Neurol Clin 26 (2008) 409–426

Management of Traumatic Brain Injury in the Intensive Care Unit
Geoffrey S.F. Ling, MD, PhDa,b,*, Scott A. Marshall, MDa,b

Department of Neurology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 21042, USA b Neurosciences Critical Care, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD, USA

Within the medical and scientific communities, traumatic brain injury (TBI) has long been recognized as the leading cause of traumatic death and disability. In the United States, a brain injury occurs every 7 seconds and results in death every 5 minutes. This results in approximately 52,000 patients dying from TBI each year and accounts for almost one third of all trauma-related deaths. Most of these injuries are a direct result of falls, motor vehicle accidents, and assaults. The cost for direct TBI medical care is estimated at more than $56 billion per year [1,2]. The rising numbers of military patients injured while serving in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) in Afghanistan will increase these estimates. Most victims of civilian and military TBI are younger men [3,4]. The long-term burden of TBI in human and financial terms is staggering. Currently, the number of TBI survivors is numbered in the millions and is growing. Many require extended rehabilitation. Because many of these patients are less than 40 years old when injured and are otherwise in good physical health, they can live for decades, even if severely injured. The societal cost is large both in terms of direct care and lost productivity. A TBI patient who was a potentially productive member of society now becomes a consumer of services and chronic care resources. Further, this occurs in the period of life when his or her contribution to society may be greatest
The opinions expressed in this work belong solely to those of the authors. They do not and should not be interpreted as being representative or endorsed by the Uniformed Services University, US Army, Department of Defense, or any other agency of the federal government. * Corresponding author. E-mail address: (G.S.F. Ling). 0733-8619/08/$ - see front matter. Published by Elsevier Inc. doi:10.1016/j.ncl.2008.02.001



[3]. Even minor injury can lead to significant disability. Up to 79% of mildmoderate TBI patients had residual symptoms 3 months after injury. Many were unable to return to their jobs. Considering that the estimated total number of new TBI cases is greater than 1.4 million per year in the United States, the problem of brain injury is more fully appreciated [4,5]. Over the past 20 years, there has been marked improvement in the overall mortality associated with TBI. The reasons for this decrease in mortality may be attributed to improved medical and surgical care. A retrospective review compared a database of severely injured traumatic head injury patients from the period 1984 to 1987 with a similarly matched group from 1988 to 1996. There was a decrease in overall mortality, which remained significant despite adjustment for age, motor score, and pupillary reaction. The overall mortality from severe TBI in 1996 was reported as 27%, compared with 39% in 1984 [6]. The increasing role of specialized intensive care units with neurologically trained medical and nursing providers using evidencebased clinical management is believed to have had a favorable impact on both the consistency and level of care. Advances in neuromonitoring, neuroimaging, and early aggressive neurosurgical interventions may also be important contributors to improved TBI outcome. Preventing and treating comorbid conditions, such as venous thromboembolism, infection, and decubitus ulcers, also likely had a positive role. Historically, 15% to 20% of injuries incurred in battle involve the head [7,8]. The available epidemiologic evidence suggests that this is true also for casualties sustained in OIF and OEF [9]. One remarkable improvement in the medical outcome in these modern wars that may impact the prevalence of TBI is the very high survival rate among combat-injured United States soldiers. At present, the killed/wounded ratio is less than 1 in 10, which is a dramatic improvement over the 1 in 4 ratio of World War II. The reason for this is the introduction of modern body armor coupled with improved battlefield medical care. Modern military body armor is a scientific and engineering achievement [10]. When fitted with ballistic plates, it can protect the wearer from most shrapnel and small arms bullets. Combat helmets have also evolved and are similarly effective in mitigating injury from common battle-related threats. Body armor and combat helmets have undoubtedly reduced the incidence of injuries to the head, chest, and abdomen, and injury severity [11]. These devices, however, are not perfect. An unanticipated consequence is that more war fighters are surviving what previously would have been fatal injuries, and other injury conditions like TBI from explosive blast are now becoming relatively more prevalent [12]. Future efforts need to center on treatment methods that lead to improved neurologic and functional recovery of survivors of TBI [13,14]. Battlefield medicine has also evolved. It is reported that most fatal injuries on the battlefield result from injuries that are nonsurvivable in any setting [15]. The modern triage and evacuation system is highly effective and far forward medical providers are able to respond within seconds of an injury.



