Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Related articles

Management of acute severe traumatic brain injury

INTRODUCTION

Traumatic brain injury (TBI) is the leading cause of death in North America for individuals between the ages of 1 to 45 [1,2]. Many survivors live with significant disabilities, resulting in major socioeconomic burden as well. In 2000, the economic impact of TBI in the United States was estimated to be $9.2 billion in lifetime medical costs and $51.2 billion in productivity losses.

One of the major advances over the past two decades in the care of patients with severe head injury has been the development of standardized approaches that follow international and national guidelines [3-6]. The intent of these guidelines has been to use existing evidence to provide recommendations for current care in order to lessen heterogeneity and improve patient outcomes. Unfortunately, the lack of randomized clinical trials addressing many aspects of care of the severe TBI patient has meant that the strength of supporting data for most treatment concepts is relatively weak. Despite this caveat, there is evidence that treatment in centers with neurosurgical support, especially in settings where protocol-driven neurointensive care units operate based on the above-referenced guidelines, is associated with better patient outcomes [7-14]. Many expert panels recommend that treatment of severe TBI should be centralized in large trauma centers that offer neurosurgical treatment and access to specialized neurocritical care.

Patients with severe head injury may frequently have other traumatic injuries to internal organs, lungs, limbs, or the spinal cord. Thus, the management of the patient with severe head injury is often complex and requires a multi-disciplinary approach and lends itself to protocol-based treatment and standardized hospital order sets derived from the previously referenced guidelines.

This topic discusses the management of acute severe traumatic brain injury. The epidemiology and pathophysiology of traumatic brain injury, the management of mild traumatic brain injury, acute spinal cord injury, and other aspects of care of the trauma patient are discussed separately. (See "Traumatic brain injury: Epidemiology, classification, and pathophysiology" and "Concussion and mild traumatic brain injury" and "Acute traumatic spinal cord injury" and "Skull fractures in adults".)

INITIAL EVALUATION AND TREATMENT

Prehospital — The primary goal of prehospital management for severe head injury is to prevent hypotension and hypoxia, two systemic insults known to be major causes of secondary injury after TBI [15-20]. In a meta-analysis of clinical trials and population-based studies, hypoxia (PaO2 <60 mmHg) and hypotension (systolic BP <90 mmHg) were present in 50 and 30 percent of patients, respectively, and were each associated with a higher likelihood of a poor outcome: hypoxia (OR 2.14); hypotension (OR 2.67) [16]. Changes in prehospital management that aim to normalize oxygenation and blood pressure have improved outcomes [21-25]:

                            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Oct 2014. | This topic last updated: Aug 21, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 2006; 21:544.
  2. Rosenfeld JV, Maas AI, Bragge P, et al. Early management of severe traumatic brain injury. Lancet 2012; 380:1088.
  3. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. Introduction. J Neurotrauma 2007; 24 Suppl 1:S1.
  4. Maas AI, Dearden M, Teasdale GM, et al. EBIC-guidelines for management of severe head injury in adults. European Brain Injury Consortium. Acta Neurochir (Wien) 1997; 139:286.
  5. Newcombe R, Merry G. The management of acute neurotrauma in rural and remote locations: A set of guidelines for the care of head and spinal injuries. J Clin Neurosci 1999; 6:85.
  6. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 1: Introduction. Pediatr Crit Care Med 2003; 4:S2.
  7. Patel HC, Bouamra O, Woodford M, et al. Trends in head injury outcome from 1989 to 2003 and the effect of neurosurgical care: an observational study. Lancet 2005; 366:1538.
  8. Suarez JI, Zaidat OO, Suri MF, et al. Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team. Crit Care Med 2004; 32:2311.
  9. Thillai M. Neurosurgical units working beyond safe capacity. BMJ 2000; 320:399.
  10. Varelas PN, Conti MM, Spanaki MV, et al. The impact of a neurointensivist-led team on a semiclosed neurosciences intensive care unit. Crit Care Med 2004; 32:2191.
  11. Visca A, Faccani G, Massaro F, et al. Clinical and neuroimaging features of severely brain-injured patients treated in a neurosurgical unit compared with patients treated in peripheral non-neurosurgical hospitals. Br J Neurosurg 2006; 20:82.
