Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
Contents lists available at ScienceDirect
Best Practice & Research Clinical Anaesthesiology journal homepage: www.elsevier.com/locate/bean
8
Volume therapy in trauma and neurotrauma M.F.M. James, MBChB, PhD, FRCA, FFA(SA), Emeritus Professor * Department of Anaesthesia, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa
Keywords: trauma fluid therapy blood transfusion resuscitation crystalloids colloids
Volume therapy in trauma should be directed at the restitution of disordered physiology including volume replacement to reestablishment of tissue perfusion, correction of coagulation deficits and avoidance of fluid overload. Recent literature has emphasised the importance of damage control resuscitation, focussing on the restoration of normal coagulation through increased use of blood products including fresh frozen plasma, platelets and cryoprecipitate. However, once these targets have been met, and in patients not in need of damage control resuscitation, clear fluid volume replacement remains essential. Such volume therapy should include a balance of crystalloids and colloids. Pre-hospital resuscitation should be limited to that required to sustain a palpable radial artery and adequate mentation. Neurotrauma patients require special consideration in both pre-hospital and in-hospital management. © 2014 Elsevier Ltd. All rights reserved.
Trauma of various kinds is the leading cause of death in people under the age of 40 years, worldwide. The top priority in fluid resuscitation in the traumatised patient is the control of haemorrhage and the replacement of lost circulating volume with appropriate fluid therapy [1].
* Tel.: þ27 (0) 21 531 8295. E-mail addresses: [email protected], [email protected].
http://dx.doi.org/10.1016/j.bpa.2014.06.005 1521-6896/© 2014 Elsevier Ltd. All rights reserved.
286
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
Physiological consequences of trauma Circulatory adaptation Physical injury initiates a stress response aimed at directing blood flow and supply of basic nutrients to the so-called “fight or flight organs” e the heart, lungs, skeletal muscle and the brain e at the expense of a reduction in perfusion of the rest of the body. Redistribution of intra-renal blood flow, secretion of aldosterone and antidiuretic hormone result in sodium retention, minimal urine volume and retention of water in excess of sodium. The consequences are a reduction in urine volume, an increase in the urine concentration and a reduction in the concentration of plasma sodium with loss of potassium. Where these adaptive mechanisms fail to maintain adequate tissue perfusion in the face of trauma and volume loss, dire metabolic consequences ensue, resulting in tissue ischaemia and the metabolic consequences of cellular hypoxia. Even more deleterious is the global release of cytokines in response to injury. These substances are primarily designed for the mediation of local inflammatory responses, but with extensive injury, widespread release of cytokines predisposes to the development of systemic inflammation and endothelial damage. Endothelial glycocalyx The endothelial glycocalyx is essential for the functioning of infused fluids and damage to this surface layer may reduce or even eliminate the benefits of colloidal infusions. In trauma, the glycocalyx is readily damaged and shedding of the components of this layer occurs early and in proportion to the degree of injury [2]. Jacob and Chappell review the role of the glycocalyx elsewhere in this edition of Best Practice & Research: Clinical Anaesthesiology. Coagulopathy in trauma The physiology of coagulation is significantly disturbed in trauma as well as by resuscitation strategies. Trauma induced coagulopathy (TIC) has long been considered to be a secondary event related to consumption of coagulation factors and dilution of those factors by aggressive fluid administration, together with hypothermia and acidosis. When it occurs, it is a significant predictor of mortality [3] with an incidence ranging between 10 and 34% [4]. However, more recently it has been suggested that trauma itself induces a significant derangement of the clotting process. Consumptive coagulopathy has been advocated as a major mechanism for the development of TIC and has been associated with adverse outcomes including prolonged intensive care stay and multiple organ dysfunction syndromes [5]. A more recent alternative concept has been advocated suggesting that damage to the endothelial glycocalyx results in excess of production of activated protein C that not only inhibits normal thrombin activation of the coagulation cascade but also inhibits plasminogen activator inhibitor, resulting in enhanced fibrinolysis [4,6,7]. Severe tissue hypoxaemia and endothelial damage have also been postulated as drivers of the coagulopathic state [8]. In a recent study of TIC, two cohorts of moderately injured patients were studied, divided into those with and without early TIC (ETIC). Both cohorts showed increased thrombin activation with fibrin generation and increased fibrinolysis, but the ETIC group had received greater volumes of crystalloid prior to admission to hospital and these authors concluded that decreasing the