# 02 - 311 Approach to the Patient with Critical Illness

### 311 Approach to the Patient with Critical Illness

Section 1	 Respiratory Critical Care
Rebecca M. Baron, Anthony F. Massaro

Approach to the Patient 

with Critical Illness
The care of critically ill patients requires a thorough understand­
ing of pathophysiology and centers initially on the resuscitation of 
patients at the extremes of physiologic deterioration. This resuscita­
tion is often fast-paced and occurs early when a detailed awareness 
of the patient’s chronic medical problems may not yet be possible. 
While physiologic stabilization is taking place, intensivists attempt to 
gather important background medical information to supplement the 
real-time assessment of the patient’s current physiologic condition. 
Numerous tools are available to assist intensivists in the assessment 
of pathophysiology and management of incipient organ failure, offer­
ing a window of opportunity for diagnosing and treating underlying 
disease(s) in a stabilized patient. However, despite these tools, ongo­
ing clinical bedside assessment is imperative for care of the critically 
ill patient. Indeed, the use of interventions to support the patient, 
such as mechanical ventilation and renal replacement therapy, is 
commonplace in the intensive care unit (ICU). An appreciation of 
the risks and benefits of such aggressive and often invasive interven­
tions is vital to ensure an optimal outcome. Nonetheless, intensivists 
must recognize when a patient’s chances for recovery are remote or 
nonexistent and must counsel and comfort dying patients and their 
significant others if an initial trial of invasive supportive care is either 
not effective or is not appropriate for the patient’s current condition. 
Critical care physicians often must redirect the goals of care from 
resuscitation and cure to comfort when the resolution of an underly­
ing illness is not possible. The COVID-19 pandemic has heightened 
the need and priority for effective critical care practices (Chap. 205), 
as well as the need for additional support for post-ICU care and 
recovery for ICU survivors
TABLE 311-1  Calculation of SOFA Scorea
SYSTEM

Respiration
 
 
 
 
 
  Pao2/FIo2, mmHg (kPa)
≥400 (53.3)
<400 (53.3)
<300 (40)
<200 (26.7) with respiratory 
support
Coagulation
 
 
 
 
 
  Platelets, × 103/μL
≥150
<150
<100
<50
<20
Liver
 
 
 
 
 
  Bilirubin, mg/dL (μmol/L)
<1.2 (20)
1.2–1.9 (20–32)
2.0–5.9 (33–101)
6.0–11.9 (102–204)
>12.0 (204)
Cardiovascular
MAP ≥70 mmHg
MAP <70 mmHg
Dopamine <5 or 

dobutamine (any dose)b
Dopamine 5.1–15 or 

epinephrine ≤0.1 or 
norepinephrine ≤0.1b
Central nervous system
 
 
 
 
 
  Glasgow Coma Scalec

13–14
10–12
6–9
<6
Renal
 
 
 
 
 
  Creatinine, mg/dL (μmol/L) 

<1.2 (110)
1.2–1.9 (110–170)
2.0–3.4 (171–299)
3.5–4.9 (300–440)
or
<500
or urine output, mL/d
aAdapted from JL Vincent et al: Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related Organ Failure 
Assessment) score to describe organ dysfunction/failure. Intensive Care Med 22(7):707, 1996. bCatecholamine doses are given as μg/kg per min for at least 1 h. cGlasgow 
Coma Scale scores range from 3 to 15; higher score indicates better neurological function.
Abbreviations: FIo2, fraction of inspired oxygen; MAP, mean arterial pressure; Pao2, partial pressure of oxygen.

Critical Care Medicine
PART 8
ASSESSMENT OF ILLNESS SEVERITY
In the ICU, illnesses are frequently categorized by degree of severity. 
Numerous severity-of-illness (SOI) scoring systems have been devel­
oped and validated over the past three decades. Although these scoring 
systems have been validated as tools to assess populations of critically 
ill patients, their utility in predicting individual patient outcomes at 
the bedside is not clear. Their utility may be more applicable toward 
defining patient populations for clinical trial outcomes and broader 
epidemiologic studies. SOI scores are also useful in guiding hospital 
administrative policies, directing the allocation of resources such as 
nursing and ancillary care, and assisting in assessments of quality of 
ICU care over time. Scoring system validations are based on the prem­
ise that age, chronic medical illnesses, and derangements from normal 
physiology are associated with increased mortality rates. All existing 
SOI scoring systems are derived from patients who have already been 
admitted to the ICU. Nevertheless, there has been increased recent 
clinical use of scoring systems due to revised consensus guidelines for 
definitions of sepsis, as will be detailed below.
The most commonly utilized scoring systems are the SOFA (Sequen­
tial Organ Failure Assessment) and the APACHE (Acute Physiology 
and Chronic Health Evaluation). There has been more recent interest 
in the use of a “quick” SOFA, or qSOFA, scoring system for prognosti­
cation of sepsis outcomes.
■
■THE SOFA SCORING SYSTEM
The SOFA scoring system is composed of scores from six organ 
systems, graded from 0 to 4 according to the degree of dysfunction 
(Table 311-1). The score accounts for clinical interventions; it can be 
measured repeatedly (i.e., each day), and rising scores correlate with 
increasing mortality. The most recent sepsis consensus conference 
guidelines incorporated an increase of at least two points in the SOFA 
score from baseline as diagnostic of sepsis in the setting of suspected 
or documented infection. Patients with suspected infection can be 
predicted to have poor outcomes typical of sepsis if they have at least 
two of the following clinical criteria: respiratory rate ≥22 breaths/min, 
altered mental status, or systolic blood pressure ≤100 mmHg. Recently, 
a new bedside clinical score using two or more of the above clinical 
criteria has emerged and is termed quick SOFA (qSOFA). qSOFA is 
intended to screen patients for risk of poor outcomes from sepsis from 
SCORE
<100 (13.3) with 
respiratory support
Dopamine >15 or 
epinephrine >0.1 or 
norepinephrine >0.1b
>5.0 (440)
or
<200

out-of-hospital, emergency department, and hospital ward settings. 
qSOFA was not developed, nor is it currently recommended, as a sep­
sis diagnostic screening tool, but studies are investigating its utility as 
such, especially in resource-poor settings that may not have the ability 
to measure all the components of the SOFA score.