  12. Brown JB, Stassen NA, Cheng JD, et al. Trauma center designation correlates with functional independence after severe but not moderate traumatic brain injury. J Trauma 2010; 69:263.
  13. Tepas JJ 3rd, Pracht EE, Orban BL, Flint LM. High-volume trauma centers have better outcomes treating traumatic brain injury. J Trauma Acute Care Surg 2013; 74:143.
  14. Pineda JA, Leonard JR, Mazotas IG, et al. Effect of implementation of a paediatric neurocritical care programme on outcomes after severe traumatic brain injury: a retrospective cohort study. Lancet Neurol 2013; 12:45.
  15. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. I. Blood pressure and oxygenation. J Neurotrauma 2007; 24 Suppl 1:S7.
  16. McHugh GS, Engel DC, Butcher I, et al. Prognostic value of secondary insults in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007; 24:287.
  17. Silverston P. Pulse oximetry at the roadside: a study of pulse oximetry in immediate care. BMJ 1989; 298:711.
  18. Stocchetti N, Furlan A, Volta F. Hypoxemia and arterial hypotension at the accident scene in head injury. J Trauma 1996; 40:764.
  19. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993; 34:216.
  20. Manley G, Knudson MM, Morabito D, et al. Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 2001; 136:1118.
  21. Andrews PJ, Sleeman DH, Statham PF, et al. Predicting recovery in patients suffering from traumatic brain injury by using admission variables and physiological data: a comparison between decision tree analysis and logistic regression. J Neurosurg 2002; 97:326.
  22. Clifton GL, Miller ER, Choi SC, Levin HS. Fluid thresholds and outcome from severe brain injury. Crit Care Med 2002; 30:739.
  23. Winchell RJ, Hoyt DB. Endotracheal intubation in the field improves survival in patients with severe head injury. Trauma Research and Education Foundation of San Diego. Arch Surg 1997; 132:592.
  24. Rudehill A, Bellander BM, Weitzberg E, et al. Outcome of traumatic brain injuries in 1,508 patients: impact of prehospital care. J Neurotrauma 2002; 19:855.
  25. Davis DP, Peay J, Sise MJ, et al. Prehospital airway and ventilation management: a trauma score and injury severity score-based analysis. J Trauma 2010; 69:294.
  26. Gaither JB, Spaite DW, Bobrow BJ, et al. Balancing the potential risks and benefits of out-of-hospital intubation in traumatic brain injury: the intubation/hyperventilation effect. Ann Emerg Med 2012; 60:732.
  27. Bernard SA, Nguyen V, Cameron P, et al. Prehospital rapid sequence intubation improves functional outcome for patients with severe traumatic brain injury: a randomized controlled trial. Ann Surg 2010; 252:959.
  28. Davis DP, Hoyt DB, Ochs M, et al. The effect of paramedic rapid sequence intubation on outcome in patients with severe traumatic brain injury. J Trauma 2003; 54:444.
  29. Perkins ZB, Wittenberg MD, Nevin D, et al. The relationship between head injury severity and hemodynamic response to tracheal intubation. J Trauma Acute Care Surg 2013; 74:1074.
  30. Davis DP, Fakhry SM, Wang HE, et al. Paramedic rapid sequence intubation for severe traumatic brain injury: perspectives from an expert panel. Prehosp Emerg Care 2007; 11:1.
  31. Cooper DJ, Myles PS, McDermott FT, et al. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial. JAMA 2004; 291:1350.
  32. Bulger EM, May S, Brasel KJ, et al. Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial. JAMA 2010; 304:1455.
  33. SAFE Study Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group, Australian Red Cross Blood Service, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357:874.
  34. Servadei F, Murray GD, Penny K, et al. The value of the "worst" computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium. Neurosurgery 2000; 46:70.
  35. Chang EF, Meeker M, Holland MC. Acute traumatic intraparenchymal hemorrhage: risk factors for progression in the early post-injury period. Neurosurgery 2006; 58:647.
  36. Oertel M, Kelly DF, McArthur D, et al. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg 2002; 96:109.
  37. Narayan RK, Maas AI, Servadei F, et al. Progression of traumatic intracerebral hemorrhage: a prospective observational study. J Neurotrauma 2008; 25:629.
  38. Thomas BW, Mejia VA, Maxwell RA, et al. Scheduled repeat CT scanning for traumatic brain injury remains important in assessing head injury progression. J Am Coll Surg 2010; 210:824.
