaemic cardiac chest pain.
Clinical assessment
Cardiorespiratory examination may detect clinical signs that help
guide ongoing investigation. Patients with a history compatible with
myocardial ischaemia should have a 12-lead electrocardiogram
(ECG) performed while clinical examination proceeds. Ongoing
chest pain with clinical features of shock or pulmonary oedema,
or ECG evidence of ventricular arrhythmia or complete heart
block should prompt urgent cardiology review and referral to a
higher level of care.
Chest pain that is accompanied by clinical evidence of
increased intracardiac pressure (especially a raised jugular venous
pressure) increases the likelihood of myocardial ischaemia or
massive PE. The legs should be examined for clinical evidence
of deep vein thrombosis.
A large pneumothorax should be evident on clinical examination,
with absent breath sounds and a hyper-resonant percussion
note on the affected side. Other unilateral chest signs, such
as bronchial breathing or crackles, are most likely to indicate a
respiratory tract infection, and a chest X-ray should be expedited.
Pericarditis may be accompanied by a pericardial friction
rub. In aortic dissection, syncope or neurological deficit may
occur. Examination may reveal asymmetrical pulses, features of
undiagnosed Marfan’s syndrome (p. 508) or a new early diastolic
murmur representing aortic regurgitation.
Any disease process involving the pleura may restrict rib
movement and a pleural rub may be audible on the affected
Fig. 10.1 Identifying ischaemic cardiac pain: the ‘balance’ of evidence.
Ischaemic
cardiac chest pain
Non-cardiac chest pain
Relieving factors
Respiratory, gastrointestinal,
locomotor or psychological
Rest
Quick response to nitrates
Precipitation
Spontaneous, not related to exertion,
provoked by posture, respiration or palpation
Precipitated by exertion
and/or emotion
Character
Sharp, stabbing, catching
Tight, squeezing, choking
Radiation
Other or no radiation
Jaw/neck/shoulder/arm
(occasionally back)
Location
Peripheral, localised
Central, diffuse
Associated
features
Not relieved by rest
Slow or no response to nitrates
Breathlessness
Presenting problems in acute medicine • 179
differential diagnosis list to chronic exertional breathlessness. The
presence of associated cardiovascular (chest pain, palpitations,
sweating and nausea) or respiratory symptoms (cough, wheeze,
haemoptysis, stridor) can narrow the differential diagnosis yet
further. A previous history of left ventricular dysfunction, asthma or
exacerbations of chronic obstructive pulmonary disease (COPD)
is important. In the severely ill patient, it may be necessary to
obtain the history from accompanying witnesses. In children,
the possibility of inhalation of a foreign body (Fig. 10.2) or acute
epiglottitis should always be considered. There is often more
than one underlying diagnosis; a thorough assessment should
continue, even after a possible diagnosis has been reached,
particularly if the severity of symptoms does not seem to be
adequately explained. The causes of acute severe breathlessness
are covered here; chronic exertional dyspnoea is discussed
further on page 557.
Clinical assessment
Airway obstruction, anaphylaxis and tension pneumothorax
require immediate identification and treatment. If any of these
is suspected, treatment should not be delayed while additional
investigations are performed, and anaesthetic support is likely
to be required. In the absence of an immediately life-threatening
cause, the following should be assessed and documented:
• level of consciousness
• degree of central cyanosis
• work of breathing (rate, depth, pattern, use of accessory
muscles)
• adequacy of oxygenation (SpO2)
patients. In the context of a compatible history, an ECG showing
ischaemic changes that do not meet STEMI criteria should prompt
regular repeat ECGs and treatment for non-ST segment elevation
myocardial infarction (NSTEMI)/unstable angina. Measurement
of serum troponin concentration on admission is often helpful in
cases where there is diagnostic doubt, but a negative result should
always prompt a repeat sample 6–12 hours after maximal pain.
Acute coronary syndrome may be diagnosed with confidence in
patients with a convincing history of ischaemic pain (Fig. 10.1)
and either ECG evidence of ischaemia or an elevated serum
troponin. If an elevated serum troponin is found in a patient
who has an atypical history or is at low risk of ischaemic heart
disease, then alternative causes of raised troponin should be
considered (Box 10.3). Further management of acute coronary
syndromes is discussed on page 498.
In the absence of convincing ECG evidence of myocardial
ischaemia, other life-threatening causes of chest pain, such as
aortic dissection, massive PE and oesophageal rupture, should
be considered. Suspicion of aortic dissection (background of
hypertension, trauma, pregnancy or previous aortic surgery)
should prompt urgent thoracic computed tomography (CT) or
transoesophageal echocardiography. An ECG in the context of
massive PE most commonly reveals only a sinus tachycardia,
but may show new right axis deviation, right bundle branch block
or a dominant R wave in V1. The classical finding of S1Q3T3 (a
deep S wave in lead I, with a Q wave and T wave inversion in
lead III) is rare. If massive PE is suspected and the patient is
haemodynamically unstable, a transthoracic echocardiogram,
to seek evidence of right heart strain and exclude alternative
diagnoses such as tamponade, is extremely useful.
If the patient is deemed to be at low risk of PE, a D-dimer test
can be informative, as a negative result effectively excludes the
diagnosis. The D-dimer test should be performed only if there
is clinical suspicion of PE, as false-positive results can lead to
unnecessary investigations. If the D-dimer is positive, there is
high clinical suspicion, or there is other convincing evidence of
PE (such as features of right heart strain on the ECG), prompt
imaging should be arranged (p. 619 and Fig. 17.67).
Acute breathlessness
In acute breathlessness, the history, along with a rapid but
careful examination, will usually suggest a diagnosis that can
be confirmed by routine investigations including chest X-ray,
12-lead ECG and arterial blood gas (ABG) sampling.
Presentation
A key feature of the history is the speed of onset of breathlessness.
Acute severe breathlessness (over minutes or hours) has a distinct
Fig. 10.2 Inhaled foreign body. A Chest X-ray showing a tooth lodged
in a main bronchus. B Bronchoscopic appearance of inhaled foreign body
(tooth) with a covering mucous film.
A
B
10.3 Causes of elevated serum troponin other than
acute coronary syndrome
Cardiorespiratory causes
• Pulmonary embolism
• Acute pulmonary oedema
• Tachyarrhythmias
• Myocarditis/myopericarditis
• Aortic dissection
• Cardiac trauma
• Cardiac surgery/ablation
Non-cardiorespiratory causes
• Prolonged hypotension
• Severe sepsis
• Severe burns
• Stroke
• Subarachnoid haemorrhage
• End-stage renal failure
180 • ACUTE MEDICINE AND CRITICAL ILLNESS
onset of atrial fibrillation in a patient with mitral stenosis. In such
cases, the classic mid-diastolic rumbling murmur with pre-systolic
accentuation may be heard. Patients sometimes describe chest
tightness as ‘breathlessness’. However, myocardial ischaemia
may also induce true breathlessness by provoking transient left
ventricular dysfunction. When breathlessness is the dominant
or sole feature of myocardial ischaemia, it is known as ‘angina
equivalent’. A history of chest tightness or close correlation with
exercise should be sought.
Initial investigations
As shown in Box 10.4, amalgamation of a clear history and
thorough clinical examination with chest X-ray, ECG and ABG
findings will usually indicate the primary cause of breathlessness.
If bronchospasm is suspected, measurement of peak expiratory
flow will assist in the assessment of severity and should be
performed whenever possible. An ABG will often provide additional
information to SpO2 measurement alone, particularly if there is
clinical evidence (drowsiness, delirium, asterixis) or a strong
likelihood of hypercapnia. An acute rise in PaCO2 will increase
the HCO3
− by only a small amount, resulting in inadequate
buffering and acidaemia. Renal compensation and a large rise in
HCO3
− will take at least 12 hours. In acute type II respiratory failure
(p. 565), the rate of rise of PaCO2 is a better indicator of severity
than the absolute value.
An ABG is essential in the context of smoke inhalation
to measure carboxyhaemoglobin level, and is central to the
identification of metabolic acidosis or the diagnosis of psychogenic
hyperventilation (Box 10.4). If ‘angina equivalent’ is suspected,
• ability to speak (in single words or sentences)
• cardiovascular status (heart rate and rhythm, blood
pressure (BP) and peripheral perfusion).
Pulmonary oedema is suggested by a raised jugular venous
pressure and bi-basal crackles or diffuse wheeze, while asthma
or COPD is characterised by wheeze and prolonged expiration.
A hyper-resonant hemithorax with absent breath sounds raises
the possibility of pneumothorax, while severe breathlessness
with normal breath sounds may indicate PE. Leg swelling may
suggest cardiac failure or, if asymmetrical, venous thrombosis.
The presence of wheeze is not always indicative of
bronchospasm. In acute left heart failure, an increase in the
left ventricular diastolic pressure causes the pressure in the left
atrium, pulmonary veins and pulmonary capillaries to rise. When
the hydrostatic pressure of the pulmonary capillaries exceeds the
oncotic pressure of plasma (about 25–30 mmHg), fluid moves
from the capillaries into the interstitium. This stimulates respiration
through a series of autonomic reflexes, producing rapid, shallow
respiration, and congestion of the bronchial mucosa may cause
wheeze (sometimes known as cardiac asthma). Sitting upright or
standing may provide some relief by helping to reduce congestion
at the apices of the lungs. The patient may be unable to speak
and is typically distressed, agitated, sweaty and pale. Respiration
is rapid, with recruitment of accessory muscles, coughing and
wheezing. Sputum may be profuse, frothy and blood-streaked
or pink. Extensive crepitations and rhonchi are usually audible
in the chest and there may also be signs of right heart failure.
Any arrhythmia may cause breathlessness, but usually does
so only if the heart is structurally abnormal, such as with the
10.4 Clinical features in acute breathlessness
Condition
History
Signs
Chest X-ray
ABG
ECG
Pulmonary
oedema
Chest pain, palpitations,
orthopnoea, cardiac
history*
Central cyanosis, ↑JVP,
sweating, cool extremities,
basal crackles*
Cardiomegaly,
oedema/pleural
effusions*
↓PaO2
↓PaCO2
Sinus tachycardia,
ischaemia*,
arrhythmia
Massive
pulmonary
embolus
Risk factors, chest pain,
pleurisy, syncope*,
dizziness*
Central cyanosis, ↑JVP*,
absence of signs in the
lung*, shock (tachycardia,
hypotension)
Often normal
Prominent hilar
vessels, oligaemic
lung fields*
↓PaO2
↓PaCO2
Sinus tachycardia,
RBBB, S1Q3T3 pattern
↑T(V1–V4)
Acute severe
asthma
History of asthma,
asthma medications,
wheeze*
Tachycardia, pulsus
paradoxus, cyanosis (late),
→JVP*, ↓peak flow,
wheeze*
Hyperinflation only
(unless complicated
by pneumothorax)*
↓PaO2
↓PaCO2 (↑PaCO2 in
extremis)
Sinus tachycardia
(bradycardia in
extremis)
Acute
exacerbation
of COPD
Previous episodes*,
smoker. If in type II
respiratory failure, may
be drowsy
Cyanosis, hyperinflation*,
signs of CO2 retention
(flapping tremor, bounding
pulses)*
Hyperinflation*,
bullae, complicating
pneumothorax
↓ or ↓↓PaO2
↑PaCO2 in type II failure
± ↑H+, ↑HCO3
− in
chronic type II failure
Normal, or signs of
right ventricular
strain
Pneumonia
Prodromal illness*,
fever*, rigors*, pleurisy*
Fever, delirium, pleural
rub*, consolidation*,
cyanosis (if severe)
Pneumonic
consolidation*
↓PaO2
↓PaCO2 (↑ in extremis)
Tachycardia
Metabolic
acidosis
Evidence of diabetes
mellitus or renal disease,
aspirin or ethylene glycol
overdose
Fetor (ketones),
hyperventilation without
heart or lung signs*,
dehydration*, air hunger
Normal
PaO2 normal
↓↓PaCO2, ↑H+
↓HCO3
−
Psychogenic
Previous episodes, digital
or perioral dysaesthesia
No cyanosis, no heart or
lung signs, carpopedal
spasm
Normal
PaO2 normal*
↓↓PaCO2, ↓H+*
*Valuable discriminatory feature.
(ABG = arterial blood gas; COPD = chronic obstructive pulmonary disease; JVP = jugular venous pressure; RBBB = right bundle branch block)
Presenting problems in acute medicine • 181
Presentation
The history from the patient and a witness is the key to establishing
a diagnosis. The terms used for describing the symptoms
associated with syncope vary so much among patients that
they should not be taken for granted. Some patients use the
term ‘blackout’ to describe a purely visual symptom, rather
than loss of consciousness. Some may understand ‘dizziness’
to mean an abnormal perception of movement (vertigo), some
will consider this a feeling of faintness, and others will regard
it as unsteadiness. The clinician thus needs to elucidate the
exact nature of the symptoms that the patient experiences. The
potential differential diagnoses of syncope and presyncope, on
the basis of the symptoms described, is shown in Figure 10.3.
The history should always be supplemented by a direct eyewitness account if available. Careful history with corroboration
will usually establish whether there has been full consciousness,
altered consciousness, vertigo, transient amnesia or something
else. Attention should be paid to potential triggers (e.g. medication,
micturition, exertion, prolonged standing), the patient’s appearance
(e.g. colour, seizure activity), the duration of the episode, and
the speed of recovery (Box 10.6). Cardiac syncope is usually
sudden but can be associated with premonitory lightheadedness,
palpitation or chest discomfort. The blackout is usually brief and
recovery rapid. Exercise-induced syncope can be the presenting
feature of a number of serious pathologies (such as hypertrophic
obstructive cardiomyopathy or exercise-induced arrhythmia) and
always requires further investigation. Neurocardiogenic syncope
will often be associated with a situational trigger (such as pain
or emotion), and the patient may experience flushing, nausea,
malaise and clamminess for several minutes afterwards. Recovery
is usually quick and without subsequent delirium, provided the
patient has assumed a supine position. There is often some brief
stiffening and limb-twitching, which requires differentiation from
seizure-like movements. It is rare for syncope to cause injury or to
cause amnesia after regaining awareness. Patients with seizures
do not exhibit pallor, may have abnormal movements, usually
take more than 5 minutes to recover and are often confused.
Aspects of the history that can help to differentiate seizure from
syncope are shown in Box 10.7.
A diagnosis of psychogenic blackout (also known as nonepileptic seizure, pseudoseizure or psychogenic seizure) may be
suggested by specific emotional triggers, dramatic movements
objective evidence of myocardial ischaemia from stress testing
may help to establish the diagnosis.
Syncope/presyncope
The term ‘syncope’ refers to sudden loss of consciousness
due to reduced cerebral perfusion. ‘Presyncope’ refers to
lightheadedness, in which the individual thinks he or she may
‘black out’. Dizziness and presyncope are particularly common
in old age (Box 10.5). Symptoms are disabling, undermine
confidence and independence, and can affect a person’s ability
to work or to drive.
There are three principal mechanisms that underlie recurrent
presyncope or syncope:
• cardiac syncope due to mechanical cardiac dysfunction or
arrhythmia
• neurocardiogenic syncope (also known as vasovagal or
reflex syncope), in which an abnormal autonomic reflex
causes bradycardia and/or hypotension
• postural hypotension, in which physiological peripheral
vasoconstriction on standing is impaired, leading to
hypotension.
There are, however, other causes of loss of consciousness,
and differentiating syncope from seizure is a particular challenge.
Psychogenic blackouts (also known as non-epileptic seizures or
pseudoseizures) also need to be considered in the differential
diagnosis.
10.5 Dizziness in old age
• Prevalence: common, affecting up to 30% of people aged
65 years.
• Symptoms: most frequently described as a combination of
unsteadiness and lightheadedness.
• Most common causes: postural hypotension and cardiovascular
disease. Many patients have more than one underlying cause.
• Arrhythmia: can present with lightheadedness either at rest or on
activity.
• Anxiety: frequently associated with dizziness but rarely the only
cause.
• Falls: multidisciplinary workup is required if dizziness is associated
with falls.
10.6 Typical features of cardiac syncope, neurocardiogenic syncope and seizures
Cardiac syncope
Neurocardiogenic syncope
Seizures
Premonitory symptoms
Often none
Lightheadedness
Palpitation
Chest pain
Breathlessness
Nausea
Lightheadedness
Sweating
Delirium
Hyperexcitability
Olfactory hallucinations
‘Aura’
Unconscious period
Extreme ‘death-like’ pallor
Pallor
Prolonged (> 1 min)
unconsciousness
Motor seizure activity*
Tongue-biting
Urinary incontinence
Recovery
Rapid (< 1 min)
Flushing
Slow
Nausea
Lightheadedness
Prolonged delirium (> 5 mins)
Headache
Focal neurological signs
*N.B. Cardiac syncope can also cause convulsions by inducing cerebral anoxia.
182 • ACUTE MEDICINE AND CRITICAL ILLNESS
10.7 How to differentiate seizures from syncope
Seizure
Syncope
Aura (e.g. olfactory)
+
−
Cyanosis
+
−
Lateral tongue-biting
+
−/+
Post-ictal delirium
+
−
Post-ictal amnesia
+
−
Post-ictal headache
+
−
Rapid recovery
−
+
Fig. 10.3 The differential diagnosis of syncope and presyncope.
Labyrinthine dysfunction
• Infection
• ‘Vestibular neuronitis’
• Benign positional vertigo
• Ménière’s disease
• Ischaemia/infarction
• Trauma
• Perilymph fistula
• Other (e.g. drugs, otosclerosis)
Central vestibular dysfunction
• ‘Physiological’ (visual–
vestibular mismatch)
• Demyelination
• Migraine
• Posterior fossa mass lesion
• Vertebro-basilar ischaemia
• Other (e.g. disorders of
cranio-vertebral junction)
• Ataxia
• Weakness
• Loss of joint position sense
• Gait dyspraxia
• Joint disease
• Visual disturbance
• Fear of falling (Chs 24 and 25)
Impaired cerebral perfusion
Cardiac disease
• Arrhythmia
• Left ventricular dysfunction
• Aortic stenosis
• Hypertrophic obstructive
cardiomyopathy
Other causes
• Vasovagal syncope
• Postural hypotension
• Micturition syncope
• Cough syncope
• Carotid sinus sensitivity
• Hypoglycaemia (Ch. 20)
• Anxiety*
• Hyperventilation
• Post-concussive syndrome
• Panic attack
• Non-epileptic attack
• Epileptic seizure
Presyncope
(reduced cerebral
perfusion)
Syncope
(loss of cerebral
perfusion)
Sensation of
movement?
(vertigo)
Loss of
balance?
Lightheaded?
Other
description
Funny turn
or blackout
Anxiety is the most
common cause of
dizziness in those
under 65 years
Loss of
consciousness
(‘blackout’)
or vocalisation, or by very prolonged duration (hours). A history
of rotational vertigo is suggestive of a labyrinthine or vestibular
disorder (p. 1086). Postural hypotension is normally obvious from
the history, with presyncope or, less commonly, syncope occurring
within a few seconds of standing. The history should include
enquiry about predisposing medications (diuretics, vasodilators,
antidepressants) and conditions (such as diabetes mellitus and
Parkinson’s disease).
Clinical assessment
Examination of the patient may be entirely normal, but may
reveal clinical signs that favour one form of syncope. The
systolic murmurs of aortic stenosis or hypertrophic obstructive
Presenting problems in acute medicine • 183
cardiomyopathy are important findings, particularly if paired with
a history of lightheadedness or syncope on exertion. BP taken
when supine and then after 1 and 3 minutes of standing may,
when combined with symptoms, provide robust evidence of
symptomatic postural hypotension.
