Current Trauma Reports https://doi.org/10.1007/s40719-018-0133-3

THE MILITARY PERSPECTIVE (MJ MARTIN AND M SCHREIBER, SECTION EDITORS)

Traumatic Brain Injury in Combat Casualties Patrick Walker 1,2 & Joseph Bozzay 1,2 & Randy Bell 1 & Matthew Bradley 1,2 & Carlos Rodriguez 1

# This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Abstract Purpose of Review The purpose of this review is to give an overview of recent updates in the management of traumatic brain injury (TBI) in military settings. Recent Findings Studies from the recent conflicts in Central and Southwest Asia have demonstrated that appropriate aggressive neurosurgical intervention in austere settings has been associated with improved outcomes. Summary Modern management of military TBI has evolved from the era of Cushing in WWI to damage control and rapid aeromedical evacuation today. Aggressive management of severe injuries has been shown to increase survival. These interventions have included an emphasis on measures to reduce secondary brain injury—aggressive cranial decompression, addressing intracranial vascular injuries, and aeromedical evacuation to facilities with neurosurgical capability. Additionally, advances in the screening of mild TBI have led to increased awareness of the prevalence of this injury and potential associated long-term effects. Keywords Military traumatic brain injury . Penetrating brain injury . Neurocritical care . Decompressive craniectomy . Aeromedical evacuation

Introduction With multiple components contributing to brain injury in combat service members, blast-related traumatic brain injury (TBI) has become a common injury pattern in modern warfare. Primary blast injury is related to the effects of the blast pressure wave on the brain. Secondary blast injury occurs with penetration of fragments through the cranium into the brain. Acceleration and deceleration effects from blasts lead to tertiary blast injury, and quaternary blast injury occurs from exposure to heat and other toxins released from explosions [1]. Although there have been some recent comparable events in civilian trauma, weapons used in combat typically generate more kinetic energy and more tissue injury than those seen in civilian settings, and penetrating craniocerebral injuries from these weapons have commonly been associated with worse neurologic outcomes [2]. Further brain injury also This article is part of the Topical Collection on The Military Perspective * Carlos Rodriguez [email protected] 1

Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed Military Medical Center, Bethesda, MD, USA

2

Naval Medical Research Center, Silver Spring, MD, USA

occurs from mass effect related to intracranial hemorrhage, secondary insults from hypoxia, hypotension, hyperthermia, and the prolonged inflammatory state induced by polytrauma. However, the combat trauma population is also generally younger and healthier than similar civilian trauma populations and thus may warrant a more aggressive approach in terms of interventions and resuscitation efforts. In this review, we will give an overview of the epidemiology of combat-related TBI as well as the evolution of neurosurgical intervention in combat. Current medical and surgical management of combatrelated TBI will be described, as will considerations for aeromedical evacuation, definitive care in the USA, and outcomes.

Epidemiology The recent wars in Iraq and Afghanistan have seen the largest incidence of both closed and penetrating brain injury to US service members since Vietnam [3]. Since 2000, more than 310,000 have been diagnosed with TBI. Most of these have been mild TBIs (82.4%) while only 1% have been severe TBIs. Approximately 1.5% have been penetrating TBIs [4]. Among moderate to severe TBIs, penetrating TBI occurred at an incidence greater than 2:1 compared to closed TBI in Operation Iraqi Freedom (OIF). However, in Operation Enduring Freedom (OEF) in Afghanistan, that ratio was less

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at 1.3:1. Penetrating TBIs in combat are typically more severe and associated with worse outcomes than blunt or blast closed head injuries [5]. A study of service members killed in action in Iraq and Afghanistan demonstrated that brain injury was associated with near-instantaneous death in 38.3%, and 53% of deaths that occurred en route to a military treatment facility (MTF) [6]. Moreover, when reviewing casualties that died of wounds in these two wars, 83% of deaths deemed non-survivable were attributable to TBI, whereas only 9% of deaths from potentially survivable injuries were from TBI [7]. Furthermore, it has been reported that up to 90% of casualties sustaining craniocerebral gunshot wounds die before reaching a medical facility while only approximately 50% of those patients who make it to a hospital survive [2]. When compared to a matched cohort of civilian patients with severe TBI, military casualties with TBI were more likely to undergo intracranial pressure (ICP) monitoring and neurosurgical intervention. However, mortality was found to be lower in military patients that arrived to military treatment facilities with severe TBI compared to civilian patients (7.7 vs. 21.0%, p < 0.001), particularly after penetrating mechanisms of injury (5.6 vs. 47.9%) [8].