They provide early effective care using tourniquets; hemostatic agents (eg, HemCon bandages); and, importantly, arrange fast evacuation [16]. Modern combat evacuation procedures used during OIF and OEF provide a model for delivery of forward critical care [17]. At the combat support hospital, modern trauma care provided by appropriate specialty physicians and nurses is available and includes CT scan, advanced emergency medical services, early surgical intervention, and intensive care. Once stabilized, patients are evacuated out of the war zone to Europe or the United States. This too has likely contributed to the remarkable survival rate of modern war casualties. The goal of the chain of medical providers is to provide early clinical stabilization of the brain-injured patient, to arrest ongoing injury, to preserve and restore neurologic function, and to avoid secondary medical complications. In the field this first requires recognition that the brain is injured. Appropriate management can be instituted and rapid evacuation initiated to centers where neurointensivists, neurosurgeons, and other providers deliver more advanced care.

Pathogenesis of traumatic brain injury Classically, TBI is thought to have at least two phases. The first or initial injury occurs as a direct result of the primary traumatic event. A second injury phase occurs from multiple neuropathologic processes that can continue for days to weeks after the initial insult [18]. One of the principal goals of neurocritical care is to intervene in a timely fashion to prevent and disrupt secondary injury mechanisms. Primary injury Primary injury is immediate and not amenable to treatment. If severe, death can occur almost instantaneously. Typically, the damage that occurs from this primary phase is often complete by the time medical care can be instituted. The best way to mitigate primary injury is prevention. Education and devices, such as motorcycle helmets, can contribute to reducing TBI [19]. There are two classical types of head injury: closed head injury (CHI) and penetrating TBI. In CHI, direct impact of neuronal tissue against the bony vault, and shearing of neurovascular structures from rotational or rebounding forces, results in cell damage at the cell body and axon level. In the United States, most CHI is caused by motor vehicle accidents [20]. Other causes are falls, sporting event injuries, and assault. Motor vehicle accidents, which are high-speed collisions with very rapid deceleration, are particularly injurious. Because the neuronal structures reside in a fluid-filled compartment, they often lag behind the bony structure as it moves during the sudden stopping of the body in motion. The structures strike both in the



direct and opposite plane of motion against the inner bony table. This is the basis of the coup–contre-coup lesion pattern, where contusional or other injury to the brain is seen deep to the site of skull impact, and 180 degrees opposite the site of impact. If there is a rotational component, structures torque and twist and shearing can occur. This is the cause of diffuse axonal injury, commonly seen radiographically as punctuate hemorrhages on CT or MRI after TBI. In penetrating TBI, the calvarial vault is violated by a foreign body. That body may be large and moving slowly as with a knife, or small and moving rapidly as with a bullet. In both circumstances, the intruding body tears neural, vascular, and support structures as it traverses through the brain. If moving at very high velocity (eg, supersonic), the vacuum created by the projectile’s wake gives rise to tissue cavitation. Fired projectiles, based on shape and entry velocity, may cause more or less of this type of injury. Of note, the temporary cavity may be several times larger that the projectile itself, and although transient, the expansion of tissue is sufficient to cause significant irreversible damage. Based on experience gathered during OIF and OEF, there is increasing awareness of another class of head injury, referred to as ‘‘blast TBI’’ (bTBI). The most common agent associated with modern bTBI is explosive ordinance in the form of an improvised explosive device. bTBI may be considered a subtype of CHI. Many warfighters, who are exposed to explosions, suffer isolated bTBI and do not typically have penetrating injury to the brain. Their injuries result from explosive forces transmitted into brain parenchyma without breach of the calvarium. The mechanism of injury seems to be different from other forms of CHI as described previously. The most widely accepted opinion, although speculative, is that disruption of brain function following exposure to an explosion is caused by a concussive pressure wave. This concept may be an incomplete explanation for this mechanism of injury, because an explosion is composed of more than pressure phenomenon and there are many other physical forces emanating from an explosion, such as electromagnetic energy, acoustics, toxic fumes, and others, that may be injurious to brain. TBI may be further classified as focal or diffuse. Focal injuries occur at the site of impact. Neurologic deficits are referable to those areas. The orbitofrontal and anterior temporal lobes are most commonly affected because of the location of the brain over the rough surface of the skull base. Because of the tendency for head trauma to occur in an anteroposterior direction, the brain moves similarly and is injured as it traverses over the skull base. Particular vigilance must be made to identify the occurrence of delayed hematomas, which can develop up to several days after the inciting trauma [21]. Diffuse axonal injury is shearing of axons in cerebral white matter, which causes nonlateralizing neurologic deficits, such as encephalopathy. The consequences of this type of injury can be delayed by up to 12 hours following initial trauma [22]. Diffuse axonal injury can be identified as petechial white



