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Haemorrhagic Shock
BASIC SCIENCE
transfusion attempts carried a high mortality, and the procedure was banned in France in the 1670s. One of the earliest uses of transfusion in cardiovascular resuscitation was by the English physiologist James Blundell, who successfully used human-to-human transfusion in 1829 to treat severe post-partum haemorrhage. However, such therapies were not safe or reliable until the science underpinning blood typing, storage and donation were discovered throughout the twentieth century.
Haemorrhagic Shock M A Babb A D Farmery
Aetiology The aetiology of haemorrhagic shock is shown in Figure 1. Definitions Shock occurs when perfusion is inadequate to supply the metabolic requirements of the tissues. Classically it is divided into: • hypovolaemic • cardiogenic • distributive (septic/toxic/anaphylactic/neurogenic) • obstructive (mechanical, e.g. tension pneumothorax, pulmonary embolism, cardiac tamponade). Haemorrhage is defined as an acute loss of circulating blood. Haemorrhagic shock is the most common cause of hypovolaemic shock, and results in a combination of anaemic and ischaemic tissue hypoxia. The tissue hypoxia causes a progressive failure of cellular metabolism. Compensatory mechanisms and different oxygen requirements in various tissue beds cause a spectrum of severities of organ damage, which may result in early or late multiple-organ dysfunction and death. Haemorrhagic shock may coexist with other types of shock, for example after trauma where cardiogenic (from cardiac contusion) and septic shock (from wound contamination) may occur. History A relationship between blood and health has been recognized for some time, although the nature of the importance of blood was misunderstood. Galen (c. 130–200 AD) systematized the humoral theory of Hippocrates, and proved that arteries contain blood, although he suggested that blood travelled to all parts of the body through the veins. His descriptions of vivisection underline his understanding that haemorrhage would result from arterial damage, and that the resultant haemorrhage might kill the subject. He was a visionary when he wrote, ‘nothing upsets any operation like haemorrhage’. The concept of the importance of ‘intravascular volume’ as opposed to ‘blood’ was not fully appreciated until the nineteenth century. Richard Lower (1665) in London, UK, and Jean-Baptiste Denis (1667) in Paris, France, independently performed animalto-human blood transfusion. However, this was performed for the perceived benefits of blood as a therapeutic ‘humour’, rather than as an act of restorative homeostatic physiology. These early
Pathophysiology of haemorrhage Haemorrhage results in a fall in blood volume and therefore a fall in venous pressure and venous return to the heart. The consequent fall in preload to the atria causes a reduction in stroke volume of both right and left ventricles. The reduced arterial pulse pressure diminishes stretch on arterial baroreceptors, which results in an increased sympathetic output, causing vasoconstriction and reflex tachycardia which tends to compensate for the reduced stroke volume, so cardiac output is initially preserved. As haemorrhage increases (but while shock is still reversible), bradycardia occurs. With continued haemorrhage, however, the tachycardia reappears. The vessels of the heart and brain are the only ones spared from vasoconstriction, which serves to preserve the blood flow to these two organs least able to recover from ischaemia. Coronary vasodilation occurs because of the increased metabolic demands of the myocardium resulting from the tachycardia. The vasoconstriction is most marked in the skin, kidneys and viscera, which explains some of the symptoms, signs and late sequelae of haemorrhagic shock. Widespread reflex venoconstriction also helps to maintain the filling pressure of the heart. Adrenal medullary secretion is also stimulated by haemorrhage, and circulating catecholamines may lead to stimulation of the reticular formation, causing restlessness and apprehension. Restlessness may increase the muscular and thoracic pumping of venous blood. Reduction in oxygen-carrying capacity and flow cause anaemic and stagnant hypoxia, which combine with acidosis to stimulate chemoreceptors. This stimulates respiration and excites the vasomotor centre, causing further vasoconstriction. Increased plasma renin activity causes increased circulating levels of angiotensin II, which helps to maintain blood pressure and stimulates thirst by an action on the subfornical organ (ingestion of fluid would help to restore extracellular fluid volume). Vaso-
Aetiology of haemorrhagic shock • • • • • • • •
M A Babb is a Specialist Registrar at the John Radcliffe Hospital, Oxford, UK. A D Farmery is a Senior Lecturer in Anaesthetics, Oxford University, Oxford, UK.
