Diagnosis and management of traumatic brain injury by Kirk Andrew

DIAGNOSIS AND MANAGEMENT OF TRAUMATIC BRAIN INJURY

KEY POINTS

Geoffrey S. F. Ling, Scott A. Marshall, David F. Moore

ABSTRACT This article will provide an overview of the initial evaluation and management of traumatic brain injury (TBI). In cases of mild injury, conventional imaging in the absence of focal neurologic deficits is generally unrevealing. In the case of moderate or severe TBI, a review of neurocritical care is provided. Continuum Lifelong Learning Neurol 2010;16(6):27â&#x20AC;&#x201C;40.

INTRODUCTION Traumatic brain injury (TBI) is unfortunately an all too common disorder. In the United States, an estimated 1.7 million new TBI cases occur per year. TBI may result in significant long-term consequences, including death and chronic disability in severe cases. Approximately 1.4 million emergency department visits per year are for TBI. Of these visits, about 275,000 patients are admitted to the hospital. In addition, close to 52,000 patients with TBI die each year. TBI accounts for almost one-third of all injury-related deaths, highlighting the importance of primary prevention.1,2 Mild TBI (mTBI) and acute concussion account for approximately 75% of all TBI cases. However, the actual number of mTBI cases is uncertain as many patients may receive care by nonmedical professionals or do not seek medical attention at all. Estimates suggest that as

The actual number of mild traumatic brain injury (mTBI) cases is uncertain as many patients may receive care by nonmedical professionals or do not seek medical attention at all. The total cost of TBI is estimated to be a staggering $60 billion per year.

many as 8 million head injuries occur each year in the United States alone.1â&#x20AC;&#x201C;4 TBI afflicts patients of all ages and both sexes. However, prevalence is greater among males, the very young (younger than 4 years), adolescents (aged 15 to 19 years) and older adults (older than 65 years). Close to 500,000 of all TBI emergency department visits (or approximately one-third of the total) are for children younger than 4 years old, where consideration of nonaccidental injury is important.2 The etiology of TBI varies with age. Falls and nonaccidental trauma are more frequent in the very young. Sportsrelated injuries and motor vehicle accidents are more common among adolescents, while falling is usually the reason for TBI in older adults.5 The total cost of TBI is estimated to be a staggering $60 billion per year. Direct medical costs for treating a patient

Relationship Disclosure: Dr Ling has received personal compensation for speaking engagements from BristolMyers Squibb and Sanofi-Aventis and holds stock and/or stock options in Wyeth Pharmaceuticals. Dr Marshall has received personal compensation as an expert witness. Dr Moore has nothing to disclose. Unlabeled Use of Products/Investigational Use Disclosure: Drs Ling and Moore have nothing to disclose. Dr Marshall discusses the unlabeled use of hypertonic saline in the treatment of traumatic brain injury.

" DIAGNOSIS AND MANAGEMENT

KEY POINTS

Concussion refers to altered function. mTBI describes a pathologic state of brain after the concussive event. The AAN concussion grades are grade 1, altered mental status less than 15 minutes; grade 2, altered mental status more than 15 minutes; and grade 3, loss of consciousness.

with mTBI can be as high as $85,000 and for a patient with severe TBI, $3 million. In terms of human and family suffering, it is incalculable. An estimated 80,000 survivors from civilian injury each year are left with residual neurologic deficit that results in loss of function. These patients require extended rehabilitation. Many of these patients are younger than 40 years and are otherwise in good physical health and, thus, may live for decades following the injury. Beyond the direct medical expense, invisible costs come into play when a previously productive member of society, usually at an early age, has instead become dependent.1,6â&#x20AC;&#x201C;8 Even mTBI or concussion can lead to significant disability. A study of patients who sustained relatively minor injuries revealed up to 7% to 9% had residual symptoms 3 months after injury. Onethird of these patients were unable to return to their previous jobs.3,4 SEVERITY OF TRAUMATIC BRAIN INJURY TBI traditionally has been divided into three major categories. These are mild, moderate, and severe. The Glasgow Coma Scale (GCS) score may used to differentiate among the three.9 A traumatic injury to the brain resulting in a GCS of 13 to 15 is defined as mild. If the GCS is 9 to 12, the TBI is defined as moderate. If the GCS is 8 or less, the TBI is defined as severe. mTBI is further defined by the Mild Traumatic Brain Injury Section of the American Congress of Rehabilitation Medicine (1993)10 as the loss of consciousness for less than 30 minutes, loss of memory preceding or following injury (amnesia) for less than 24 hours, alteration in mental status at time of injury, and/or focal neurologic deficit.10 The level of mTBI severity (as described below) is based mainly on the duration of altered mental status or altered si-

