Anaesthesia, 2011, 66, pages 10351047doi:10.1111/j.1365-2044.2011.06874.

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REVIEW ARTICLE

Early hospital care of severe traumatic brain injury

R. T. Protheroe1 and C. L. Gwinnutt2
1 Consultant in Intensive Care Medicine and Anaesthesia, 2 Consultant Anaesthetist, Salford Royal NHS Foundation Trust, Salford, UK

Summary

Head injury is one of the major causes of trauma-related morbidity and mortality in all age groups in the United Kingdom, and anaesthetists encounter this problem in many areas of their work. Despite a better understanding of the pathophysiological processes following traumatic brain injury and a wealth of research, there is currently no specic treatment. Outcome remains dependant on basic clinical care: management of the patients airway with particular attenti on to preventing hypoxia; avoidance of the extremes of lung ventilation; and the maintenance of adequate cerebral perfusion, in an attempt to avoid exacerbating any secondary injury. Hypertonic uids show promise in the management of patients with raised intracranial pressure. Computed tomography scanning has had a major impact on the early identication of lesions amenable to surgery, and recent guidelines have rationalised its use in those with less severe injuries. Within critical care, the importance of controlling blood glucose is becoming clearer, along with the potential benecial effects of hyperoxia. The major improvement in outcome reects the use of protocols to guide resuscitation, investigation and treatment and the role of specialist neurosciences centres in caring for these patients. Finally, certain groups are now recognised as being at greater risk, in particular the elderly, anticoagulated patient.

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Correspondence to: Dr Richard Protheroe Email: richard.protheroe@srft.nhs.uk Accepted: 22 July 2011

Head injury is a common problem in the UK. Approximately 1 000 000 patients attend emergency departments annually, 100 000 are admitted, 10 000 will require treatment in a neurosurgical unit and the overall mortality is 610 per 100 000 persons per annum [1]. Many more will survive with long-term disabilities, and the overall cost, both nancial and societal, of caring for these patients is enormous. In the younger population, it is mainly men who are affected, usually as a result of road trafc accidents or assaults, whereas falls tend to predominate in the more elderly age group [2]. Alcohol consumption is a major factor, contributing to both the immediate trauma through acute intoxication and long-term outcomes through chronic abuse. It is now accepted that the fundamental principles of the early management of head-injured patients should focus on establishing and maintaining a clear airway by intubation, using appropriate analgesia and sedation, to

allow oxygenation and ventilation, resuscitation of the circulation to ensure adequate and stable cerebral perfusion, avoidance of hypo- and hyperglycaemia and the rapid identication of a surgically treatable lesion (typically an intracerebral haematoma). Although often described as the ABCDE approach, each of these stages should be tailored specically to the needs of the head-injured patient, starting in the prehospital environment and continuing in a seamless fashion throughout their time in hospital. In the past decade, investigations into the therapeutic use of steroids and hypothermia appeared to offer the prospect of improving outcome. However, the CRASH study demonstrated that corticosteroids should not be used routinely in the treatment of head injury [3], and a Cochrane review found no evidence that hypothermia is benecial in the treatment of head injury [4]. However, there is now evidence to support the view that optimal care and outcome is best achieved by taking all

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moderate and severe head injuries either directly, or transferring them rapidly, to a specialist neurosciences centre for multi disciplinary management including neuroradiology, anaesthesia, neurosurgery and critical care [5].

management of head-injured patients can be summed up as the need for speed.

