/clinical/,/clinical/references/,/clinical/references/trauma-manual/,/clinical/references/trauma-manual/head-and-neck/,/clinical/references/trauma-manual/head-and-neck/traumatic-brain-injury-management/,

/clinical/references/trauma-manual/head-and-neck/traumatic-brain-injury-management/

20170238

page

100

UWHC,UWMF,

Patient Care,

https://uconnect.wisc.edu/media/u-connect/clinical-hub/references/trauma-manual/feature_trauma.jpg
Clinical Hub,References,Level I Adult Trauma Center Manual,Head and Neck

Traumatic Brain Injury Management

Traumatic Brain Injury Management - Clinical Hub, References, Level I Adult Trauma Center Manual, Head and Neck

Focus

Introduction

Severe brain injury, defined as a Glasgow Coma Score (GCS) < 8, and the subsequent elevation in ICP are challenging problems in the management of critically ill patients.1 Nearly 1.6 million head injuries occur every year in the United States, many of which can lead to an elevation in ICP.2 However, other processes such as intracranial hemorrhage, malignancy, meningo-encephalitis, and severe metabolic derangements may also cause an elevation in ICP.1 

Severe brain injury is the result of two distinct phases, primary and secondary brain injury. Following primary brain injury (i.e. head trauma), secondary brain injury may occur resulting in neuronal damage due to the physiologic response from the initial insult.2 Edema and an increase in the ICP may occur secondary to a defect in the blood-brain barrier and an increase in osmolality from the breakdown of cellular structures within the brain.1 The Monro-Kellie principle states that the cranial vault is a fixed space (closed box) comprised of brain tissue, cerebrospinal fluid (CSF), extracellular fluid, and blood.2 Several mechanisms exist to compensate for the elevation in ICP such as shunting CSF to the spinal subarachnoid space, decreasing CSF production, and shunting venous blood out of the skull.1 Once these mechanisms become overwhelmed, an elevation in ICP can occur. This may cause a reduction in cerebral perfusion pressure (CPP) and subsequent cerebral ischemia.

CPP is a derived clinical parameter that is used to predict cerebral blood flow and cerebral oxygenation. CPP is the difference between mean arterial pressure (MAP) and ICP:2, 3

CPP = MAP – ICP

The Brain Trauma Foundation recommends maintaining a CPP > 60 mmHg and initiating treatment when the ICP reaches an upper threshold of 20-25 mm Hg.3 Lowering ICP can be achieved by elevating the head-of-bed >45°, inducing hypothermia, providing pharmacologic sedation, reducing edema (i.e. mannitol), CSF drainage, hyperventilation-induced vasoconstriction, and surgical procedures.1 

Using This Guideline

The following two pages include flow diagrams for the initial management of severe brain injury (Figure 1) and the management of elevated ICP in the intensive care unit (Figure 2). More information can be found about each recommendation by referencing the letter next to each box with the corresponding text in this guideline.

Initial Management of Severe Brain

Initial Management of Elevated ICP‌

Section A. Endotracheal Intubation: Pre-Induction Agents

Rationale: Endotracheal intubation is associated with increased sympathetic discharge resulting in hypertension and tachycardia. Fentanyl, when used as a pre-induction agent, reduces the hypertensive response following intubation.4 Lidocaine may be used to blunt the catecholamine response seen with intubation and prevent elevations in ICP. 

Recommendation:

  1. Fentanyl 50-100mcg slow IVP over 1-2 min
    • Administer 2-5 minutes before intubation
    • Monitoring
      • Hypotension, chest wall rigidity
  2. Lidocaine 100mg IVP
    • Administer 2-5 minutes before intubation
    • Monitoring
      • Hypotension

Section B. Endotracheal Intubation: Induction Agents

Rationale: Induction agents such as etomidate are used to facilitate endotracheal intubation by providing immediate unconsciousness. Etomidate has a rapid onset, short duration of action, and does not cause hypotension.4 

Recommendation:

  1. Etomidate 0.3 mg/kg IVP
    • Administer 1 minute before intubation

Section C. Endotracheal Intubation: Neuromuscular Blocking Agents

Rationale: NMBAs facilitate endotracheal intubation by causing relaxation of the skeletal muscle. Succinylcholine, a depolarizing NMBA, has a rapid onset and short duration of action. Rocuronium and vecuronium, both non-depolarizing NMBAs, may also be used. These agents have a rapid onset, but a longer duration of action than succinylcholine. 