tuational awareness. mTBI and concussion are often associated with brief (less than 5 minutes) loss of consciousness or situational awareness in which the person experiences a performance decrement within the required environmental context.11 In clinical practice, concussion and mTBI are often used synonymously. However, they are distinct terms. Concussion refers to altered function. mTBI describes a pathologic state of brain after the concussive event. Three grades of concussion have been identified according to AAN criteria. The grades are differentiated by duration of altered mental status and any of loss of consciousness. Amnesia, although not part of the AAN criteria, is an independent diagnostic indicator of TBI severity, with the loss of memory preceding (retrograde) or following (posttraumatic or anterograde) injury. A grade 1 concussion is defined as having altered mental status lasting less than 15 minutes without loss of consciousness. In grade 2, concussion is altered mental status lasting more than 15 minutes, again without a loss of consciousness. Grade 3 concussion according to the AAN scale is characterized by any loss of consciousness.11 Moderate TBI occurs when a patient sustains a head injury that results in a GCS of 9 to 12, and usually is associated with prolonged loss of consciousness and/or neurologic deficit.12 Patients with moderate TBI require advanced medical care, including neurosurgical consultation. Later, as they recover, they may develop postconcussive syndrome or persistent postconcussive symptoms.13 Severe TBI occurs when the injury causes the patient to be obtunded or comatose (ie, the presenting GCS is 8 or less). Such injury is typically associated with significant neurologic injury, often with structural lesions revealed by neuroimaging (eg, head CT scan revealing skull fracture, intracranial hemorrhage,

Continuum Lifelong Learning Neurol 2010;16(6)

and early diffuse cerebral edema). These patients usually require advanced medical care even in the prehospital setting. After initial resuscitation and stabilization in the field, patients with severe TBI should be evacuated to the nearest level 1 trauma center with neurosurgical capability. Such patients will need airway protection, mechanical ventilation, neurosurgical evaluation, and intracranial pressure (ICP) monitoring with skilled nursing neurocritical care in a trauma unit or neuro-intensive care unit. It is expected that recovery will be prolonged and often incomplete, with many patients not surviving beyond one year.12–14 MECHANISM OF INJURY Two distinct phases are associated with TBI. The first phase is the tissue injury that is a direct consequence of the primary traumatic event, resulting in stressinduced strain deformation of the CNS tissue and skull. The second phase is multiple related neuropathologic processes that are responses to the traumatic event. This later secondary phase can last for days to weeks.15 The primary injury phase occurs almost immediately and is not generally thought to be amenable to treatment. When sufficiently severe, it can lead to death. The damage that occurs from this primary phase is often complete by the time medical care can be instituted. The best approach to mitigating primary injury is prevention with the use of personal protective equipment, such as an appropriately quality-assured helmet for sports-related concussion. The secondary injury phase is delayed, which offers an opportunity for therapy. This phase begins very quickly after the primary phase and can continue for an extended period of time. Injury usually involves both neurons and glia. It is thought that most neurologic injury occurs after the primary event and is related to this secondary

injury. The processes that contribute to this ‘‘neuronal suicide’’ include hypoxia, effects of free radicals, excitatory amino acids, certain ions (eg, calcium), ischemia, and inflammation.16 For practical reasons based on the time and effort to develop therapeutics, approaches to TBI have focused on secondary injury processes. Although significant research efforts have been devoted to this issue, current clinical treatment for mTBI is largely confined to symptomatic relief, rest, and recuperation. For moderate to severe TBI, focus is on supportive measures with particular emphasis on maintaining cerebral perfusion pressure, minimizing intracranial hypertension, and treating indirectly cerebral edema. Efforts to develop neuroprotective treatments that are clinically effective in patients are ongoing. ETIOLOGIES OF INJURY TBI can be caused by a number of different mechanisms that involve varying strain rates of brain deformation, ranging from lower strain rates in direct impact TBI to ballistic-induced head injury to blast-associated neurotrauma at high strain rates. Injuries can be divided into two main categories—penetrating and nonpenetrating (or open head and closed head) (Case 2-1). Penetrating or open head TBI is caused by violation of the skull. This can result from foreign body entry, such as a bullet or knife. It can also be caused by direct blunt force, such as being struck with an object (eg, baseball bat), as well as mild to moderate explosive blast injuries. TBI associated with penetration is typically moderate to severe (Case 2-2). Nonpenetrating or closed head injury is most often caused by direct blunt force. Other pathoanatomic features of TBI include focal contusions, hypoxic-anoxic injury, diffuse axonal injury, and diffuse microvascular injury. Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

