2 Shock, haemorrhage and transfusion

After haemorrhage control
Blood and blood products
Blood groups and cross-matching
Blood substitutes
Classiﬁcation of shock
Clinical consequences of shock
Complications of blood transfusion
Conduct of resuscitation
Cross-matching
Damage control resuscitation
Degree of haemorrhage and classiﬁcation
Deﬁnitions
End points of resuscitation
FURTHER READING
HAEMORRHAGE RESUSCITATION
HAEMORRHAGE
Identify haemorrhage
Indications for blood transfusion
Introduction
Learning objectives
Monitoring
Pathophysiology
Recognition and diagnosis of shock
SHOCK RESUSCITATION
SHOCK
TRANSFUSION
Transfusion reactions
Vasopressor and inotropic support

After haemorrhage control

Once haemorrhage is controlled, patients should be deﬁni - tively resuscitated, warmed and have coagulopathy corrected. Attention should be paid to ﬂuid responsiveness and the end - points of resuscitation to ensure that patients are fully resusci - tated and to reduce the incidence and severity of organ failure ( Figure 2.2 and Shock resuscitation ). - After haemorrhage control
Once haemorrhage is controlled, patients should be deﬁni - tively resuscitated, warmed and have coagulopathy corrected. Attention should be paid to ﬂuid responsiveness and the end - points of resuscitation to ensure that patients are fully resusci - tated and to reduce the incidence and severity of organ failure ( Figure 2.2 and Shock resuscitation ). - After haemorrhage control
Once haemorrhage is controlled, patients should be deﬁni - tively resuscitated, warmed and have coagulopathy corrected. Attention should be paid to ﬂuid responsiveness and the end - points of resuscitation to ensure that patients are fully resusci - tated and to reduce the incidence and severity of organ failure ( Figure 2.2 and Shock resuscitation ). -

Blood and blood products

Blood is collected from donors who have been previously screened before donating to exclude any donor whose blood may have the potential to harm the patient or to prevent possible harm that donating a unit of blood may have for the donor. In the UK, up to 450 /uni00A0 mL of blood is drawn, a maximum of three times each year. Each unit is tested for evidence of - hepatitis B, hepatitis C, human immunodeﬁciency virus - (HIV)-1, HIV-2 and syphilis. Donations are leukodepleted as a precaution against variant Creutzfeldt–Jakob disease (this may also reduce the immunogenicity of the transfusion). as the presence of irregular red cell antibodies. The blood is then processed into subcomponents. Whole blood Whole blood is now rarely available in civilian practice because it has been seen as an ine ﬃ cient use of the limited resource. However, whole blood transfusion has signiﬁcant advantages over packed cells as it is coagulation factor rich and, if fresh, more metabolically active than stored blood. Packed red cells Packed red blood cells are spun-down and concentrated packs of red blood cells. Each unit is approximately 330 /uni00A0 mL and has a haematocrit of 50–70%. Packed cells are stored in a SAG-M (saline–adenine–glucose–mannitol) solution to increase shelf life to 5 weeks at 2–6°C. (Older storage regimes included storage in CPD [citrate–phosphate–dextrose] solutions, which have a shelf life of 2–3 weeks.) Fresh-frozen plasma Fresh-frozen plasma (FFP) is rich in coagulation factors and is removed from fresh blood and stored at − 40°C to − 50°C with a 2-year shelf life. It is the ﬁrst-line therapy in the treatment of coagulopathic haemorrhage (see Management of coag ulopathy ). Rhesus D-positive FFP may be given to a rhesus D-negative woman, although it is possible for seroconversion to occur with large volumes owing to the presence of red cell fragments and Rh-D immunisa tion should be considered. Cryoprecipitate Cryoprecipitate is a supernatant precipitate of FFP and is rich in ﬁbrinogen, factor VIII and factor XIII. It is stored at − 30°C with a 2-year shelf life. It is given in low-ﬁbrinogen states or factor VIII deﬁciency . Platelets Platelets are supplied as a pooled platelet concentrate and 9 contain about 250 /uni00A0×/uni00A0 10 /litre. Platelets are stored on a special agitator at 20–24°C and have a shelf life of only 5 days. Plate let transfusions are given to patients with thrombocytopenia or with platelet dysfunction who are bleeding or undergoing surgery . Patients are increasingly presenting on antiplatelet therapy such as aspirin or clopidogrel for reduction of cardiovascu lar risk. Aspirin therapy rarely poses a problem b ut control of haemorrhage on the more potent platelet inhibitors can be extremely di ﬃ cult. Patients on clopidogrel who are actively bleeding and undergoing major surgery may require almost continuous infusion of platelets during the course of the proce dure. Arginine vasopressin or its analogues (DDA VP) have also been used in this patient group, although with limited success. Prothrombin complex concentrates Prothrombin complex concentrates are highly puriﬁed concen trates prepared from pooled plasma. They contain factors II, IX and X. Factor VII may be included or produced separately . It is indicated for the emergency reversal of anticoagulant (warfarin) therapy in uncontrolled haemorrhage. It is possible for patients undergoing elective surgery to pre-donate their own blood up to 3 weeks before surgery for re-transfusion during the operation. Similarly , during surgery blood can be collected in a cell saver, which washes and collects red blood cells that can then be returned to the patient. Blood and blood products

Blood groups and cross-matching

Human red cells have on their cell surface many di ﬀ erent - antigens. Two groups of antigens are of major importance in surgical practice /uni00A0 – /uni00A0 the ABO and rhesus systems. ABO system These proteins are strongly antigenic and are associated with - naturally occurring antibodies in the serum. The system consists of three allelic genes /uni00A0 – /uni00A0 A, B and O /uni00A0 – /uni00A0 which control synthesis of enzymes that add carbohydrate residues to cell surface glycoproteins. A and B genes add speciﬁc residues while the O gene is an amorph and does not transform the glycoprotein. The system allows for six possible genotypes although there are only four phenotypes. Naturally occurring antibodies are found in the serum of those lacking the corresponding antigen ( Table 2.7 ). Blood group O is the universal donor type as it contains no antigens to provoke a reaction. Conversely , group AB individ uals are ‘universal recipients’ and can receive an y ABO blood type because they have no circulating antibodies. Rhesus system The rhesus D (Rh(D)) antigen is strongly antigenic and is present in approximately 85% of the population in the UK. Antibodies to the D antigen are not naturally present in the serum of the remaining 15% of individuals, but their formation may be stimulated by the transfusion of Rh-positive red cells or they may be acquired during delivery of a Rh(D)-positive baby . Acquired antibodies are capable, during pregnancy , of crossing the placenta and, if present in a Rh(D)-negative mother, may cause sever e haemolytic anaemia and even death (hydrops fetalis) in a Rh(D)-positive fetus in utero. The other minor blood group antigens may be associated with naturally occurring antibodies, or may stimulate the formation of anti bodies on relatively rare occasions.