■
■THE APACHE II SCORING SYSTEM
The APACHE II system is the most commonly used SOI scoring 
system in North America. Age, type of ICU admission (after elective 
surgery vs nonsurgical or after emergency surgery), chronic health 
problems, and 12 physiologic variables (the worst values for each in 
the first 24 h after ICU admission) are used to derive a score. The 
predicted hospital mortality rate is derived from a formula that takes 
into account the APACHE II score, the need for emergency surgery, 
and a weighted, disease-specific diagnostic category (Table 311-2). 
The relationship between APACHE II score and mortality risk is illus­
trated in Fig. 311-1. Updated versions of the APACHE scoring system 
(APACHE III and APACHE IV) have been published.
PART 8
Critical Care Medicine
■
■OTHER SCORING SYSTEMS
There are numerous other scoring systems that have been developed, 
and there are ongoing studies evaluating their utility. In particular, 
TABLE 311-2  Calculation of Acute Physiology and Chronic Health Evaluation II (APACHE II) Scorea
Acute Physiology Score
SCORE
+4
+3
+2
+1
+0
+1
+2
+3
+4
Rectal temperature (°C)
≥41
39.0–40.9
 
38.5–38.9
36.0–38.4
34.0–35.9
32.0–33.9
30.0–31.9
≤29.9
Mean blood pressure (mmHg)
≥160
130–159
110–129
 
70–109
 
50–69
 
≤49
Heart rate (beats/min)
≥180
140–179
110–139
 
70–109
 
55–69
40–54
≤39
Respiratory rate (breaths/min)
≥50
35–49
 
25–34
12–24
10–11
6–9
 
≤5
Arterial pH
≥7.70
7.60–7.69
 
7.50–7.59
7.33–7.49
 
7.25–7.32
7.15–7.24
<7.15
Oxygenation
  If FIo2 >0.5, use (A – a) Do2
 
≥500
 
350–499
 
200–349
  If FIo2 ≤0.5, use Pao2
 
 
 
 
>70
61–70
 
55–60
<55
Serum sodium (meq/L)
≥180
160–179
155–159
150–154
130–149
 
120–129
111–119
≤110
Serum potassium (meq/L)
≥7.0
6.0–6.9
 
5.5–5.9
3.5–5.4
3.0–3.4
2.5–2.9
 
<2.5
Serum creatinine (mg/dL)
≥3.5
2.0–3.4
1.5–1.9
 
0.6–1.4
 
<0.6
 
 
Hematocrit (%)
≥60
 
50–59.9
46–49.9
30–45.9
 
20–29.9
 
<20
WBC count (103/mL)
≥40
 
20–39.9
15–19.9
3–14.9
 
1–2.9
 
<1
Glasgow Coma Scoreb,c
EYE OPENING
VERBAL (NONINTUBATED)
VERBAL (INTUBATED)
MOTOR ACTIVITY
4—Spontaneous
5—Oriented and talks
5—Seems able to talk
6—Verbal command
3—Verbal stimuli
4—Disoriented and talks
3—Questionable ability to talk
5—Localizes to pain
2—Painful stimuli
3—Inappropriate words
1—Generally unresponsive
4—Withdraws from pain
1—No response
2—Incomprehensible sounds
 
3—Decorticate
 
1—No response
 
2—Decerebrate
 
 
 
1—No response
Points Assigned to Age and Chronic Disease
AGE, YEARS
SCORE
 
<45

45–54

55–64

65–74

≥75

CHRONIC HEALTH (HISTORY OF CHRONIC CONDITIONS)d
 
 
SCORE
 
 
 
None
 
 

If patient is admitted after elective surgery
 
 

If patient is admitted after emergency surgery or for reason other than after elective surgery
 

aThe APACHE II score is the sum of the acute physiology score (vital signs, oxygenation, laboratory values), the Glasgow coma score, age, and chronic health points. The 
worst values during the first 24 h in the ICU should be used. For serum creatinine, double the point score for acute renal failure. bGlasgow coma score (GCS) = eye-opening 
score + verbal (intubated or nonintubated) score + motor score. cFor GCS component of acute physiology score, subtract GCS from 15 to obtain points assigned. dHepatic: 
cirrhosis with portal hypertension or encephalopathy; cardiovascular: class IV angina (at rest or with minimal self-care activities); pulmonary: chronic hypoxemia or 
hypercapnia, polycythemia, ventilator dependence; renal: chronic peritoneal or hemodialysis; immune: immunocompromised host.
Abbreviations: (A – a) Do2, alveolar-arterial oxygen difference; FIo2, fraction of inspired oxygen; Pao2, partial pressure of oxygen; WBC, white blood cell count.

there is increasing interest in utilizing electronic health medical record 
scoring systems that might better incorporate larger and real-time data 
sets from patients, and that can alert providers to patients at risk for 
sepsis and/or poor outcomes from clinical illness.
SHOCK (SEE ALSO CHAP. 314)
■
■INITIAL EVALUATION
Shock, a common condition necessitating ICU admission or occurring 
in the course of critical care, is defined by the presence of multisys­
tem end-organ hypoperfusion. Clinical indicators include reduced 
mean arterial pressure (MAP), tachycardia, tachypnea, cool skin and 
extremities, acute altered mental status, and oliguria. The end result of 
multiorgan hypoperfusion is tissue hypoxia, often with accompanying 
lactic acidosis. Because the MAP is the product of cardiac output and 
systemic vascular resistance (SVR), reductions in blood pressure can 
be caused by decreases in cardiac output and/or SVR. Accordingly, 
once shock is contemplated, the initial evaluation of a hypotensive 
patient should include an early bedside assessment of the adequacy 
of cardiac output (Fig. 311-2). Clinical evidence of diminished car­
diac output includes a narrow pulse pressure (systolic blood pressure 
minus diastolic blood pressure)—a marker that correlates with stroke 
 
 
<200

Mortality rate, %

0–4
10–14
5–9
15–19
25–29
35+
20–24
30–34
APACHE II Score
FIGURE 311-1  APACHE II survival curve. Blue, nonoperative; green, postoperative.
volume—and cool extremities with delayed capillary refill, colloquially 
termed “cold shock.” It is important to palpate proximal extremities 
(e.g., thigh region) rather than distal extremities to determine rela­
tive “coolness,” because patients with peripheral vascular disease may 
always have cool distal extremities. Signs of increased cardiac output 
include a widened pulse pressure (particularly with a reduced diastolic 
pressure), warm extremities with bounding pulses, and rapid capillary 
refill, colloquially termed “warm shock.” If a hypotensive patient has 
clinical signs of increased cardiac output, it can be inferred that the 
reduced blood pressure is from decreased SVR.
SHOCK
Cold, clammy
extremities
Warm, bounding
extremities
Low cardiac output
High cardiac output
May
convert
to
Septic shock,
liver failure
JVP, crackles
JVP, orthostasis
Heart is “full”
(cardiogenic shock)
Antibiotics, aggressive
resuscitation
Evaluate for myocardial
ischemia
Heart is “empty”
(hypovolemic shock)
Consider echocardiogram,
invasive vascular monitoring
Intravenous fluids
No improvement
Inotropes, afterload
reduction
What does not fit?
Adrenal crisis, right heart syndrome,
pericardial disease
Consider echocardiogram,
invasive vascular monitoring
FIGURE 311-2  Approach to the patient in shock. JVP, jugular venous pressure.

