Management of Acute Severe Traumatic Brain Injury

19/6/2016 Management of acute severe traumatic brain injury
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®
Management of acute severe traumatic brain injury
Authors Section Editors Deputy Editor

J Claude Hemphill, III, MD, MAS Michael J Aminoff, MD, DSc Janet L Wilterdink, MD
Nicholas Phan, MD, FRCSC, FACS Maria E Moreira, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2016. | This topic last updated: Feb 10, 2015.
INTRODUCTION — Traumatic brain injury (TBI) is the leading cause of death in North America for individuals between
the ages of 1 to 45 [1,2]. Many survivors live with significant disabilities, resulting in major socioeconomic burden as well.
In 2000, the economic impact of TBI in the United States was estimated to be $9.2 billion in lifetime medical costs and
$51.2 billion in productivity losses.
One of the major advances over the past two decades in the care of patients with severe head injury has been the
development of standardized approaches that follow international and national guidelines [36]. The intent of these
guidelines has been to use existing evidence to provide recommendations for current care in order to lessen heterogeneity
and improve patient outcomes. Unfortunately, the lack of randomized clinical trials addressing many aspects of care of the
severe TBI patient has meant that the strength of supporting data for most treatment concepts is relatively weak. Despite
this caveat, there is evidence that treatment in centers with neurosurgical support, especially in settings where protocol
driven neurointensive care units operate based on the abovereferenced guidelines, is associated with better patient
outcomes [714]. Many expert panels recommend that treatment of severe TBI should be centralized in large trauma
centers that offer neurosurgical treatment and access to specialized neurocritical care.
Patients with severe head injury may frequently have other traumatic injuries to internal organs, lungs, limbs, or the spinal
cord. Thus, the management of the patient with severe head injury is often complex and requires a multidisciplinary
approach and lends itself to protocolbased treatment and standardized hospital order sets derived from the previously
referenced guidelines.
This topic discusses the management of acute severe traumatic brain injury. The epidemiology and pathophysiology of
traumatic brain injury, the management of mild traumatic brain injury, acute spinal cord injury, and other aspects of care of
the trauma patient are discussed separately. (See "Traumatic brain injury: Epidemiology, classification, and
pathophysiology" and "Concussion and mild traumatic brain injury" and "Acute traumatic spinal cord injury" and "Skull
fractures in adults".)
INITIAL EVALUATION AND TREATMENT
Prehospital — The primary goal of prehospital management for severe head injury is to prevent hypotension and hypoxia,
two systemic insults known to be major causes of secondary injury after TBI [1520]. In a metaanalysis of clinical trials
and populationbased studies, hypoxia (PaO2 <60 mmHg) and hypotension (systolic BP <90 mmHg) were present in 50
and 30 percent of patients, respectively, and were each associated with a higher likelihood of a poor outcome: hypoxia
(OR 2.14); hypotension (OR 2.67) [16]. Changes in prehospital management that aim to normalize oxygenation and blood
pressure have improved outcomes [2125]:
● Early endotracheal intubation is generally recommended for patients with a Glasgow coma scale score of 8 or less if
performed by welltrained personnel (table 1). The value of prehospital intubation is controversial, with studies finding
conflicting results [26]. In one randomized trial of 312 patients with severe TBI performed in Australia, prehospital
rapid sequence intubation by paramedics was associated with better functional outcome at six months compared
with intubation in hospital (51 versus 39 percent of patients with favorable outcome on Glasgow outcome scale) [27].
However, another study in San Diego, CA found that prehospital intubation was associated with an increased
mortality, perhaps due to inadvertent hyperventilation, transient hypoxia, or longer time at scene prior to transport
[28]; hemodynamic instability induced during intubation is another potential explanation for adverse outcome [29]. A
benefit from prehospital intubation by paramedics requires extensive training and is not widely generalizable [30]. If
this expertise is not available, bagmask ventilation is recommended.
● Prevention of hypotension in the prehospital setting is best accomplished by adequate fluid resuscitation using
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isotonic crystalloids. Studies of hypertonic saline in the prehospital setting have not suggested benefit [31,32]. Saline
is preferred over albumin; the latter was associated with increased mortality in one randomized study of patients with
TBI [33].
Patients with TBI should be assumed to have a spinal fracture and appropriate precautions taken to stabilize and
immobilize the spine during transport. (See "Acute traumatic spinal cord injury".)
A prehospital assessment of the Glasgow coma scale can be helpful for early triage decisions (table 1).
The prehospital management of the trauma patient is discussed in detail separately. (See "Prehospital care of the adult
trauma patient".)
Emergency department — In the early hospital admission phase of patients with severe head injury, treatment and
diagnostic assessment is done according to the ATLS (Advanced Trauma Life Support) protocol:
● Adequate oxygenation (PaO2 >60 mmHg) and blood pressure support (systolic BP >90 mmHg) continue to be
priorities [15]. (See "Emergency airway management in the patient with elevated ICP".)
● Vital signs including heart rate, blood pressure, respiratory status (pulse oximetry, capnography), and temperature
require ongoing monitoring.
● A neurologic examination should be completed as soon as possible to determine the clinical severity of the TBI. The
Glasgow coma scale (GCS) is commonly used to assess and communicate neurologic status in this setting (table
1). A GCS score of 8 or lower is considered a severe TBI. Neurologic status should be continuously assessed.
Deterioration is common in the initial hours after the injury.
● The patient should be assessed for other systemic trauma.