Recognising at risk patients

Pathophysiology

Pathophysiologically, head injury is classically divided into primary and secondary injuries. Primary injury is the result of energy transfer to the brain at the time of the traumatic event, damaging neural, glial and vascular structures. As a result, there is damage to cell membranes, which increases permeability and disrupts ionic homeostasis with axonal tissue being the most vulnerable [6]. Subsequently, there is cellular swelling and numerous neurotoxic events mediated through increased levels of intracellular calcium [7]. The primary injury can only be addressed by prevention and improved safety such as legislation on the use of seat belts and motor cycle crash helmets, air-bags in motor vehicles and speed restrictions and, more recently, in the prevention of falls in the elderly [8]. Traditionally, secondary injury has been described as the consequence of physiological insults that may occur following traumatic injury to the brain or other body areas resulting in hypoxia, hypotension, hypo- or hypercapnia, hypo- or hyperglycaemia, hyperthermia and seizures. However, this may be too simplistic as experimental evidence suggests that separation of these two injury events is somewhat articial, with secondary injury being initiated at the time of the primary injury in the areas of damaged brain and spreading to the surrounding areas [7]. It may be more accurate to view the secondary injury as an inevitable process that is exacerbated by the physiological insults described above, but may be modied by medical intervention. This view of the pathophysiology may explain the historical observation that around one third of patients who died as a result of their head injury either talked or obeyed commands before their death, suggesting that their primary injuries were not lethal and death was due to an ongoing process that may be compounded by relatively poor care. Not surprisingly, therefore, rapid recognition of the severity of the injury, targeted resuscitation and early specialist medical and surgical management have long been recognised as playing an important role in improving outcome [5, 912]. The need for this rapidity of intervention at all stages, in the early

Although young adult men are particularly at risk of moderate and severe head injury due to occupational and recreational activities [13], it is the elderly who have the worst outcomes [1315], with mortality and functional disability rates almost twice those of younger patients [16]. Gender is also important; women have a signicantly greater frequency of brain swelling and intracranial hypertension compared with male patients [17], and lower rates of survival 6 months after injury [18]. However, in the early management of the headinjured patient, the one key group of patients that must be identied rapidly are those taking anticoagulants and antiplatelet drugs. Intracerebral haemorrhage may be both the cause and effect of trauma in the elderly, particularly if the patient is anticoagulated [19]. Warfarin use appears to be associated with a higher frequency of isolated head trauma, more severe head trauma and a greater likelihood of death [20]. Even after a simple fall, patients > 65 years-old taking warfarin have mortality greater than twice those not warfarinised [21]. The elderly are also more likely to present with a supratherapeutic international normalised ratio (INR) due to poor compliance, poor nutrition or hepatic disease. In anticoagulated patients with a severe head injury (Glasgow Coma Scale (GCS) 8), the INR at presentation was greater than 5.0 in 50%, and the overall mortality was almost 90%. Of 77 patients with GCS 1315, 56 deteriorated clinically with a mortality rate of > 80% [22]. In view of the devastating effects of anticoagulation, all elderly patients should have their coagulation checked on admission. Whether warfarin should be reversed with either fresh frozen plasma or prothrombin complex is unclear, as there are insufcient data from studies to determine the optimum use and timing of reversal therapy [23]. A more liberal computed tomography (CT) scanning policy, making it mandatory in patients with a coagulopathy independent of head trauma severity, would seem pragmatic. It has been estimated that instituting such a policy would increase the CT scanner workload by less than 2%, with a one in four probability of identifying an intracranial lesion [24]. The situation in those patients taking antiplatelet therapy is less clear. Tauber et al. described 100 consecutive trauma patients > 65 years-old, with a

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mild head injury (GCS = 15) and taking low-dose aspirin who were rescanned 1224 h after an initial negative scan. Four patients were identied as having secondary intracranial haemorrhages, one of whom died. The authors suggested that this group of patients should either have a repeat CT scan after 1224 h or, alternatively, be observed in hospital for at least 48 h [25]. In a retrospective review of head-injured patients, 25% of those taking aspirin who fullled the criteria for a CT scan had an intracerebral haemorrhage compared with 15% of those taking warfarin. The authors concluded that the risk of intracranial bleeding in patients receiving antiplatelet therapy may be increased and clinical judgment should be used to assess the need for an urgent scan in these patients [26].

Management

Severe traumatic brain injury is a clinical situation in which basic resuscitation and management has to be initiated before a complete investigation of the full extent of the injuries can be performed. Consequently, discussion of the early management with the relevant evidence is presented here ahead of the investigations. For nearly 20 years, the profoundly detrimental effect of hypoxia and hypotension on outcome after head injury has been well known [12, 27]. Early, safe establishment of a denitive airway, followed by controlled lung ventilation, will allow control of the arterial gas content, in particular, the prevention of hypoxia. Venous access, adequate uid resuscitation and, probably, inotropic or vasopressor support will be needed to counter the hypotensive effects of sedatives and analgesics to maintain the cerebral perfusion pressure (CPP). However, even now such management is not ubiquitous [28]. Furthermore, the situation may be compounded in the patient with multiple injuries, where the strategy of permissive hypotensive for the management of penetrating thoraco-abdominal trauma may lead to clinical conict with a co-existing head injury [29, 30].

