Pragmatic Evidence-based Review

Best-evidence Review of Acute Care for Moderate to Severe Traumatic Brain Injury

Reviewer Mark Ayson MBChB DPH

Date Report Completed August 2011

Important Note: • It is not intended to replace clinical judgement, or be used as a clinical protocol. • A reasonable attempt has been made to find and review papers relevant to the focus

of this report; however it does not claim to be exhaustive. • The document has been prepared by the staff of the Research Unit, ACC. The

content does not necessarily represent the official view of ACC or represent ACC policy.

• This report is based upon information supplied up to 12 May 2011. Purpose

The purpose of this brief report is to summarise the best evidence for acute care of people with moderate and severe traumatic brain injury.

This report is focused on adults with moderate to severe TBI.

1 Key Messages 1.1 Pre-hospital setting

• The first priority is to treat the greatest threat to life and avoid further harm

• Assess and manage according to clear principles and standard practice such as the Advanced Trauma Life Support (ATLS) system

• Initiate prompt referral to an Emergency Department if there are risk factors for acute intracranial complications of TBI

• Rapid transfer to an Emergency Department using emergency services is appropriate if the signs of acute complications are more serious or there is deterioration of the person’s condition, loss of consciousness, focal neurological deficit, skull fracture, or penetrating head injury, seizure or suspected neck injury

• The Glasgow Coma Scale (GCS) should be used for assessment and classification of people with a suspected TBI

• Full cervical spine immobilisation if GCS < 15, neck pain or tenderness, focal neurological deficit, paraesthesia in the extremities, or any other clinical suspicion of cervical spine injury

• Transport patient directly to a facility where TBI is managed in its entirety, if possible. Otherwise, transport the patient to a facility identified as having the appropriate resources to resuscitate, investigate and initially manage any patient with multiple injuries

• For people with a severe TBI (GCS ≤ 8), make a standby call to the destination to ensure appropriately experienced professionals are available to treat patient and to prepare for imaging

• Pain should be managed effectively because it can lead to a rise in intracranial pressure. Reassurance and splintage of limb fractures are helpful; catheterisation of a full bladder will reduce irritability

1.2 Emergency Department setting

• The priority is to stabilise airway, breathing and circulation before attending to other injuries

• All patients presenting to an emergency department with a head injury should be assessed by a trained member of staff within a maximum of 15 minutes of arrival at hospital

• Anyone presenting to an Emergency Department with a suspected traumatic brain injury should receive a triage assessment by a trained staff member on arrival. Part of this triage assessment should establish whether they are high or low risk for clinically significant brain injury and/or cervical spine injury, using validated CT rules

• Anyone presenting to an Emergency Department with impaired consciousness (GCS < 15) should be assessed immediately by a trained staff member (such as a triage nurse)

• In patients with a GCS ≤ 8 there should be early involvement of an anaesthetist or critical care physician early and an early referral to a neuroscience specialist should be made

• Depressed conscious level should be ascribed to intoxication only after a significant brain injury has been excluded

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• The primary investigation of choice for detection of clinically significant acute complication of TBI is CT imaging of the head

• Manage pain effectively because it can lead to a rise in intracranial pressure.

• Avoid the use of corticosteroids in the management of people with TBI of any kind

1.3 Hospital care

• Any person with a deteriorating GCS or GCS <15 after imaging, or any indication for CT scan should be admitted to hospital

• Minimum observations included GCS, pupil size and reactivity, limb movements, respiratory rate, BP, temperature, heart rate, blood oxygen saturation, and any unusual behaviour

• Consider immediate CT scan and reassessment of patient’s condition if agitation or abnormal behaviour develops, decrease in GCS, severe or worsening headache, persistent vomiting or any new or evolving neurological symptoms or signs

1.4 Intensive care

• Optimum oxygenation, perfusion, nutrition, glycaemic control & temperature homeostasis are essential

• Benefits of prophylactic anti-seizure treatment must be balanced against the potential risks; recommended indications include penetrating brain injury & depressed skull fracture in patients with PTA >24 hours in whom a dural lesion is suspected

• Sedation & artificial ventilation are used to reduce brain swelling & raised intracranial pressure (ICP) in patients with severe TBI

• ICP should be monitored in all comatose patients with a TBI and an abnormal CT scan

• Osmotherapy is currently considered as second line treatment after sedation & artificial ventilation have failed to lower raised ICP. There is insufficient evidence to support the use of hypertonic saline over mannitol because of the risks of hypernatraemia with hypertonic saline. Osmotherapy is best reserved for patients in whom ICP is being monitored

• Hyperventilation has been used to reduce ICP effectively however there is a risk of worsening ischaemia. Arterial CO2 < 30 mmHg should be avoided

• Decompressive craniectomy is controversial as it does not produce improved outcome in all people & has many side-effects, some severe. There is a consensus that the craniectomy should be large enough & done early & with duraplasty.

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2 Findings

2.1 Pre-hospital setting

2.1.1 Pre-hospital assessment

The goals of pre-hospital assessment are:

• To establish whether trauma to the head has occurred1

• To estimate the severity of any injury to the brain1

• To identify and prevent hypoxia and/or hypotension1 2

• Identify risk factors for acute complications of TBI which may require intervention*1

• Identify other injuries that may require urgent treatment1.

2.1.1.1 Hypoxia and hypotension

Hypoxia (defined here as O2 saturation < 90% or PaO2 < 60 mmHg) and hypotension (systolic blood pressure < 90 mmHg) are very prevalent when assessed before hospital admission (44-55% of cases have a oxygen saturation below 90% and 20-30% are hypotensive2). In addition, both hypoxia and/or hypotension increase morbidity and mortality from TBI1-4 and are strongly associated with poor outcome (hypoxia odds ratio [OR] 2.1, 95% Confidence Interval [CI] 1.7-2.6; hypotension: OR 2.7, 95% CI 2.1-3.4).