Phenotype Genotype Antigens O OO O A AA or AO A B BB or BO B AB AB AB

Blood groups and cross-matching

Phenotype Genotype Antigens O OO O A AA or AO A B BB or BO B AB AB AB

Blood groups and cross-matching

Phenotype Genotype Antigens O OO O A AA or AO A B BB or BO B AB AB AB

Blood substitutes

Blood substitutes are an attractive alternative to the costly process of donating, checking, storing and administering blood, especially given the immunogenic and potential infec tious complications associated with transfusion. There are several oxygen-carrying blood substitutes under investigation in experimental animal or early clinical trials. Blood substitutes are either biomimetic or abiotic. Biomimetic the blood and are haemoglobin based. Abiotic substitutes ar e synthetic oxygen carriers and are currently primarily per- ﬂuorocarbon based. Haemoglobin is seen as the ob vious candidate for devel - oping an e ﬀ ective blood substitute, and one free haemoglobin - solution is available in some countries where blood compo - nents are not readily available. Various other engineered molecules are under clinical trials and are based on human, bovine or recombinant technologies. Second-generation per - ﬂuorocarbon emulsions are also showing potential in clinical trials. Blood substitutes

Classiﬁcation of shock

There are numerous ways to classify shock, but the most common and most clinically applicable is one based on the initiating mechanism. All states are characterised by systemic tissue hypoperfusion, and di ﬀ erent states may coexist within the same patient. Summary box 2.1 Classiﬁcation of shock /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Haemorrhagic and hypovolaemic shock Hypovolaemic shock is due to a reduced circulating volume. Hypovolaemia may be due to haemorrhagic or non- haemorrhagic causes. Non-haemorrhagic causes include poor ﬂuid intake (dehydration), excessive ﬂuid loss due to vomiting, diarrhoea, urinary loss (e.g. diabetes), evaporation or ‘third-spacing’, where ﬂuid is lost into the gastrointestinal tract and interstitial spaces, as for example in bowel obstruction or pancreatitis. Hypovolaemia is the most common form of shock, and to some degree is a component of all other forms of shock. Absolute or relative hypovolaemia must be excluded or treated in the management of the shocked state, regardless of cause. Cardiogenic shock Cardiogenic shock is due to primary failure of the heart to pump blood to the tissues. Causes of cardiogenic shock include myocardial infarction, cardiac dysrhythmias, valvular heart disease, blunt myocardial injury and cardiomyopathy . Cardiac insu ﬃ ciency may also be due to myocardial depression caused by endogenous factors (e.g. bacterial and humoral agents agents or drug abuse. Evidence of venous hypertension with pulmonary or systemic oedema may coexist with the classical signs of shock. - Obstructive shock In obstructive shock there is a reduction in preload owing to mechanical obstruction of cardiac ﬁlling. Common causes of obstructive shock include cardiac tamponade, tension pneumothorax, massive pulmonary embolus or air embolus. In each case, there is reduced ﬁlling of the left and/or right sides of the heart, leading to low cardiac output. Distributive shock Distributive shock describes the pattern of cardiovascular responses characterising a variety of conditions, including septic shock, anaphylaxis and spinal cord injury . Inadequate organ perfusion is accompanied by vascular dilatation with hypotension, low systemic vascular resistance, inadequate afterload and a resulting abnormally high cardiac output. In anaphylaxis, vasodilatation is due to histamine release, while in high spinal cord injury there is failure of sympathetic outﬂow and adequate vascular tone (neurogenic shock). The cause in sepsis is less clear but is related to the release of bac - terial products (endotoxin) and the activation of cellular and humoral components of the immune system. There is mal- distribution of blood ﬂow at a microvascular level, with arte - riovenous shunting and dysfunction of cellular utilisation of oxygen. In the later phases of septic shock there is hypovolaemia from ﬂuid loss into interstitial spaces and there may be con - comitant my ocardial depression, complicating the clinical pic - ture ( Table 2.1 ). Endocrine shock Endocrine shock may present as a combination of hypovolae- mic, cardiogenic or distributive shock. Causes of endocrine shock include hypo- and hyperthyroidism and adrenal insuf - ﬁciency . Hypothyroidism causes a shock state similar to that of neurogenic shock due to disordered vascular and cardiac responsiveness to circulating catecholamines. Cardiac output falls as a result of low inotropy and bradycardia. There may also be an associated cardiomyopathy . Thyrotoxicosis may cause a high-output cardiac failure. Adrenal insu ﬃ ciency leads to shock due to hypovolae- mia and a poor response to circulating and exogenous

Haemorrhagic/hypovolaemic shock Cardiogenic shock Obstructive shock Distributive shock Endocrine shock TABLE 2.1 Cardiovascular and metabolic characteristics of shock. Hypovolaemic Cardiac output Low Systemic vascular resistance High Venous pressure Low Mixed venous saturation Low Base de /f_i cit High Cardiogenic Obstructive Distributive Low Low High High High Low High High Low Low Low High High High High

existing Addison’s disease or be a relative insu ﬃ ciency due to a pathological disease state, such as systemic sepsis. Classiﬁcation of shock

existing Addison’s disease or be a relative insu ﬃ ciency due to a pathological disease state, such as systemic sepsis.

Clinical consequences of shock

Unresuscitatable shock Patients who are in profound shock for a prolonged period of time become ‘unresuscitatable’. Cell death follows from cellu lar ischaemia and the ability of the body to compensate is lost. In the heart there is myocardial cell death from poor coronary perfusion and myocardial depression from severe acidaemia and hyperkalaemia. This leads to poor cardiac output and limited response to ﬂuids or inotropic therapy . Peripherally there may also be loss of the ability to maintain systemic vascu lar resistance and further hypotension ensues. The peripheries no longer respond appropriately to vasopressor agents. Once patients enter this stage of systemic ischaemic injury , death is inevitable. Ischaemia–reperfusion and the systemic inﬂammatory response syndrome (SIRS) During the period of systemic hypoperfusion, cellular and organ damage progresses owing to the direct e ﬀ ects of tissue hypoxia and local activation of inﬂammation. Further injury occurs once normal circulation is restored to these tissues. The acid and potassium load that has built up can lead to direct myocardial depression, vascular dilatation and further hypotension. Molecules released from the interior of cells are released into the circulation. These are sensed by and activate leukocytes. These, together with cellular and humoral elements activated by the hypoxia (complement, neutrophils, micro vascular thrombi), overwhelm the local anti-inﬂammatory response and are ﬂushed back into the systemic circulation, where they cause injury to distant organs such as the lungs and the kidneys. This leads to acute lung injury , acute renal injury , cerebral oedema, multiple organ failure and death. Reperfu sion injury can currently only be attenuated by reducing the extent and duration of tissue hypoperfusion. Multiple organ failure As techniques of resuscitation have improved, more and more patients are surviving shock. Where intervention is timely and the period of shock is limited, patients may make a rapid, uncomplicated recovery . However, the result of prolonged systemic ischaemia and reperfusion injury is end-organ damage and multiple organ failure. Multiple organ failure is deﬁned as two or more failed organ systems. There is no speciﬁc treatment for multiple organ fail ure. Management is support of organ systems, with v entilation, cardiovascular support and haemoﬁltration/dialysis until there is recovery of organ function. Multiple organ failure currently carries a mortality of 60%; thus, prevention is vital by early aggressive identiﬁcation and reversal of shock. Thomas Addison , 1799–1860, physician, Guy’s Hospital, London, UK, described the e ﬀ ects of disease of the suprarenal capsules in 1849. Effects of organ failure /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF -

Cardiac: Cardiovascular failure Lung: Acute respiratory distress syndrome Kidney: Acute renal insuf /f_i ciency Liver: Liver failure and coagulopathy Brain: Cerebral swelling and dysfunction

Clinical consequences of shock

Cardiac: Cardiovascular failure Lung: Acute respiratory distress syndrome Kidney: Acute renal insuf /f_i ciency Liver: Liver failure and coagulopathy Brain: Cerebral swelling and dysfunction

Clinical consequences of shock

Cardiac: Cardiovascular failure Lung: Acute respiratory distress syndrome Kidney: Acute renal insuf /f_i ciency Liver: Liver failure and coagulopathy Brain: Cerebral swelling and dysfunction