Clinical suspicion of hypersensitive carotid sinus syndrome
(sensitivity of carotid baroreceptors to external pressure such
as a tight collar) should prompt monitoring of the ECG and BP
during carotid sinus pressure, provided there is no carotid bruit
or history of cerebrovascular disease. A positive cardio-inhibitory
response is defined as a sinus pause of 3 seconds or more; a
positive vasodepressor response is defined as a fall in systolic
BP of more than 50 mmHg. Carotid sinus pressure will produce
positive findings in about 10% of elderly individuals, but fewer
than 25% of these experience spontaneous syncope. Symptoms
should not, therefore, be attributed to hypersensitive carotid sinus
syndrome unless they are reproduced by carotid sinus pressure.
Initial investigations
A 12-lead ECG is essential in all patients presenting with
syncope or presyncope. Lightheadedness may occur with many
arrhythmias, but blackouts (Stokes–Adams attacks, p. 477) are
usually due to profound bradycardia or malignant ventricular
tachyarrhythmias. The ECG may show evidence of conducting
system disease (e.g. sinus bradycardia, atrioventricular block,
bundle branch block), which would predispose a patient to
bradycardia, but the key to establishing a diagnosis is to obtain
an ECG recording while symptoms are present. Since minor
rhythm disturbances are common, especially in the elderly,
symptoms must occur at the same time as a recorded arrhythmia
before a diagnosis can be made. Ambulatory ECG recordings
are helpful only if symptoms occur several times per week.
Patient-activated ECG recorders are useful for examining the
rhythm in patients with recurrent dizziness but are not helpful
in assessing sudden blackouts. When these investigations fail
to establish a cause in patients with presyncope or syncope, an
implantable ECG recorder can be sited subcutaneously over the
upper left chest. This device continuously records the cardiac
rhythm and will activate automatically if extreme bradycardia or
tachycardia occurs. The ECG memory can also be tagged by
the patient, using a hand-held activator as a form of ‘symptom
diary’. Stored ECGs can be accessed by the implanting centre,
using a telemetry device in a clinic, or using a home monitoring
system via an online link.
Head-up tilt-table testing is a provocation test used to establish
the diagnosis of vasovagal syncope. It involves positioning the
patient supine on a padded table that is then tilted to an angle of
60–70° for up to 45 minutes, while the ECG and BP responses
are monitored. A positive test is characterised by bradycardia
(cardio-inhibitory response) and/or hypotension (vasodepressor
response), associated with typical symptoms.
Delirium
Delirium is a syndrome of transient, reversible cognitive dysfunction
that is more common in old age. It is associated with high rates
of mortality, complications and institutionalisation, and with
longer lengths of stay. The recognised risk factors for delirium
are shown in Box 10.8.
Presentation
Delirium manifests as a disturbance of arousal with global
impairment of mental function, causing drowsiness with
10.8 Risk factors for delirium
Predisposing factors
• Old age
• Dementia
• Frailty
• Sensory impairment
• Polypharmacy
• Renal impairment
Precipitating factors
• Intercurrent illness
• Surgery
• Change of environment
or ward
• Sensory deprivation
(e.g. darkness) or overload
(e.g. noise)
• Medications (e.g. opioids,
psychotropics)
• Dehydration
• Pain
• Constipation
• Urinary catheterisation
• Acute urinary retention
• Hypoxia
• Fever
• Alcohol withdrawal
10.9 How to make a diagnosis of delirium: the 4AT
Alertness
This includes patients who may be markedly drowsy (e.g. difficult to
rouse and/or obviously sleepy during assessment) or agitated/
hyperactive. Observe the patient. If asleep, attempt to wake with
speech or gentle touch on shoulder. Ask the patient to state their
name and address to assist rating:
• Normal (fully alert, but not agitated, throughout assessment)
• Mild sleepiness for <10 secs after waking, then normal
• Clearly abnormal
AMT4
Age, date of birth, place (name of the hospital or building), current
year:
• No mistakes
• 1 mistake
• ≥2 mistakes/untestable
Attention
Say to the patient: ‘Please tell me the months of the year in backwards
order, starting at December.’ To assist initial understanding, one
prompt of ‘What is the month before December?’ is permitted:
• Achieves ≥7 months correctly
• Starts but scores < 7 months/refuses to start
• Untestable (cannot start because unwell, drowsy, inattentive)
Acute change or fluctuating course
Evidence of significant change or fluctuation in: alertness, cognition,
other mental function (e.g. paranoia, hallucinations) arising over the
last 2 weeks and still evident in last 24 hrs:
• No
• Yes
Total 4AT score (maximum possible score 12)
≥4: possible delirium ± cognitive impairment
1–3: possible cognitive impairment
0:
delirium or severe cognitive impairment unlikely (but delirium still
possible if information in 4 incomplete)
(AMT4 = Abbreviated Mental Test 4)
disorientation, perceptual errors and muddled thinking. The
three broad subtypes of delirium – hypoactive, hyperactive
and mixed – can be differentiated on the basis of psychomotor
changes. Patients with hyperactive delirium are often agitated
and restless, whereas hypoactive delirium can present as lethargy
and sedation, and is frequently misdiagnosed as depression or
dementia. Fluctuation is typical and delirium is often worse at
184 • ACUTE MEDICINE AND CRITICAL ILLNESS
• pyrexia and any signs of infection in the chest, skin,
abdomen or urine (on dipstick testing)
• oxygen saturation and signs of CO2 retention
• signs of alcohol withdrawal or psychoactive drug use,
such as tremor or sweating
• any focal neurological signs.
Certain psychiatric conditions, such as depressive pseudodementia and dissociative disorder, can easily be mistaken for
delirium. Mental state examination is necessary to seek evidence of
associated mood disorder, hallucinations, delusions or behavioural
abnormalities. Examination should also include cognitive testing
with a tool such as the Mini-Mental State Examination (MMSE)
or the Montreal Cognitive Assessment (MoCA) (p. 1181).
Investigations and management
Common causes of delirium, along with appropriate investigative
pathways, are shown in Figure 10.4. Alongside investigation
and treatment of underlying causes, delirium and disorientation
should be minimised by a well-lit and quiet environment, with
hearing aids and glasses readily available. Good nursing is
needed to preserve orientation, prevent pressure sores and falls,
and maintain hydration, nutrition and continence. Sedatives may
worsen delirium and should be used as a last resort. Resolution of
delirium, particularly in the elderly, may be slow and incomplete.
Many patients fail to recover to their pre-morbid level of cognition.
night, when delirious patients can present significant management
difficulties. Emotional disturbance (anxiety, irritability or depression)
is common. History-taking from a delirious patient is frequently
impossible, and every effort should be made to obtain a
collateral history from a close friend or relative. As delirium is
particularly common in patients with dementia, the collateral
history should ask specifically about onset and course of delirium,
along with any functional consequences in comparison to the
patient’s norm.
Clinical assessment
In order to manage delirium effectively, the first step is to make
a diagnosis. Tools such as the 4AT (Box 10.9) or the Confusion
Assessment Method (CAM) can be used to detect delirium
and differentiate it from dementia; such screening tools should
be applied to all older patients admitted to hospital. Once a
diagnosis of delirium has been established, attempts should
be made to identify all of the reversible precipitating factors.
Symptoms suggestive of a physical illness, such as an infection
or stroke, should be elicited. An accurate drug and alcohol history
is required, especially to ascertain whether any drugs have
been recently stopped or started (see Fig. 10.4 for commonly
implicated drugs). Although not always possible in its entirety,
a full physical examination of all delirious patients should be
attempted, noting in particular:
Fig. 10.4 Common causes and investigation of delirium. All investigations are performed routinely, except those in italics. Tend to present over
weeks to months rather than hours to days. The chest X-ray shows right mid- and lower zone consolidation. The CT scan shows a subdural haematoma.
(COPD = chronic obstructive pulmonary disease; CRP = C-reactive protein; MI = myocardial infarction; SSRI = selective serotonin re-uptake inhibitor; UTI =
urinary tract infection)
Infection
Metabolic
disturbance
Toxic insult
Acute
neurological
conditions
Pain, hypoxia
Pneumonia
UTI
Skin: cellulitis, abscess
Gram-negative sepsis
Full blood count, CRP
Chest X-ray
Urinalysis and culture
Others as appropriate: sputum,
blood cultures, wound swabs
Digoxin level if prescribed
Urea and electrolytes
Plasma calcium
Capillary blood and plasma glucose
Liver function tests
Thyroid function tests
B12 and folate
CT brain: only when intracranial
lesion is suspected (focal neurological
signs, recent fall or head injury) or no
other physical cause of delirium is
identified
Lumbar puncture: only if meningitis or
encephalitis is suspected
Pulse oximetry (arterial blood gases
if low)
Chest X-ray
ECG
Acute renal impairment
Hyponatraemia/hypernatraemia
Hypercalcaemia
Hypoglycaemia
Hepatic encephalopathy
Thiamin deficiency
Hypothyroidism
B12 deficiency*
Any drug but particularly
• Anticholinergics
• Digoxin
• Opiates
• Psychotropics
• High-dose glucocorticoids
Withdrawal of alcohol, opiate, SSRI
or benzodiazepine
Acute stroke
Subdural haematoma
Encephalitis or meningitis
Seizure (post-ictal)
Space-occupying lesion, e.g. tumour
Pulmonary embolism
Pneumonia
Pulmonary oedema
COPD exacerbation
Acute MI
Presenting problems in acute medicine • 185
photophobia/phonophobia, may support a diagnosis of migraine
but others, such as progressive focal symptoms or constitutional
upset like weight loss, may suggest a more sinister cause. The
headache of cerebral venous thrombosis may be ‘throbbing’ or
‘band-like’ and associated with nausea, vomiting or hemiparesis.
Raised intracranial pressure (ICP) headache tends to be worse
in the morning and when lying flat or coughing, and associated
with nausea and/or vomiting.
A description of neck stiffness along with headache and
photophobia should raise the suspicion of meningitis (Box 10.12),
although this may present in atypical ways in immunosuppressed,
alcoholic or pregnant patients. The behaviour of the patient
during headache is often instructive; migraine patients typically
retire to bed to sleep in a dark room, whereas cluster headache
often induces agitated and restless behaviour. The pain of a
subarachnoid haemorrhage frequently causes significant distress.
Headache duration is also important to elicit; headaches that
have been present for months or years are almost never sinister,
whereas new-onset headache, especially in the elderly, is more
of a concern. In a patient over 60 years with head pain localised
to one or both temples, scalp tenderness or jaw claudication,
temporal arteritis (p. 1042) should be considered.
Clinical assessment
An assessment of conscious level (using the Glasgow Coma
Scale (GCS); Fig. 10.5) should be performed early and constantly
reassessed. A decreased conscious level suggests raised ICP
and urgent CT scanning (with airway protection if necessary) is
indicated. A full neurological examination may provide clues as to
the pathology involved; for example, brainstem signs in the context
of acute-onset occipital headache may indicate vertebrobasilar
dissection. Neurological signs may, however, be ‘falsely localising’,
as in large subarachnoid haemorrhage or bacterial meningitis.
Care should be taken to examine for other evidence of meningitis
such as a rash (not always petechial), fever or signs of shock.
Unilateral headache with agitation, ipsilateral lacrimation, facial
sweating and conjunctival injection is typical of cluster headache.
Conjunctival injection may also be seen in acute glaucoma,
accompanied by peri- or retro-orbital pain, clouding of the cornea,
decreased visual acuity and, often, systemic upset. Temporal
headaches in patients over 60 should prompt examination for
enlarged or tender temporal arteries and palpation of temporal
pulses (often absent in temporal arteritis). Visual acuity should be
assessed promptly, as visual loss is an important complication
of temporal arteritis.
Initial investigations
If there is any alteration of conscious level, focal neurological signs,
new-onset seizures or a history of head injury, then CT scanning
of the head is indicated. The urgency of scanning will depend
on the clinical picture and trajectory but in many circumstances
10.10 Primary and secondary headache syndromes
Primary headache syndromes
• Migraine (with or without aura)
• Tension-type headache
• Trigeminal autonomic cephalalgia (including cluster headache)
• Primary stabbing/coughing/exertional/sex-related headache
• Thunderclap headache
• New daily persistent headache syndrome
Secondary causes of headache
• Medication overuse headache (chronic daily headache)
• Intracranial bleeding (subdural haematoma, subarachnoid or
intracerebral haemorrhage)
• Raised intracranial pressure (brain tumour, idiopathic intracranial
hypertension)
• Infection (meningitis, encephalitis, brain abscess)
• Inflammatory disease (temporal arteritis, other vasculitis, arthritis)
• Referred pain from other structures (orbit, temporomandibular
joint, neck)
Headache
Headache is common and causes considerable worry amongst
both patients and clinicians, but rarely represents sinister disease.
The causes may be divided into primary or secondary, with primary
headache syndromes being vastly more common (Box 10.10).
Presentation
The primary purpose of the history and clinical examination in
patients presenting with headache is to identify the small minority
of patients with serious underlying pathology. Key features of the
history include the temporal evolution of a headache; a headache
that reached maximal intensity immediately or within 5 minutes
of onset requires rapid assessment for possible subarachnoid
haemorrhage. Other ‘red flag’ symptoms are shown in Box 10.11.
It is important to establish whether the headache comes and
goes, with periods of no headache in between (usually migraine),
or whether it is present all or almost all of the time. Associated
features, such as preceding visual symptoms, nausea/vomiting or
10.11 ‘Red flag’ symptoms in headache
Symptom
Possible explanation
Sudden onset (maximal immediately or
within 5 mins)
Subarachnoid haemorrhage
Cerebral venous sinus
thrombosis
Pituitary apoplexy
Meningitis
Focal neurological symptoms (other
than for typically migrainous)
Intracranial mass lesion:
Vascular
Neoplastic
Infection
Constitutional symptoms:
Weight loss
General malaise
Pyrexia
Meningism
Rash
Meningitis
Encephalitis
Neoplasm (lymphoma or
metastases)
Inflammation (vasculitis)
Raised intracranial pressure (worse on
waking/lying down, associated vomiting)
Intracranial mass lesion
New onset aged > 60 years
Temporal arteritis
10.12 Identification of bacterial meningitis
In patients presenting with headache, identification of those with
bacterial meningitis is a top priority to facilitate rapid antibiotic
treatment. In almost all cases there will be one of the following
features:
• meningism (neck stiffness, photophobia, positive Kernig’s sign)
• fever > 38°C
• signs of shock (tachycardia, hypotension, elevated serum lactate)
• rash (not always petechial)
186 • ACUTE MEDICINE AND CRITICAL ILLNESS
after headache onset, to look for evidence of xanthochromia. It is
increasingly accepted, however, that a negative CT scan within 6
hours of headache onset has such a high degree of sensitivity for
excluding subarachnoid haemorrhage that an LP is not necessary.
In such circumstances, a CT angiogram should be considered
to exclude other pathology, such as arterial dissection. Many
headaches require prompt involvement of specialists. Features of
acute glaucoma, for example, require immediate ophthalmological
review for measurement of intraocular pressures. Suspected
temporal arteritis with an erythrocyte sedimentation rate (ESR) of
50 mm/hr should prompt immediate glucocorticoid therapy and
rheumatological referral (see p. 1042 for management). Features
of raised ICP in the absence of a mass lesion on neuroimaging
may indicate idiopathic intracranial hypertension; CSF opening
pressure is likely to be informative.
Unilateral leg swelling
Most leg swelling is caused by oedema, the accumulation of
fluid within the interstitial space. There are three explanatory
mechanisms for development of oedema that are described
in Box 10.13. Unilateral swelling usually indicates a localised
pathology in either the venous or the lymphatic system, while
bilateral oedema often represents generalised fluid overload
combined with the effects of gravity. However, all causes of
unilateral leg swelling may present bilaterally, and generalised
fluid overload may present with asymmetrical (and therefore
apparently unilateral) oedema. Fluid overload may be the result of
cardiac failure, pulmonary hypertension (even in the absence of
right ventricular failure), renal failure, hypoalbuminaemia or drugs
(calcium channel blockers, glucocorticoids, mineralocorticoids,
non-steroidal anti-inflammatory drugs (NSAIDs) and others);
see Box 16.14 (p. 463) for other causes. The remainder of this
section focuses on the causes of ‘unilateral’ oedema.
Presentation
Any patient who presents with unilateral leg swelling should
be assessed with the possibility of deep vein thrombosis (DVT)
in mind. The pain and swelling of a DVT is often fairly gradual
in onset, over hours or even days. Sudden-onset pain in the
posterior aspect of the leg is more consistent with gastrocnemius
muscle tear (which may be traumatic or spontaneous) or a
ruptured Baker’s cyst. Leg swelling and pain associated with
paraesthesia or paresis, or in the context of lower limb injury
or reduced conscious level, should always prompt concern
regarding the possibility of compartment syndrome (Box 10.14).
Clinical assessment
Lower limb DVT characteristically starts in the distal veins,
causing an increase in temperature of the limb and dilatation
of the superficial veins. Often, however, symptoms and signs
are minimal.
will be immediately required. Intracranial haemorrhage or a
space-occupying lesion with mass effect should prompt urgent
neurosurgical referral. If bacterial meningitis is suspected (Box
10.12), cerebrospinal fluid (CSF) analysis is required to make a
definite diagnosis. Antibiotics should not be delayed for lumbar
puncture (LP), which needs to be preceded by CT scanning only if
raised ICP is suspected. In cases of thunderclap headache (peak
intensity within 5 minutes and lasting over an hour), a normal CT
scan should be followed by an LP performed more than 12 hours
Fig. 10.5 Assessment of the Glasgow Coma Scale (GCS) score in an
obtunded patient. Avoid using a sternal rub, as it causes bruising.
Hello, Mr XXX.
Can you open your
eyes, please?
Score best eyes/
motor/verbal response
Trapezius pinch
Score response looking
at arms for localisation/
flexion/abnormal flexion
Pressure on
supra-orbital ridge
Score response
Firm nail-bed
pressure
Score if withdrawal present
or any eye/verbal response
No response
No response
No response
10.13 Mechanisms of oedema
There are three explanatory mechanisms for the development of
oedema that may occur in isolation or combination:
• increased hydrostatic pressure in the venous system due to
increased intravascular volume or venous obstruction
• decreased oncotic pressure secondary to a decrease in the plasma
proteins that retain fluid within the circulation
• obstruction to lymphatic drainage (‘lymphoedema’)
Presenting problems in acute medicine • 187
10.14 Identification of compartment syndrome
• Compartment syndrome classically occurs following extrinsic
compression of a limb due to trauma or reduced conscious level
(especially when caused by drugs or alcohol)
• It usually presents with a tense, firm and exquisitely painful limb
• The pain is characteristically exacerbated by passive muscle
stretching or squeezing the compartment
• Altered sensation may be evident distally
• Absent peripheral pulses are a late sign and their presence does
not exclude the diagnosis
• Clinical suspicion of compartment syndrome should prompt
measurement of creatine kinase and urgent surgical review
Cellulitis is usually characterised by erythema and skin warmth
localised to a well-demarcated area of the leg and may be
associated with an obvious source of entry of infection (e.g. leg
ulcer or insect bite). The patient may be febrile and systemically
unwell. Superficial thrombophlebitis is more localised; erythema
and tenderness occur along the course of a firm, palpable vein.
Examination of any patient presenting with leg swelling should
include assessment for malignancy (evidence of weight loss, a
palpable mass or lymphadenopathy). Malignancy is a risk factor
for DVT, but pelvic or lower abdominal masses can also produce
leg swelling by compressing the pelvic veins or lymphatics.
Early lymphoedema is indistinguishable from other causes of
oedema. More chronic lymphoedema is firm and non-pitting,
often with thickening of the overlying skin, which may develop
a ‘cobblestone’ appearance.
Chronic venous insufficiency is a cause of long-standing
oedema that, particularly when combined with another cause
of leg swelling, may acutely worsen. Characteristic skin changes
(haemosiderin deposition, hair loss, varicose eczema, ulceration)
and prominent varicosities are common, and sometimes cause
diagnostic confusion with cellulitis. See Box 10.14 for the
examination findings associated with compartment syndrome.