The importance of frequent or continuous monitoring of oxygen saturation has been shown in one study where any oxygen desaturation of <70% during intubation and any desaturation of <90% were associated with higher mortality (OR = 3.89, 95% CI 1.12-13.52 and OR = 3.86, 95% CI 1.18-12.61)5.

The only guidelines for pre-hospital management of severe TBI5 make the following recommendations about the assessment of oxygenation and blood pressure:

• Patients with suspected severe traumatic brain injury (TBI) should be monitored in the prehospital setting for hypoxemia (<90% arterial hemoglobin oxygen saturation) or hypotension (<90 mmHg systolic blood pressure [SBP])

• Percentage of blood oxygen saturation should be measured continuously in the field with a pulse oximeter

• Systolic (SBP) and diastolic blood pressure (DBP) should be measured using the most accurate method available under the circumstances

• Oxygenation and blood pressure should be measured as often as possible, and should be monitored continuously if possible5.

2.1.1.2 Glasgow Coma Scale

The Glasgow Coma Scale should be used for the assessment and classification of people who have had a head injury [C]. The risk of intracranial complications and consequent need for surgery increases as the GCS declines (RR = 5.58)6. Urgent investigation and/or referral is indicated if there is a fall 2 or more points on the GCS, as this may represent the

* especially intracranial bleeding

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development of intracranial bleeding [GAP]. Hence GCS is included as a referral criterion as can be seen in Table 2.

The GCS also allows the severity of the TBI to be assessed. An example of one classification system can be seen in Table 1. The severity of TBI will influence the consequent management including referral, the rapidity of transport, and medical intervention(s). For example, NICE (2007)7 recommends that for all people with a GCS of ≤ 8 make a standby call to the destination to ensure appropriately experienced professionals are available to treat the patient and to prepare for imaging.

Table 1: Criteria for classifying the severity of TBI

Severity of Injury GCS Score Duration of PTA

Mild 13-15 <24 hrs

Moderate 9-12 1-6 days

Severe 3-8 ≥7 days

Specific recommendations are made regarding the how and when to use the GCS, for example:

• Prehospital measurement of the Glasgow Coma Scale (GCS) should be used repeatedly to identify improvement or deterioration over time

• The GCS should be measured after airway, breathing, and circulation are assessed, after a clear airway is established, and after necessary ventilatory or circulatory resuscitation has been performed

• The GCS should be measured preferably prior to administering sedative or paralytic agents, or after these drugs have been metabolised5.

Other recommendations regarding the use of the GCS can be seen in the relevant evidence tables in the separate evidence table document. 2.1.1.3 Cerebral Herniation

The clinical signs of cerebral herniation include dilated and unreactive pupils, asymmetric pupils, a motor examination that shows either extensor posturing or no response, or progressive neurological deterioration (a decrease in the GCS of >2 points from the prior best score in people with an initial GCS <9)5. These signs are all part of the GCS assessment and the guideline for the pre-hospital management of severe TBI recommends that patients should be assessed frequently for clinical signs of cerebral herniation.

2.1.1.4 Risk factors for intracranial complications

Many variables have been identified that elevate the risk of clinically important TBI and the acute intracranial complications of TBI (see Table 2).

2.1.1.4.1 Loss of consciousness: Altered consciousness after TBI is associated with an increased risk of developing an intracranial complication1 6 7 although the absolute risk remains low7. Loss of consciousness was found to have a relative risk (RR) of 2.23 of an intracranial lesion in one study6. Loss of, or change in, consciousness may have other causes and the ACC (2006)1 guideline recommends the routine check of blood glucose levels in all people with altered consciousness [GPP].

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2.1.1.4.2 Post-traumatic amnesia Amnesia of events before or after head injury increases the risk of intracranial complications6

7, although the evidence on the type (before or after injury) and length of amnesia are less compelling than the evidence for other risk factors1 7.

2.1.1.4.3 Neurological signs Focal neurological signs post-trauma are highly associated with the risk of an intracranial complication1 6 7 (RR = 9.43)6.

2.1.1.4.4 Bleeding disorders and use of anticoagulants People who have a bleeding or clotting disorder or who are taking anticoagulant medication, like warfarin, are at an increased risk of intracranial complications, however the strength of association has not been well established1 6 7. People taking medications that have an antiplatelet effect, like aspirin and clopidogrel, should also be considered for referral to hospital1 6 [GPP]. In addition, the ACC (2006)1 guideline includes complementary and alternative medicines like Ginkgo biloba in this group.

2.1.1.4.5 Skull fracture People with a diagnosed skull fracture have a higher risk of intracranial complications. It is estimated that the risk of an intracranial haematoma to be 12 times higher in people with an x-ray detected skull fracture than in people without this diagnosis1 7. Signs of a skull fracture are also a strong predictor of an intracranial lesion (RR = 6.13)6. These signs include: clear fluid running from the ears or nose, black eye with no associated damage around the eyes, bleeding from one or both ears, new deafness in one or both ears, bruising behind one or both ears, penetrating injury signs, depressed or open skull injury, and visible trauma to the scalp or skull of concern to the professional1 6 7. Of note, the routine use of skull x-rays is not recommended1 7.

2.1.1.4.6 Seizure The rationale for the recommendations regarding post-traumatic seizure in the guidelines is inconsistent, even though seizure is included as a risk factor in all the guidelines. SIGN (2009)6 reported an unadjusted RR of 3.37 (95% CI: 1.76-6.45) for seizure from a meta-analysis as predictive of intracranial injury whereas NICE (2007)7 included seizure under the ‘neurological signs’ criterion which was reported as being highly associated with the risk of intracranial complications. In contrast, ACC (2006)1 reported that seizure alone, with no neurological signs and full recovery, is rarely a sign of an intracranial haematoma, however, alteration in consciousness (either as a result of the seizure itself or the drugs used to treat it) is indistinguishable from that caused by an intracranial bleeding complication of TBI. As a result, post-traumatic seizure is included as a criterion for referral to hospital.