Complications of blood transfusion

Complications from blood transfusion can be categorised as those arising from a single transfusion and those related to massive transfusion. - Complications from a single transfusion Complications from a single transfusion include: /uni25CF incompatibility haemolytic transfusion reaction; /uni25CF febrile transfusion reaction; /uni25CF allergic reaction; /uni25CF infection: - /uni25CF bacterial infection (usually due to faulty storage); - /uni25CF hepatitis; /uni25CF HIV; /uni25CF malaria; /uni25CF air embolism; /uni25CF thrombophlebitis; /uni25CF transfusion-related acute lung injury (usually from FFP). Complications from massive transfusion Complications from massive transfusion include: /uni25CF coagulopathy; /uni25CF hypocalcaemia; /uni25CF hyperkalaemia; /uni25CF hypokalaemia; /uni25CF hypothermia. In addition, patients who receive repeated transfusions over long periods of time (e.g. patients with thalassaemia) may develop iron overload. (Each transfused unit of red blood cells contains appr oximately 250 /uni00A0 mg of elemental iron.) Correction of coagulopathy is not necessary if there is no active bleeding and haemorrhage is not anticipated (not due for surgery). However, coagulopathy will occur during major haemorrhage and should be anticipated and managed actively . Prevention of dilutional coagulopathy is central to the dam age control resuscitation of patients who are actively bleeding. This is the prime reason for delivering balanced transfusion regimes that deliv er a resuscitation which approximates that of whole blood. In most practice this means delivering matched units of red blood cells, plasma and platelets in a 1:1:1 ratio. Crystalloids and colloids should be avoided if at all possible. The balanced transfusion approach will not correct an established coagulopathy . Most bleeding patients are hyper ﬁbrinolytic, and should be empirically given tranexamic acid, an antiﬁbrinolytic agent, as quickly as possible. Low ﬁbrinogen levels are v ery common, and ﬁbrinogen is vital to clot formation and stabilisation. Cryoprecipitate can be given empirically or guided by laboratory or point-of-care tests of clotting (e.g. thr omboelastometry). Similarly platelet con centrates are given for low platelet counts or observed platelet dysfunction. Clotting function should be assayed frequently during haemorrhage and acted upon until bleeding has been controlled. Complications of blood transfusion

Conduct of resuscitation

Resuscitation should not be delayed in order to deﬁnitively diagnose the source of the shocked state. However, the timing and nature of resuscitation will depend on the type of shock and the timing and severity of the insult. Rapid clinical exam - ination will provide adequate clues to make an appropriate ﬁrst determination, even if a source of bleeding or sepsis is not immediately identiﬁable. If there is initial doubt about the cause of shock, it is safer to assume the cause is hypo- volaemia and begin with ﬂuid resuscitation, and then assess the response. Correction of shock is important in the pre- and peri- operative period for all cases of urgent surgery . For e xample, a patient with bowel obstruction and hypovolaemic shock must be adequately resuscitated before undergoing surgery . If not, the additional surgical injury and hypovolaemia induced during the procedure will increase the physiological demand on the heart, increasing the risk of myocardial infarction; will exacerbate the inﬂammatory activation and thus the incidence and severity of organ damage (especially acute kidney injury); will increase susceptibility to infection and venous thrombo - - embolism; and will prolong the period of gut dysfunction and overall recovery from surgery . In all cases of shock, regardless of classiﬁcation, hypovolaemia and inadequate preload must be addressed before other ther apy is instituted. Administration of inotropic or chronotropic agents to an empty heart will rapidly and permanently deplete the myocardium of oxygen stores and dramatically reduce diastolic ﬁlling and therefore coronary perfusion. Correction of preload by ensuring adequate volume resuscitation should be prioritised before introducing vasopressors or inotropic agents. First-line therapy , therefore, is intravenous access and administration of intravenous ﬂuids. Access should be through short, wide-bore catheters that allow rapid infusion of ﬂuids as necessary . Long, narr ow lines, such as central venous catheters, have too high a resistance to allow rapid infusion and are more appropriate for monitoring than ﬂuid replacement therapy . Type of ﬂuids As a general rule, the ideal replacement ﬂuid is one that approximates the ﬂuid lost by the underlying cause of shock. If blood is being lost, the replacement ﬂuid is whole blood or its equivalent in components /uni00A0 – /uni00A0 although crystalloid therapy may be required while awaiting blood products. Other causes of shock will require crystalloid resuscitation with appropriate electrolyte supplementation. In most studies of shock resuscitation there is no overt dif ference in response or outcome between crystalloid solutions (normal saline, Hartmann’s solution, Ringer’s lactate) and colloids (albumin or commercially available products). Fur ther more, there is less volume beneﬁt to the administration of colloids than had previously been thought, with only 1.3 times more crystalloid than colloid administered in blinded trials. On balance, there is little evidence to support the administration of colloids, which are more expensive and have worse side-e ﬀ ect proﬁles. Hypotonic solutions (e.g. dextrose) are poor volume expand ers and should not be used in the treatment of shock unless the deﬁcit is free water loss (e.g. diabetes insipidus) or patients are sodium overloaded (e.g. cirrhosis). Conduct of resuscitation

Cross-matching

To prevent transfusion reactions, all transfusions are preceded by ABO and rhesus typing of both donor and recipient blood to ensure compatibility . The recipient’s serum is then mixed with the donor’s cells to conﬁrm ABO compatibility and to test for rhesus and any other blood group antigen–antibody reaction. Full cross-matching of blood may take up to 45 minutes in most laboratories. In more urgent situations, ‘type-speciﬁc’ blood is provided; this is only ABO/rhesus matched and can be issued within 10–15 minutes . Where blood must be given in an emergency , group O (universal donor) blood is given (O– to - females, O+ to males). When blood transfusion is prescribed and blood is admin - istered, it is essential that the correct patient receives the cor - rect transfusion. Two healthcare personnel should check the patient’s details against the prescription and the label of the donor blood. In addition, the donor blood serial number should also be checked against the issue slip for that patient. Provided these principles are strictly adhered to, the number of severe and fatal ABO incompatibility reactions can be minimised.

Antibodies Frequency (%) Anti-A, anti-B 46 Anti-B 42 Anti-A 9 None 3

Cross-matching

Antibodies Frequency (%) Anti-A, anti-B 46 Anti-B 42 Anti-A 9 None 3

Cross-matching

Antibodies Frequency (%) Anti-A, anti-B 46 Anti-B 42 Anti-A 9 None 3

Damage control resuscitation

Damage control resuscitation (DCR), also known as haemo - static resuscitation, is a paradigm that prioritises haemorrhage control in patients who are still actively bleeding. The rationale is that no aspect of the shock state /uni00A0 – /uni00A0 end-organ perfusion, blood pressure, temperature, lactic acidosis /uni00A0 – /uni00A0 can be corrected

