Early fluid resuscitation in severe trauma

How can patients who need DCR be identified?

A DCR strategy applies to patients who present with suspected major haemorrhage. While many definitions exist, the most practical in the acute trauma setting is for estimated blood transfusion volumes of over four units in the initial 2-4 h. Identifying these patients can be a challenge because they are often young with good physiological reserve and may have no physiological evidence of hypovolaemic shock.7 A number of tools have been developed to identify this group of patients; however, physician decision and experience have been found to be just as accurate.^{w9 w10 w11 w12 w13} Failure to identify these patients early and to apply DCR is associated with excess mortality.8

How can trauma patients in shock be identified?

Shock may be defined as a life threatening condition characterised by inadequate delivery of oxygen to vital organs in relation to their metabolic requirements.9 A systolic blood pressure of 90 mm Hg is commonly used to define both hypotension and shock; however, oxygen delivery depends on cardiac output rather than blood pressure. Homeostasis with peripheral vasoconstriction acts to preserve blood pressure even as circulating volume is lost. In patients who have had trauma, adequate cardiac output cannot be inferred from blood pressure. Only when blood loss approaches half the circulating volume or occurs rapidly is there a relation between the cardiac output and blood pressure.10 Patients presenting with hypotension, tachycardia, and obvious blood loss are readily identified as being in a state of haemorrhagic shock. However, many patients will maintain their pulse and blood pressure even after massive blood loss and tissue hypoxia. This condition is termed cryptic shock and is associated with increased mortality.^w14

The role of basic physiological parameters to estimate the severity of blood loss has been popularised in the advanced trauma life support courses and manuals.5 These materials describe physiological deterioration with increasing volumes of blood loss, and categorise four stages of shock. But data from a 1989-2007 analysis of the United Kingdom Trauma Audit Research Network database suggest that this model is not reflected in practice. Patients with progressive levels of blood loss to stage 4 haemorrhagic shock (equating to >2 L blood loss) were found to increase their pulse rates from 82 to 95 beats per minute, not to change respiratory rates or Glasgow coma scale, and maintain systolic blood pressures above 120 mm Hg.11 Although an important part of the initial assessment, physiological derangement alone is neither sensitive nor specific as a tool to identify shock in trauma patients.7

There is observational evidence from large datasets in the UK and United States that mortality increases in trauma patients in both blunt and penetrating trauma, while systolic blood pressure falls below 110 mm Hg.12 ^{w15 w16 w17 w18 w19} A US review of 870 634 sets of trauma records identified that for every 10 mm Hg below 110 mm Hg, mortality increased by 4.8%.12 Shock index does not improve after risk stratification of trauma patients.^w20

Metabolic assessment with lactate^{w21 w22} and base excess^{w23 w24} also predicts blood loss and mortality. Furthermore, these parameters may be increased from exercise around the time of injury (running, fighting) or may be (falsely) low if the hypoxic tissues are not being perfused sufficiently to wash anaerobic products into the circulation (for example, when a tourniquet is applied). For patients in whom central access is obtained, mixed venous oxygen saturation is also a good indicator of blood loss, with levels below 70% suggesting inadequate oxygen delivery.^w25

Estimated injuries and associated blood loss are an important part of the initial trauma assessment. Clinical examination is augmented by focused ultrasound assessment of the chest, pericardium, and peritoneal cavity (extended focused assessment with sonography in trauma (eFAST), a specific but insensitive test for blood loss); and computed tomography (a sensitive and specific test for blood loss).

What is permissive hypotension (hypovolaemic) resuscitation?

Permissive (hypotension) hypovolaemic resuscitation is used to describe a process that minimises administration of fluid resuscitation until haemorrhage control has been achieved, or is deemed unnecessary on definitive imaging. Resuscitation is the restoration of oxygen delivery and organ perfusion to match requirements. In the 1960s and 1970s, a strategy of high volume crystalloid resuscitation in a ratio of 3 mL per 1 mL of blood loss was promoted, which was thought to replace intravascular and interstitial losses and reduce the risk of organ failure.13 However, vigorous fluid resuscitation increases blood pressure, the effect of which increases hydrostatic forces on newly formed clot, dilutes clotting factors and haemoglobin, and reduces body temperature. These effects could promote further bleeding. In permissive hypotension, definitive resuscitation is deferred until haemostasis is obtained. It is now recognised that aggressive crystalloid resuscitation also impairs organ perfusion.14 ^w26

What evidence do we have for hypovolaemic resuscitation?

Considerable animal work has informed our understanding of hypovolaemic resuscitation. In summary, this research found that withholding fluid resuscitation from animals with critical blood loss (about half their circulating volume) was associated with death, whereas animals with less severe blood loss had a lower mortality with no fluid resuscitation.15

The table⇓ summarises three randomised controlled trials exploring the risks and benefits of hypovolaemic resuscitation.16 17 ^w27 These trials provide evidence of a mortality advantage in favour of this resuscitation strategy for truncal penetrating trauma and evidence of no harm in blunt trauma.

The National Institute for Health and Clinical Excellence has recommended that in older children and adults with blunt trauma, no fluid be administered in the prehospital resuscitation phase if a radial pulse can be felt, or for penetrating trauma if a central pulse is palpable.18 In the absence of this, 250 mL crystalloid fluid boluses are administered and the patient is reassessed until these pulses, as described, return.

Much of the evidence for hypovolaemic resuscitation was developed before the advent of haemostatic resuscitation, as described below. This period of hypovolaemic resuscitation is maintained for as short a period as possible, until the injury complex is defined and any sites of blood loss treated surgically or embolised.