● A complete blood count, electrolytes, glucose, coagulation parameters, blood alcohol level, and urine toxicology
should be checked. Coagulopathy is common in patients with severe TBI, either resulting from patient medications or
as a consequence of the trauma itself. When the INR is elevated, then efforts to reverse the coagulopathy should
begin immediately. (See 'Hemostatic therapy' below and "Coagulopathy associated with trauma".)
Efforts to evaluate and manage increased intracranial pressure (ICP) should begin in the emergency department. Patients
with severe TBI (GCS ≤8) and clinical symptoms suggesting possible impending herniation from elevated ICP (unilaterally
or bilaterally fixed and dilated pupil(s), decorticate or decerebrate posturing, bradycardia, hypertension, and/or respiratory
depression) should be treated urgently, with head elevation and osmotic therapy (mannitol 1 g/kg iv) concurrently with
neuroimaging and other assessments. The evaluation and management of increased ICP are discussed in detail below.
(See 'Intracranial pressure' below.)
Patients with TBI should be transferred to a hospital with neurosurgical services as soon as they are hemodynamically
stable [711].
Neuroimaging — Computed tomography (CT) is the preferred imaging modality in the acute phase of head trauma and
should be performed as quickly as possible. CT scan will detect skull fractures, intracranial hematomas, and cerebral
edema (image 1AD). Current guidelines recommend head CT in all TBI patients with a Glasgow coma scale of 14 or
lower (table 1).
Followup CT scanning should be performed if there is any clinical deterioration. Evolution of CT findings is common and
may indicate an alternative treatment approach in a significant number of patients [3438]. While there is no clear
indication for routine followup CT scans in the absence of clinical change or changes in physiological parameters such as
ICP, practice varies considerably in this regard [39,40]. Many centers do routinely order followup imaging. Of note,
parenchymal contrast extravasation, as with spontaneous intracerebral hemorrhage, may predict a higher risk of
hemorrhage progression [41]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and
diagnosis", section on 'Hemorrhage enlargement'.)
SURGICAL TREATMENT — Indications for emergency surgery after severe head injury are based upon neurologic
status, usually defined by the Glasgow coma scale (GCS) (table 1), and findings on head CT criteria such as large
hematoma volume or thickness and evidence of mass effect including midline shift (image 1A).
Epidural hematoma — Surgical guidelines recommend evacuation of an epidural hematoma (EDH) larger than 30 mL in
volume regardless of a patient's GCS score; urgent surgical evacuation is recommended for patients with acute EDH and
coma (GCS score ≤8) who have pupillary abnormalities (anisocoria) [42]. (See "Intracranial epidural hematoma in adults",
section on 'Management'.)
Subdural hematoma — Acute subdural hematomas (SDH) >10 mm in thickness or associated with midline shift >5 mm
on CT should be surgically evacuated, regardless of the patient's GCS score [43]. In addition, surgery is recommended if
the GCS score is ≤8 or if the GCS score has decreased by ≥2 points from the time of injury to hospital admission, and/or
the patient presents with asymmetric or fixed and dilated pupils, and/or intracranial pressure measurements are
consistently >20 mmHg. (See "Subdural hematoma in adults: Prognosis and management", section on 'Acute SDH'.)
Intracerebral hemorrhage — Surgical evacuation of a traumatic intracerebral hemorrhage (ICH) in the posterior fossa is
recommended when there is evidence of significant mass effect (distortion, dislocation, obliteration of the fourth ventricle,
compression of the basal cisterns, or obstructive hydrocephalus) [44].
For traumatic ICH involving the cerebral hemispheres, surgical indications are not as clearly defined. Consensus surgical
guidelines recommend craniotomy with evacuation if the hemorrhage exceeds 50 cm3 in volume, or if the GCS score is 6
to 8 in a patient with a frontal or temporal hemorrhage greater than 20 cm3 with midline shift of at least 5 mm and/or
cisternal compression on CT scan [45].
Penetrating injury — Superficial debridement and dural closure to prevent CSF leak is generally recommended [46].
Small entry wounds can be treated with simple closure. Aggressive debridement and removal of deep foreign bodies such
as bone or bullet fragments have not been shown to be effective in preventing delayed infection. The use of prophylactic
broadspectrum antibiotics (usually a cephalosporin) is routine in this setting and is believed to have contributed to the
reduced incidence of infection in this setting [47].
Depressed skull fracture — Elevation and debridement are recommended for open skull fractures depressed greater than
the thickness of the cranium or if there is dural penetration, significant intracranial hematoma, frontal sinus involvement,
cosmetic deformity, wound infection or contamination, or pneumocephalus [48]. (See "Skull fractures in adults" and "Skull
fractures in children".)
Decompressive craniectomy — In a decompressive craniectomy, a substantial portion of the skull is removed in order to
reduce increased intracranial pressure (ICP). This can be done in combination with an evacuation procedure or as a
primary treatment for increased ICP [49]. Use of this technique is controversial and its efficacy in TBI is uncertain [5055].
Clinical trials are in progress, with a pilot study in children suggesting favorable results on both ICP and clinical outcome
[56].
A randomized trial in 155 adults with severe diffuse TBI with elevated ICP refractory to other therapies compared bifrontal
decompressive craniectomy with continued standard care [57]. Surgery was associated with decreased ICP and shorter
stays in the intensive care unit, but worse outcome on the extended Glasgow outcome scale at six months. The study has
been criticized for having a baseline imbalance in TBI severity between the treatment groups, a relatively low threshold for
elevated ICP, and a short time window for defining it to be treatment resistant [58]. Also, the surgical procedure used in
this study is not representative of that most often performed in clinical care. Other clinical trials are in progress.