Haemostasis Time Prioritise perfusion Perfusion-targeted resuscitation Goal: End-organ perfusion Adequate preload and afterload ( /f_l uids and pressors) Thromboprophylaxis Monitor : Cardiovascular: BP , HR, CO, SVR Perfusion: base excess, lactate, S O v 2 Organ function: PaO /F O , UO, GCS 2 i 2 Abdominal compartment: IAP O , fraction of inspired oxygen; i 2 , arterial oxygen tension; PT, prothrombin time; RBC, red 2 O , mixed venous oxygen saturation; TEG, thrombo

v 2

resuscitation will exacerbate coagulopathy , hypothermia and metabolic derangements (acidosis, hyperkalaemia, hypocal caemia). The introduction of DCR has been associated with substantial reductions in mortality from haemorrhagic shock in the last decade. DCR applies only while patients are bleeding and is based on four key principles /uni00A0 – /uni00A0 rapid haemorrhage control; permissive hypotension; avoiding dilutional coagulopathy; and trea existing coagulation deﬁcits ( Figure 2.2 ). Rapid haemorrhage control At all times, control of bleeding is the priority . Direct pres sure should be placed over the site of external haemorrhage. Temporary bleeding control should be achieved with tour niquets, balloon occlusion or other techniques. Intracavitary haemorrhage should be suspected and searched for, and the pathway should actively move patients forwards to the oper ating theatre or interventional radiology room to achieve this. The damage control approach is extended to the conduct of surgery to prioritise rapid bleeding control. In damage con trol surgery , surgical intervention is limited to the minimum necessary to stop bleeding and contr ol sepsis, in order to avoid additional tissue damage, bleeding and physiological stress. More deﬁnitive repairs can be delayed until the patient is hae modynamically stable and physiologically capable of sustain ing the procedure. Thus the operation is tailored to match the patient’s physiology , and is not focused on reconstructing anat omy . ‘Damage control’ is a term borrowed from the military: it ensures continued functioning of a damaged ship above con ducting complete repairs, which would prevent rapid return to battle. Summary box 2.3 Damage control surgery /uni25CF /uni25CF /uni25CF /uni25CF Permissive hypotension Permissive hypotension allows the patient to set their own blood pressure while bleeding and avoids continued volume resuscitation in the vain attempt to normalise perfusion while bleeding. This reduces blood loss from bleeding sites and reduces dilutional coagulopathy and hypothermia induced by ﬂuids. It is important to maintain baseline perfusion of the coronary arteries at minimum, and thus a palpable central pulse (mean arterial pressure above ~50 /uni00A0 mmHg) must be maintained by whatever means are available. Avoid dilutional coagulopathy Avoid dilutional coagulopathy by avoiding clear ﬂuids (crystal loids or colloids) and by giving a transfusion that approximates red blood cells and plasma. - Treat existing coagulation deﬁcits Treat existing coagulopathies either empirically or by regular coagulation testing and acting on the results. Tranexamic acid should be given as soon as possible in almost all bleeding patients to stop hyperﬁbrinolysis. Blood component concen - ting trates should be given to correct existing deﬁcits, such as cryoprecipitate for low ﬁbrinogen levels or platelet transfusions for platelet dysfunctions. -

Arrest haemorrhage Control sepsis Protect from further injury Nothing else

Damage control resuscitation

Haemostasis Time Prioritise perfusion Perfusion-targeted resuscitation Goal: End-organ perfusion Adequate preload and afterload ( /f_l uids and pressors) Thromboprophylaxis Monitor : Cardiovascular: BP , HR, CO, SVR Perfusion: base excess, lactate, S O v 2 Organ function: PaO /F O , UO, GCS 2 i 2 Abdominal compartment: IAP O , fraction of inspired oxygen; i 2 , arterial oxygen tension; PT, prothrombin time; RBC, red 2 O , mixed venous oxygen saturation; TEG, thrombo

v 2

Arrest haemorrhage Control sepsis Protect from further injury Nothing else

Damage control resuscitation

Haemostasis Time Prioritise perfusion Perfusion-targeted resuscitation Goal: End-organ perfusion Adequate preload and afterload ( /f_l uids and pressors) Thromboprophylaxis Monitor : Cardiovascular: BP , HR, CO, SVR Perfusion: base excess, lactate, S O v 2 Organ function: PaO /F O , UO, GCS 2 i 2 Abdominal compartment: IAP O , fraction of inspired oxygen; i 2 , arterial oxygen tension; PT, prothrombin time; RBC, red 2 O , mixed venous oxygen saturation; TEG, thrombo

v 2

Arrest haemorrhage Control sepsis Protect from further injury Nothing else

Degree of haemorrhage and classiﬁcation

The adult human has approximately 5 litres of blood (70 /uni00A0 mL/kg for children and adults, 80 /uni00A0 mL/kg for neonates). Estimation of the amount of blood that has been lost is di ﬃ cult, inaccurate and usually underestimates the actual value. External haemorrhage is obvious, but it may be di ﬃ cult to estimate the actual volume lost. In the operating theatre, blood collected in suction apparatus can be measur ed and swabs soaked in blood weighed. - The haemoglobin level is a poor indicator of the degree of haemorrhage because it represents a concentration and not an absolute amount. In the early stages of rapid haemorrhage, the haemoglobin concentra tion is unchanged (as whole blood is lost). Later, as ﬂuid shifts from the intracellular and interstitial - spaces into the vascular compartment, the haemoglobin and haematocrit levels will fall.

Class 2 3 4 15–30% 30–40%

40%

classes 1–4 based on the estimated blood loss required to pro duce certain physiological compensatory changes ( Table 2.3 Although conceptually useful, this classiﬁcation system is never applied clinically , and indeed is di ﬃ cult if not impossible to determine. There is variation in clinical response across ages (the young compensate well, the old very poorly), variation among individuals (e.g. athletes versus the obese) and variation owing to confounding factors (e.g. concomitant medications, pain). Degree of haemorrhage and classiﬁcation

Class 2 3 4 15–30% 30–40%

40%

Class 2 3 4 15–30% 30–40%

40%

Deﬁnitions

Revealed and concealed haemorrhage Haemorrhage may be revealed or concealed. Revealed haemorrhage is obvious external haemorrhage, such as exsanguination from an open arterial wound or from massive haematemesis from a duodenal ulcer. Concealed haemorrhage is contained within the body cav ity and must be suspected, actively investigated and controlled. In trauma, haemorrhage may be concealed within the chest, abdomen, pelvis, r etroperitoneum or in the limbs with con tained vascular injury or associated with long-bone fractures. Examples of non-traumatic concealed haemorrhage include occult gastrointestinal bleeding or ruptured aortic aneurysm. Primary, reactionary and secondary haemorrhage Primary haemorrhage is haemorrhage occurring immediately as a result of an injury (or surgery). Reactionary haemorrhage is delayed haemorrhage (within 24 hours) and is usually due to dislodgement of a clot by resus citation, normalisation of blood pressure and vasodilatation. Reactionary haemorrhage may also be due to technical failure, such as slippage of a ligature. Secondary haemorrhage is due to sloughing of the wall of a vessel. It usually occurs 7–14 days after injury and is precip itated by factors such as infection, pressure necrosis (such as from a drain) or malignancy . Surgical haemorrhage is due to a direct injury and is amenable to surgical control (e.g. suture ligation) or other techniques such as angioembolisation. Non-surgical haemorrhage is general bleeding from raw surfaces and mucous membranes due to coagulopathy and cannot be stopped by surgical means (except packing). Treat - ment requires correction of the coagula tion abnormalities. Diagnosis of active bleeding: response to ﬂuid therapy The mode of resuscitation is determined by whether patients are actively bleeding, which requires a dynamic assessment of the blood pressure response to volume infusion. Patients who are ‘non-responders’ or ‘transient responders’ are still bleeding and must have the site of haemorrhage identiﬁed and controlled. Responder There is a good and sustained improvement in blood pressure in response to a bolus transfusion. Transient responder There is an improvement in the blood pressure but this is not sustained. The rate of haemorrhage is less than the rate of volume administration. Non-responder There is no improvement in the blood pressure to a bolus transfusion. The rate of haemorrhage is greater than the rate - of volume administration. -