Untreated hypovolaemic shock leads to microvascular hypoperfusion and hypoxia, leading to multiorgan failure.19 Hypovolaemic resuscitation sacrifices perfusion for coagulation and haemorrhage control. The trauma team carefully balances the resuscitation process to maintain organ perfusion but at lower than normal blood pressure to regulate bleeding. Based on the evidence available, we suggest that fluid resuscitation before haemorrhage control should aim to maintain a systolic blood pressure of 80 mm Hg or a palpable radial pulse or cerebration by using small volume boluses of 250 mL. This value is arbitrary with little evidence to support it. The 250 mL boluses are able to increase blood pressure, since the circulation is highly constricted with a small volume of distribution. In practice, achieving target blood pressures is challenging. Patients with severe injuries will probably need blood product based resuscitation, as described below.

Fluid resuscitation in traumatic brain injury

This review does not deal in detail with the complexities of resuscitation in brain injury; however, retrospective observational data for patients with traumatic brain injury suggest that any single reduction in mean arterial blood pressure below 90 mm Hg is associated with a doubling in mortality.^{w28 w29} Guidelines published by the Brain Trauma Foundation advocate maintaining a systolic blood pressure above 90 mm Hg but do not specifically state whether this is during active haemorrhage.^w30 Currently, there is controversy about whether the guidelines for permissive hypotension should be changed in the presence of head injury because there is no human evidence from prospective studies.

What is the role of blood products in trauma resuscitation?

Severe bleeding in trauma patients can result in disordered blood clotting. Until recently, this effect was thought to be a late phenomenon arising primarily from loss of coagulation factors during haemorrhage and dilution from resuscitation fluids. However, it is now recognised that trauma induced coagulopathy occurs within minutes of injury, and is associated with a fourfold increase in mortality.20 The process is multifactorial21 but is partly due to an endogenous coagulopathy that occurs as a result of tissue damage in severe shock.^w31 This understanding has led to changes in the management of trauma haemorrhage.

Haemostatic resuscitation

Haemostatic resuscitation is a combination of strategies targeting trauma induced coagulopathy to reduce bleeding and improve outcomes.^{w32 w33}

How do I identify patients with trauma induced coagulopathy?

Standard clotting tests from laboratories such as the prothrombin time do not show any of the key derangements in trauma induced coagulopathy, such as reduced clot strength and fibrinolysis.25 Furthermore, in a trauma setting, it is impractical to wait for tests that can take up 1 h to process. The point of care versions of these tests (such as the prothrombin time) are prone to be under-read in the presence of low haematocrits. These difficulties have led to a renewed interest in the use of thromboelastography—a point of care assessment of clot generation, strength, and breakdown. This procedure has the potential to provide a rapid assessment of the whole clotting process, but it has not yet been validated in the acute setting.25 In the absence of a validated diagnostic test at the point of care, management is therefore blind to the status of the coagulation system and relies on clinical judgment and empiric therapy.

What fluids should be used to resuscitate trauma patients who do not need DCR?

Patients who do not need DCR need no immediate resuscitation until definitive imaging has identified the underlying injuries. These patients should be observed carefully for signs of physiological and metabolic deterioration, consequent on disease progression with blood loss, visceral injury, and pericardial or pleural tamponade. Debate continues on the relative merits of colloid or crystalloid based resuscitation strategies, with a recent Cochrane review concluding that there was no evidence that survival was better with one or the other solution.26

However, a subgroup analysis of 460 patients with traumatic brain injury (Glasgow coma scale ≤13) from a large randomised controlled trial comparing the safety of albumin in normal saline with normal saline identified a survival advantage in the crystalloid group (33.2% v 20.4%, P=0.003).27

Hypertonic solutions have been proposed to improve cerebral perfusion and reduce cerebral oedema, and have been advocated for resuscitation of patients with traumatic brain injury.^w40 A meta-analysis of eight randomised trials identified a survival advantage in this group,^w41 but a randomised controlled trial of 229 patients with hypotension and severe traumatic brain injury (Glasgow coma scale <9) who received prehospital resuscitation with hypertonic or normal saline had almost identical survival and neurological function six months after injury.28 Furthermore, a recent randomised controlled trial of prehospital use of hypertonic solutions was terminated by the data and safety monitoring board after randomisation of 1331 patients, having met prespecified futility criteria. Among patients with severe traumatic brain injury not in hypovolaemic shock, initial resuscitation with either hypertonic saline or hypertonic saline or dextran, compared with normal saline, did not result in improved neurological outcome or survival at six months.29 Thus, we suggest the use of crystalloid based fluid administration in this cohort of patients who are less severely injured.

Once haemostasis is achieved, what should be done to ensure adequate resuscitation in severe trauma?

Once haemostasis has been achieved with surgical intervention, fracture splintage or angiography, or the requirement for these interventions identified as not necessary, then definitive resuscitation is required. If patients are resuscitated to normal blood pressure and pulse without further parameters being used to evaluate for tissue hypoxia, over half of patients would be inadequately resuscitated, with increased morbidity and mortality.30 ^w42 Resuscitation to targets of oxygen delivery or use is termed goal directed therapy, and good quality evidence from randomised trials indicates that this approach should be used in trauma; indeed, the original evidence for this approach came from trauma studies.^{w43 w44 w45 w46 w47} 31 32

What other agents should be used in the initial resuscitation period?

Hyperfibrinolysis is common after trauma, owing to associated hypovolaemic shock and tissue injury.^w48 In a recent, large, multinational randomised controlled trial researchers targeted a specific component of trauma induced coagulopathy—hyperfibrinolysis. They showed a reduction in mortality with the use of tranexamic acid, which has antifibrinolytic properties (1 g delivered over 15 min, then 1 g over 4 h, commenced within 3 h of injury).33