matter hemorrhages on CT and MRI studies after TBI; however, findings may be subtle or absent on imaging. Recent evidence also suggests that the incidence of diffuse axonal injury may be higher with forces occurring in a lateral orientation, as opposed to a frontal or oblique impact in CHI [23]. Secondary injury Therapeutic interventions are based on attenuating the secondary injury phase of TBI. This phase of injury begins quickly after the primary phase and can continue for a prolonged period involving dysfunction and death of neurons and glial supporting structures. It is thought that the most significant burden of neurologic injury following TBI is related to this secondary injury. A broad range of mechanisms are involved in secondary injury and include hypoxia; ischemia; free radicals; excitatory amino acids; ion imbalance (eg, calcium); temperature dysregulation; and inflammation [21]. Many attempts at developing therapeutic strategies have focused on secondary injury processes. Despite considerable research efforts, current clinical treatment is largely confined to supportive measures with particular emphasis on maintaining perfusion pressure and tissue oxygenation; minimizing intracompartment hypertension (eg, increased intracranial pressure [ICP]); and treatment of cerebral edema. Scientific efforts to develop effective treatment strategies aimed at improving meaningful clinical outcomes are ongoing. Hypoxia and hypoperfusion are recognized as leading contributing factors to secondary brain injury. The injured brain is more susceptible to hypoxic-ischemic states because of impaired cerebral vascular autoregulation. The most susceptible areas are the hippocampus and border zone or watershed regions. It has been hypothesized that delayed neurologic compromise can be attributed to the effects of ischemia [21]. Previous work has shown that a single episode of hypotension where systolic blood pressures falls below 90 mm Hg is associated with worse outcomes in severe TBI [24]. Diffuse microvascular damage is associated with loss of cerebral vascular autoregulation and loss of blood-brain barrier integrity. Laceration of microvasculature exacerbates this injury. Microvascular damage contributes to the prominent pattern of vasogenic edema observed after TBI [25].

Traumatic brain injury taxonomy Classification and initial evaluation TBI severity is classified as mild, moderate, or severe depending on the level of consciousness on admission. Patients with mild TBI have an admission Glasgow Coma Score (GCS) of greater than 13. Mild TBI is frequently referred to as ‘‘concussion.’’ These patients have experienced a brief (!30 minute) loss of consciousness, and presenting complaints include headache,



confusion, and amnesia [26]. Following the acute period, a postconcussive syndrome may develop, which usually lasts a few weeks but can persist up to a year or more [5]. Postconcussive syndrome is a constellation of symptoms that include headache, dizziness, difficulty concentrating, anxiety, depression, and insomnia. The American Academy of Neurology has published guidelines for concussion management that includes recommended periods of recovery (Table 1). Other guidelines can also be used, such as the Cantu Grading system and the Colorado Medical Society Guidelines, which have been developed for sports-related TBI, but are widely applied and meaningful for the management of both civilian and military patients with head injury [27–30]. Moderate TBI is defined as an admission GCS of 9 to 13, and is often associated with prolonged loss of consciousness or neurologic deficit [31]. Clinically, patients with moderate TBI require hospitalization and may need neurosurgical intervention. Moderate TBI is associated with a greater likelihood of abnormal findings on craniocerebral imaging. These patients may also develop a postconcussive syndrome. Patients with GCS scores of 8 or less have severe TBI. They suffer from significant neurologic injury. Typically, they have abnormal neuroimaging (eg, CT scan revealing skull fracture or intracranial hemorrhage) [31]. These patients require admission to the ICU, and institution of rapid measures for control of the airway, mechanical ventilation, neurosurgical evaluation or intervention, and ICP monitoring. Recovery is prolonged and usually incomplete. A significant percentage of severe TBI patients do not survive to 1 year [32]. A new classification for bTBI is being proposed by the Defense and Veterans Brain Injury Center (DVBIC). The DVBIC conducts clinical research on military-relevant TBI, such as bTBI. The increasing clinical experience with this disease suggests that the existing severity definitions for classical TBI may not be appropriate for bTBI. Mild bTBI is defined as loss of consciousness less than 1 hour and posttraumatic amnesia less than 24 hours. Moderate bTBI is loss of consciousness for more than 1 but less than 24 hours and amnesia lasting more than 1 but less than 7 days. Severe bTBI is loss of consciousness for more than 24 hours and amnesia for more than 7 days. It should be understood that this new bTBI classification
Table 1 Glasgow coma score Best motor response (M) Follows commands Localizes to pain Withdrawal to pain Flexor posturing Extensor posturing No response 6 5 4 3 2 1 Best verbal response (V) Oriented, alert Confused, appropriate Disoriented, inappropriate Incomprehensible speech No response 5 4 3 2 1 Best eye opening (E)

