early hospital care of severe traumatic brain injury

Anaesthesia, 2011, 66, pages 1035–1047doi:10.1111/j.1365-2044.2011.06874.x.....................................................................................................................................................................................................................

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 FoundationTrust, Salford, UK

Summary

Head injury is one of the major causes of trauma-related morbidity and mortality in all age groupsin 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 injuryand a wealth of research, there is currently no specific treatment. Outcome remains dependant onbasic clinical care: management of the patient’s airway with particular attention to preventinghypoxia; avoidance of the extremes of lung ventilation; and the maintenance of adequate cerebralperfusion, in an attempt to avoid exacerbating any secondary injury. Hypertonic fluids showpromise in the management of patients with raised intracranial pressure. Computed tomographyscanning has had a major impact on the early identification of lesions amenable to surgery, andrecent guidelines have rationalised its use in those with less severe injuries. Within critical care, theimportance of controlling blood glucose is becoming clearer, along with the potential beneficialeffects of hyperoxia. The major improvement in outcome reflects the use of protocols to guideresuscitation, investigation and treatment and the role of specialist neurosciences centres in caringfor these patients. Finally, certain groups are now recognised as being at greater risk, in particularthe elderly, anticoagulated patient.

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Correspondence to: Dr Richard ProtheroeEmail: [email protected]: 22 July 2011

Head injury is a common problem in the UK.Approximately 1 000 000 patients attend emergencydepartments annually, 100 000 are admitted, 10 000will require treatment in a neurosurgical unit and theoverall mortality is 6–10 per 100 000 persons perannum [1]. Many more will survive with long-termdisabilities, and the overall cost, both financial andsocietal, of caring for these patients is enormous. In theyounger population, it is mainly men who are affected,usually as a result of road traffic accidents or assaults,whereas falls tend to predominate in the more elderlyage group [2]. Alcohol consumption is a major factor,contributing to both the immediate trauma throughacute intoxication and long-term outcomes throughchronic abuse. It is now accepted that the fundamental principles ofthe early management of head-injured patients shouldfocus on establishing and maintaining a clear airway byintubation, using appropriate analgesia and sedation, toÓ 2011 The AuthorsAnaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland

allow oxygenation and ventilation, resuscitation of thecirculation to ensure adequate and stable cerebralperfusion, avoidance of hypo- and hyperglycaemiaand the rapid identification of a surgically treatablelesion (typically an intracerebral haematoma). Althoughoften described as the ‘ABCDE’ approach, each ofthese stages should be tailored specifically to the needsof the head-injured patient, starting in the prehospitalenvironment and continuing in a seamless fashionthroughout their time in hospital. In the past decade,investigations into the therapeutic use of steroids andhypothermia appeared to offer the prospect of improv-ing outcome. However, the CRASH study demon-strated that corticosteroids should not be used routinelyin the treatment of head injury [3], and a Cochranereview found no evidence that hypothermia is bene-ficial in the treatment of head injury [4]. However,there is now evidence to support the view that optimalcare and outcome is best achieved by taking all

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R. T. Protheroe and C. L. GwinnuttEarly hospital care of severe traumatic brain injuryAnaesthesia, 2011, 66, pages 1035–1047. ....................................................................................................................................................................................................................Æ

moderate and severe head injuries either directly, ortransferring them rapidly, to a specialist neurosciencescentre for multi disciplinary management includingneuroradiology, anaesthesia, neurosurgery and criticalcare [5].

Pathophysiology

management of head-injured patients can be summedup as ‘the need for speed’.