Recommendation:

  1. Succinylcholine 1-1.5 mg/kg IVP
    • Administer 1 minute before endotracheal intubation
    • Contraindicated in patients with a personal or family history of malignant hyperthermia 4
    • Monitoring
      • Hyperkalemia can occur in patients with congenital or acquired myopathies, cerebral vascular accidents, and muscle crush injuries.4
  2. Rocuronium 1-1.2 mg/kg IVP
    • Administer 1 minute before endotracheal intubation
  3. Vecuronium 0.1-0.15 mg/kg IVP
    • Administer 3-5 minutes before endotracheal intubation

Section D. Oxygenation and Ventilation 

Rationale: In patients with severe head injury, hypoxemia can propagate secondary brain injury. Adequate oxygenation (SaO2 > 94%) must be maintained at all times during both the initial management and ICU care of these patients.3, 5 Hyperventilation is thought to lower ICP by causing cerebral vasoconstriction, thereby reducing cerebral blood flow (CBF) and cerebral blood volume (CBV). However, reducing CBF below a critical threshold by hyperventilation may further compromise perfusion to already ischemic regions of the brain. Thus, aggressive hyperventilation (PaCO2 < 35 mmHg) should be avoided unless clinical signs of herniation are present.3

Recommendation:

  1. Maintain SaO2 > 94%
  2. Maintain PaCO2 35-40 mmHg

Section E. Correct Arterial Hypotension

Rationale: Hypotension is one of the five most powerful predictors of outcome. A single hypotensive episode (systolic blood pressure [SBP] < 90 mmHg) is associated with increased morbidity and mortality. The goal is to maintain SBP > 90 mmHg in an attempt to maintain a CPP of ≥ 60 mmHg.3 Hypotonic solutions should not be used because they may worsen cerebral edema.2 

Recommendations:

  1. Use 0.9% normal saline or Lactated Ringer’s if fluid resuscitation is indicated
  2. Maintain SBP > 90 mmHg and CPP ≥ 60 mmHg
    • May use vasopressors (phenylephrine, norepinephrine) if indicated
  3. Consult neurosurgery for patient-specific hemodynamic parameters 

Section F. Herniation or Deterioration? 

Rationale: If an ICP monitor has not yet been placed, mannitol is indicated if there are clinical signs of herniation or neurologic deterioration. Mannitol should be given only in the presence of adequate volume resuscitation.3

Recommendation:

  1. Mannitol 0.25-1 g/kg IV push
    • May repeat q3-6hr as needed
    • See Section L for more complete instructions on the dosing, monitoring, and administration of mannitol
  2. 23.4% HTS 30mL IV q3-6 hrs for ICP > 20 mmHg
    • For use when patient is refractory to mannitol
    • Infuse over 15-30 minutes via CENTRAL LINE
    • Supplied as 30mL of 23.4% HTS undiluted in a 50mL viaflex bag
    • Monitoring
      • Continuous ICP monitoring – goal < 20 mmHg
      • Measure serum osmolality prior to each dose – goal serum osmolality < 320 mOsm
      • Serum sodium every 2-4 hours – goal < 155 mEq/L
      • Central pontine myelinolysis – although not substantiated by case reports, do not increase serum sodium more than 10-20 mEq/L in 24 hours
    • Nursing instructions
      • Prime the line using normal saline to avoid wasting any HTS
      • Hang the bag of HTS and infuse over 15-30 minutes via a central line only
      • After the infusion of HTS has been completed, infuse normal saline at a rate of 60 mL/hr for 20-30 minutes to ensure that the HTS has been completely flushed from the line
  3. In an acute setting, may hyperventilate the patient to a PaCO2 of no less than 30 mmHg for a short period of time only

ICU Management of Elevated ICP 

Section G. Correct Arterial Hypotension

Rationale: Hypotension is one of the five most powerful predictors of outcome. A single hypotensive episode (systolic blood pressure [SBP] < 90 mmHg) is associated with increased morbidity and mortality. The goal is to maintain SBP > 90 mmHg in an attempt to maintain a CPP of ≥ 60 mmHg.3

Recommendation:

  1. Fluids – indicated for hypotensive patients with a central venous pressure (CVP) < 12 mmHg
  2. Packed red blood cells – indicated for hypotensive patients with a CVP > 12 mmHg and inadequate oxygen delivery to the tissues (lactate > 2 mmol/L or mixed venous oxygen saturation [SvO2] < 70%)
  3. Vasopressors – indicated for hypotensive patients with a CVP > 12 mmHg and adequate oxygen delivery to the tissues (lactate < 2 mmol/L or SvO2 > 70%)