TABLE 2.3 Traditional classi /f_i cation of haemorrhagic shock. 1 Blood volume lost as percentage of total <15%

Deﬁnitions

TABLE 2.3 Traditional classi /f_i cation of haemorrhagic shock. 1 Blood volume lost as percentage of total <15%

Deﬁnitions

TABLE 2.3 Traditional classi /f_i cation of haemorrhagic shock. 1 Blood volume lost as percentage of total <15%

End points of resuscitation

It is much easier to know when to start resuscitation than when to stop. Traditionally , patients have been resuscitated until they have a normal pulse, blood pressure and urine output. However, these parameters are monitoring organ systems whose blood ﬂow is preserved until the late stages of shock. A patient therefore may be resuscitated to restore central perfusion to the brain, lungs and kidneys and yet continue to underperfuse the gut and muscle beds. Thus, activation of inﬂammation and coagulation may be ongoing and lead to reperfusion injury when these organs are ﬁnally perfused, and ultimately multiple organ failure. This state of normal vital signs and continued underperfu sion is termed ‘occult hypoperfusion’. With current monitoring techniques, it is manifested only by a persistent lactic acidosis and low mixed venous oxygen saturation. T he time spent by patients in this hypoperfused state has a dramatic e ﬀ ect on outcome. Patients with occult hypoperfusion for more than 12 /uni00A0 hours have two to three times the mortality of patients with a limited duration of shock. Resuscitation algorithms directed at correcting global perfusion end points (base deﬁcit, lactate, mixed venous oxygen saturation) rather than traditional end points have been shown to improve mortality and morbidity in high-risk surgical patients. However, it is also clear that aggressive crystalloid resus citation regimens can lead to tissue oedema and organ fail ure, especially acute respira tory distress syndrome, abdominal compartment syndrome and cerebral oedema. Some patients cannot be resuscitated to normal parameters within 12 hours Karl Landsteiner , 1868–1943, Professor of Pathological Anatomy , University of Vienna, Austria. In 1909 he classiﬁed the human blood groups into A, B, AB and O. For this he was awarded the Nobel Prize in Physiology or Medicine in 1930. Hans Gerhard Creutzfeldt , 1885–1946, neurologist, Kiel, Germany . Alfons Maria Jakob , 1884–1931, neurologist, Hamburg, Germany . patients to be judicious in the approach to all therapies as end points are approached. End points of resuscitation

HAEMORRHAGE RESUSCITATION

The conduct and goals of resuscitation change depending on whether the patient is actively bleeding. In this case, the resusci tation focuses on achieving rapid haemostasis and maintaining the ability of the blood to clot. This paradigm is called damage control resuscitation (see Damage control resuscitation If the patient is not actively bleeding, has stopped bleeding or the cause of shock is not haemorrhage, then resuscitation is directed at correcting the shock state and restoring perfusion to end organs. HAEMORRHAGE RESUSCITATION

HAEMORRHAGE

Uncontrolled bleeding will lead to a hypovolaemic shock - state, or haemorrhagic shock. While haemorrhage and shock often coexist, they are not the same. Patients who are actively bleeding may not yet be in shock. Conversely , patients may be in shock as a consequence of haemorrhage, but they may no longer be actively bleeding. ) are Resuscitation is very di ﬀ erent if patients are actively bleed - - ing or if they are not bleeding. In patients who are bleeding, the priority is to stop bleeding. In patients who are not bleeding, the priority shifts to normalising end-organ perfusion (correct - ing the shock state). Thus it is vital to recognise patients who are actively bleeding, and this is di ﬀ erent from recognising that a patient is in shock. Haemorrhage must be recognised and managed rapidly and decisively to reduce the severity and duration of shock. Haemorrhage is treated by arresting the bleeding /uni00A0 – /uni00A0 not by ﬂuid resuscita tion or blood transfusion. Although necessary as supportive measures to maintain organ (especially cardiac) perfusion, repeated volume resuscitation of patients who have ongoing haemorrhage will lead to physiological exhaustion (profound coagulopathy , acidosis and hypothermia) and sub - sequently death. HAEMORRHAGE

Identify haemorrhage

External haemorrhage may be obvious, but the diagnosis of concealed haemorrhage may be more di ﬃ cult. Any shock should be assumed to be hypovolaemic until proven otherwise and, similarly , hypovolaemia should be assumed to be due to haemorrhage until this has been excluded. Once haemorrhage has been identiﬁed, the institution’s major haemorrhage protocol should be activated, which will Figure 2.2 - ate resuscitative measures include the assessment of airway and ). breathing and control of life-threatening issues as necessary . Large-bore intra venous access should be instituted and blood drawn for cross-matching (see Cross-matching ). Transfusion should start with emergency (type O) blood (see Transfusion ). Once haemorrhage has been considered, the site of hae - morrhage must be rapidly identiﬁed. Note that this is not to identify the exact location deﬁnitively , but rather to deﬁne the next step in haemorrhage control (operation, angioembolisa - tion, endoscopic control). Clues may be in the histor y (previous episodes, known aneurysm, non-steroidal therapy for gastro - intestinal bleeding) or examination (nature of blood /uni00A0 – /uni00A0 fresh, melaena; abdominal tenderness, etc.). For shocked trauma - patients, the external signs of injury may suggest internal hae - morrhage, but haemorrhage into a body cavity (thorax, abdo - men) must be excluded with rapid investigations (chest and ). pelvis radiographs, abdominal ultrasound). Investigations for blood loss must be appropriate to the patient’s physiological condition. Rapid bedside tests such as ultrasound are more appropriate for profound shock and exsanguinating haemorrhage than investiga tions such as com - puted tomography . Patients who are not actively bleeding can have a more methodical, deﬁnitive work-up.

Bleeding Prioritise coagulation Recognise active bleeding Hypotension. Transient/Non-responder Damage control resuscitation Goal: Coagulation function. Coronary perfusion Damage control surgery Permissive hypotension Balanced transfusion (1:1 RBC and FFP) Treat coagulopathy (tranexamic acid, platelets, /f_i brinogen) Monitor : Cardiovascular: BP , HR 2+ + Electrolytes: Ca , K Coagulation: PT, /f_i brinogen, ROTEM/TEG Perfusion: pH, base excess, lactate, temperature Haemorrhage resuscitation. BP , blood pressure; CO, cardiac output; FFP , fresh-frozen plasma; F GCS, Glasgow Coma Scale score; HR, heart rate; IAP , intra-abdominal pressure; PaO blood cells; ROTEM, rotational thromboelastometry; SVR, systemic vascular resistance; S elastography; UO, urine output.