Oxygenation and ventilation The devastating effects of hypoxia in head-injured patients are well known. Despite improvements in prehospital care, hypoxia is still a threat. Patients with a potentially survivable head injury who suffer at least one hypoxic episode (SpO2 < 92%) during transfer to hospital are more than twice as likely to die as those who are not hypoxic [31]. In an attempt to address this issue, there has been an increased emphasis on the use

of tracheal intubation, but the evidence of its efcacy appears to be conicting. It should be noted that in many studies, prehospital airway management is predominantly non-physician led, with the most seriously injured often undergoing intubation without the use of sedation [32]. In a retrospective analysis of 2491 patients from the National Trauma Data Bank, patients with multiple injuries and a GCS score of 3 had almost double the mortality with prehospital intubation compared with intubation on arrival at hospital. Those with isolated head trauma and intubation prehospital were also more likely to die (OR 2.0; 95% CI 1.4 2.9) [33]. However, in a prospective, controlled trial in adults with severe traumatic brain injury in an urban setting, patients were randomly assigned to either prehospital rapid sequence intubation by paramedics or transported to a hospital emergency department for intubation by physicians. The proportion of patients with a favourable outcome was 51% in the paramedic intubation group compared with 39% in the hospital intubation group (RR 1.28; 95% CI 1.001.64, p = 0.046) [34]. These ndings may reect the suboptimal performance of intubation or the adverse effects of inappropriate lung ventilation that may offset the potential benets of the procedure, rather than intubation itself being detrimental. The effects of uncontrolled ventilation prehospital via either a face mask or tracheal tube can be dramatic; both hypocarbia and hypercarbia as assessed by analysis of arterial blood gases on presentation at hospital are associated with increased in-hospital morbidity and mortality [35, 36]. When targeted lung ventilation (arterial PCO2 4 5.2 kPa) was used in the emergency department for head-injured patients undergoing intubation before arrival at hospital, those in whom the target was achieved had a mortality of 21.2% compared with 33.7% for those who remained outside this range (p = 0.03) [37]. Although it would seem easy to address this by ensuring that all head-injured patients have their lung ventilation monitored, in the early phases of care this is most likely to be through the use of end-tidal devices, and in patients with severe chest trauma or hypotension and metabolic acidosis, there may be a signicant discrepancy between arterial PCO2 and end-tidal PCO2, leading to an underestimation of the former [38]. Hyperventilation has been used widely to reduce increased intracranial pressure (ICP) [39], but this reduces cerebral blood ow (CBF) at a time when it may already be compromised, risking cerebral ischaemia and contributing to secondary injury. In 1991,

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Muizelaar et al., in a randomised controlled study, found a worse outcome in patients treated with prophylactic hyperventilation [40]. More recently, studies using positron emission tomography to investigate oxygen utilisation have demonstrated the deleterious effects of hyperventilation on the injured brain, despite improvements in CPP and IPP [41]. Hyperventilation appears consistently to reduce CBF and result in an increase in both oxygen extraction ratio and ischaemic brain volume. These ndings led Cole and colleagues to conclude that hyperventilation causes an acute reduction in cerebral blood ow and increase in cerebral metabolic rate for oxygen (CMRO2) that presents a physiological challenge to the traumatised brain, compromising oxidative metabolism. Such ischaemia is underestimated by common bedside monitoring tools, and may represent a signicant mechanism of avoidable neuronal injury following head trauma [42]. Hyperventilation should only be considered as a rescue therapy in patients with raised ICP and signs of imminent brainstem herniation, and it should be avoided in the rst 24 h after injury when CBF is often critically reduced. If moderate hyperventilation is used, it should be initiated in a critical care area in conjunction with monitoring to ensure adequate cerebral oxygenation (such as jugular venous oxygen saturation or brain tissue oxygen tension) [43]. If prevention of hypoxia is so critical, does increasing the amount of oxygen have any potential benet? Recently, interest has been shown in the use of hyperoxia as a treatment for patients with traumatic brain injury, on the basis that mitochondrial dysfunction is known to occur in both stroke and traumatic brain injury [44]. Early studies showed that hyperoxia decreased lactate levels in brain microdialysate, suggesting improved aerobic metabolism [45, 46]. In 69 patients with severe traumatic brain injury, a comparison of hyperbaric oxygen, normobaric oxygen (FIO2 1.0) and standard care found improved indices of cerebral oxygenation and aerobic metabolism with a brain tissue PO2 (PbtO2) of 26 kPa or greater [47]. However, using PET scanning to directly measure CMRO2 before and after ventilation with 100% oxygen, Diringer and colleagues found that there was no change in either CBF or CMRO2, indicating that normobaric hyperoxia did not improve brain oxygen metabolism [48]. In a registry-based analysis of the effect of hypoxaemia and hyperoxaemia on outcome following moderate to severe traumatic brain injury, both hypoxaemia and extreme hyperoxaemia were