Section H. Oxygenation and Ventilation 

Rationale: Maintaining adequate oxygenation in the ICU is essential to prevent cerebral ischemia and subsequent secondary brain injury in patients with elevated ICP.3 Hyperventilation can cause cerebral vasoconstriction and a reduction in CBF, thereby reducing CBV and ICP. Reducing CBF below a critical threshold may further compromise perfusion to already ischemic regions of the brain. Slight hyperventilation is not recommended in all patients, particularly within the first 24 hours of hospital management. Even beyond 24 hours, some data suggests that slight hyperventilation (~30 mmHg) increases ischemic brain volume and reduces regional cerebral oxygen metabolism despite a marked increase in oxygen extraction.6 The long-term neurological and cognitive outcomes of these observations remain unknown.

Recommendation:

  1. Maintain SaO2 > 94%
  2. Maintain PaCO2 35-40 mmHg

Section I. Sedation and Analgesia

Rationale: Agitation is a common ICU problem that may result in sympathetic hyperactivity causing tachycardia, tachypnea, diaphoresis, and increased posturing. In patients with severe head injury and elevated ICP where cerebral oxygen supply is already compromised, any increase in cerebral oxygen metabolism may have deleterious consequences. Propofol, the sedative of choice when frequent neurological examinations are necessary, has been shown to independently decrease ICP, CBF, and cerebral metabolism in head injury patients.7 Additionally, fentanyl should be added for acute pain control.

Recommendation:

  1. Propofol 5-50 mcg/kg/min IV continuous infusion
    • Titrate to a Riker score of 3-4
    • Monitoring
      • Hypotension – use cautiously in patients with labile blood pressure
      • Bradycardia
      • Hypertriglyceridemia – obtain baseline triglyceride level and every 3-5 days thereafter
      • Pancreatitis
      • Propofol-related infusion syndrome – cardiac arrhythmias, metabolic acidosis, rhabdomyolysis
  2. Fentanyl 25-200 mcg/hr IV continuous infusion in all patients with traumatic brain injury
    • Titrate to a Riker score of 3-4
    • Monitoring
      • Constipation
      • Delayed gastric emptying in patients receiving enteral nutrition
  3. Benzodiazepines may be used if approved by Neurosurgery 

Section J. Management of a Ventriculostomy Catheter

Rationale: Continuous ICP monitoring can aid in the management of the severely head-injured patient. ICP monitoring is indicated for patients with a GCS < 8 and an abnormal CT scan upon admission. ICP monitoring is indicated in patients with a normal CT scan if any two of the following are present upon admission: age over 40 years, unilateral or bilateral motor posturing, SBP < 90 mmHg.3

Prophylactic Antibiotics for Ventriculostomy

There are no randomized, controlled trials evaluating the effect of prophylactic antibiotics on reducing the rate of infections in patients with a ventriculostomy. Only small, observational studies have shown a reduction in infection rates when prophylactic antibiotics were part of a larger practice guideline aimed at minimizing infectious complications.8

Section K. Prevention of Hyperthermia and External Cooling

Rationale: Fever is common in patients with acute neurologic illness and is an independent predictor of poor outcome.9 Avoiding hyperthermia protects against secondary ischemic insult by decreasing oxygen consumption and ICP. For each 1°C drop in temperature, the cerebral metabolic rate of oxygen drops by 6-7%. Therefore it is recommended to keep temperature < 38°C or < 38.5°C (internal) to prevent the exacerbation of preexisting hypoxia and damage. 

Recommendations:

  1. Acetaminophen 650mg Q 6 hours (Max 4000mg/day)
  2. If fever persists > 38.5°C add a cooling blanket and cool the patient to 35.5-36.5°C
  3. Due to a marked elevation in metabolic rate and oxygen consumption, shivering should be avoided by maximizing sedation or adding a neuromuscular blocker

Section L. Mannitol and Hypertonic Saline (HTS)

Rationale: Cerebral edema following primary brain injury is a result of the disruption in the blood-brain barrier (BBB) and a marked increase in osmolality due to a breakdown of cellular structures.1 Osmotic agents such as mannitol and HTS can be used to reduce cerebral edema and thus, decrease ICP. In addition to its osmotic effects, HTS has vasoregulatory, immunomodulatory, and neurochemical effects when used in severe head injury.10, 11 There is some data to suggest that HTS lowers ICP greater than mannitol and has a longer duration of action.12 Due to a lower affinity for crossing the BBB when compared to mannitol, HTS may not cause a rebound increase in ICP after discontinuation following prolonged use. Although not substantiated by any case reports, HTS carries the risk of causing central pontine myelinolysis if the serum sodium increases by more than 10-20 mEq/L in 24 hours.10, 11 