Recognising ‘at risk’ patients

Pathophysiologically, head injury is classically dividedinto primary and secondary injuries. Primary injury isthe result of energy transfer to the brain at the timeof the traumatic event, damaging neural, glial andvascular structures. As a result, there is damage tocell membranes, which increases permeability anddisrupts ionic homeostasis with axonal tissue beingthe most vulnerable [6]. Subsequently, there iscellular swelling and numerous neurotoxic eventsmediated through increased levels of intracellularcalcium [7]. The primary injury can only beaddressed by prevention and improved safety suchas legislation on the use of seat belts and motor cyclecrash helmets, air-bags in motor vehicles and speedrestrictions and, more recently, in the prevention offalls in the elderly [8]. Traditionally, secondary injuryhas been described as the consequence of physiolog-ical insults that may occur following traumatic injuryto the brain or other body areas resulting in hypoxia,hypotension, hypo- or hypercapnia, hypo- or hyper-glycaemia, hyperthermia and seizures. However, thismay be too simplistic as experimental evidencesuggests that separation of these two injury eventsis somewhat artificial, with secondary injury beinginitiated at the time of the primary injury in theareas of damaged brain and spreading to thesurrounding areas [7]. It may be more accurate toview the secondary injury as an inevitable processthat is exacerbated by the physiological insultsdescribed above, but may be modified by medicalintervention. This view of the pathophysiology mayexplain the historical observation that around onethird of patients who died as a result of their headinjury either talked or obeyed commands beforetheir death, suggesting that their primary injurieswere not lethal and death was due to an ongoingprocess that may be compounded by relatively poorcare. Not surprisingly, therefore, rapid recognition ofthe severity of the injury, targeted resuscitation andearly specialist medical and surgical management havelong been recognised as playing an important role inimproving outcome [5, 9–12]. The need for thisrapidity of intervention at all stages, in the early

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Although young adult men are particularly at risk ofmoderate and severe head injury due to occupationaland recreational activities [13], it is the elderly whohave the worst outcomes [13–15], with mortality andfunctional disability rates almost twice those of youngerpatients [16]. Gender is also important; women have asignificantly greater frequency of brain swelling andintracranial hypertension compared with male patients[17], and lower rates of survival 6 months after injury[18]. However, in the early management of the head-injured patient, the one key group of patients that mustbe identified rapidly are those taking anticoagulants andantiplatelet drugs. Intracerebral haemorrhage may be both the causeand effect of trauma in the elderly, particularly if thepatient is anticoagulated [19]. Warfarin use appears tobe associated with a higher frequency of isolated headtrauma, more severe head trauma and a greaterlikelihood of death [20]. Even after a simple fall,patients > 65 years-old taking warfarin have mortalitygreater than twice those not warfarinised [21]. Theelderly are also more likely to present with a supra-therapeutic international normalised ratio (INR) due topoor compliance, poor nutrition or hepatic disease. Inanticoagulated patients with a severe head injury(Glasgow Coma Scale (GCS) £ 8), the INR atpresentation was greater than 5.0 in 50%, and theoverall mortality was almost 90%. Of 77 patients withGCS 13–15, 56 deteriorated clinically with a mortalityrate of > 80% [22]. In view of the devastating effects ofanticoagulation, all elderly patients should have theircoagulation checked on admission. Whether warfarinshould be reversed with either fresh frozen plasma orprothrombin complex is unclear, as there are insuffi-cient data from studies to determine the optimum useand timing of reversal therapy [23]. A more liberalcomputed tomography (CT) scanning policy, makingit mandatory in patients with a coagulopathy indepen-dent of head trauma severity, would seem pragmatic. Ithas been estimated that instituting such a policy wouldincrease the CT scanner workload by less than 2%,with a one in four probability of identifying anintracranial lesion [24]. The situation in those patients taking antiplatelettherapy is less clear. Tauber et al. described 100consecutive trauma patients > 65 years-old, with a

Ó 2011 The AuthorsAnaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland

Anaesthesia, 2011, 66, pages 1035–1047R. T. Protheroe and C. L. GwinnuttEarly hospital care of severe traumatic brain injury. ....................................................................................................................................................................................................................Æ

mild head injury (GCS = 15) and taking low-doseaspirin who were rescanned 12–24 h after an initialnegative scan. Four patients were identified as havingsecondary intracranial haemorrhages, one of whomdied. The authors suggested that this group of patientsshould either have a repeat CT scan after 12–24 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 fulfilled the criteria fora CT scan had an intracerebral haemorrhage comparedwith 15% of those taking warfarin. The authorsconcluded that the risk of intracranial bleeding inpatients receiving antiplatelet therapy may be increasedand clinical judgment should be used to assess the needfor an urgent scan in these patients [26].Management

Severe traumatic brain injury is a clinical situation inwhich basic resuscitation and management has to beinitiated before a complete investigation of the fullextent of the injuries can be performed. Consequently,discussion of the early management with the relevantevidence is presented here ahead of the investigations. For nearly 20 years, the profoundly detrimentaleffect of hypoxia and hypotension on outcome afterhead injury has been well known [12, 27]. Early, safeestablishment of a definitive airway, followed bycontrolled lung ventilation, will allow control of thearterial gas content, in particular, the prevention ofhypoxia. Venous access, adequate fluid resuscitationand, probably, inotropic or vasopressor support will beneeded to counter the hypotensive effects of sedativesand analgesics to maintain the cerebral perfusionpressure (CPP). However, even now such manage-ment is not ubiquitous [28]. Furthermore, the situationmay be compounded in the patient with multipleinjuries, where the strategy of permissive hypotensivefor the management of penetrating thoraco-abdominaltrauma may lead to clinical conflict with a co-existinghead injury [29, 30].