associated with decreased survival, with data suggesting an optimal arterial PO2 in the range 14.664.9 kPa [49]. Using PbtO2 in addition to normal monitoring (ICP, CPP), to ensure adequate cerebral oxygenation in patients with severe traumatic brain injury, PbtO2directed care (including eubaric hyperoxia, triple H therapy (hypertension, haemodilution and hypervolaemia) and maintaining haemoglobin concentration > 12.5 g.dl)1) PO2 (PbtO2) was associated with a lower mortality rate than conventional therapy (25.7% vs 45.3%, p < 0.05). The authors suggested that when a low PbtO2 can be corrected, such treatment maybe associated with reduced patient mortality and improved patient outcome after severe traumatic brain injury [50]. In a retrospective review of their results using PbtO2-directed therapy compared with historic controls using ICP CPP directed therapy, Narotam et al. found that a combination of increased ICP and reduced PbtO2 2 h after admission resulted in an increased risk of death at 48 h (OR 14.3). Six months after the injury, patients treated with PbtO2-directed therapy had a better outcome as assessed using the Glasgow Outcome Scale (GOS) [51]. In contrast, Martini and colleagues, investigating the use of PbtO2 monitoring in conjunction with ICP monitoring, found no reduction in mortality compared with ICP monitoring alone. In fact, brain tissue oxygen monitoring was associated with worse neurological outcome and increased hospital resource utilisation [52]. The need for rapid identication and correction of hypoxia remains undisputed. However, the evidence for using supranormal concentrations of oxygen remains unclear, and it would seem that it is most likely to be of benet when its use is targeted. This requires invasive PbtO2 monitoring a technique currently restricted to critical care areas. Further studies are required to identify the role of hyperoxia in the management of patients with brain injury.

Blood pressure management Hypotension has a signicant adverse effect on outcome after head injury. In a prospective study published nearly 20 years ago, early hypotension was shown to cause a doubling of mortality (55% vs 27%), which increased to 65% if shock was present on admission to hospital. These effects were independent of age, admission GCS motor score, hypoxia or associated severe extracranial trauma [53]. In a prospective cohort study, mortality increased with the number and duration of hypotensive episodes (systolic