Evolution of Combat-Related TBI Management Coinciding with the founding of the field of neurosurgery, modern management of penetrating head injuries during wartime was first described in significant detail by Dr. Harvey Cushing in World War I [9]. Radical cranial debridement and removal of all intracranial foreign bodies was advocated by Dr. Cushing at that time, with the recognition that early neurosurgical intervention could improve prognosis. In 1958, Dr. Donald Matson further described the tenets of forwarddeployed neurosurgery based on lessons learned in World War II. His emphasis was placed on performing timely lifesaving decompressive procedures, preventing intracranial infection while preserving neurological function and restoring anatomic structure [10]. In the Korean Conflict, early neurosurgical intervention was credited with decreasing the rate of meningocerebral infection, known to worsen prognosis if present [11]. Vietnamera neurosurgeons, as described by Dr. William Hammon, advocated Cushing’s writings with aggressive debridement and removal of any intracranial bone fragments visible on xray [12]. The Lebanon War from 1982 to 1985 brought advanced imaging capability closer to the frontlines as Israeli casualties were among the first to have their injuries diagnosed with CT scans near the point of injury [13]. Surgical management of penetrating TBI also evolved to one that involved less operative intervention as aggressive debridement to include

retrieval of intracranial fragments was not shown to make a difference in long-term outcomes, including infection and post-traumatic seizures. These and other lessons have been applied to neurosurgical intervention for penetrating and severe TBI in Iraq and Afghanistan. In these conflicts, an emphasis on aggressive cranial decompression to accommodate brain swelling as opposed to aggressive debridement of cerebral tissue or removal of intracranial foreign bodies has been associated with improved outcomes.

Mild TBI Mild TBI (mTBI) is classified on the basis of loss of consciousness up to 30 min, post-traumatic amnesia not exceeding 24 h, and a GCS of 13–15 within 30 min of presentation [14]. Most patients with mTBI make a complete recovery; however, some remain symptomatic even years after injury, often complaining of physical, cognitive, and behavioral symptoms consistent with post-concussive syndrome [14–17]. Risk factors for incomplete recovery include preexisting psychological disorders and lack of social support [15]. For combat casualties, post-traumatic stress disorder (PTSD) and suicidality are not infrequent consequences of deployment and may be exacerbated in TBI cases [17, 18]. A review of OIF/OEF service members found that 21.6% screened positive for TBI [19], most of which were mTBI [17]. There has been a large focus in the military on treating service members suffering from mTBI and current therapies include cognitive and behavioral health interventions [20].

Pre-hospital/Field Care and Initial Resuscitation in TBI The evidence-based 2017 Joint Trauma System (JTS) Clinical Practice Guidelines (CPG) for Neurosurgery and Severe Head Injury offer guidance for the treatment of presumed head injury and are heavily based on the Brain Trauma Foundation Guidelines [21••, 22••]. Care for the combatant suffering from a presumed TBI begins in the field at the point of injury. While each warfighter receives basic medical training, firstresponder military medical providers, such as navy corpsmen and army medics, embedded with the combatants, can administer more advanced care almost immediately after injury in the battlefield. The Advanced Trauma Life Support (ATLS) protocols and the Tactical Combat Casualty Care (TCCC) guidelines are used in the initial management of the patient with head trauma [21••, 23]. Unlike in ATLS, TCCC stresses circulation first, followed by airway and breathing [24]. Military Acute Concussion Evaluation Cards (MACE) are