2.1.1.4.7 Mechanism of injury High energy mechanism of injury is included in all three guidelines as a risk factor; however, what they are is difficult to define. However, one study has proposed that a pedestrian struck by a motor vehicle, an occupant ejected from a motor vehicle, and a fall of greater than 1 metre or more than five stairs, as high risk mechanisms for a clinically significant TBI1 7. Mechanisms of injury that are risk factors for a significant cervical spine injury are also listed. They include: high-speed motor vehicle collision, rollover motor vehicle accident, ejection from a motor vehicle, and an accident involving a recreational vehicle or bicycle1 7.

2.1.1.4.8 Age Increasing age is associated with an increased risk of intracranial complications1 6 7 and a poorer prognosis following a TBI1 7. An age threshold of over 65 yrs was chosen to be included in the referral criteria for two of the guidelines1 7.

2.1.1.4.9 Alcohol or drug intoxication

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Alcohol or drug intoxication can produce signs and symptoms that are risk factors for intracranial complications, including a reduction in the GCS. Drug and/or alcohol use has also been identified as independent risk factors for poorer outcomes following TBI, and may impact on rehabilitation from TBI1. Although alcohol intoxication can reduce the Glasgow Coma Scale, it is always safer to assume that such signs are due to TBI or a complication of TBI rather than intoxication and proceed accordingly1 6 7.

2.1.1.4.10 Headache Even though the evidence is conflicting7, headache may be both a symptom associated with raised intracranial pressure and a risk factor for intracranial complications of a head injury1 (RR = 1.02 for an intracranial lesion6). ‘Persistent headache’ is included in the referral criteria in two guidelines1 7, and ‘severe and persistent headache’ in the other6.

2.1.1.4.11 Vomiting Vomiting is included in all guidelines as a risk factor for intracranial complications but there is some debate about the number of episodes required1 6 7.

2.1.1.4.12 Irritability and altered behaviour Irritability and altered behaviour are included in two guidelines1 7 as risk factors, even though it was reported that there was little evidence to support their use. However, they are an important sign in young children where other symptoms like headache and amnesia cannot be detected1 7.

2.1.1.4.13 A history of cranial neurosurgical interventions A history of cranial neurosurgical interventions has been included in two guidelines as a referral criterion1 7, based on expert opinion that such intervention is likely to increase the risk of developing a subdural haematoma1. The ACC (2006)1 guideline explicitly recommends that any cranial neurosurgery should be recorded, especially in the 6 weeks prior to injury, or if there is a shunt in place for hydrocephalus.

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2.1.2 Referral to emergency department (ED)

Consistent criteria was reported in the identified guidelines for referral to an ED for further assessment, based on the presence of risk factors for acute intracranial complications of TBI as discussed in a previous section.

An example of these referral criteria can be seen in Table 2. Some of the details of the recommendations differ e.g. the NICE7 guideline doesn’t specify how many episodes of vomiting are required whereas the SIGN6 guideline does, but for the purposes of brevity these differences will not be mentioned in this report.

Table 2: Criteria for referral to ED (adapted from NICE 20077, ACC 20061 & SIGN 20096)

Criteria for referral to a hospital emergency department, using the ambulance service if deemed necessary:

Any of the following:

• Unconsciousness or lack of full consciousness†

• Any loss of consciousness as a result of the injury

• GCS < 15 on initial assessment

• Any focal neurological deficit since the injury‡

• Any suspicion of a skull fracture or penetrating head injury since the injury§

• Amnesia for events before or after the injury**

• Persistent headache since the injury

• Any vomiting episodes since the injury

• Any seizure since the injury

• Any previous cranial neurosurgical interventions(s)

• A high-energy head injury††

• History of bleeding or clotting disorder

• Current anticoagulant therapy such as warfarin

• Current drug or alcohol intoxication

† e.g. problems keeping eyes open ‡ e.g. problems understanding, speaking, reading or writing; decreased sensation; loss of balance; general weakness; visual changes; abnormal reflexes; and problems walking. § e.g. clear fluid running from the ears or nose, black eye with no associated damage around the eyes, bleeding from one or both ears, new deafness in one or both ears, bruising behind one or both ears, penetrating injury signs, visible trauma to the scalp or skull of concern to the professional. ** assessment of amnesia will not be possible in pre-verbal children and is unlikely to be possible in any child aged under 5 years. †† e.g. pedestrian struck by motor vehicle, occupant ejected from motor vehicle, fall from a height of greater than 1 m or more than five stairs, diving accident, high-speed motor vehicle collision, rollover motor accident, accident involving motorized recreational vehicles, bicycle collision, or any other potentially high-energy mechanism.

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• Age 65 years or older

• Suspicion of non-accidental injury

• Continuing concern by the professional about the diagnosis.

In the absence of any the factors listed above, the professional should consider referral to an emergency department if any of the following factors are present depending on their own judgement of severity:

• Irritability or altered behaviour, particularly in infants and young children‡‡

• Visible trauma to the head not covered above but still of concern to the professional.

• Adverse social factors§§

• Continuing concern by the injured person or their carer about the diagnosis. [D]

Other factors included in the guidelines include:

• Significant medical comorbidity6

• People taking antiplatelet medication*** should be considered for referral to hospital6 [GPP]

2.1.3 Pre-hospital management

Three guidelines referred to so far1 6 7 do not give advice about specific pre-hospital management, but they do give these general recommendations: • The first priority is to treat the greatest threat to life and avoid further harm1 7

• Assess and manage according to clear principles and standard practice such as the Advanced Trauma Life Support (ATLS) system1 6 7

• A person who has sustained a suspected traumatic brain injury should have full cervical spine immobilisation attempted†††1 7 8

• Transport patient directly to a facility where TBI is managed in its entirety, if possible1. Otherwise, transport the patient to a facility identified as having the appropriate resources to resuscitate, investigate and initially manage any patient with multiple injuries7.

• For people with a GCS ≤ 8, make a standby call to the destination to ensure appropriately experienced professionals are available to treat patient and to prepare for imaging7.