amount of pre-hospital crystalloid administration together with early administration of coagulation factors may prevent the development of TIC [9]. The key message is that, through a variety of mechanisms, coagulation pathways are disrupted in severe trauma and attention to these disruptions is essential if improved survival is to be attained. Ideally, the presence of coagulopathy should be established prior to embarking on aggressive coagulation resuscitation unless it is obvious from the outset that the patient will require massive transfusion. Recent research has emphasised the value of point-of-care (POC) testing of coagulation such as thrombelastography (TEG® Coagulation Analyzer, Haemoscope Corporation, Niles, IL, USA) and thrombelastometry (ROTEM® Whole Blood Haemostasis Analyser, Pentapharm GmbH, Munich, Germany) to provide rapid assessment of clot formation [10]. Numerous reports attest to the potential
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
287
value of these technologies, but further evidence is required before they can be considered the standard of care [11e13]. Neural tissue injury Neurological injury represents a specific form of trauma with its own considerations. Damage suffered at the time of injury is largely irreversible, but substantial secondary insults frequently occur that are largely treatable or avoidable. Such secondary injuries can have serious implications for the long-term outcome of injured patients. Cerebral ischaemia and inflammatory mediators result in neuronal and astrocytic swelling which, together with vasogenic oedema, contribute to brain oedema [14]. These secondary insults are influenced by changes in cerebral blood flow (hypo- and hyperperfusion), impairment of cerebrovascular autoregulation, cerebral metabolic dysfunction and inadequate cerebral oxygenation. Furthermore, excitotoxic cell damage and inflammation may lead to apoptotic and necrotic cell death [14]. The damaged brain is particularly sensitive to changes in plasma osmotic pressure and the management of neural injury requires an appreciation of the constituents of resuscitation fluids and their possible effects on osmotic swelling of neural tissues. Spinal cord trauma raises additional complications in the form of spinal shock resulting in hypotension disproportionate to the volume of fluid lost. There is also emerging evidence that high-level spinal-cord injury (above T6) may result in disordered cerebral blood flow regulation [15]. The early management phase following cerebral trauma aims to achieve haemodynamic stability and limit secondary insults (e.g. hypotension, hypoxia) prior to definitive management. [16,17] Principles of volume therapy The objective of volume therapy in trauma is the restoration of tissue perfusion through the replacement of lost volume and the components of shed blood. However, both the volume and content of intravenous solutions have been highly controversial over the last hundred years and remain so today. History The advent of the First World War led to substantial advances in blood transfusion for trauma victims. The earlier discovery of sodium citrate as an anticoagulant allowed for the storage of whole blood that could be prepared in advance and held in reserve for the management of casualties, a practice that has been hailed as perhaps the most important medical advance of the war [18]. Only Group O blood was used as it had already been recognised as the “universal donor” [19]. The use of gelatin to replace lost plasma was also advocated by Robertson [19] and the efficacy of this colloid in haemorrhagic shock was supported by Hogan [20]. Similar practices using saline, colloid and whole blood were adopted in the Second World War, but by this time albumin and freeze-dried plasma were available to expand the pool of blood-based volume therapy. Following the Second World War, a paradigm shift occurred in trauma resuscitation with greater emphasis on resuscitation of the extracellular fluid space. This philosophy, initiated by Wiggers [21], was subsequently supported by Dillon [22] and Shires [23] and advocated the administration of a 3:1 ratio of crystalloid to shed blood. This ratio became widely used for resuscitation into the 21st-century despite a lack of evidence for its validity in the clinical situation. Although survival from the initial injury improved and the incidence of acute renal failure diminished, these strategies led to the emergence of pulmonary fluid overload and the Acute Respiratory Distress Syndrome (ARDS) [24]. In parallel with these high-crystalloid strategies, logistical issues led to the almost universal adoption of component therapy instead of whole blood, although there is a lack of evidence demonstrating that such an approach is equivalent, let alone superior to a whole blood strategy [25]. These high-volume crystalloid strategies have been widely criticised recently as increasing complications [26,27]. Surgical studies in the 21st Century demonstrated a significant reduction in perioperative complication rates, particularly those related to gut function, following the introduction of more conservative crystalloid administration strategies [28,29]. Clear evidence of the dangers of highvolume crystalloid resuscitation in trauma patients emanated from a study of supra-normal oxygen