Initial investigations
Clinical criteria can be used to rank patients according to their
likelihood of DVT, by using scoring systems such as the Wells
score (Box 10.15). Figure 10.6 gives an algorithm for investigation
of suspected DVT based on initial Wells score. In patients with
a low (‘unlikely’) pre-test probability of DVT, D-dimer levels can
be measured; if these are normal, further investigation for DVT is
unnecessary. In those with a moderate or high (‘likely’) probability
of DVT or with elevated D-dimer levels, objective diagnosis of
DVT should be obtained using appropriate imaging, usually a
Doppler ultrasound scan. The investigative pathway for DVT,
therefore, differs according to the pre-test probability (p. 11) of
DVT. For low-probability DVT, the negative predictive value of
the D-dimer test (the most important parameter in this context)
is over 99%; if the test is negative, the clinician can discharge
the patient with confidence. In patients with a high probability
of DVT, the negative predictive value of a D-dimer test falls to
somewhere in the region of 97–98%. While this may initially
appear to be a high figure, to discharge 2 or 3 patients in every
100 incorrectly would generally be considered an unacceptable
error rate. Hence, with the exception of pregnancy (Box 10.16),
a combination of clinical probability and blood test results should
be used in the diagnosis of venous thromboembolism.
If cellulitis is suspected, serum inflammatory markers, skin
swabs and blood cultures should be sent, ideally before antibiotics
10.15 Predicting the pre-test probability of deep vein
thrombosis (DVT) using the Wells score*
Clinical characteristic
Score
Previous documented DVT
Active cancer (patient receiving treatment for cancer
within previous 6 months or currently receiving
palliative treatment)
Paralysis, paresis or recent plaster immobilisation of
lower extremities
Recently bedridden for ≥ 3 days, or major surgery
within previous 4 weeks
Localised tenderness along distribution of deep venous
system
Entire leg swollen
Calf swelling at least 3 cm larger than that on
asymptomatic side (measured 10 cm below tibial
tuberosity)
Pitting oedema confined to symptomatic leg
Collateral superficial veins (non-varicose)
Alternative diagnosis at least as likely as DVT
–2
Clinical probability
Total score
DVT low probability
< 1
DVT moderate probability
1–2
DVT high probability
2
From Wells PS. Evaluation of D-dimer in the diagnosis of suspected deep-vein
thrombosis. N Engl J Med 2003; 349:1227; copyright © 2003 Massachusetts
Medical Society.
*A dichotomised revised Wells score, which classifies patients as ‘unlikely’ or
‘likely’, may also be used.
Fig. 10.6 Investigation of suspected deep vein thrombosis. Pre-test
probability is calculated in Box 10.15. See also page 11.
Pre-test probability
(see Box 10.15)
Low
D-dimer −ve
D-dimer +ve
+ve
+ve
−ve
−ve
Probability low,
or moderate
with −ve D-dimer
Probability high,
or moderate
with +ve D-dimer
Repeat compression
ultrasound in 7 days
Treat
Exclude
Compression
ultrasound
Moderate
or high
are given. Ruptured Baker’s cyst and calf muscle tear can both
be readily diagnosed on ultrasound. If pelvic or lower abdominal
malignancy is suspected, a prostate-specific antigen (PSA)
level should be measured in males and appropriate imaging
with ultrasound (transabdominal or transvaginal) or CT should
be undertaken.
188 • ACUTE MEDICINE AND CRITICAL ILLNESS
Fig. 10.7 Identifying and responding to physiological deterioration.
A An example of an early warning score chart. (NEWS = National Early
Warning Score; V/P/U = Verbal/Pain/Unresponsive)
NEWS Key
Sp02
Date:
Time:
≥25
21–24
12–20
9–11
≤8
Default
Chronic
Hypoxia
≥91
≥39°
38°
37°
36°
≤35°
140
Regular Y/N
Alert
V/P/U
New confusion
Unrecordable
≥88
94–95
Medical signature
required to use scale
for patients with
Chronic Hypoxia
Sign
92–93
86–87
≤91
≤85
Unrecordable
% or litres
Inspired 02
Temperature
NEWS
SCORE
uses
Systolic BP
If manual BP
mark as
M
Heart Rate
Conscious
Level
Respiratory
Rate
A
Identification and assessment
of deterioration
Early warning scores and the role of the
medical emergency team
There are many systems that have been developed with the aim
of rapidly identifying and managing physiological deterioration.
These are referred to as ‘rapid response systems’. One popular
example of a rapid response system is a medical emergency
team (MET). A MET system operates on the basis that when a
patient meets certain physiological criteria, the team is alerted.
The team is expected to make a rapid assessment and institute
immediate management. This may include escalation to critical
care or, following liaison with the parent clinical team, ongoing
ward-based care.
The trigger for a ‘MET’ call may be a single parameter – such
as a low BP or tachycardia – or may consist of a composite
early warning score. Early warning score systems function by the
observer allocating a value between 0 and 3 for abnormalities in
respiratory rate, SpO2, temperature, BP, heart rate, neurological
response and urine output (Fig. 10.7). The values are summed
and the composite score gives an indication of the severity
of physiological derangement. Early warning systems can be
automated into an electronic format that calculates the score and
even alerts the responsible clinician(s) by email or text message.
There are advantages and disadvantages to having a separate
MET system, compared with allowing the responsible clinical
team to manage deterioration, and to having a composite score
or a single parameter detection system. These are outlined in
Box 10.17.
Immediate assessment of the
deteriorating patient
An approach to assessment of the deteriorating patient can be
summarised by the mnemonic ‘C-A-B-C-D-E’.
C – Control of obvious problem
For example, if the patient has ventricular tachycardia on the
monitor or significant blood loss is apparent, immediate action
is required.
A and B – Airway and breathing
If the patient is talking in full sentences, then the airway is clear
and breathing is adequate. A rapid history should be obtained
while the initial assessment is undertaken. Breathing should
be assessed with a focused respiratory examination. Oxygen
saturations and ABGs should be checked early (p. 190).
10.16 Swollen legs in pregnancy
• Benign swollen legs: common in pregnancy; this is usually
benign.
• DVT: pregnancy is a significant risk factor, however.
• D-dimer: should not be measured in pregnancy; it has not been
validated in this group.
• Imaging: should be arranged on the basis of clinical suspicion
alone, and the threshold for undertaking a definite diagnostic test
should be low.
Identification and assessment of deterioration • 189
• Inform registered nurse
• Registered nurse assessment using ABCDE
• Review frequency of observations
• Inform Nurse in Charge
• If ongoing concern, escalate to Medical Team
• Continue routine NEWS monitoring with every set of observations
Minimum 12 hourly/4 hourly
in admission areas
Frequency of Observations
NEWS Score
Total 0*
Total 1–4*
Total 7*
or more
Total 5–6*
or
3 in one
parameter
*Regardless of NEWS always escalate if concerned about a patient’s condition
Clinical Response
Minimum 4 hourly
Consider Structured Response Tool
Consider Fluid Balance Chart
Increase frequency to a
minimum of 1 hourly
Start Structured Response Tool
Start Fluid Balance Chart
Continuous monitoring
of vital signs
Start Structured Response Tool
Start Fluid Balance Chart
• Registered nurse assessment
• Inform Nurse in Charge
• Escalate to Medical Team as per local escalation
• Urgent medical assessment
• Management plan to be discussed with Senior Trainee or above
• Consider level of monitoring required in relation to clinical care
• Registered nurse to assess immediately
• Inform Nurse in Charge
• Request immediate assessment by Senior Trainee or above
• Case to be discussed with supervising Consultant
• If appropriate contact Critical Care for review
B
B Responses to physiological deterioration. A and B, From Royal College of Physicians. National Early Warning Score (NEWS):
standardising the assessment of acute-illness severity in the NHS. Report of a working party. London: RCP, 2012.
Fig. 10.7, cont’d
10.17 Advantages and disadvantages of different rapid response systems
System
Advantages
Disadvantages
Single parameter trigger
High sensitivity. Probably picks up subclinical
deterioration and allows optimisation
Low specificity. Much time will be spent with patients who are
not deteriorating
Composite early warning
scoring system,
e.g. NEWS or MEWS score
Combines good sensitivity with improved
specificity
May miss single parameter deterioration that is still significant,
e.g. a drop of 2 GCS points may not trigger an alert
MET system
Brings expertise in deteriorating patients
immediately to the bedside
Expensive to have well-trained individuals who are free from
other clinical duties. May deskill the ward-based teams in acute
care. May not have expertise in highly specific areas of medicine
Clinical team review
Patient is seen by clinicians familiar with the
patient and condition
Clinical team may be busy with other urgent duties. There may
not be expertise in acute care within the ward-based team
(GCS = Glasgow Coma Scale; MET = Medical Emergency Team; MEWS = Modified Early Warning Score; NEWS = National Early Warning Score)
C – Circulation
A focused cardiovascular examination should include heart rate
and rhythm, jugular venous pressure, evidence of bleeding,
signs of shock and abnormal heart sounds. The carotid pulse
should be palpated in the collapsed or unconscious patient, but
peripheral pulses also should be checked in conscious patients.
The radial, brachial, foot and femoral pulses may disappear as
shock progresses, and this indicates the severity of circulatory
compromise.
D – Disability
Conscious level should be assessed using the GCS (see Fig. 10.5
and Box 10.24, pp. 186 and 194). A brief neurological examination
looking for focal signs should be performed. Capillary blood
glucose should always be measured to exclude hypoglycaemia
or severe hyperglycaemia.
E – Exposure and evidence
‘Exposure’ indicates the need for targeted clinical examination
of the remaining body systems, particularly the abdomen and
lower limbs. ‘Evidence’ may be gathered via a collateral history
from other health-care professionals or family members, recent
investigations, prescriptions or monitoring charts.
Selecting the appropriate location for
ongoing management
Any patient who will gain benefit from a critical care area should be
admitted. Such patients generally fall into two groups: those with
organ dysfunction severe enough to require organ support and
those in whom the disease process is clearly setting them on a
downward trajectory and in whom early, aggressive management
may alter the outcome. Whether an individual patient should be
190 • ACUTE MEDICINE AND CRITICAL ILLNESS
Analysis of an arterial blood sample is especially helpful
in narrowing the differential diagnosis and confirming clinical
suspicion of severity. The ‘base excess’ provides rapid
quantification of the component of disease that is metabolic
in origin. A base excess lower than −2 mEq/L (or, put another
way, a ‘base deficit’ of more than 2 mEq/L) is likely to represent
a metabolic acidosis. A simple rule of thumb is that a lactate of
more than 4 mmol/L or a base deficit of more than 10 mEq/L
should cause concern and trigger escalation to a higher level of
care. In addition to clinical examination, chest radiography and
bedside ultrasound can help to distinguish the cause of poor
air entry; consolidation and effusion can be readily identified
and a significant pneumothorax can be excluded (as shown
in Fig. 10.8).
Hypoxaemia
Pathophysiology
Low arterial partial pressure of oxygen (PaO2) is termed
hypoxaemia. It is a common presenting feature of deterioration.
Hypoxia is defined as an inadequate amount of oxygen in tissues
(or the inability of cells to use the available oxygen for cellular
respiration). Hypoxia may be due to hypoxaemia, or may be
secondary to impaired cardiac output, the presence of inadequate
or dysfunctional haemoglobin, or intracellular dysfunction (such
as in cyanide poisoning, where oxygen utilisation at the cellular
level is impaired).
Over 97% of oxygen carried in the blood is bound to
haemoglobin. The haemoglobin–oxygen dissociation curve
delineates the relationship between the percentage saturation
of haemoglobin with oxygen (SO2) and the partial pressure
(PO2) of oxygen in the blood. A shift in the curve will influence
the uptake and release of oxygen by the haemoglobin
molecule. As capillary PCO2 rises, the curve moves to the
right, increasing the offloading of oxygen in the tissues (the
Bohr effect). This increases capillary PO2 and hence cellular
oxygen supply. Shifts of the oxyhaemoglobin dissociation curve
can have significant implications in certain disease processes
(Fig. 10.9).
admitted to the intensive care or high-dependency unit (ICU/
HDU) will depend on local arrangements. A useful tool to assist
with the decision regarding location is the ‘level of care’ required
(Box 10.18). Many intensive care units are a mix of level 2 and
level 3 beds, which streamlines the admission process.
Common presentations of deterioration
As patients become critically unwell, they usually manifest
physiological derangement. The principle underpinning critical
care is the simultaneous assessment of illness severity and
the stabilisation of life-threatening physiological abnormalities.
The goal is to prevent deterioration and effect improvements,
as the diagnosis is established and treatment of the underlying
disease process is initiated.
It can be useful to consider the physiological changes as a
starting point to help delineate urgent investigations and supportive
treatment, which should proceed alongside the search for a
definitive diagnosis.
Tachypnoea
Pathophysiology
A raised respiratory rate (tachypnoea) is the earliest and most
sensitive sign of clinical deterioration. Tachypnoea may be primary
(i.e. a problem within the respiratory system) or secondary to
pathology elsewhere in the body. Cardiopulmonary causes
of tachypnoea have been covered on page 179. Secondary
tachypnoea is usually due to a metabolic acidosis, most commonly
observed in the context of sepsis, haemorrhage, ketoacidosis
or visceral ischaemia. More detailed information on metabolic
acidosis can be found on page 364.
Assessment and management
A simple assessment of a patient’s clinical status and basic
physiology will usually indicate whether urgent intervention is
required. In the examination, attention should be paid to the
adequacy of chest expansion, air entry and the presence of
added sounds such as wheeze.
10.18 Levels of care and the corresponding admission criteria for intensive care unit (ICU) and high-dependency unit (HDU)
Level of care
Criteria
Appropriate location
Patients requiring/likely to require endotracheal intubation and invasive mechanical ventilatory support
Patients requiring support of two or more organ systems (e.g. inotropes and haemofiltration)
Patients with chronic impairment of one or more organ systems (e.g. COPD or severe ischaemic heart
disease) who require support for acute reversible failure of another organ
ICU
Patients requiring detailed observation or monitoring that cannot be provided at ward level:
Direct arterial BP monitoring
CVP monitoring
Fluid balance
Neurological observations, regular GCS recording
Patients requiring support for a single failing organ system, excluding invasive ventilatory support (IPPV):
Non-invasive respiratory support (p. 202)
Moderate inotropic or vasopressor support
Renal replacement therapy in an otherwise stable patient
Step-down from intensive care requiring additional monitoring or single organ support
HDU
Patients in whom frequent but intermittent observations and medical review are sufficient
General ward setting
(BP = blood pressure; COPD = chronic obstructive pulmonary disease; CVP = central venous pressure; GCS = Glasgow Coma Scale; IPPV = intermittent positive pressure
ventilation)
Common presentations of deterioration • 191
with acute stroke, those with MI and those who chronically retain
CO2. Adverse effects of hyperoxia include:
• free radical-induced tissue damage
• less efficient buffering of carbon dioxide by
oxyhaemoglobin (compared to deoxyhaemoglobin)
• less efficient ventilation–perfusion matching in lung units
(due to loss of hypoxic vasoconstriction of under-ventilated
lung units)
• decreased hypoxic respiratory drive in individuals with
chronic hypercapnia.
When attempting to determine the cause of hypoxaemia,
it is useful to consider whether the primary physiological
mechanism is a type of shunt, or one of the many causes
of ventilation–perfusion mismatch, such as alveolar or central
hypoventilation (Fig. 10.10). A classification of common causes
of hypoxaemia in hospitalised patients is shown in Box 10.20.
In reality, the observed physiological abnormality may represent
a combination of inter-related processes, such as severe
pulmonary oedema leading to exhaustion, which in turn causes
hypoventilation.
Evaluation of risk factors, history and examination will help to
differentiate the likely aetiology and guide specific management.
Further management of respiratory failure is discussed on page 202.
Tachycardia
Pathophysiology
A heart rate of > 110 beats/min in an adult should always be
considered abnormal and not attributed to anxiety until other
causes have been excluded. Intrinsic cardiac causes (atrial
fibrillation (AF), atrial flutter, supraventricular tachycardia and
Due to the shape of the curve, a small drop in arterial PO2
(PaO2) below 8 kPa (60 mmHg) will cause a marked fall in SaO2.
Relative hypoxaemia refers to the comparison between the
observed PaO2 and that which might be expected for a given
fraction of inspired oxygen (FiO2). With the patient breathing
air, PaO2 of 12–14 kPa (90–105 mmHg) would be expected;
with the patient breathing 100% oxygen, a PaO2 of > 60 kPa
(450 mmHg) would be normal.
Assessment and management
Oxygen therapy should be titrated to avoid hyperoxia (too high a
PaO2; Box 10.19). Hyperoxia is theoretically harmful via a number
of mechanisms. This has a clinically significant effect in patients
Fig. 10.8 Using ultrasound to rule out an anterior pneumothorax. A Probe position and orientation. B and C Two-dimensional (2D) ultrasound
images. D and E M-mode ultrasound images. Key: (1) Intercostal muscle. (2) Rib. (3) Normal bright pleural line –‘shimmering appearance’ of sliding
pleura. (4) Lung. (5) Absent ‘shimmering’ in pneumothorax and lung not visible. (6) Normal – ‘sea shore’ sign excludes pneumothorax at that location.
The ‘sea shore’ is represented by the bright granular line with lung (sea) deeper to the bright line. (7) Absent granular pleural line and a repeating linear
pattern or ‘barcode’ sign suggest the presence of pneumothorax.
Normal
(no pneumothorax)
Normal
(no pneumothorax)
3 4
B
D
C
A
E
Abnormal
(pneumothorax cannot
be excluded)
Abnormal
(pneumothorax cannot
be excluded)
Fig. 10.9 The haemoglobin–oxygen dissociation curve and the effect
of CO2 on oxygen saturations. In pulmonary embolism, compensatory
hyperventilation often occurs. PaCO2 decreases, shifting the
oxyhaemoglobin saturation curve to the left (green line). Therefore, despite
a low PaO2 (8 kPa/60 mmHg), the saturation reading is 93%.
= 6.0 kPa
= 45 mmHg
PO2 (kPa or mmHg)
Haemoglobin saturation (SO2) %
= 4.1 kPa
= 31 mmHg
kPa
mmHg
P75
P50
9 10 11 12 13 14
10.19 Prescribing oxygen in critical illness
• Oxygen should be prescribed to achieve a target saturation of
94–98% for most critically unwell patients.
• 88–92% is a more appropriate target range for those at risk of
hypercapnic respiratory failure.
192 • ACUTE MEDICINE AND CRITICAL ILLNESS
Hypovolaemia should not be missed. Concealed bleeding (e.g.
into the pleura, gastrointestinal tract or retroperitoneum) may not
be apparent initially and assessment of haemoglobin in an acute
haemorrhage, when < 30 mL/kg of fluid has been administered,
can be misleadingly high. Sepsis and other hyper-metabolic
conditions may present with a tachycardia that is accompanied by
tachypnoea, peripheral vasodilatation and a raised temperature.
Other organ dysfunction should be noted from a brief general
examination and salient points from the history.
Assessment and management
The management of a tachycardic patient should focus on
treating the cause. Treating the rate alone with beta-blockade
in an unwell or deteriorating patient should be done only under
specialist guidance, in controlled conditions, and when a clear
evaluation of the risk–benefit ratio has been undertaken.
The recognition and management of primary cardiac
dysrhythmias are discussed on page 468. The most appropriate
method of rate control in AF depends primarily on the degree
of haemodynamic compromise. An intravenous loading dose of
amiodarone is well tolerated and efficacious in the majority of
critically ill patients with AF and a very rapid ventricular rate. There
are thromboembolic concerns regarding chemical cardioversion
of AF of unknown duration. However, in deteriorating patients,
the low incidence of embolic events makes this concern of
secondary importance to achieving haemodynamic stability.
