Traumatic Brain Injury (TBI) is the Leading Cause of Death for Patients Age 1-45 y/o in North America [MEDLINE]
Many Survivors Have Significant Disability
Physiology
Primary Brain Injury
General Comments: primary brain injury occurs at the time of trauma
Mechanisms of Primary Brain Injury
Diffuse Axonal Injury Due to Shearing: usually involves the hemispheric gray-white matter junction, corpus callosum, and/or midbrain
Usually present with coma without an increase in intracranial pressure
Focal Cerebral Contusion: common in basal frontal and temporal regions (due to susceptibility to direct impact on the basal skull surface during acceleration/deceleration injuries)
These are the most frequently observed lesions
Intraparenchymal hematoma may occur from coalescence of cerebral contusions or disruption of intraparenchymal blood vessels
Extra-Axial Hematoma
Epidural Hematoma (see Epidural Hematoma): due to tear in dural vessels (middle meningeal artery, etc)
Almost always associated with skull fracture
Tend to not be associated with underlying parenchymal brain injury
Intraventricular Hemorrhage: due to tearing of subependymal veins, extension from adjacent intraparenchymal hemorrhage, or extension from subarachnoid hemorrhage
Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage): due to disruption of small pial vessels, extension from intraventricular hemorrhage, or extension from superficial parenchymal hemorrhage
Tend to occur in the sylvian fissures and interpeduncular cisterns
Subdural Hematoma (SDH) (see Subdural Hematoma): due to damage to bridging veins (which drain cerebral cortical surfaces to dural venous sinuses) or from extension from superficial cortical contusions
Tend to be associated with underlying parenchymal brain injury
Secondary Brain Injury
General Comments: secondary brain injury occurs subsequent to the initial trauma and continues for hours-days
Mechanisms of Secondary Brain Injury
Apoptosis
Electrolyte Imbalance
Inflammatory Response
Mitochondrial Dysfunction
Neurotransmitter-Mediated Excitotoxicity Resulting in Glutamate, Free-Radical Injury to Cell Membranes
Secondary Brain Ischemia Resulting from Vasospasm, Focal Microvascular Occlusion, and Vascular Injury
Other Aspects
Impaired Cerebral Autoregulation
Normally, Via Autoregulation, the Brain Maintains an Adequate Cerebral Blood Flow Across a Wide Range of Mean Arterial Blood Pressures (MAP) From 50-100 Meg Hg
In TBI, Cerebral Autoregulation is Impaired in Approximately 33% of TBI Cases: resulting in the brain demonstrating “pressure-passive” hemodynamics
Increased MAP (hypertension) may then result in increased cerebral blood flow and hypermedia, resulting in elevated intracranial pressure (ICP)
Decreased MAP (hypotension) may result in brain hypoperfusion and ischemia
Epidemiology: approximately 33% of TBI patients develop coagulopathy -> this is associated with increased risk of hemorrhage, poor neurologic outcome, and increased mortality rate
Physiology: systemic release of tissue factor and brain phospholipid -> Intravascular coagulation and consumptive coagulopathy
Fever is a Common After Brain Injury (Due to Traumatic Brain Injury, Ischemic CVA, and/or Intracerebral Hemorrhage) (J Intensive Care Med, 2015) [MEDLINE]
Fever is a Risk Factor for In-Hospital Mortality (J Intensive Care Med, 2015) [MEDLINE]
In Patients with Patients with Ischemic CVA/TBI, Fever (with Peak Temperature Below 37 Degrees C or Above 39 Degrees C) Increased In-Hospital Mortality, as Compared to Normothermia (Intensive Care Med, 2015) [MEDLINE]
However, for Patients with Central Nervous System Infection, Elevated Peak Temperature was Not Associated with Increased Mortality, as Compared to Normothermia (37-37.4 Degrees C) (Intensive Care Med, 2015) [MEDLINE]