Opens eyes spontaneously Opens eyes to voice Opens eyes to pain No response

4 3 2 1



was only recently proposed and has not yet gained wide acceptance in the medical community [33,34]. Patients with mild or moderate TBI often have recovered or are rapidly recovering by the time they reach the emergency department. The critical element in their subsequent management is the duration of amnesia or any history of a loss of consciousness. The American Academy of Neurology grading scale for concussion is based primarily on these two aspects of the neurologic history (Table 2). Longer periods of abnormal sensorium are associated with higher grades of concussion. The higher grades necessitate longer periods of convalescence and removal of the patient from an environment in which any further trauma is likely to occur. The DVBIC uses this grading scale based on loss of consciousness and the presence of posttraumatic amnesia, but other factors including GCS and alteration of consciousness are taken into account. Essentially, a patient with any degree of alteration of consciousness or feeling ‘‘dazed’’ after exposure to head trauma or concussive blast is classified and treated as having sustained at least a mild TBI [35]. Second impact syndrome A subsequent head injury during the vulnerable recovery period may result in ‘‘second impact syndrome.’’ Second impact syndrome is seen mostly in children and adolescents and has been associated with significantly worse clinical outcomes. In severe instances, coma can rapidly develop following
Table 2 American Academy of Neurology concussion management Grade 1 (mild) Remove from duty/work/play Examine immediately and at 5-min intervals May return to duty/work if clear within 15 min Grade 2 (moderate) Remove from duty for the rest of the day Examine frequently for signs of central nervous system deterioration Physician’s neuroexamination as soon as possible (within 24 h) Return to duty after 1 full asymptomatic week (after being cleared by physician) Grade 3 (severe) Take to emergency department Neurologic evaluation, including appropriate neuroimaging Consider hospital admission Grade of concussion Return to play/work Grade 1 (first) 15 min Grade 1 (second) 1 wk Grade 2 (first) 1 wk Grade 2 (second) 2 wk Grade 3 (first) (brief LOC) 1 wk Grade 3 (first) (long LOC) 2 wk Grade 3 (second) 1 mo Grade 3 (third) Consult a neurologist



a second injury, often within minutes. The exact mechanisms by which second impact syndrome occurs is not fully understood but it is postulated that the additional injury leads to an exacerbation in already impaired cerebral autoregulation, diffuse cerebral edema, and intracranial hypertension. Fortunately, second impact syndrome is uncommon in its most severe form. When it occurs, however, there is up to 50% mortality.

Clinical management Early intervention An organized team approach is essential to proper management of TBI. The initial goals of care should be immediate attention to airway and cardiopulmonary function (ABCs); early identification of the potential for TBI in any trauma victim; and minimization of secondary insults, such as hypoxicischemic injury. In the first few minutes, nonphysician health care providers, such as emergency medical technicians, can make rapid initial neurologic evaluations using a standardized grading scheme, such as the GCS. In the absence of a formal GCS, this information can often be elicited from first responder data or interviews. The GCS is important in categorizing and triage of TBI patients, and providing a quantifiable measure of impairment, which can help decide early management sequences in an organized algorithm. This initial examination also helps guide prognosis for the outcome of severe TBI. It is crucial that prehospital providers optimize perfusion and oxygenation, because it is well recognized that the duration and severity of hypoxia and hypotension in this critical early period has dramatic consequences on clinical outcome [14,36]. Avoidance of hypotension (systolic blood pressure !90 mm Hg) and maintenance of adequate oxygen saturation (O90%) are level II and level III recommendations from the Brain Trauma Foundation, respectively [37]. In many patients with moderate and all patients with severe TBI, airway protective mechanisms are impaired and tracheal intubation should be performed. The cervical spine should be immobilized with a rigid neck collar and the head placed in midline position and elevated to 30 degrees. The neck collar serves not only to protect the cervical spine until appropriate imaging can be performed to rule out instability, but it also keeps the head midline to avoid compromising venous drainage, which can increase ICP. Surgical management may be beneficial in selected patients with traumatic lesions. There are many injuries that do not warrant surgical intervention and management is primarily medical. Diffuse or disseminated injuries, such as diffuse axonal injury and contusional injury, typically are not managed surgically. Conditions in which neurosurgery is warranted are those related to breach of the calvarium, presence of expanding intracranial hematoma, or malignant cerebral edema. Depressed skull fractures often requires elevation.