This procedure, its complications, and its efficacy in settings other than TBI are discussed in detail separately. (See
"Evaluation and management of elevated intracranial pressure in adults", section on 'Decompressive craniectomy' and
"Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction".)
INTENSIVE CARE MANAGEMENT — The principal focus of critical care management for severe TBI is to limit
secondary brain injury. In general, treatment efforts are aimed at intracranial pressure management and maintenance of
cerebral perfusion as well as optimizing oxygenation and blood pressure and managing temperature, glucose, seizures,
and other potential secondary brain insults.
General medical care — Maintenance of BP (systolic >90 mmHg) and oxygenation (PaO2 >60 mmHg) remain priorities in
the management of TBI patients in the ICU [15]. These should be continuously monitored. Isotonic fluids (normal saline)
should be used to maintain euvolemia. A subgroup analysis in the large SAFE study found that for patients with TBI, fluid
resuscitation with albumin was associated with a higher mortality as compared with normal saline (33 versus 20 percent);
this risk was even more pronounced in those with severe TBI (42 versus 22 percent) [33]. Electrolyte imbalances are
common in patients with TBI and should be regularly assessed along with other laboratory parameters.
Other extracranial traumatic injuries are managed simultaneously. (See appropriate topic reviews.)
The prevention of deep venous thrombosis (DVT) is a difficult management issue in TBI. Patients with TBI are at
increased risk of DVT which can be reduced by the use of mechanical thromboprophylaxis using intermittent pneumatic
compression stockings [59,60]. While DVT risk can be further reduced with antithrombotic therapy, this has to be weighed
against the potential risk of hemorrhage expansion, which is greatest in the first 24 to 48 hours [6163]. The use and timing
of antithrombotic agents in patients with TBI must therefore be individualized according to the degree of intracranial
bleeding and the perceived risk of DVT. No randomized studies have examined the risks and benefits of antithrombotic
agents in this setting. While some observational studies suggest that antithrombotic therapy may not be associated with
the increased risk of intracranial hemorrhage expansion [6466], others have found a higher rate of hemorrhage progression
with the use of low molecular weight heparin [67]. One pilot study randomly assigned 62 patients with lowrisk TBI to
enoxaparin or placebo [68]. Subclinical, radiographic progression of intracranial hemorrhage was nonsignificantly more
common in the treated patient group; no patient suffered a clinical progression; one patient in the placebo group had a
DVT. (See "The use of antithrombotic therapy in patients with an acute or prior intracerebral hemorrhage", section on
'Prevention' and "Prevention of venous thromboembolic disease in surgical patients".)
Nutritional support should not be neglected in patients with TBI. Undernutrition is associated with higher mortality [69,70].
Patients should be fed to full caloric replacement by day seven postinjury [71]. (See "Nutrition support in critically ill
patients: An overview".)
TBI patients are at risk for other complications (eg, infection, gastrointestinal stress ulceration), which can be reduced by
appropriate interventions. Other aspects of the general medical care of the trauma patient are discussed in detail
separately. (See "Overview of inpatient management in the adult trauma patient".)
Intracranial pressure — Elevated intracranial pressure (ICP) is associated with increased mortality and worsened
outcome [7274].
Specific measures regarding ICP management in the setting of TBI are discussed here. The evaluation and management
of elevated ICP in other settings is discussed in detail separately. (See "Evaluation and management of elevated
intracranial pressure in adults".)
Initial treatment and ICP monitoring — Several approaches are used in the intensive care setting to prevent and
treat elevated ICP. Simple techniques should be instituted as soon as possible:
● Head of bed elevation to 30 degrees
● Optimization of venous drainage: keeping the neck in neutral position, loosening neck braces if too tight
● Monitoring central venous pressure and avoiding excessive hypervolemia
Indications for ICP monitoring in TBI are a GCS score ≤8 and an abnormal CT scan showing evidence of mass effect from
lesions such as hematomas, contusions, or swelling [75]. ICP monitoring in severe TBI patients with a normal CT scan
may be indicated if two of the following features are present: age >40 years; motor posturing; systolic BP <90 mmHg. A
ventricular catheter connected to a strain gauge transducer is the most accurate and costeffective method of ICP
monitoring and has the therapeutic advantage of allowing for CSF drainage to treat rises in ICP (figure 1) [75]. Other
monitor types are discussed separately. (See "Evaluation and management of elevated intracranial pressure in adults",
section on 'Types of monitors'.)
While ICP monitoring has long been central to the management of patients with severe head injury, the strength of this
recommendation has been limited by the lack of large randomized trials examining the effect of ICP monitoring and
treatment on outcome [7678]. One randomized study of 324 patients with severe TBI hospitalized in Bolivia or Ecuador
found no differences in outcomes among those patients assigned to a protocol for monitoring ICP and focusing treatment
on maintaining pressures at 20 mm Hg or less compared with patients assigned to a treatment protocol based on imaging
and clinical examination [79]. The results of this study suggests that further research is needed to assess the role of ICP
monitoring as well as targeted treatments of ICP in the management of severe TBI.
Most guidelines and clinical protocols recommend that treatment for elevated ICP should be initiated when ICP rises
above 20 mmHg [80]. Ventricular drainage is generally attempted first. CSF should be removed at a rate of approximately
1 to 2 mL/minute, for two to three minutes at a time, with intervals of two to three minutes in between until a satisfactory
ICP has been achieved (ICP <20 mmHg) or until CSF is no longer easily obtained. Slow removal can also be
accomplished by passive gravitational drainage through the ventriculostomy.
If ICP remains elevated, other targeted interventions include osmotic therapy, hyperventilation, and sedation. In refractory
cases, barbiturate coma, induced hypothermia, and decompressive craniectomy may be considered [81].