In hypotensive patients with signs of reduced cardiac output, an 
assessment of intravascular volume status is appropriate. A hypoten­
sive patient with decreased intravascular volume status may have a 
history suggesting hemorrhage or other volume losses (e.g., vomiting, 
diarrhea, polyuria). Although evidence of a reduced jugular venous 
pressure (JVP) is often sought, static measures of right atrial pressure 
do not predict fluid responsiveness reliably; the change in right atrial 
pressure as a function of spontaneous respiration is a better predictor 
of fluid responsiveness (Fig. 311-3). Patients with fluid-responsive 
(i.e., hypovolemic) shock also may manifest large changes in pulse 
pressure as a function of respiration during mechanical ventilation 
(Fig. 311-4). Other bedside metrics can help with judging whether a 
patient remains fluid-responsive, including responses to volume chal­
lenge or a straight leg raise (that increases venous return) that correlate 
with improved perfusion. Such tools include judging changes in JVP 
or central venous oxygen saturation, assessing changes in pulse pres­
sure variation, determining changes in inferior vena cava collapse by 
ultrasound, and examining changes in left ventricular stroke volume 
using echocardiography. None of these measurements has been shown 
to be independently correlative, but a combination of these assessments 
with clinical judgment can help determine whether a patient remains 
volume-responsive. A hypotensive patient with increased intravascular 
volume and cardiac dysfunction may have S3 and/or S4 gallops on 
examination, increased JVP, extremity edema, and crackles on lung 
auscultation. The chest x-ray may show cardiomegaly, widening of 
the vascular pedicle, Kerley B lines, and pulmonary edema. There is 
increasing use of ultrasonography in place of chest radiography in 
resource-limited settings. Chest pain and electrocardiographic changes 
consistent with ischemia may be noted (Chap. 316).

CHAPTER 311
Approach to the Patient with Critical Illness 
In hypotensive patients with clinical evidence of increased cardiac 
output, a search for causes of decreased SVR is appropriate. These 
patients usually require targeted initial volume resuscitation (as 
described above), after an initial fluid bolus, to achieve euvolemia, and 
often require vasopressors to maintain vascular tone. The most com­
mon cause of high-cardiac-output hypotension is sepsis (Chap. 315). 
Patients with suspected sepsis should receive early broad-spectrum, 
appropriately dosed antibiotics and source control when feasible. Other 
causes of high-cardiac output hypotension include liver failure, severe 
pancreatitis, adrenal insufficiency, burns, trauma, anaphylaxis, thyro­
toxicosis, and peripheral arteriovenous shunts.
Insertion of lines for monitoring and caring for critically ill patients 
may be necessary. Over the last two decades, management of shock 
has improved to the point where not all patients will require central 
venous and arterial lines, and recent sepsis guidelines support use of 
peripheral lines for pressors administration, if needed, while central 
access is being obtained. However, if a patient demonstrates that shock 
is not quickly resolving, as indicated by a persistent need for vasopres­
sors and/or repeated measurement of the JVP and/or central venous 
O2 saturation, then insertion of an arterial line for monitoring blood 
pressures and arterial blood gases, as well as a central venous line for 
administration of vasoactive agents and monitoring of the JVP and/
or central venous O2 saturation, may be required. Ideally, lines should 
be inserted under sterile conditions using a protocolized checklist 
approach, and lines should be removed as soon as they are no longer 
necessary to avoid risk of line-associated infection.
In summary, the most common categories of shock are hypovole­
mic, cardiogenic, and high-cardiac-output with decreased SVR (highoutput hypotension). Certainly, more than one category can occur 
simultaneously (e.g., hypovolemic and septic shock). It may often be 
the case that an initial presentation with septic shock can present a 
cardiac strain, especially in patients with underlying heart dysfunction, 
such that later cardiac insufficiency may arise.
The initial assessment of a patient in shock should take only a 
few minutes. It is important that aggressive targeted resuscitation 
is instituted on the basis of the initial assessment, particularly since 
early resuscitation from septic and cardiogenic shock may improve 
survival (see below). If the initial bedside assessment yields equivocal 
or confounding data, more objective assessments such as ultrasound/
echocardiography may be useful as described above. In spontaneously

Spontaneous inspiration
Pressure
Time
FIGURE 311-3  Right atrial pressure change during spontaneous respiration in a patient with shock whose cardiac 
output will increase in response to intravenous fluid administration. The right atrial pressure decreases from 7 mmHg to 
4 mmHg. The horizontal bar marks the time of spontaneous inspiration.
breathing patients, inferior vena cava collapse seen on ultrasound may 
predict a fluid-responsive state. Increasingly, ultrasound of the thorax 
and abdomen is used by intensivists as an extension of the physi­
cal examination to assess rapidly imputed filling volumes, adequacy 
of cardiac performance, and for indices of other specific conditions 
(e.g., pericardial tamponade, pulmonary embolus, pulmonary edema, 
pneumothorax). The goal of aggressive resuscitation is to reestablish 
adequate tissue perfusion and thus to prevent or minimize end-organ 
injury. It is equally important not to over-resuscitate patients, as it is 
increasingly appreciated that excess fluid resuscitation is likely not 
beneficial. Thus, targeted fluid resuscitation is the goal.
PART 8
Critical Care Medicine
■
■MECHANICAL VENTILATORY SUPPORT 

(SEE ALSO CHAP. 313)
During the initial resuscitation of patients in shock, principles of 
advanced cardiac life support should be followed. An early assess­
ment of the ability of a patient to protect their airway and to maintain 
adequate gas exchange is mandatory. Early intubation and mechanical 
ventilation often are required. Reasons for the institution of endotra­
cheal intubation and mechanical ventilation include acute hypoxemic 
respiratory failure and ventilatory failure, which frequently accompany 
shock. Acute hypoxemic respiratory failure may occur in patients with 
cardiogenic shock and pulmonary edema (Chap. 316) as well as in 
those who are in septic shock with pneumonia or acute respiratory dis­
tress syndrome (ARDS) (Chaps. 204, 312, and 315). Ventilatory failure 
often occurs as a consequence of an increased load on the respiratory 
system in the form of acute metabolic (often lactic) or respiratory aci­
dosis, or decreased lung compliance (e.g., from pulmonary edema or 
pneumonia). Inadequate perfusion to respiratory muscles in the setting 
of shock may be another reason for early intubation and mechanical 
ventilation. Normally, the respiratory muscles receive a very small per­
centage of the cardiac output. However, in patients who are in shock 
with respiratory distress, the percentage of cardiac output dedicated 
to respiratory muscles may increase by 10-fold or more. Lactic acid 
production from inefficient respiratory muscle activity can present an 
additional ventilatory load.
Mechanical ventilation may relieve the work of breathing and 
allow redistribution of a limited cardiac output to other vital organs. 
Patients demonstrate respiratory distress by an inability to speak full 
sentences, accessory use of respiratory muscles, paradoxical abdominal 
muscle activity, extreme tachypnea (>40 breaths/min), and decreasing 
respiratory rate despite an increasing drive to breathe. When patients 
with shock are supported with mechanical ventilation, a major goal is 
for the ventilator to initially assume all or the majority of the work of 