SURGERY
Trauma blunt/penetrating Vascular disease congenital/acquired Gastrointestinal haemorrhage Oncological Gynaecological Obstetric Failure of coagulation congenital/acquired (haemophilia drugs) Iatrogenic medical/surgical
1
208 208a
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
‘Tennis-score’ classification of graded haemorrhage Class
Percentage blood loss
Volume loss in a 70 kg adult
Importance
Symptoms
Signs
I
<15%
<840 ml
Minimal
II
15–30%
840–1680 ml
Significant
Anxiety Thirst
Tachycardia Tachypnoea Decreased pulse pressure (elevated diastolic, systolic may be normal) Minimal reduction in urinary output 20–30 ml per hour
III
30–40%
1680–2240 ml
Serious
Altered mental state
Marked tachycardia Marked tachypnoea Reduced systolic blood pressure
IV
>40%
2240 ml
Immediately lifethreatening
Significantly reduced level Marked tachycardia of consciousness Reduced systolic blood pressure Narrow pulse pressure or unrecordable diastolic pressure Negligible urine output Cold, pale skin
Slight tachycardia
2
pressin also helps to maintain blood pressure. Angiotensin II and renin increase aldosterone secretion which, combined with renin, cause salt and water retention to re-expand the blood volume. Constricted arterioles and reduced venous pressure combine to reduce the hydrostatic pressure in capillaries, which causes a net shift of fluid from the interstitial fluid to the capillaries, and in turn, from cells to the interstitium. After moderate (1000 ml) blood loss in a normal subject, plasma volume is restored in 12–72 hours. Preformed albumin rapidly enters the circulation from extravascular stores, protein-free fluid is mobilized from tissue fluids, which dilute plasma proteins and cells, but the reduction in haematocrit may take several hours. The rest of the plasma protein losses are replaced by synthesis over 3–4 days. Erythropoietin synthesis is induced, and the resulting reticulocytosis peaks at 10 days. Red cell mass is restored to normal over 4–8 weeks. The degree of haemorrhage combined with any co-existing pathology (and its treatment) determine the outcome and appropriate therapy. It is therefore useful to recognize the signs of various grades of haemorrhage (Figure 2). The percentage gradings of haemorrhage run like a tennis score, where the percentage blood volume loss is described as follows: • Class I (love–15%) • Class II (15–30%) • Class III (30–40%) is ‘match-point’ • Class IV (>40%) is virtually game, set and match. The symptoms, signs and severity in Figure 2 are relevant to a fit, healthy adult. However, they may be made more severe or even masked by other pathology or drug therapy. The response to initial therapy is more important than the class to which the patient initially belongs. Consequences of shock at the cellular level Ischaemia leads to generalized cellular damage, although the
SURGERY
degree of this damage varies considerably between tissues as a result of the diversity of normal oxygen consumption and magnitude of reduced blood flow in different tissue beds. The organs most sensitive to ischaemia are the: • heart • kidneys • liver • gastrointestinal tract • lungs • brain. The effects of ischaemia on all of these tissues have consequences for individual organ function which, when deranged, can have further cascading effects on the other organ systems. Anaerobic cellular metabolism causes the following: • Depletion of ATP and failure of sodium potassium pumps in the cell membrane. Sodium and water influx cause cellular swelling. • Progressive metabolic acidosis as a result of lactic acid production. Mitochondrial calcium loss further impairs the efficiency of oxidative phosphorylation and therefore interferes with organ-specific functions. Various substances such as histamine, serotonin, cytokines and lysosomal enzymes with localised and systemic inflammatory, cytotoxic, and vasoactive effects are then released from dying cells into the circulation. These substances result in progressive: • vasodilation • myocardial depression • increased vascular permeability • intravascular coagulation. These effects in turn may result in secondary damage to other organs (multi-organ dysfunction syndrome) 209 208b
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
Refractory shock (Figure 3) The outcome of haemorrhagic shock depends largely on the volume of blood lost. Some patients will die soon after haemorrhage, while others recover as compensatory mechanisms (combined with treatment) restore the circulation to normal. An intermediate group of patients remain in a shocked state for several hours and gradually become unresponsive to vasopressor drugs and even when blood volume is restored to normal, cardiac output remains depressed. Refractory shock occurs when the compensatory response of vasoconstriction is prolonged and causes hypoxic tissue damage, particularly in the splanchnic region. After about 4 hours, the precapillary sphincters dilate so that blood can enter these capillaries, but it stagnates because the venules remain constricted. Capillary hydrostatic pressure increases, causing net loss of fluid to the interstitium. Free radicals (e.g superoxide, hydroxyl) are released when granulocytes adhere to damaged vessel walls, which causes further tissue damage. Mucosal damage to the gastrointestinal system allows bacteria and their toxins from the gut to enter the circulation (translocation). The damaged reticulo-endothelial system of the liver is less able to remove these pathogens, hence they gain access to the systemic circulation. Cerebral ischaemia depresses the vasomotor and cardiac areas of the brain, causing vasodilation and reduced heart rate. The blood pressure further decreases, which worsens the reduced cerebral blood flow and therefore further