Hematomas, in particular symptomatic subdural and epidural hematomas, may need evacuation. Subdural hematoma is the basis of approximately 50% of hospital admissions for head injury; epidural hematoma accounts for only 3% [34,38]. When there is a skull fracture, especially at the temporoparietal junction, the incidence of epidural hematoma tends to increase, most commonly because of disruption of the middle meningeal artery. Decompressive craniectomy is an emerging clinical management approach in the early intervention and management of TBI. The reported experience to date is conflicting. In a study of 57 young patients with severe TBI (age !50), early decompressive craniectomy was associated with a good outcome, defined as social rehabilitation, in 58% of patients. The authors reported a relatively low mortality of less than 20% [39]. A retrospective French study was able to show a similar outcome in only 25% of severe TBI patients [40]. The more recent Early Decompressive Craniectomy for Severe TBI study reported that patients who underwent decompressive craniectomy for uncontrolled ICP had significant improvement in ICP control and better clinical outcomes compared with historical controls [41]. This is countered, however, by a retrospective study of the Trauma Coma Data Bank that suggested there was no significant improvement with craniectomy [42]. One of the difficulties in interpreting the available data is the lack of agreement regarding surgical technique (release the dura or not, timing of surgery, cut-off age, and TBI severity on presentation) [43]. At present, the Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intra-Cranial Pressure trial is under way. This is a large multicenter trial in Europe comparing decompressive craniectomy with medical management in TBI. One application of decompressive craniectomy is treatment of severe bTBI. United States military neurosurgeons report favorable outcomes in bTBI patients who undergo early decompressive craniectomy [33,44]. Neurologic intensive care unit management of severe traumatic brain injury After initial emergency care, patients with severe TBI require admission to the ICU. Limited available data suggest that outcomes may be improved when specialized neurologic intensive care teams or algorithms are present to guide management [45]. The presence of other traumatic injuries may require a broad multidisciplinary approach for these patients, including input from trauma, orthopedic, craniofacial, ophthalmologic, and other specialty physicians. Continuous neurologic evaluations There is no better diagnostic approach than clinically to examine the patient, and track changes over time with serial evaluations. In the acute period, these evaluations may be as often as every hour with increasing



intervals as the patient’s condition stabilizes. If needed, ICP and cerebral perfusion pressure (CPP) measurements should be made continuously. Even in the presence of ICP monitoring, the importance of the clinical examination and neurologic assessment cannot be overstated. Generally, the peak period of cerebral edema is from 48 to 96 hours after TBI. Thereafter, this resolves and clinical improvement should follow with improved ICP control. Imaging and intracranial pressure monitoring Neuroimaging with a non–contrast enhanced CT scan should be done as soon as possible in the emergency department. The goal is to identify as early as possible any lesions amenable to neurosurgical intervention. If such a lesion is not identified, the patient should be admitted to the ICU for further treatment. If the patient has a GCS of 8 or less, any acute abnormality on CT, a systolic pressure of less than 90 mm Hg, or age greater than 40 years, an ICP monitoring device should be placed. The external ventricular drain provides the most accurate and reliable data and also provides a means to control ICP by cerebrospinal fluid removal. Other monitoring options, which do not have this treatment advantage but are less invasive, include the subdural bolt and fiberoptic catheter. If there is any degree of hydrocephalus on imaging studies, an external ventricular drain is the best choice for monitoring and treating ICP. Increased intracranial pressure Increasing volume within a closed rigid container, such as the skull, inevitability leads to increasing pressure within that confined space. The increased pressure, particularly if it is compartmentalized, compresses vital structures, such as brain and blood vessels. If blood vessels are compressed, then ischemia ensues. If brain is compressed, ICP can rise significantly and if allowed to progress can lead to herniation. General management of increased ICP and herniation includes control of the airway; elevation of the patient’s head to 30 degrees; and administration of mannitol, 0.5 to 1 g/kg over 10 minutes. Another option, particularly for patients with compromised intravascular volume, is to administer hypertonic saline. Recent data suggest that an intravenous bolus of 23.4% saline, 30 mL, given over 10 to 15 minutes, may effectively reverse herniation and decrease ICP, with only transient hemodynamic repercussions [46]. Hyperventilation may also be considered, but only as an emergent, temporary intervention, because prolonged hyperventilation has been associated with exacerbation of cerebral ischemia [47]. Short durations of hyperventilation are acceptable as a temporizing measure until other (surgical, hyperosmolar) means of managing increased ICP are available. If hyperventilation is continued for longer than 12 hours, metabolic compensation negates the ameliorative