Time
FIGURE 311-4  Pulse pressure change during mechanical ventilation in a patient with shock whose cardiac output 
will increase in response to intravenous fluid administration. The pulse pressure (systolic minus diastolic blood 
pressure) changes during mechanical ventilation in a patient with septic shock.

breathing, facilitating a state of mini­
mal respiratory muscle work. With the 
institution of mechanical ventilation 
for shock, further declines in MAP are 
frequently seen. The reasons include 
impeded venous return from positivepressure ventilation, reduced endog­
enous catecholamine secretion once the 
stress associated with respiratory failure 
abates, and the actions of drugs used to 
facilitate endotracheal intubation (e.g., 
propofol, opiates). Patients with right 
heart dysfunction or preexisting pulmonary hypertension may also 
have diminished cardiac output related to the increases in right ventric­
ular afterload resulting from positive-pressure ventilation. Accordingly, 
hypotension should be anticipated during and following endotracheal 
intubation. Because many of these patients may be fluid-responsive, IV 
volume administration should be considered, and vasopressor support 
peri-intubation may also be necessary. Figure 311-2 summarizes the diag­
nosis and treatment of different types of shock. For further discussion 
of individual forms of shock, see Chaps. 314, 315, and 316.
RESPIRATORY FAILURE
Respiratory failure is one of the most common reasons for ICU admis­
sion. In some ICUs, ≥75% of patients require mechanical ventilation 
during their stay. Respiratory failure can be categorized mechanistically 
on the basis of pathophysiologic derangements in respiratory function.
■
■TYPE I: ACUTE HYPOXEMIC 

RESPIRATORY FAILURE
This type of respiratory failure occurs with alveolar flooding and sub­
sequent ventilation-perfusion mismatch and intrapulmonary shunt 
physiology. Alveolar flooding may be a consequence of pulmonary 
edema, lung injury, pneumonia, or alveolar hemorrhage. Pulmonary 
edema can be further categorized as occurring due to elevated pul­
monary microvascular pressures, as seen in heart failure and intravas­
cular volume overload or ARDS (“low-pressure pulmonary edema,” 
Chap. 312). This syndrome is defined by acute onset (≤1 week) of 
bilateral opacities on chest imaging that are not fully explained by car­
diac failure or fluid overload and often includes ventilation-perfusion 
mismatch and shunt physiology requiring positive end-expiratory 
pressure (PEEP). A new global definition for ARDS has been proposed 
that does not rely upon chest radiography, arterial blood gases, or use 
of ventilatory support with PEEP. Type I respiratory failure occurs in 
clinical settings such as sepsis, gastric aspiration, pneumonia, COVID-19 
(Chap. 205), near-drowning, multiple blood transfusions, and pancre­
atitis. The mortality rate among patients with ARDS was traditionally 
very high (50–70%), although changes in patient care have led to 
mortality rates closer to 30% (see below). The COVID-19 pandemic 
resulted in a substantially increased incidence of viral-mediated ARDS.
It is well established that mechanical ventilation of patients with 
ARDS may propagate lung injury. As seen in Fig. 311-5, the pressurevolume relationship of the lung in ARDS is not linear. Alveoli may 
collapse at very low lung volumes. Animal studies have suggested 
that repeated stretching and overdistention of injured alveoli dur­
ing mechanical ventilation can further injure the lung. Concern 
over this alveolar overdistention, termed 
ventilator-induced “volutrauma,” led to a 
multicenter, randomized, prospective trial 
comparing traditional ventilator strategies 
for ARDS (large tidal volume: 12 mL/kg 

of ideal body weight) with a low tidal 
volume (6  mL/kg of ideal body weight). 
This study showed a dramatic reduction 
in mortality rate in the low-tidal-volume 
group from that in the high-tidal-volume 
group (31 vs 39.8%). Other studies have 
suggested that large tidal volumes may 
lead to ARDS in patients who initially do 

Pressure (mmHg)

Alveoli
D

C
Upper inflection
point
Volume, mL

B
Lower inflection
point
A

Pressure, cmH2O
FIGURE 311-5  Pressure-volume relationship in the lungs of a patient with acute 
respiratory distress syndrome (ARDS). At the lower inflection point, collapsed 
alveoli begin to open and lung compliance changes. At the upper deflection point, 
alveoli become overdistended. The shape and size of alveoli are illustrated at the 
top of the figure.
not have this problem. Prone positioning has been shown to improve 
survival in those with severe ARDS and has been more broadly applied 
in many centers in COVID-19 ARDS. Select patients may benefit from 
neuromuscular blockade in ARDS. In addition, a “fluid-conservative” 
management strategy (maintaining a low central venous pressure 
[CVP] or pulmonary capillary wedge pressure [PCWP]) is associated 
with fewer days of mechanical ventilation than a “fluid-liberal” strat­
egy (maintaining a relatively high CVP or PCWP) in ARDS in those 
patients who have been resuscitated from shock. There is growing 
interest in avoiding intubation in patients with ARDS by the use of a 
variety of devices, such as masks, high-flow oxygen delivery systems, 
and helmets for respiratory support that were more broadly applied 
during the COVID pandemic and likely more so in resource-limited 
settings when feasible; however, this must be balanced by concern that 
higher tidal volumes during spontaneous breathing with these devices 
could result in progression of preexisting lung injury.
■
■TYPE II RESPIRATORY FAILURE: 

HYPERCAPNEIC RESPIRATORY FAILURE
This type of respiratory failure is a consequence of alveolar hypoventi­
lation and results from the inability to eliminate carbon dioxide effec­
tively. Mechanisms are categorized by impaired central nervous system 
(CNS) drive to breathe (colloquially termed, “won’t breathe”), impaired 
strength with failure of neuromuscular function in the respiratory sys­
tem, and increased load(s) on the respiratory system (with the latter two 
colloquially termed, “can’t breathe”). Reasons for diminished CNS drive 
to breathe include drug overdose, brainstem injury, sleep-disordered 
breathing, and severe hypothyroidism. Reduced strength can be due 
to impaired neuromuscular transmission (e.g., myasthenia gravis, 
Guillain-Barré syndrome, amyotrophic lateral sclerosis) or respiratory 
muscle weakness (e.g., myopathy, electrolyte derangements, fatigue).
The overall load on the respiratory system can be subclassified into 
resistive loads (e.g., bronchospasm), loads due to reduced lung compli­
ance (e.g., alveolar edema, atelectasis, intrinsic positive end-expiratory 
pressure [auto-PEEP]—see below), loads due to reduced chest wall 
compliance (e.g., pneumothorax, pleural effusion, abdominal disten­
tion), and loads due to increased minute ventilation requirements (e.g., 
pulmonary embolus with increased dead-space fraction, sepsis).
The mainstays of therapy for hypercapnic respiratory failure are 
directed at reversing the underlying cause(s) of ventilatory failure. 
Noninvasive positive-pressure ventilation with a tight-fitting facial or 
nasal mask, with avoidance of endotracheal intubation, may stabilize 
these patients in certain circumstances. This approach has been shown 
to be beneficial in treating patients with exacerbations of chronic 
obstructive pulmonary disease; it has been tested less extensively in 

other kinds of respiratory failure but may be attempted nonetheless 
with close monitoring in the absence of contraindications (e.g., hemo­
dynamic instability, inability to protect the airway, respiratory arrest, 
significant airway secretions, significant aspiration risk).