Recommendations:

  1. Mannitol 0.25-1 g/kg IV q3-6 hrs for ICP > 20 mmHg
    • Infuse over 15-30 minutes via central line
    • Supplied as 12.5g/50mL vials
    • Inspect solution for crystals before use
    • Monitoring
      • Continuous ICP monitoring – goal < 20 mmHg
      • Hypovolemia
      • Measure serum osmolality prior to each dose – goal serum osmolality < 320 mOsm
      • Serum sodium and potassium every 2-4 hours
      • Central venous pressure every 2 hours
      • Serum creatinine and BUN everyday
  2. 23.4% HTS 30mL IV q3-6 hrs for ICP > 20 mmHg
    • For use when patient is refractory to mannitol
    • Infuse over 15-30 minutes via CENTRAL LINE
    • Supplied as 30mL of 23.4% HTS undiluted in a 50mL viaflex bag
    • Monitoring
      • Continuous ICP monitoring – goal < 20 mmHg
      • Measure serum osmolality prior to each dose – goal serum osmolality < 320 mOsm
      • Serum sodium every 2-4 hours – goal < 155 mEq/L
      • Central pontine myelinolysis – although not substantiated by case reports, do not increase serum sodium more than 10-20 mEq/L in 24 hours
    • Nursing instructions
      • Prime the line using normal saline to avoid wasting any HTS
      • Hang the bag of HTS and infuse over 15-30 minutes via a central line only
      • After the infusion of HTS has been completed, infuse normal saline at a rate of 60 mL/hr for 20-30 minutes to ensure that the HTS has been completely flushed from the line
  3. 3% HTS IV infused at 75 to 150 mL/hr for ICP > 20 mmHg
    • For use when patient is refractory to mannitol
    • Infuse via CENTRAL LINE
    • Supplied in 500 mL bags
    • Monitoring
      • Continuous ICP monitoring – goal < 20 mmHg
      • Measure serum osmolality prior to each dose – goal serum osmolality < 320 mOsm
      • Serum sodium every 4-6 hours – goal < 155 mEq/L
      • Caution with use > 24 hours

Section M. Neuromuscular Blockade

Rationale: After mannitol and HTS have been exhausted and/or are no longer effective for reducing ICP, and sedation has been maximized, NMBAs may be used. However, osmotherapy may still be given. NMBAs may be beneficial in attenuating intractable elevated ICP by preventing skeletal muscle contraction, thereby reducing energy expenditure and oxygen consumption. Since NMBAs have NO sedative or analgesic properties, it is imperative that sedation be maximized to a Riker score of 1 prior to initiating therapy. Intermittent bolus dosing is preferred over a continuous infusion to reduce the risk of prolonged paralysis and potentially devastating myopathies.

Section N: Pentobarbital Coma

Rationale: Barbiturate coma may be considered in hemodynamically stable patients with refractory ICP. There are no randomized controlled trials assessing the effects on outcomes. Barbiturates decrease the metabolic requirements of the brain by decreasing cerebral blood flow requirements and subsequently reducing CBV and ICP.3, 13

Recommendations:

  1. Loading dose:
    • Low dose: 5-10 mg/kg IVPB over 1-2 hours, based on actual body weight (ABW)
    • High dose: 25-30 mg/kg ABW IVPB over 3 hours
    • Do not administer faster than 50 mg/min
    • Wean all other sedatives once pentobarbital loading is complete
      • Pentobarbital has no effect on pain threshold, continue analgesia
  2. Maintenance dose: 1-3 mg/kg/hr continuous infusion
  3. Breakthrough dosing: 100-200mg IVP Q 30 min prn ICP > 20 mmHg or breakthrough observed on EEG monitor
  4. Monitoring
    • Continuous ICP monitoring with a goal ICP < 20 mmHg
    • Maintain burst suppression on EEG monitor
      • EEG pattern of burst suppression correlates well with observed maximal reductions in cerebral metabolic rate of oxygen
      • Observation is dose-dependent & therefore a more reliable marker for monitoring the efficacy of a pentobarbital infusion (BTG)
    • Monitor cardiac status
      • Consider placement of a Swan-Ganz catheter
    • Serum pentobarbital levels do not correlate with clinical outcomes and toxicity
      • Do not use to titrate dosing
    • Pentobarbital contains propylene glycol. Monitor osmol gap if there is prolonged use or if the patient is receiving a concomitant lorazepam continuous infusion.
  5. Supportive Care
    • Eye Care
    • Bowel Regimen
    • Nutrition
      • Patients in a pentobarbital coma can be fed enterally after proper placement of a post-pyloric feeding tube has been confirmed.
      • Consult nutrition support team
  6. The decision to initiate pentobarbital for intractable elevated ICP should be made between the critical care attending and the neurosurgery service