Digoxin continues to have a role in the treatment of AF in
critically unwell but haemodynamically stable patients, when
ventricular dysrhythmias) are less common in the general inpatient
population than secondary causes of tachycardia.
A cardiac monitor or 12-lead ECG early in the examination will
help both determine severity (heart rate > 160 beats/min should
prompt urgent escalation to a higher level of care) and narrow
the differential diagnosis. AF with a rapid ventricular response
should usually be regarded as secondary to another insult (mostly
commonly, infection) until other diagnoses have been excluded.
Fig. 10.10 Theoretical mechanisms of hypoxaemia. A Normal physiology. B Shunt caused by alveolar filling, e.g. in pneumonia or alveolar
haemorrhage. The mixture of oxygenated and deoxygenated blood causes arterial desaturation. C Shunt caused by interstitial pathology, e.g. pulmonary
oedema or fibrosis. Interstitial thickening causes inadequate transfer of oxygen from the alveolus to the blood, leading to shunting and arterial desaturation.
Because minute volume is usually maintained, this causes type I respiratory failure. D Ventilation–perfusion (V/Q ) mismatch caused by alveolar
hypoventilation, e.g. in chronic obstructive pulmonary disease (COPD)/asthma. Alveoli are under-ventilated relative to perfusion. Alveolar PO2 falls and PCO2
rises, causing type II respiratory failure. E V/Q mismatch caused by central hypoventilation, e.g. in neuromuscular disease or narcotic use. The alveoli are
relatively over-perfused, causing type II respiratory failure. F V/Q mismatch caused by a perfusion defect, e.g. a small pulmonary embolism. Pulmonary
blood flow is diverted to other alveoli, causing them to be relatively over-perfused and thus reducing alveolar PO2. Minute volume is increased, so PCO2 is
not elevated.
Terminal bronchus
Alveolus
Alveolus filled with blood/secretions
or collapsed. Blood will pass this
alveolus without becoming oxygenated
Pulmonary
vein
SO2 98%
Pulmonary
artery
SO2 75%
Pulmonary vein
SO2 98%
SO2 75%
SO2 75%
SO2 98%
A
B
SO2 90%
SO2 75%
SO2 90%
Interstitium thickened by fluid,
inflammatory exudate or cells
SO2 75%
SO2 98%
C
D
SO2 75%
SO2 75%
SO2 94%
SO2 90%
↓[O2]
↑[CO2]
↓[O2]
↑[CO2]
↓[O2]
↓[CO2]
SO2 75%
SO2 90%
E
F
10.20 Common causes of hypoxaemia in
hospitalised patients
Hypoxaemia due to shunt
• Lung collapse
• Consolidation/alveolar haemorrhage
• Interstitial oedema or interstitial infiltration (e.g. fibrosis)
• Silent aspiration of gastric contents
Hypoxaemia due to ventilation–perfusion mismatch
• Pulmonary embolism
• Acute exacerbation of asthma
• COPD (with high minute volume)
Hypoxaemia from hypoventilation
• Effects of opiates
• Severe COPD (with low minute volume)
• Neuromuscular disease/general weakness from other illness
(COPD = chronic obstructive pulmonary disease)
Common presentations of deterioration • 193
early identification. If shock is suspected, resuscitation should be
commenced (p. 204).
Hypotensive patients who do not have any evidence of shock
are still at significant risk of organ dysfunction. Hypotension
should serve as a ‘red flag’ that there may be serious underlying
pathology. Organ failure occurs despite normal or elevated
oxygen delivery, so a full assessment of the patient is indicated.
A review of the drug chart is essential, as many inpatients
will be on antihypertensive medications that are contributing
to hypotension. Non-cardiac medications may also have a
negative influence on BP; for example, some drugs used for
urine outflow tract obstruction, such as tamsulosin, have an
α-adrenoceptor-blocking effect.
Hypertension
Pathophysiology
High BP (hypertension) is common and is usually benign in a
critical care context. However, it can be the presenting feature
of a number of serious disease processes. Furthermore, acute
hypertension can result in an acute rise in vascular tone that
increases left ventricular end-systolic pressure (afterload). The
left ventricle may be unable to eject blood against the increased
aortic pressure, and acute pulmonary oedema can result (referred
to as ‘flash’ pulmonary oedema.)
Assessment and management
Before treating an acute rise in BP, it is worth considering a
few important diagnoses that may impact on the immediate
management:
• Intracranial event. Ischaemia of the brainstem (commonly
via a pressure effect) will cause acute increases in BP. A
neurological examination and CT scan of the head should
be considered.
• Fluid overload. Once the capacity of the venous blood
reservoir becomes saturated, increases in fluid volume will
lead to increases in BP. This can occur in younger
patients without the onset of peripheral oedema and
originate from myocardial dysfunction or impaired renal
clearance.
• Underlying medical problems. A brief search for a history
of renal disease, spinal injury and less common metabolic
causes such as phaeochromocytoma can be worthwhile.
In women of child-bearing age, pregnancy-induced
its inotropic properties can be helpful. Electrical cardioversion
is reserved for dysrhythmias with extremely high heart rates,
following failure of pharmacological management, and/or for
those of ventricular origin. It is rarely successful in dysrhythmias
secondary to systemic illness.
Hypotension
Pathophysiology
Low BP (hypotension) should always be defined in relation to
a patient’s usual BP. The calculation of mean arterial pressure
(MAP) is shown in Box 10.21; it unifies the systolic and diastolic
BPs into a single reference value. A MAP of > 65 mmHg will
maintain renal perfusion in the majority of patients, although
a MAP of up to 80 mmHg may be required in patients with
chronic hypertension.
Assessment and management
The first stage of assessment is to decide if the hypotension
is physiological or pathological. The MAP is useful as, despite
low systolic pressures, it is rare to see a physiological MAP of
< 65 mmHg. Urine output is particularly useful in the determination
of the desirable MAP for an individual patient; oliguria suggests
that measures to increase the MAP should be sought (p. 204).
If the hypotension is pathological, an assessment of severity
should look at whether it is causing physiological harm to the
patient (i.e. the patient is shocked).
Shock
Shock means ‘circulatory failure’. It can be defined as a level of
oxygen delivery (DO2) that fails to meet the metabolic requirements
of the tissues (Box 10.22). Hypotension is a common presentation
of shock but the terms are not synonymous. Patients can be
hypotensive but not shocked, and oxygen delivery can be
critically low in the context of a ‘normal’ BP. Along with the
signs of low cardiac output (Box 10.23), objective markers of
inadequate tissue oxygen delivery, such as increasing base
deficit, elevated blood lactate and reduced urine output, can aid
10.21 Calculation of mean arterial pressure (MAP)
MAP
Diastolic blood pressure
systolic
diastolic
−
(
)
At normal heart rates, the heart, on average, spends two-thirds of the
cycle in diastole. The MAP reflects this by weighting the value towards
the diastolic blood pressure
*Oxygen is almost exclusively bound to haemoglobin; only tiny amounts are
dissolved in blood at atmospheric pressure.
10.22 Oxygen content and delivery
• Oxygen content of blood = *Haemoglobin level × oxygen saturation
× constant
• Cardiac output = Heart rate × stroke volume
• Stroke volume is dependent on cardiac filling (preload) and
contractility
• In shock, the most productive measures to improve oxygen delivery
are optimising the haemoglobin level and the cardiac output
10.23 Hypotension in relation to cardiac output:
clinical signs and possible causes
High cardiac output
Low cardiac output
Signs
Warm hands
Pulsatile head movement
High-volume/strong pulse
Low venous pressure
Cold/clammy peripheries
Peripheral cyanosis
Raised venous pressure
Causes
Sepsis
Allergy
Drug overdose (e.g.
antihypertensive)
Acidosis (e.g. diabetic
ketoacidosis)
Thyrotoxicosis
Beri-beri
Bleeding
Aortic stenosis and failed
compensation
Dysrhythmia
Obstructive (pulmonary
embolism/tamponade/
dynamic hyperinflation as
in severe asthma)
Chronic heart failure
194 • ACUTE MEDICINE AND CRITICAL ILLNESS
aspiration or obstruction), but a motor score of less than 5 would
suggest significant risk.
Coma is defined as a persisting state of deep unconsciousness.
In practice, this means a sustained GCS of 8 or less. There
are many causes of coma (Box 10.26), including neurological
(structural or non-structural brain disease) and non-neurological
(e.g. type II respiratory failure) ones. The mode of onset of coma
and any precipitating event is crucial to establishing the cause,
and should be obtained from witnesses. Failure to obtain an
adequate history for patients in coma is a common cause of
diagnostic delay.
Once the patient is stable from a cardiorespiratory perspective,
examination should include accurate assessment of conscious
level and a thorough general medical examination, looking for
clues such as needle tracks indicating drug abuse, rashes, fever
and focal signs of infection, including neck stiffness or evidence
of head injury. Focal neurological signs may suggest a structural
explanation (stroke or tumour) or may be falsely localising (for
example, 6th nerve palsy can occur as a consequence of raised
intracerebral pressure). It is vital to exclude non-neurological
causes of coma. Sodium and glucose should be measured
urgently as part of the initial assessment, as acute hyponatraemia
(p. 358) and hypoglycaemia (p. 738) are easily corrected and
can cause irreversible brain injury if missed.
hypertension and pre-eclampsia must always be
considered.
• Primary cardiac problems. Myocardial ischaemia, acute
heart failure and aortic dissection can all present with
hypertension.
• Drug-related problems. Most commonly, these involve a
missed antihypertensive medication, but sympathomimetic
drugs such as cocaine and amphetamines can be
implicated.
The management of hypertension is discussed further on
page 510.
Decreased conscious level
Assessment
A reduction in conscious level should prompt an urgent
assessment of the patient, a search for the likely cause and an
evaluation of the risk of airway loss. The GCS was developed
to risk-stratify head injury, but it has become the most widely
recognised assessment tool for conscious level (see Box 10.24
for breakdown of GCS assessment, Box 10.25 for how to
communicate the findings and Fig. 10.5 for how to assess
GCS). While disorders that affect language or limb function
(e.g. left hemisphere stroke, locked-in syndrome) may reduce
its usefulness, evaluation of the GCS usually provides helpful
prognostic information, and serial recordings can plot improvement
or deterioration. It is not possible to define a total score below
which a patient is unlikely to be able to protect the airway (from
10.25 How to communicate conscious level to other
health-care professionals
• It is best to state the physical response along with the numerical
score
• For example, ‘a patient who doesn’t open his eyes, withdraws to
pain and makes groaning noises, having a GCS of E1, M4, V2,
making a total of 7’ is preferable to ‘a male with a GCS of 7’
Record the best score observed. When the patient is intubated, there can be no
verbal response. The suffix ‘T’ should replace the verbal component of the score,
and the remainder of the score is therefore a maximum of 10.
10.24 Glasgow Coma Scale (GCS)
Eye-opening (E)
• Spontaneous
• To speech
• To pain
• Nil
Best motor response (M)
• Obeys commands
• Localises to painful stimulus
• Flexion to painful stimulus or withdraws
hand from pain
• Abnormal flexion (internal rotation of
shoulder, flexion of wrist)
• Extensor response (external rotation of
shoulder, extension of wrist)
• Nil
Verbal response (V)
• Orientated
• Confused conversation
• Inappropriate words
• Incomprehensible sounds
• Nil
Coma score = E + M + V
Always present GCS as breakdown, not a sum score (unless
3 or 15)
• Minimum sum
• Maximum sum
10.26 Causes of coma
Metabolic disturbance
• Drug overdose
• Diabetes mellitus:
Hypoglycaemia
Ketoacidosis
Hyperosmolar coma
• Hyponatraemia
• Uraemia
• Hepatic failure
(hyperammonaemia)
• Inborn errors of metabolism
causing hyperammonaemia
• Hyperammonaemia on
refeeding following profound
anorexia
• Respiratory failure
• Hypothermia
• Hypothyroidism
Trauma
• Cerebral contusion
• Extradural haematoma
• Subdural haematoma
• Diffuse axonal injury
Vascular disease
• Subarachnoid haemorrhage
• Brainstem infarction/
haemorrhage
• Intracerebral haemorrhage
• Cerebral venous sinus
thrombosis
Infections
• Meningitis
• Encephalitis
• Cerebral abscess
• Systemic sepsis
Others
• Epilepsy
• Brain tumour
• Functional (‘pseudo-coma’)
Common presentations of deterioration • 195
Further investigations should be guided by the clinical
presentation and examination findings; a sudden onset suggests
a vascular cause. An early CT scan of the brain may demonstrate
any gross pathology but if a brainstem stroke is suspected
(Fig. 10.11), a CT angiogram of the circle of Willis will provide
more useful information, as a non-contrast CT is frequently
negative in this context. If there are features suggestive of cerebral
venous thrombosis, such as thrombophilia or sinus infection, a
CT venogram should be performed. Meningitis or encephalitis
may be suggested by the history, signs of infection or subtle
radiological findings. If these diagnoses are considered, it is best
to commence treatment with broad-spectrum antibiotics and
antivirals while awaiting more definitive diagnostic information.
Other drug, metabolic and hepatic causes of reduced conscious
level are dealt with in the relevant chapters. An ammonia level
(sent on ice) can narrow the differential diagnosis to a metabolic
or hepatic cause if there is diagnostic doubt; levels > 100 μmol/L
(140 μg/dL) are significantly abnormal. Psychiatric conditions
such as catatonic depression or neurological conditions such
as the autoimmune encephalitides can cause a reduced level
of consciousness, but they are diagnoses of exclusion and will
require specialist input.
Management
Moving an unconscious patient into the recovery position is best
for airway protection while preparations are made for escalation
to a higher level of care. The decision regarding intubation for
airway protection is always difficult. Length of stay in intensive
care is significantly reduced if there is no secondary organ
Fig. 10.11 Hyperacute changes in conscious state are commonly of
vascular origin. CT of the brain is unlikely to identify many vascular
causes but a CT angiogram of the circle of Willis is a high-yield
investigation in this context. A Non-contrast CT of the head showing
hyperdense thrombus in the basilar artery (arrow). This is a specific, but
not sensitive, sign. B CT angiogram of the circle of Willis demonstrating
thrombosis in the basilar artery (arrow). This has better sensitivity for acute
vascular occlusion.
B
A
dysfunction. Therefore, early intubation and the prevention
of lung injury constitute the safer option if there is any doubt
about a patient’s ability to protect the airway from obstruction
or aspiration.
Decreased urine output/deteriorating
renal function
Assessment
A urine output of 0.5 mL/kg/hr is a commonly quoted, though
admittedly arbitrary target. Although some patients can produce
urine volumes below this level with no change in their renal
biochemistry, such low volumes should alert the clinician to the
possibility of suboptimal renal perfusion.
Oliguria in association with hypotension or an increase in serum
creatinine level (even if small) should prompt examination for the
underlying cause. Pre-renal causes predominate in the general
inpatient population, so optimising the MAP by administration of
intravenous fluids (and possibly vasopressors) is the first priority.
In the majority of inpatients there is no role for high volumes (i.e.
30 mL/kg) of intravenous fluid if the MAP is normal. Exceptions
to this rule include patients with clinical dehydration or high fluid
losses such as in burns, diabetes emergencies (pp. 735 and
and diabetes insipidus (p. 687), where fluid management
should be guided by local protocols.
Diagnosis and management
Further assessment and management of oliguria are explained
on page 391. Two other important causes of renal failure in the
inpatient population are abdominal compartment syndrome and
rhabdomyolysis.
Abdominal compartment syndrome
Abdominal compartment syndrome occurs when raised pressure
within the abdomen reduces perfusion to the abdominal organs.
It is most commonly seen in surgical patients, but can occur
in medical conditions with extreme fluid retention such as liver
cirrhosis. When it is suspected, intra-abdominal pressure can
be monitored via a pressure transducer connected to a urinary
catheter (following instillation of 25 mL of 0.9% saline into the
bladder). Values over 20 mmHg suggest abdominal compartment
syndrome is present. Urgent measures should be taken to reduce
the pressure, such as decompression of the stomach, bladder
and peritoneum if ascites is present. If conservative measures
fail, a laparostomy should be considered.
Rhabdomyolysis
Rhabdomyolysis occurs when there is an injury to a large volume
of skeletal muscle, usually because a single limb or muscle
compartment has been ischaemic for a prolonged period.
It can also occur following trauma and crush injury or after
over-exertion of muscles. Over-exertion can occur after intense
physical exercise or as part of a medical condition that causes
widespread muscular activity, such as malignant hyperpyrexia
or neuroleptic malignant syndrome. A creatine kinase (CK)
level of > 1000 U/L is highly suggestive, although it can rise to
tens of thousands in severe cases. Management should focus
on identification and correction of the underlying cause and
support for multi-organ dysfunction. Forced alkaline diuresis
(using intravenous bicarbonate infusion and furosemide) can be
used to maintain a good flow of less acidic fluid within the renal
tubules and reduce myoglobin precipitation.
196 • ACUTE MEDICINE AND CRITICAL ILLNESS
non-infective processes, such as pancreatitis, burns, trauma,
major surgery and drug reactions, can cause alarmins to be
released and initiate the process of systemic inflammation.
Propagation of the inflammatory response
Once activated, immune cells such as macrophages release
the inflammatory cytokines interleukin-2 (IL-2), IL-6 and tumour
necrosis factor alpha, which, in turn, activate neutrophils.
Activated neutrophils express adhesion factors and release
various other inflammatory and toxic substances; the net effects
are vasodilatation (via activation of inducible nitric oxide synthase
enzymes) and damage to the endothelium. Neutrophils migrate
into the interstitial space; fluid and plasma proteins will also leak
through the damaged endothelium, leading to oedema and
intravascular fluid depletion.
Activation of the coagulation system
Damaged endothelium triggers the coagulation cascade (via tissue
factor, factor VII, and reduced activity of proteins C and S) and
thrombus forms within the microvasculature. A vicious circle of
endothelial injury, intravascular coagulation and microvascular
occlusion develops, causing more tissue damage and further
release of inflammatory mediators. In severe sepsis, intravascular
coagulation can become widespread. This is referred to as
disseminated intravascular coagulation (DIC) and usually heralds
the onset of multi-organ failure. Specific aspects of the diagnosis
and management of DIC are discussed on page 978.
Organ damage from sepsis
Any and all organs may be injured by severe sepsis. The
pathological mechanisms are shown in Figure 10.12.
Lactate physiology
Lactate is an excellent biomarker for the severity of sepsis.
Hyperlactataemia (serum lactate > 2.4 mmol/L or 22 mg/dL)
is used as a marker of severity. Figure 10.13 explains the
physiology of hyperlactataemia; it is caused by all types of
shock and therefore is not specific to sepsis. A lactate level of
8 mmol/L (>73 mg/dL) is associated with an extremely high
mortality and should trigger immediate escalation. Measures to
optimise oxygen delivery should be sought, and the adequacy
of resuscitation measured by lactate clearance.
The anti-inflammatory cascade
As the inflammatory state develops, a compensatory antiinflammatory system is activated involving the release of antiinflammatory cytokines such as IL-4 and IL-10 from immune
cells. While such mechanisms are necessary to keep the
inflammatory response in check, they may lead to a period
of immunosuppression after the initial septic episode. Patients
recovering from severe sepsis are prone to developing secondary
infections due to a combination of this immunosuppression and
the presence of indwelling devices.
Management
The most important action is to consider sepsis as the cause
of a patient’s deterioration. Aligned to this is the requirement to
consider other diagnoses that could be causing the presentation,
such as haemorrhage, PE, anaphylaxis or a low cardiac
output state.
Resuscitation in sepsis
General resuscitative measures are discussed on page 204. Early
resuscitation can be aided by following the requirements of the
From the Third International Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3).