Treatment
General Measures
Correction of Electrolyte Imbalances: when present
Care in Specialized Trauma Center: associated with improved outcome
Study of the Impact of High-Volume Trauma Centers on Outcome After TBI (J Trauma Acute Care Surg, 2013) [MEDLINE]
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Graduated Compression Stockings/Sequential Compression Device (SCD’s) are Recommended (Level III Recommendation): continue use until patient is ambulatory
Low Molecular Weight Heparin or Low Dose Unfractionated Heparin Should Be Used in Combination with Mechanical Prophyaxis (Level III Recommendation): however, there is an increased risk of expansion of intracranial hemorrhage
Insufficient Evidence to Determine the Preferred Agent, Dose, or Timing of Pharmacologic DVT Prophylaxis
Hemodynamic Management
Rationale
Hypotension Causes Cerebral Vasodilation: therefore, should be avoided
Hemodynamic Monitoring
Monitor Central Venous Pressure (CVP) (see Hemodynamics): to maintain adequate fluid status
Clinical Efficacy
SAFE Study: Comparing Crystalloid (Normal Saline) vs Colloid (4% Albumin) in Heterogenous Population of ICU Patients (2004) [MEDLINE]: colloid (albumin) use in the subgroup of patients with TBI resulted in a higher mortality rate
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Hypotension <90 mm Hg Should Be Avoided (Level II Recommendation)
Avoid Hypervolemia
Hemostatic Therapy
Recommendations
Management of Non-Coagulopathic Patients: hemostatic therapy is not indicated
Management of Elevated INR (Unrelated to Coumadin): maintain INR <1.4 with FFP, prothrombin complex concentrate, etc
Role of Recombinant Factor VIIa (NovoSeven RT) (see Factor VIIa)
FVIIa Traumatic ICH Study Group Prospective Trial in TBI (Neurosurgery, 2008) [MEDLINE]: recombinant factor VIIa decreased hematoma progression, but did not decrease the mortality rate (but there was a trend toward increased rate of DVT’s at day 3)
Management of Coumadin Anticoagulation (If Present): maintain INR <1.4
Management of Platelet Dysfunction (Drug-Induced, etc)
Systematic Review of Platelet Transfusion in TBI in Patients on Pre-Injury Antiplatelet Therapy (J Trauma Acute Care Surg, 2012) [MEDLINE]: platelet transfusion in this setting is of unclear benefit (due to poor quality data)
Management of Thrombocytopenia (If Present): maintain platelet count >75k
Infection Prophylaxis
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Peri-Procedural Antibiotics are Recommended for Intubation to Decrease the Risk of Pneumonia (Level II Recommendation): however, these do not decrease length of stay or mortality rate
Early Tracheostomy Should Be Performed to Decrease Ventilator Days (see Tracheostomy): however, it does not decrease mortality rate or rate of pneumonia
Routine Ventricular Catheter Exchange to Prevent Infection is Not Recommended (Level III Recommendation)
Prophylactic Antibiotics to Prevent Ventricular Catheter Infection are Not Recommended (Level III Recommendation)
Early Extubation in Qualified Patients Can Be Done Without an Increased Risk of Pneumonia (Level III Recommendation)
Systematic Review of Sedation in TBI (Crit Care Med, 2011) [MEDLINE]
No Evidence that One Sedative is Superior to the Others in Terms of Improvement in Patient-Centered Outcomes, Intracranial Pressure, or Cerebral Perfusion Pressure in TBI
High Bolus Doses of Opiates, Have Potentially Deleterious Adverse Effects on Intracranial Pressure and Cerebral Perfusion Pressure
Corticosteroids Increased the Mortality Rate within the First 2 wks Following TBI
MRC CRASH Trial Follow-Up Study (Lancet, 2005) [MEDLINE]
Corticosteroids Increased the Mortality Rate at 6 mo in TBI