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used to diagnose suspected TBI on the battlefield for awake and alert patients who can respond to the test questions [17, 25, 26]. This tool includes history and examination components and has been clinically validated for assessment in the acute phase of TBI [25, 26]. In the far-forward environment, intubation or cricothyroidotomy may be performed in the patient with a low Glasgow Comas Scale (GCS) or an inability to protect their airway [23]. However, while out-of-hospital intubation in TBI enables better oxygenation, it may also cause unintended hypo or hyperventilation, which can lead to adverse effects including cerebral vasoconstriction [27, 28]. Thus, any decrease in intracranial pressure (ICP) caused by hyperventilation may also be accompanied by cerebral ischemia due to decreased cerebral blood flow, thus exacerbating secondary brain injury [29]. Prophylactic hyperventilation is not recommended, especially within the first 24 h after injury, except as a temporizing measure for suspected increased ICP or herniation. Otherwise, the goal PaCO2 is 35–40 mmHg [21••, 27]. Hypoxemia, specifically a PaO2 < 60 mmHg or SaO2 < 90%, is associated with poor outcomes in brain injury [28, 30, 31]. JTS guidelines recommend SaO2 > 93–95% and PaO2 > 80 mmHg, which has been attainable despite the challenges associate with combat medical care, such as frequent handoffs, varying level of skills in personnel, and austere environments [17, 21••]. Patients who survive the initial brain injury may still experience secondary insults, such as hypotension, hypoxia, and tissue edema which can lead to an increase in ICP [30, 32•]. This can result in excitotoxicity, loss of cerebral autoregulation, and other metabolic and physiologic derangements, all of which can contribute to neurodegeneration [30–33]. Avoiding a systolic blood pressure of less than 90 mmHg is highly recommended, given the increased mortality risk associated with hypotension in TBI [21••, 28, 30, 31, 34]. Based on the Brain Trauma Foundation guidelines, a goal of SBP ≥ 100 mmHg should be targeted for patients 50–69 years old or ≥ 110 mmHg for patients 15–49 or over 70 years old, with a goal mean arterial pressure (MAP) of > 60 mmHg [21••, 34]. In this regard, ketamine has become a first-line analgesic in the battlefield as it has minimal effects on hemodynamics and intracranial pressure [24, 35]. Normal or 3% saline is the preferred crystalloid for resuscitation in severe TBI, and blood products should be transfused if indicated [21••, 36, 37]. Albumin is avoided, given the risk of increased ICP and mortality compared to saline resuscitation in brain injury [36, 38]. If increased ICP is diagnosed or clinically suspected, 3% saline is recommended as the firstline treatment on the battlefield, starting with a 250-ml bolus followed by infusion rate of 50–100 ml/h while en route to a facility with neurosurgical capability [21••]. Central access is recommended, and the goal serum sodium level is 150– 160 mEq/l [21••, 37]. Mannitol can be selectively used as an

alternative to 3% saline or as an adjunct if there is further deterioration in neurologic status [21••]. However, providers need to be mindful of the potential consequences of Mannitol’s use. In general, it should be avoided in hypotensive or under-resuscitated casualties given its osmotic diuretic properties. As combat casualties typically have multi-system injuries and a much higher rate of associated hemorrhage and shock compared to civilian TBI populations, hypertonic saline is preferred for the dual benefits of volume expansion and ICP reduction. In addition, mannitol has been associated with rebound elevation in ICP [39]. Serum sodium and osmolality should be frequently monitored and urine output replaced with isotonic fluids, with the goal of maintaining a hyperosmolar yet euvolemic status [21••]. Mannitol should be administered as a 1 g/kg bolus IV followed by 0.25 g/kg every 4 h while awaiting neurosurgical support [21••]. Antibiotics should be administered in cases of suspected penetrating injuries, open-skull fractures, or pre-operatively given the risk of infection and the association between infection and worse outcomes. Recommended regimens include cefazolin and clindamycin, with metronidazole advised if organic contamination is present [21••, 40]. Steroids should not be administered as they have not been shown to improve outcomes and have an associated mortality risk [21••, 34, 41, 42]. Throughout the initial stabilization and resuscitation of a patient with a severe TBI, GCS, localizing neurologic signs, and pupil exam should be serially documented, using the TCCC Casualty Card [21••, 23]. A non-contrast CT scan of the head should be obtained as soon as possible after injury. Given the challenges of the far-forward environment, the JTS guidelines stipulate a goal of obtaining head CT within 4 h of injury [21••]. An observational study of 99 TBI casualties from Iraq and Afghanistan demonstrated a high incidence of contributing factors to secondary brain injury—hypotension, hypoxia, and both hypercarbia and hypocarbia—on arrival to a military treatment facility (MTF) in a combat zone, which emphasized the importance of initiating effective TBI care as far-forward as possible [43].