effects of respiratory alkalosis caused by a hypocapnic state and continued hyperventilation may be harmful. Induced hypothermia for TBI remains controversial because of the lack of compelling outcome-modifying results from clinical trials. Eventually, it may prove to be beneficial in subsets of patients [14,48,49]. Recent animal data show promise for induced hypothermia with improved neurophysiologic metrics in asphyxial (nontraumatic) brain injury [50]. Current use of prophylactic hypothermia for severe TBI is not substantiated, however, based on a level III recommendation from the Brain Trauma Foundation [37]. The use of hypertonic saline for cerebral edema merits further discussion. A single dose of 23.4% hypertonic saline can reduce ICP. There is some evidence to suggest that this is as effective in lowering ICP and may possibly have a longer duration of effect compared with mannitol [51]. This concentration is a low-volume infusion, and may be beneficial in cases where the volume status of the patient dictates caution with large infusions. The benefit of hypertonic saline is that it helps maintain a high serum sodium concentration and thereby promotes water movement from the intracranial compartment into the vasculature. When used clinically, 2% saline solutions can be given by a peripheral line, but 3% and higher concentrations of saline should be administered through a central venous catheter to minimize venous phlebitis. When used as a continuous infusion, hypertonic saline solutions are commonly prepared as a 1:1 ratio of sodium acetate to sodium chloride so as to minimize the development of hyperchloremic metabolic acidosis. The use of hypertonics has not received a level III or better recommendation for use in trauma-induced increased ICP [35,52–54]. Sustained treatment of increased intracranial pressure Current guidelines recommend maintaining the ICP less than 20 mm Hg and the CPP greater than 60 mm Hg. If ICP remains poorly controlled after efforts described previously, 23.4% saline may be administered through a central venous catheter. If this should also be unsuccessful in reduction of ICP, consideration should be made toward pharmacologic coma or surgical decompression. The postulated effect of pharmacologic coma on ICP is through reduction of cerebral metabolism (CMRO2) with concomitant reductions in cerebral blood flow and reduced tissue oxygen demand. The most commonly used agent for pharmacologic coma, pentobarbital, can be administered intravenously at a loading dose of 5 mg/kg, followed by an infusion of 1 to 3 mg/kg/h; a high-dose regimen may also be used with an intravenous bolus dose of 10 mg/kg over 30 minutes followed by 5 mg/kg/h infusion for 3 hours, followed by 1 mg/kg/h titrated to either burst suppression on continuous electroencephalogram monitoring or a reduction in ICP. Another option for pharmacologic coma is propofol, which is given in an intravenous loading dose of 2 mg/kg, followed by a titrated infusion of up to 200 mg/kg/min. The use of propofol for this clinical indication is