■
■TYPE III RESPIRATORY FAILURE: 

LUNG ATELECTASIS
This form of respiratory failure results from lung atelectasis. Because 
atelectasis occurs so commonly in the perioperative period, this form 
is also called perioperative respiratory failure. After general anesthesia, 
decreases in functional residual capacity lead to collapse of dependent 
lung units. Such atelectasis can be treated by frequent changes in posi­
tion, chest physiotherapy, upright positioning, and control of incisional 
and/or abdominal pain. Noninvasive positive-pressure ventilation may 
also be used to reverse regional atelectasis.
■
■TYPE IV RESPIRATORY FAILURE: 

METABOLIC DEMANDS
This form most often results from hypoperfusion of respiratory 
muscles in patients in shock. Normally, respiratory muscles consume 
<5% of total cardiac output and oxygen delivery. Patients in shock often 
experience respiratory distress due to pulmonary edema (e.g., in car­
diogenic shock), lactic acidosis, and anemia. In this setting, up to 40% 
of cardiac output may be distributed to the respiratory muscles. Intuba­
tion and mechanical ventilation can allow redistribution of the cardiac 
output away from the respiratory muscles and back to vital organs 
while the shock is treated. In addition, other causes of significant 
metabolic acidosis might require ventilatory support while reversal of 
the underlying cause of the acidosis is addressed.
CHAPTER 311
Approach to the Patient with Critical Illness 
CARE OF THE MECHANICALLY 
VENTILATED PATIENT
Mechanically ventilated patients frequently require sedatives and anal­
gesics. Opiates are the mainstay of therapy for analgesia in mechani­
cally ventilated patients. After adequate pain control has been ensured, 
additional indications for sedation include anxiolysis; treatment of 
subjective dyspnea; reduction of autonomic hyperactivity, which may 
precipitate myocardial ischemia; and reduction of total O2 consump­
tion (Vo2). Nonbenzodiazepine sedatives are preferred because ben­
zodiazepines are associated with increased delirium and worse patient 
outcomes.
The neuromuscular blocking agent cisatracurium is occasionally 
used to facilitate mechanical ventilation in patients with profound 
ventilator dyssynchrony despite optimal sedation, particularly in the 
setting of severe ARDS. Use of these agents may result in prolonged 
weakness—a myopathy known as the postparalytic syndrome. For 
this reason, neuromuscular blocking agents typically are used as a 
last resort when aggressive sedation fails to achieve patient–ventilator 
synchrony. Because neuromuscular blocking agents result in phar­
macologic paralysis without altering mental status, sedative-induced 
amnesia is mandatory when these agents are administered.
Amnesia can be achieved reliably with propofol and benzodi­
azepines such as lorazepam and midazolam. Outside the setting of 
pharmacologic paralysis, few data support the idea that amnesia is 
mandatory in all patients who require intubation and mechanical 
ventilation. Because many of these critically ill patients have impaired 
hepatic and renal function, sedatives and opiates may accumulate when 
given for prolonged periods. A nursing protocol–driven approach to 
sedation of mechanically ventilated patients or daily interruption of 
sedative infusions paired with daily spontaneous breathing trials has 
been shown to prevent excessive drug accumulation and shorten the 
duration of both mechanical ventilation and ICU stay (see below).
(See also Chap. 313.) Whereas a thorough understanding of the 
pathophysiology of respiratory failure is essential for optimal patient 
care, recognition of a patient’s readiness to be liberated from mechani­
cal ventilation is likewise important. Several studies have shown that 
daily spontaneous breathing trials can identify patients who are ready 
for extubation. Accordingly, all intubated, mechanically ventilated 
patients should undergo daily screening of respiratory function.

If oxygenation is stable (i.e., Pao2/FIo2 [partial pressure of oxygen/
fraction of inspired oxygen] >200 and PEEP ≤5 cmH2O), cough and 
airway reflexes are intact, and no vasopressor agents or sedatives are 
being administered, the patient has passed the screening test and 
should undergo a spontaneous breathing trial (SBT). If sedatives are 
being administered, the patient can undergo a spontaneous awak­
ening trial (SAT), as well, to determine if they are able to maintain 
adequate alertness and respiratory status without sedatives. The SAT/
SBT trial consists of a period of breathing through the endotracheal 
tube without significant ventilator support (continuous positive airway 
pressure [CPAP] of 5 cmH2O with or without low-level pressure sup­
port [e.g., 5 cmH2O] and an open T-piece breathing system have all been 
validated) for 30–120 min. The spontaneous breathing trial is declared 
a failure and stopped if any of the following occur: (1) respiratory rate 
>35/min for >5 min, (2) O2 saturation <90%, (3) heart rate >140/min 
or a 20% increase or decrease from baseline, (4) systolic blood pressure 
<90 mmHg or >180 mmHg, or (5) increased anxiety or diaphoresis. If, 
at the end of the spontaneous breathing trial, none of the above events 
has occurred, the patient can be considered for an extubation trial. 
Such protocol-driven approaches to patient care can have an important 
impact on the duration of mechanical ventilation and ICU stay. Despite 
such a careful approach to liberation from mechanical ventilation, up 
to 10% of patients develop respiratory distress after extubation and may 
require resumption of mechanical ventilation. Many of these patients 
will require reintubation. The use of noninvasive ventilation as a res­
cue strategy in patients in whom extubation fails may be associated in 
some patients with worse outcomes than are obtained with immediate 
reintubation. Some studies suggest that there are subgroups of patients 
who might benefit from administration of noninvasive ventilation or 
high-flow nasal oxygen therapy upon extubation, as it is believed that 
low levels of PEEP and/or inspiratory flow delivered by these devices 
after extubation may be helpful.