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pressure < 90 mmHg) during resuscitation within the emergency department, with an OR of 8.1 for death, when there were more than two episodes of hypotension [28]. In a retrospective case-control study, nonsurviving patients with traumatic brain injury were found to have had lower mean arterial pressures 4 h after arrival than survivors, with a fourfold increase in the odds of non-survival if the mean arterial pressure was < 65 mmHg during this period [27]. Despite this clear message, hypotension remains a signicant cause of morbidity and mortality after head injury. In the early resuscitation of head-injured patients systolic blood pressure is usually measured, but it is the CPP that determines adequacy of cerebral blood ow. This is dependent on mean arterial blood pressure and ICP, and the latter is rarely measured until patients reach a critical care unit. The optimal mean arterial pressure or CPP varies depending on the guidelines used (see below), but it is becoming clear that perfusion requirements may not only vary within the injured brain but may also differ depending on the elapsed time since the injury. Such heterogeneity, which exists both within and between patients, suggests that individualised therapy may be an appropriate treatment strategy, and in patients with lower GCS scores, a higher CPP may be appropriate [54, 55]. Intravenous uids are the primary means to maintain blood pressure. However, there is continuing debate about the volumes and formulation of uid used and the potential exacerbation of cerebral oedema in the face of a disrupted blood-brain barrier. Although it is widely accepted that hypotonic uids should not be used, more recent interest has been in the use of hypertonic uids for resuscitation of patients with traumatic brain injury. The benets include smaller volumes that can be given more rapidly to restore cerebral perfusion, a reduction in cerebral oedema and modulation of the inammatory response, helping reduce subsequent neuronal injury [56, 57]. Early studies of their use suggested that they were benecial [5860], but more recent studies have found mixed results. In hypotensive head-injured patients (GCS 8), hypertonic saline (HTS) was associated with a 20% increase in CPP, and an elevation in PbtO2, resulting in improved brain tissue oxygenation [61]. Using S100B, neuron-specic enolase and myelin-basic protein as biomarkers of brain injury, giving 250 ml 7.5% hypertonic saline 6% dextran70 (HSD) correlated with a better outcome after severe traumatic brain injury compared with 0.9% saline [62]. A prospective

observational study of 51 trauma patients receiving 500 ml 5% HTS during initial resuscitation found no difference in mortality compared with controls. However, there was a trend towards decreased mortality in patients with a GCS 8 and a Head Abbreviated Injury Scale score 3 (25.0% vs 42.5%). No adverse sequelae were seen as a result of hypernatraemia in the HTS group (Na+ = 150 vs 143 mmol.l)1) [63]. More recently, a large multicentre trial in North America, investigating the use of a single bolus of HSD, HTS or 0.9% saline in trauma patients with a GCS 8 without hypovolaemic shock, was terminated by the data and safety monitoring board having met prespecied futility criteria. There was no improvement in neurological outcome or survival at 6 months after initial resuscitation with either HTS or HSD, compared with normal saline [64]. Despite its theoretical advantages it appears that, the role of HTS with or without dextran is less clear than originally perceived, and there is no obvious clinical advantage or justication in replacing the currently used isotonic uids with HTS. The problem is compounded by the heterogeneity of the studies, in particular the types and volumes of solutions used. What can be said with greater certainty is that albumin no longer has a role in the resuscitation of patients with head injuries. In a post hoc analysis of the SAFE data looking specically at patients with severe brain injury, investigators found a worse outcome in those patients resuscitated with human albumin as opposed to saline [65].

Management of raised ICP Before utilising the more advanced approaches to control the ICP, the more basic and simple manoeuvres should not be forgotten. Patient positioning can have a dramatic effect on the ICP and should be regularly reviewed. The gravitational effects of positioning head-up (to 30) to aid venous drainage and prevent venous congestion are well known. The neck should be maintained in a neutral position to avoid the venous obstruction caused by excessive exion or rotation. Semi-rigid collars should also be removed as early as possible as they may also contribute to raised ICP [66]. Adequate sedation and analgesia are important. Intubated patients require ongoing sedation, for example, with propofol or midazolam, supplemented with an analgesic. Care with the dosage is essential to avoid both over- and undersedation. In the immediate management, neuromuscular blocking drugs are also frequently used to facilitate mechanical ventilation and prevent coughing.