depresses the vasomotor and cardiac areas. Similarly, coronary blood flow is reduced because of hypotension and tachycardia, despite coronary vasodilation. Myocardial depression worsens the shock and acidosis, which in turn worsen the myocardial failure. If the myocardium is sufficiently compromised, it reaches a point where it can no longer restore normal cardiac output even when the blood volume is restored to normal. Pulmonary damage in the form of adult respiratory distress syndrome (ARDS, see Gunning, K E J, Surgery 2003; 21(3): 72–6) can occur as a late complication of haemorrhage (and its treatment). Pulmonary micro-emboli occur due to intravascular coagulation caused by damaged cells which release coagulants, and aggregates of platelets and erythrocytes washed out of hypoxic tissues. Monitoring/diagnostics Clinical monitoring: a patient who is haemorrhaging may rapidly progress through the clinical stages depending on the: • volume of the blood loss • rate of blood loss • the resuscitative measures. The situation is dynamic and therefore frequent clinical monitoring of the condition of the patient is vital. The following should be monitored: • heart rate
Refractory haemorrhagic shock �������������������������������������� ������������������������������������������ ����������������������������
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BP: blood pressure 3
SURGERY
210 208c
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
• respiratory rate • skin circulation (capillary refill) • pulse pressure and urine output (via a urinary catheter). The table of symptoms and signs demonstrates that the commonly used sign of blood pressure measurement is a late and therefore less useful sign. Non-clinical methods of monitoring can assist in the rapid recognition of deteriorating patients and the assessment of their response to treatment, but the clinician must be aware of the drawbacks of any of the techniques chosen. The following are used in both pre-hospital and hospital care: • pulse oximetry • non-invasive automated blood pressure cuffs • continuous ECG recordings. All of these monitors have specific limitations. In the monitoring of the haemorrhaging patient, the specific problems are poor function of pulse oximetry due to poor perfusion of extremities, difficulty in adhering ECG electrodes to sweaty skin and inaccuracy or failure to record blood pressure using non-invasive methods in hypotensive patients. Invasive blood pressure monitoring can facilitate: • accurate pulse rate measurement • blood pressure measurement • regular arterial sampling to measure blood gases, electrolyte, acid–base status, renal and hepatic function, blood glucose, coagulation, full blood count. The arterial blood pressure waveform normally displays a low frequency ‘swing’ in phase with respiration (Figure 4), showing a reduction during inspiration and an increase during expiration. This phasic pattern can be observed using continuous invasive blood pressure monitoring. It is exaggerated in hypovolaemia, and reduced in response to successful therapy. This phenomenon further supports the use of invasive blood pressure monitoring in hypovolaemic shock. This technique, however, requires specific expertise and takes longer to institute. Its use must not delay resuscitation and haemostasis. Central venous catheterization can be used to assess trends in right ventricular preload, and is a useful window into the left heart in patients with no lung disease and no selective right or
left ventricular dysfunction. These trends may be of assistance in assessing response to therapy or continuing blood loss. Pulmonary artery catheterization may be useful in situations where the central venous pressure is a less reliable indicator of left ventricular filling pressure. Neither central venous nor pulmonary artery catheterization provide a reliable assessment of circulating blood volume. Both require specialist expertise and time for insertion and have significant complications (e.g. pneumothorax, haemorrhage, ventricular perforation and tamponade, pulmonary infarction) associated with their use. It is therefore inappropriate to delay urgent investigations or surgery to allow their use. Fluid challenge – observation of the response to a fluid challenge is a valuable tool in the further assessment of the potentially hypovolaemic patient. If 1000–2000 ml Hartmann’s solution or saline is infused as rapidly as possible, the response will be determined by the severity of blood loss. • Some patients respond rapidly to a fluid challenge, and then remain haemodynamically normal on maintenance fluid. These patients have sustained minimal haemorrhage. • Some patients show a transient improvement after the fluid challenge, but the haemodynamic status deteriorates again, indicating continuing haemorrhage or inadequate resuscitation: these patients have lost 20–40% of their blood volume. • The remaining patients show little or no improvement following their fluid challenge (and continuing fluid resuscitation), and are likely to have lost more than 40% or their blood volume. Management Immediate management: the management of acute severe haemorrhage must be swift yet systematic, treating coexisting problems as they are found. Greater detail is given in the ATLS® protocol and (with minor adjustments) this forms a useful basic framework for the management of major haemorrhage even from non-traumatic causes. In common with any other emergency, the priorities are to assess and secure the: • Airway (with cervical spine control). • Breathing (high concentration of oxygen, treatment of any immediately life-threatening pathologies likely to compromise respiration). • Circulation (two wide-bore intravenous cannulae, blood drawn
a
120 115 110 105 100 95 90 85 80 75 70 65 60
Pressure (mmHg)
Pressure (mmHg)
Arterial pressure waveforms
0
Time (seconds)
6
b
120 115 110 105 100 95 90 85 80 75 70 65 60
0
Time (seconds)
6
Arterial pressure waveforms in normovolaemic a and hypovolaemic b subjects. Note how in b there is a low-frequency ‘swing’ in phase with respiration.