PART 8
Critical Care Medicine
MULTIORGAN SYSTEM FAILURE
Multiorgan system failure, which is commonly associated with critical 
illness, is defined by the simultaneous presence of physiologic dysfunc­
tion and/or failure of two or more organs. Typically, this syndrome 
occurs in the setting of severe sepsis, shock of any kind, severe inflam­
matory conditions such as pancreatitis, and trauma. The fact that 
multiorgan system failure occurs commonly in the ICU is a testament 
to our current ability to stabilize and support single-organ failure. The 
ability to support single-organ failure aggressively (e.g., by mechanical 
ventilation or by renal replacement therapy) has reduced rates of early 
mortality in critical illness. As a result, it is less common for critically 
ill patients to die in the initial stages of resuscitation. Instead, many 
patients succumb to critical illness later in the ICU stay, after the initial 
presenting problem may have been stabilized.
Although there is debate regarding specific definitions of organ fail­
ure, several general principles governing the syndrome of multiorgan 
system failure apply. First, organ failure, no matter how it is defined, 
must persist beyond 24 h. Second, mortality risk increases with the 
accrual of failing organs. Third, the prognosis worsens with increased 
duration of organ failure. These observations remain true across vari­
ous critical care settings (e.g., medical vs surgical).
MONITORING IN THE ICU
Because respiratory failure and circulatory failure are common in 
critically ill patients, monitoring of the respiratory and cardiovascu­
lar systems is undertaken frequently. Evaluation of respiratory gas 
exchange is routine in critical illness. The “gold standard” remains arte­
rial blood-gas analysis, in which pH, Pao2, partial pressure of carbon 
dioxide (Pco2), and O2 saturation are measured directly. With arterial 
blood-gas analysis, the two main functions of the lung—oxygenation 
of arterial blood and elimination of CO2—can be assessed directly. 
In fact, the arterial blood pH, which has a profound effect on the 
drive to breathe, can be assessed only by such sampling. Venous pH 
obtained through an indwelling central venous line can approximate 
arterial pH. Although sampling of arterial blood is generally safe and 
may be undertaken more frequently through insertion of a temporary 

indwelling arterial line, it may be painful and cannot provide continu­
ous information. In light of these limitations, noninvasive monitoring 
of respiratory function is often employed.
■
■PULSE OXIMETRY
The most commonly utilized noninvasive technique for monitoring 
respiratory function, pulse oximetry takes advantage of differences 
in the absorptive properties of oxygenated and deoxygenated hemo­
globin. At wavelengths of 660 nm, oxyhemoglobin reflects light more 
effectively than does deoxyhemoglobin, whereas the reverse is true 
in the infrared spectrum (940 nm). A pulse oximeter passes both 
wavelengths of light through a perfused digit such as a finger, and 
the relative intensity of light transmission at these two wavelengths 
is recorded. From this information, the relative percentage of oxyhe­
moglobin is derived. Since arterial pulsations produce phasic changes 
in the intensity of transmitted light, the pulse oximeter is designed to 
detect only light of alternating intensity. This feature allows distinction 
of arterial and venous blood O2 saturations. Studies during the COVID 
pandemic noted that pulse oximetry overestimates oxygen saturation 
in patients with darker skin, thus making correlation with arterial Pao2 
more imperative.
■
■RESPIRATORY SYSTEM MECHANICS
Respiratory system mechanics can be measured in patients during 
mechanical ventilation (Chap. 313). When volume-controlled modes 
of mechanical ventilation are used, accompanying airway pressures 
can easily be measured as long as the patient is breathing passively. 
The peak airway pressure is determined by two variables: airway 
resistance and respiratory system compliance. At the end of inspira­
tion, inspiratory flow can be stopped transiently. This end-inspiratory 
pause (plateau pressure) is a static measurement, affected only by 
respiratory system compliance and not by airway resistance. There­
fore, during volume-controlled ventilation, the difference between 
the peak (airway resistance + respiratory system compliance) and 
plateau (respiratory system compliance only) airway pressures pro­
vides a quantitative assessment of airway resistance. Accordingly, dur­
ing volume-controlled ventilation, patients with increases in airway 
resistance typically have increased peak airway pressures as well as 
abnormally high gradients between peak and plateau airway pressures 
(typically >10–15 cmH2O) at a constant inspiratory flow rate of 1 L/s. 
The compliance of the respiratory system is defined by the change in 
volume of the respiratory system per unit change in pressure; thus, a 
quantitative assessment of compliance is provided by the tidal volume 
divided by the plateau pressure minus PEEP.
The respiratory system can be divided into two components: the 
lungs and the chest wall. Normally, respiratory system compliance is 
~100 mL/cmH2O. Pathophysiologic processes such as pleural effu­
sions, pneumothorax, and increased abdominal girth all reduce chest 
wall compliance. Lung compliance may be reduced by pneumonia, 
pulmonary edema, alveolar hemorrhage, interstitial lung disease, or 
auto-PEEP. Accordingly, patients with abnormalities in compliance of 
the respiratory system (lungs and/or chest wall) typically have elevated 
peak and plateau airway pressures but a normal gradient between 
these two pressures. Auto-PEEP occurs when there is insufficient time 
for emptying of alveoli before the next inspiratory cycle. Because the 
alveoli have not decompressed completely, alveolar pressure remains 
positive at the end of exhalation (functional residual capacity). This 
phenomenon results most commonly from obstruction of distal 
airways in disease processes such as asthma and COPD. Auto-PEEP 
with resulting alveolar overdistention may result in diminished lung 
compliance, reflected by abnormally increased plateau airway pres­
sures. Modern mechanical ventilators allow breath-to-breath display of 
pressure and flow, permitting detection of potential problems such as 
patient–ventilator dyssynchrony, airflow obstruction, and auto-PEEP 
(Fig. 311-6).
■
■CIRCULATORY STATUS
Oxygen delivery (Qo2) is a function of cardiac output and the content 
of O2 in the arterial blood (Cao2). The Cao2 is determined by the

cmH2O
Pressure–Time

L/s
Flow–Time
1.2

–1.2
FIGURE 311-6  Increased airway resistance with auto–positive end-expiratory 
pressure (PEEP). The top waveform (airway pressure vs time) shows a large 
difference between the peak airway pressure (80 cmH2O) and the plateau airway 
pressure (20 cmH2O). The bottom waveform (flow vs time) demonstrates airflow 
throughout expiration (reflected by the flow tracing on the negative portion of the 
abscissa) that persists up to the next inspiratory effort.
hemoglobin concentration, the arterial hemoglobin saturation, and 
dissolved O2 not bound to hemoglobin. For normal adults:
Qo2	= 50 dL/min × (1.39 × 15 g/dL [hemoglobin concentration]
	
	 × 1.0 [hemoglobin % saturation] + 0.0031 × 10 [Pao2])
	
= 50 dL/min (cardiac output) × 21.6 mL O2 per dL blood (Cao2)
	