  39. Connon FF, Namdarian B, Ee JL, et al. Do routinely repeated computed tomography scans in traumatic brain injury influence management? A prospective observational study in a level 1 trauma center. Ann Surg 2011; 254:1028.
  40. Kaups KL, Davis JW, Parks SN. Routinely repeated computed tomography after blunt head trauma: does it benefit patients? J Trauma 2004; 56:475.
  41. Huang AP, Lee CW, Hsieh HJ, et al. Early parenchymal contrast extravasation predicts subsequent hemorrhage progression, clinical deterioration, and need for surgery in patients with traumatic cerebral contusion. J Trauma 2011; 71:1593.
  42. Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of acute epidural hematomas. Neurosurgery 2006; 58:S7.
  43. Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of acute subdural hematomas. Neurosurgery 2006; 58:S16.
  44. Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of posterior fossa mass lesions. Neurosurgery 2006; 58:S47.
  45. Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of traumatic parenchymal lesions. Neurosurgery 2006; 58:S25.
  46. Surgical management of penetrating brain injury. J Trauma 2001; 51:S16.
  47. Antibiotic prophylaxis for penetrating brain injury. J Trauma 2001; 51:S34.
  48. Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of depressed cranial fractures. Neurosurgery 2006; 58:S56.
  49. Compagnone C, Murray GD, Teasdale GM, et al. The management of patients with intradural post-traumatic mass lesions: a multicenter survey of current approaches to surgical management in 729 patients coordinated by the European Brain Injury Consortium. Neurosurgery 2005; 57:1183.
  50. Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol 2008; 7:728.
  51. Citerio G, Andrews PJ. Refractory elevated intracranial pressure: intensivist's role in solving the dilemma of decompressive craniectomy. Intensive Care Med 2007; 33:45.
  52. Münch E, Horn P, Schürer L, et al. Management of severe traumatic brain injury by decompressive craniectomy. Neurosurgery 2000; 47:315.
  53. Polin RS, Shaffrey ME, Bogaev CA, et al. Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral edema. Neurosurgery 1997; 41:84.
  54. Jiang JY, Xu W, Li WP, et al. Efficacy of standard trauma craniectomy for refractory intracranial hypertension with severe traumatic brain injury: a multicenter, prospective, randomized controlled study. J Neurotrauma 2005; 22:623.
  55. Ho KM, Honeybul S, Lind CR, et al. Cost-effectiveness of decompressive craniectomy as a lifesaving rescue procedure for patients with severe traumatic brain injury. J Trauma 2011; 71:1637.
  56. Hutchinson PJ, Corteen E, Czosnyka M, et al. Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com). Acta Neurochir Suppl 2006; 96:17.
  57. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011; 364:1493.
  58. Servadei F. Clinical value of decompressive craniectomy. N Engl J Med 2011; 364:1558.
  59. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. V. Deep vein thrombosis prophylaxis. J Neurotrauma 2007; 24 Suppl 1:S32.
  60. Reiff DA, Haricharan RN, Bullington NM, et al. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 2009; 66:1436.
  61. Norwood SH, Berne JD, Rowe SA, et al. Early venous thromboembolism prophylaxis with enoxaparin in patients with blunt traumatic brain injury. J Trauma 2008; 65:1021.
  62. Norwood SH, McAuley CE, Berne JD, et al. Prospective evaluation of the safety of enoxaparin prophylaxis for venous thromboembolism in patients with intracranial hemorrhagic injuries. Arch Surg 2002; 137:696.
  63. Salottolo K, Offner P, Levy AS, et al. Interrupted pharmocologic thromboprophylaxis increases venous thromboembolism in traumatic brain injury. J Trauma 2011; 70:19.
  64. Koehler DM, Shipman J, Davidson MA, Guillamondegui O. Is early venous thromboembolism prophylaxis safe in trauma patients with intracranial hemorrhage. J Trauma 2011; 70:324.
  65. Scudday T, Brasel K, Webb T, et al. Safety and efficacy of prophylactic anticoagulation in patients with traumatic brain injury. J Am Coll Surg 2011; 213:148.
  66. Saadeh Y, Gohil K, Bill C, et al. Chemical venous thromboembolic prophylaxis is safe and effective for patients with traumatic brain injury when started 24 hours after the absence of hemorrhage progression on head CT. J Trauma Acute Care Surg 2012; 73:426.