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The use of mannitol for the reduction of elevated ICP was rst described in the 1960s, and it has subsequently remained the rst-line osmotic agent for the reduction of ICP [67, 68]. In 2007, a Cochrane review of the use of mannitol therapy for raised ICP concluded that although it may have a benecial effect on mortality when compared with pentobarbital treatment, there may be a detrimental effect on mortality when compared with HTS [69]. Since this review, there have been a number of studies, many of which report only a small number of patients and using different treatment protocols, comparing the efcacy of mannitol and HTS as a treatment for raised ICP. When equimolar infusions of mannitol and HTS are used, their action on reducing ICP appears to be similar in duration and efcacy [70, 71]. An evaluation of the use of 30 ml 23.4% saline for raised ICP found a decrease in ICP and an improvement in PbtO2 and CPP greatest in patients with a high baseline ICP [72]. Other studies have claimed that compared with mannitol, HTS has a greater effect in reducing raised ICP [73, 74]. However, in one of these studies, a xed dose of HTS (30 ml of 23.4%) was compared with a variable dose of mannitol (1575 g), whereas in another study, the osmotic load administered using HTS was 641 mOsm compared with 412 mOsm using mannitol. Although the authors commented on the minimal effect of HTS on serum sodium concentration, neither commented on the effect on serum chloride or pH. Recently, alternative approaches to providing an osmotic load to control ICP have been described. In a prospective study of ten episodes of unprovoked ICP rise in seven patients, 85 ml 8.4% sodium bicarbonate (170 mOsm) was given over 30 min. The mean ICP fell from 28.5 mmHg to 10.33 mmHg, and remained below 20 mmHg at all time points for 6 h. Mean arterial pressure was unchanged resulting in an increased CPP. The serum sodium increased, but without generation of a hyperchloraemic metabolic acidosis [75]. The osmotic load was relatively small, equivalent to 160 ml 20% mannitol. In 34 patients with severe TBI and raised ICP, Ichai et al. used the same volumes of equally hyperosmolar therapy, consisting of either 20% mannitol or 0.5 M sodium lactate. Although the effect of the lactate solution on ICP was more pronounced, the actual reduction was small (7 vs 4 mmHg). Sodium lactate also increased blood glucose and pH compared with mannitol. Although long-term outcome, as judged by the GOS, seemed better in those receiving lactate compared with mannitol, the study lacked sufcient power to allow further interpretation [76].

It would seem that HTS is safe and as effective as mannitol at reducing ICP when given in the same osmolar load. However, there is no strong evidence to suggest better neurological outcome or survival. Again, this is largely due to heterogeneity of the studies, and there is no clear indication of the optimal concentration or volume of HTS that should be used. This is reected in the ndings of a survey for the use of hypertonic saline amongst neuro critical care units in the UK [77]. Furthermore, there are signicant risks of biochemical disturbances if repeated or large doses are used.

Blood glucose Traumatic brain injury is associated with activation of the hypothalamic-pituitary-adrenal axis, triggering the release of catecholamines and glucocorticoids resulting in an increase in blood glucose concentrations. The increase in blood glucose appears to correlate with the severity of injury, and is a signicant predictor of outcome [78, 79], an effect that has been demonstrated at admission and during the rst 24 h [80]. It has been assumed that this effect is a result of the increase in blood glucose levels, promoting anaerobic metabolism within the brain and accumulation of lactic acid, which in turn contributes to the secondary injury. Control of blood glucose levels may prevent this and have a benecial effect on outcome [81]. To investigate the risks and possible benets of routine vs intensive insulin therapy, Bilotta and colleagues randomly assigned 97 patients with severe traumatic brain injury to receive insulin either at conventional rates when blood glucose exceeded 12.2 mmol.l)1 or be administered intensively to maintain blood glucose at 4.4 6.6 mmol.l)1. Episodes of hypoglycaemia (dened as blood glucose < 4.4 mmol.l)1) were more common in patients receiving intensive insulin therapy. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs 10.0 days), whereas infection rates during ICU stay (25.0% vs 38.8%), and GOS scores and mortality at 6 months were similar in the two groups [82]. In a similar prospective study of 240 adult patients with severe traumatic brain injury, investigating conventional vs intensive insulin regimes, Yang and colleagues found that mortality rates at 6 months were similar in the two groups, though more patients in the intensive insulin therapy group had good outcomes (aGOS score of 45) than the conventional therapy patients (29.1% vs 22.4%). In addition, intensive insulin therapy was associated with a lower infection rate and shorter ICU stay. However,

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the incidence of severe hypoglycaemia in the tight glucose control group was not reported [83]. Although it is clear that in patients with traumatic brain injury, hyperglycaemia is common soon after the injury and persists for several days, the majority of the available evidence does not suggest that aggressive reduction and control of the blood glucose (blood glucose < 66.6 mmol.l)1) improves neurological outcomes and it may exacerbate brain metabolic distress, increasing morbidity [84].