ICU Management of Moderate to Severe TBI ICP monitoring is recommended in all severe TBI patients as elevated ICP is associated with poor clinical outcomes and mortality [21••, 34, 44, 45]. A 2012 randomized control trial showed no difference in survival, neurological, or functional outcomes for ICP monitoring compared to care based on imaging and clinical exam [32•]. However, based on more recent studies showing improved survival, both the Brain Trauma Foundation guidelines and JTS CPGs recommend invasive ICP monitoring and treatment in severe TBI [21••, 44, 46]. Patients with potentially survivable severe TBI and a CT scan showing hematomas, contusions, swelling, herniation, or

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compressed basal cisterns should be considered for ICP monitoring [21••, 34, 44]. Furthermore, ICP monitoring is indicated in severe TBI with normal CT scan if two of the following are met: age > 40, unilateral or bilateral posturing, and/or SBP < 90 mmHg [21••, 34, 44]. Options for cerebral monitoring include external ventricular drain (EVD) or intraparenchymal ICP monitors, of which the Codman ICP monitor is the only device with aeromedical certification [21••, 34]. Goal ICP is < 22 mmHg, and target cerebral perfusion pressure (CPP) is 60– 70 mmHg [21••, 34, 47]. ICP monitoring is not recommend for those patients with injuries deemed non-survivable. These injuries include brain evisceration, transcranial penetrating injury, brain stem injury, or involvement of deep nuclei or critical vasculature [6]. TBI patients are at a much higher risk for venous thromboembolism (VTE) events among trauma patients [48–50]. However, potential protective benefits of VTE chemoprophylaxis must be balanced against the risk of intracranial hemorrhage progression [48, 51]. Consideration of VTE prophylaxis initiation should involve discussion with the neurosurgeon [21••]. Civilian literature has shown initiation of chemoprophylaxis within 24–48 h of injury to be safe, especially when CT indicates an absence of progression of intracranial bleeding [50, 52]. However, early or late low-molecular-weight heparin administration may place patients at higher risk for hemorrhage progression [49]. Recent data from combat-related TBIs suggests that chemoprophylaxis administration approximately 24 h after injury does not lead to progression in penetrating brain injury, and current JTS guidelines recommend that chemoprophylaxis (enoxaparin 30 mg twice daily or subcutaneous heparin) be initiated as long as the patient does not have ongoing or progressive intracranial hemorrhage [21••, 48]. Post-traumatic seizures can occur in up to 25% of TBI patients, and current Brain Trauma guidelines recommend the use of prophylactic antiepileptic therapy for the first 7 days with the goal of preventing early seizures [46, 53, 54]. Those at high risk for post-traumatic seizures include patients with admission GCS < 10, cortical contusion, depressed skull fractures, penetrating head wounds, seizure within 24 h of injury, and subdural, epidural, and intracerebral hematoma [21••, 55]. Prophylaxis longer than 7 days has not been shown to decrease the development of late seizures [54]. Phenytoin has commonly been the drug of choice, but newer evidence suggests that use of levetiracetam may offer a similar reduced incidence of early seizures after TBI with the added benefit of not requiring drug level monitoring as is needed for phenytoin [34, 53]. JTS guidelines currently recommend that phenytoin, fosphenytoin, or levetiracetam can be used for seizure prophylaxis in the first 7 days after moderate or severe TBI while the Brain Trauma Foundation recommends antiepileptics when the benefits of therapy outweigh potential complications. In addition, lorazepam or midazolam followed by the addition of another antiepileptic should be administered

for acute seizures and this antiepileptic should be continued for 3 to 6 months [21••]. Both hyperglycemia and hypoglycemia have been associated with poor outcomes in TBI, likely due to hyperosmolarity or alterations in metabolism [56, 57]. Aggressive glucose control has been associated with poor outcomes in the critically ill [58]. JTS guidelines recommend that glucose be monitored every 6 h with the goal of avoiding hypoglycemia but keeping levels < 180 mg/dl [21••]. Providers should ensure TBI patients are euthermic. Hyperthermia should be treated using simple conductive maneuvers such as ice packs to various commercially available convective cooling devices to intravascular cooling catheters, depending on the severity of the hyperthermia [21••, 34]. Prophylactic hypothermia, while helpful in out-of-hospital cardiac arrest patients, is not recommended as it has not been shown to improve outcomes and has been shown to be associated with an increase in the development of pneumonia [34, 59, 60•]. The head of bed should be elevated to 30–45° to optimize venous drainage. Reverse Trendelenburg positioning should be used if spinal injury is suspected [21••]. Additional critical care considerations in the TBI patient include early enteral nutrition (within the first 48 h) and gastric ulcer prophylaxis [21••, 46]. Performance and adherence measures for the JTS CPG for Neurosurgery and Severe Head Injury are shown in Table 1.