‡‡ i.e. aged under 5 years. §§ e.g, no one is able to supervise the injured person at home. *** e.g. aspirin, clopidogrel ††† unless they have all of the following: no alteration of consciousness, no neck pain/tenderness, no focal neurological deficit, or no major distracting injury

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• Pain should be managed effectively because it can lead to a rise in intracranial pressure. Reassurance and splintage of limb fractures are helpful; catheterisation of a full bladder will reduce irritability7. NB: ACC (2006)1 makes no recommendations about pain relief in this setting and explicitly states to avoid strong systemic analgesia until a full assessment is done.

Both NICE (2007)7 and Reed (2007)4 both recommend assessment and stabilisation of ABCDE’s‡‡‡ and the following management is then dependent on the severity of the TBI as assessed by the GCS score (using the same severity criteria as in Table 1). See section 2.2.2.1 and 2.2.2.2 for the initial management of severe and moderate TBI respectively for more details. One guideline5 and one best evidence review8 give specific guidance regarding the management of severe TBI. Rapid transfer to an appropriate secondary care facility is essential as time from injury to definitive neurosurgical care can affect outcomes for people with severe TBI; patients with mass lesions have a better outcome if they receive neurosurgical care within 4 hours of injury8. Implementation of measures to expediate rapid transfer and prevent secondary brain injury from hypoxia and/or hypotension have been shown to improve outcomes when these parameters were specifically targeted in the pre-hospital setting8. More specifically, the introduction of a system in the pre-hospital setting capable of normalising oxygenation and blood pressure has been associated with improved outcomes2.

The Brain Trauma Foundation5 guideline for severe TBI makes the following recommendations: 2.1.3.1 Airway, Ventilation and Oxygen

• Hypoxemia should be avoided, and corrected immediately upon identification

• An airway should be established, by the most appropriate means available, in patients with severe TBI, who are unable to maintain an adequate airway, or who have hypoxemia not corrected by supplemental O2

• The routine use of paralytics to assist endotracheal (ET) intubation in patients who are spontaneously breathing, and maintaining an SpO2 above 90% on supplemental oxygen, is not recommended

• Emergency services implementing ET intubation protocols should monitor blood pressure, oxygenation, and when feasible, end-tidal CO2 (ETCO2)

• Patients should be maintained with normal breathing rates (ETCO2 35-40 mmHg), and hyperventilation (ETCO2 < 35 mmHg) should be avoided unless the patient shows signs of cerebral herniation

Airway compromise is common after severe TBI and has an important contribution to the development of secondary brain injury. The Hammell (2009)8 review suggests that basic airway adjuncts should be used initially and high flow O2 administered. Inevitably ET intubation is required in almost all patients with severe TBI, although the evidence for its benefit in the pre-hospital setting is controversial8; several retrospective studies have shown that ET intubation by paramedics in this situation with minimal use of sedatives and muscle relaxants have a high risk of complications. A recent systematic review9 of 17 studies (15,

‡‡‡ A = airway maintenance with cervical spine protection ; B = breathing; C = circulation; D = disability (neurological evaluation); E = exposure/environmental control

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335 subjects) comparing pre-hospital intubation with other airway management§§§ concluded that the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI. Hammell (2009)8 suggests that true rapid sequence induction of anaesthesia performed by physicians is more promising.

Administering anaesthetic and neuromuscular blocking drugs to assist in intubation has been shown to lead to better outcomes in people with head injuries8 and, after intubation, adequate sedation and neuromuscular blockade must be maintained to avoid rises in ICP due to coughing8.

According to Hammell (2009)8, monitoring ETCO2 is now considered a routine monitoring standard for all mechanically ventilated patients during transfer and has been shown to reduce the incidence of hyperventilation by 50%. Hyperventilation can lead to cerebral vasoconstriction and ischaemia and therefore should be avoided in patients with head injuries8.

2.1.3.2 Hypotension and Fluid Resuscitation

The ideal resuscitation fluid for patients with severe TBI is unknown, however, isotonic fluids are the commonest used fluid in the pre-hospital resuscitation of people with a TBI, however, little data has been published to support its use5. Evidence for the efficacy of hypertonic fluids is inconsistent but suggestive of a survival benefit for hypertonic fluids in people with severe TBI5. • Hypotensive patients should be treated with boluses of no more than 250mls10 of

isotonic crystalloid fluids8

• Hypertonic resuscitation is a treatment option for TBI patients with a Glasgow Coma Scale Score (GCS) < 8

Patients with severe TBI who are hypotensive have a doubled risk of death compared to those who are normotensive and results in reduced cerebral perfusion and ischaemia. It is often multifactorial, however, Hammell (2009)8 suggests that it is best to assume that the hypotension is due to hypovolaemia until proven otherwise8 and that guidelines10 have recommended the use of small boluses (250ml) of isotonic crystalloid fluids to correct hypotension in patients with severe TBI.

2.1.3.3 Raised ICP and cerebral herniation

ICP is often raised in patients with severe TBI8 and Hammell (2009)8 recommends that specific treatment should be given to lower it if clinical signs are present**** and if transfer time allows and stresses that hypoxaemia, hypotension, hypercapnia and inadequate sedation (in an intubated patient) should all be addressed before specific treatment8.

Hammell (2009) then states that there is little evidence about strategies to reduce ICP in the pre-hospital environment. A recent Cochrane review concluded that there are insufficient data on the effectiveness of pre-hospital administration of mannitol11. Hypertonic saline can be used as an alternative to mannitol, however the evidence is conflicting8.

Hyperventilation in the acute setting reduces ICP but has also been shown to decrease cerebral blood flow, a deleterious effect5. People who are chronically hyperventilated in

§§§ e.g. bag-valve-mask or O2 administration

**** includes: dilated and unreactive pupils, asymmetric pupils, a motor examination that shows either extensor posturing or no response, or progressive neurological deterioration (a decrease in the GCS of >2 points from the prior best score in people with an initial GCS <9)

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hospital have been shown to have worse outcomes at 3 and 6 months but equivalent outcomes at one year but it appears that in some people with progressive cerebral oedema, hyperventilation can temporise impending herniation. In this situation the benefits of hyperventilation outweigh the potential detrimental effects5. In the prehospital phase, clinical criteria must be used to identify people at risk of herniation (in contrast to the hospital setting where ICP is used), therefore hyperventilation is used as a temporising measure in people with severe TBI who shows signs of herniation5.