Case 2-1 An armed service member in full-body armor and helmet faced incoming firepower that detonated an ammunition storage area with multiple ensuing explosions. Thinking it was safe, she stepped out from a bunker but experienced a large blast occurring on the left side at an approximately 125-m (410-ft) standoff. She reported head and chest pressure, with a sensation of having her ‘‘bell rung’’ associated with a brief loss of situational awareness. The intensity of incoming fire and ammunition dump explosions forced her to remain inside the open bunker for over 2 hours. Immediately after the large blast, she experienced severe headache, ringing in the left ear, and aching ribs. Ten hours later, she began vomiting and was medically observed for 2 days while receiving IV hydration. Symptoms of dizziness, balance difficulties, problems with thinking, anxiety, insomnia, and nightmares developed and continued prominently for 2 weeks. Medical evacuation to the United States occurred 3 months later, as she continued to have severe headaches. Neurologic consultation confirmed a normal neurologic examination. MR imaging showed an area of T2 hypointensity in the left internal auditory canal consistent with a hematoma and a larger area of hyperintensity of the left cerebellum. Diffusion tensor imaging tractography demonstrated more robust cerebellar fiber pathways on the right side than on the left, especially those traveling from right to left. Fluid-attenuated inversion recovery (FLAIR) imaging was consistent with a subacute vascular event of a segmental artery. Comment. This case represents an account of primary blast injury with symptoms consistent with a concussion (grade 1). The abnormality noted on FLAIR imaging was consistent with a segmental arterial infarct of the cerebellum possibly due to traumatic cerebral vasospasm. Adapted from Warden DL, French LM, Shupenko L, et al. Case report of a soldier with primary blast brain injury. Neuroimage 2009;47(suppl 2): T152–T153. Copyright # 2009, with permission from Elsevier.

Focal injuries occur at the site of impact, and neurologic deficits are therefore referable to the injured areas. The orbitofrontal region and anterior temporal lobes are most commonly affected. Particular vigilance must be made to identify the development of delayed hematomas, which can manifest days after injury.16 Hypoxic and hypoperfusion injuries are well recognized as leading contributors to secondary brain injury. In TBI, a transient increase occurs in systemic arterial pressure. Apnea and cerebral dysfunction may develop. Depending on the degree of injury, spontaneous resolution may be delayed. Laceration of microvasculature will exacerbate this type of injury. Furthermore, the injured brain is more susceptible to hypoxic ischemia. The most commonly affected areas are the hippocampus and vascular ‘‘watershed’’ areas between external ce-

rebral arterial territories and the deep penetrating cerebral vessels. It has also been hypothesized that delayed neurologic compromise can be attributed to delayed ischemia in TBI, particularly when traumatic cerebral vasospasm occurs.17,18 Diffuse axonal injury is a result of rapid acceleration and deceleration, as is often experienced in motor vehicle accidents. This leads to shearing of axons in the cerebral white matter, which causes neurologic deficits such as encephalopathy. The consequences of this type of injury can be delayed for up to 12 hours following initial trauma.19 Diffuse microvascular damage is caused by an early loss of cerebral vascular autoregulation and a loss of bloodbrain barrier integrity. This leads to endothelial changes, such as the formation of intraluminal microvilli. Although the clinical significance of this injury is

Continuum Lifelong Learning Neurol 2010;16(6)

KEY POINT

Case 2-2 A 28-year-old man in combat received a penetrating bullet wound to the left occiput with lodging of the bullet in the corpus callosum. He arrived 3 days later at a tertiary medical center intubated and having been put into pentobarbital coma. In addition, he had received a left-sided hemicraniectomy. Over the course of the next week, he had diffuse cerebral edema extending past the craniotomy margins that resolved. He received medical treatment in the intensive care unit and after 1 month was transferred to a regular hospital bed with a hemianopsia and a right-sided hemiplegia. After rehabilitation, he was discharged home with persistent upper quadrantanopsia and mild right lower limb weakness. He later returned to the hospital to have a replacement skull plate inserted. Comment. This case illustrates the changing prognosis for severe brain injury. It is likely that the hemicraniectomy, which allowed brain swelling, may have avoided further neuronal injury and an evolving herniation syndrome. This case also illustrates persistent neuroplasticity occurring during the rehabilitation period, even in an older-age individual.

uncertain, it may play a role in cerebral edema associated with TBI.20 Explosive blast TBI results when physical forces from detonation of explosive devices couples to neuronal tissue. Which of the many physical forces is important is not known, but likely candidates include blast overpressure and underpressure; and acoustic, electromagnetic, and thermal energy; with toxic agents such as chemical products of detonation perhaps also involved. Following these insults, brain cells can undergo both apoptotic and necrotic changes, with subacute to chronic neurodegeneration also potentially occurring. Brain vascular endothelial structures may also be injured, leading to vasospasm and pseudoaneurysm formation.18 When vascular injury is mild, the primary neurologic deficits are cognitive and neurobehavioral. As vascular injury severity increases, the neurologic state worsens from focal neurologic deficits to coma.21 REPEATED INJURY There is a growing appreciation that repeated re-injury, even years later, may lead to a worse neurologic outcome. The syndrome of chronic traumatic encephalopathy (CTE) is thought to be a

Second-impact syndrome is another potentially serious complication of mTBI.