Emerging Medical Therapies There are emerging therapies and novel agents that have shown promise in treating TBI but are not yet included in TBI treatment guidelines. Amantadine may improve the rate of functional recovery after severe TBI when started within 4 weeks after injury [61]. Hyperbaric oxygen therapy (HBOT) may reduce the risk of death and improve clinical outcomes when administered in the acute phases of TBI [62, 63]. Sulfonylurea receptor-1 antagonists, such as glibenclamide (glyburide), have been shown to reduce inflammation, Table 1 Performance and adherence measures in the Joint Trauma System Clinical Practice Guidelines (JTS CPG) for Neurosurgery and Severe Head Injury [21] - SBP > 110 mmHg, MAP > 60, and/or SaO2 > 93% documented upon discharge - Steroids were not administered - Neurological assessment and documentation of ICP/CPP and ventriculostomy output were recorded hourly in the ICU - Patients in whom neurological status cannot be monitored clinically, and patients with severe TBI, had ICP or ventriculostomy placed prior to transport out of theater - Patients with moderate to severe TBI had head CT performed - Patients with open-skull fractures received prophylactic antibiotics

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decrease the size of intracranial lesions, and enhance functional recovery in animal models. Studies are currently underway to determine if these effects are translatable into human TBI casualties [41, 64]. Beta blockers may improve survival and outcomes in TBI, and randomized trials are currently underway [41, 64–66]. Tranexamic acid (TXA) has been associated with a reduction in the rate of intracranial hemorrhage progression, but its long-term effects on outcomes are currently unclear [64, 67]. A randomized, prospective trial (CRASH-3) is underway to quantify the effects of early TXA administration on death and disability in TBI patients [68]. Other therapies being studied as TBI treatments include progesterone, statins, nerve growth factors, and minocycline, which may exert neuroprotective or neurorestorative effects [41, 64].

In-theater Neurosurgical Intervention Recent experience with severe combat-related TBI has demonstrated that early aggressive cranial decompression can be effective in salvaging patients with injuries that might be otherwise fatal. Bell, et al. studied 188 patients who underwent decompressive craniectomy in theater, 82% of whom had penetrating head injuries [69]. These patients had lower initial GCS scores (7.7 ± 4.2 vs. 10.8 ± 4.0, p < 0.05) and higher ISS (32.5 ± 9.4 vs. 26.8 ± 11.8, p < 0.05) compared to patients who did not undergo craniectomy. Although Glasgow Outcome Scores (GOS) were initially lower in those that had a craniectomy at discharge (3.0 ± 0.9 vs. 3.7 ± 0.9, p < 0.05) and remained lower at 1-year follow-up (3.7 ± 1.2 vs. 4.4 ± 0.9, p < 0.05), they improved over that time based on intragroup analysis (p < 0.05). Several recommendations were made regarding these findings [69]: 1. Early aggressive decompressive craniectomy should be considered in all military patients with severe TBI. 2. This excludes injuries that transverse the zona fatalis or are otherwise clearly non-survivable [70], as selection is important to optimize neurological outcomes and avoid postoperative vegetative states. 3. Watertight dural closure to avoid cerebrospinal fluid leak and adequate cranialization of violated sinuses should be performed. 4. Apart from local nationals, removed bone should also generally be discarded instead of implanted into the abdominal wall due to infectious concerns. The decision for early decompressive craniectomy allows for the ability to safely transfer patients with combat-related severe head injuries while minimizing risk for elevated ICP and further secondary brain injury. Specific indications for decompressive craniectomy in theater include [71]:

1. Penetrating head injuries from high-energy missiles with significant risk of associated brain swelling 2. Persistent intracranial hypertension despite traditional maneuvers to decrease ICP 3. Patients deemed to be at high risk to develop intracranial hypertension during transport. When performed, care should be taken to ensure that the craniectomy is large enough that brain does not herniate around the bone edges, placing it at risk for strangulation. Further regarding damage control maneuvers, packing has been described as an effective means of providing tamponade to relentless bleeding [72]. In select patients with bilateral or supra- and infra-tentorial swelling from severe combat-related TBI, bilateral or bicompartmental decompressive craniectomy has also been shown to be effective, with 60% of patients achieving a GOS score of 4 or 5 (disabled but independent or fully functional, respectively) at long-term follow-up [73]. Routine removal of intracranial metallic or bone fragments is generally not advisable. There may be a decrease in the incidence of post-traumatic seizures, however, with removal of fragments from the sensory, motor, or language cortex [74]. Debridement of devitalized brain tissue is an option in penetrating head injuries as well as in select open-skull fractures if encountered during surgical exploration [21••]. Table 2 lists CT scan features associated with a poor prognosis in penetrating TBI, and examples of CT scan slices for a penetrating are shown in Figs. 1 and 2. The DECRA trial, published in 2011, evaluated decompressive craniectomy in 155 patients with severe traumatic brain injury without hematoma and intracranial hypertension refractory to medical therapy. Patients with ICP > 20 mmHg for 15 min in a 1-h period in the first 72 h of injury were randomized to undergo bifrontotemporoparietal decompressive craniectomy or standard medical care [75]. The authors found that despite having less time with elevated ICP Table 2 Computed tomography (CT) scan findings associated with poor prognosis after penetrating traumatic brain injury (TBI) [2] - Multilobar or bihemispheric injury - Ventricular injury with hemorrhage - Diffuse fragmentation - Missile passing through geographic center of the brain, i.e., zona fatalis (4 cm above the dorsum sellae) - Trajectory crossing the x, y, and z planes - Midline shift > 10 mm - Compressed or obliterated basal cisterns - Large intracerebral hemorrhage - Subarachnoid hemorrhage - Large volume of contused brain - Posterior fossa wound with brainstem involvement - Tram track sign hemorrhage on either side of a dark center missile track

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Fig. 1 Axial head CT through the posterior fossa of a casualty with penetrating TBI. The arrow identifies a fragment, and the arrow direction is the approximate trajectory of the fragment from supra to infra-tentorial

and fewer ICU days, the patients who underwent craniectomy had a greater risk of unfavorable outcome (death, vegetative state, or severe disability) at 6 months’ follow-up (OR 2.21, 95% CI 1.14–4.26, p = 0.02). More recently, the rescueICP trial, published in 2016, also evaluated decompressive craniectomy as a last-resort intervention for patients with severe TBI and elevated ICP. This study randomized 408 patients with traumatic brain injury and refractory intracranial hypertension to undergo decompressive craniectomy or continue to receive medical care [76•]. In contrast to the DECRA trial, the authors in rescueICP defined refractory elevated ICP as greater than 25 mmHg for 1 to 12 h despite maximal medical therapy. Additionally, a unilateral frontotemporoparietal craniectomy was performed unless both hemispheres were involved, where a bifrontal craniectomy was performed. The median time from randomization to surgery was 2.2 h. Unlike DECRA, the authors of

rescueICP reported a roughly 22% improvement in mortality (30.4 vs. 52%, p < 0.001) as well as a 13% improvement in Bfavorable outcome^ on the extended GOS scale (45.5 vs. 32.4%, p = 0.01) at 12 months for the patients that underwent craniectomy. Thus, decompressive craniectomy may be considered for patients with severe TBI (closed or penetrating) and refractory intracranial hypertension as an intervention to potentially improve neurologic outcomes. Regarding surgical intervention for intracranial hemorrhage, epidural hematomas (EDH) > 30 ml should be surgically evacuated regardless of underlying GCS. EDH < 30 ml that are less than 15-mm thick with < 5 mm midline shift and a GCS > 8 can be managed non-operatively with ICU monitoring and close interval CT scans within 6 h [77]. Acute subdural hematomas (SDH) with a thickness > 10 mm or midline shift > 5 mm regardless of GCS should be evacuated with craniotomy. Evacuation should also be performed for acute SDH if there is a decrease in GCS of 2 or more, developing pupillary dilation, or ICP > 20 mmHg [78]. Traumatic parenchymal lesions > 50 ml in salvageable patients should be evacuated as should contusions > 20 ml with midline shift at least 5 mm or cisternal compression in patients with a GCS of 6–8 [79]. Posterior fossa lesions with mass effect seen on CT or with abnormal neurologic exam should be emergently decompressed [77]. Exploratory burr holes have limited utility and should only be performed after consultation with a neurosurgeon, if possible, and at locations where CT scans are not available. Beyond these considerations, additional criteria for burr holes include a localizing but deteriorating neurologic exam with unilateral pupillary changes [21••, 80]. During the recent military conflicts, however, non-neurosurgeons (i.e., general surgeons) have been trained to successfully perform a variety of neurosurgical procedures ranging from placement of ICP monitors to damage control decompressive craniectomies when neurosurgeons were not available [81]. Prior to future deployments,