Identify haemorrhage

Indications for blood transfusion

Blood transfusions should be avoided if possible, and many previous uses of blood and blood products are now no longer considered appropriate. The indications for blood transfusion are as follows: /uni25CF Acute blood loss, to replace circulating volume and main - tain oxygen delivery; /uni25CF Perioperative anaemia, to ensure adequate oxygen delivery during the perioperative phase; /uni25CF Symptomatic chronic anaemia, without haemorrhage or impending surgery . Transfusion trigger Historically , patients were transfused to achieve a haemoglobin >10 /uni00A0 g/dL. This has now been shown not only to be unneces - sary but also to be associated with an increased morbidity and - mortality compared with lower target values. A haemoglobin level of 6 /uni00A0 g/dL is acceptable in patients who are not actively bleeding, those who are not about to undergo major surgery and those who are not symptomatic. There is some controversy as to the optimal haemoglobin level in some patient groups, such as those with cardiovascular disease, sepsis and traumatic brain injury . Although, conceptually , a higher haemoglobin level improves oxygen delivery , there is little clinical evidence at this stage to support higher levels in these groups ( Table 2.6 ). - -

TABLE 2.6 Perioperative red blood cell transfusion criteria. Haemoglobin level (g/dL) Indications <6 Probably will bene /f_i t from transfusion 6–8 Transfusion unlikely to be of bene /f_i t in the absence of bleeding or impending surgery

8 No indication for transfusion in the absence of other risk factors

Indications for blood transfusion

8 No indication for transfusion in the absence of other risk factors

Indications for blood transfusion

8 No indication for transfusion in the absence of other risk factors

Introduction

INTRODUCTION

Shock is the most common cause of death of surgical patients. Death may occur rapidly because of a profound state of shock or may occur later because of the consequences of organ ischaemia and reperfusion injury . It is important therefore that every surgeon understands the pathophysiology , diagnosis and priorities in management of shock and haemorrhage.

Learning objectives

To understand: The pathophysiology of shock • The different patterns of shock and the principles and • priorities of resuscitation Appropriate monitoring and end points of resuscitation • Learning objectives

To understand: The pathophysiology of shock • The different patterns of shock and the principles and • priorities of resuscitation Appropriate monitoring and end points of resuscitation •

Monitoring

The minimum standard for monitoring of the patient in shock is continuous heart rate and oxygen saturation moni - toring, frequent non-invasive blood pressure monitoring and hourly urine output measurements. Most patients will need more aggressive invasive monitoring, including central venous pressure (CVP) and invasive blood pressure monitoring. Summary box 2.4 Monitoring for patients in shock /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF - Cardiovascular - Cardiovascular monitoring at minimum should include continuous heart rate (electrocardiogram, oxygen saturation and pulse waveform and non-invasive blood pressure). Patients whose state of shock is not rapidly corrected with a small amount of ﬂuid should have CVP monitoring and continuous blood pressure monitoring through an arterial line. - Central venous pressure There is no ‘normal’ CVP for a shocked patient, and reliance cannot be placed on an individual pressure measurement to assess volume status. Some patients may require a CVP of 5 /uni00A0 cmH O, whereas some may require a CVP of 15 /uni00A0 cmH O 2 2 or higher. Further, ventricular compliance can change from minute to minute in the shocked state, and CVP is a poor reﬂection of end-diastolic volume (preload). CVP measurements should be assessed dynamically as the - response to a ﬂuid challenge. A ﬂuid bolus (250–500 /uni00A0 mL) is infused rapidly over 5–10 minutes. - The normal CVP response is a rise of 2–5 /uni00A0 cmH O, which 2 gradually drifts back to the original level over 10–20 minutes. tion Patients with no change in their CVP are empty and require further ﬂuid resuscitation. Patients with a large, sustained rise - in CVP have high preload and an element of cardiac insu ﬃ - - ciency or volume overload.

Minimum Additional modalities ECG Central venous pressure Pulse oximetry Invasive blood pressure Blood pressure Cardiac output Urine output Base de /f_i cit and serum lactate

Cardiac output monitoring allows assessment of not only the cardiac output but also the systemic vascular resistance and, depending on the technique used, end-diastolic volume (preload) and blood volume. Use of invasive cardiac monitor ing with pulmonary artery catheters is becoming less frequent as new non-invasive monitoring techniques, such as Doppler ultrasound, pulse waveform analysis and indicator dilution methods, provide similar information without many of the drawbacks of more invasive techniques. Measurement of cardiac output, systemic vascular resis tance and preload can help distinguish the types of shock present (hypovolaemia, distributive, cardiogenic), especially when they coexist. The information pr ovided guides ﬂuid and vasopressor therapy by providing real-time monitoring of the cardiovascular response. Measurement of cardiac output is desirable in patients who do not respond as expected to ﬁrst-line therapy or who have evidence of cardiogenic shock or myocardial dysfunction. Early consideration should be giv en to instituting cardiac out put monitoring for patients who require vasopressor or inotro pic support. Systemic and organ perfusion Ultimately , the goal of treatment is to restore cellular and organ perfusion. Ideally , therefore, monitoring of organ perfusion should guide the management of shock. The best measure of organ perfusion and the best monitor of the adequacy of shock therapy remains the urine output. However, this is an hourly measure and does not give a minute-to-minute view of the shocked state. The level of consciousness is an important marker of cerebral perfusion, but brain perfusion is maintained until the very late stages of shock and hence is a poor marker of adequacy of resuscitation ( Table 2.4 ). Currently , the only clinical indicators of perfusion of the gastrointestinal tract and muscular beds are the global Christian Johann Doppler , 1803–1853, Professor of Experimental Physics, Vienna, Austria, en mixed venous oxygen saturation. Base deﬁcit and lactate Lactic acid is generated by cells undergoing anaerobic respi - - ration. The degree of lactic acidosis, as measured by serum lactate level and/or the base deﬁcit, is sensitive for both diagnosis of shock and monitoring the response to therapy . Patients with a base deﬁcit of more than 6 /uni00A0 mmol/L have a much higher morbidity and mortality than those with no metabolic acidosis. Furthermore, the length of time in shock - with an increased base deﬁcit is important, even if all other vital signs have returned to normal (see occult hypoperfusion below under End points of resuscitation ). These parameters are measured from arterial blood gas analyses, and therefore the frequency of measurements is limited and they do not pr ovide minute-to-minute data on systemic perfusion or the response to therapy . Nevertheless, the base deﬁcit and/or lactate should be measured routinely in these patients until they have returned to normal levels. - - Mixed venous oxygen saturation The percentage saturation of oxygen returning to the heart from the body is a measure of the oxygen delivery and extraction by the tissues. Accurate measurement is via analysis of blood drawn from a long central line placed in the right atrium. Estimations can be made from blood drawn from lines in the superior vena cava, but these values will be slightly higher than those of a mixed venous sample (as there is rela - tively more oxygen extraction from the lower half of the body). Normal mixed venous oxygen saturation levels are 50–70%. Levels below 50% indicate inadequate oxygen delivery and increased oxygen extraction by the cells. This is consistent with hypovolaemic or cardiogenic shock. High mixed venous saturations (>70%) are seen in sepsis and some other forms of distributive shock. In sepsis, there is disordered utilisation of oxygen at the cellular level and unciated the Doppler principle in 1842.