Oxygenation and ventilationThe devastating effects of hypoxia in head-injuredpatients are well known. Despite improvements inprehospital care, hypoxia is still a threat. Patients with apotentially survivable head injury who suffer at leastone hypoxic episode (SpO2 < 92%) during transfer tohospital are more than twice as likely to die as thosewho are not hypoxic [31]. In an attempt to address thisissue, there has been an increased emphasis on the useÓ 2011 The AuthorsAnaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland

of tracheal intubation, but the evidence of its efficacyappears to be conflicting. It should be noted that inmany studies, prehospital airway management is pre-dominantly non-physician led, with the most seriouslyinjured often undergoing intubation without the use ofsedation [32]. In a retrospective analysis of 2491patients from the National Trauma Data Bank, patientswith multiple injuries and a GCS score of 3 had almostdouble the mortality with prehospital intubationcompared with intubation on arrival at hospital. Thosewith isolated head trauma and intubation prehospitalwere also more likely to die (OR 2.0; 95% CI 1.4–2.9)[33]. However, in a prospective, controlled trial inadults with severe traumatic brain injury in an urbansetting, patients were randomly assigned to eitherprehospital rapid sequence intubation by paramedics ortransported to a hospital emergency department forintubation by physicians. The proportion of patientswith a favourable outcome was 51% in the paramedicintubation group compared with 39% in the hospitalintubation group (RR 1.28; 95% CI 1.00–1.64,p = 0.046) [34]. These findings may reflect thesuboptimal performance of intubation or the adverseeffects of inappropriate lung ventilation that may offsetthe potential benefits of the procedure, rather thanintubation itself being detrimental. The effects ofuncontrolled ventilation prehospital via either a facemask or tracheal tube can be dramatic; both hypocarbiaand hypercarbia as assessed by analysis of arterial bloodgases on presentation at hospital are associated withincreased in-hospital morbidity and mortality [35, 36].When targeted lung ventilation (arterial PCO2 4–5.2 kPa) was used in the emergency department forhead-injured patients undergoing intubation beforearrival at hospital, those in whom the target wasachieved had a mortality of 21.2% compared with33.7% for those who remained outside this range(p = 0.03) [37]. Although it would seem easy toaddress this by ensuring that all head-injured patientshave their lung ventilation monitored, in the earlyphases of care this is most likely to be through the useof end-tidal devices, and in patients with severe chesttrauma or hypotension and metabolic acidosis, theremay be a significant discrepancy between arterial PCO2

and end-tidal PCO2, leading to an underestimation ofthe former [38]. Hyperventilation has been used widely to reduceincreased intracranial pressure (ICP) [39], but thisreduces cerebral blood flow (CBF) at a time when itmay already be compromised, risking cerebral ischae-mia 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 withprophylactic hyperventilation [40]. More recently,studies using positron emission tomography to inves-tigate oxygen utilisation have demonstrated the dele-terious effects of hyperventilation on the injured brain,despite improvements in CPP and IPP [41]. Hyper-ventilation appears consistently to reduce CBF andresult in an increase in both oxygen extraction ratioand ischaemic brain volume. These findings led Coleand colleagues to conclude that ‘hyperventilationcauses an acute reduction in cerebral blood flow andincrease in cerebral metabolic rate for oxygen(CMRO2) that presents a physiological challenge tothe traumatised brain, compromising oxidative metab-olism. Such ischaemia is underestimated by com-mon bedside monitoring tools, and may represent asignificant mechanism of avoidable neuronal injuryfollowing head trauma’ [42]. Hyperventilation shouldonly be considered as a rescue therapy in patients withraised ICP and signs of imminent brainstem herniation,and it should be avoided in the first 24 h after injurywhen CBF is often critically reduced. If moderatehyperventilation is used, it should be initiated in acritical care area in conjunction with monitoring toensure adequate cerebral oxygenation (such as jugularvenous oxygen saturation or brain tissue oxygentension) [43]. If prevention of hypoxia is so critical, does increasingthe amount of oxygen have any potential benefit?Recently, interest has been shown in the use ofhyperoxia as a treatment for patients with traumaticbrain injury, on the basis that mitochondrial dysfunc-tion is known to occur in both stroke and traumaticbrain injury [44]. Early studies showed that hyperoxiadecreased lactate levels in brain microdialysate, sug-gesting improved aerobic metabolism [45, 46]. In 69patients with severe traumatic brain injury, a compar-ison of hyperbaric oxygen, normobaric oxygen (FIO2