consequence of this re-injury.22 Identified in boxers, dementia pugilistica, a form of CTE, is arguably the first clearly described syndrome in which permanent neurocognitive deficits develop as a result of repeated head blows.23 An increasing concern is that other professional athletes who are at risk for repeated concussions are also at risk for CTE. A recent case series of autopsies of former professional athletes (two boxers and one American football player) demonstrates that significant structural brain damage can occur in these high-risk patients.22 Second-impact syndrome (SIS) is another potentially serious complication of mTBI.24 A disorder that seems to affect children more than adults, SIS occurs as a consequence of sustaining another TBI before fully recovering from the initial one. Tragically, patients with SIS develop rapid cerebral edema, leading to severe neurologic deficits, including coma and death. The fatality rate of this fortunately rare disorder is very high, approaching 50%. The mechanism underlying SIS development is uncertain. A leading hypothesis is that cerebral autoregulation is impaired. Subsequent injury initiates the secondary injury cascade, often Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

KEY POINTS

Most patients with mTBI recover from this disorder with full resolution of symptoms. In mTBI, the most common head CT or MRI finding is a normal image.

exacerbating the presumed underlying inflammatory condition, thus allowing cerebral edema to develop, which in turn leads to intracranial hypertension. The existence of this disorder has not been fully accepted as limited cases of SIS have been reported. Given its potential for high morbidity and mortality, however, patients are usually counseled not to return to prior high-risk activities until a period of convalescence has passed. POSTCONCUSSIVE SYNDROME mTBI can lead to headache, confusion, amnesia, difficulty concentrating, mood alteration, sleep disturbance, and anxiety.25 Typically, these symptoms resolve within a few hours or days. Often, a patient with mTBI may not recognize it as such. The first indication of injury may be the manifestation of postconcussive symptoms. These are typically headaches, vertigo, short-term memory loss, or difficulty concentrating or with multitasking.26 As these symptoms can be subtle, a detailed mental status evaluation is necessary. An important part of this evaluation should be objective neuropsychological testing, even though initially it may only consist of limited bedside testing. Efforts are underway to develop neuropsychological tests that can be automated on a laptop computer or are more easily interpretable to allow use by less-trained providers. Fortunately, most patients with mTBI recover from this disorder with full resolution of symptoms. Some patients, however, have persistent symptoms that can last 6 months or more. When symptoms persist greater than a few days, postconcussive syndrome should be considered. TBI of any severity can lead to postconcussive syndrome. NEUROIMAGING The decision to obtain neuroimaging is based on the risk for intracranial pa-

thology. The presence of intracranial blood, intracranial air, skull fracture, or parenchymal contusion on routine CT or MRI suggests a more severe traumatic brain injury. Patients with such findings will need neurosurgical evaluation. The indication for neuroimaging is a presenting history of trauma and signs and symptoms concerning for structural lesions, such as focal neurologic signs and prolonged depressed levels of consciousness. These patients are at highest risk following concussion and should have neuroimaging (ie, AAN grade 2 or 3 concussion). Moderaterisk patients are those who have had a recent history of brief altered mental status only, eg, an AAN grade 1 concussion. Patients at minimal risk are asymptomatic, experience only headache or scalp laceration, and thus do not meet criteria for having sustained a concussion. This last group should not have neuroimaging for mTBI.27,28 In mTBI, the most common head CT or MRI finding is a normal image.29 Patients with mTBI typically do not require hospital admission and can be followed as outpatients. It is generally recommended, however, that a friend or family member monitor them in the acute period (12 to 24 hours after injury) for any signs of deterioration.30,31 TREATMENT Recognition that an mTBI has occurred is important. This can be difficult as the history may be unclear in a patient who presents with a normal general neurologic examination. If mTBI is suspected, a detailed mental status examination that includes frontal lobe tasks should be conducted. A useful aid is the Defense and Veterans Brain Injury Centerâ&#x20AC;&#x2122;s military acute concussion evaluation (MACE),32 a paper-based, rapid bedside neuropsychological tool modeled after the Standard Assessment of Concussion used by the National Football League.

Continuum Lifelong Learning Neurol 2010;16(6)

Other tools, such as computer-based reaction time testing and ocular motor testing, are becoming available. TBI treatment has greatly improved over the past 15 years, largely because of the widespread use of evidence-based guidelines for clinical management. In 1995, The Brain Trauma Foundation published the first edition of the ‘‘Guidelines for Management of Severe Traumatic Brain Injury.’’ Since then, two updated editions have been released, with the most recent in 2007.33 The guidelines were developed jointly by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. Other guidelines have also been released so as to optimize prehospital care and neurosurgical intervention. They are the ‘‘Prehospital Guidelines for Management of Severe Traumatic Brain Injury,’’ the ‘‘Guidelines for the Field Management of Combat-Related Head Trauma,’’ and the ‘‘Surgical Management of Traumatic Brain Injury.’’34–36 Treatment begins at the site of injury. Anyone suspected of sustaining a TBI, no matter how minor, should be immediately removed from further play or work. For mild injury, if the individual has had no mental status changes and is neurologically normal, he or she may return to previous activity. If any confusion is noted, the injured person should be evaluated by a trained provider. If any loss of consciousness is present, the person should be evaluated by an experienced medical provider, ideally in a hospital emergency department. If the TBI is severe, it is a medical emergency requiring rapid evacuation to a level 1 trauma center with neurosurgical capability. While in the field and during transport, it is important to remember the ABCs, ie, airway protection, maintenance of ventilation, bleeding control, and circulation maintenance. Hypoxia and hypotension should be avoided by maintaining oxygen saturation greater