= 1058 mL O2 per min
It is apparent that nearly all the O2 delivered to tissues is bound to 
hemoglobin and that the dissolved O2 (Pao2) contributes very little to 
O2 content in arterial blood or to O2 delivery. Normally, the content 
of O2 in mixed venous blood (C–vo2) is 15.76 mL/dL since the mixed 
venous blood is 75% saturated. Therefore, the normal tissue extraction 
ratio for O2 is Cao2 – C–vo2/Cao2 ([21.16 – 15.76]/21.16) or ~25%. A 
pulmonary artery catheter (see discussion below) allows measurements 
of O2 delivery and the O2 extraction ratio.
Information on the venous O2 saturation allows assessment of global 
tissue perfusion. A reduced venous O2 saturation may be caused by inad­
equate cardiac output, reduced hemoglobin concentration, and/or reduced 
arterial O2 saturation. An abnormally high oxygen consumption (Vo2) may 
also lead to a reduced venous O2 saturation if O2 delivery is not concomi­
tantly increased. Abnormally increased Vo2 in peripheral tissues may be 
caused by problems such as fever, agitation, shivering, and thyrotoxicosis.
The pulmonary artery catheter originally was designed as a tool to 
guide therapy for acute myocardial infarction but has been used in the 
ICU for evaluation and treatment of a variety of other conditions, such 
as ARDS, septic shock, congestive heart failure, and acute renal failure. 
This device has never been validated as a tool associated with reduction 
in morbidity and mortality rates. Indeed, despite numerous prospec­
tive studies, mortality or morbidity rate benefits associated with use of 
the pulmonary artery catheter have never been reported in any setting. 
Accordingly, it appears that routine pulmonary artery catheterization is 
not indicated as a means of monitoring and characterizing circulatory 
status in most critically ill patients, especially as monitoring of the venous 
O2 saturation via an indwelling central venous line has proven helpful in 
many critical illness settings. However, there are still select circumstances 
where pulmonary artery catheterization may prove helpful when used by 
those with appropriate experience in its insertion and data interpretation.
PREVENTION OF COMPLICATIONS OF 
CRITICAL ILLNESS
■
■SEPSIS IN THE CRITICAL CARE UNIT
(See also Chap. 315) Sepsis is defined as life-threatening organ dys­
function (i.e., an increase in SOFA of 2 points or more) caused by a 

dysregulated response to infection. Poor outcomes can be anticipated 
in patients with two or more of the following: respiratory rate ≥22 
breaths/min, altered mentation, and systolic blood pressure ≤100 
mmHg. Sepsis is a leading cause of death in noncoronary ICUs in the 
United States, with case rates expected to increase as the population 
ages and a higher percentage of people are vulnerable to infection.

■
■NOSOCOMIAL INFECTIONS IN THE ICU
Many therapeutic interventions in the ICU are invasive and predis­
pose patients to infectious complications. These interventions include 
endotracheal intubation, indwelling vascular catheters, transurethral 
bladder catheters, and other catheters placed into sterile body cavi­
ties (e.g., tube thoracostomy, percutaneous intraabdominal drainage 
catheterization). The longer such devices remain in place, the more 
prone to infections patients become from these devices. For example, 
ventilator-associated events such as ventilator-associated pneumonia 
correlate strongly with the duration of intubation and mechanical ven­
tilation. Therefore, an important aspect of preventive care is the timely 
removal of invasive devices as soon as they are no longer needed. 
Moreover, multidrug-resistant organisms are commonplace in the ICU.

CHAPTER 311
Infection control is critical in the ICU. Care bundles, which include 
measures such as frequent hand washing, are effective but underuti­
lized strategies. Other components of care bundles, such as protective 
isolation of patients colonized or infected by drug-resistant organisms, 
are also commonly used. Studies evaluating multifaceted, evidencebased strategies to decrease catheter-related bloodstream infections 
have shown improved outcomes with strict adherence to measures 
such as hand washing, full-barrier precautions during catheter inser­
tion, chlorhexidine skin preparation, avoidance of the femoral site, and 
timely catheter removal.
Approach to the Patient with Critical Illness 
■
■DEEP-VENOUS THROMBOSIS (DVT) 

(SEE ALSO CHAP. 290)
All ICU patients are at high risk for this complication because of their 
predilection for immobility. Therefore, all should receive some form 
of prophylaxis against DVT if feasible. The most commonly employed 
forms of prophylaxis are subcutaneous chemoprophylaxis (e.g., lowdose heparin) injections and sequential compression devices for the 
lower extremities. Observational studies report an alarming incidence 
of DVTs despite the use of these standard prophylactic regimens. Fur­
thermore, heparin prophylaxis may result in heparin-induced throm­
bocytopenia, another nosocomial complication in critically ill patients.
Low-molecular-weight heparins such as enoxaparin are more effec­
tive than unfractionated heparin for DVT prophylaxis in high-risk 
patients (e.g., those undergoing orthopedic surgery) and are associ­
ated with a lower incidence of heparin-induced thrombocytopenia, 
although their use may be limited in patients with renal dysfunction 
given their renal clearance.
■
■STRESS ULCERS
Prophylaxis against stress ulcers is not necessary for all ICU patients. It 
should only be administered to high-risk patients, such as those with 
coagulopathy or respiratory failure requiring mechanical ventilation. 
While there has been debate about the optimal agent for stress ulcer 
prophylaxis, a number of recent studies have supported improved 
efficacy of proton pump inhibitors (PPIs) in reducing bleeding risk 
compared with other agents (e.g., histamine-2 receptor antagonist [H2 
blocker] or sucralfate). There exist concerns for increased risk of pneu­
monia and Clostridium difficile colitis with PPIs compared with other 
agents, although the data are not definitive, and the improved efficacy 
of PPIs in patients at high risk for stress ulcers may outweigh these 
potential infectious risks.
■
■NUTRITION AND GLYCEMIC CONTROL
Nutrition and glycemic control are important issues that may be asso­
ciated with respiratory failure, impaired wound healing, and dysfunc­
tional immune response in critically ill patients. Early enteral feeding 
is reasonable, with some data suggesting that permissive underfeeding 
of nonprotein calories is not inferior to full-goal feeding. Certainly, 
enteral feeding, if possible, is preferred over parenteral nutrition, which

is associated with numerous complications, including hyperglycemia, 
fatty liver, cholestasis, and sepsis. When parenteral feeding is necessary 
to supplement enteral nutrition, delaying this intervention until day 8 
in the ICU results in better recovery and fewer ICU-related complica­
tions. Tight glucose control has been an area of controversy in critical 
care. Although one study showed a significant mortality benefit when 
glucose levels were aggressively normalized in a large group of surgical 
ICU patients, other studies of both medical and surgical ICU patients 
suggested that tight glucose control resulted in increased rates of 
mortality likely attributable, in part, to hypoglycemic episodes. Thus, 
current guidelines suggest targeting glucose levels of ≤180 mg/dL in 
critically ill patients, rather than targeting tighter control.