TABLE 2.4 Monitors for organ/systemic perfusion. Clinical Systemic perfusion Organ perfusion Muscle – Gut – Kidney Urine output Brain Conscious level Investigational Base de /f_i cit Lactate Mixed venous oxygen saturation Near-infrared spectroscopy Tissue oxygen electrode Sublingual capnometry Gut mucosal pH Laser Doppler /f_l owmetry – Tissue oxygen electrode Near-infrared spectroscopy

Therefore, less oxygen is presented to the cells, and those cells cannot utilise what little oxygen is presented. Thus, venous blood has a higher oxygen concentration than normal. Patients who are septic should therefore have mixed venous oxygen saturations above 70%; below this level, they are not only in septic shock but also in hypovolaemic or cardiogenic shock. Although the S O level is in the ‘normal’ range, it is low v 2 for the septic state, and inadequate oxygen is being supplied to cells that cannot utilise oxygen appropriately . This must be cor rected rapidly . Hypovolaemia should be corrected with ﬂuid therapy , and low cardiac output due to myocardial depression or failure should be treated with inotropes (dobutamine) to achieve a mixed venous saturation greater than 70% (normal for the septic state). New methods for monitoring regional tissue perfusion and oxygenation are becoming available, the most promising of whic h are muscle tissue oxygen probes, near-infrared spectros copy and sublingual capnometry . While these techniques pro vide information regarding perfusion of speciﬁc tissue beds, it is as yet unclear whether there are signiﬁcant advantages over existing measurements of global hypoperfusion (base deﬁcit, lactate). Monitoring

Minimum Additional modalities ECG Central venous pressure Pulse oximetry Invasive blood pressure Blood pressure Cardiac output Urine output Base de /f_i cit and serum lactate

Pathophysiology

Cellular As perfusion to the tissues is reduced, cells are deprived of oxygen and must switch from aerobic to anaerobic metabolism. The product of anaerobic respiration is not carbon dioxide but lactic acid. When enough tissue is underperfused the accumulation of lactic acid in the blood produces a systemic metabolic acidosis. As glucose within cells is exhausted, anaerobic respiration ceases and there is failure of sodium/potassium pumps in the cell membrane and intracellular organelles. Intracellular lysosomes release autodigestive enzymes and cell lysis ensues. Intracellular contents , including potassium, are released into the bloodstream. Microvascular As tissue ischaemia progresses, changes in the local milieu result in activation of the immune and coagulation systems. Hypoxia and acidosis activate complement and prime leuko cytes, resulting in the generation of oxygen free radicals and cytokine release. These mechanisms lead to injury of the capillary endothelial cells. These, in turn, further activate the immune and coagulation systems. Damaged endothelium loses its integrity and becomes ‘leaky’. Spaces between endothelial cells allow ﬂuid to leak out and tissue oedema ensues, exacer - bating cellular hypoxia. Ischaemic cell death releases potassium into the circula - tion, leading to systemic hyperkalaemia and acidosis, as well as further damage to molecules that systemically activate the immune system. - Systemic Cardiovascular As preload and afterload decrease, there is a compensatory baroreceptor response, resulting in increased sympathetic activity and release of catecholamines into the circulation. This results in tachycardia and systemic vasoconstriction (except in sepsis /uni00A0 – /uni00A0 see Distributive shock ). Respiratory The metabolic acidosis and increased sympathetic response result in an increased respiratory rate and minute ventilation to increase the excretion of carbon dioxide (and so produce a compensatory respiratory alkalosis). Renal Decreased perfusion pressure in the kidney leads to reduced ﬁltration at the glomerulus and a decreased urine output. The renin–angiotensin–aldosterone axis is stimulated, resulting in further vasoconstriction and increased sodium and water reabsorption by the kidney . Endocrine As well as activation of the adrenal and renin–angiotensin systems, vasopressin (antidiuretic hormone) is released in -

Recognition and management of bleeding • Use of blood and blood products, the bene /f_i ts and risks of • blood transfusion

and resorption of water in the renal collecting system. Cortisol is also released from the adrenal cortex, contributing to the sodium and water resorption and sensitising cells to catechol amines. Pathophysiology

In trauma and surgery , the combination of tissue trauma and hypovolaemic shock leads to the development of an endog - enous coagulopathy called acute traumatic coagulopathy - (ATC). Up to 25% of all trauma patients develop ATC within minutes of injury and it is associated with a fourfold increase in mortality . ATC is characterised by systemic hyperﬁbrinolysis, low ﬁbrinogen levels and platelet dysfunction. ATC evolves into a more complex, multifactorial ‘trauma- - induced coagulopathy’ owing to further derangements induced by resuscitation ( Figure 2.1 ). Fluid and red b lood cell trans- fusions lead to dilution of coagulation factors, which worsens the pre-existing coagulopathy . Underperfused muscle is unable to generate hea t and hypothermia ensues, again worsened by cold ﬂuid or blood transfusion. Further heat is lost by opening Figure 2.1 body cavities during surgery . Severe acidosis and hypothermia both inhibit coagulation proteases and reduce coagulation function. These then lead to further bleeding and a downward spiral, leading to physiological exhaustion and death.

ATC Haemorrhage Acidaemia Hypothermia In /f_l ammation Fibrinolysis Genetics Loss, dilution TRAUMA-INDUCED COAGULOPATHY (TIC) Trauma-induced coagulopathy. ATC, acute traumatic coagulopathy.

Pathophysiology

Recognition and management of bleeding • Use of blood and blood products, the bene /f_i ts and risks of • blood transfusion

ATC Haemorrhage Acidaemia Hypothermia In /f_l ammation Fibrinolysis Genetics Loss, dilution TRAUMA-INDUCED COAGULOPATHY (TIC) Trauma-induced coagulopathy. ATC, acute traumatic coagulopathy.

Pathophysiology

Recognition and management of bleeding • Use of blood and blood products, the bene /f_i ts and risks of • blood transfusion

ATC Haemorrhage Acidaemia Hypothermia In /f_l ammation Fibrinolysis Genetics Loss, dilution TRAUMA-INDUCED COAGULOPATHY (TIC) Trauma-induced coagulopathy. ATC, acute traumatic coagulopathy.

Recognition and diagnosis of shock

Shock may be profound and easily recognised or it may be - subtle and only diagnosed with directed clinical examination and cardiovascular and metabolic monitoring. Compensated shock As shock progresses, the body’s cardiovascular and endocrine compensatory responses reduce ﬂow to non-essential organs to preserve preload and ﬂow to the lungs and brain. In compen - sated shock, there is adequate cardiovascular compensation to maintain central blood volume and preserve ﬂow to the kidneys, lungs and brain. Apart from a tachycardia and cool peripheries (vasoconstriction, circulating catecholamines), there may be no other clinical signs of hypovolaemia. However, this cardiovascular state is only maintained by reducing perfusion to the skin, muscle and gastrointestinal tract. These organs are underperfused: their cells are respiring anaerobically and sustaining ischaemic damage. There is sys - temic metabolic acidosis and both local and systemic activation of humoral and cellular inﬂammation. - Although clinically occult, this state will lead to multiple organ failure and death if prolonged. Patients with occult hypoperfusion (metabolic acidosis despite normal urine output and cardiorespiratory vital signs) for more than 12 hours have a signiﬁcantly higher mortality , infection rate and incidence of - multiple organ failure (see Multiple organ failure ). Decompensation Further loss of circulating volume overloads the body’s compensatory mechanisms and there is progressive renal, respiratory and cardiovascular decompensation. In general, loss of around 15% of the circulating blood volume is within normal compensatory mechanisms. Blood pressure is usually well maintained and only falls after 30–40% of circulating volume has been lost. Mild (compensated) shock - Initially there is tachycardia, tachypnoea, a mild reduction in urine output and the patient may exhibit mild anxiety . Blood pressure is maintained, although there is a decrease in pulse pressure. The peripheries are cool and sweaty with prolonged capillary reﬁll times (except in septic distributive shock). Moderate shock As shock progresses, renal compensatory mechanisms fail, renal perfusion falls and urine output dips below 0.5 /uni00A0 mL/kg/hour. There is further tachycardia, and now the blood pressure starts to fall. Patients become drowsy and mildly confused. Severe shock In severe shock, there is profound tachycardia and hypoten sion. Urine output falls to zero and patients are unconscious with laboured respiration. Clinical features The classic cardiovascular responses described ( Table 2.2 not seen in every patient. It is important to recognise the limita tions of the clinical examination and to recognise patients who are in shock despite the absence of classic signs. Capillary reﬁll Most patients in hypovolaemic shock will have cool, pale peripheries, with prolonged capillary reﬁll times. However, the actual capillary reﬁll time varies so much in adults that it is not a speciﬁc marker of whether a patient is shocked, and patients with short capillary reﬁll times may be in the early stages of shock. In distributive (septic) shock, the peripheries will be warm and capillary reﬁll will be brisk, despite profound shock. Tachycardia Tachycardia may not always accompany shock. Patients who are on β -blockers or who have implanted pacemakers are unable to mount a tachycardia. A pulse rate of 80 in a ﬁt young adult who normally has a pulse rate of 50 is very abnormal. Furthermore, in some young patients with penetrating trauma, where there is haemorrhage but little tissue damage, there may be a paradoxical bradycardia rather than tachycardia accom panying the shocked state. Blood pressure It is important to recognise that hypotension is one of the last signs of shock. Children and ﬁt young adults are able to main tain blood pressure until the ﬁnal stages of shock by dramatic increases in stroke volume and peripheral vasoconstriction. These patients can be in profound shock with a normal blood pressure. Elderly patients who are normally hypertensive may present with a ‘normal’ blood pressure for the general population but be hypovolaemic and hypotensive relative to their usual blood pressur e. β -blockers or other medications may prevent a tachy - cardic response. T he diagnosis of shock may be di ﬃ cult unless one is alert to these pitfalls.