Therapeutic hypothermia Following severe traumatic brain injury, a number of pathophysiological processes at a cellular level occur that contribute to the evolving injury. These include the inux of calcium, accumulation of glutamate, lipase activation and cell membrane damage the so called excitotoxic cascade. In addition, there is free radical formation, mitochondrial dysfunction, proteolysis and initiation of apoptosis. Increased vascular permeability and capillary leak lead to loss of function of the blood brain barrier and oedema formation. Cerebral blood ow may also be impaired by the formation of microthrombi. In a variety of experimental and clinical studies, all these processes are reduced by moderate degrees of hypothermia [85]. Not surprisingly, there has been interest in the use of therapeutic hypothermia in the management of traumatic brain injury. A number of systematic reviews of the data have reported disappointing results. McIntyre and colleagues found a small reduction in the risks of death and poor neurological outcome, but concluded that the evidence was not sufcient to recommend routine use of therapeutic hypothermia for traumatic brain injury outside of research settings [86]. In a more recent review, Peterson and colleagues found that in patients treated with hypothermia, the reduction in mortality was greatest (RR 0.51; 95% CI 0.330.79) and a favourable neurological outcome more common (RR 1.91; 95% CI 1.282.85) when hypothermia was used for more than 48 h. However, these benets may be offset by an increased risk of pneumonia (RR 2.37: 95% CI 1.374.1 [87]. However, a recent prospective, randomised, multicentre trial (The National Acute Brain Injury Study: Hypothermia II (NABIS II)) was recently terminated for futility with no differences in outcome between patients treated with hypothermia compared with normothermia [88]. One of the key criticisms in the studies reported to date is the heterogeneity of their design, with differences in when to start cooling, how long to cool, how low to take the

temperature and how quickly to rewarm. It is hoped that the answers to many of these issues will be provided by the ongoing Eurotherm 3235 trial [89]. Until that time, normothermia should be maintained, particularly in the presence of other injuries. For those patients who are pyrexial, the current accepted paradigm is to attempt to return their temperature to normal, especially in the presence of raised ICP. Although there is supportive experimental work for this approach, it has not been translated into benecial outcomes in human studies. The relationship between temperature and outcome after traumatic brain injury may not be entirely clear [90, 91].

Protocol-driven management

Following the initial resuscitation phase, early diagnosis and referral to a neurosurgical centre becomes imperative. It has been stated that time is brain and it is paramount to limit further secondary damage. It has been recognised for over 30 years and conrmed as recently as 2006 [92] that accessing denitive surgical intervention for intracranial haematomas is time critical. Evidence shows that this should be within 2 h for patients with extradural haematomas [9] and 4 h for subdural haematomas [10]. Sadly, even within the authors own conurbation, there is still a struggle to achieve such targets in all patients [93, 94]. In the emergency department, guidelines rather than strict protocols are available to guide the initial assessment and management of head-injured patients. In the USA, the Brain Trauma Foundation issues a comprehensive, evidenced-based document to cover severe traumatic brain injury [43]. In a survey of compliance amongst emergency physicians, the majority appeared to be adhering to the guidelines with the exception of the use of hyperventilation [95]. Furthermore, there appears to be considerable national variation in the care of severely head-injured patients, with better outcomes in those centres adhering more closely to the Brain Trauma Foundation guidelines [96]. In an evaluation of physicians compliance with Scandinavian Guidelines, Heskestad et al. found that although overall compliance with the guidelines was observed in 51% of patients, there was overtreatment of mild and moderate head injuries at considerable nancial cost [97]. Within the UK, there has been widespread adoption of ATLS principles for the initial resuscitation and assessment of head-injured patients, and the Association of Anaesthetists of Great Britain and