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Corticosteroids are Not Recommended to Decrease Intracranial Pressure: high dose methylprednisolone is associated with increased mortality in moderate-severe TBI
Bifrontotemporoparietal Decompressive Craniectomy in Adults with TBI and Refractory Increased ICP Decreased ICP and Length of ICU Stay, But was Associated with No Impact on Mortality and a Higher Number of Unfavorable Outcomes
Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) Study: results pending
Comparison of Mannitol with 23.4% Hypertonic Saline in Decreasing Intracranial Pressure in TBI (Neurosurgery, 2005) [MEDLINE]
No Difference Between Mannitol and Hypertonic Saline (23.4%) in Decreasing in ICP in TBI: however, duration of hypertonic saline effect (96 min) was longer than that of mannitol (59 min)
Systematic Review and Meta-Analysis of Hypertonic Saline (Crit Care Med, 2013) [MEDLINE]
Hypertonic Saline (23.4%) Decreased Intracranial Pressure by 50% within 60 min in TBI
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Insufficient Evidence to Make Recommendation for Use of Hypertonic Saline
Hyperventilation
Clinical Efficacy
Randomized Trial of Prolonged Hyperventilation in TBI (J Neurosurg, 1991)[MEDLINE]
Prophylactic Hyperventilation is Deleterious in TBI Patients with Motor Scores of 4-5
Study of the Effects of Moderate Hyperventilation in TBI (J Neurosurg, 2002) [MEDLINE]
Hyperventilation (Even if Moderate) Can Frequently Result in Harmful Local Reductions in Cerebral Perfusion Which Cannot Be Detected by SjvO2
Hyperventilation Should Not Be Considered Safe
Study of the Effects of Hyperventilation on Cerebral Blood Flow in TBI (Crit Care Med, 2002) [MEDLINE]
Hyperventilation Increases the Volume of Severely Hypoperfused Tissue within the Injured Brain, Despite Improvements in Cerebral Perfusion Pressure and Intracranial Pressure
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Prophylactic Hyperventilation (pCO2 <25 mm Hg) is Not Recommended (Level II Recommendation)
Hyperventilation is Recommended as a Temporizing Measure to Decrease an Elevated Intracranial Pressure (Level III Recommendation)
However, Hyperventilation Should be Avoided During the First 24 hrs After Injury
During this Period, Cerebral Blood Flow is Often Critically Decreased
If Hyperventilation is Used, Jugular Venous Oxygen Saturation (SjO2) or Brain Tissue Oxygenation are Recommended to Monitor Therapy
Cerebral Perfusion Pressure is a Surrogate for Cerebral Blood Flow
Cerebral Perfusion Pressure (CPP) = MAP – ICP
Episodes of Hypotension, Increased ICP, and Low CPP are Associated with Secondary Brain Injury and Worse Outcome (J Neurosurg, 2002) [MEDLINE]
Allows Drainage of Cerebrospinal Fluid from Ventricle: when using an external ventricular drain
Indications (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
All Salvageable Patients with Severe TBI, GCS 3-8 After Resuscitation, and an Abnormal CT Scan (Hematoma, Contusion, Edema, Herniation, Compressed Basal Cisterns) (Level II Recommendation)
Severe TBI with Normal CT Scan with Two or More Criteria at Admission: Age >40 y/o, Unilateral or Bilateral Motor Posturing, SBP <90 mm Hg (Level III Recommendation)
Contraindications
Coagulopathy Which Cannot Be Corrected (see Coagulopathy)
Culture of Tip of External Ventricular Drains May Demonstrate Bacterial Colonization: however, the rate of invasive infection is lower
Risk of Infection is Higher with Ventricular Catheter (1-27%) Than with Parenchymal Monitor
Risk Factors for Infection
Leakage Around the Ventriculostomy Site
Longer Duration of Catheter Placement
Presence of Open Skull Fracture with Leakage of Cerebrospinal Fluid
Clinical Efficacy