Osmotic therapy — The intravascular injection of hyperosmolar agents (mannitol, hypertonic saline) creates an
osmolar gradient, drawing water across the bloodbrain barrier [82]. This leads to a decrease in interstitial volume and a
decrease in ICP.
● Mannitol is the agent used most consistently to achieve ICP control in various settings, and it has also been shown
to improve cerebral blood flow [77,8387]. Mannitol is administered in boluses of 0.25 to 1 g/kg every four to six
hours as needed. Monitoring of serum osmolality (maintained <320 mMol/L), fluid balance, renal function, and
electrolytes is required. (See "Evaluation and management of elevated intracranial pressure in adults", section on
'Mannitol'.)
● Hypertonic saline is being used increasingly in this setting, but with varying volumes and tonicity (3 to 23.4 percent)
and either as a bolus or continuous infusion [88,89].
Two small studies have compared mannitol and hypertonic saline in patients with TBI:
● In one study, nine patients received two treatments each of 200 mL 20 percent mannitol and 100 mL of 7.5 percent
saline with 6 percent dextran70 solution (HSD) in a random order [90]. Median ICP reductions were greater with
HSD than mannitol infusion (13 versus 7.5 mmHg).
● In another study, 20 patients were randomly assigned treatment with either 20 percent mannitol or 7.5 percent
hypertonic saline solution, each given as a dose of 2 mL/kg [91]. The mean number and duration of recurrent
elevated ICP episodes were higher in patients treated with mannitol than with hypertonic saline.
Clinical outcomes were not a focus of either of these studies. Further work is required to clarify what role hypertonic saline
infusion has in the management of elevated ICP [77,92].
Hyperventilation — Most patients with severe TBI are sedated and artificially ventilated during the first several days
[93]. Regarding ICP management, control of ventilation helps prevent increases in intrathoracic pressure that may elevate
central venous pressures and impair cerebral venous drainage.
Hyperventilation can be used to reduce ICP. With hyperventilation, PaCO2 decreases thereby leading to cerebral
vasoconstriction, which then results in decreased cerebral blood volume and ICP. However, hyperventilationinduced
vasoconstriction may also cause secondary ischemia and may thereby worsen outcomes [9496]. Hyperventilation can
also increase extracellular lactate and glutamate levels that may contribute to secondary brain injury [97]. In one
randomized study, patients hyperventilated to a PaCO2 of 25 mmHg for five days had a worse clinical outcome than
nonhyperventilated controls [98].
Based upon these competing concerns, guidelines recommend avoiding hyperventilation, especially in the acute phase
(the first 24 to 48 hours) following TBI. Mild to moderate hyperventilation can be considered at later stages, but PaCO2 of
less than 30 mmHg should be avoided [99]. Multimodality monitoring of cerebral oxygenation and metabolism (see
'Advanced neuromonitoring' below) should also be used where available with therapeutic hyperventilation to monitor its
effects and prevent ischemic episodes [95,96,100].
Sedation — Sedative medications and pharmacological paralysis are often used in patients with severe head injury
and elevated ICP. The rationale is that appropriate sedation may lower ICP by reducing metabolic demand. Sedation may
also ameliorate ventilator asynchrony and blunt sympathetic responses of hypertension and tachycardia. These possible
beneficial effects are counterbalanced by the potential for these drugs to cause hypotension and cerebral vasodilation that
in turn may aggravate cerebral hypoperfusion and elevate ICP.
While there are a number of agents that can be used, we prefer to use propofol at our institution because of its short
duration of action that allows intermittent clinical neurologic assessment [101]. Anecdotally, propofol sedation can produce
ICP reductions. Propofol also has putative neuroprotective effects [102]. In one trial, propofol appeared to be associated
with better ICP control and a trend toward better outcomes compared with morphine sedation [103]. However, some
reports suggest that patients with TBI are at particular risk of developing the rare, but potentially fatal propofol infusion
syndrome (severe metabolic acidosis, rhabdomyolysis, hyperkalemia, renal failure, and cardiovascular collapse) [104,105].
As a result, it is suggested that when used in TBI, the infusion rate of propofol not exceed 4 mg/kg per hour and that
patients be monitored for ECG changes, lactic acidosis, and elevations in creatinine kinase and myoglobin. (See
"Sedativeanalgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal", section on
'Available agents'.)
Barbiturate coma has been used traditionally in this setting. However, there is little clinical data to support its use [106]:
● In a randomized trial of 73 patients with severe TBI, pentobarbital coma was associated with more effective ICP
control compared to control treatment, but not improved 30day mortality [107].
● Thiopental was compared to pentobarbital in a small study of 44 patients with TBI [108]. While thiopental appeared
more effective in terms of ICP control, conclusions drawn from this study are limited by its small size and an
imbalance in baseline CT characteristics in the treatment groups [108].
In addition, highdose barbiturates often cause hypotension necessitating treatment with pressor agents [106,109].
Pentobarbital remains a treatment option for elevated ICP refractory to other therapies [110]. A loading dose of 5 to 20
mg/kg is given as a bolus, followed by 1 to 4 mg/kg per hour. Continuous EEG monitoring is used, with the pentobarbital
infusion titrated to produce a burstsuppression pattern.
Other sedative agents may also be used, although none have been well studied in patients with severe TBI. These may
include benzodiazepines or opiates (eg, midazolam, morphine, fentanyl) individually or in combination with barbiturates
and/or neuromuscular blockade [110112]. A systematic review of trials of sedative agents in this setting found no
convincing evidence to support the use of one agent over another [113]. However, high bolus doses of opioids were found
to cause transient increases in intracranial pressure, which may warrant avoidance of that treatment approach. (See
"Sedativeanalgesic medications in critically ill adults: Selection, initiation, maintenance, and withdrawal".)