288
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
delivery in an attempt to improve outcome. To achieve these targets, large volumes of crystalloid were required (>13L in the first 24 h) and this resulted in increased occurrence of abdominal compartment syndrome, multiple organ failure and death compared to a standard resuscitation group who received in the order of 7L [30]. Timing of resuscitation Timing of resuscitation is also controversial. During the First World War, it was found that soldiers treated appropriately within 1 h of being wounded sustained a mortality of 10%, whereas those who had treatment rendered 8 h post-injury had mortality rates as high as 75%, thus defining the ‘‘Golden Hour’’ concept [31]. However, at the same time, Cannon and Fraser called for the limited use of fluids and blood during haemorrhage, indicating that “Injection of a fluid that will increase blood pressure has dangers in itself. Haemorrhage in a case of shock may not have occurred to a marked degree because the blood pressure has been too low and the flow too scant to overcome the obstacle offered by a clot. If the pressure is raised before the surgeon is ready to check any bleeding that may take place, blood that is sorely needed may be lost” [32]. These authors also stated as follows: “When a patient must wait for a considerable period, elevation of his systolic blood pressure to approximately 85 mm Hg is all that is necessary and when profuse internal bleeding is present, it is wasteful of time and blood to attempt to get the patient's blood pressure up to normal.” This principle has recently been revisited. In 1994, Bickell et al. performed a randomised trial of 598 patients with penetrating torso injuries who presented with a prehospital systolic arterial pressure (SBP) 90 mmHg. An immediate resuscitation group received standard fluid therapy during hospital transfer whereas the delayed-resuscitation group received no fluid until they arrived in the operating room. The authors reported a small but significant 8% reduction in mortality in the delayed group, but this was confined to patients with cardiac injuries [33]. A subsequent trial randomised patients in haemorrhagic shock to one of 2 protocols: SBP > 100 mmHg (conventional) or a target SBP of 70 mmHg. Overall survival was virtually identical between the two groups, which these authors attributed to better in-hospital management [34]. These evolving ideas and strategies have resulted in the concept of damage control procedures, involving both damage control surgery and damage control resuscitation (DCR). The two concepts are inextricably linked. Current concepts of early resuscitation, particularly for penetrating trauma, involve a coordinated sequence starting with the pre-hospital phase with rapid hospital transport, hypotensive resuscitation for uncontrolled haemorrhage and maintenance of baseline tissue energy delivery [35]. Pre-hospital resuscitation The use of pre-hospital fluid resuscitation is controversial. In a large retrospective study, with rapid hospital transit times, initial SBP affected mortality, but fluid infusion had no influence [36]. An extensive review of 776,734 patients extracted from the TRAUMA Data Bank concluded that patients who received pre-hospital intravenous cannulation had an increased mortality [37]. However, this finding was widely criticised, predominantly on the basis that a causal relationship could not be established from the data available [38,39]. By contrast, a prospective study using data from 10 Level 1 trauma centres found that patients receiving limited pre-hospital intravenous fluid (up to 700 mL) had a decreased hospital mortality compared to those who received no fluid [40]. A retrospective review of the German Trauma Registry examined data from 948 matched pairs in which one group received
Contents lists available at ScienceDirect
Best Practice & Research Clinical Anaesthesiology journal homepage: www.elsevier.com/locate/bean
8
Volume therapy in trauma and neurotrauma M.F.M. James, MBChB, PhD, FRCA, FFA(SA), Emeritus Professor * Department of Anaesthesia, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa
Keywords: trauma fluid therapy blood transfusion resuscitation crystalloids colloids
Volume therapy in trauma should be directed at the restitution of disordered physiology including volume replacement to reestablishment of tissue perfusion, correction of coagulation deficits and avoidance of fluid overload. Recent literature has emphasised the importance of damage control resuscitation, focussing on the restoration of normal coagulation through increased use of blood products including fresh frozen plasma, platelets and cryoprecipitate. However, once these targets have been met, and in patients not in need of damage control resuscitation, clear fluid volume replacement remains essential. Such volume therapy should include a balance of crystalloids and colloids. Pre-hospital resuscitation should be limited to that required to sustain a palpable radial artery and adequate mentation. Neurotrauma patients require special consideration in both pre-hospital and in-hospital management. © 2014 Elsevier Ltd. All rights reserved.