Study of Intracranial Pressure Monitoring in TBI (Crit Care Med, 2005) [MEDLINE]
Intracranial Pressure/Cerebral Perfusion Pressure-Targeted Intensive Care Results in Prolonged Mechanical Ventilation and Increased Levels of Therapy Intensity without Evidence of Improved Outcome (in Those Who Survive >24 hrs)
Trial of Intracranial Pressure Monitoring in TBI (NEJM, 2012) [MEDLINE]
Maintaining ICP <20 mm Hg Did Not Improve Outcome (Based on Functional and Cognitive Status), 6-Month Mortality Rate, or Median Length of ICU Stay, as Compared to Clinical Exam/Imaging-Based Management
Recommendations for Intracranial Pressure Thresholds (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Treatment Should Be Initiated for ICP >20 mm Hg (Level II Recommendation)
Combination of ICP + Clinical Findings + Brain Findings Should Be Used to Determine the Need for Treatment of ICP (Level III Recommendation)
Recommendations for Cerebral Perfusion Pressure Thresholds (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Target Cerebral Perfusion Pressure 50-70 mm Hg
Patients with Intact Cerebral Autoregulation Will Tolerate Higher Cerebral Perfusion Pressure Values
Maintenance of Cerebral Perfusion Pressure >70 mm Hg with Fluids/Pressors Should Be Avoided Due to Risk of ARDS (Level II Recommendation)
Excessive Hypervolemia Should Be Avoided
Cerebral Perfusion Pressure <50 mm Hg Should Be Avoided (Level III Recommendation)
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Mannitol (Dose: 0.25-1.00 g/kg) is Effective to Control Increased Intracranial Pressure (Level II Recommendation)
Hypotension (SBP <90 mm Hg) Should Be Avoided
Restrict Mannitol Use Prior to Intracranial Pressure Monitoring to Patients with Transtentorial Herniation or Progressive Neurologic Deterioration Not Attributable to an Extracranial Etiology (Level III Recommendation)
Systematic Review of Sedation in TBI (Crit Care Med, 2011) [MEDLINE]
No Evidence that One Sedative is Superior to the Others in Terms of Improvement in Patient-Centered Outcomes, Intracranial Pressure, or Cerebral Perfusion Pressure in TBI
High Bolus Doses of Opiates, Have Potentially Deleterious Adverse Effects on Intracranial Pressure and Cerebral Perfusion Pressure
Systematic Review of Ketamine in Traumatic Brain Injury (Neurocrit Care, 2014) [MEDLINE]
Ketamine Does Not Increase ICP in TBI and May Decrease it in Selected Cases (Oxford Level 2b, GRADE C Evidence)
Large Lipid Load: requiring adjustment of enteral/parenteral nutritional support
Clinical Efficacy
Systematic Review of Sedatives in TBI (Crit Care MED, 2011) [MEDLINE]
No Evidence that Any Sedative is Superior to Another in TBI in Terms of Patient-Centered Outcomes, Intracranial Pressure, or Cerebral Perfusion Pressure
High Bolus Doses of Opiates Have Potentially Deleterious Effects on Intracranial Pressure and Cerebral Perfusion Pressure
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Propofol is Recommended for Increased Intracranial Pressure: however, propofol has not been shown to improve mortality or 6-mo outcome (in addition, high dose propofol can produce significant morbidity)
Barbiturates are Recommended for Increased Intracranial Pressure Refractory to Other Medical/Surgical Therapies
Propofol (Diprivan) (see Propofol): increases seizure threshold
Clinical Efficacy
Systematic Review of Anti-Epileptic Drugs for Seizures Following TBI (Cochrane Database Syst Rev, 2001) [MEDLINE]
Prophylactic Anti-Epileptics are Effective in Decreasing Early Seizures
Prophylactic Anti-Epileptics Do Not Decrease the Occurrence of Late Seizures or Impact Neurologic Disability or Mortality Rate
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Anticonvulsants are Recommended to Decrease the Incidence of Early Post-Traumatic Seizures (Within 7 Days of Injury): however, post-traumatic seizures are not associated with worse outcomes