1.0) and standard care found improved indices ofcerebral oxygenation and aerobic metabolism with abrain tissue PO2 (PbtO2) of 26 kPa or greater [47].However, using PET scanning to directly measureCMRO2 before and after ventilation with 100%oxygen, Diringer and colleagues found that there wasno change in either CBF or CMRO2, indicating thatnormobaric hyperoxia did not improve brain oxygenmetabolism [48]. In a registry-based analysis of theeffect of hypoxaemia and hyperoxaemia on outcomefollowing moderate to severe traumatic brain injury,both hypoxaemia and extreme hyperoxaemia were

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associated with decreased survival, with data suggestingan optimal arterial PO2 in the range 14.6–64.9 kPa[49]. Using PbtO2 in addition to normal monitoring (ICP,CPP), to ensure adequate cerebral oxygenation inpatients with severe traumatic brain injury, PbtO2-directed care (including eubaric hyperoxia, ‘triple H’therapy (hypertension, haemodilution and hypervola-emia) and maintaining haemoglobin concentration> 12.5 g.dl)1) PO2 (PbtO2) was associated with a lowermortality rate than conventional therapy (25.7% vs45.3%, p < 0.05). The authors suggested that when alow PbtO2 can be corrected, such treatment maybeassociated with reduced patient mortality and improvedpatient outcome after severe traumatic brain injury[50]. In a retrospective review of their results usingPbtO2-directed therapy compared with historic controlsusing ICP ⁄ CPP directed therapy, Narotam et al. foundthat a combination of increased ICP and reduced PbtO2

2 h after admission resulted in an increased risk of deathat 48 h (OR 14.3). Six months after the injury, patientstreated with PbtO2-directed therapy had a betteroutcome as assessed using the Glasgow Outcome Scale(GOS) [51]. In contrast, Martini and colleagues,investigating the use of PbtO2 monitoring in conjunc-tion with ICP monitoring, found no reduction inmortality compared with ICP monitoring alone. Infact, brain tissue oxygen monitoring was associatedwith worse neurological outcome and increased hos-pital resource utilisation [52]. The need for rapid identification and correction ofhypoxia remains undisputed. However, the evidencefor using supranormal concentrations of oxygenremains unclear, and it would seem that it is mostlikely to be of benefit when its use is targeted. Thisrequires invasive PbtO2 monitoring – a techniquecurrently restricted to critical care areas. Further studiesare required to identify the role of hyperoxia in themanagement of patients with brain injury.

Blood pressure managementHypotension has a significant adverse effect onoutcome after head injury. In a prospective studypublished nearly 20 years ago, early hypotension wasshown to cause a doubling of mortality (55% vs 27%),which increased to 65% if shock was present onadmission to hospital. These effects were independentof age, admission GCS motor score, hypoxia orassociated severe extracranial trauma [53]. In a pro-spective cohort study, mortality increased with thenumber and duration of hypotensive episodes (systolic