Fig. 2 Features of a penetrating TBI on CT scan. Shown are in-driven bone fragments (a, c), penetrating metallic fragment to the interhemispheric fissure with surrounding hemorrhage (b), and extent of decompressive craniectomy (a–c)

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general surgeons may be called upon to complete training in neurosurgical interventions. The DOD JTS has recently developed a CPG regarding non-neurosurgeons and emergency cranial procedures [82]. Before considering the performance of an emergency cranial procedure, non-neurosurgeons should first attempt to evacuate a patient to a facility where neurosurgery is available within 4 h. In situations where this is not possible, an emphasis is made on obtaining teleconsultation with a neurosurgeon. If a CT scanner is not available, there is a high likelihood that cranial procedures if performed will be done so without correctly localizing pathology. Thus, every effort should be made to obtain an accurate diagnosis, resuscitate, and utilize all medical adjuncts prior to any intervention in these scenarios.

Aeromedical Evacuation Neurosurgical support was typically available at Role III medical facilities in Iraq and Afghanistan. These Role III facilities essentially functioned as level 1 trauma centers in austere deployed environments [17, 21••]. Aeromedical evacuation was often required to transport TBI patients to Role III facilities. However, in general, the availability and type of transport is influenced by several tactical factors such as enemy contact and the presence of friendly troops in the area [31]. JTS guidelines recommend the avoidance of long-acting sedation and paralysis for aeromedical evacuation. However, medications that may be necessary to facilitate safe transfer are left up to the discretion of the transporting medical team [21••]. Vecuronium is the preferred agent for paralysis as it does not require refrigeration and is more easily available in the austere environment and bolus dosing is preferred over continuous infusion [21••]. Propofol is the recommended sedation agent due to its rapid offset of action and reduction in ICP [21••, 34, 83]. Intermittent narcotics are preferred over continuous infusions for analgesia [21••]. Aeromedical evacuation is a challenging component in the care of casualties with TBI. Vibration, noise, movement, light, and changes in temperature, oxygen pressure, and altitude can adversely affect the patient and may delay transport for the patient with unsatisfactory ICP [21••, 31]. Altitude changes and hypobaric conditions can lead to reduced PaO2, cerebral blood flow, and CPP and may exacerbate secondary brain injury with an adverse effect on outcomes [31, 33]. Although transport to the initial Role 3 facility is usually less than an hour and generally involves rotary wing aircraft, the evacuation outside the combat theater of operation and back to the USA is performed using fixed wing aircraft and can last up to 6 h [31, 33]. The critical care transport team on this aircraft usually includes a physician, nurse, and respiratory therapist, and their focus is primarily on the management of elevated ICP, hypoxia, and hypotension [17, 21••]. Presently, studies

involving animal models are being carried out to characterize the impact of aeromedical evacuation on TBI outcomes [33].