  67. Kwiatt ME, Patel MS, Ross SE, et al. Is low-molecular-weight heparin safe for venous thromboembolism prophylaxis in patients with traumatic brain injury? A Western Trauma Association multicenter study. J Trauma Acute Care Surg 2012; 73:625.
  68. Phelan HA, Wolf SE, Norwood SH, et al. A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: The Delayed Versus Early Enoxaparin Prophylaxis I (DEEP I) study. J Trauma Acute Care Surg 2012; 73:1434.
  69. Rapp RP, Young B, Twyman D, et al. The favorable effect of early parenteral feeding on survival in head-injured patients. J Neurosurg 1983; 58:906.
  70. Perel P, Yanagawa T, Bunn F, et al. Nutritional support for head-injured patients. Cochrane Database Syst Rev 2006; :CD001530.
  71. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. XII. Nutrition. J Neurotrauma 2007; 24 Suppl 1:S77.
  72. Marmarou, A, Anderson, L, Ward, J, et al. Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 1991; 75:159.
  73. Schreiber MA, Aoki N, Scott BG, Beck JR. Determinants of mortality in patients with severe blunt head injury. Arch Surg 2002; 137:285.
  74. Badri S, Chen J, Barber J, et al. Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med 2012; 38:1800.
  75. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma 2007; 24 Suppl 1:S37.
  76. Lundberg N, Troupp H, Lorin H. Continuous recording of the ventricular-fluid pressure in patients with severe acute traumatic brain injury. A preliminary report. J Neurosurg 1965; 22:581.
  77. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma 2007; 24 Suppl 1:S14.
  78. Biersteker HA, Andriessen TM, Horn J, et al. Factors influencing intracranial pressure monitoring guideline compliance and outcome after severe traumatic brain injury. Crit Care Med 2012; 40:1914.
  79. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012; 367:2471.
  80. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. VIII. Intracranial pressure thresholds. J Neurotrauma 2007; 24 Suppl 1:S55.
  81. Stocchetti N, Zanaboni C, Colombo A, et al. Refractory intracranial hypertension and "second-tier" therapies in traumatic brain injury. Intensive Care Med 2008; 34:461.
  82. Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy in critical care neurology. J Intensive Care Med 2013; 28:3.
  83. James HE. Methodology for the control of intracranial pressure with hypertonic mannitol. Acta Neurochir (Wien) 1980; 51:161.
  84. McGraw CP, Howard G. Effect of mannitol on increased intracranial pressure. Neurosurgery 1983; 13:269.
  85. Muizelaar JP, Wei EP, Kontos HA, Becker DP. Mannitol causes compensatory cerebral vasoconstriction and vasodilation in response to blood viscosity changes. J Neurosurg 1983; 59:822.
  86. Sakowitz OW, Stover JF, Sarrafzadeh AS, et al. Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma 2007; 62:292.
  87. Ropper AH. Hyperosmolar therapy for raised intracranial pressure. N Engl J Med 2012; 367:746.
  88. Shackford SR, Bourguignon PR, Wald SL, et al. Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma 1998; 44:50.
  89. Ware ML, Nemani VM, Meeker M, et al. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 2005; 57:727.
  90. Battison C, Andrews PJ, Graham C, Petty T. Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Crit Care Med 2005; 33:196.
  91. Vialet R, Albanèse J, Thomachot L, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med 2003; 31:1683.
  92. Bhardwaj A, Ulatowski JA. Hypertonic saline solutions in brain injury. Curr Opin Crit Care 2004; 10:126.
  93. Vandromme MJ, Melton SM, Griffin R, et al. Intubation patterns and outcomes in patients with computed tomography-verified traumatic brain injury. J Trauma 2011; 71:1615.
  94. Stocchetti N, Maas AI, Chieregato A, van der Plas AA. Hyperventilation in head injury: a review. Chest 2005; 127:1812.
  95. Imberti R, Bellinzona G, Langer M. Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg 2002; 96:97.
  96. Coles JP, Minhas PS, Fryer TD, et al. Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med 2002; 30:1950.
  97. Marion DW, Puccio A, Wisniewski SR, et al. Effect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood flow in patients with severe traumatic brain injury. Crit Care Med 2002; 30:2619.
  98. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991; 75:731.