In the absence of clinical trial data to support the use of any specific protocol, we suggest that the use of sedation be
individualized according to specific clinical circumstances and that the choice of agent(s) be similarly individualized,
considering also the specific institutional expertise. Monitoring of cerebral perfusion pressure is advised (see 'Cerebral
perfusion pressure' below) to evaluate the somewhat unpredictable effects of these agents on blood pressure and ICP.
Cerebral perfusion pressure — Through autoregulation, the normal cerebral vasculature maintains an adequate cerebral
blood flow (CBF) across a wide range (50 to 150 mmHg) of mean arterial blood pressure (MAP). Cerebral autoregulation is
disrupted in about a third of patients with severe TBI [114116]. In these patients, a rise in MAP can lead to elevated ICP
due to increased cerebral blood volume and hyperemia, while drops in MAP may be associated with hypoperfusion and
ischemia. Patients with impaired cerebral autoregulation are described as "pressurepassive".
While optimization of CBF is a foundation of TBI treatment, bedside measurement of CBF is not easily obtained. Cerebral
perfusion pressure (CPP), the difference between the mean arterial pressure (MAP) and the intracranial pressure: CPP =
MAP ICP, is a surrogate measure. Episodes of hypotension (low MAP), raised ICP, and/or low CPP are associated with
secondary brain injury and worse clinical outcomes [21,22,117].
An early approach to induce hypertension to target CPP >70 mmHg using volume expansion and vasopressor agents
appeared to reduce mortality and morbidity [118,119]. However, subsequent studies have suggested that this strategy
does not improve outcome and rather risks severe extracerebral complications such as acute respiratory distress
syndrome [119121]. According to guidelines published in 2007, the recommended CPP target is 60 mmHg, avoiding levels
below 50 mmHg and above 70 mmHg [122124]. In children these thresholds may be lower, 40 to 65 mmHg [125]. Efforts
to optimize CPP should first treat and maintain ICP at low levels when possible [126]. This may have a more substantial
effect on CBF and obviate the use of fluids and inotropic agents. Patients with more severely impaired autoregulation in
particular may be more likely to respond to efforts to lower ICP than to hypertensivefocused CPP therapy [120].
Antiepileptic drugs — Overall, the incidence of early posttraumatic seizures (within the first week or two) is about 6 to
10 percent but may be as high as 30 percent in patients with severe TBI [127129]. In addition, case series suggest that
about 15 to 25 percent of patients with coma and severe head injury will have nonconvulsive seizures identified on
continuous monitoring with electroencephalography (EEG) [129,130]. However, the clinical significance of clinically silent
electrographic seizures and whether they should be treated is unclear.
The use of antiepileptic drugs (AEDs) in the acute management of TBI has been shown to reduce the incidence of early
seizures, but does not prevent the later development of epilepsy [131,132]. Reasons to prevent early seizures include the
risk of status epilepticus, which has a high fatality rate in this setting, and the potential of convulsions to aggravate a
systemic injury [129]. In addition, recurrent seizures may increase cerebral blood flow and could thereby increase ICP.
Another potential concern is that seizures place a metabolic demand on damaged brain tissue and may aggravate
secondary brain injury.
Based upon the available information, we use the following approach to seizure management in patients with severe TBI:
● Use a sevenday course of prophylactic phenytoin or valproic acid. Levetiracetam can be considered as an
alternative.
● Do not use AED prophylaxis longterm
● Consider EEG and/or EEG monitoring in patients with coma
● Treat both clinical and electrographiconly seizures with AEDs
Posttraumatic seizures and epilepsy are discussed in detail separately. (See "Posttraumatic seizures and epilepsy".)
Temperature management — Fever worsens outcome after stroke and probably severe head injury, presumably by
aggravating secondary brain injury [21]. Current approaches emphasize maintaining normothermia through the use of
antipyretic medications, surface cooling devices, or even endovascular temperature management catheters. However, this
approach has not been systematically tested with regard to clinical outcome. Similarly noninduced hypothermia has been
associated with an increase in mortality after TBI [133], but the efficacy of efforts to avoid this complication have not been
evaluated.
Induced hypothermia — Induced hypothermia has been a proposed treatment for TBI based upon its potential to
reduce ICP as well as to provide neuroprotection and prevent secondary brain injury [134]. Induced hypothermia has been
shown to be effective in improving neurologic outcome after ventricular fibrillation cardiac arrest. (See "Hypoxicischemic
brain injury: Evaluation and prognosis", section on 'Therapeutic (induced) hypothermia'.)
A systematic review of 22 randomized controlled trials of mildtomoderate hypothermia (32 to 35ºC) following TBI noted a
small but significant decrease in the risk of death (RR 0.76, 95% CI 0.600.97) or poor neurologic outcome (RR 0.69, 95%
CI 0.550.86) among more than 1300 patients treated, but noted that significant benefit was seen only in low quality trials
[135]. Other systematic reviews and metaanalyses found similar but more borderline benefits for death and neurologic
outcome as well as an increased risk for pneumonia [134,136139]. Substantial variability among studies in the depth and
duration of hypothermia, as well as the rate of rewarming limit the ability to draw conclusions from these studies. A
subsequently published trial examined the potential benefit of hypothermia when initiated within two to five hours of TBI in
a selected group of younger patients and found no benefit of treatment on mortality or neurologic outcomes [140].