than 90% and systolic blood pressure greater than 90 mm Hg.34,35 The most important treatment for mTBI or acute concussion is the prevention of further injury. Removal from play or work followed by adequate rest and recuperation is the mainstay of therapy.11 Symptomatic treatment is indicated to help ameliorate the condition. The Veterans Administration and Department of Defense have issued clinical practice guidelines for concussion/ mTBI.36 These are evidence-based pharmacologic and nonpharmacologic strategies designed to be symptom targeted. For example, it is recommended that headaches be treated with nonsteroidal anti-inflammatory agents as well as physical therapy, relaxation, and sleep. Cognitive disorders can be treated with selective serotonin reuptake inhibitors as well as reassurance, sleep, and physical activity. In general, this condition will last just a few weeks but, in some cases, can persist up to 1 year or more.37 Moderate and severe TBI are serious conditions that require immediate and advanced medical care. Initially, attention must be made to ensure airway patency, control of bleeding, and adequate circulation, the ABCs. Such patients require hospital admission, typically to a neurocritical care unit. Early neuroimaging is important as these patients often require neurosurgical intervention. Clinically deteriorating patients and those with GCS scores of 8 or less should be intubated as they are unable to adequately protect their airway. They should also be placed in a rigid neck collar with the head elevated 308. The neck collar performs two important functions: (1) to protect the cervical spine so that appropriate neuroimaging can be conducted to ensure there is no spine injury; and (2) to keep the head midline to avoid compromising venous drainage.33

KEY POINT

Hypoxia and hypotension should be avoided by maintaining oxygen saturation greater than 90% and systolic blood pressure greater than 90 mm Hg.

Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

KEY POINT

Cerebral perfusion pressure should be maintained between 50 mm Hg and 70 mm Hg, with a target of 60 mm Hg.

If any evidence of brain herniation, such as asymmetric pupils, is present, mannitol should be given intravenously at a dose of 0.5 g/kg to 1.0 g/kg. Thereafter, lower intermittent boluses can be used with IV doses of 25 g to 50 g administered every 4 to 6 hours until serum osmolality exceeds 315 mOsm/L. The decision to use induced hypothermia is difficult as it is not yet standard care for TBI. Preclinical studies are promising, but no compelling human clinical evidence of efficacy has yet been shown.37–40 An ICP monitor is needed for a TBI patient with a GCS score of 8 or less. The external ventricular drainage device or intraventricular catheter has two benefits. The first is that among all ICP monitors, it provides the most reliable data. The second and equally important benefit is that it is also a treatment option as it allows CSF drainage so that ICP and abnormal intracranial compliance can be controlled according to MonroKellie doctrine. This essentially states that the intracranial volume is a constant and that contributing volumes of CSF, intracranial blood volume, and brain parenchyma together with any spaceoccupying lesion remain constant. Therapeutic measures to alter ICP and move down the intracranial compliance curve are to reduce the intracranial blood volume, alter production/drainage of CSF, and use osmotherapy to reduce the CNS tissue volume. Other options for monitoring ICP, such as subdural bolt and fiber optic epidural catheter, are less invasive but less reliable.33 ICP should be 20 mm Hg or less. If ICP remains elevated after the above measures, induced hyperventilation may be tried. Respiratory rate should be increased to decrease arterial PCO2 to 34 mm HG to 36 mm Hg. Often the respiratory rate to achieve this is about 16 breaths per minute. It must be understood that this is only a temporizing therapy. The clinical response is very

fast and lasts a few hours but then rapidly loses efficacy because of local metabolic compensation within the CSF and brain tissue. When employed, efforts should be made to wean the patient from this type of therapy as soon as other interventions become effective.33 If these efforts are unable to control the ICP, other options are to induce barbiturate coma or undertake neurosurgical decompression or hemicraniectomy. If barbiturate coma is to be used, pentobarbital can be administered at a loading dose of 5 mg/kg IV followed by an infusion of 1 mg/kg/h to 3 mg/kg/h. The goal is to induce a burst-suppression pattern on EEG, obligating use of continuous EEG monitoring. Barbiturates are myocardial depressants and, thus, aggressive cardiovascular management will probably be necessary to maintain systemic blood pressure. Unresponsive ICP after induction of barbiturate coma is an ominous sign, and neurosurgical consideration should be made regarding frontal or temporal lobe decompression and/or hemicraniectomy.33 As ICP issues are being addressed, attention must be paid to the cerebral perfusion pressure (CPP). ICP and CPP are related by