pressure < 90 mmHg) during resuscitation within theemergency department, with an OR of 8.1 for death,when there were more than two episodes of hypoten-sion [28]. In a retrospective case-control study, non-surviving patients with traumatic brain injury werefound to have had lower mean arterial pressures 4 hafter arrival than survivors, with a fourfold increase inthe odds of non-survival if the mean arterial pressurewas < 65 mmHg during this period [27]. Despite thisclear message, hypotension remains a significant causeof morbidity and mortality after head injury. In the early resuscitation of head-injured patientssystolic blood pressure is usually measured, but it is theCPP that determines adequacy of cerebral blood flow.This is dependent on mean arterial blood pressure andICP, and the latter is rarely measured until patientsreach a critical care unit. The optimal mean arterialpressure or CPP varies depending on the guidelinesused (see below), but it is becoming clear that perfusionrequirements may not only vary within the injuredbrain but may also differ depending on the elapsed timesince the injury. Such heterogeneity, which exists bothwithin and between patients, suggests that individua-lised therapy may be an appropriate treatment strategy,and in patients with lower GCS scores, a higher CPPmay be appropriate [54, 55]. Intravenous fluids are the primary means to maintainblood pressure. However, there is continuing debateabout the volumes and formulation of fluid used andthe potential exacerbation of cerebral oedema in theface of a disrupted blood-brain barrier. Although it iswidely accepted that hypotonic fluids should not beused, more recent interest has been in the use ofhypertonic fluids for resuscitation of patients withtraumatic brain injury. The benefits include smallervolumes that can be given more rapidly to restorecerebral perfusion, a reduction in cerebral oedema andmodulation of the inflammatory response, helpingreduce subsequent neuronal injury [56, 57]. Earlystudies of their use suggested that they were beneficial[58–60], but more recent studies have found mixedresults. In hypotensive head-injured patients (GCS £ 8),hypertonic saline (HTS) was associated with a 20%increase in CPP, and an elevation in PbtO2, resulting inimproved brain tissue oxygenation [61]. Using S100B,neuron-specific enolase and myelin-basic protein asbiomarkers of brain injury, giving 250 ml 7.5%hypertonic saline ⁄ 6% dextran70 (HSD) correlated witha better outcome after severe traumatic brain injurycompared with 0.9% saline [62]. A prospectiveÓ 2011 The AuthorsAnaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland

observational study of 51 trauma patients receiving500 ml 5% HTS during initial resuscitation found nodifference in mortality compared with controls. How-ever, there was a trend towards decreased mortality inpatients with a GCS £ 8 and a Head AbbreviatedInjury Scale score £ 3 (25.0% vs 42.5%). No adversesequelae were seen as a result of hypernatraemia in theHTS group (Na+ = 150 vs 143 mmol.l)1) [63]. Morerecently, a large multicentre trial in North America,investigating the use of a single bolus of HSD, HTS or0.9% saline in trauma patients with a GCS £ 8without hypovolaemic shock, was terminated by thedata and safety monitoring board having met prespec-ified futility criteria. There was no improvement inneurological outcome or survival at 6 months afterinitial resuscitation with either HTS or HSD, com-pared with normal saline [64]. Despite its theoreticaladvantages it appears that, the role of HTS with orwithout dextran is less clear than originally perceived,and there is no obvious clinical advantage or justifica-tion in replacing the currently used isotonic fluids withHTS. The problem is compounded by the heteroge-neity of the studies, in particular the types and volumesof solutions used. What can be said with greatercertainty is that albumin no longer has a role in theresuscitation of patients with head injuries. In a posthoc analysis of the SAFE data looking specifically atpatients with severe brain injury, investigators found aworse outcome in those patients resuscitated withhuman albumin as opposed to saline [65].

Management of raised ICPBefore utilising the more advanced approaches tocontrol the ICP, the more basic and simple manoeu-vres should not be forgotten. Patient positioning canhave a dramatic effect on the ICP and should beregularly reviewed. The gravitational effects of posi-tioning head-up (to 30º) to aid venous drainage andprevent venous congestion are well known. The neckshould be maintained in a neutral position to avoid thevenous obstruction caused by excessive flexion orrotation. Semi-rigid collars should also be removed asearly as possible as they may also contribute to raisedICP [66]. Adequate sedation and analgesia are impor-tant. Intubated patients require ongoing sedation, forexample, with propofol or midazolam, supplementedwith an analgesic. Care with the dosage is essential toavoid both over- and undersedation. In the immediatemanagement, neuromuscular blocking drugs are alsofrequently used to facilitate mechanical ventilation andprevent coughing.