Trauma of various kinds is the leading cause of death in people under the age of 40 years, worldwide. The top priority in fluid resuscitation in the traumatised patient is the control of haemorrhage and the replacement of lost circulating volume with appropriate fluid therapy [1].
* Tel.: þ27 (0) 21 531 8295. E-mail addresses: [email protected], [email protected].
http://dx.doi.org/10.1016/j.bpa.2014.06.005 1521-6896/© 2014 Elsevier Ltd. All rights reserved.
286
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
Physiological consequences of trauma Circulatory adaptation Physical injury initiates a stress response aimed at directing blood flow and supply of basic nutrients to the so-called “fight or flight organs” e the heart, lungs, skeletal muscle and the brain e at the expense of a reduction in perfusion of the rest of the body. Redistribution of intra-renal blood flow, secretion of aldosterone and antidiuretic hormone result in sodium retention, minimal urine volume and retention of water in excess of sodium. The consequences are a reduction in urine volume, an increase in the urine concentration and a reduction in the concentration of plasma sodium with loss of potassium. Where these adaptive mechanisms fail to maintain adequate tissue perfusion in the face of trauma and volume loss, dire metabolic consequences ensue, resulting in tissue ischaemia and the metabolic consequences of cellular hypoxia. Even more deleterious is the global release of cytokines in response to injury. These substances are primarily designed for the mediation of local inflammatory responses, but with extensive injury, widespread release of cytokines predisposes to the development of systemic inflammation and endothelial damage. Endothelial glycocalyx The endothelial glycocalyx is essential for the functioning of infused fluids and damage to this surface layer may reduce or even eliminate the benefits of colloidal infusions. In trauma, the glycocalyx is readily damaged and shedding of the components of this layer occurs early and in proportion to the degree of injury [2]. Jacob and Chappell review the role of the glycocalyx elsewhere in this edition of Best Practice & Research: Clinical Anaesthesiology. Coagulopathy in trauma The physiology of coagulation is significantly disturbed in trauma as well as by resuscitation strategies. Trauma induced coagulopathy (TIC) has long been considered to be a secondary event related to consumption of coagulation factors and dilution of those factors by aggressive fluid administration, together with hypothermia and acidosis. When it occurs, it is a significant predictor of mortality [3] with an incidence ranging between 10 and 34% [4]. However, more recently it has been suggested that trauma itself induces a significant derangement of the clotting process. Consumptive coagulopathy has been advocated as a major mechanism for the development of TIC and has been associated with adverse outcomes including prolonged intensive care stay and multiple organ dysfunction syndromes [5]. A more recent alternative concept has been advocated suggesting that damage to the endothelial glycocalyx results in excess of production of activated protein C that not only inhibits normal thrombin activation of the coagulation cascade but also inhibits plasminogen activator inhibitor, resulting in enhanced fibrinolysis [4,6,7]. Severe tissue hypoxaemia and endothelial damage have also been postulated as drivers of the coagulopathic state [8]. In a recent study of TIC, two cohorts of moderately injured patients were studied, divided into those with and without early TIC (ETIC). Both cohorts showed increased thrombin activation with fibrin generation and increased fibrinolysis, but the ETIC group had received greater volumes of crystalloid prior to admission to hospital and these authors concluded that decreasing the amount of pre-hospital crystalloid administration together with early administration of coagulation factors may prevent the development of TIC [9]. The key message is that, through a variety of mechanisms, coagulation pathways are disrupted in severe trauma and attention to these disruptions is essential if improved survival is to be attained. Ideally, the presence of coagulopathy should be established prior to embarking on aggressive coagulation resuscitation unless it is obvious from the outset that the patient will require massive transfusion. Recent research has emphasised the value of point-of-care (POC) testing of coagulation such as thrombelastography (TEG® Coagulation Analyzer, Haemoscope Corporation, Niles, IL, USA) and thrombelastometry (ROTEM® Whole Blood Haemostasis Analyser, Pentapharm GmbH, Munich, Germany) to provide rapid assessment of clot formation [10]. Numerous reports attest to the potential