4
SURGERY
208d 211
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
for type and crossmatch and baseline laboratory tests, haemostasis and intravenous fluid therapy). • Disability (refers to neurological condition, which may reflect oxygenation and perfusion and/or cerebral pathology). • Exposure/environmental control (to allow thorough examination of the patient and protect the patient from hypothermia by drying and covering him or her with warm blankets, and using warm intravenous fluids for the resuscitation). • Monitoring (as detailed above) should be instituted as soon as possible, but should not delay treatment. Further investigation and treatment will depend upon the precipitating cause of the haemorrhage. Lengthy radiological procedures in an unstable patient are inappropriate, particularly if the site of haemorrhage is known or strongly suspected as a result of history and clinical examination. Continued resuscitation and surgical intervention to arrest further blood loss should be used to treat the haemorrhage.
Acceptable transfusion threshold – there are two opposing mechanisms which govern oxygen utilization in the anaemic patient. • As the haemoglobin concentration falls, the oxygen content per unit of blood is reduced in a linear way. • However, as the haemoglobin concentration falls, so too does the haematocrit, and hence the viscosity of the blood is reduced. This is beneficial in terms of microcirculatory blood flow. Given that oxygen utilization and extraction by tissues is a property of both the oxygen content (better with high haemoglobin) of the blood and its flow rate (better with low haemoglobin), the relationship between haematocrit and oxygen extraction is nonlinear. Hence, it is found empirically that a haemoglobin of around 8 to 9 g/dl is optimum. This has had the effect of minimizing the use of homologous blood transfusion, without adversely affecting outcome. Other strategies to reduce the need for homologous blood are beyond the scope of this article.
Fluid choice: The choice of fluid to use in the initial stages of resuscitation is the subject of debate. Most centres suggest that a balanced salt solution should be the first-line treatment, though debate continues between the choice of 0.9% saline or Hartmann’s solution. The point at which a colloid should be initially used (if at all) is also controversial. If the aim is prolonged haemodynamic improvement, colloid is superior to crystalloid, because colloid has the benefit of more effectively expanding the intravascular volume, and having a longer intravascular half-life. This assumes that the vascular endothelium is intact (which is invalid in pathological conditions). However, despite the lesser degree of oedema in the short term, colloids ultimately reach the interstitial space and may prolong tissue oedema and therefore organ dysfunction. An ‘ideal’ resuscitation fluid would be one with all the benefits of blood (not least its oxygen-carrying capacity and clotting factors) combined with the exclusive expansion of the intravascular compartment. More recently, the benefit of using aggressive fluid resuscitation has been questioned, with studies suggesting that immediate or aggressive fluid resuscitation in the setting of uncontrolled haemorrhage may be harmful, because it results in an increased haemorrhage volume and subsequently a greater mortality. This increased overall haemorrhage may result from higher perfusion pressures and dilution of clotting factors at the site of untreated injury. Postponement of fluid therapy until arrival in the operating theatre and restriction of fluid resuscitation have both been studied, and shown to be associated with no increased mortality and, in some publications, improved survival has been reported.
Donated human blood is at present the only substance in regular use to successfully carry oxygen in the clinical setting of human haemorrhagic shock, although many other potential solutions are under research (e.g. perfluorocarbons, haemopure, lysosome-encapsulated synthetic haemoglobin) and, in some cases, available clinically. The benefit of blood transfusion is that it can carry oxygen in the same physiological manner as the patient’s own blood, albeit with the reduced capacity as a result of storage. The side-effects associated with massive blood transfusion are significant. They include: • major and minor blood transfusion reactions • infectious diseases • hypothermia • coagulopathy • acidosis • ARDS.
Blood transfusion: after initial crystalloid/colloid resuscitation, blood transfusion will be required to improve the oxygen-carrying capacity of the circulating fluid. This will initially be in the form of packed cells, followed by appropriate blood components (e.g. platelets, clotting factors). The help of the haematologist should ideally be enlisted early in the management of massive haemorrhage. The volume and type of fluid chosen in the initial resuscitation and later management of patients presenting with haemorrhagic shock should be guided by response to therapy in terms of clinical, haemodynamic, haematological and biochemical status.
SURGERY
Treatment summary In the initial resuscitative stage of haemorrhagic shock, the priority is maintenance of perfusion with oxygen-rich blood, particularly of vital organs. This should be achieved by following the ‘airway, breathing and circulation’ protocol and securing haemostasis. If patients fail to respond to fluid replacement in this initial period, a search for other causes of hypotension should be made. If vasopressors become necessary to support perfusion at this stage, treatment is failing. Later, in patients with refractory shock, vasopressors may become necessary to protect the perfusion of vital organs. However, this will be achieved only at the expense of the perfusion of other tissue beds, whose ischaemia may be responsible for the refractory nature of the patient’s condition. Where massive blood loss has already occured, and surgery to secure haemostasis is failing because of coagulopathy (unresponsive to treatment with clotting products derived from blood), it may be appropriate to consider the use of antifibrinolytic or haemostatic drugs (e.g. tranexamic acid, aprotinin). u
FURTHER READING American College of Surgeons. Advanced Trauma Life Support for Doctors, 6th edition. Chicago: American College of Surgeons, 1997.