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The use of mannitol for the reduction of elevatedICP was first described in the 1960s, and it hassubsequently remained the first-line osmotic agent forthe reduction of ICP [67, 68]. In 2007, a Cochranereview of the use of mannitol therapy for raised ICPconcluded that although it may have a beneficial effecton mortality when compared with pentobarbitaltreatment, there may be a detrimental effect onmortality when compared with HTS [69]. Since thisreview, there have been a number of studies, many ofwhich report only a small number of patients and usingdifferent treatment protocols, comparing the efficacy ofmannitol and HTS as a treatment for raised ICP. Whenequimolar infusions of mannitol and HTS are used,their action on reducing ICP appears to be similar induration and efficacy [70, 71]. An evaluation of the useof 30 ml 23.4% saline for raised ICP found a decreasein ICP and an improvement in PbtO2 and CPP greatestin patients with a high baseline ICP [72]. Other studieshave claimed that compared with mannitol, HTS has agreater effect in reducing raised ICP [73, 74]. How-ever, in one of these studies, a fixed dose of HTS(30 ml of 23.4%) was compared with a variable dose ofmannitol (15–75 g), whereas in another study, theosmotic load administered using HTS was 641 mOsmcompared with 412 mOsm using mannitol. Althoughthe authors commented on the minimal effect of HTSon serum sodium concentration, neither commentedon the effect on serum chloride or pH. Recently, alternative approaches to providing anosmotic load to control ICP have been described. In aprospective study of ten episodes of unprovoked ICPrise in seven patients, 85 ml 8.4% sodium bicarbonate(170 mOsm) was given over 30 min. The mean ICP fellfrom 28.5 mmHg to 10.33 mmHg, and remainedbelow 20 mmHg at all time points for 6 h. Mean arterialpressure was unchanged resulting in an increased CPP.The serum sodium increased, but without generation ofa hyperchloraemic metabolic acidosis [75]. The osmoticload 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 hyper-osmolar therapy, consisting of either 20% mannitol or0.5 M sodium lactate. Although the effect of the lactatesolution on ICP was more pronounced, the actualreduction was small (7 vs 4 mmHg). Sodium lactate alsoincreased blood glucose and pH compared with man-nitol. Although long-term outcome, as judged by theGOS, seemed better in those receiving lactate comparedwith mannitol, the study lacked sufficient power toallow further interpretation [76].

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It would seem that HTS is safe and as effective asmannitol at reducing ICP when given in the sameosmolar load. However, there is no strong evidence tosuggest better neurological outcome or survival. Again,this is largely due to heterogeneity of the studies, andthere is no clear indication of the optimal concentra-tion or volume of HTS that should be used. This isreflected in the findings of a survey for the use ofhypertonic saline amongst neuro critical care units inthe UK [77]. Furthermore, there are significant risks ofbiochemical disturbances if repeated or large doses areused.

Blood glucoseTraumatic brain injury is associated with activation ofthe hypothalamic-pituitary-adrenal axis, triggering therelease of catecholamines and glucocorticoids resultingin an increase in blood glucose concentrations. Theincrease in blood glucose appears to correlate with theseverity of injury, and is a significant predictor ofoutcome [78, 79], an effect that has been demonstratedat admission and during the first 24 h [80]. It has beenassumed that this effect is a result of the increase inblood glucose levels, promoting anaerobic metabolismwithin the brain and accumulation of lactic acid, whichin turn contributes to the secondary injury. Control ofblood glucose levels may prevent this and have abeneficial effect on outcome [81]. To investigate therisks and possible benefits of routine vs intensiveinsulin therapy, Bilotta and colleagues randomlyassigned 97 patients with severe traumatic brain injuryto receive insulin either at conventional rates whenblood glucose exceeded 12.2 mmol.l)1 or be admin-istered intensively to maintain blood glucose at 4.4–6.6 mmol.l)1. Episodes of hypoglycaemia (defined asblood glucose < 4.4 mmol.l)1) were more common inpatients receiving intensive insulin therapy. Durationof ICU stay was shorter in patients receiving intensiveinsulin therapy (7.3 vs 10.0 days), whereas infectionrates during ICU stay (25.0% vs 38.8%), and GOSscores and mortality at 6 months were similar in thetwo groups [82]. In a similar prospective study of 240adult patients with severe traumatic brain injury,investigating conventional vs intensive insulin regimes,Yang and colleagues found that mortality rates at6 months were similar in the two groups, though morepatients in the intensive insulin therapy group hadgood outcomes (aGOS score of 4–5) than theconventional therapy patients (29.1% vs 22.4%). Inaddition, intensive insulin therapy was associated witha lower infection rate and shorter ICU stay. However,



the incidence of severe hypoglycaemia in the tightglucose control group was not reported [83]. Although it is clear that in patients with traumaticbrain injury, hyperglycaemia is common soon after theinjury and persists for several days, the majority of theavailable evidence does not suggest that aggressivereduction and control of the blood glucose (bloodglucose < 6–6.6 mmol.l)1) improves neurological out-comes and it may exacerbate brain metabolic distress,increasing morbidity [84].