CPP ¼ MAP ICP ðequation 1Þ in which MAP is the mean arterial pressure. The goal is to maintain the CPP between 50 mm Hg and 70 mm Hg, with a target of 60 mm Hg.33,41 Addressing CPP begins with placing an arterial line and providing isotonic fluid resuscitation to euvolemia. Adequate hydration must be maintained. In order to increase the osmolar gradient between the systemic vasculature and the brain, hyperosmolar IV solutions should be used. Normal saline is most commonly used and is hyperosmolar relative to blood. Another option is hypertonic saline.33

Continuum Lifelong Learning Neurol 2010;16(6)

Hypertonic saline is a useful adjunctive therapy in managing cerebral edema and intracranial hypertension.42 It can be administered either as a 2% or 3% continuous IV infusion. The rate of infusion is determined to be what is necessary to maintain euvolemia. Conceptually, hypertonic saline creates an osmotic gradient, which favors reduction of intracerebral water. This will reduce brain volume and thus ICP. When 2% or higher saline solutions are used, a mixture of 50% sodium chloride and 50% sodium acetate is helpful. This helps minimize hyperchloremia. Infusions are administered until a serum sodium goal is met, typically 150 mEq/L to 155 mEq/L or higher as needed. These serum sodium levels will result in serum osmolality of approximately 310 mOsm/kg to 320 mOsm/kg. Once ICP is controlled, hypertonic saline can be switched to normal saline. When the time is appropriate to discontinue the infusion, it can be stopped abruptly. Serum sodium will normalize over the next 24 to 48 hours. Potential untoward effects of hypertonic saline use are thrombophlebitis, seizures, and central pontine myelinolysis. By administering the solution through a central venous line, thrombophlebitis can be avoided. Seizure risk is highest with serum sodium levels above 160 mEq/L to 165 mEq/L. Central pontine myelinolysis is generally not an issue as the rise and fall of serum sodium associated with hypertonic saline infusion and discontinuation is less than 1 mEq/L/h unless a loop diuretic is given simultaneously. Another option in the case of acute herniation syndromes is very high hyperosmotic saline (23%) given as a slow IV administration of 30 cc to 60 cc (total dose). The onset of effect is rapid, often within minutes, and the ICP lowering effect can last several hours. One major benefit of this approach is that intravascular volume is not compromised. This is especially helpful for the polytrauma

patient who may be experiencing hemorrhagic shock.42â&#x20AC;&#x201C;44 If meeting CPP goals continues to be difficult with IV fluids alone, vasoactive pharmacologic agents, such as phenylephrine and norepinephrine, may be required. Dopamine is less often used as it has the potential to further elevate ICP. Invasive hemodynamic monitoring with a central venous catheter or pulmonary artery/Swan-Ganz catheter may be needed.33 Hypoxia, seizures, and fever need to be avoided. Maintaining PO2 at approximately 80 mm Hg to 100 mm Hg is sufficient. No benefit to higher levels of oxygen has been documented, but a potential for toxicity exists. Studies have shown that phenytoin will reduce early posttraumatic seizures, ie, those that occur during the first 7 days after TBI.45 However, further phenytoin treatment does not appear to reduce the rate of developing late posttraumatic seizures, ie, seizures that develop beyond 7 days from injury. Thus, phenytoin should be administered only for the first 7 days after injury and then stopped. Only if the patient should have a seizure thereafter should antiepileptic medications be restarted. Valproate was also shown to be effective in reducing early posttraumatic seizures, but it, too, did not reduce late posttraumatic seizure rate. Unfortunately, valproate was also associated with a higher mortality rate. Thus, phenytoin is the preferred agent.46 Fever increases cerebral metabolic rate and therefore should be minimized. Although TBI alone can induce a fever, this should be a diagnosis of exclusion. Febrile patients should be appropriately worked up for an underlying infection to include blood count, chest x-ray, urinalysis, and cultures of blood and urine. At the same time, the fever needs to be reduced. This can be achieved with acetaminophen and cooling blankets. If a patient develops severe shivering, one should consider administering Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

KEY POINT

The AAN’s guidelines for concussion management include recommended periods of recovery and are a practical clinical guide.

meperidine and/or inducing pharmacologic paralysis, eg, with vecuronium. If using paralysis, sedation is mandatory. Other important clinical issues are nutrition, stress ulcer prophylaxis, and deep vein thrombosis prevention with sequential compression devices and anticoagulation using low-molecularweight heparin or low-dose unfractionated heparin, with or without mechanical compression devices such as graduated compression stockings and sequential compression devices.33,47 If intracerebral blood is present, it is recommended that only sequential compression devices be used until the risk of further bleeding decreases, at which time anticoagulation may be started.33,47 To ensure adequate nutrition, a nasogastric or orogastric tube should be placed. Since most patients with TBI have some cerebral edema, hypo-osmotic feeds should not be used to minimize free water, which could worsen cerebral edema. Again, the injured brain is hypermetabolic so patients with TBI typically require 140% of their basal metabolic caloric needs.33 While in the acute period, all patients with TBI should be examined neurologically on a regular basis—at least every hour for the first 24 hours, which is a hyperacute period, and then less often as clinically indicated. For patients with intracranial lesions, continuous ICP and CPP measurements should be made. In general, the period of time after injury during which cerebral edema is greatest is from 48 to 96 hours. Thereafter, edema should begin to resolve, and the patient should improve clinically. RETURN TO PLAY OR WORK The decision to return to play or work is difficult as many patients do not recognize the need for convalescence, especially in the case of mTBI. This lack of insight may be attributed to the relatively mild symptoms experienced by the patient or be a direct result of the brain injury itself. Patients and their