Section O. General ICU Care

Glycemic Control

Rationale: The stress response and subsequent increase in circulating catecholamines following severe brain injury may cause hyperglycemia. In trauma patients, particularly those with head injury, hyperglycemia is a predictor of poor outcome.15, 16 Intensive insulin therapy has a proven mortality benefit in the surgical population and morbidity benefit in the medical population. However, little data exists on its benefit, or lack thereof, in patients with severe head injury and elevated ICP.

Recommendation:

  1. Initiate intensive insulin therapy in patients with two consecutive blood glucose values > 150 mg/dL
    • Use the “Critical Care Insulin Infusion” protocol built into Sunrise Clinical Manager
    • Titrate the infusion according to the unit-specific target blood glucose range (i.e. HSICU 80-120 mg/dL, HMICU 90-150 mg/dL)
    • While on a continuous insulin infusion, attempts should be made to minimize the amount of intravenous dextrose a patient receives to prevent worsening cerebral edema

Seizure Prophylaxis

Rationale: Post-traumatic seizures (PTS) occur in up to 20% of head-injured patients and are classified as either early (within 7 days of injury) or late (after 7 days of injury).1 When used for seizure prophylaxis, phenytoin has been shown to reduce the risk of early PTS when compared to placebo. However, phenytoin does NOT reduce the risk of late PTS and should not be used as prophylaxis beyond 7 days from the initial injury.3, 17, 18

Recommendation:

  1. Phenytoin 15-20 mg/kg IV loading dose for head-injury patients at high risk for PTS
  2. Phenytoin 5-7 mg/kg/day (based on ideal body weight) IV maintenance dose for 7 days only
    • Begin maintenance dose 4 hours after loading dose, provided 2-hour post-load level is within the therapeutic range
  3. Monitoring
    • Therapeutic range: 10-20 mcg/mL (1-2 mcg/mL free phenytoin level)
    • Draw a level 2 hours after the loading dose
    • Levels should be monitored 2-3 times over the course of 7 days 

Hyperthermia

See Section K. Prevention of Hyperthermia and External Cooling

Stress Ulcer Prophylaxis

Rationale: Stress-related mucosal damage (SRMD) is common following traumatic brain injury. Maintaining adequate perfusion through aggressive fluid resuscitation is the key to preventing SRMD.19

DVT Prophylaxis

Rationale: The incidence of DVT in neurosurgery patients is approximately 22%. However, the benefits of pharmacologic thromboprophylaxis must be carefully balanced against the risk for intracranial bleeding. Head injury without overt hemorrhage is NOT a contraindication to pharmacologic thromboprophylaxis.20 No difference in the incidence of intracranial bleeding was found when UFH was started within 72 hours of severe head injury compared to beyond 72 hours.21

Recommendation:

  1. Intermittent pneumatic compression boots should be placed on all patients upon admission unless contraindicated
  2. UFH 5,000 units sq tid20
  3. Pharmacologic thromboprophylaxis can be safely commenced within 24 hours of head injury with stable CT scan
  4. However, thromboprophylaxis should be deferred for 5 days following craniotomy
  5. Please consult neurosurgery for when to safely initiate thromboprophylaxis

Eye Care

Rationale: Impaired eyelid closure and loss of corneal reflex often occurs in paralyzed or heavily sedated patients. When the cornea is exposed, the eye is at risk for serious complications including infection, corneal ulceration, and loss of vision.

Recommendation:

  1. Apply an ophthalmic lubricantQID 

Bowel Preparation

Rationale: Care should be taken to ensure that all patients in a pentobarbital coma and those receiving opioids for analgesia have regular bowel movements. All patients in a pentobarbital coma must have scheduled bowel regimens to ensure regular bowel movements.