208e 212
© 2003 The Medicine Publishing Company Ltd
transfusion attempts carried a high mortality, and the procedure was banned in France in the 1670s. One of the earliest uses of transfusion in cardiovascular resuscitation was by the English physiologist James Blundell, who successfully used human-to-human transfusion in 1829 to treat severe post-partum haemorrhage. However, such therapies were not safe or reliable until the science underpinning blood typing, storage and donation were discovered throughout the twentieth century.
Haemorrhagic Shock M A Babb A D Farmery
Aetiology The aetiology of haemorrhagic shock is shown in Figure 1. Definitions Shock occurs when perfusion is inadequate to supply the metabolic requirements of the tissues. Classically it is divided into: • hypovolaemic • cardiogenic • distributive (septic/toxic/anaphylactic/neurogenic) • obstructive (mechanical, e.g. tension pneumothorax, pulmonary embolism, cardiac tamponade). Haemorrhage is defined as an acute loss of circulating blood. Haemorrhagic shock is the most common cause of hypovolaemic shock, and results in a combination of anaemic and ischaemic tissue hypoxia. The tissue hypoxia causes a progressive failure of cellular metabolism. Compensatory mechanisms and different oxygen requirements in various tissue beds cause a spectrum of severities of organ damage, which may result in early or late multiple-organ dysfunction and death. Haemorrhagic shock may coexist with other types of shock, for example after trauma where cardiogenic (from cardiac contusion) and septic shock (from wound contamination) may occur. History A relationship between blood and health has been recognized for some time, although the nature of the importance of blood was misunderstood. Galen (c. 130–200 AD) systematized the humoral theory of Hippocrates, and proved that arteries contain blood, although he suggested that blood travelled to all parts of the body through the veins. His descriptions of vivisection underline his understanding that haemorrhage would result from arterial damage, and that the resultant haemorrhage might kill the subject. He was a visionary when he wrote, ‘nothing upsets any operation like haemorrhage’. The concept of the importance of ‘intravascular volume’ as opposed to ‘blood’ was not fully appreciated until the nineteenth century. Richard Lower (1665) in London, UK, and Jean-Baptiste Denis (1667) in Paris, France, independently performed animalto-human blood transfusion. However, this was performed for the perceived benefits of blood as a therapeutic ‘humour’, rather than as an act of restorative homeostatic physiology. These early
Pathophysiology of haemorrhage Haemorrhage results in a fall in blood volume and therefore a fall in venous pressure and venous return to the heart. The consequent fall in preload to the atria causes a reduction in stroke volume of both right and left ventricles. The reduced arterial pulse pressure diminishes stretch on arterial baroreceptors, which results in an increased sympathetic output, causing vasoconstriction and reflex tachycardia which tends to compensate for the reduced stroke volume, so cardiac output is initially preserved. As haemorrhage increases (but while shock is still reversible), bradycardia occurs. With continued haemorrhage, however, the tachycardia reappears. The vessels of the heart and brain are the only ones spared from vasoconstriction, which serves to preserve the blood flow to these two organs least able to recover from ischaemia. Coronary vasodilation occurs because of the increased metabolic demands of the myocardium resulting from the tachycardia. The vasoconstriction is most marked in the skin, kidneys and viscera, which explains some of the symptoms, signs and late sequelae of haemorrhagic shock. Widespread reflex venoconstriction also helps to maintain the filling pressure of the heart. Adrenal medullary secretion is also stimulated by haemorrhage, and circulating catecholamines may lead to stimulation of the reticular formation, causing restlessness and apprehension. Restlessness may increase the muscular and thoracic pumping of venous blood. Reduction in oxygen-carrying capacity and flow cause anaemic and stagnant hypoxia, which combine with acidosis to stimulate chemoreceptors. This stimulates respiration and excites the vasomotor centre, causing further vasoconstriction. Increased plasma renin activity causes increased circulating levels of angiotensin II, which helps to maintain blood pressure and stimulates thirst by an action on the subfornical organ (ingestion of fluid would help to restore extracellular fluid volume). Vaso-
Aetiology of haemorrhagic shock • • • • • • • •
M A Babb is a Specialist Registrar at the John Radcliffe Hospital, Oxford, UK. A D Farmery is a Senior Lecturer in Anaesthetics, Oxford University, Oxford, UK.