controversial. Propofol has been associated with the development of a ‘‘propofol infusion syndrome’’ of renal failure, hyperkalemia, myocardial failure, and metabolic acidosis, often resulting in death. The mechanism for this is not fully understood. If these efforts fail to control ICP, or as an alternative to pharmacologic coma, decompressive craniectomy or lobectomy may be considered. Should the patient be unsuitable for surgery and if the ICP elevation remains recalcitrant, then the patient’s condition is likely terminal [37,55–57]. Recent experience with head injuries sustained in combat has suggested a new paradigm for the early surgical management for bTBI and TBI. Experience has shown that early hyperemia and severe cerebral edema occurs frequently in the setting of a significant blast injury; a decompressive craniectomy permits the swelling brain to avoid compression by the bony skull. From a practical military standpoint, craniectomy provides an additional measure of safety for ICP control through the air-evacuation process where, at times, ICP management can be challenging. Another benefit of early decompressive craniectomy is that it may obviate the need to use more conventional methods to control ICP, such as pharmacologic coma, which is difficult to execute in a deployed and hostile setting because of the limited number of neurologic critical care specialists and lack of electroencephalogram support in a war zone. In this setting, decompressive craniectomy may be the most practical, if seemingly aggressive, approach [33,38,44]. Hemodynamic management The recommended CPP goal is greater than 60 mm Hg. To achieve this, fluid resuscitation to euvolemia is the first step. Hypo-osomolar solutions, such as 0.50 normal saline or 5% dextrose in water, are to be avoided. A commonly used hyperosmolar fluid is normal saline. Other options as clinically warranted are hypertonic saline (eg, 2% or 3% sodium solutions); colloids; and blood products. If CPP cannot be maintained with intravenous fluids alone, vasoactive pharmacologic agents, such as norepinephrine or phenylephrine, may be required. These two agents are preferred because they have minimal effects on cerebral vasomotor tone. Invasive hemodynamic monitoring with a central venous pressure catheter and an arterial catheter may be needed. It should be remembered that barbiturates and propofol are myocardial depressants and peripheral vasodilators, and invasive hemodynamic monitoring and support are often necessary when pharmacologic coma is induced. Vasospasm and pseudoaneurysms after traumatic brain injury Vasospasm is a common finding after bTBI. Recent data by Armonda and colleagues [58] reveal that up to 50% of patients suffering moderate to severe bTBI developed cerebral vasospasm. Transcranial Doppler studies in theater reveal that vasospasm can develop early, often within 48 hours of



injury [59]. Vasospasm can also present later in postinjury phase, typically 10 or more days after initial insult. Penetrating head injury and bTBI may be associated with pseudoaneurysm formation. Such blast-related pseudoaneurysms have been found to expand despite endovascular ablation attempts. Patients with such lesions often require craniotomy and aneurysm clipping [58]. The accuracy of noninvasive forms of vascular imaging, such as MR angiogram and CT angiogram, in diagnosing pseudoaneurysms may be limited. Furthermore, many military patients have retained fragments that obviate the use of MRI. The military causalities in OIF and OEF evaluated at Walter Reed Army Medical Center and the National Naval Medical Center undergo four-vessel cerebral angiography as the favored diagnostic approach. Sedation If the TBI patient is agitated, evaluation must be made to determine whether the patient is in pain, hypoxic, delirious, or poorly tolerating mechanical ventilation. If pain is a concern, then a narcotic analgesic, such as fentanyl or other short-acting medication, should be administered. Longer-acting narcotics, such as morphine or hydromorphone, are discouraged even though they can be easily reversed by naloxone. Administration of naloxone should not be done routinely to facilitate a neurologic examination because of the likely discomfort that this may cause a victim of recent trauma. Preferably, a short-acting narcotic infusion is held for a brief time, which allows reassessment of neurologic status. If delirium or agitation alone is the issue, then haloperidol or an atypical antipsychotic can be used. In the acute period after TBI, haloperidol is nonsedating, which preserves the neurologic examination. In the more subacute period, when observation of subtle examination changes is not as crucial, atypical antipsychotics, most of which do not have haloperidol’s nonsedating property but are better tolerated, may be a better choice for controlling agitation. Recent work in animals has suggested that, in addition to typical and atypical neuroleptic’s dissimilar side effect profiles, there may be differences in their use and effect on long-term neurologic outcomes, although this area needs further research [60]. Avoidance of other exacerbating complications Hypoxic states, seizures, and fevers are to be avoided. Maintaining PaO2 at approximately 80 to 100 mm Hg is sufficient; there is no documented benefit to higher levels of oxygen but there is potential for toxicity. Studies have demonstrated that phenytoin is beneficial in reducing the risk of seizures during the first week after TBI [61]. It has not been shown to prevent late seizures (ie, those developing after 7 days). Because fewer than 50% of TBI patients develop late seizures, the recommended approach is to stop seizure prophylaxis after the first 7 days and only reinstitute