  99. Diringer MN, Yundt K, Videen TO, et al. No reduction in cerebral metabolism as a result of early moderate hyperventilation following severe traumatic brain injury. J Neurosurg 2000; 92:7.
  100. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. XIV. Hyperventilation. J Neurotrauma 2007; 24 Suppl 1:S87.
  101. Skoglund K, Enblad P, Marklund N. Effects of the neurological wake-up test on intracranial pressure and cerebral perfusion pressure in brain-injured patients. Neurocrit Care 2009; 11:135.
  102. Rossaint J, Rossaint R, Weis J, et al. Propofol: neuroprotection in an in vitro model of traumatic brain injury. Crit Care 2009; 13:R61.
  103. Kelly DF, Goodale DB, Williams J, et al. Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial. J Neurosurg 1999; 90:1042.
  104. Otterspoor LC, Kalkman CJ, Cremer OL. Update on the propofol infusion syndrome in ICU management of patients with head injury. Curr Opin Anaesthesiol 2008; 21:544.
  105. Sabsovich I, Rehman Z, Yunen J, Coritsidis G. Propofol infusion syndrome: a case of increasing morbidity with traumatic brain injury. Am J Crit Care 2007; 16:82.
  106. Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev 2012; 12:CD000033.
  107. Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg 1988; 69:15.
  108. Pérez-Bárcena J, Llompart-Pou JA, Homar J, et al. Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial. Crit Care 2008; 12:R112.
  109. Roberts I. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev 2000; :CD000033.
  110. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics, and sedatives. J Neurotrauma 2007; 24 Suppl 1:S71.
  111. Olivecrona M, Zetterlund B, Rodling-Wahlström M, et al. Absence of electroencephalographic seizure activity in patients treated for head injury with an intracranial pressure-targeted therapy. J Neurosurg 2009; 110:300.
  112. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 9. Use of sedation and neuromuscular blockade in the treatment of severe pediatric traumatic brain injury. Pediatr Crit Care Med 2003; 4:S34.
  113. Roberts DJ, Hall RI, Kramer AH, et al. Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med 2011; 39:2743.
  114. Bouma GJ, Muizelaar JP. Cerebral blood flow, cerebral blood volume, and cerebrovascular reactivity after severe head injury. J Neurotrauma 1992; 9 Suppl 1:S333.
  115. Bouma GJ, Muizelaar JP, Bandoh K, Marmarou A. Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurg 1992; 77:15.
  116. Muizelaar JP, Ward JD, Marmarou A, et al. Cerebral blood flow and metabolism in severely head-injured children. Part 2: Autoregulation. J Neurosurg 1989; 71:72.
  117. Juul N, Morris GF, Marshall SB, Marshall LF. Intracranial hypertension and cerebral perfusion pressure: influence on neurological deterioration and outcome in severe head injury. The Executive Committee of the International Selfotel Trial. J Neurosurg 2000; 92:1.
  118. Rosner MJ, Daughton S. Cerebral perfusion pressure management in head injury. J Trauma 1990; 30:933.
  119. Robertson CS, Valadka AB, Hannay HJ, et al. Prevention of secondary ischemic insults after severe head injury. Crit Care Med 1999; 27:2086.
  120. Howells T, Elf K, Jones PA, et al. Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma. J Neurosurg 2005; 102:311.
  121. Contant CF, Valadka AB, Gopinath SP, et al. Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury. J Neurosurg 2001; 95:560.
  122. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma 2007; 24 Suppl 1:S59.
  123. Elf K, Nilsson P, Ronne-Engström E, et al. Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head-injured patients: a computerized secondary insult monitoring study. Neurosurgery 2005; 56:962.
  124. Jaeger M, Dengl M, Meixensberger J, Schuhmann MU. Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury. Crit Care Med 2010; 38:1343.
  125. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 8. Cerebral perfusion pressure. Pediatr Crit Care Med 2003; 4:S31.
  126. Grände PO. The "Lund Concept" for the treatment of severe head trauma--physiological principles and clinical application. Intensive Care Med 2006; 32:1475.
  127. Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia 2003; 44 Suppl 10:18.
  128. Frey LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 2003; 44 Suppl 10:11.
  129. Vespa PM, Nuwer MR, Nenov V, et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg 1999; 91:750.
  130. Ronne-Engstrom E, Winkler T. Continuous EEG monitoring in patients with traumatic brain injury reveals a high incidence of epileptiform activity. Acta Neurol Scand 2006; 114:47.