Therapeutic hypothermiaFollowing severe traumatic brain injury, a number ofpathophysiological processes at a cellular level occurthat contribute to the evolving injury. These includethe influx of calcium, accumulation of glutamate, lipaseactivation and cell membrane damage – the so called‘excitotoxic cascade’. In addition, there is free radicalformation, mitochondrial dysfunction, proteolysis andinitiation of apoptosis. Increased vascular permeabilityand capillary leak lead to loss of function of the blood–brain barrier and oedema formation. Cerebral bloodflow may also be impaired by the formation ofmicrothrombi. In a variety of experimental and clinicalstudies, all these processes are reduced by moderatedegrees of hypothermia [85]. Not surprisingly, therehas been interest in the use of therapeutic hypothermiain the management of traumatic brain injury. Anumber of systematic reviews of the data have reporteddisappointing results. McIntyre and colleagues found asmall reduction in the risks of death and poorneurological outcome, but concluded that the evidencewas not sufficient to recommend routine use oftherapeutic hypothermia for traumatic brain injuryoutside of research settings [86]. In a more recentreview, Peterson and colleagues found that in patientstreated with hypothermia, the reduction in mortalitywas greatest (RR 0.51; 95% CI 0.33–0.79) and afavourable neurological outcome more common (RR1.91; 95% CI 1.28–2.85) when hypothermia was usedfor more than 48 h. However, these benefits may beoffset by an increased risk of pneumonia (RR 2.37:95% CI 1.37–4.1 [87]. However, a recent prospective,randomised, multicentre trial (The National AcuteBrain Injury Study: Hypothermia II (NABIS II)) wasrecently terminated for futility with no differences inoutcome between patients treated with hypothermiacompared with normothermia [88]. One of the keycriticisms in the studies reported to date is theheterogeneity of their design, with differences in whento start cooling, how long to cool, how low to take the


temperature and how quickly to rewarm. It is hopedthat the answers to many of these issues will beprovided 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 currentaccepted paradigm is to attempt to return theirtemperature to normal, especially in the presence ofraised ICP. Although there is supportive experimen-tal work for this approach, it has not been translatedinto beneficial outcomes in human studies. Therelationship between temperature and outcome aftertraumatic brain injury may not be entirely clear [90,91].

Protocol-driven management

Following the initial resuscitation phase, early diagnosisand referral to a neurosurgical centre becomes imper-ative. It has been stated that ‘time is brain’ and it isparamount to limit further secondary damage. It hasbeen recognised for over 30 years and confirmed asrecently as 2006 [92] that accessing definitive surgicalintervention for intracranial haematomas is time crit-ical. Evidence shows that this should be within 2 h forpatients with extradural haematomas [9] and 4 h forsubdural haematomas [10]. Sadly, even within theauthors’ own conurbation, there is still a struggle toachieve such targets in all patients [93, 94]. In theemergency department, guidelines rather than strictprotocols are available to guide the initial assessmentand management of head-injured patients. In the USA,the Brain Trauma Foundation issues a comprehensive,evidenced-based document to cover severe traumaticbrain injury [43]. In a survey of compliance amongstemergency physicians, the majority appeared to beadhering to the guidelines with the exception of theuse of hyperventilation [95]. Furthermore, thereappears to be considerable national variation in thecare of severely head-injured patients, with betteroutcomes in those centres adhering more closely to theBrain Trauma Foundation guidelines [96]. In anevaluation of physicians’ compliance with Scandina-vian Guidelines, Heskestad et al. found that althoughoverall compliance with the guidelines was observed in51% of patients, there was overtreatment of mild andmoderate head injuries at considerable financial cost[97]. Within the UK, there has been widespreadadoption of ATLS principles for the initial resuscitationand assessment of head-injured patients, and theAssociation of Anaesthetists of Great Britain and