• Mild or prophylactic hyperventilation (PaCO2 < 35 mmHg) should be avoided, except as below

• In patients who are normoventilated, well oxygenated, and normotensive - and still have signs of cerebral herniation - hyperventilation should be used as a temporizing measure, and discontinued when clinical signs of herniation resolve. The goal of hyperventilation is ETCO2 of 30-35 mmHg. 5.

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2.2 Emergency Department setting

The ED assessment and management of people with suspected TBI should focus on:

• Preventing and treating hypotension and hypoxia1

• Obtaining early imaging 1

• Attending to co-existing injuries1.

2.2.1 Assessment in ED

The main focus of ED assessment in people who have sustained a head injury should be the identification of actual or potential hypotension and/or hypoxia1, risk of clinically important brain injuries1 7, appropriate referral for imaging1 7 and injuries to the cervical spine7.

Due attention should also be paid to co-existing injuries and other concerns the clinician may have e.g. non-accidental injury, and early imaging, rather than admission and observation, will reduce the time to detecting life-threatening complications and is associated with better outcomes7.

2.2.1.1 Hypoxia and/or hypotension

Recommendations from the Brain Trauma Foundation severe TBI management guideline3:

• Blood pressure should be monitored and hypotension (systolic blood pressure < 90 mm Hg) avoided [II]

• Oxygenation should be monitored and hypoxia (PaO2 < 60 mm Hg or O2 saturation < 90%) avoided [III]

2.2.1.2 Investigation for clinically important brain injury

The guidelines are unanimous that the primary investigation of choice for detection of clinically significant acute complication of TBI is CT imaging of the head1 4 6 7. This guidance is based upon high level evidence, including a systematic review of the literature on diagnostic procedures and selection rules for imaging of people with head injury1, however, for the purposes of this review, the details of this evidence will not be discussed.

An example of selection rules for adults for CT imaging of the head can be seen in Table 3 below. There is some slight variation in the details of the guidance, particularly on the timing of the CT scan, but in general terms the criteria are consistent. The full criteria and criteria for the urgency in performing CT imaging of the head are included in the relevant evidence tables.

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Table 3: Selection of Adults For Head CT(adapted from NICE 20077, ACC 20061 & SIGN 20096)

CT scans should be immediately requested for adults who have sustained a head injury, if they have any one of the following risk factors:

• any deterioration in condition

• a GCS <13 when assessed, irrespective of the time elapsed since the injury

• a GCS <15 two hours after the injury

• a suspected open or depressed skull fracture

• any sign of basal skull fracture

• post-traumatic seizure

• focal neurological deficit

• one episode of vomiting

• amnesia for > 30 minutes for events before the injury.

CT scanning should be immediately requested for adults with any of the following risk factors who have experienced an injury to the head with some loss of consciousness or amnesia since the injury:

• ≥ 65 years

• coagulopathy

• high-risk mechanism of injury.

If patient presents out of hours and is:

• ≥ 65 years

• has amnesia for events > 30 minutes before impact or

• there was a dangerous mechanism of injury

it is acceptable to admit for overnight observation, with CT imaging the next morning, unless CT result is required within 1 hour because of the presence of additional clinical findings listed above.

2.2.2 Management in ED:

The following recommendations are taken from the Reed (2009)4 guideline algorithm for the initial management of moderate and severe TBI which may occur in different settings but is included here for convenience. In addition, pain management, signs of neurological deterioration and indications for referral to neuroscience are included in this section.

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2.2.2.1 Initial management of severe TBI (GCS 3-8)

Standard care†††† includes4:

• Early intubation

• Initial assessment & resuscitation of ABCDE’s

• Supportive care of ABCDE’s with appropriate attention, posturing (30° head up), basic nursing care and avoidance of hyperventilation

• Prevent secondary injury by avoiding hypoxia (O2 saturation >90%) and hypotension (systolic BP <90)

• Early CT scan to identify neurosurgically correctable focal intracranial haematomas

• Early neurosurgical consult

• Consider ICP monitoring to guide management of cerebral perfusion pressure

• Optional use of anticonvulsants to prevent early post-traumatic seizures

• ICU admission

• Routine brain injury rehabilitation consult.

2.2.2.2 Initial management of moderate TBI (GCS 9-13)

Standard care includes4

• Initial assessment & resuscitation of ABCDE’s

• Early CT scan to identify neurosurgically correctable focal intracranial haematomas

• Period of ED observation

• Prevention of secondary brain injury by avoiding hypoxaemia (O2 saturation <90%) & hypotension (systolic BP <90)

• Supportive care of ABCDE’s

• Admit for prolonged hospital observation (24-48 hours) unless rapid clinical improvement, normal CT scan & absence of other risk factors‡‡‡‡

• Early neurosurgical consult if not clinically improving and/or abnormal CT scan

• Routine post-traumatic amnesia (PTA) testing and referral to brain injury rehabilitation service (or neurologist) due to high risk of cognitive behavioural social sequelae.

2.2.2.3 Pain Management:

There is some apparent conflicting guidance regarding pain management. For example, NICE (2007)7 recommends to manage pain effectively because it can lead to a rise in

†††† based on Brain Trauma Foundation 2000, Management & Prognosis of Severe TBI; American College of Surgeons Committee on Trauma 1997, Advanced Trauma Life Support for Doctors; and seven Cochrane reviews 2002-2003 ‡‡‡‡ see relevant evidence table for full details

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intracranial pressure and to treat significant pain with low dose of intravenous opioids. They also recommend that reassurance and splintage of limb fractures are helpful; catheterisation of a full bladder will reduce irritability. In contrast, the ACC (2006)1 guidance is that in general, people with a suspected TBI should not receive strong systemic analgesia until they have been fully assessed, so that an accurate measure can be made of consciousness and other neurological signs. No of the other guidelines make any recommendations concerning pain management.