SURGERY
Trauma blunt/penetrating Vascular disease congenital/acquired Gastrointestinal haemorrhage Oncological Gynaecological Obstetric Failure of coagulation congenital/acquired (haemophilia drugs) Iatrogenic medical/surgical
1
208 208a
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
‘Tennis-score’ classification of graded haemorrhage Class
Percentage blood loss
Volume loss in a 70 kg adult
Importance
Symptoms
Signs
I
<15%
<840 ml
Minimal
II
15–30%
840–1680 ml
Significant
Anxiety Thirst
Tachycardia Tachypnoea Decreased pulse pressure (elevated diastolic, systolic may be normal) Minimal reduction in urinary output 20–30 ml per hour
III
30–40%
1680–2240 ml
Serious
Altered mental state
Marked tachycardia Marked tachypnoea Reduced systolic blood pressure
IV
>40%
2240 ml
Immediately lifethreatening
Significantly reduced level Marked tachycardia of consciousness Reduced systolic blood pressure Narrow pulse pressure or unrecordable diastolic pressure Negligible urine output Cold, pale skin
Slight tachycardia
2
pressin also helps to maintain blood pressure. Angiotensin II and renin increase aldosterone secretion which, combined with renin, cause salt and water retention to re-expand the blood volume. Constricted arterioles and reduced venous pressure combine to reduce the hydrostatic pressure in capillaries, which causes a net shift of fluid from the interstitial fluid to the capillaries, and in turn, from cells to the interstitium. After moderate (1000 ml) blood loss in a normal subject, plasma volume is restored in 12–72 hours. Preformed albumin rapidly enters the circulation from extravascular stores, protein-free fluid is mobilized from tissue fluids, which dilute plasma proteins and cells, but the reduction in haematocrit may take several hours. The rest of the plasma protein losses are replaced by synthesis over 3–4 days. Erythropoietin synthesis is induced, and the resulting reticulocytosis peaks at 10 days. Red cell mass is restored to normal over 4–8 weeks. The degree of haemorrhage combined with any co-existing pathology (and its treatment) determine the outcome and appropriate therapy. It is therefore useful to recognize the signs of various grades of haemorrhage (Figure 2). The percentage gradings of haemorrhage run like a tennis score, where the percentage blood volume loss is described as follows: • Class I (love–15%) • Class II (15–30%) • Class III (30–40%) is ‘match-point’ • Class IV (>40%) is virtually game, set and match. The symptoms, signs and severity in Figure 2 are relevant to a fit, healthy adult. However, they may be made more severe or even masked by other pathology or drug therapy. The response to initial therapy is more important than the class to which the patient initially belongs. Consequences of shock at the cellular level Ischaemia leads to generalized cellular damage, although the
SURGERY
degree of this damage varies considerably between tissues as a result of the diversity of normal oxygen consumption and magnitude of reduced blood flow in different tissue beds. The organs most sensitive to ischaemia are the: • heart • kidneys • liver • gastrointestinal tract • lungs • brain. The effects of ischaemia on all of these tissues have consequences for individual organ function which, when deranged, can have further cascading effects on the other organ systems. Anaerobic cellular metabolism causes the following: • Depletion of ATP and failure of sodium potassium pumps in the cell membrane. Sodium and water influx cause cellular swelling. • Progressive metabolic acidosis as a result of lactic acid production. Mitochondrial calcium loss further impairs the efficiency of oxidative phosphorylation and therefore interferes with organ-specific functions. Various substances such as histamine, serotonin, cytokines and lysosomal enzymes with localised and systemic inflammatory, cytotoxic, and vasoactive effects are then released from dying cells into the circulation. These substances result in progressive: • vasodilation • myocardial depression • increased vascular permeability • intravascular coagulation. These effects in turn may result in secondary damage to other organs (multi-organ dysfunction syndrome) 209 208b
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
Refractory shock (Figure 3) The outcome of haemorrhagic shock depends largely on the volume of blood lost. Some patients will die soon after haemorrhage, while others recover as compensatory mechanisms (combined with treatment) restore the circulation to normal. An intermediate group of patients remain in a shocked state for several hours and gradually become unresponsive to vasopressor drugs and even when blood volume is restored to normal, cardiac output remains depressed. Refractory shock occurs when the compensatory response of vasoconstriction is prolonged and causes hypoxic tissue damage, particularly in the splanchnic region. After about 4 hours, the precapillary sphincters dilate so that blood can enter these capillaries, but it stagnates because the venules remain constricted. Capillary hydrostatic pressure increases, causing net loss of fluid to the interstitium. Free radicals (e.g superoxide, hydroxyl) are released when granulocytes adhere to damaged vessel walls, which causes further tissue damage. Mucosal damage to the gastrointestinal system allows bacteria and their toxins from the gut to enter the circulation (translocation). The damaged reticulo-endothelial system of the liver is less able to remove these pathogens, hence they gain access to the systemic circulation. Cerebral ischaemia depresses the vasomotor and cardiac areas of the brain, causing vasodilation and reduced heart rate. The blood pressure further decreases, which worsens the reduced cerebral blood flow and therefore further