  131. Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 1990; 323:497.
  132. Schierhout G, Roberts I. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Cochrane Database Syst Rev 2001; :CD000173.
  133. Konstantinidis A, Inaba K, Dubose J, et al. The impact of nontherapeutic hypothermia on outcomes after severe traumatic brain injury. J Trauma 2011; 71:1627.
  134. Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001; 344:556.
  135. Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev 2009; :CD001048.
  136. McIntyre LA, Fergusson DA, Hébert PC, et al. Prolonged therapeutic hypothermia after traumatic brain injury in adults: a systematic review. JAMA 2003; 289:2992.
  137. Henderson WR, Dhingra VK, Chittock DR, et al. Hypothermia in the management of traumatic brain injury. A systematic review and meta-analysis. Intensive Care Med 2003; 29:1637.
  138. Harris OA, Colford JM Jr, Good MC, Matz PG. The role of hypothermia in the management of severe brain injury: a meta-analysis. Arch Neurol 2002; 59:1077.
  139. Georgiou AP, Manara AR. Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review. Br J Anaesth 2013; 110:357.
  140. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011; 10:131.
  141. Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008; 358:2447.
  142. Adelson PD, Wisniewski SR, Beca J, et al. Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial. Lancet Neurol 2013; 12:546.
  143. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. III. Prophylactic hypothermia. J Neurotrauma 2007; 24 Suppl 1:S21.
  144. Adelson PD. Hypothermia following pediatric traumatic brain injury. J Neurotrauma 2009; 26:429.
  145. Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000; 46:335.
  146. Jeremitsky E, Omert LA, Dunham CM, et al. The impact of hyperglycemia on patients with severe brain injury. J Trauma 2005; 58:47.
  147. Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991; 75:545.
  148. Oddo M, Schmidt JM, Carrera E, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med 2008; 36:3233.
  149. Harhangi BS, Kompanje EJ, Leebeek FW, Maas AI. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien) 2008; 150:165.
  150. Allard CB, Scarpelini S, Rhind SG, et al. Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J Trauma 2009; 67:959.
  151. Wafaisade A, Lefering R, Tjardes T, et al. Acute coagulopathy in isolated blunt traumatic brain injury. Neurocrit Care 2010; 12:211.
  152. Stein SC, Young GS, Talucci RC, et al. Delayed brain injury after head trauma: significance of coagulopathy. Neurosurgery 1992; 30:160.
  153. Murray GD, Butcher I, McHugh GS, et al. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007; 24:329.
  154. Zehtabchi S, Soghoian S, Liu Y, et al. The association of coagulopathy and traumatic brain injury in patients with isolated head injury. Resuscitation 2008; 76:52.
  155. Nishijima DK, Zehtabchi S, Berrong J, Legome E. Utility of platelet transfusion in adult patients with traumatic intracranial hemorrhage and preinjury antiplatelet use: a systematic review. J Trauma Acute Care Surg 2012; 72:1658.
  156. Perel P, Roberts I, Shakur H, et al. Haemostatic drugs for traumatic brain injury. Cochrane Database Syst Rev 2010; :CD007877.
  157. Narayan RK, Maas AI, Marshall LF, et al. Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial. Neurosurgery 2008; 62:776.
  158. Winter JP, Plummer D, Bottini A, et al. Early fresh frozen plasma prophylaxis of abnormal coagulation parameters in the severely head-injured patient is not effective. Ann Emerg Med 1989; 18:553.
  159. Etemadrezaie H, Baharvahdat H, Shariati Z, et al. The effect of fresh frozen plasma in severe closed head injury. Clin Neurol Neurosurg 2007; 109:166.
  160. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004; 364:1321.
  161. Edwards P, Arango M, Balica L, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet 2005; 365:1957.
  162. Wright DW, Kellermann AL, Hertzberg VS, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 2007; 49:391.
  163. Ma J, Huang S, Qin S, You C. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2012; 10:CD008409.
  164. Arango MF, Bainbridge D. Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev 2008; :CD005400.
  165. Bennett MH, Trytko B, Jonker B. Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Database Syst Rev 2012; 12:CD004609.