2.2.2.4 Corticosteroids

The ACC (2206)1 and the ERABI12 group recommend to avoid the use of corticosteroids in the management of people with TBI of any kind. This is an ‘A’ grade recommendation based on a multicentre study of over 10000 participants with acute TBI which showed an increase of 18% in two-week all-cause mortality in the group receiving methylprednisolone.

2.2.2.5 Acute neurological deterioration4

Indications of deterioration:

• GCS falls by 2 or more points

• Develops dilated pupil(s)

• Develops focal neurological deficit

• Delayed or focal seizure

• Cushing’s response i.e. bradycardia & hypertension

Clinical approach:

• Re-assess ABCDE’s to exclude a non-head injury cause

• Supportive care of ABCDE’s e.g. perfusion & oxygenation

• Consider early intubation & short term hyperventilation to PaCO2 25-30

• Immediate CT scan if available

• Consult neurosurgical service

• Consult retrieval service early

• Consider the use of mannitol boluses (1g/kg) in consultation with neurosurgical service, to reduce ICP for transfer

• Consider local burr holes under local anaesthesia in consultation with the neurosurgical service if transfer likely to take more than 2 hours & CT scanning is available and has demonstrated a large extra axial haematoma§§§§

2.2.2.6 Indications for referral to neuroscience

Discuss the care of all patients with new, surgically significant***** abnormalities on imaging with a neurosurgeon1 4 6 7

§§§§ statement revised after personal communication with Dr R Bullock

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Regardless of imaging, other reasons for discussing a patient’s care plan with a neurosurgeon include:

• persisting coma (GCS ≤ 8†††††) after initial resuscitation1 4 6 7

• unexplained confusion for more than 4 hours6 7

• deterioration in GCS after admission (pay greater attention to motor response deterioration)7, especially a fall of ≥2, development of pupil dilation or other new neurological deficit1 4

• severe neurological deficit following TBI1

• progressive focal neurological signs4 6 7

• seizure without full recovery6 7

• definite or suspected penetrating injury6 7

• compound depressed skull fracture4 6

• cerebrospinal fluid leak7 or other sign of a basal skull fracture6

• when a person fulfils the criteria for CT scanning but facilities are unavailable6

• normal CT but not improving4.

Reed (2007)4 formats the recommendations with respect to severity but the guidance is very similar to above. Moreover, they recommend consultation with a neuroscience specialist when in doubt and that patients should be observed in facilities that can manage any complications that are likely to arise and that early neurosurgical consultation is advised.

***** definition of ‘surgically significant’ to be developed by local neurosurgical unit and agreed with referring hospitals ††††† i.e. all people with severe TBI

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2.3 Hospital care

Included in this section are indications for admission, type and frequency of clinical observations, indications for review and management in intensive care. Again, as in the last section, the separation into the various clinical settings is artificial and are grouped here together for convenience.

2.3.3 Indications for admission

These criteria are composed from the NICE (2007)7, ACC (2006)1 and SIGN (2009)6 guidelines.

Admit to hospital if there are ANY of the following:

• a deteriorating GCS1

• clinically significant abnormalities on imaging1 7

• GCS <15 after imaging1 6 7

• any indication for a CT scan6

• criteria for CT scanning are met but CT scanning is not possible1 7

• focal or abnormal neurological signs1

• early post-traumatic seizure1

• skull fracture

• high-risk mechanism of injury1

• continuing signs of concern to the clinician (e.g., vomiting, severe headaches, amnesia)1 7

• other reasons for clinician concern, including drug or alcohol intoxication, other injuries, shock, suspected non-accidental injury, signs of meningeal irritation, cerebrospinal fluid leak, where a scalp laceration overlies a fracture, or the person’s age1 7

• when there is no responsible family/whanau member, caregiver or close friend under whose care the person could be discharged1 6

• where there are significant comorbidities6 e.g. anticoagulant use

• ‘mild’ head injuries with symptoms such as headache, photophobia, nausea and vomiting, or amnesia requiring management1

Other relevant recommendations from the ACC (2006) guideline: • People who require an extended period in a recovery setting due to the use of sedation

or general anaesthetic during CT imaging should not normally require admission1

• Resuscitation and stabilisation of the injured person should be completed before transfer. A person persistently hypotensive despite resuscitation should not be transported until stabilised1

• People with multiple injuries should be admitted under the care of the team appropriate to their most severe and urgent problem1.

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2.3.3.1 In-hospital observation

Minimum neurological observations should include ALL the following:

• GCS

• pupil size and reactivity

• limb movements

• respiratory rate

• heart rate

• blood pressure

• temperature1 6 7

• blood oxygen saturation6 7

• unusual behaviour or temperament or speech impairment6.

Perform and record observations at least every 15 minutes until GCS is 15 on two consecutive occasions1 (NB: NICE (2007)7 and SIGN (2009)6 recommend half-hourly observations).

The ACC (2006)1 guideline also adds to assess for post-traumatic amnesia and focal neurological signs at regular intervals1.

For people with an initial GCS of 15, or who have returned to a GCS of 15 on two consecutive observations, the minimum frequency of observations following the initial assessment should be:

• half-hourly for the first two hours, then

• one-hourly for four hours, then

• two-hourly thereafter1 7

If the person deteriorates to GCS <15 after initial 2-hour period, revert to 15 minute observations and follow original schedule1 7

2.3.3.2 Indications for review

Consider immediate CT scan, re-assess patient’s clinical condition and manage appropriately, if

• Agitation or abnormal behaviour developed6 7

• GCS dropped by 1 point and lasted for at least 30 minutes (give greater weight to a drop of 1 point in the motor response score)1 6 7

• Any drop of 3 or more points in the eye-opening or verbal response scores, or 2 or more points1 in the motor response score6 7

• Severe or increasing headache developed or persistent vomiting1 6 7

• New or evolving neurological symptoms or signs, such as pupil inequality or asymmetry of limb or facial movement1 6 7.