10.27 Definitions of sepsis and septic shock
Sepsis
Patients with suspected infection who have 2 or more of:
• Hypotension – systolic blood pressure < 100 mmHg
• Altered mental status – Glasgow Coma Scale score ≤ 14
• Tachypnoea – respiratory rate ≥ 22 breaths/min
Sepsis can also be diagnosed by suspected infection and an increase
of ≥ 2 points on the Sequential Organ Failure Assessment (SOFA) score
(p. 214)
Septic shock
A subset of sepsis with underlying circulatory or cellular/metabolic
abnormalities associated with a substantially increased mortality:
• Sepsis and both of (after fluid resuscitation):
Persistent hypotension requiring vasopressors to maintain a MAP
65 mmHg
Serum lactate > 2 mmol/L (18 mg/dL)
Disorders causing critical illness
Sepsis and the systemic
inflammatory response
Sepsis is one of the most common causes of multi-organ failure.
Sepsis requires the presence of infection with a resultant systemic
inflammatory state; organ dysfunction occurs from a combination
of the two processes. The definition of sepsis has undergone
various iterations and there is still a lack of consensus as to
the exact wording that best reflects this complex, multisystem
process (Box 10.27).
Aetiology and pathogenesis
To understand how an infection can lead to progressive multiorgan failure, it is essential to have a grasp of the pathophysiology.
Initiation of the inflammatory response
The process begins with infection in one part of the body that
triggers a localised inflammatory response. Appropriate source
control and a competent immune system will, in most cases,
contain the infection at this stage. However, if certain factors
are present, the infection may become systemic. The causative
factors are not fully elucidated but probably include:
• a genetic predisposition to sepsis
• a large microbiological load
• high virulence of the organism
• delay in source control (either surgical or antimicrobial)
• resistance of the organism to treatment
• patient factors (immune status, nutrition, frailty).
Mediators are released from damaged cells (called ‘alarmins’)
and these, coupled with direct stimulation of immune cells
by the molecular patterns of the microorganism, trigger the
inflammatory response. An example of such direct stimulation
is that of lipopolysaccharide, which is found on the surface
of Gram-negative bacteria. It strongly stimulates an immune
response and is commonly used in research settings to initiate
a septic cascade.
Viral and fungal infections can cause a syndrome that is clinically
indistinguishable from bacterial sepsis. Likewise, numerous
Disorders causing critical illness • 197
crystalloid. Early intubation is recommended in severe cases
to facilitate further management and reduce oxygen demand.
Appropriate antibiotics should be administered as early as
possible (Box 10.29). The antibiotic choice will depend on local
patterns of resistance, patient risk factors and the likely source
of infection. Information on likely organisms and appropriate
antibiotics can be found on pages 117 and 226. Microbiological
samples (such as blood cultures, urine or CSF) should be taken,
but this should not delay antibiotic administration, if obtaining
samples is difficult.
Early source control
Source control requires an accurate diagnosis; urgent
investigations should be performed as soon as physiological
stability has been established. A CT scan of the chest and
abdomen with contrast is a high-yield test in this context. Specific
points in the history should be reviewed, such as risk factors for
human immunodeficiency virus (HIV), contacts with tuberculosis
and underlying immune status. Immunocompromised patients
will be susceptible to a far broader spectrum of infectious
microorganisms (p. 223).
‘Sepsis Six’ (Box 10.28). Red cell transfusion should be used
to target a haemoglobin concentration of 70–90 g/L (7–9 g/dL).
Albumin 4% can be used as colloid solution and has the theoretical
benefit of remaining in the intravascular space for longer than
Fig. 10.12 Pathophysiology of organ damage in sepsis. Macrovascular.
Severe hypovolaemia, vasodilatation or septic cardiomyopathy can reduce
oxygen delivery, causing tissue hypoxia. Paradoxically, most patients with
sepsis have an increased cardiac output and oxygen delivery. Microvascular.
Tissue injury can occur from hypoxia secondary to microvascular injury and
thrombosis. Damaged epithelium permits neutrophils, proteins and fluid to
leak out. Shunting. Organs fail in sepsis despite supranormal blood flow. It is
likely that arteriovenous shunt pathways exist within vascular beds; these
shunts open up in septic shock. Cellular. Cells are damaged by a number of
mechanisms in sepsis: (1) direct injury by microorganisms; (2) injury from
toxins produced by immune cells, e.g. oxygen free radicals; (3)
mitochondrial injury causing cytopathic hypoxia – cells are unable to
metabolise oxygen; (4) apoptosis – if the cell injury is sufficient, capsase
enzymes are activated within the nucleus and programmed cell death
occurs; (5) hypoxia from micro- and macrovascular pathology.
Arterioles
M
A
C
R
O
V
A
S
C
U
L
A
R
Capillaries
Mitochondria
Neutrophil
Bacteria
Nucleus
Neutrophil
Arteriovenous
shunt
Venules
Microemboli
M
I
C
R
O
V
A
S
C
U
L
A
R
C
E
L
L
U
L
A
R
Fig. 10.13 Physiology of hyperlactataemia.
Inadequate
oxygen
delivery
Tissue hypoxia
e.g. Ischaemic
gut
Shock
(from any cause)
Drugs
e.g. Adrenaline
(epinephrine)
Salbutamol
Excess muscle
activity
e.g. Extreme
exercise
Seizure
Anaerobic
metabolism
Excess
production
Inadequate
clearance
β2-adrenoceptor
stimulation
High
lactate
Excess tissue
production
Hepatic
failure
Congenital enzyme
deficiencies (rare)
Other causes:
Metformin
Thiamin deficiency
Haematological malignancy
Drugs, e.g. antiretrovirals
International recommendations for the immediate management of suspected
sepsis from the Surviving Sepsis Campaign (all to be delivered within 1 hr of the
initial diagnosis of sepsis).
10.28 The ‘Sepsis Six’
Deliver high-flow oxygen
Take blood cultures
Administer intravenous antibiotics
Measure serum lactate and send full blood count
Start intravenous fluid replacement
Commence accurate measurement of urine output
10.29 Early administration of antibiotics in
suspected sepsis
• Broad-spectrum antibiotics should be administered as soon as
possible after sepsis is suspected
• Every hour of delayed treatment is associated with a 5–10%
increase in mortality
198 • ACUTE MEDICINE AND CRITICAL ILLNESS
Acute respiratory distress syndrome
Aetiology and pathogenesis
Acute respiratory distress syndrome (ARDS) is a diffuse
neutrophilic alveolitis caused by a range of conditions and
characterised by bilateral radiographic infiltrates and hypoxaemia
(Box 10.32). Activated neutrophils are sequestered into the lungs
and capillary permeability is increased, with damage to cells
within the alveoli. The pathophysiology is part of the inflammatory
spectrum described in ‘Sepsis’ above, and the triggers are
similar: infective and non-infective inflammatory processes. These
processes result in exudation and accumulation of protein-rich
cellular fluid within alveoli and the formation of characteristic
‘hyaline membranes’. Local release of cytokines and chemokines
by activated macrophages and neutrophils results in progressive
recruitment of inflammatory cells. Secondary effects include loss
of surfactant and impaired surfactant production. The net effect is
alveolar collapse and reduced lung compliance, most marked in
dependent regions of the lung (mainly dorsal in supine patients).
The affected airspaces become fluid-filled and can no longer
contribute to ventilation, resulting in hypoxaemia (due to increased
pulmonary shunt) and hypercapnia (due to inadequate ventilation
in some areas of the lung): that is, ventilation–perfusion mismatch.
Diagnosis and management
ARDS can be difficult to distinguish from fluid overload or cardiac
failure. Classic chest X-ray and CT appearances are shown in
Figures 10.14 and 10.15, respectively. Occasionally, conditions
may present in a similar way to ARDS but respond to alternative
treatments; an example of this might be a glucocorticoidresponsive interstitial pneumonia (p. 605). Management of ARDS is
supportive, including use of lung-protective mechanical ventilation,
inducing a negative fluid balance and treating the underlying
cause. Establishing the severity of ARDS (Box 10.33) is useful,
as severe disease will require more proactive management such
as prone positioning or extracorporeal membrane oxygenation
(ECMO; p. 204).
Noradrenaline (norepinephrine) for refractory hypotension
Central venous access should be established early in the
resuscitation process and a noradrenaline infusion commenced.
If there is severe hypotension, it is not necessary to wait until
30 mL/kg of fluid has been administered before commencing
noradrenaline; early vasopressor use may improve the outcome
from acute kidney injury. Measurement of central and mixed
venous oxygen saturations may provide additional prognostic
information (Box 10.30).
Other therapies for refractory hypotension
Refractory hypotension is due to either inadequate cardiac output
or inadequate systemic vascular resistance (vasoplegia). When
vasoplegia is suspected, it may be necessary to add vasopressin
(antidiuretic hormone, ADH). This is a potent vasoconstrictor
that may be used to augment noradrenaline (norepinephrine) in
achieving an acceptable MAP. Intravenous glucocorticoids are
also commonly used in refractory hypotension. There is little
evidence that they improve the overall outcome, but they do lead
to a more rapid reversal of the shocked state. There is a small
increased risk of secondary infection following glucocorticoid use.
Septic cardiomyopathy
The myocardium can be affected by the septic process, presenting
as either acute left or right ventricular dysfunction. A bedside
echocardiogram is particularly useful to confirm the diagnosis, as
ECG changes are usually non-specific. Dobutamine or adrenaline
(epinephrine) can be used to augment cardiac output, and
intravenous calcium should be replaced if ionised calcium is low.
Other interventions such as intravenous bicarbonate in profound
metabolic acidosis, high-volume haemofiltration/haemodialysis
and extracorporeal support are sometimes used, but currently
lack evidence of benefit.
Review of the underlying pathology
While sepsis is the most common cause of acute systemic
inflammation, up to 20% of patients initially treated for sepsis
will have a non-infectious cause: that is, a sepsis mimic (Box
10.31). These conditions should be considered where the clinical
picture is not typical, no source of sepsis can be found, or the
inflammatory response seems excessive in the context of local
infection. Early reconsideration of the diagnosis of sepsis is
crucial, as many of the ‘sepsis mimics’ offer a finite time window
for specific intervention, after which irreversible organ damage
will have occurred.
10.31 Sepsis mimics
• Pancreatitis
• Drug reactions
• Widespread vasculitis – catastrophic antiphospholipid syndrome,
Goodpasture’s syndrome
• Autoimmune diseases – inflammatory bowel disease, rheumatoid
arthritis, systemic lupus erythematosus
• Malignancy – carcinoid syndrome
• Haematological conditions – haemophagocytic syndrome, diffuse
lymphoma, thrombotic thrombocytopenic purpura
10.32 Berlin definition of ARDS
• Onset within 1 week of a known clinical insult, or new or worsening
respiratory symptoms
• Bilateral opacities on chest X-ray, not fully explained by effusions,
lobar/lung collapse or nodules
• Respiratory failure not fully explained by cardiac failure or fluid
overload. Objective assessment (e.g. by echocardiography) must
exclude hydrostatic oedema if no risk factor is present
• Impaired oxygenation (see Box 10.33)
10.30 Central and mixed venous oxygen saturations
• Saturation of venous blood sampled from the right atrium or
superior vena cava (central) or pulmonary artery (mixed venous)
• Both values reflect the balance of supply and demand of oxygen to
the tissues
• Mixed venous oxygen saturation is a measure of whole-body supply
and demand of oxygen; central venous oxygen saturation measures
the supply and demand of oxygen from the upper body. Normal
mixed venous oxygen saturation is 70%. Lower values than this
suggest inadequate oxygen delivery
• Central venous oxygen saturation is more variable, depending on
whether the patient is awake or anaesthetised, but a value of 70%
is considered normal
• Where cytopathic hypoxia occurs, oxygen extraction is impaired and
the central and mixed venous oxygen saturations may be > 80%.
This is often a poor prognostic sign
Disorders causing critical illness • 199
infarction and rupture of the septum) and acute mitral regurgitation
(due to infarction or rupture of the papillary muscles).
Severe myocardial systolic dysfunction causes a fall in cardiac
output, BP and coronary perfusion pressure. Diastolic dysfunction
causes a rise in left ventricular end-diastolic pressure, pulmonary
congestion and oedema, leading to hypoxaemia that worsens
myocardial ischaemia. This is further exacerbated by peripheral
vasoconstriction. These factors combine to create the ‘downward
spiral’ of cardiogenic shock (Fig. 10.17). Hypotension, oliguria,
delirium and cold, clammy peripheries are the manifestations
of a low cardiac output, whereas breathlessness, hypoxaemia,
cyanosis and inspiratory crackles at the lung bases are typical
features of pulmonary oedema. If necessary, a Swan–Ganz
catheter can be used to measure the pulmonary artery pressures
and cardiac output (p. 206). These findings can be used to
categorise patients with acute MI into four haemodynamic
subsets (Box 10.34) and titrate therapy accordingly.
In cardiogenic shock associated with acute MI, immediate
percutaneous coronary intervention should be performed (p. 491).
The viable myocardium surrounding a fresh infarct may contract
poorly for a few days and then recover. This phenomenon is
known as myocardial stunning and means that acute heart failure
Fig. 10.14 Chest X-ray in acute respiratory distress syndrome
(ARDS). Note bilateral lung infiltrates, pneumomediastinum,
pneumothoraces with bilateral chest drains, surgical emphysema, and
fractures of the ribs, right clavicle and left scapula.
Fig. 10.15 CT scan of the thorax in a patient with severe ARDS. Note
the pathology is mainly in the dorsal (dependent) parts of the lung.
10.33 Determining the severity of ARDS
Severity of hypoxaemia is calculated using a Pa/FiO2 ratio. This is a
number calculated by using the PaO2 from an arterial blood gas
measurement divided by the fraction of inspired oxygen (FiO2,
expressed as a fraction).
For example, a patient with a PaO2 of 10 kPa (75 mmHg) on 50%
oxygen, i.e. FiO2 of 0.5, would have a Pa/FiO2 ratio of 20 kPa
(150 mmHg). This would be defined as moderately severe ARDS, if the
other Berlin criteria were met (see Box 10.32). All measurements
should be taken on a minimum of 5 cmH2O of PEEP or CPAP.
• Mild: 40–26.6 kPa (300–200 mmHg)
• Moderate: 26.6–13.3 kPa (200–100 mmHg)
• Severe: ≤ 13.3 kPa (≤ 100 mmHg)
(CPAP = continuous positive airway pressure; PEEP = positive end-expiratory
pressure)
10.34 Acute myocardial infarction:
haemodynamic subsets
Cardiac
output
Pulmonary oedema
No
Yes
Normal
Good prognosis and
requires no treatment for
heart failure
Due to moderate left
ventricular dysfunction.
Treat with vasodilators
and diuretics
Low
Due to right ventricular
dysfunction or concomitant
hypovolaemia. Give fluid
challenge and consider
pulmonary artery catheter
to guide therapy
Extensive myocardial
infarction and poor
prognosis. Consider
intra-aortic balloon pump,
vasodilators, diuretics and
inotropes
Acute circulatory failure
(cardiogenic shock)
Definition and aetiology
Cardiogenic shock is defined as hypoperfusion due to inadequate
cardiac output or, more technically, a cardiac index of < 2.2 L/min/
m2 (see Box 10.42). While cardiogenic shock is the final common
pathway of many disease processes (e.g. sepsis, anaphylaxis,
haemorrhage), the important primary causes of acute heart failure
or cardiogenic shock (Fig. 10.16) are described here.
Myocardial infarction
In the majority of cases, cardiogenic shock following acute MI
is due to left ventricular dysfunction. However, it may also be
due to infarction of the right ventricle, or a variety of mechanical
complications, including tamponade (due to infarction and rupture
of the free wall), an acquired ventricular septal defect (due to
200 • ACUTE MEDICINE AND CRITICAL ILLNESS
should be treated intensively because overall cardiac function
may subsequently improve.
Acute massive pulmonary embolism
Massive PE may complicate leg or pelvic vein thrombosis and
usually presents with sudden collapse. The clinical features and
treatment are discussed on page 619. Bedside echocardiography
may demonstrate a small, under-filled, vigorous left ventricle with
a dilated right ventricle; it is sometimes possible to see thrombus
in the right ventricular outflow tract or main pulmonary artery.
In practice, it can be difficult to distinguish massive PE from a
right ventricular infarct on transthoracic echocardiogram. CT
pulmonary angiography usually provides a definitive diagnosis.
Acute valvular pathology, aortic dissection and
cardiac tamponade
These conditions should be considered in an undifferentiated
presentation of shock. The diagnosis and management of these
conditions is discussed on pages 514, 506 and 544.
Post cardiac arrest
The initial management of cardiac arrest is discussed on
page 456. Following the return of spontaneous circulation (ROSC),
the majority of cardiac arrest survivors will need a period of
time in intensive care to achieve physiological stability, identify
Fig. 10.16 Some common causes of cardiogenic shock.
Aorta
Cardiac
tamponade
PA
RA
RV
LV
LA
Aorta
Endocarditis
of mitral valve
PA
RA
RV
LV
LA
Aorta
Right ventricular
infarct
PA
RA
RV
LV
LA
Aorta
Pulmonary
embolism
PA
RA
RV
LV
LA
Aorta
Dysrhythmia caused by:
Left ventricular damage
Myocardial infarction
Myocarditis
PA
RA
RV
LV
LA
Ventricular
tachycardia
Aorta
PA
RA
RV
LV
LA
Left ventricular
infarct
Fig. 10.17 The downward spiral of cardiogenic shock.
Ventricular
dysfunction
Systolic Diastolic
↓ Cardiac
output
↓ Blood
pressure
↓ Coronary
perfusion
Further
ischaemia
↑ Left ventricular
diastolic pressure
↑ Pulmonary
congestion
Hypoxaemia
Critical care medicine • 201
the most specific test to predict irrecoverable brain injury. This
test is performed by administering an electrical impulse over a
peripheral nerve and recording the electrical impulses measured
by the scalp electrodes overlying the part of the brain expected
to receive the impulse. Where this is not available, prognostication
based on all other available information, along with the perceived
wishes relating to the level of disability the individual would be
prepared to accept, should allow a decision regarding ongoing
treatment to be made. Where there is doubt, more time should
be given to allow assessment of neurological recovery.
Other causes of multi-organ failure
As previously discussed, sepsis is the most common cause
of multi-organ failure. However, multi-organ failure secondary
to single organ dysfunction, such as cardiac failure, liver
failure, renal failure or respiratory failure, is also common. The
multisystem insult in these disease processes goes beyond
the direct biochemical damage and tissue hypoxia caused by
the primary organ dysfunction. It probably reflects cellular signalling
pathways and the release of other systemic toxins by the failing
organ, referred to as organ ‘crosstalk’.
Multi-organ failure can also be caused by a physiological
insult that damages a wide variety of cells in different organs,
including toxins from extrinsic sources such as envenomation
and intrinsic sources such as myoglobin in rhabdomyolysis
(p. 195). Multi-organ failure can also be caused by profound
physical injury to cells from processes such as nuclear radiation,
heat exposure or blast trauma.
Critical care medicine
Decisions around intensive care admission
Being a patient in intensive care is seldom a pleasant experience.
The interventions are usually painful and the loss of liberties that
are normally taken for granted can be devastating. While much of
the unpleasant sensory and emotional experience can be modified
with high-quality care and analgesia, there is a strong case that
it can only be morally ‘right’ to admit a patient to intensive care
if the end justifies the means. There must be a realistic hope
that the patient will regain a quality of life that would be worth
the pain and suffering that he or she will experience in intensive
care. Few patients are able to comprehend fully what it means
to be critically ill, so the physician should guide the process of
determining who should be admitted to intensive care.
Selecting the appropriate level of intervention for an individual
patient can be very difficult. The decision-making process
should involve an assessment of the likelihood of reversibility
of the disease, the magnitude of the interventions required, the
underlying level of frailty, and the personal beliefs and wishes
of the patient (commonly expressed through their next of kin).