Prophylactic Phenytoin/Valproic Acid is Not Recommended to Prevent Late Post-Traumatic Seizures (Level II Recommendation)
Management of Serum Glucose
Clinical Efficacy
Study of Hyperglycemia in Traumatic Brain Injury (J Trauma, 2005) [MEDLINE]: early hyperglycemia is associated with poor outcome in severe TBI
Recommendations
Maintain Normoglycemia
Management of Body Temperature
Rationale
Fever Causes Cerebral Vasodilation, Which Can Increase Intracranial Pressure: therefore, treatment is critical
Cochrane Database Systematic Review of Therapeutic Hypothermia in Traumatic Brain Injury (Cochrane Database Syst Rev, 2009) [MEDLINE]: therapeutic hypothermia may be effective in reducing death and unfavourable outcomes for traumatic head injured patients, but significant benefit was found only in the low quality trials -> therapeutic hypothermia is not recommended in traumatic brain injury
Systematic Review of Therapeutic Hypothermia in Traumatic Brain Injury (CJEM, 2010) [MEDLINE]: prophylactic mild-to-moderate therapeutic hypothermia (32-34 degrees C) in traumatic brain injury (Glasgow coma scale score < or = 8) decreased mortality and improved rates of good neurologic recovery
Maximal benefit occurred with cooling continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hrs
National Acute Brain Injury Study: Hypothermia II Trial (Lancet, 2011) [MEDLINE]: therapeutic hypothermia to 33 or 35 degrees C (in patients enrolled within 2.5 hrs of injury) had no clinical benefit in terms of Glasgow outcome scale score at 6 mo
Greater benefit from therapeutic hypothermia was observed in patients undergoing surgical removal of hematomas, as compared with those with diffuse axonal/brain injury
Systematic Review of Therapeutic Hypothermia in Traumatic Brain Injury (Brain Injury, 2012) [MEDLINE]: therapeutic hypothermia decreased intracranial pressure
Adverse Effects
Rewarming Can Increase Intracranial Pressure
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Prophylactic Therapeutic Hypothermia is Not Associated with Decreased Mortality in Traumatic Brain Injury (When Compared to Normothermic Controls) (Level III Recommendation)
However, When Maintained for >48 hrs, Mortality May Be Decreased
Prophylactic Therapeutic Hypothermia is Associated with Significantly Higher GCS Scores (When Compared to Normothermic Controls)
Recommendations
Therapeutic Hypothermia Has Unclear Clinical Benefit in TBI: however, may be considered in patients with refractory elevations in intracranial pressure, despite other therapy
Nutrition
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Patients Should Be Fed to Attain Full Caloric Replacement by Day 7 Post-Injury
Renal Management
Choice of Intermittent Hemodialysis vs Continuous Venovenous Hemodialysis (CVVHD)
If Hemodialysis is Required, CVVHD is Preferred Over Intermittent HD, Due to Rapid Solute Changes and Potential for Hypotension with Intermittent HD (Which May Exacerbate Cerebral Ischemia) (see Hemodialysis)
Respiratory Management
Indications for Intubation/Mechanical Ventilation
Glasgow Coma Scale Score <8: early intubation is recommended, if prehospital expertise is available
Hypercapnia Causes Cerebral Vasodilation and Therefore, Should Be Avoided
Avoid Patient-Ventilator Dyssynchrony
Patient-Ventilator Dyssynchrony Increases Venous Pressure and Therefore, Should Be Avoided
Clinical Efficacy
Randomized Trial of Prolonged Hyperventilation in TBI (J Neurosurg, 1991) [MEDLINE]
Prophylactic Hyperventilation is Deleterious in TBI Patients with Motor Scores of 4-5
Study of the Effects of Moderate Hyperventilation in TBI (J Neurosurg, 2002) [MEDLINE]