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Ireland and the Intensive Care Society have producedcomprehensive guidelines for the safe transfer of thesepatients. However, there are still delays between arrivalat the local emergency department and transfer to theneurosurgical unit, transfers undertaken with an unse-cured airway, inadequate cervical spine imaging andpatients arriving hypoxic and hypotensive [98]. Many critical care units have introduced protocol-driven management in an attempt to standardise patientcare. The aim is to ensure early achievement ofresuscitation endpoints, early identification and responseto deterioration using protocol-based escalation oftreatment, and early surgical intervention when re-quired. Several groups have confirmed improvements inoutcome, comparing protocol-driven therapy againsthistorical outcome data in terms of reduced ICU and in-hospital mortality [99, 100], with an increase in favour-able outcome at 6 months in patients with severe headinjury [5]. Others have found mixed effects on durationof stay on ITU or in hospital, depending on compliancewith policies on monitoring, hyperventilation andprophylactic use of anti-seizure drugs [101]. Not allthe published work has supported the use of protocol-driven therapy, with some suggesting increased intensityof management and resource use with little evidence ofbeneficial outcomes [102]. Interestingly, despite varia-tion amongst the various protocols described, the overalltrend is towards improvement. This suggests that someof the effect, at least, is due to ensuring the delivery ofstandardised treatment for all patients irrespective of thetime of day or experience of staff.

Investigations

Table 1 Criteria for immediate CT scan of the head inadults.

GCS < 13 on initial assessment in the emergency departmentGCS < 15 2 h after the injury on assessment in the emergency departmentSuspected open or depressed skull fractureAny sign of basal skull fracture (haemotympanum, ‘panda’ eyes, cerebrospinal fluid leakage from the ear or nose, Battle’s sign)Post-traumatic seizureFocal neurological deficitMore than one episode of vomitingAmnesia for events > 30 min before impactAny 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 five stairs).

GCS = Glasgow Coma Scale score.

There is no doubt that CT scanning has revolutionisedthe management of head injuries. The findings on CTcorrelate with severity of injury [103–105], as well asaiding prognostication [106]. The success of CTscanning has led to its increasing availability and use.However, with this comes the need to identify thosepatients who will benefit, particularly amongst thosewith seemingly minor trauma, to prevent unnecessaryscans, accompanying workload and exposure tounnecessary radiation. The National Institute forHealth and Clinical Excellence (2007) and the ScottishIntercollegiate Guidelines Network (2009) issuedguidelines on the early management of head injury ininfants, children and adults, emphasising the early useof CT as the investigation of choice for the detection ofacute, clinically important brain injuries [107, 108].The current guidelines state that a head CT should be

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requested immediately and be performed and analysedwithin 1 h in any adult patient who has sustained ahead injury and presents with any risk factors describedin Table 1. Due to the coincidence of injury to the cervicalspine in patients with a head injury, where a request forurgent CT imaging of the head has been received, CTimaging of the cervical spine should be carried outsimultaneously. Although magnetic resonance imagingcan reveal additional information in patients withsubtle or diffuse injuries and aid with prognosis, it isnot currently indicated as the primary investigation inthe acute phase in patients who have sustained a headinjury. Magnetic resonance imaging is relatively slowand requires the patient to be isolated, monitoring ofthe patient is limited, and it is contraindicated in thepresence of incompatible implants or foreign bodies.Conclusion

Despite the introduction of measures to try and reducethe risk of trauma in our daily lives, head injuryremains a major public health problem in all agegroups. Nearly 20 years ago, the influence of hypoxia,hypotension and hyperventilation was confirmed, butdespite significant research in the intervening period,no specific treatment has been identified to help treathead injuries. Some treatments that were accepted arenow known to be associated with worse outcomes andhave been abandoned. The current evidence for the



management of head injuries supports the avoidance ofcontinuing insults such as hypoxia, hypotension andhyperventilation, coupled with control of blood glu-cose. In the future, with improved monitoring, it maybe possible to tailor the extent to which we manipulatethese parameters to each individual patient’s require-ments, thereby optimising their outcome. At present,our best opportunity may be the acceptance andimplementation of guidelines, while working togetherto facilitate robust clinical trials for generating theanswers to our questions.

Acknowledgements

The authors thank Mr Peter Driscoll, Consultant inEmergency Medicine, for his thoughtful commentsand Karen Gwinnutt for her help in preparing themanuscript. No external funding or conflicts of interestdeclared.

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