depresses the vasomotor and cardiac areas. Similarly, coronary blood flow is reduced because of hypotension and tachycardia, despite coronary vasodilation. Myocardial depression worsens the shock and acidosis, which in turn worsen the myocardial failure. If the myocardium is sufficiently compromised, it reaches a point where it can no longer restore normal cardiac output even when the blood volume is restored to normal. Pulmonary damage in the form of adult respiratory distress syndrome (ARDS, see Gunning, K E J, Surgery 2003; 21(3): 72–6) can occur as a late complication of haemorrhage (and its treatment). Pulmonary micro-emboli occur due to intravascular coagulation caused by damaged cells which release coagulants, and aggregates of platelets and erythrocytes washed out of hypoxic tissues. Monitoring/diagnostics Clinical monitoring: a patient who is haemorrhaging may rapidly progress through the clinical stages depending on the: • volume of the blood loss • rate of blood loss • the resuscitative measures. The situation is dynamic and therefore frequent clinical monitoring of the condition of the patient is vital. The following should be monitored: • heart rate
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BP: blood pressure 3
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BASIC SCIENCE
• respiratory rate • skin circulation (capillary refill) • pulse pressure and urine output (via a urinary catheter). The table of symptoms and signs demonstrates that the commonly used sign of blood pressure measurement is a late and therefore less useful sign. Non-clinical methods of monitoring can assist in the rapid recognition of deteriorating patients and the assessment of their response to treatment, but the clinician must be aware of the drawbacks of any of the techniques chosen. The following are used in both pre-hospital and hospital care: • pulse oximetry • non-invasive automated blood pressure cuffs • continuous ECG recordings. All of these monitors have specific limitations. In the monitoring of the haemorrhaging patient, the specific problems are poor function of pulse oximetry due to poor perfusion of extremities, difficulty in adhering ECG electrodes to sweaty skin and inaccuracy or failure to record blood pressure using non-invasive methods in hypotensive patients. Invasive blood pressure monitoring can facilitate: • accurate pulse rate measurement • blood pressure measurement • regular arterial sampling to measure blood gases, electrolyte, acid–base status, renal and hepatic function, blood glucose, coagulation, full blood count. The arterial blood pressure waveform normally displays a low frequency ‘swing’ in phase with respiration (Figure 4), showing a reduction during inspiration and an increase during expiration. This phasic pattern can be observed using continuous invasive blood pressure monitoring. It is exaggerated in hypovolaemia, and reduced in response to successful therapy. This phenomenon further supports the use of invasive blood pressure monitoring in hypovolaemic shock. This technique, however, requires specific expertise and takes longer to institute. Its use must not delay resuscitation and haemostasis. Central venous catheterization can be used to assess trends in right ventricular preload, and is a useful window into the left heart in patients with no lung disease and no selective right or
left ventricular dysfunction. These trends may be of assistance in assessing response to therapy or continuing blood loss. Pulmonary artery catheterization may be useful in situations where the central venous pressure is a less reliable indicator of left ventricular filling pressure. Neither central venous nor pulmonary artery catheterization provide a reliable assessment of circulating blood volume. Both require specialist expertise and time for insertion and have significant complications (e.g. pneumothorax, haemorrhage, ventricular perforation and tamponade, pulmonary infarction) associated with their use. It is therefore inappropriate to delay urgent investigations or surgery to allow their use. Fluid challenge – observation of the response to a fluid challenge is a valuable tool in the further assessment of the potentially hypovolaemic patient. If 1000–2000 ml Hartmann’s solution or saline is infused as rapidly as possible, the response will be determined by the severity of blood loss. • Some patients respond rapidly to a fluid challenge, and then remain haemodynamically normal on maintenance fluid. These patients have sustained minimal haemorrhage. • Some patients show a transient improvement after the fluid challenge, but the haemodynamic status deteriorates again, indicating continuing haemorrhage or inadequate resuscitation: these patients have lost 20–40% of their blood volume. • The remaining patients show little or no improvement following their fluid challenge (and continuing fluid resuscitation), and are likely to have lost more than 40% or their blood volume. Management Immediate management: the management of acute severe haemorrhage must be swift yet systematic, treating coexisting problems as they are found. Greater detail is given in the ATLS® protocol and (with minor adjustments) this forms a useful basic framework for the management of major haemorrhage even from non-traumatic causes. In common with any other emergency, the priorities are to assess and secure the: • Airway (with cervical spine control). • Breathing (high concentration of oxygen, treatment of any immediately life-threatening pathologies likely to compromise respiration). • Circulation (two wide-bore intravenous cannulae, blood drawn
a
120 115 110 105 100 95 90 85 80 75 70 65 60
Pressure (mmHg)
Pressure (mmHg)
Arterial pressure waveforms
0
Time (seconds)
6
b
120 115 110 105 100 95 90 85 80 75 70 65 60
0
Time (seconds)
6
Arterial pressure waveforms in normovolaemic a and hypovolaemic b subjects. Note how in b there is a low-frequency ‘swing’ in phase with respiration.