Two trials of hypothermia therapy in children with TBI have shown no improvement in neurologic or other outcomes; one
showed a nonsignificant increase in mortality [141,142]. (See "Elevated intracranial pressure (ICP) in children", section on
'Contraindicated therapies'.)
Given the uncertainties surrounding its appropriate use, therapeutic hypothermia treatment should be limited to clinical
trials, or to patients with elevated ICP refractory to other therapies [135,143,144].
Glucose management — Both hyper and hypoglycemia are associated with worsened outcome in a variety of neurologic
conditions including severe TBI [145147]. In a retrospective cohort study of 77 patients with severe traumatic brain injury,
hyperglycemia (blood glucose ≥170 mg/dL [9.4 mmol/L]) at the time of ICU admission was an independent predictor of a
poor GCS score five days later [146]. This has been presumed to be at least in part related to aggravation of secondary
brain injury. Several mechanisms for this are proposed including increased tissue acidosis from anaerobic metabolism, free
radical generation, and increased blood brain barrier permeability.
Increased use of insulin infusions to maintain tight glucose control in critically ill patients has been studied, but the optimal
glucose target and best treatment regimen is uncertain. One case series using cerebral microdialysis found that tight
glycemic control was associated with reduced cerebral glucose availability and elevated lactate/pyruvate ratio which in
turn was associated with increased mortality [148].
At present, avoidance of both hypo and hyperglycemia is appropriate, but further studies are needed to clarify the optimal
serum glucose target range and duration of therapy. To avoid extremes of very high or low blood glucose levels, a broad
target range of up to 140 mg/dL or possibly even 180 mg/dL may be appropriate. (See "Glycemic control and intensive
insulin therapy in critical illness".)
Hemostatic therapy — Approximately onethird of patients with severe TBI develop a coagulopathy, which is associated
with an increased risk of hemorrhage enlargement, poor neurologic outcomes and death [149153]. The coagulopathy may
result from existing patient medications such as warfarin or antiplatelet agents. Acute TBI is also thought to produce a
coagulopathy through the systemic release of tissue factor and brain phospholipids into the circulation leading to
inappropriate intravascular coagulation and a consumptive coagulopathy [154]. Coagulation parameters should be
measured in the emergency department in all patients with severe TBI and efforts to correct any identified coagulopathy
should begin immediately.
● Patients taking warfarin may be managed with prothrombin complex concentrate (PCC), fresh frozen plasma (FFP),
and/or vitamin K as recommended for patients with warfarinassociated intracerebral hemorrhage. (See "Reversal of
anticoagulation in warfarinassociated intracerebral hemorrhage".)
● In patients with thrombocytopenia, many centers choose to maintain a platelet count > 75,000 with platelet
transfusions if necessary. The utility of platelet transfusions in TBI patients who arrive on antiplatelet medications is
not known [155]. (See "Use of blood products in the critically ill", section on 'Platelets'.)
Recommendations for hemostatic therapy in other categories of patients with severe TBI are limited by lack of evidence
[156]. When a coagulopathy is identified, it is reasonable to use FFP, PCC, and/or vitamin K as for warfarinreversal. A
reasonable, if somewhat arbitrary target is an INR < 1.4. A phase II doseescalation clinical trial of recombinant factor VIIa
in TBI patients demonstrated a nonsignificant trend towards limiting hematoma expansion but no mortality benefit,
although this was not directed exclusively at patients with TBIrelated INR elevation [157]. Similarly hemostatic therapy
has not been shown to be of overall benefit in patients with nontraumatic intracerebral hemorrhage, including those that are
warfarinassociated. (See "Spontaneous intracerebral hemorrhage: Treatment and prognosis", section on 'Hemostatic
therapy'.) There is no evidence that hemostatic therapy benefits noncoagulopathic patients with severe TBI [158,159].
Coagulopathy associated with trauma is discussed in detail separately. (See "Coagulopathy associated with trauma".)
Glucocorticoids — The use of glucocorticoid therapy following head trauma was found to be harmful rather than
beneficial in a large trial of patients with moderate to severe TBI [160]. More than 10,000 patients within eight hours of
presentation were randomly assigned to treatment with methylprednisolone or to placebo. Treated patients had increased
mortality at two weeks (21 versus 18 percent; RR 1.18) and at sixmonth followup (26 versus 22 percent; RR 1.15) [161].
Neuroprotective treatment — The use of a wide range of agents targeting various aspects of the TBI injury cascade has
been tested in clinical trials. To date, no neuroprotective agents or strategies (including induced hypothermia) have been
shown to produce improved outcome [50]. Based on two positive phase II studies, intravenous progesterone is being
tested in two pivotal phase III clinical trials as a neuroprotective agent for severe head injury [162,163]. Other agents being
investigated include magnesium [164], hyperbaric oxygen [165], and cyclosporine [166] among others [167]. Citicoline was
not found to be effective at improving outcomes in a randomized trial of 1213 patients with TBI [168].
Erythropoietin has been postulated to have neuroprotective effects. In a retrospective case control study in 267 patients
with severe TBI, matched for both GCS and severity of systemic injuries, inhospital mortality was lower among 89
patients treated with erythropoietin compared with 178 control patients (8 versus 24 percent) [169]. A number of
confounding factors may have biased these results, which require prospective validation in a clinical trial before such
treatment can be recommended [170]. Such a trial is ongoing.
ADVANCED NEUROMONITORING — In order to supplement ICP monitoring, several technologies have recently been
developed for the treatment of severe TBI. These techniques allow for the measurement of cerebral physiologic and
metabolic parameters related to oxygen delivery, cerebral blood flow, and metabolism with the goal of improving the
detection and management of secondary brain injury.