families must be educated about the need to allow for an adequate period of recuperation. Potentially the encounter with health care providers is an opportunity to facilitate greater awareness of primary prevention of TBI in the patient and family members. Typically this entails the effective use of some taskspecific personal protective equipment, such as a helmet. The AAN’s guidelines for concussion management include recommended periods of recovery and are a practical clinical guide.25 Other guidelines that can also be used are the Cantu Grading system, the Colorado Medical Society Guidelines, and the Zurich Consensus 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.48–54 CONCLUSION TBI is not a new disorder. It has existed as long as man has existed. However, recent insights are improving the understanding of the pathophysiology of this condition as well as directing new efforts to improve diagnosis and treatment. Although a specific brain rescue drug remains elusive, evidenced-based clinical practice guidelines for treatment and return to play/work/duty provide a rational approach to managing these patients and improving outcome. DISCLAIMER The opinions expressed herein belong solely to the authors. They are not, nor should they be interpreted as, representative of or endorsed by the Uniformed Services University of the Health Sciences, the Defense Advanced Research Projects Agency, the Defense and Veterans Brain Injury Center, the United States Army, or the Department of Defense.

Continuum Lifelong Learning Neurol 2010;16(6)

REFERENCES 1. Centers for Disease Control and Prevention (CDC), National Center for Injury Prevention and Control: Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. www.cdc. gov/ncipc/pub-res/mtbi/report.htm. Updated September, 2003. Accessed August 31, 2010. 2. Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths 2002–2006. www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf. Updated March 2010. Accessed August 31, 2010. 3. Rimel RW, Giordani B, Barth JT, et al. Disability caused by minor head injury. Neurosurgery 1981;9(3):221–228. 4. Alexander MP. Mild traumatic brain injury: pathophysiology, natural history, and clinical management. Neurology 1995;45(7):1253–1260. 5. Centers for Disease Control and Prevention. Injury prevention and control: traumatic brain injury. www.cdc.gov/traumaticbraininjury/statistics.html. 2010. Accessed October 17, 2010. 6. Giacino J, Zasler N. Outcome after severe traumatic brain injury: coma, the vegetative state, and the minimally responsive state. J Head Trauma Rehabil 1995;10:40–56. 7. Finkelstein EA, Corso PS, Miller TR. Incidence and economic burden of injuries in the United States. New York: Oxford University Press, 2006. 8. Holder S. Paying for medical costs of a brain injury. www.headbraininjuries.com. June 25, 2008. Accessed August 31, 2010. 9. Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974;2(7872):81–84. 10. Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma Rehabil 1993;8(3):86–87. 11. Kelly JP, Rosenberg J; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: the management of concussion in sports (summary statement); report of the Quality Standards Subcommittee. Neurology 1997;48(3):581–585. 12. Geocadin RG. Traumatic brain injury. In: Bhardwaj A, Mirski MA, Ulatowski JA. Handbook of neurocritical care. Totowa, NJ: Humana Press, 2004:73–89. 13. Jarell AD, Ecklund JM, Ling GSF. Traumatic brain injury. In: Tsokos GC, Atkins JL. Combat medicine. Totowa, NJ: Humana Press, 2003:351–370. 14. The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (1). N Engl J Med 1994;330(21):1499–1508. 15. Casey KF, McIntosh T. The role of novel pharmacotherapy in brain injury. J Head Trauma Rehabil 1994;9(1):82–90.

Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

16. Chestnut RM, Marshall LF. Management of severe head injury. In: Ropper AH, editor. Neurological and neurosurgical intensive care. 3rd ed. New York: Raven Press, 1993:203–246. 17. Miller JD. Head injury and brain ischaemia—implications for therapy. Br J Anaesth 1985;57(1):120–130. 18. Armonda RA, Bell RS, Vo AH, et al. Wartime traumatic cerebral vasospasm: recent review of combat casualties. Neurosurgery 2006;59(6):1215–1225. 19. Reilly PI, Bullock R, editors. Head injury: pathophysiology and management. 2nd ed. London: Hodder Arnold, 2005. 20. Salazar AM. Traumatic brain injury: the continuing epidemic. In: Challenges in neurology, Hachinski VC, ed. Philadelphia: FA Davis Co, 1990:55–67. 21. Ling G, Bandak F, Armonda R, et al. Explosive blast neurotrauma. J Neurotrauma 2009;26(6):815–825. 22. McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009;68(7):709–735. 23. Martland HS. Punch drunk. J Amer Med Assn 1928;91:1103–1107. 24. Saunders RL, Harbaugh RE. The second impact in catastrophic contact-sports head trauma. JAMA 1984;252(4):538–539. 25. Quality Standards Subcommittee. Practice parameter: the management of concussion in sports (summary statement): report of the Quality Standards Subcommittee. Neurology 1997;48:581–585. 26. Ropper AH, Gorson KC. Clinical practice: concussion. N Engl J Med 2007;356(2): 166–172. 27. Mirvis SE, Shanmuganathan K. Trauma radiology, part IV: imaging of acute craniocerebral trauma J Intensive Care Med 1994;9(6):305–315. 28. Zee CS, Go JL. CT of head trauma. Neuroimaging Clin North Am 1998;8:525–539.