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
287
value of these technologies, but further evidence is required before they can be considered the standard of care [11e13]. Neural tissue injury Neurological injury represents a specific form of trauma with its own considerations. Damage suffered at the time of injury is largely irreversible, but substantial secondary insults frequently occur that are largely treatable or avoidable. Such secondary injuries can have serious implications for the long-term outcome of injured patients. Cerebral ischaemia and inflammatory mediators result in neuronal and astrocytic swelling which, together with vasogenic oedema, contribute to brain oedema [14]. These secondary insults are influenced by changes in cerebral blood flow (hypo- and hyperperfusion), impairment of cerebrovascular autoregulation, cerebral metabolic dysfunction and inadequate cerebral oxygenation. Furthermore, excitotoxic cell damage and inflammation may lead to apoptotic and necrotic cell death [14]. The damaged brain is particularly sensitive to changes in plasma osmotic pressure and the management of neural injury requires an appreciation of the constituents of resuscitation fluids and their possible effects on osmotic swelling of neural tissues. Spinal cord trauma raises additional complications in the form of spinal shock resulting in hypotension disproportionate to the volume of fluid lost. There is also emerging evidence that high-level spinal-cord injury (above T6) may result in disordered cerebral blood flow regulation [15]. The early management phase following cerebral trauma aims to achieve haemodynamic stability and limit secondary insults (e.g. hypotension, hypoxia) prior to definitive management. [16,17] Principles of volume therapy The objective of volume therapy in trauma is the restoration of tissue perfusion through the replacement of lost volume and the components of shed blood. However, both the volume and content of intravenous solutions have been highly controversial over the last hundred years and remain so today. History The advent of the First World War led to substantial advances in blood transfusion for trauma victims. The earlier discovery of sodium citrate as an anticoagulant allowed for the storage of whole blood that could be prepared in advance and held in reserve for the management of casualties, a practice that has been hailed as perhaps the most important medical advance of the war [18]. Only Group O blood was used as it had already been recognised as the “universal donor” [19]. The use of gelatin to replace lost plasma was also advocated by Robertson [19] and the efficacy of this colloid in haemorrhagic shock was supported by Hogan [20]. Similar practices using saline, colloid and whole blood were adopted in the Second World War, but by this time albumin and freeze-dried plasma were available to expand the pool of blood-based volume therapy. Following the Second World War, a paradigm shift occurred in trauma resuscitation with greater emphasis on resuscitation of the extracellular fluid space. This philosophy, initiated by Wiggers [21], was subsequently supported by Dillon [22] and Shires [23] and advocated the administration of a 3:1 ratio of crystalloid to shed blood. This ratio became widely used for resuscitation into the 21st-century despite a lack of evidence for its validity in the clinical situation. Although survival from the initial injury improved and the incidence of acute renal failure diminished, these strategies led to the emergence of pulmonary fluid overload and the Acute Respiratory Distress Syndrome (ARDS) [24]. In parallel with these high-crystalloid strategies, logistical issues led to the almost universal adoption of component therapy instead of whole blood, although there is a lack of evidence demonstrating that such an approach is equivalent, let alone superior to a whole blood strategy [25]. These high-volume crystalloid strategies have been widely criticised recently as increasing complications [26,27]. Surgical studies in the 21st Century demonstrated a significant reduction in perioperative complication rates, particularly those related to gut function, following the introduction of more conservative crystalloid administration strategies [28,29]. Clear evidence of the dangers of highvolume crystalloid resuscitation in trauma patients emanated from a study of supra-normal oxygen