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In addition, if GCS 15 not achieved after 24 hours’ observation, but CT scan normal: consider further CT imaging or MRI scanning and discuss with radiology department1 7.

SIGN (2009)6 has given the following additional guidance, mainly based on expert opinion:

• Clinical signs of shock in a patient with a head injury should be assumed, until proven otherwise, to be due to hypovolaemia caused by associated injuries

• Whilst an intoxicating agent may confuse the clinical picture, the assumption that deterioration or failure to improve is due to drugs or alcohol must be resisted

• If systemic causes of deterioration such as hypoxia, fluid and electrolyte imbalance, or hypoglycaemia can be excluded, then resuscitation should continue according to ATLS principles while anaesthetic help and neurosurgical advice are sought

• After traumatic brain injury remedial causes of agitation should be excluded before therapies are started.

2.3.4 Intensive care management

The major focus for intensive care is:

• The prevention & limitation of ongoing brain damage2

• To provide the best conditions for natural brain recovery by reducing brain swelling & raised ICP2

Due to the clinical complexity of patients who are admitted to intensive care for management of their TBI and the limited scope of this document, evidence will only be presented for the efficacy of interventions for post-traumatic seizures and treatment of raised ICP.

As in general intensive care, optimum oxygenation, perfusion, nutrition, glycaemic control & temperature homeostasis are essential2.

2.3.4.1 Post-traumatic seizure

• Benefits of prophylactic anti-seizure treatment must be balanced against the potential risks; recommended indications include penetrating brain injury & depressed skull fracture in patients with PTA >24 hours in whom a dural lesion is suspected2

According to the ERABI12 Research Group, seizure can occur with in hours of the initial head trauma (immediate seizures), within the first week of sustaining the injury (early seizures) or several months post injury (late seizures). These seizures can further complicate the injury has they can lead to increased damage. It has also been noted that the risk for developing or having late seizures post TBI is related to the severity of injury.

The Brain Trauma Foundation3 does not recommend the prophylactic use of phenytoin or valproate for preventing late post-traumatic seizures. Their prophylactic use results in similar incidences of early or late seizures and similar mortality rates12. If late post-traumatic seizures occur, they recommend patients should be managed in accordance with standard approaches to patients with new onset seizures. The ERABI group12 suggest, from one case study, that intramuscular midazolam may be effective for acute seizure cessation12. It also appears to have less adverse effects than other commonly used intramuscular drugs such as diazepam and lorazepam12.

The Foundation also states that anticonvulsants are indicated to decrease the incidence of early post-traumatic seizures (within 7 days of injury). However, early post-traumatic seizures

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are not associated with worse outcomes3 and ERABI12 conclude that anticonvulsants provided shortly post-TBI do not reduce long-term mortality, morbidity or late seizures and that anticonvulsants provided immediately post-TBI reduce the occurrence of seizures only within the first week.

Phenytoin has been shown to reduce the incidence of early post-traumatic seizures3 12 and may reduce the risk of late seizures12. Valproate may have a comparable effect to phenytoin on reducing early post-traumatic seizures but may be associated with a higher mortality3. On the other hand, levetiracetam is as effective as phenytoin in treating and preventing seizures in individuals in the intensive care unit post TBI12. In addition, both phenytoin and carbemazepine have negative effects on cognitive performance, particularly those tasks with a motor and speed components12. There is also some lower level evidence‡‡‡‡‡ that carbemazepine improves seizure control and is less harmful to cognitive performance and behaviour than other anticonvulsants12.

2.3.4.2 Raised Intracranial Pressure

2.3.4.2.1 Monitoring • ICP should be monitored in all people with a severe TBI (in a coma) and an abnormal

CT scan3

There is evidence to support the use of ICP monitoring in people with a severe TBI who are at risk for intracranial haemorrhage3. Not monitoring ICP while treating raised ICP can be deleterious and result in a poor outcome3

2.3.4.2.2 Sedation and ventilation • Sedation & artificial ventilation are used to reduce brain swelling & raised ICP in

patients with severe TBI2 13

The Brain Trauma Foundation3 recommends propofol for the control of ICP, but not for improvement in mortality or 6 month outcome. In addition, high-dose propofol (>4mg/kg per hour12) can produce significant morbidity13. ERABI found that propofol may help to reduce ICP and the need for other ICP and sedative interventions when used in conjunction with morphine12 13.

High-dose barbiturate administration is also recommended to control elevated ICP that is refractory to maximum standard medical and surgical treatment. Of note, haemodynamic stability is essential before and during barbiturate therapy3. ERABI12 makes the further recommendations: there is conflicting evidence regarding the efficacy of pentobarbital over conventional ICP management measures13; thiopental is more effective than pentobarbital for controlling unmanageable refractory ICP13; pentobarbital is not better than mannitol for the control of elevated ICP13; barbiturate therapy plus hypothermia may improve clinical outcomes§§§§§; patients undergoing barbiturate therapy should have their immunological response and systemic blood pressure monitored13.

2.3.4.2.3 Hyperventilation • Hyperventilation has been used to reduce ICP effectively however there is a risk of

worsening ischaemia2

• Arterial CO2 < 30 mmHg should be avoided2

‡‡‡‡‡ Level 4 = case series, pre-post or post-study, or retrospective chart review

§§§§§ based on one level 4 study

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Prophylactic hyperventilation (pCO2 ≤25 mmHg) is not recommended by the Brain Trauma Foundation but may be used as a temporising measure for the reduction of raised ICP3. They also add that it should be avoided during the first 24 hours after injury when cerebral blood flow (CBF) is often critically reduced. If hyperventilation is used, they recommend that jugular venous oxygen saturation (SjO2) or brain tissue oxygen tension (PbrO2) measurements are used to monitor oxygen delivery3. In addition ERABI make the following statements: hyperventilation below 34 mmHg PaCO2 may cause an increase in hypoperfused brain tissue; tromethamine counteracts the detrimental effects of prolonged hyperventilation for the control of ICP leading to better outcomes post-TBI; hyperoxia may counteract the adverse effects of prolonged hyperventilation for the control of ICP post-TBI12.