  166. Mazzeo AT, Brophy GM, Gilman CB, et al. Safety and tolerability of cyclosporin a in severe traumatic brain injury patients: results from a prospective randomized trial. J Neurotrauma 2009; 26:2195.
  167. Xiong Y, Mahmood A, Chopp M. Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs 2009; 14:67.
  168. Zafonte RD, Bagiella E, Ansel BM, et al. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA 2012; 308:1993.
  169. Talving P, Lustenberger T, Kobayashi L, et al. Erythropoiesis stimulating agent administration improves survival after severe traumatic brain injury: a matched case control study. Ann Surg 2010; 251:1.
  170. Velmahos GC. Erythropoiesis and the mystery of an unexplained survival benefit. Ann Surg 2010; 251:5.
  171. Cruz J. The first decade of continuous monitoring of jugular bulb oxyhemoglobinsaturation: management strategies and clinical outcome. Crit Care Med 1998; 26:344.
  172. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. X. Brain oxygen monitoring and thresholds. J Neurotrauma 2007; 24 Suppl 1:S65.
  173. Maloney-Wilensky E, Gracias V, Itkin A, et al. Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review. Crit Care Med 2009; 37:2057.
  174. Stiefel MF, Spiotta A, Gracias VH, et al. Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg 2005; 103:805.
  175. Goodman JC, Robertson CS. Microdialysis: is it ready for prime time? Curr Opin Crit Care 2009; 15:110.
  176. Jiang JY, Gao GY, Li WP, et al. Early indicators of prognosis in 846 cases of severe traumatic brain injury. J Neurotrauma 2002; 19:869.
  177. Lingsma HF, Roozenbeek B, Steyerberg EW, et al. Early prognosis in traumatic brain injury: from prophecies to predictions. Lancet Neurol 2010; 9:543.
  178. Schnüriger B, Inaba K, Abdelsayed GA, et al. The impact of platelets on the progression of traumatic intracranial hemorrhage. J Trauma 2010; 68:881.
  179. Calvi MR, Beretta L, Dell'Acqua A, et al. Early prognosis after severe traumatic brain injury with minor or absent computed tomography scan lesions. J Trauma 2011; 70:447.
  180. Timmons SD, Bee T, Webb S, et al. Using the abbreviated injury severity and Glasgow Coma Scale scores to predict 2-week mortality after traumatic brain injury. J Trauma 2011; 71:1172.
  181. Lingsma H, Andriessen TM, Haitsema I, et al. Prognosis in moderate and severe traumatic brain injury: external validation of the IMPACT models and the role of extracranial injuries. J Trauma Acute Care Surg 2013; 74:639.
  182. Lin TK, Tsai HC, Hsieh TC. The impact of traumatic subarachnoid hemorrhage on outcome: a study with grouping of traumatic subarachnoid hemorrhage and transcranial Doppler sonography. J Trauma Acute Care Surg 2012; 73:131.
  183. Mondello S, Buki A, Italiano D, Jeromin A. α-Synuclein in CSF of patients with severe traumatic brain injury. Neurology 2013; 80:1662.
  184. Mercier E, Boutin A, Lauzier F, et al. Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ 2013; 346:f1757.
  185. Chabok SY, Moghadam AD, Saneei Z, et al. Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury. J Trauma Acute Care Surg 2012; 72:1654.
  186. Roozenbeek B, Lingsma HF, Lecky FE, et al. Prediction of outcome after moderate and severe traumatic brain injury: external validation of the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models. Crit Care Med 2012; 40:1609.
  187. Yuan F, Ding J, Chen H, et al. Predicting outcomes after traumatic brain injury: the development and validation of prognostic models based on admission characteristics. J Trauma Acute Care Surg 2012; 73:137.
  188. McMillan TM, Teasdale GM, Weir CJ, Stewart E. Death after head injury: the 13 year outcome of a case control study. J Neurol Neurosurg Psychiatry 2011; 82:931.
  189. Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: management protocol and clinical results. J Neurosurg 1995; 83:949.
  190. Levin HS, Saydjari C, Eisenberg HM, et al. Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report. Arch Neurol 1991; 48:580.
  191. Xu W, Jiang G, Chen Y, et al. Prediction of minimally conscious state with somatosensory evoked potentials in long-term unconscious patients after traumatic brain injury. J Trauma Acute Care Surg 2012; 72:1024.
  192. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012; 366:819.