288
M.F.M. James / Best Practice & Research Clinical Anaesthesiology 28 (2014) 285e296
delivery in an attempt to improve outcome. To achieve these targets, large volumes of crystalloid were required (>13L in the first 24 h) and this resulted in increased occurrence of abdominal compartment syndrome, multiple organ failure and death compared to a standard resuscitation group who received in the order of 7L [30]. Timing of resuscitation Timing of resuscitation is also controversial. During the First World War, it was found that soldiers treated appropriately within 1 h of being wounded sustained a mortality of 10%, whereas those who had treatment rendered 8 h post-injury had mortality rates as high as 75%, thus defining the ‘‘Golden Hour’’ concept [31]. However, at the same time, Cannon and Fraser called for the limited use of fluids and blood during haemorrhage, indicating that “Injection of a fluid that will increase blood pressure has dangers in itself. Haemorrhage in a case of shock may not have occurred to a marked degree because the blood pressure has been too low and the flow too scant to overcome the obstacle offered by a clot. If the pressure is raised before the surgeon is ready to check any bleeding that may take place, blood that is sorely needed may be lost” [32]. These authors also stated as follows: “When a patient must wait for a considerable period, elevation of his systolic blood pressure to approximately 85 mm Hg is all that is necessary and when profuse internal bleeding is present, it is wasteful of time and blood to attempt to get the patient's blood pressure up to normal.” This principle has recently been revisited. In 1994, Bickell et al. performed a randomised trial of 598 patients with penetrating torso injuries who presented with a prehospital systolic arterial pressure (SBP) 90 mmHg. An immediate resuscitation group received standard fluid therapy during hospital transfer whereas the delayed-resuscitation group received no fluid until they arrived in the operating room. The authors reported a small but significant 8% reduction in mortality in the delayed group, but this was confined to patients with cardiac injuries [33]. A subsequent trial randomised patients in haemorrhagic shock to one of 2 protocols: SBP > 100 mmHg (conventional) or a target SBP of 70 mmHg. Overall survival was virtually identical between the two groups, which these authors attributed to better in-hospital management [34]. These evolving ideas and strategies have resulted in the concept of damage control procedures, involving both damage control surgery and damage control resuscitation (DCR). The two concepts are inextricably linked. Current concepts of early resuscitation, particularly for penetrating trauma, involve a coordinated sequence starting with the pre-hospital phase with rapid hospital transport, hypotensive resuscitation for uncontrolled haemorrhage and maintenance of baseline tissue energy delivery [35]. Pre-hospital resuscitation The use of pre-hospital fluid resuscitation is controversial. In a large retrospective study, with rapid hospital transit times, initial SBP affected mortality, but fluid infusion had no influence [36]. An extensive review of 776,734 patients extracted from the TRAUMA Data Bank concluded that patients who received pre-hospital intravenous cannulation had an increased mortality [37]. However, this finding was widely criticised, predominantly on the basis that a causal relationship could not be established from the data available [38,39]. By contrast, a prospective study using data from 10 Level 1 trauma centres found that patients receiving limited pre-hospital intravenous fluid (up to 700 mL) had a decreased hospital mortality compared to those who received no fluid [40]. A retrospective review of the German Trauma Registry examined data from 948 matched pairs in which one group received