29. Belanger HG, Vanderploeg RD, Curtiss G, Warden DL. Recent neuroimaging techniques in mild traumatic brain injury. J Neuropsychiatry Clin Neurosci 2007;19(1):5–20. 30. Stiell IG, Wells GA, Vandemheen K, for the CCC Study Group. The Canadian CT head rule for patients with minor head injury. Lancet 2001;357(9266):1391–1396. 31. Smits M, Dippel DW, Steyerberg EW, et al. Predicting intracranial traumatic findings on computed tomography in patients with minor head injury: the CHIP prediction rule. Ann Int Med 2007;146(6):397–405. 32. Defense and Veterans Brain Injury Center. Military acute concussion evaluation. www.pdhealth.mil/downloads/MACE.pdf. Accessed September 2, 2010. 33. Bullock MR, Povlishock JT, eds. Guidelines for the management of severe traumatic brain injury. J Neurotrauma 2007;24:S1–S106.

Continuum Lifelong Learning Neurol 2010;16(6)

34. Badjatia N, Carney N, Crocco TJ, et al. Guidelines for prehospital management of traumatic brain injury. 2nd ed. Prehosp Emerg Care 2008;12:S1–S52. 35. Knuth T, LeTarte PB, Ling G, et al. Guidelines for the field management of combat-related head trauma. Brain Trauma Foundation. www.guideline.gov/ content.aspx?id=11009. Updated 2005. Accessed August 31, 2010. 36. Bullock MR, Chestnut R, Ghajar J, et al. Guidelines for the surgical management of severe traumatic brain injury. Neurosurgery 2006;58(3 suppl):S2–S46. 37. Management of Concussion/mTBI Working Group. The VA/DoD clinical practice guidelines for management of concussion/mild traumatic brain injury. J Rehabil Res Dev 2009;46(6):CP1–CP68. 38. Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 1997;336(8):540–546. 39. Marion DW. Head and spinal cord injury. Neurol Clin 1998 May;16(2):485–502. 40. Clifton GL, Choi SC, Miller ER, Intercenter variance in clinical trials of head trauma—experience of the National Acute Brain Injury Study: Hypothermia. J Neurosurg 2001;95(5):751–755. 41. Ling G, Neal CJ. Maintaining cerebral perfusion pressure is a worthy clinical goal. Neurocrit Care 2005;2(1):75–81. 42. Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000;28(9):3301–3313. 43. Koenig MA, Bryan M, Lewin JL 3rd, et al. Reversal of transtentorial herniation with hypertonic saline. Neurology 2008;70(13):1023–1029. 44. Ling GS, Marshall SA. Management of traumatic brain injury in the intensive care unit. Neurol Clin 2008;26(2):409–426. 45. Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. New Engl J Med 1990;323(8):497–02. 46. Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg 1999;91(4):593–600. 47. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians, evidence-based clinical practice guidelines (8th edition). Chest 2008;133(6 suppl):381S–453S. 48. Cantu RC. Guidelines for return to contact sports after a cerebral concussion. Phys Sportsmed 1986;14(10):75–83. 49. Colorado Medical Society School and Sports Medicine Committee. Guidelines for the management of concussion in sports. Colo Med 1990;87:4. 50. Kelly JP, Nichols JS, Filley CM, et al. Concussion in sports: guidelines for the prevention of catastrophic outcome. JAMA 1991;266(20):2867–2869. 51. Cantu RC. Cerebral concussion in sport: management and prevention. Sports Med 1992;14(1):64–74.

Continuum Lifelong Learning Neurol 2010;16(6)

" DIAGNOSIS AND MANAGEMENT

52. Bailes JE, Cantu RC. Head injury in athletes. Neurosurgery 2001;48(1):26–45. 53. Bleiberg J, Cernich AN, Cameron K, et al. Duration of cognitive impairment after sports concussion. Neurosurgery 2004;54(5):1073–1078; discussion 1078–1080. 54. McCrory P, Meeuwisse W, Johnston K, et al. Consensus statement on concussion in sport—the 3rd international conference on concussion in sport held in Zurich. J Clin Neurosci 2009;16(6):755–763.

Continuum Lifelong Learning Neurol 2010;16(6)