Compensated Mild Lactic acidosis + Urine output Normal Conscious level Mild anxiety Respiratory rate Increased Pulse rate Increased Blood pressure Normal Uncompensated Moderate Severe ++ +++ Reduced Anuric Drowsy Comatose Increased Laboured Increased Increased Mild hypotension Severe hypotension

Recognition and diagnosis of shock

SHOCK RESUSCITATION

Immediate resuscitation manoeuvres for patients presenting in - shock are to ensure a patent airway and adequate oxygenation and ventilation. Once ‘airway’ and ‘breathing’ are assessed and - controlled, attention is directed to cardiovascular resuscitation. Haemorrhagic shock resuscitation should proceed as damage - control resuscitation while bleeding continues (as discussed earlier). After bleeding is controlled, and for all other causes, shock resuscitation is guided by measures of tissue perfusion, as described in Monitoring . SHOCK RESUSCITATION
Immediate resuscitation manoeuvres for patients presenting in - shock are to ensure a patent airway and adequate oxygenation and ventilation. Once ‘airway’ and ‘breathing’ are assessed and - controlled, attention is directed to cardiovascular resuscitation. Haemorrhagic shock resuscitation should proceed as damage - control resuscitation while bleeding continues (as discussed earlier). After bleeding is controlled, and for all other causes, shock resuscitation is guided by measures of tissue perfusion, as described in Monitoring . SHOCK RESUSCITATION
Immediate resuscitation manoeuvres for patients presenting in - shock are to ensure a patent airway and adequate oxygenation and ventilation. Once ‘airway’ and ‘breathing’ are assessed and - controlled, attention is directed to cardiovascular resuscitation. Haemorrhagic shock resuscitation should proceed as damage - control resuscitation while bleeding continues (as discussed earlier). After bleeding is controlled, and for all other causes, shock resuscitation is guided by measures of tissue perfusion, as described in Monitoring .

SHOCK

Shock is a systemic state of low tissue perfusion that is inade quate for normal cellular respiration. With insu ﬃ cient delivery of oxygen and glucose, cells switch from aerobic to anaerobic metabolism. If perfusion is not restored in a timely fashion, cell death ensues. SHOCK

TRANSFUSION

The transfusion of blood and blood products has become commonplace since the ﬁrst successful transfusion in 1818. Although the incidence of severe transfusion reactions and infections is now very low , in recent years it has become - apparent that there is an immunological price to be paid for the transfusion of heterologous blood, leading to increased morbidity and decreased survival in certain population groups (trauma, malignancy). Supplies are also limited, and therefore the use of blood and blood products must always be judicious and justiﬁable for clinical need ( Table 2.5 ). - - -

TABLE 2.5 History of blood transfusion. 1492 Pope Innocent VIII suffers a stroke and receives a blood transfusion from three 10-year-old boys (paid a ducat each). All three boys died, as did the pope later that year 1665 Richard Lower in Oxford conducts the /f_i rst successful canine transfusions 1667 Jean-Baptiste Denis reports successful sheep–human transfusions 1678 Animal–human transfusions are banned in France because of the poor results 1818 James Blundell performs the /f_i rst successful documented human transfusion in a woman suffering postpartum haemorrhage. She received blood from her husband and survived 1901 Karl Landsteiner discovers the ABO system 1914 The Belgian physician Albert Hustin performed the /f_i rst non-direct transfusion, using sodium citrate as an anticoagulant 1926 The British Red Cross instituted the /f_i rst blood transfusion service in the world 1939 The rhesus system was identi /f_i ed and recognised as the major cause of transfusion reactions

TRANSFUSION

Transfusion reactions

If antibodies present in the recipient’s serum are incompatible with the donor’s cells, a transfusion reaction will result. This usually takes the form of an acute haemolytic reaction. Severe immune-related transfusion reactions due to ABO incompat ibility result in potentially fatal complement-mediated intra vascular haemolysis and multiple organ failure. Transfusion reactions from other antigen systems are usually milder and self-limiting. Febrile transfusion reactions are non-haemolytic and are usually caused by a graft-versus-host-response from leukocytes in transfused components. Such reactions are associated with fe ver, chills or rigors. The blood transfusion should be stopped immediately . This form of transfusion reaction is rare with leukodepleted blood. Transfusion reactions

Vasopressor and inotropic support

Vasopressor or inotropic therapy is not indicated as ﬁrst-line therapy in hypovolaemia. Administration of these agents in the absence of adequate preload rapidly leads to decreased coro nary perfusion and depletion of myocardial oxygen reserves. Vasopressor agents (phenylephrine, noradrenaline [nor epinephrine]) are indicated in distributive shock states (sepsis, neurogenic shock) where there is peripheral vasodilata and a low systemic vascular resistance, leading to hypotension despite a high cardiac output. Where the vasodilatation is resis tant to catecholamines (e.g. absolute or relative steroid deﬁ ciency), vasopressin may be used as an alternative vasopressor. Alexis Frank Hartmann , 1898–1964, paediatrician, St Louis, MO, USA, described the solution; should not be confused with the name of Henri Albert Charles Antoine Hartmann, French surgeon, who described the operation that goes by his name. Sidney Ringer , 1835–1910, Professor of Clinical Medicine, University College Hospital, London, UK. complicated a shock state (e.g. severe septic shock with low car - diac output), inotropic therapy ma y be required to increase - cardiac output and therefore oxygen delivery . The inodilator dobutamine is the agent of choice. Vasopressor and inotropic support

2 Shock, haemorrhage and transfusion

After haemorrhage control

Blood and blood products

Blood groups and cross-matching

Blood substitutes

Classiﬁcation of shock

Clinical consequences of shock

Complications of blood transfusion

Conduct of resuscitation

Cross-matching

Damage control resuscitation

Degree of haemorrhage and classiﬁcation

Deﬁnitions

End points of resuscitation

FURTHER READING

HAEMORRHAGE RESUSCITATION

HAEMORRHAGE

Identify haemorrhage

Indications for blood transfusion

Introduction

Learning objectives

Monitoring

Pathophysiology

Recognition and diagnosis of shock

SHOCK RESUSCITATION

SHOCK

TRANSFUSION

Transfusion reactions

Vasopressor and inotropic support