As technology and science have improved, conditions that
were previously regarded as terminal can now be supported and
life can be considerably prolonged (Box 10.37). There have been
several prominent examples of individuals who have received
intensive care, but where an onlooker might have considered
treatment to be futile owing to frailty, comorbidity or profound
neurological injury. Such cases will, in part, shape the views and
expectations of society, and it is unlikely that making decisions
in this area will become any easier. Some suggested techniques
to aid decision-making are listed in Box 10.38.
10.36 Prognostication after cardiac arrest: predictors
of poor neurological recovery
Coexisting problems
• Multi-organ failure
• Significant comorbidities
Clinical
• Persisting and generalised myoclonus
• Absence of pupillary or corneal reflexes
• Poor motor response (absent or extensor response)
Biochemical
• A neuron-specific enolase > 33 μg/L
Imaging
• CT showing loss of grey–white differentiation
• Focal cause or consequence of cardiac arrest, e.g. subarachnoid
haemorrhage
Electrophysiology
• EEG patterns may suggest brain injury, e.g. burst suppression
• Somato-sensory evoked potentials – bilateral absence of the N20
spike (recorded from scalp electrodes from cutaneous electrical
impulse over the median nerve)
10.35 Physiological targets following a return of
spontaneous circulation (ROSC)
• Temperature management. Facilitate maintenance of temperature at
36°C and avoidance of pyrexia by the use of a cooling blanket. This
should be continued for 72 hrs. Muscle relaxants may be required
to prevent shivering
• Blood pressure management. Aim for a MAP of at least 70 mmHg
and a systolic blood pressure of > 120 mmHg
• Glucose control. Control the glucose to 6–10 mmol/L (108–
180 mg/dL)
• Normal CO2 (4.5–6 kPa, 33–45 mmHg) and oxygen saturation
(94–98%). Avoid both hypoxaemia and hyperoxia
and manage the underlying cause of the arrest, and optimise
neurological recovery.
Acute management
A MAP of > 70 mmHg should be maintained to optimise cerebral
perfusion. Shock is common following ROSC and is caused by
a combination of the underlying condition leading to the arrest,
myocardial stunning and a post-arrest vasodilated state. Support
with inotropes, vasopressors and occasionally mechanical support
from an intra-aortic balloon pump or venous–arterial ECMO
(p. 207) may be required. Specific cardiac interventions and their
indications are described in Chapter 16. Other physiological
targets are listed in Box 10.35.
Prognosis
Predicting which patients will not recover from the brain injury
sustained at the time of cardiac arrest is very difficult. Certain
features suggest that the outcome will be poor: for example, the
absence of pupillary and corneal reflexes, absence of a motor
response and persistent myoclonic jerking.
Tools to assist prognostication following cardiac arrest are
shown in Box 10.36. The clinician should, where feasible, delay
prognostication until a period of 72 hours of targeted temperature
management has been completed. The bilateral absence of
the ‘N20’ spike on the somato-sensory evoked potential is
202 • ACUTE MEDICINE AND CRITICAL ILLNESS
Respiratory support
Non-invasive respiratory support
Non-invasive respiratory support provides a bridge between
simple oxygen delivery devices and invasive ventilation. It can
be used in patients who are in respiratory distress but do not
have an indication for invasive ventilation, or in those who are
not suitable for intubation and ventilation for chronic health
reasons. Patients must be cooperative, able to protect their
airway, and have the strength to breathe spontaneously and
cough effectively. Clinicians should avoid using non-invasive
respiratory support to prolong the dying process in irreversible
conditions such as end-stage lung disease. Likewise, a failure
to respond to treatment or further deterioration should trigger
a decision regarding intubation, as delayed invasive ventilation
in this context is associated with worse outcome.
High-flow nasal cannulae
High-flow nasal cannulae (HFNCs) are devices that provide very
high gas flows of fully humidified oxygen and air. They offer
distinct advantages over non-invasive ventilation (NIV) in selected
patients, mainly those with type I respiratory failure (particularly
pneumonia) who have not reached an indication for invasive
ventilation. They allow patient comfort and increased expectoration
while providing some degree of positive end-expiratory pressure
(PEEP) and a high oxygen concentration that can be titrated to
the SO2.
Continuous positive pressure ventilation
Continuous positive pressure ventilation therapy involves the
application of a continuous positive airway pressure (CPAP)
throughout the patient’s breathing cycle, typically 5–10 cmH2O.
It helps to recruit collapsed alveoli and can enhance clearance
of alveolar fluid. It is particularly effective at treating pulmonary
atelectasis (which may be post-operative) and pulmonary oedema.
It uses a simpler device than NIV but otherwise offers no direct
benefit over it.
Non-invasive ventilation or bi-level ventilation
NIV provides ventilatory support via a tight-fitting nasal or facial
mask. It can be delivered by using a simple bi-level ventilation
(BiPAP) turbine ventilator, or an intensive care ventilator. These
machines can deliver pressure at a higher level (approximately
15–25 cmH2O) for inspiration and a lower pressure (usually
4–10 cmH2O) to allow expiration. Ventilation can be spontaneous
(triggered by a patient’s breaths) or timed (occurring at a set
frequency). Systems that synchronise with a patient’s efforts
are better tolerated and tend to be more effective in respiratory
failure. Timed breaths are used for patients with central apnoea.
NIV is the first-line therapy in patients with type II respiratory
failure secondary to an acute exacerbation of COPD because
it reduces the work of breathing and offloads the diaphragm,
allowing it to recover strength. It is also useful in pulmonary
oedema, obesity hypoventilation syndromes and some
neuromuscular disorders. It should be initiated early, especially
when severe respiratory acidosis secondary to hypercapnia is
present. NIV can also be used to support selected patients
with hypercapnia secondary to pneumonia, or during weaning
from invasive ventilation, but its effectiveness in these contexts
is less certain; early intubation or re-intubation is probably
more beneficial.
Stabilisation and institution of
organ support
In order to stabilise a critically unwell patient, the primary problem
should be corrected as quickly as possible: for example, source
control in sepsis and control of the bleeding point in haemorrhage.
Immediate resuscitation and prioritisation of the safety of the
patient are clearly important, but there is only a limited role for
‘optimising’ the patient if such measures may significantly delay a
definitive treatment, such as laparotomy for a perforated viscus.
In some cases, the definitive treatment is not readily apparent
or treatments take time to have their full effect. In these cases,
adequate organ support to stabilise the patient while the treatment
is given becomes the main goal of care.
10.38 Techniques to improve admission
decision-making
• Always act in the best interests of the patient: external influences
are commonly present but these should be of only secondary
importance
• Maximise patient capacity: wherever possible, the patient should be
involved in discussions of escalation and resuscitation status
• Communicate openly and honestly with the next of kin: when
communicating potential outcomes, it is best to use natural
frequencies rather than percentages. For example, ‘If we had 100
patients with the same illness as your mother, only 10 would
survive’ is easier for most people to understand than ‘there is a
90% chance of death’
• Reach mutual agreement with the next of kin: it is rare for there to
be discord between clinicians and family, and in most cases the
most appropriate course of action is clear
• Seek additional opinions: other clinicians involved in the care of the
patient will provide useful input. The premise should be to err on
the side of escalation where the most appropriate course of action
is unclear. Where there is an unresolvable difference in opinion, a
mediation process or court ruling may be required to make the final
decision. Thankfully, this is a very infrequent occurrence
• Plan ahead: advance planning in chronic, progressive disease can
make the decision easier. Some health facilities use an escalation
form, which specifies the interventions that should be offered or are
acceptable to the patient. This can be useful as the binary decision
of for/not for resuscitation fails to account for the array of
interventions that can be performed before cardiac arrest occurs
10.37 Critical illness in the context of
congenital conditions
• Longer survival: there are many congenital conditions that would,
in the past, have been fatal in childhood, but now patients survive
into adulthood. Decision-making can be difficult when the
adolescent has impaired decision-making capacity.
• Parental views: in such circumstances, the views of the parent or
legal guardian become paramount.
• Goals of care: often a detailed explanation of what is, and is not,
achievable in intensive care allows the direction of care to be
switched to palliative when life expectancy is poor and quality of life
is severely impaired.
• Decision-making: such conversations may require input from
experts in the patient’s congenital condition(s), and advanced
decision-making regarding ICU admission should be encouraged
whenever patients and families feel able to discuss such issues.
Stabilisation and institution of organ support • 203
breathe spontaneously once it is safe to do so. The determination
of what constitutes critical will depend on the status of each
patient. For example, a patient with raised ICP will have a strong
indication for normocapnia (because hypercapnia increases ICP).
Unfortunately, achieving the minute volumes required to maintain
normocapnia can, in itself, be harmful to the lungs (p. 204).
Ventilator modes
Following intubation, most patients have a period of paralysis
from the muscle relaxation. Mandatory ventilation is, therefore,
required for a variable period, depending on the severity of the lung
injury, the underlying disease process and the general condition
of the patient. Mandatory ventilation means that the ventilator
will deliver set parameters (either a set tidal volume or a set
inspiratory pressure), regardless of patient effort. A physician can
choose to support additional patient effort in between mandatory
breaths with pressure support. This requires sufficient patient
effort to ‘trigger’ the ventilator to deliver a synchronised breath,
in time with the patient’s own ventilation. Other parameters that
should be considered when using mechanical ventilation are
shown in Figure 10.18.
As a patient’s illness resolves, or if the lung injury necessitating
intubation is not severe, periods of spontaneous breathing with
pressure support are commenced. While spontaneous breathing
is preferable to mandatory ventilation modes, the shearing
forces of patient effort can exacerbate lung injury in patients
with severely damaged lungs. It is, therefore, important that a
patient is permitted to breathe in a planned and controlled way.
Intubation and intermittent positive
pressure ventilation
Taking control of the respiratory system in a critically ill patient
is one of the most significant and risky periods in a patient’s
journey. Critical incidents are common because the patient is
often deteriorating rapidly and is exhausted. The potential for
cardiovascular collapse is further exacerbated by the negatively
inotropic and vasodilating drugs used to induce anaesthesia, and
the period of apnoea invoked to facilitate intubation (Box 10.39).
The main aims of intermittent positive pressure ventilation
(IPPV) are to avoid critical hypoxaemia and hypercapnia while
minimising damage to the alveoli and encouraging the patient to
10.39 Optimising safety during intubation
• Intervene early in the disease process (once it has become clear
that the disease trajectory is downward)
• Use a stable anaesthetic technique: low doses of sedative agents
and rapidly acting paralytic agents
• Remember that intubation should be performed by the most
experienced operator available
• Use techniques to optimise oxygenation and ventilation in the period
around intubation, e.g. keeping non-invasive ventilation in situ for
pre-oxygenation, leaving high-flow nasal cannulae on for the
intubation process, and using a video-laryngoscope in an
anticipated difficult intubation
Fig. 10.18 Settings to be considered when commencing mechanical ventilation.
Respiratory rate and minute volume
Depend on the minute volume required to
achieve the desired PCO2, and whether the
patient is breathing spontaneously. Rates are
commonly 20–30 breaths/min
Ventilator mode
Mandatory, spontaneous,
or mandatory with the ability
to take spontaneous breaths
(as shown here)
FiO2
Fraction of inspired
oxygen. This is usually
titrated to oxygen
saturations targeting
92–95%
Tidal volume
Usual target is 6 mL/kg
of predicted body
weight (PBW)
Positive end-expiratory pressure (PEEP)
The pressure within the respiratory system during expiration,
commonly 5–15 cmH2O. Higher levels of PEEP often improve
oxygenation but put strain on the right heart (as it makes it
harder to pump blood through the pulmonary circulation)
Plateau pressure
Airway pressure during an
inspiratory hold. Keeping plateau
pressure as low as possible above
PEEP is the most protective
strategy for the lungs
Pressure–time
graph
Volume–time
graph
Flow–time
graph
204 • ACUTE MEDICINE AND CRITICAL ILLNESS
in the prone position for 12–24 hours and then rotated back
to the supine position for a similar period. This cycle continues
until there is evidence of resolving lung injury.
Extracorporeal respiratory support
Sometimes, despite optimal invasive ventilation, it is not possible
to maintain adequate oxygenation or prevent a profound
respiratory acidosis. When a patient has a reversible cause of
respiratory failure (or is a potential lung transplant recipient) and
facilities are available, extracorporeal respiratory support should
be considered.
Venous–venous extracorporeal
membrane oxygenation
In venous–venous extracorporeal membrane oxygenation (V V
ECMO), large-bore central venous cannulae are inserted into the
superior vena cava (SVC) and/or the inferior vena cava (IVC) via
the femoral or jugular veins, and advanced under ultrasound or
fluoroscopic guidance (Fig. 10.19). Venous blood is then pumped
through a membrane oxygenator. This device has thousands
of tiny silicone tubes with air/oxygen gas on the other side
of the tubes (the membrane). This facilitates the passage of
oxygen into the blood and diffusion of carbon dioxide across
the membrane, where it is removed by a constant flow of gas
(sweep gas). The oxygenated blood is then returned to the
right atrium, from where it flows through the lungs as it would
in the physiological state. This means that even if the lungs are
contributing no oxygenation or carbon dioxide removal, a patient
can remain well oxygenated and normocapnic.
Extracorporeal carbon dioxide removal
In some patients it is possible to maintain oxygenation but
there is refractory hypercapnia. There are devices available
that can remove carbon dioxide using a much lower blood flow
rate than V V ECMO. Consequently, smaller venous cannulae,
similar to those used in renal dialysis, can be sufficient to have
a ‘CO2 dialysis’ effect. This can be useful in patients in whom
normocapnia is essential (such as those with a raised ICP), or
those with refractory hypercapnia and adequate oxygenation. In
addition, extracorporeal carbon dioxide removal can be used to
reduce the required minute volume, which is a beneficial strategy
for protecting the lungs against VILI or facilitating early extubation.
Cardiovascular support
Initial resuscitation
A brief assessment can usually yield enough information to
determine whether a patient is at significant risk of an imminent
cardiac arrest. If the patient is obtunded and there is no palpable
radial or brachial pulse, then treatment should proceed as
described on page 457.
In anaphylactic shock, or undifferentiated shock in a peri-arrest
situation, a single dose of intramuscular adrenaline (epinephrine)
0.5 mg (0.5 mL of 1 : 1000) can be life-saving. If expertise is
available, a small dose of intravenous adrenaline can delay
cardiac arrest long enough to identify the cause of shock and
institute other supportive measures; a suggested dose would
be 50 μg (0.5 mL of 1 : 10 000). If haemorrhage is considered
a possibility, a ‘major haemorrhage’ alert should be activated,
facilitating rapid access to large volumes of blood and blood
products. A classification of shock is shown in Box 10.40.
Ventilator-induced lung injury
Every positive-pressure breath causes cyclical inflation of alveoli
followed by deflation. The resultant damage to alveoli occurs via
several possible mechanisms:
• distending forces from the tidal volume, termed
‘volutrauma’
• the pressure used to inflate the lung, referred to as
‘barotrauma’
• alveoli collapsing at the end of expiration, called
‘atelectotrauma’
• the release of inflammatory cytokines in response to
cyclical distension, called ‘biotrauma’.
The threshold of injurious ventilation is unique to each patient.
Moderate ventilator pressures and volumes used to ventilate
healthy lungs may not cause ventilator-induced lung injury (VILI),
but the same settings may cause significant VILI if delivered to
a patient with lungs that are already damaged from another
disease process.
Strategies that may reduce the incidence and severity of
VILI include:
• Permissive hypercapnia. In the majority of patients who
are ventilated for respiratory failure, it is preferable to
tolerate moderate degrees of hypercapnia rather than
strive for normal blood gases at the expense of VILI. For
example, in a patient with isolated respiratory failure,
a physician may choose to tolerate a PaCO2 of up
to 10 kPa (75 mmHg), provided the H+ is < 63 nmol/L
(pH > 7.2).
• ‘Open lung’ ventilation. Maintaining a positive pressure
within the airways at the end of expiration prevents
atelectotrauma. Use of low tidal volumes, higher levels of
PEEP (Fig. 10.18) and recruitment manœuvres (occasional
short periods of sustained high airway pressures to open
up alveoli that have collapsed) can reduce the incidence
of VILI.
• Paralysis. When respiratory failure is severe, patient effort
may worsen VILI. An infusion of muscle relaxant can be
used to moderate dyssynchrony with the ventilator.
Advanced respiratory support
Airway pressure release ventilation
Airway pressure release ventilation (APRV) is a mode of ventilation
that lengthens the inspiratory time to the extreme, with a very
short period of time for expiration. It relies on spontaneous
movement of the diaphragm from patient effort to facilitate
the mixing of gas within the respiratory system during the long
period in full inspiration, followed by a very short period of low
pressure to allow passive expiration. It has not, however, been
demonstrated to be superior to conventional modes of ventilation,
but may have a role in moderate to severe ARDS.
Prone positioning
In ARDS, the posterior parts of the lung lose airspaces due
to atelectasis and inflammatory exudate. By placing patients
on their front, the pattern of fluid distribution within the lung
changes, and ventilation–perfusion matching is improved. This
is used to enhance oxygenation in moderate to severe ARDS,
and may have some disease-modifying effects as the dependent
areas of the lung are changed periodically. Although there are
risks associated with nursing a patient in the prone position, it
is becoming a widespread therapy. Patients are usually placed
Stabilisation and institution of organ support • 205
Fig. 10.19 Principles of extracorporeal membrane oxygenation (ECMO). A Basic ECMO circuit: venous–arterial (VA) and venous–venous (V V).
B Example of a V V ECMO circuit. C Example of a VA ECMO circuit.
Gas out
Membrane
oxygenator
Controller
console
RPM
Pressures
Saturations
Flow
Oxygenated blood returned
to vein (V–V) or artery (V–A)
Venous blood from patient
(usually inferior vena cava)
Centrifugal pump
Venous ‘return’ cannula
Superior vena cava
Right atrium now full
of oxygenated blood
Tricuspid valve
Right ventricle
Inguinal ligament
Femoral artery
Access ECMO cannula
Femoral vein
Skin puncture site
in proximal thigh
From ECMO
circuit
To ECMO circuit
Venous
‘return’
cannula
Venous
‘access’
cannula
Gas in
A
B
Pulmonary vein (left)
Pulmonary vein (right)
Right atrium
Proximal aorta
Mitral valve
Aortic valve
Left ventricle
Blood from
ECMO circuit
Blood from ‘normal’
circulation (native
circulation)
Where the two circulations meet depends on the
native cardiac output; if very low, they will meet very
proximally/at the aortic valve
Oxygenated blood at
high pressure will flow
proximally up the aorta
to perfuse organs
Blood will also
flow distally to
perfuse the legs
Arterial ‘return’ cannula
Arterial
‘return’
cannula
To ECMO circuit
From ECMO circuit
Venous
‘access’
cannula
C
206 • ACUTE MEDICINE AND CRITICAL ILLNESS
agent: for example, in cardiogenic shock or shock associated
with bradycardia. If there is evidence of low cardiac output,
adrenaline (epinephrine) or dobutamine should be commenced.
Both agents are equally effective, but dobutamine causes more
vasodilatation and additional noradrenaline may be required to
maintain an adequate MAP. Vasopressin is added if hypotension
persists despite high doses of noradrenaline and cardiac output
is thought to be adequate.
In extreme situations it is acceptable to start infusions of
inotropes through a well-sited, large-bore peripheral cannula,
although central venous access and an arterial line (for monitoring)
should be inserted as soon as possible. The actions of commonly
used vasoactive drugs are summarised in Box 10.41.
Advanced haemodynamic monitoring
There are many different devices available to estimate cardiac
output. Such devices employ a variety of mechanisms, including
the Doppler effect of moving blood, changes in electrical
impedance of the thorax, or the dilution of either an indicator
substance or heat (thermodilution). The information is processed
within the equipment, and often integrated with additional data,
such as the arterial pressure waveform, to give an estimate of
cardiac output and stroke volume.
When the aetiology of shock is straightforward and the patient
is responding as predicted to treatment, the value of devices that
estimate cardiac output is limited. Portable echocardiography
has the advantage of giving qualitative information – for example,
demonstrating aortic stenosis or a regional wall motion abnormality
– as well as quantitative information on stroke volume, but it
requires technical expertise.