Management in the Continental United States Management of severe and penetrating TBI in the Continental United States (CONUS) is focused on detecting sequelae associated with these types of injuries as well as optimizing the movement towards rehabilitation. On arrival in CONUS, patients generally undergo repeat head CT scan as well as transcranial Doppler (TCD). CT angiography is usually deferred in penetrating TBI given the artifact produced by metal fragments. Cerebrovascular complications to be aware of include traumatic aneurysms, traumatic vasospasm, dissections, and arteriovenous fistulae. Patients undergo cerebral angiography for the following indications: TCD evidence of vasospasm, history of a blast injury (closed or penetrating TBI) with initial GCS < 8, known pseudoaneurysm or vascular injury seen on initial surgical exploration, decrease in cerebral blood flow/ brain tissue oxygen, penetrating injury through the pterional/ orbitofrontal region, or lack of improvement in GCS without identifiable cause [84, 85]. A retrospective series analyzed 15 cases of traumatic intracranial aneurysms—these were all false aneurysms, and 80% were associated with intracerebral hematomas [86]. Intervention, therefore, is frequently recommended for traumatic aneurysms. A retrospective evaluation by Armonda and colleagues of 57 casualties that had cerebral angiography showed a 47.4% incidence of traumatic vasospasm [84]. This occurred at a mean of 14.3 days from injury and was associated with worse outcomes when vasospasm occurred. Early endovascular therapy was seen to be effective in the management of traumatic vasospasm in addition to medical management including volume expansion, hypertension, and hemodilution. A subsequent study by Bell and colleagues further characterized that 26.2% of patients who underwent diagnostic cerebral angiography after combat-related brain injury were found to have an associated intracranial vascular injury. They also demonstrated that endovascular management of these vascular lesions is safe and can be particularly effective while patients recover from the initial sequelae of acute head injury [85]. In a study of 108 patients who underwent cranial reconstruction in CONUS, the average time between injury and cranioplasty was 190 days [87]. After obtaining fine-cut head CT, polymethylmethacrylate was used as prosthesis material in 82% of patients and woven titanium mesh was used in the remaining 18%. The authors reported a complication rate of 24%, with an infection rate of 12%, seizure rate of 7.4%, and extra-axial hematoma rate of 7.4%. Eleven percent of patients required removal of their prosthesis for extra-axial hematoma or infection. Tantawi and colleagues reported success in staging the cranial reconstruction in patients with high risk of failure,

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including patients with large endocranial dead space as well as frontal orbital bar bone loss in close proximity to the frontal sinuses [88]. The use of a staged free latissimus dorsi transfer with tissue expander and custom polyetheretherketone implant has been described in six patients who had previously failed an average of 1.6 cranioplasties [89].

Outcomes Weisbrod and colleagues reported the long-term outcomes of 137 patients who had combat-relatedpenetrating TBI [90]. Of these casualties, 31% sustained gunshot wounds and 69% suffered blast injuries. Thirtytwo percent of patients who presented with an initial GCS of 3–5 progressed to functional independence at a follow-up of 2 years. For patients with an initial GCS of 6–8, the functional independence rate was 63% at 2 years. This rate increased to 74% for an initial GCS of 9–11 and 100% for an initial GCS of 12–15. In another review of neurosurgery consults for patients with combat-related TBI evacuated to CONUS, mortality upon reaching the USA was 4.4% [3]. In this cohort, patients who presented initially with a GCS of 3–5 had an average GOS of 2.8 at 1 to 2 years, with 40.4% of these patients having a GOS of 3 or higher.

Compliance with Ethical Standards Conflicts of Interest The authors have no conflicts of interest to declare and have received no financial or material support related to this manuscript. The results and opinions expressed in this article are those of the authors, and do not reflect the opinions or official policy of any of the listed affiliated institutions, the US Army, the US Navy, or the Department of Defense. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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Conclusion The recent military conflicts in Iraq and Afghanistan have seen substantial developments in far-forward neurosurgical and neurocritical care with associated survival from injuries that would have been fatal in prior military engagements. Aggressive cranial decompression for severe combatrelated TBI was one of several damage control neurosurgery concepts that was reinforced. Further advances in minimizing secondary brain injury while also rapidly evacuating patients to neurosurgical capabilities and through the continuum of care were also stressed. The DoD JTS remains committed to retaining these lessons learned and building upon them in the future. Disclaimer We are military service members. This work was prepared as part of our official duties. Title 17, USC, §105 provides that Bcopyright protection under this title is not available for any work of the United States Government.^ Title 17, USC, §101 defines a U.S. Government work as a work prepared by military servicemember or employee of the U.S. Government as part of that person’s official duties. The opinions or assertions contained herein are the private ones of the authors and are not to be construedas official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government.

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