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Ireland and the Intensive Care Society have produced comprehensive guidelines for the safe transfer of these patients. However, there are still delays between arrival at the local emergency department and transfer to the neurosurgical unit, transfers undertaken with an unsecured airway, inadequate cervical spine imaging and patients arriving hypoxic and hypotensive [98]. Many critical care units have introduced protocoldriven management in an attempt to standardise patient care. The aim is to ensure early achievement of resuscitation endpoints, early identication and response to deterioration using protocol-based escalation of treatment, and early surgical intervention when required. Several groups have conrmed improvements in outcome, comparing protocol-driven therapy against historical outcome data in terms of reduced ICU and inhospital mortality [99, 100], with an increase in favourable outcome at 6 months in patients with severe head injury [5]. Others have found mixed effects on duration of stay on ITU or in hospital, depending on compliance with policies on monitoring, hyperventilation and prophylactic use of anti-seizure drugs [101]. Not all the published work has supported the use of protocoldriven therapy, with some suggesting increased intensity of management and resource use with little evidence of benecial outcomes [102]. Interestingly, despite variation amongst the various protocols described, the overall trend is towards improvement. This suggests that some of the effect, at least, is due to ensuring the delivery of standardised treatment for all patients irrespective of the time of day or experience of staff.

Table 1 Criteria for immediate CT scan of the head in

adults.
GCS < 13 on initial assessment in the emergency department GCS < 15 2 h after the injury on assessment in the emergency department Suspected open or depressed skull fracture Any sign of basal skull fracture (haemotympanum, panda eyes, cerebrospinal uid leakage from the ear or nose, Battles sign) Post-traumatic seizure Focal neurological decit More than one episode of vomiting Amnesia for events > 30 min before impact Any patient who has experienced some loss of consciousness or amnesia since the injury and: is aged 65 years or older is at risk of coagulopathy (history of bleeding, clotting disorder, current treatment with warfarin) there is a dangerous mechanism of injury (a pedestrian or cyclist struck by a motor vehicle, an occupant ejected from a motor vehicle or a fall from a height of > than 1 m or ve stairs).

GCS = Glasgow Coma Scale score.

Investigations

There is no doubt that CT scanning has revolutionised the management of head injuries. The ndings on CT correlate with severity of injury [103105], as well as aiding prognostication [106]. The success of CT scanning has led to its increasing availability and use. However, with this comes the need to identify those patients who will benet, particularly amongst those with seemingly minor trauma, to prevent unnecessary scans, accompanying workload and exposure to unnecessary radiation. The National Institute for Health and Clinical Excellence (2007) and the Scottish Intercollegiate Guidelines Network (2009) issued guidelines on the early management of head injury in infants, children and adults, emphasising the early use of CT as the investigation of choice for the detection of acute, clinically important brain injuries [107, 108]. The current guidelines state that a head CT should be

requested immediately and be performed and analysed within 1 h in any adult patient who has sustained a head injury and presents with any risk factors described in Table 1. Due to the coincidence of injury to the cervical spine in patients with a head injury, where a request for urgent CT imaging of the head has been received, CT imaging of the cervical spine should be carried out simultaneously. Although magnetic resonance imaging can reveal additional information in patients with subtle or diffuse injuries and aid with prognosis, it is not currently indicated as the primary investigation in the acute phase in patients who have sustained a head injury. Magnetic resonance imaging is relatively slow and requires the patient to be isolated, monitoring of the patient is limited, and it is contraindicated in the presence of incompatible implants or foreign bodies.

Conclusion

Despite the introduction of measures to try and reduce the risk of trauma in our daily lives, head injury remains a major public health problem in all age groups. Nearly 20 years ago, the inuence of hypoxia, hypotension and hyperventilation was conrmed, but despite signicant research in the intervening period, no specic treatment has been identied to help treat head injuries. Some treatments that were accepted are now known to be associated with worse outcomes and have been abandoned. The current evidence for the

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Anaesthesia, 2011, 66, pages 10351047R. T. Protheroe and C. L. GwinnuttEarly hospital care of severe traumatic brain injury
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management of head injuries supports the avoidance of continuing insults such as hypoxia, hypotension and hyperventilation, coupled with control of blood glucose. In the future, with improved monitoring, it may be possible to tailor the extent to which we manipulate these parameters to each individual patients requirements, thereby optimising their outcome. At present, our best opportunity may be the acceptance and implementation of guidelines, while working together to facilitate robust clinical trials for generating the answers to our questions.

Acknowledgements

The authors thank Mr Peter Driscoll, Consultant in Emergency Medicine, for his thoughtful comments and Karen Gwinnutt for her help in preparing the manuscript. No external funding or conicts of interest declared.

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