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BASIC SCIENCE
for type and crossmatch and baseline laboratory tests, haemostasis and intravenous fluid therapy). • Disability (refers to neurological condition, which may reflect oxygenation and perfusion and/or cerebral pathology). • Exposure/environmental control (to allow thorough examination of the patient and protect the patient from hypothermia by drying and covering him or her with warm blankets, and using warm intravenous fluids for the resuscitation). • Monitoring (as detailed above) should be instituted as soon as possible, but should not delay treatment. Further investigation and treatment will depend upon the precipitating cause of the haemorrhage. Lengthy radiological procedures in an unstable patient are inappropriate, particularly if the site of haemorrhage is known or strongly suspected as a result of history and clinical examination. Continued resuscitation and surgical intervention to arrest further blood loss should be used to treat the haemorrhage.
Acceptable transfusion threshold – there are two opposing mechanisms which govern oxygen utilization in the anaemic patient. • As the haemoglobin concentration falls, the oxygen content per unit of blood is reduced in a linear way. • However, as the haemoglobin concentration falls, so too does the haematocrit, and hence the viscosity of the blood is reduced. This is beneficial in terms of microcirculatory blood flow. Given that oxygen utilization and extraction by tissues is a property of both the oxygen content (better with high haemoglobin) of the blood and its flow rate (better with low haemoglobin), the relationship between haematocrit and oxygen extraction is nonlinear. Hence, it is found empirically that a haemoglobin of around 8 to 9 g/dl is optimum. This has had the effect of minimizing the use of homologous blood transfusion, without adversely affecting outcome. Other strategies to reduce the need for homologous blood are beyond the scope of this article.
Fluid choice: The choice of fluid to use in the initial stages of resuscitation is the subject of debate. Most centres suggest that a balanced salt solution should be the first-line treatment, though debate continues between the choice of 0.9% saline or Hartmann’s solution. The point at which a colloid should be initially used (if at all) is also controversial. If the aim is prolonged haemodynamic improvement, colloid is superior to crystalloid, because colloid has the benefit of more effectively expanding the intravascular volume, and having a longer intravascular half-life. This assumes that the vascular endothelium is intact (which is invalid in pathological conditions). However, despite the lesser degree of oedema in the short term, colloids ultimately reach the interstitial space and may prolong tissue oedema and therefore organ dysfunction. An ‘ideal’ resuscitation fluid would be one with all the benefits of blood (not least its oxygen-carrying capacity and clotting factors) combined with the exclusive expansion of the intravascular compartment. More recently, the benefit of using aggressive fluid resuscitation has been questioned, with studies suggesting that immediate or aggressive fluid resuscitation in the setting of uncontrolled haemorrhage may be harmful, because it results in an increased haemorrhage volume and subsequently a greater mortality. This increased overall haemorrhage may result from higher perfusion pressures and dilution of clotting factors at the site of untreated injury. Postponement of fluid therapy until arrival in the operating theatre and restriction of fluid resuscitation have both been studied, and shown to be associated with no increased mortality and, in some publications, improved survival has been reported.
Donated human blood is at present the only substance in regular use to successfully carry oxygen in the clinical setting of human haemorrhagic shock, although many other potential solutions are under research (e.g. perfluorocarbons, haemopure, lysosome-encapsulated synthetic haemoglobin) and, in some cases, available clinically. The benefit of blood transfusion is that it can carry oxygen in the same physiological manner as the patient’s own blood, albeit with the reduced capacity as a result of storage. The side-effects associated with massive blood transfusion are significant. They include: • major and minor blood transfusion reactions • infectious diseases • hypothermia • coagulopathy • acidosis • ARDS.
Blood transfusion: after initial crystalloid/colloid resuscitation, blood transfusion will be required to improve the oxygen-carrying capacity of the circulating fluid. This will initially be in the form of packed cells, followed by appropriate blood components (e.g. platelets, clotting factors). The help of the haematologist should ideally be enlisted early in the management of massive haemorrhage. The volume and type of fluid chosen in the initial resuscitation and later management of patients presenting with haemorrhagic shock should be guided by response to therapy in terms of clinical, haemodynamic, haematological and biochemical status.
SURGERY
Treatment summary In the initial resuscitative stage of haemorrhagic shock, the priority is maintenance of perfusion with oxygen-rich blood, particularly of vital organs. This should be achieved by following the ‘airway, breathing and circulation’ protocol and securing haemostasis. If patients fail to respond to fluid replacement in this initial period, a search for other causes of hypotension should be made. If vasopressors become necessary to support perfusion at this stage, treatment is failing. Later, in patients with refractory shock, vasopressors may become necessary to protect the perfusion of vital organs. However, this will be achieved only at the expense of the perfusion of other tissue beds, whose ischaemia may be responsible for the refractory nature of the patient’s condition. Where massive blood loss has already occured, and surgery to secure haemostasis is failing because of coagulopathy (unresponsive to treatment with clotting products derived from blood), it may be appropriate to consider the use of antifibrinolytic or haemostatic drugs (e.g. tranexamic acid, aprotinin). u
FURTHER READING American College of Surgeons. Advanced Trauma Life Support for Doctors, 6th edition. Chicago: American College of Surgeons, 1997.
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