Pulmonary artery (PA) catheters, sometimes referred to as
Swan–Ganz catheters (Fig. 10.20), are invasive but provide useful
information on pulmonary pressures, cardiac output, mixed venous
oxygen saturations (see Box 10.30) and, by extrapolation, whether
the cause of the shock is vasodilatation or pump failure. They
can be helpful in complex cases, such as shock after cardiac
surgery, or in patients with suspected pulmonary hypertension
(Box 10.42). However, PA catheters are associated with some rare
but serious complications, including lung infarction, PA rupture
and thrombosis of the catheter itself. Such complications occur
infrequently in centres that use PA catheters regularly; it should
be stressed that a lack of familiarity within the wider clinical team
is a relative contraindication to their use.
Mechanical cardiovascular support
When shock is so severe that it is not possible to maintain
sufficient organ perfusion with fluids and inotropic support, it is
Venous access for the administration of drugs and fluids is
vital but often difficult in critically unwell patients. Wide-bore
cannulae are required for rapid fluid administration. In extremis,
the external jugular vein can be cannulated; it is often prominent
in low cardiac output states and readily visible on the lateral
aspect of the neck. Occluding the vein distally with finger pressure
makes it easier to cannulate, but care must be taken to remain
high in the neck to avoid causing a pneumothorax. Intra-osseous
or central venous access can be established if there are no
visible peripheral veins. Ultrasound can provide assistance for
rapid and safe venous cannulation. Rapid infusion devices are
widely available and should be used for the delivery of warmed,
air-free fluid and blood products.
Fluid and vasopressor use
Resuscitation of the shocked patient should include a 10 mL/
kg fluid challenge. Using colloid or crystalloid is acceptable;
starch solutions are associated with additional renal
dysfunction and should be avoided. The fluid challenge can
be repeated if shock persists, to a maximum total of 30 mL/
kg of fluid. However, commencing vasopressor therapy early
in resuscitation is better than delaying until a large volume
of fluid has been given. Amongst other beneficial effects,
vasopressors induce venoconstriction, reducing the capacitance
of the circulation and effectively mobilising more fluid into the
circulation.
If a patient remains shocked after 30 mL/kg of fluid has been
administered, a re-evaluation of the likely cause is required,
looking particularly for concealed haemorrhage or an obstructive
pathology. A bedside echocardiogram is especially useful at
this stage to evaluate cardiac output and exclude tamponade.
Noradrenaline (norepinephrine) should be commenced as
the first-line vasoactive agent in most cases, unless there is
a strong indication to use a pure inotropic or chronotropic
10.40 Categories of shock
Category
Description
Hypovolaemic
Can be haemorrhagic or non-haemorrhagic in
conditions such as hyperglycaemic hyperosmolar
state (p. 738) and burns
Cardiogenic
See page 199
Obstructive
Obstruction to blood flow around the circulation,
e.g. major pulmonary embolism, cardiac
tamponade, tension pneumothorax
Septic
See page 196
Anaphylactic
Inappropriate vasodilatation triggered by an allergen
(e.g. bee sting), often associated with endothelial
disruption and capillary leak (p. 75)
Neurogenic
Caused by major brain or spinal injury, which
disrupts brainstem and neurogenic vasomotor
control. High cervical cord trauma may result in
disruption of the sympathetic outflow tracts, leading
to inappropriate bradycardia and hypotension.
Guillain–Barré syndrome (p. 1140) can involve the
autonomic nervous system, resulting in periods of
severe hypo- or hypertension
Others
e.g. Drug-related such as calcium channel blocker
overdose; Addisonian crisis
10.41 Actions of commonly used vasoactive agents
Drug
Action
Vasoconstrictor
Inotrope
Chronotrope
Adrenaline
(epinephrine)
++
+++
++
Noradrenaline
(norepinephrine)
++++
+
+
Dobutamine
–
++++
+++
Vasopressin
+++++
No action
– (reflex
bradycardia)
Stabilisation and institution of organ support • 207
in cardiogenic shock. There are risks associated with thrombosis
formation on the balloon, mesenteric ischaemia and femoral artery
pseudo-aneurysm following removal of the device.
Venous–arterial extracorporeal
membrane oxygenation
Venous–arterial extracorporeal membrane oxygenation (VA
ECMO) can be life-saving in profound cardiogenic shock and
has even been used effectively in refractory cardiac arrest. The
circuit and principles are very similar to those described in ‘V V
ECMO’ above (see p. 204 and Fig. 10.19) with one important
difference: oxygenated blood is returned to the arterial system
(rather than into the right atrium). This means that the pump
needs to generate sufficient pressure to allow blood to flow
sometimes necessary to use an internal device to augment or
replace the inadequate native cardiac output.
Intra-aortic balloon pump
An intra-aortic balloon counter-pulsation device is a long tube
that is usually inserted into the femoral artery and fed proximally
into the thoracic aorta. The basic principle is that a helium-filled
balloon is able to inflate and deflate rapidly in time with the
cardiac cycle. It is inflated in diastole, thus augmenting forward
flow of blood to the abdominal organs and improving diastolic
pressure proximal to the balloon, thereby optimising coronary
perfusion. While the principle is appealing, and an intra-aortic
balloon pump (IABP) is often effective in achieving predetermined
physiological goals, this does not translate into improved survival
Fig. 10.20 A pulmonary artery (Swan–Ganz) catheter. A There is a small balloon at the tip of the catheter and pressure can be measured through
the central lumen. The catheter is inserted via an internal jugular, subclavian or femoral vein and advanced through the right heart until the tip lies in the
pulmonary artery. When the balloon is deflated, the pulmonary artery pressure can be recorded. B Advancing the catheter with the balloon inflated will
‘wedge’ the catheter in the pulmonary artery. Blood cannot then flow past the balloon, so the tip of the catheter will now record the pressure transmitted
from the pulmonary veins and left atrium (known as the pulmonary artery capillary wedge pressure), which provides an indirect measure of the left atrial
pressure. (LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle)
mmHg
Right
ventricular
pressure
Wedge
(left atrial)
pressure
Balloon
inflated
Balloon
Right atrial
pressure
Pulmonary
artery
pressure
A
B
Aorta
RA
RV
LV
LA
Pulmonary
artery
10.42 Interpreting haemodynamic data
Variable
Units
Reference range
Interpretation
Cardiac output (CO)
litres/minute (L/min)
4–8 L/min
Low cardiac output suggests pump failure
Cardiac index (CI)
Cardiac output referenced to the
size of the patient
litres/minute/metre2
(L/min/m2)
2.5–4 L/min/m2
More useful than raw cardiac output alone, especially in
smaller patients
Central venous pressure (CVP)
mmHg
0–6 mmHg
Reflects right atrial pressure – a non-specific measurement of
right ventricular (RV) function and volume status
Low levels suggest good RV function or hypovolaemia
Pulmonary artery systolic
pressure (PA systolic)
mmHg
15–30 mmHg
Difficult to interpret in isolation
Low levels suggest vasodilatation, hypovolaemia or right heart
failure
High levels are seen in many pathologies, e.g. left heart failure,
primary pulmonary arterial hypertension (PAH), fluid overload
Pulmonary artery diastolic
pressure (PA diastolic)
mmHg
5–15 mmHg
As with PA systolic pressure, difficult to interpret in isolation
Pulmonary artery capillary
wedge pressure (PACWP)
mmHg
2–10 mmHg (should
be within a few mmHg
of PA diastolic)
Reasonable indication of left atrial pressure – raised in left
heart failure and fluid overload
Measurement is associated with injury to PA so should only be
taken occasionally
Transpulmonary gradient
(PA diastolic – PACWP)
mmHg
1–5 mmHg
A high gradient suggests the pathology is in the pulmonary
arteries, e.g. primary PAH
208 • ACUTE MEDICINE AND CRITICAL ILLNESS
• Manage status epilepticus using antiepileptic agents such
as levetiracetam, phenytoin and benzodiazepines. In
refractory cases an infusion of sodium thiopental or
ketamine may be required.
The aim of management in acute brain injury is to optimise
cerebral oxygen delivery by maintaining normal arterial oxygen
content and a cerebral perfusion pressure (CPP) of > 60 mmHg.
Secondary insults to the brain, such as hypoxaemia, hyper-/
hypoglycaemia and prolonged seizures, must be avoided. ICP
rises in acute brain injury as a result of haematoma, contusions,
oedema or ischaemic swelling. Raised ICP causes damage to
the brain in two ways: direct damage to the brainstem and
motor tracts as a result of downward pressure and herniation
through the tentorium cerebelli and foramen magnum, and indirect
damage by reducing CPP. Cerebral blood flow is dependent
on an adequate CPP. The CPP is determined by the formula:
CPP
MAP
ICP
−
ICP can be measured by pressure transducers that are inserted
directly into the brain tissue. The normal upper limit for ICP is
15 mmHg and an upper acceptable limit of 20 mmHg is usually
adopted in intensive care. Sustained pressures of > 30 mmHg are
associated with a poor prognosis. Various strategies are used to
control ICP: maintaining normocapnia, preventing any impedance
to venous drainage from the head, giving osmotic agents such
as mannitol and hypertonic saline, and using hypothermia and
decompressive craniectomy. No single technique has been
shown to improve outcome in severe intracranial hypertension.
CPP should be maintained above 60 mmHg by ensuring
adequate fluid replacement and, if necessary, by treating
hypotension with a vasopressor such as noradrenaline
(norepinephrine). Complex neurological monitoring must be
combined with frequent clinical assessment of GCS, pupillary
response to light, and focal neurological signs.
Daily clinical management in
intensive care
Clinical review
In intensive care, detailed clinical examination should be performed
daily to identify changes to a patient’s condition and review the
latest diagnostic information. Further focused clinical reviews are
usually incorporated into twice-daily ward rounds. Each ward
round offers an ideal opportunity to monitor and document
compliance with relevant care bundles. A care bundle is a group of
interventions that, when implemented concurrently, have provided
evidence of clinical benefit. The mnemonic ‘FAST HUG’ provides
a useful checklist of interventions that reduce intensive care
complications: feeding, analgesia, sedation, thromboprophylaxis,
head of bed elevation (to reduce the incidence of passive
aspiration), ulcer prophylaxis and glucose control.
Other key aspects of the daily review are outlined on page 174.
The overarching aim of the review is to identify the issues that
are impeding recovery from critical illness, and make alterations
to address them. In addition, specific and realistic goals for
each relevant organ system should be defined, facilitating the
autonomous titration of therapy by the bedside critical care nurse.
An example of daily goals may be: ‘Titrate the noradrenaline
(norepinephrine) to achieve a MAP of 65 mmHg, aim for a
negative fluid balance, titrate FiO2 to achieve oxygen saturations
through the systemic circulation. The sites of venous and arterial
access can be either central (via a thoracotomy or sternotomy)
or peripheral via cannulae in the IVC/SVC and the femoral/
subclavian artery. If the return cannula is peripherally sited (e.g.
in the femoral artery), blood will flow back up the aorta from
distal to proximal and perfuse the organs.
The outcome depends on the avoidance of complications
(primarily, bleeding at the cannula site, intracranial haematoma,
air embolism, infection and thrombosis) and improvement of
the underlying condition. Most causes of profound cardiogenic
shock are unlikely to resolve, and the potential availability of a
longer-term solution, such as cardiac transplantation or insertion
of a ventricular assist device, is a prerequisite for commencing
VA ECMO in most centres.
Renal support
Renal replacement therapy (RRT) is explained in detail on
page 420. The key points relating to RRT in an intensive care
context are:
• Haemodynamic instability is common. Continuous
therapies are widely believed to cause less haemodynamic
instability than intermittent dialysis. However, many units
use intermittent dialysis without significant problems.
• Haemodialysis and haemofiltration are equally good.
Although there are theoretical benefits to removing
inflammatory cytokines with haemofiltration, this does not
translate into improved survival.
• Anticoagulation is usually achieved using citrate or heparin.
Citrate has a better profile for anticoagulating the
extracorporeal circuit without inducing an increased
bleeding risk, but may accumulate in patients with
profound multi-organ failure and should be avoided in very
unstable individuals.
• Most patients who survive intensive care will regain
adequate renal function to live without long-term renal
support.
• A thorough investigation for reversible causes of renal
dysfunction should always be undertaken in conjunction
with instigation of renal support (see Fig. 15.18, p. 411).
• Shock appears to reverse more rapidly when renal support
is instituted. Commencing renal support soon after a
patient develops renal ‘injury’ (when serum creatinine is
more than two times higher than baseline) is probably
beneficial in the context of septic shock.
Neurological support
A diverse range of neurological conditions require management in
intensive care. These include the various causes of coma, spinal
cord injury, peripheral neuromuscular disease and prolonged
seizures.
The goals of care in such cases are to:
• Protect the airway, if necessary by endotracheal
intubation.
• Provide respiratory support to correct hypoxaemia and
hypercapnia.
• Treat circulatory problems, e.g. neurogenic pulmonary
oedema in subarachnoid haemorrhage, autonomic
disturbances in Guillain–Barré syndrome, and spinal shock
following high spinal cord injuries.
• Manage acute brain injury with control of ICP.
Daily clinical management in intensive care • 209
noise reduction, cessation of drugs known to precipitate delirium,
and treatment of potential underlying causes such as thiamin
replacement in patients at risk of Wernicke’s encephalopathy.
Patients with agitated delirium that is refractory to verbal
de-escalation should initially be managed with small doses
of intramuscular antipsychotics, changed to the enteral route
once control is established. Atypical antipsychotics such as
olanzapine and quetiapine are more efficacious than traditional
drugs such as haloperidol. Pharmacological interventions are
not useful as prophylaxis or in hypoactive delirium. Additional
information on diagnosis and management of delirium can be
found on page 184.
Weaning from respiratory support
As the condition that necessitated ventilation resolves, respiratory
support is gradually reduced: the process of ‘weaning’ from
ventilation. Some approaches to weaning are described below.
of 92–95% and titrate sedation to a RASS score of 0 to −1’
(Box 10.44).
Sedation and analgesia
Most patients require sedation and analgesia to ensure comfort,
relieve anxiety and tolerate mechanical ventilation. Some
conditions, such as critically high ICP or critical hypoxaemia,
require deep sedation to reduce tissue oxygen requirements
and protect the brain from the peaks in ICP associated with
coughing or gagging. For the majority of patients, however, optimal
sedation is an awake and lucid patient who is comfortable and
able to tolerate an endotracheal tube (termed ‘tube tolerance’).
Over-sedation is associated with longer ICU stays, a higher
prevalence of delirium, prolonged requirement for mechanical
ventilation, and an increased incidence of ICU-acquired infection.
Box 10.43 compares the various agents used for sedation in
intensive care. The key principles are that the patient should
primarily receive analgesia, rather than anaesthesia, and caution
should be used with drugs that accumulate in hepatic and renal
dysfunction. Often a combination of drugs is used to achieve
the optimal balance of sedation and analgesia.
Sedation is monitored via clinical sedation scales that record
responses to voice and physical stimulation. The Richmond
Agitation–Sedation Scale (RASS) is the best-recognised tool
(see Box 10.44 for details). Regular use of a scoring system
to adjust sedation is associated with a shorter ICU stay. Many
ICUs also have a daily ‘sedation break’, when all sedation is
stopped in appropriate cases for a short period. This is commonly
combined with a trial of spontaneous breathing aiming to shorten
the duration of mechanical ventilation.
Delirium in intensive care
Delirium is discussed on page 183. It is extremely common in
critically ill patients and often becomes apparent as sedation
is reduced. Hypoactive delirium is far more common than
hyperactive delirium, but is easily missed unless routine screening
is undertaken. A widely used bedside assessment is the CAM-ICU
score. The patient is requested to squeeze the examiner’s hand
in response to instruction and questions, aiming to ascertain
whether disordered thought or sensory inattention is present.
Delirium of any type is associated with poorer outcome.
Management is focused on non-pharmacological interventions
such as early mobilisation, reinstatement of day–night routine,
10.44 Richmond Agitation–Sedation Scale (RASS)
Score
Term
Description
+4
Combative
Overtly combative, violent or
immediate danger to staff
+3
Very agitated
Pulls on/removes tubes or catheters,
or aggressive to staff
+2
Agitated
Frequent non-purposeful movement
or patient–ventilator dyssynchrony
+1
Restless
Anxious or apprehensive but no
aggressive or vigorous movements
Alert and calm
−1
Drowsy
Not fully alert but sustained
awakening (> 10 secs) with eye
opening/contact to voice
−2
Light sedation
Brief awakening (<10 secs) with eye
contact to voice
−3
Moderate sedation
Movement but no eye contact to voice
−4
Deep sedation
Movement to physical stimulation but
no response to voice
−5
Unrousable
No response to voice or physical
stimulation
10.43 Properties of sedative and analgesic agents used in ICU
Drug
Mode of action
Advantages
Disadvantages
Propofol
Intravenous anaesthetic
Rapid onset and offset
Large cumulative doses can cause multi-organ failure,
especially in children – the ‘propofol infusion syndrome’
Alfentanil
Potent opiate analgesic
Rapid onset and offset
High doses may be required
Agitation may persist
Morphine
Opioid
Analgesia
Active metabolites and accumulation cause slow offset
Midazolam
Benzodiazepine sedative
Can be used in children
Active metabolites and accumulation cause slow offset
Remifentanil
Very potent opiate
Analgesia and tube tolerance
Respiratory depression – extreme caution in non-intubated
patients
Dexmedetomidine
α2-adrenergic agonist
Excellent tube tolerance
Less delirium
Can be used in awake patients
Cost and availability
210 • ACUTE MEDICINE AND CRITICAL ILLNESS
patients are important to identify, as emergency management in
the event of a tracheostomy problem (blockage or displacement)
must be through the tracheostomy site; access will not be
possible via the upper airway.
Nutrition
It is crucial that critically ill patients receive adequate calories,
protein and essential vitamins and minerals. Calculation of exact
requirements is complex and requires the expertise of a dietitian.
It is, however, useful to make a rough estimation of requirements
(p. 705). Under-feeding leads to muscle wasting and delayed
recovery, while over-feeding can lead to biliary stasis, jaundice
and steatosis. Enteral feeding is preferred where possible because
it avoids the infective complications of total parenteral nutrition
(TPN) and helps to maintain gut integrity. However, TPN is
recommended for patients who are likely to have a sustained
period without effective enteral feeding, or who are already
malnourished. Caution must be taken to avoid the consequences
of refeeding syndrome (p. 706).
Other essential components of
intensive care
Survival after critical illness depends, to a large extent, on the
prevention of medical complications during recovery from the
primary insult.
Thromboprophylaxis
DVT, venous catheter-related thrombosis and PE are common in
critically ill patients. Low-molecular-weight heparin (LMWH) should
be administered to all patients, unless there is a contraindication.
Often patients at highest risk of thrombosis, such as those
with hepatic dysfunction or those who have suffered major
trauma, have a relative contraindication to heparin. Such
cases mandate daily evaluation of the risk–benefit ratio, and
LMWH should be administered as soon as it is deemed safe
to do so. Mechanical thromboprophylaxis, such as intermittent
calf compression devices, are useful adjuvants in high-risk
patients.
Glucose control
Hyperglycaemia is harmful in critical illness and may occur in
people with pre-existing diabetes or undiagnosed diabetes,
following administration of high-dose glucocorticoids, or as
Spontaneous breathing trials
A spontaneous breathing trial involves the removal of all respiratory
support followed by close observation of how long the patient
is able to breathe unassisted. The technique is particularly
effective when linked to a reduction in sedation. PEEP and
pressure support are reduced to low levels, or patients are
disconnected from the ventilator and breathe oxygen or humidified
air through the endotracheal tube. Signs of failure include rapid
shallow breathing, hypoxaemia, rising PaCO2, sweating and
agitation. Patients who pass a spontaneous breathing trial
are assessed for suitability of extubation (endotracheal tube
removal).