■
■ICU-ACQUIRED WEAKNESS
ICU-acquired weakness occurs frequently in patients who survive 
critical illness. Both neuropathies and myopathies have been described, 
most commonly after ~1 week in the ICU. The mechanisms behind 
ICU-acquired weakness syndromes are poorly understood, and they 
are known to present with heterogeneous muscle pathophysiol­
ogy. Very early physical and occupational therapy in mechanically 
ventilated patients reportedly results in significant improvements in 
functional independence at hospital discharge as well as in reduced 
durations of mechanical ventilation and delirium.
PART 8
Critical Care Medicine
■
■ANEMIA
Studies have shown that most ICU patients are anemic as a result of 
chronic inflammation. Phlebotomy also contributes to ICU anemia. A 
large multicenter study involving patients in many different ICU set­
tings challenged the conventional notion that a hemoglobin level of 
100 g/L (10 g/dL) is needed in critically ill patients, with similar out­
comes noted in those whose transfusion trigger was 7 g/dL. Red blood 
cell transfusion is associated with impairment of immune function and 
increased risk of infections as well as of ARDS and volume overload, all 
of which may explain the findings in this study. A conservative transfu­
sion strategy has shown similar outcomes in septic shock, postcardiac 
surgery, and post–hip surgery patients.
■
■ACUTE KIDNEY FAILURE
(See also Chap. 321) Acute kidney failure occurs in a significant per­
centage of critically ill patients. The most common underlying etiology 
is acute tubular necrosis, usually precipitated by hypoperfusion and/or 
nephrotoxic agents. Currently, no pharmacologic agents are available 
for prevention of kidney injury in critical illness. Studies have shown 
convincingly that low-dose dopamine, fenoldopam, and vasopressin 
are not effective in protecting the kidneys from acute injury.
NEUROLOGIC DYSFUNCTION IN 
CRITICALLY ILL PATIENTS
■
■DELIRIUM
(See also Chap. 29) Delirium is defined by (1) an acute onset of 
changes or fluctuations in mental status, (2) inattention, (3) disorga­
nized thinking, and (4) an altered level of consciousness (i.e., a state 
other than alertness). Delirium is reported to occur in a wide range 
of mechanically ventilated ICU patients and can be detected by the 
Confusion Assessment Method for the ICU (CAM-ICU) or the Inten­
sive Care Delirium Screening Checklist (ICDSC). These tools are used 
to ask patients to answer simple questions and perform simple tasks 
and can be used readily at the bedside. The differential diagnosis of 
delirium in ICU patients is broad and includes infectious etiologies 
(including sepsis), medications (particularly sedatives and analgesics), 
drug withdrawal, metabolic/electrolyte derangements, intracranial 
pathology (e.g., stroke, intracranial hemorrhage), seizures, hypoxia, 
hypertensive crisis, shock, and vitamin deficiencies (particularly thia­
mine). The etiology of a patient’s ICU delirium impacts the prognosis. 
Those with persistent ICU delirium not related to sedatives have 
increases in length of hospital stay, time on mechanical ventilation, 
cognitive impairment at hospital discharge, and 6-month mortality 
rate. Interventions to reduce ICU delirium are limited. The sedative 
dexmedetomidine has been less strongly associated with ICU delirium 

than midazolam in some studies. In addition, very early physical and 
occupational therapy in mechanically ventilated patients has been 
demonstrated to reduce delirium.
■
■ANOXIC CEREBRAL INJURY
(See also Chap. 318) This condition is common after cardiac arrest 
and often results in severe and permanent brain injury in survivors. 
Active cooling of patients to 33°C after cardiac arrest is controversial, 
with some studies showing improved neurologic outcomes and oth­
ers showing no such improvement when compared to maintaining 
normothermia. Certainly, patients post cardiac arrest should have a 
temperature targeted to no higher than normothermia.
■
■STROKE
(See also Chap. 437) Stroke is a common cause of neurologic critical 
illness. Hypertension must be managed carefully, because abrupt reduc­
tions in blood pressure may be associated with further brain ischemia 
and injury. Acute ischemic stroke treated with tissue plasminogen 
activator (tPA) has an improved neurologic outcome when treatment is 
given within 4.5 h of onset of symptoms, with likely increased benefit 
associated with earlier administration. The mortality rate is not reduced 
when tPA is compared with placebo, despite the improved neurologic 
outcome. The risk of cerebral hemorrhage is significantly higher in 
patients given tPA. No consistent overall benefit is seen when tPA ther­
apy is given beyond 4.5 h after symptom onset. Heparin has not been 
convincingly shown to improve outcomes in patients with acute isch­
emic stroke. Decompressive craniectomy is a surgical procedure that 
relieves increased intracranial pressure in the setting of space-occupying 
brain lesions or brain swelling from stroke; available evidence suggests 
that this procedure may improve survival among select patients (e.g., 
≤55 years of age), albeit at a cost of increased disability for some.
■
■SUBARACHNOID HEMORRHAGE
(See also Chap. 437) Subarachnoid hemorrhage may occur secondary 
to aneurysm rupture and is often complicated by cerebral vasospasm, 
re-bleeding, and hydrocephalus. Vasospasm can be detected by either 
transcranial Doppler assessment or cerebral angiography; it is typi­
cally treated with the calcium channel blocker nimodipine, aggressive 
IV fluid administration to avoid hypovolemia, and therapy aimed at 
maintaining adequate central perfusion pressure, typically with vaso­
active drugs such as phenylephrine. IV fluids and vasoactive drugs 
(hypertensive hypervolemic therapy) are used to overcome the cerebral 
vasospasm. Early surgical clipping or endovascular coiling of aneu­
rysms is advocated to prevent complications related to re-bleeding. 
Hydrocephalus, typically heralded by a decreased level of conscious­
ness, may require ventriculostomy drainage.
■
■STATUS EPILEPTICUS (SEE ALSO CHAP. 436)
Recurrent or relentless seizure activity is a medical emergency. Ces­
sation of seizure activity is required to prevent irreversible neurologic 
injury. Lorazepam is the most effective benzodiazepine for treating 
status epilepticus and is the treatment of choice for controlling seizures 
acutely. Maintenance of seizure control should be effected with a load­
ing dose of fosphenytoin, valproate, or levetiracetam, as these agents 
have been shown to have similar efficacy and side effects.
■
■BRAIN DEATH
(See also Chap. 318) Although deaths of critically ill patients usually 
are attributable to irreversible cessation of circulatory and respiratory 
function, a diagnosis of death also may be established by irreversible 
cessation of all functions of the entire brain, including the brainstem, 
even if circulatory and respiratory functions remain intact on artificial 
life support. Such a diagnosis requires demonstration of the absence 
of cerebral function (no response to any external stimulus) and brain­
stem functions (e.g., unreactive pupils, lack of ocular movement in 
response to head turning or ice-water irrigation of ear canals, positive 
apnea test [no drive to breathe]). Many U.S. institutions have a protocol 
based upon their state’s requirements for declaration of brain death. 
Absence of brain function must have an established cause and be per­
manent without possibility of recovery; a sedative effect, hypothermia,