treatment should late seizures manifest. The potential for cognitive side effects of phenytoin make prolonged prophylactic use of this medication less attractive. Alternatives abound, including carbamazepine and valproate, and levetiracetam, which is available in an intravenous or enteric form [62]. This medication is commonly used in the authors’ institution for this indication. Hypertension, tachycardia, and fever and dystonia may be a sign of autonomic dysregulation syndrome, frequently seen in TBI, although alternative explanations must be ruled out before accepting this diagnosis of exclusion. Bromocriptine, propanolol, and opioids can be used to treat this condition. Temperature dysregulation is common in TBI, and fever from any cause greatly increases cerebral metabolism and should be treated with the use of antipyretic interventions, such as acetaminophen and cooling blankets. Other modalities of induction of normothermia include skin-applied gel cooling systems and intravenous methods. The use of prophylactic hypothermia in brain trauma has to date failed to show a benefit in terms of postinjury outcome measurements, and is currently not recommended [63]. Other important management considerations include prevention of gastric stress ulcer, venous thromboembolism, and decubitus ulcers. Gastric stress ulcers may be prevented using such agents as H2 antagonists or proton pump inhibitors. These medications should be routinely used in all severe head injury patients. TBI patients are at high risk for developing deep venous thrombosis with subsequent thromboembolism. The optimal approach in severe TBI with intracranial hemorrhage is uncertain. Sequential compression devices on the lower extremities are minimally invasive and are not associated with any notable adverse effects. The optimal timing of introduction of unfractionated or low-molecular-weight prophylactic heparin is less clear. If there are no contraindications to heparin use, however, then treatment should be started as soon as possible, ideally within the first 36 hours of injury [64]. The routine placement of inferior vena cava filters is controversial, and placement is currently supported only by a level III recommendation with a GCS score of greater than 8 and contraindications to any anticoagulants [64].

Prognosis of traumatic brain injury Clinically, the most useful prognostic indicator following TBI is the neurologic examination at presentation. Classically, it has been taught that the better the initial neurologic examination, the less likelihood of severe neurologic damage [65]. For patients with severe TBI, the initial GCS is the most commonly used prognostic indicator (see Table 1). The lower the initial GCS score, the less likely a patient has meaningful neurologic or functional outcome. Comparisons have been made based on historical data obtained



for anoxic or non-TBI from cardiac arrest, but this mechanism of injury and patient population (ie, age) is quite different [66]. A prospective study with long-term outcomes measurements for severe TBI and bTBI has been needed for some time. Recent publication of the CRASH trial has associated long-term (6 month) outcomes in TBI with age, GCS score, pupil reactivity, and the presence of extracranial injury, in addition to radiographic and other data collected for more than 8000 TBI patients in multiple countries. Interestingly, advancing age was most associated with poor outcome in high-income countries, and low GCS was most associated with poor outcome in low-middle income countries. The absence of pupil reactivity was the third strongest predictor of poor outcome in high- and low-income countries. Radiographically, obliteration of the third ventricle and midline shift was most likely to be associated with early mortality (14 days), and nonevacuated hematoma was most likely to be associated with poor outcome at 6 months [67]. Recent work using diffusion-weighted MRI correlated with 6 to 12 months Glasgow Outcomes Scale shows MRI as a helpful addition to prognostication in TBI [68]. Other modalities including MRI diffusion tensor imaging have been helpful in prognostication in TBI [69].

Summary TBI is a common and complex clinical entity and deserves better and continued research on interventions and initial treatment postinjury. Blastrelated TBI is increasingly recognized and characterized in part because of the military’s current demographics of casualties sustained in OIF and OEF. Treatment of moderate to severe TBI and bTBI is optimally delivered in the ICU, where the first few hours and days after injury are likely to have a significant impact on patient outcome. Mortality following TBI has been greatly reduced, although morbidity from TBI and bTBI remains a significant problem. With respect to bTBI, a comprehensive epidemiologic study is desperately needed to determine the prevalence, risk factors, natural history, and outcomes of this condition. Additionally, a better comprehensive clinical description of bTBI with strict diagnostic criteria could greatly facilitate study of this illness. Current medical management of TBI is articulated on minimizing secondary injury by optimizing cerebral perfusion and oxygenation and preventing or treating nonneurologic morbidity. There are major medical research efforts examining the underlying mechanisms of secondary brain injury, which provides hope for effective therapies in the future. Presently, a number of promising therapeutic modalities are undergoing clinical trials, and as new pharmacologic and medical approaches are introduced, there will be increasing opportunity to treat these patients and improve their neurologic outcomes.



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