Current monitoring techniques include:
● Jugular venous oximetry: retrograde cannulation of the internal jugular vein that allows measurement of oxygen
saturation in the blood exiting the brain [171]. Normal jugular venous oxygen saturation (SjVO2) is about 60 percent.
SjVO2 <50 percent for 10 minutes is considered an "ischemic desaturation" and is associated with impaired CPP
and worsened outcome [172].
● Brain tissue oxygen tension (PbtO2) monitoring: intraparenchymal oxygen electrode placed in a manner similar to a
fiberoptic ICP probe that measures PbtO2 in the white matter [173]. Normal PbtO2 is >20 mmHg; duration and depth
of PbtO2 below 15 mmHg is associated with worsened outcome [172]. One case series used oxygen
supplementation to maintain PbtO2 above 25 mmHg and found better outcomes compared with historical controls
[174].
● Cerebral microdialysis: intraparenchymal probe placed in a manner similar to a PbtO2 probe that allows
measurement of extracellular glucose, lactate, pyruvate, glutamate [175]. A lactate:pyruvate ratio >40 is suggestive
of anaerobic metabolism, which is believed to exacerbate secondary brain injury.
● Thermal diffusion flowmetry: intraparenchymal probe placed in a manner similar to a PbtO2 probe that allows
continuous measurement of CBF, usually in the white matter. Correlation with CBF from neuroimaging and outcome
data is very preliminary at present.
Observational data suggests that these monitoring tools provide unique information that may help to individualize severe
head injury management for patients. Clinical trials are currently in the planning phases for use of these multimodality
advanced neuromonitoring approaches.
PROGNOSIS — Outcome from severe head injury is dependent on a range of factors including baseline patient
characteristics, severity of TBI, and the occurrence of medical complications and secondary brain insults. Specific
negative outcome predictors that have been identified from these factors include [16,1921,50,73,153,176182]:
● GCS at presentation (especially the GCS motor score)
● Presence and severity of CT abnormalities (subarachnoid hemorrhage, cisternal effacement, midline shift)
● Pupillary function
● Age
● Associated injuries and complications
● Hypotension
● Hypoxemia
● Pyrexia
● Elevated ICP
● Reduced CPP
● Bleeding diathesis (low platelet count, abnormal coagulation parameters)
Other studies are evaluating the potential of biomarkers, such as the levels of S100β protein, neuronspecific enolase,
and αsynuclein in the blood and/or cerebrospinal fluid, to predict neurologic outcome [183185].
While some have attempted to develop outcome prediction models to guide decisions about withholding early treatment,
the heterogeneity of severe head injury makes this difficult to apply to clinical decision making in individual patients
[177,186,187]. Thus, except in the most extreme cases, a trial of early aggressive neurosurgical and neurocritical care
management, including surgical removal of evacuable lesions and ICP monitoring, should be undertaken.
Cohort studies have suggested that patients with severe head injury (GCS ≤8) have about a 30 percent risk of death. At
least one cohort study found that survivors of TBI continue to have a substantially increased risk of mortality for at least
13 years after hospitalization [188].
Only about 25 percent of survivors achieve longterm functional independence [73,176,189]. Approximately 5 to 15 percent
of patients with severe TBI are discharged from acute care in a vegetative state [176,189,190]. Only half of these patients
regain consciousness over the next year and virtually all of these patients remain severely disabled. Outcomes are
somewhat better for those in the minimally conscious state. The persistent vegetative and minimally conscious states are
described separately. The use of prognostic indicators for these outcomes is better defined for hypoxicischemic brain
injury than for TBI [191]. (See "Hypoxicischemic brain injury: Evaluation and prognosis", section on 'Persistent vegetative
state' and "Hypoxicischemic brain injury: Evaluation and prognosis", section on 'Minimally conscious state'.)
A randomized trial of amantadine (starting at 100 mg twice daily) in 184 patients admitted to inpatient rehabilitation in a
vegetative or minimally conscious state after severe TBI found that amantadine treatment was associated with
accelerated recovery during the four week active treatment phase [192]. Rates of improvement subsequently slowed after
treatment withdrawal in the amantadine group and at week six, disability scores in the two groups were similar. Further
study is needed to determine a benefit for amantadine on long term prognosis and its role in the treatment of patients with
severe TBI. The mechanism of action for amantadine’s putative effect is unclear; it is speculated that antagonism of N
methylDaspartate and/or indirect agonsim of dopamine may be involved.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond
the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easytoread materials. Beyond the Basics patient education
pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level
and are best for patients who want indepth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to
your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the
keyword(s) of interest.)
● Basics topic (see "Patient information: Closed head injury (The Basics)")
SUMMARY AND RECOMMENDATIONS — Patients with severe traumatic brain injury (TBI) are most optimally
managed in a specialized neurotrauma center with neurosurgical and neurocritical care support and the use of guidelines
based standardized protocols.
● Prevention of hypoxia (PaO2 <60 mmHg) and hypotension (systolic BP <90 mmHg) are priorities in the management
of patients with severe TBI beginning with their prehospital care. (See 'Initial evaluation and treatment' above.)
● Emergency department evaluation should include frequent clinical neurologic assessments and a computed
tomography (CT) scan of the head.
When impending herniation due to elevated intracranial pressure (ICP) is suspected in a patient with severe TBI, we
recommend treatment with head of bed elevation and intravenous mannitol pending the results of the CT and
measurement of intracranial pressure (ICP) (Grade 1B). (See 'Emergency department' above.)