Progressive reduction in pressure
support ventilation
Progressive reduction in pressure support ventilation (PSV) is
applied to each breath over a period of hours or days, according
to patient response. Some ICU ventilators have software that
allows the facility to wean the support provided automatically.
A useful tool to guide the weaning process is the rapid shallow
breathing index (RSBI). This composite score of a patient’s
spontaneous respiratory rate and tidal volume (respiratory rate
divided by tidal volume in litres) gives a numerical indication of
how difficult the patient is finding breathing at that particular
level of support. A RSBI value of > 100 suggests that a
patient is working at a level that would be unsustainable for
longer periods.
Extubation
It is not possible to predict whether a patient is ready to
be extubated accurately; the timing relies heavily on clinical
judgement. There are, however, some simple rules that can
aid decision-making. Patients must have stable ABGs with
resolution of hypoxaemia and hypercapnia despite minimal
ventilator pressure support and a low FiO2. Conscious level must
be adequate to protect the airway, comply with physiotherapy,
and cough. Furthermore, an assessment must be made as to
whether the patient can sustain the required minute volume
without ventilator support. This depends on the condition of
patients’ lungs, their strength and other factors affecting the
PaCO2, such as temperature and metabolic rate. The need
for re-intubation following extubation is associated with poorer
outcome, but patients who are not given the opportunity to
breathe without a ventilator will also be at increased risk of
ventilator-associated complications such as pneumonia and
myopathy.
Tracheostomy
A tracheostomy is a percutaneous tube passed into the trachea
(usually between the first and second, or second and third tracheal
rings) to facilitate longer-term ventilation. The advantages and
disadvantages of tracheostomy insertion are listed in Box 10.45.
When ventilation weaning has been unsuccessful, a tracheostomy
provides a bridge between intubation and extubation; the
patient can have increasing periods free of ventilator support
but easily have support reinstated. A tracheostomy can be
inserted percutaneously, using a bronchoscope in the trachea for
guidance, or surgically under direct vision. Occasionally, a patient
will have a tracheostomy in situ following a laryngectomy. Such
10.45 Advantages and disadvantages
of tracheostomy
Advantages
• Patient comfort
• Improved oral hygiene
• Access for tracheal toilet
• Ability to speak with cuff
deflated and a speaking valve
attached
• Reduced equipment ‘dead
space’ (the volume of tubing)
• Earlier weaning and ICU
discharge
• Reduced sedation requirement
• Reduced vocal cord damage
Disadvantages
• Immediate complications:
hypoxaemia, haemorrhage
• Tracheostomy site infection
• Tracheal damage; late
stenosis
Complications and outcomes of critical illness • 211
function (and thus consciousness), but a lesion in the ventral
pons (usually caused by infarction) results in complete paralysis.
The term ‘vegetative state’ implies some retention of brainstem
function and minimal cortical function, with loss of awareness of
the environment. In contrast, ‘minimally conscious state’ implies
that there is some degree of awareness and intact brainstem
function. Confident distinction between these states is important
and requires careful assessment, often over a period of time.
Brain death is, by definition, irreversible but other states may
offer hope for improvement.
ICU-acquired weakness
Weakness is common among survivors of critical illness. It is
usually symmetrical, proximal and most marked in the lower
limbs. Critical illness polyneuropathy and myopathy can occur
simultaneously and, within the constraints of an altered sensorium,
it can be impossible to distinguish the two conditions clinically.
Risk factors for both processes include the severity of multi-organ
failure, poor glycaemic control and the use of muscle relaxants
and glucocorticoids.
Critical illness polyneuropathy
This is due to peripheral nerve axonal loss and characteristically
presents as proximal muscle weakness with preserved sensation.
a consequence of ‘stress hyperglycaemia’. Hyperglycaemia
is commonly managed by infusion of intravenous insulin
titrated against a ‘sliding scale’. Intensive management of
hyperglycaemia with insulin can result in hypoglycaemia, which
may also be harmful in critical illness. Therefore, a compromise
is to titrate insulin to a blood glucose level of 6–10 mmol/L
(108–180 mg/dL).
Blood transfusion
Many critically ill patients become anaemic due to reduced red
cell production and red cell loss through bleeding and blood
sampling. However, red cell transfusion carries inherent risks
of immunosuppression, fluid overload, organ dysfunction from
microemboli, and transfusion reactions. In stable patients, a
haemoglobin level of 70 g/L (7 g/dL) is a safe compromise between
optimisation of oxygen delivery and the risks of transfusion. This
transfusion threshold should be adjusted upwards for situations
where oxygen delivery is critical, such as in patients with active
myocardial ischaemia.
Peptic ulcer prophylaxis
Stress ulceration during critical illness is a serious complication.
Proton pump inhibitors or histamine-2 receptor antagonists
are effective at reducing the incidence of ulceration. There is,
however, a suggestion that the use of these agents, particularly
in conjunction with antibiotics, may increase the incidence of
nosocomial infection, especially with Clostridium difficile (p. 264).
It is therefore common practice to stop ulcer prophylaxis once
consistent absorption of enteral feed is established.
Complications and outcomes
of critical illness
The majority of patients will survive their episode of critical illness.
While some will return to full, active lives, there are many who
have ongoing physical, emotional and psychological problems.
Adverse neurological outcomes
Brain injury
Head injury, hypoxic–ischaemic injury and infective, inflammatory
and vascular pathologies can all irreversibly injure the brain.
If treatment is unsuccessful, patients will either die or be left
with a degree of disability. In the latter situation, the provision
of ongoing organ support will depend on the severity of the
injury, the prognosis, and the wishes of the patient (usually
expressed via relatives). Brain death is a state in which cortical
and brainstem function is irreversibly lost. Diagnostic criteria
for brain death vary between countries (Box 10.46); if satisfied,
these criteria allow physicians to withdraw active treatment
and discuss the potential for organ donation. Diagnosing brain
death is complex and should be done only by physicians with
appropriate expertise, as clinical differentiation from reduced
consciousness can be challenging (Box 10.47). Where there is
doubt – for example, in patients with coexisting spinal injury or
localised brainstem pathology – additional investigations should
be performed.
The ‘locked-in’ syndrome, in which the patient is paralysed
except for eye movements, requires preserved hemispheric
10.46 UK criteria for the diagnosis of brain death
Preconditions for considering a diagnosis of brain death
• The patient is deeply comatose:
a. There must be no suspicion that coma is due to depressant
drugs, such as narcotics, hypnotics, tranquillisers
b. Hypothermia has been excluded – rectal temperature must
exceed 35°C
c. There is no profound abnormality of serum electrolytes,
acid–base balance or blood glucose concentrations, and any
metabolic or endocrine cause of coma has been excluded
• The patient is maintained on a ventilator because spontaneous
respiration has been inadequate or has ceased. Drugs, including
neuromuscular blocking agents, must have been excluded as a
cause of the respiratory failure
• The diagnosis of the disorder leading to brain death has been firmly
established. There must be no doubt that the patient is suffering
from irremediable structural brain damage
Tests for confirming brain death
• All brainstem reflexes are absent:
a. The pupils are fixed and unreactive to light
b. The corneal reflexes are absent
c. The vestibulo-ocular reflexes are absent – there is no eye
movement following the injection of 20 mL of ice-cold water into
each external auditory meatus in turn
d. There are no motor responses to adequate stimulation within the
cranial nerve distribution
e. There is no gag reflex and no reflex response to a suction
catheter in the trachea
• No respiratory movement occurs when the patient is disconnected
from the ventilator for long enough to allow the carbon dioxide
tension to rise above the threshold for stimulating respiration
(PaCO2 must reach 6.7 kPa/50 mmHg)
The diagnosis of brain death should be made by two doctors of a
specified status and experience. The tests are usually repeated after
a short interval to allow blood gases to normalise before brain death
is finally confirmed
212 • ACUTE MEDICINE AND CRITICAL ILLNESS
Other long-term problems
The experience of critical illness and the necessary invasive
management can leave patients with profound psychological
sequelae akin to the post-traumatic stress syndrome seen in
many survivors of conflict. Specialist help is required in managing
these issues. Sometimes recovering patients benefit from returning
to the ICU to see the environment in a different way and gain
a better understanding of the processes and procedures that
haunt them.
Long-term physical consequences are also common. Many
diseases are not completely cured but follow a relapsing–remitting
course; patients who have been critically ill with sepsis are far
more likely than others in the general population to suffer from it
again. Organ damage often persists and iatrogenic complications
are common (e.g. damage to the vocal cords or tracheal stenosis
from mucosal pressure caused by the cuff of the endotracheal
tube). Intensive care follow-up clinics provide an excellent forum
for addressing such issues, and for coordinating care involving
a variety of medical specialties.
The older patient
Critically ill older patients present additional challenges following
intensive care discharge (Box 10.48). As the ability to make a
full recovery depends on frailty rather than chronological age, it
can be helpful to use a validated frailty scoring system (p. 1306)
to inform admission decision-making.
Rehabilitation medicine has much to offer survivors of critical
illness, and an early referral is beneficial when it is clear that a
patient is likely to survive with significant morbidity.
10.47 Classification of brain death and reduced conscious states
Diagnosis
Features
Investigation
Prognosis
Brain death
See Box 10.46
Often not required if cranial imaging
shows compatible cause and patient
meets clinical criteria
In diagnostic doubt: four-vessel
angiogram (fluoroscopic or CT) of
cerebral vessels or isotope scan of
brain to demonstrate absence of
cerebral blood flow
Time of confirmed brain death
is recorded as time of death
Potential to donate organs
– donation after brain death
(DBD) donor
Vegetative state (VS)
‘Persistent VS’ > 1
month
‘Permanent VS’ > 1 year
No reaction to verbal stimuli
Some reaction to noxious stimuli
Sleep–wake cycles (periods of eye opening)
Maintained respiratory drive
Intact brainstem reflexes
Occasional automatic movements (yawning,
swallowing)
Cranial imaging for primary cause
Maintained cortical blood flow
Poor. May be better with
traumatic aetiology
Minimally conscious
state
Some reaction to verbal stimuli
Some reaction to noxious stimuli
Spontaneous movements
Intact brainstem reflexes
EEG demonstrates reactivity
Variable. Recovery of function
more likely than in VS
Locked-in syndrome
Cortex is intact but bilateral motor tracts
are damaged
Can be partial or complete, i.e. some
response to verbal stimuli (e.g. vertical eye
movements to communicate)
Variable brainstem reflexes
No limb movement to noxious stimuli
Imaging for primary cause –
commonly MRI or CT will show
brainstem or pontine infarction
Variable and depends on cause
– progress can continue over
months to years
It may also manifest as failure to wean from the ventilator secondary
to respiratory muscle weakness. Electrophysiological studies of
the affected nerves can be helpful, especially to rule out other
potential causes such as Guillain–Barré syndrome. Conduction
studies typically show reduced amplitude of transmitted voltage
action potential with preserved velocity (compare with findings
in Guillain–Barré syndrome; pp. 1076 and 1140). There are
no specific treatments aside from resolution of the underlying
cause and rehabilitation. Weakness may persist long into the
convalescence stage of illness. In some cases, the clinical picture
may be more in keeping with individual nerve involvement. This
may be due to local pressure effects or part of a generalised
picture. Great care must be taken to avoid pressure on high-risk
areas such as the neck of the fibula where the common peroneal
nerve navigates a superficial course. Nerve palsies such as foot
drop can be permanent.
Critical illness myopathy
Although loss of muscle bulk is related to immobility and the
catabolic state of critical illness, it is likely that microvascular and
intracellular pathophysiological processes are also involved in
critical illness myopathy. These processes result in loss of actin
myofibrils and muscle weakness. Typically, the CK is normal or
only mildly elevated. Like critical illness polyneuropathy, critical
illness myopathy is usually a clinical diagnosis. Nerve conduction
studies and electromyography may be suggestive of critical
illness myopathy, and helpful in ruling out other pathology, but
a muscle biopsy is required to confirm the diagnosis (p. 1076).
It characteristically shows selective loss of the thick myofibrils
and muscle necrosis. Management is conservative and the
prognosis is good in ICU survivors.
Complications and outcomes of critical illness • 213
patient continues to be ventilated. The practice of organ
donation varies throughout the world but the principles remain
the same.
Organ donation specialists are contacted and they begin
the process of establishing the suitability of any organs for
transplantation and matching potential recipients. Many patients
will have expressed their wishes through an organ donor
registration scheme but agreement of family and next of kin
is a moral (and sometimes legal) prerequisite. Once the organ
retrieval theatre team have been assembled and all preliminary
tests have been completed, the deceased patient is transferred
to the operating theatre and the organs are sequentially removed.
Donation after cardiac death
If a patient does not meet brain death criteria but withdrawal of
treatment has been agreed, donation of organs with residual
function may be appropriate. This is termed ‘donation after
cardiac death’ (DCD). If the patient dies within a short period
following the commencement of ‘warm ischaemic time’ (the time
to asystole following the onset of physiological derangement
after the withdrawal of active treatment), then DCD can proceed.
The deceased patient is transferred to an operating theatre and
the agreed organs (often lungs, liver, kidney and pancreas) are
retrieved. As heart valves and corneas can be retrieved later (within
a longer time frame), tissue retrieval may occur in the mortuary.
Postmortem examination or autopsy
There are several indications to request a postmortem examination.
A coroner (or legal equivalent) may initiate the process if a death
is unexpected or violent, or has occurred under suspicious
circumstances. The treating physician(s) may request one if they
are unable to establish a cause of death or there is agreement
that it may yield information of interest to the family or clinical
team. The postmortem diagnosis is frequently at odds with the
antemortem diagnosis and it is a very useful learning exercise
to review the results with all those involved in the patient’s care.
Discharge from intensive care
Discharge is appropriate when the original indication for admission
has resolved and the patient has sufficient physiological reserve
to continue to recover without the facilities of intensive care.
Many ICUs and HDUs function as combined units, allowing
‘step-down’ of patients to HDU care without changing the clinical
team involved. Discharge from ICU is stressful for patients and
families, and clear communication with the clinical team accepting
responsibility is vital. Nursing ratios change from 1 : 1 (one nurse
per patient) or 1 : 2 to much lower staffing levels. Discharges from
ICU or HDU to standard wards should take place within normal
working hours to ensure adequate medical and nursing support
and detailed handover. Discharge outside normal working hours
is associated with higher ICU re-admission rates and increased
mortality. The receiving team should be provided with a written
summary, including the information listed in Box 10.49. The
ICU team should remain available for advice; many ICU teams
provide an outreach service to supply advice and facilitate
continuity of care.
Critical care scoring systems
Admission and discharge criteria vary between ICUs, so it is
important to define the characteristics of the patients admitted in
Withdrawal of active treatment and death
in intensive care
Futility
The idea of futility is not new: Hippocrates stated that physicians
should ‘refuse to treat those who are overmastered by their
disease, realising that in such cases medicine is powerless’. In
intensive care, where the concept of futility is often used as a
criterion to limit or withdraw life-sustaining treatment, it is helpful
to have a working definition on which families and physicians
can agree. It is, therefore, reasonable to define futility in such
circumstances as the point at which recovery to a quality of life
that the patient would find acceptable has passed. The primary
insult may be neurological (irreversible brain injury not meeting
criteria for brain death), or multi-organ failure that is refractory
to treatment.
Death
Whilst most patients prefer to die at home, many spend their
final days in hospital. Chapter 34 details the medical, legal
and ethical priorities that should guide patient management
once the decision to withdraw active treatment has been made
(p. 1354). The decision to shift the focus of care to palliation
should not change its intensity; it is the over-arching objective
that changes. Only interventions that will improve the quality of
a patient’s remaining life should be offered. In the ICU, it is often
appropriate to continue infusions of sedatives and analgesics,
as reducing or stopping them may cause unnecessary pain
and agitation. Measures that were instituted to prolong life
should be withdrawn (usually including cessation of inotropes
and extubation) to allow the patient to die peacefully with their
family and friends present.
Organ donation
Donation after brain death
The diagnosis of brain death is discussed on page 211. Once
brain death has been confirmed, consideration should be given
to organ donation, termed ‘donation after brain death’ (DBD).
Time of death is recorded as the time when the first series
of brain death tests are undertaken, although the deceased
10.48 The critically ill older patient
• ICU demography: increasing numbers of critically ill older patients
are admitted to the ICU; more than 50% of patients in many
general ICUs are over 65 years old.
• Outcome: affected to some extent by age, as reflected in APACHE
II (see Box 10.50), but age should not be used as the sole criterion
for withholding or withdrawing ICU support.
• Cardiopulmonary resuscitation (CPR): successful hospital
discharge following in-hospital CPR is rare in patients over 70 years
old in the presence of significant chronic disease.
• Functional independence: tends to be lost during an ICU stay and
prolonged rehabilitation may subsequently be necessary.
• Specific problems:
Skin fragility and ulceration
Poor muscle strength: difficulty weaning from ventilator and
mobilising
Delirium: compounded by sedatives and analgesics
High prevalence of underlying nutritional deficiency.
214 • ACUTE MEDICINE AND CRITICAL ILLNESS
into the management of patients with that diagnosis, in order
to identify aspects of care that could be improved.
Further information
Websites
criticalcarereviews.com Reviews and appraisal of ICU topics.
emcrit.org Online podcasts and general information on emergency
medicine and critical care.
esicm.org European Society of Intensive Care Medicine: guidelines,
recommendations, consensus conference reports.
lifeinthefastlane.com Information on a range of intensive care and
emergency medicine topics.
survivingsepsis.org Surviving Sepsis website.
order to assess the effects of the care provided on the outcomes
achieved. Two systems are widely used to measure severity of
illness (see Box 10.50 for further details):
• APACHE II: Acute Physiology Assessment and Chronic
Health Evaluation
• SOFA score: Sequential Organ Failure Assessment tool.
When combined with the admission diagnosis, scoring systems
have been shown to correlate well with the risk of death in hospital.
Such outcome predictions are useful at a population level but
lack the specificity to be of use in decision-making for individual
patients. This is in contrast to well-validated, disease-specific
tools, such as the CURB-65 tool for pneumonia, which can be
helpful in guiding individual management (see Fig. 17.32, p. 583).
Predicted mortality figures by diagnosis have been calculated
from large databases generated from a range of ICUs. These
allow a particular unit to evaluate its performance compared to
the reference ICUs by calculating standardised mortality ratios
(SMRs) for each diagnostic group. A value of unity indicates the
same performance as the reference ICUs, while a value below 1
indicates a better than predicted outcome. If a unit has a high SMR
in a certain diagnostic category, it should prompt investigation
10.50 Comparison of APACHE II and SOFA scores
APACHE II score
• An assessment of admission characteristics (e.g. age and
pre-existing organ dysfunction) and the maximum/minimum values
of 12 routine physiological measurements during the first 24 hours
of admission (e.g. temperature, blood pressure, GCS) that reflect
the physiological impact of the illness
• Composite score out of 71
• Higher scores are given to patients with more serious underlying
diagnoses, medical history or physiological instability; higher
mortality correlates with higher scores
SOFA score
• A score of 1–4 is allocated to six organ systems (respiratory,
cardiovascular, liver, renal, coagulation and neurological) to
represent the degree of organ dysfunction, e.g. platelet count
150 × 109/L scores 1 point, < 25 × 109/L scores 4 points
• Composite score out of 24
• Higher scores are associated with increased mortality
10.49 How to write an ICU discharge summary:
information to be included
• Summary of diagnosis and progress in intensive care
• Current medications and changes to regular medications with
justifications
• Antibiotic regime and suggested review dates
• Results of positive microbiological tests
• Positions of invasive devices and insertion dates
• Escalation plan in the event of deterioration
• Pending investigations and specialty consultations
• If the physiology remains abnormal due to chronic disease, rapid
response triggers should be adjusted accordingly