2.3.4.2.4 Osmotherapy • Osmotherapy is usually considered as second line treatment after sedation and artificial

ventilation have failed to control ICP****** & interest in early & extensive craniotomies is increasing2

• There is insufficient evidence to support the use of hypertonic saline over mannitol because of the risks of hypernatraemia with hypertonic saline2

• Osmotherapy is best reserved for patients in whom ICP is being monitored††††††

Rapid administration of mannitol is among the first-line treatments recommended for the management of increased ICP. However, it is associated with significant diuresis and can cause acute renal failure, hyperkalemia, hypotension, and in some cases rebound increments in ICP12. For these reasons, the Brain Trauma Foundation recommends that mannitol should only be used if a patient has signs of elevated ICP or deteriorating neurological status12.

The Brain Trauma Foundation3 concludes that mannitol is effective in reducing ICP in the management of raised ICP post-TBI at doses of 0.25 gm/kg to 1 g/kg body weight. They add that arterial hypotension (SBP < 90 mm Hg) should be avoided and advise to restrict the use of mannitol (prior to ICP monitoring) only to patients with signs of transtentorial herniation or progressive deterioration not attributable to extracranial causes3.

ERABI12 make the following statements regarding the use of mannitol for raised ICP: high dose mannitol results in lower mortality rates and better clinical outcomes compared with conventional mannitol13; early out of hospital administration of mannitol does not negatively affect blood pressure13; mannitol may only lower ICP when initial ICP values are abnormally elevated13.

With regard to hypertonic saline, the Brain Trauma Foundation3 does not make any recommendations on its use because current evidence is not strong enough. The ERABI group, however, make the following statements: hypertonic saline reduces ICP more effectively than mannitol13; hypertonic saline and Ringer’s lactate solution are similar in lowering elevated ICP and result in similar clinical outcomes and survival up to 6 months post-injury13; hypertonic saline may reduce elevated ICP uncontrolled by conventional ICP management measures; hypertonic saline may aid in resuscitation of brain injured patients by increasing cerebral oxygenation.

2.3.4.2.5 Decompressive craniectomy • Decompressive craniectomy is controversial as it does not produce improved outcome

in all people & has many side-effects, some severe2. There is a consensus that the

****** recommendation revised after personal communication with Dr R Bullock

†††††† personal communication with Dr R Bullock

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craniectomy should be large enough i.e. at least 15cmx15cm2, & done early & with duraplasty2

The Brain Trauma Foundation does not mention depressive craniectomy, however, ERABI make the following conclusions: in adults standard trauma craniectomy leads to better control of ICP and better clinical outcomes at 6 months when compared with limited craniectomy; resection of a larger bone flap during craniectomy may lead to a greater reduction in ICP, better patient outcomes and fewer post-surgical complications12.

Brain Trauma Foundation surgical guidelines14 also recommend the removal of large intraparenchymal lesions such as contusions or intracerebral haemorrhage, where there is substantial midline shift and mass effect, along with the decompressive craniectomy.

A recent systematic review15 found that in adults depressive craniectomy reduces ICP immediately after surgery and appears to be more effective when a larger bone flap is removed. They also found evidence that adults with a GCS <6 show no improvements in neurological outcomes after this procedure15.

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3 References 1. Accident Compensation Corporation. Traumatic brain injury: diagnosis, acute

management and rehabilitation. 2006. www.acc.co.nz/PRD_EXT_CSMP/groups/external.../wim2_059414.pdf

2. Maas AI, et al. Moderate and severe traumatic brain injury in adults. Lancet Neurol 2008;7(8):728-41.

3. Brain Trauma Foundation. Guidelines for the management of severe traumatic brain injury 3rd edition. Journal of Neurotrauma 2007;24(Supplement 1).

4. Reed D. Adult trauma clinical practice guideline: initial management of closed head injury in adults 2007. www.itim.nsw.gov.au/images/2/2b/Head_injury_CPG_full_report.pdf

5. Badjatia N, et al. Guidelines for prehospital management of traumatic brain injury 2nd edition. Prehospital Emergency Care 2008;12 Suppl 1:S1-52.

6. Scottish Intercollegiate Guidelines Network. Early management of patients with a head injury. A national clinical guideline. SIGN publication; no. 110 2009. http://www.sign.ac.uk/guidelines/fulltext/110/index.html

7. National Institute for Health & Clinical Excellence. Head injury: triage, assessment, investigation and early management of head injury in infants, children and adults. NICE clinical guideline 56 2007. http://guidance.nice.org.uk/CG56

8. Hammell CL, Henning JD. Prehospital management of severe traumatic brain injury. BMJ 2009;338:b1683.

9. von Elm E, et al. Pre-hospital tracheal intubation in patients with traumatic brain injury: systematic review of current evidence. British Journal of Anaesthesia 2009;103(3):371-86.

10. National Institute for Health and Clinical Excellence. The clinical and cost effectiveness of prehospital intravenous fluid therapy in trauma. 2004. www.nice.org.uk/nicemedia/pdf/ta074guidance.pdf.

11. Wakai A, et al. Mannitol for acute traumatic brain injury (Cochrane review). Cochrane Database of Systematic Reviews 2007;2007(1):CD001049.

12. ERABI Research Group. Evidence-Based Review of Moderate To Severe Acquired Brain Injury 2011. http://www.abiebr.com/

13. Meyer MJ, et al. Acute management of acquired brain injury part II: an evidence-based review of pharmacological interventions. Brain Injury 2010b;24(5):706-21.

14. Brain Trauma Foundation. Guidelines for the surgical management of traumatic brain injury. Neurosurgery 2006;58(3, supplement March 2006).

15. Meyer MJ, et al. Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions. Brain Injury 2010a;24(5):694-705.