Recommendation: The following should be ordered for all patients in a pentobarbital coma and should be considered in patients receiving scheduled doses of opiates for sedation:

  1. Senna 374mg PO/PT qhs
  2. Docusate sodium 100mg PO/PT bid
  3. Bisacodyl 10mg PR daily
  4. Monitor for every 24-48 hour bowel movements
    • If no bowel movement after 72 hours, give magnesium citrate 300mL PO/PT x 1

Nutrition

Rationale: Initiation of adequate nutritional support can impact neurologic recovery following TBI. Activation of the sympathetic nervous system following traumatic brain injury results in a hypermetabolic and catabolic state. In addition, there is a inverse correlation between GCS and energy expenditure. 14 Early enteral nutrition is the preferred route because it maintains the integrity of the gastrointestinal mucosa, attenuates the metabolic response to stress and has been shown to decrease mortality rate if given within 7 days. Patients with a TBI may experience delayed gastric emptying and feeding intolerance, therefore, duodenal or jejunal access may be required for reliable absorption.14

Recommendation:

  1. Obtain nutrition support consult
  2. Establish enteral access by placing a transpyloric small bore feeding tube
  3. Initiate enteral nutrition within 48 hours of ICU admission
    • Measured energy expenditure (MEE) in patients with TBI is 1.4 – 1.7 times the calculated basal energy expenditure (BEE). MEE for patients in a pentobarbital coma is 1.0 – 1.3 times the BEE.
  4. Protein should be at least 15% of calories for patients with a TBI or in a pentobarbital-induced coma
  5. Monitor for feed intolerance
  6. HOB > 30° if clinically appropriate
    • Elevation of the head of bed to prevent jugular venous outflow obstruction

Responsibility

Physicians, pharmacists, and nurses

Forms

References

1. Vincent J, Berre J. Primer on medical management of severe brain injury Critical Care Medicine. 2005;33:1392-1399.

2. Marik PE, Varon J, Trask T. Management of Head Trauma. Chest. August 1, 2002 2002;122:699-711.

3. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Management and prognosis of severe traumatic brain injury. Journal of Trauma. 2000;17:457-627.

4. Reynolds SF, Heffner J. Airway management of the critically ill patient: rapid-sequence intubation. Chest. April 1, 2005 2005;127:1397-1412.

5. Marik M, Chen K, Varon J, et al. Management of increased intracranial pressure: a review for clinicians The Journal of Emergency Medicine. 1999;17:711-719.

6. Coles J, Fryer T, Coleman M, et al. Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism. Critical Care Medicine. 2007;35:567-578.

7. Jacobi J, Fraiser G, Coursin D, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill patient. Critical Care Medicine. 2002;30:119-141.

8. Bader M, Littlejohns L, Palmer S. Ventriculostomy and intracranial pressure monitoring: in search of a 0% infection rate. Heart and Lung. 1995;24:166-172.

9. Diringer M. Treatment of fever in the neurologic intensive care unit with a catheter based heat exchange. Critical Care Medicine. 2004;32:559-564.

10. Doyle J, Davis D, Hoyt D. The use of hypertonic saline in the treatment of traumatic brain injury. Journal of Trauma 2001;50:367-383.

11. Qureshi A, Suarez J. Ue of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Critical Care Medicine. 2000;28:3301-3313.

12. Battison C, Andrews P, Graham C, et al. Randomized, controlled trial on the effect of 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Critical Care Medicine 2005;33:196-202.

13. Wilberger JE, Cantella D. High-dose barbiturates for intracranial pressure control. New Horizons. 1995;3:469-473.

14. Magnuson B, Hatton J, Williams S, et al. Tolerance and efficacy of enteral nutrition for neurosurgical patients in pentobarbital coma. Nutrition of Clinical Practice. 1999;14:131-134.

15. Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery. 2000;46:335-342.

16. Vogelzang V, Nijboer J, VanderHorst I, et al. Hyperglycemia has a stronger relation with outcome in trauma patients than in other critically ill patients. Journal of Trauma. 2006;60:873-879.

17. Chang B, Lowenstein D. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury. Neurology 2003;60:10-16.

18. 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. August 23, 1990 1990;323:497-502.

19. Marik P, Zaloga G. Contemporary strategies for the prevention of stress-related mucosal bleeding. American Journal of Health-System Pharmacy. 2005;62:S11-S17.

20. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. September 1, 2004 2004;126(3_suppl):338S-400.

21. Kim J, Gearhart M, Zurick A, et al. Preliminary report on the safety of heparin for deep vein thrombosis prophylaxis after severe head injury. Journal of Trauma. 2002;53:38-43.

Resources