● Surgical evacuation of epidural, subdural, and intracerebral hematomas are performed based upon blood volume and
associated mass effect, in conjunction with the patient's neurologic status. (See 'Surgical treatment' above.)
● We recommend ventriculostomy placement with ICP monitoring in patients with severe TBI and an abnormal CT
scan showing evidence of mass effect from lesions such as hematomas, contusions or swelling. (See 'Intracranial
pressure' above.)
● We recommend treatment of elevated ICP to target pressures below 20 mmHg (Grade 1B). Appropriate first
measures include removal of cerebrospinal fluid through the ventriculostomy, head of bed elevation, followed by
osmotic therapy with mannitol. (See 'Initial treatment and ICP monitoring' above and 'Osmotic therapy' above.)
For patients with elevated ICP refractory to initial therapy, treatment options include hyperventilation, barbiturate
coma, induced hypothermia, and decompressive craniectomy. Hyperventilation should be avoided in the first 24 to 48
hours and should not exceed PaCO2 <30 mmHg. (See 'Hyperventilation' above and 'Sedation' above and
'Temperature management' above and 'Decompressive craniectomy' above.)
● We recommend using normal saline to maintain euvolemia (Grade 1B). (See 'General medical care' above.)
● Cerebral perfusion pressure (CPP) (the difference between mean arterial pressure and ICP) should be continuously
assessed. The suggested CPP target is 60 mmHg, avoiding CPP >70 mmHg and <50 mmHg, which should be
achieved by optimizing ICP first and then MAP (with volume expansion, pressors) second. (See 'Cerebral perfusion
pressure' above.)
● We recommend shortterm (one week) use of antiepileptic drugs (phenytoin, valproate) for the prevention of early
seizures (Grade 1B). (See 'Antiepileptic drugs' above and "Posttraumatic seizures and epilepsy".)
● We suggest that fever and hyperglycemia be avoided for their potential to exacerbate secondary neurologic injury.
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Coagulopathy should be corrected to maintain an INR < 1.4 and a platelet count > 75,000/mm3. (See 'General
medical care' above and 'Temperature management' above and 'Glucose management' above and 'Hemostatic
therapy' above.)
● We recommend thromboprophylaxis for the prevention of venous thromboembolism (Grade 1A). The use and timing
of antithrombotic agents is individualized based upon an assessment of the competing risks of venous thrombosis
and intracranial hemorrhage expansion. Patients not receiving antithrombotic therapy should wear pneumatic
compression stockings. (See 'General medical care' above.)
● We recommend NOT using glucocorticoids for the management of patients with severe TBI (Grade 1A). (See
'Glucocorticoids' above.)
● The use of sedative medications should be individualized. Options include barbiturates, propofol, fentanyl,
benzodiazepines, and morphine. These can be used individually, in combination, and/or with neuromuscular
blockade. Blood pressure, ICP, and CPP should be monitored as these are somewhat unpredictably affected by
these medications. (See 'Sedation' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 4826 Version 15.0
GRAPHICS
Glasgow Coma Scale (GCS)
Score
Eye opening
Spontaneous 4
Response to verbal command 3
Response to pain 2
No eye opening 1
Best verbal response
Oriented 5
Confused 4
Inappropriate words 3
Incomprehensible sounds 2
No verbal response 1
Best motor response
Obeys commands 6
Localizing response to pain 5
Withdrawal response to pain 4
Flexion to pain 3
Extension to pain 2
No motor response 1
Total
The GCS is scored between 3 and 15, 3 being the worst and 15 the best. It is composed of three
parameters: best eye response (E), best verbal response (V), and best motor response (M). The
components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS score
of 9. A score of 13 or higher correlates with mild brain injury; a score of 9 to 12 correlates with
moderate injury; and a score of 8 or less represents severe brain injury.
Graphic 81854 Version 4.0
Traumatic subdural hematoma
CT scan showing a left acute subdural hematoma (SDH, arrow).
Subdural hematomas are typically crescentshape. In this case the
SDH is causing significant mass effect and shift of midline structures
to the right.
CT: computed tomography.
Reproduced with permission from: J Claude Hemphill III, MD and Nicholas
Phan, MD, FRCSC.
Diffuse axonal injury
CT scan of the brain showing diffuse axonal injury (DAI). Note the
deep shearingtype injury in or near the white matter of the left
internal capsule (arrow).
Reproduced with permission from: J Claude Hemphill II, MD and Nicholas
Phan, MD, FRCSC.
Frontal cerebral contusion
CT scan of the brain depicting cerebral contusions. The basal frontal
areas (as shown) are particularly susceptible.
Phan, MD, FRCSC.
Traumatic epidural hematoma
CT scan demonstrating a right epidural hematoma (EDH, arrow). Note
the lenticular shape.
CT: computed tomography.
Phan, MD, FRCSC.
External ventricular drain
An external ventricular drain (EVD) is a small catheter inserted through the skull
usually into the lateral ventricle, which is typically connected to a closed collecting
device to allow for drainage of cerebrospinal fluid. The EVD can also be connected
to a transducer that records intracranial pressure.
Contributor Disclosures
J Claude Hemphill, III, MD, MAS Consultant/Advisory Boards: Ornim [neuromonitoring (Cflow cerebral blood monitor)].
Equity Ownership/Stock Options: Ornim [neuromonitoring (Cflow cerebral blood monitor)]. Nicholas Phan, MD, FRCSC,
FACS Nothing to disclose. Michael J Aminoff, MD, DSc Equity Ownership/Stock Options: Trust, which is independently
managed by a financial company. The portfolio may include medical or drug companies. Maria E Moreira, MD Nothing to
disclose. Janet L Wilterdink, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multilevel review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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