Hyperventilation (Even if Moderate) Can Frequently Result in Harmful Local Reductions in Cerebral Perfusion Which Cannot Be Detected by SjvO2
Hyperventilation Should Not Be Considered Safe
Study of the Effects of Hyperventilation on Cerebral Blood Flow in TBI (Crit Care Med, 2002) [MEDLINE]
Hyperventilation Increases the Volume of Severely Hypoperfused Tissue within the Injured Brain, Despite Improvements in Cerebral Perfusion Pressure and Intracranial Pressure
Recommendations (Guidelines for the Management of Severe Traumatic Brain Injury, 2007) [MEDLINE]
Peri-Procedural Antibiotics are Recommended for Intubation to Decrease the Risk of Pneumonia (Level II Recommendation): however, these do not decrease length of stay or mortality rate
Avoid Hypoxemia (pO2 <60 mm Hg or SaO2 <90%) (Level III Recommendation)
Prophylactic Hyperventilation (pCO2 <25 mm Hg) is Not Recommended (Level II Recommendation)
Hyperventilation is Recommended as a Temporizing Measure to Decrease an Elevated Intracranial Pressure (Level III Recommendation)
However, Hyperventilation Should be Avoided During the First 24 hrs After Injury
During this Period, Cerebral Blood Flow is Often Critically Decreased
If Hyperventilation is Used, Jugular Venous Oxygen Saturation (SjO2) or Brain Tissue Oxygenation are Recommended to Monitor Therapy
Early Tracheostomy Should Be Performed to Decrease Ventilator Days (see Tracheostomy)
However, Tracheostomy Does Not Decrease the Mortality Rate or Rate of Pneumonia
Early Extubation in Qualified Patients Can Be Done Without an Increased Risk of Pneumonia* (Level III Recommendation)
Early indicators of prognosis in 846 cases of severe traumatic brain injury. J Neurotrauma 2002;19(7):869-874. doi: 10.1089/08977150260190456 [MEDLINE]
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(2):326 [MEDLINE]
Clinical
Brain injury as a risk factor for fever upon admission to the intensive care unit and association with in-hospital case fatality: a matched cohort study. J Intensive Care Med. 2015 Feb;30(2):107-14. doi: 10.1177/0885066613508266. Epub 2013 Oct 16 [MEDLINE]
Early temperature and mortality in critically ill patients with acute neurological diseases: trauma and stroke differ from infection. Intensive Care Med. 2015 May;41(5):823-32. doi: 10.1007/s00134-015-3676-6. Epub 2015 Feb 3 [MEDLINE]
Treatment
General
Management of severe head injury: institutional variations in care and effect on outcome. Crit Care Med. 2002 Aug;30(8):1870-6 [MEDLINE]
Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24 Suppl 1:S1-106 [MEDLINE]
Guidelines for the management of severe traumatic brain injury. Editor’s commentary. J Neurotrauma 2007; 24 Suppl 1:2 p preceding S1 [MEDLINE]
Prevalence and consequences of sleep disorders in traumatic brain injury. J Clin Sleep Med. 2007 Jun;3(4):349-56 [MEDLINE]
Mortality reduction after implementing a clinical practice guidelines-based management protocol for severe traumatic brain injury. J Crit Care 2010; 25:190-195 [MEDLINE]
A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012;367:2471–2481 [MEDLINE]
Critical care management of severe traumatic brain injury in adults. Scand J Trauma Resusc Emerg Med 2012; 20:12 [MEDLINE]
Early management of severe traumatic brain injury. Lancet. 2012 Sep;380(9847):1088-98 [MEDLINE]
High-volume trauma centers have better outcomes treating traumatic brain injury. J Trauma Acute Care Surg. 2013 Jan;74(1):143-7; discussion 147-8 [MEDLINE]
Pathophysiologic Mechanisms of Cerebral Ischemia and Diffusion Hypoxia in Traumatic Brain Injury. JAMA Neurol. 2016 May 1;73(5):542-50. doi: 10.1001/jamaneurol.2016.0091 [MEDLINE]
Sedation
High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988 Jul;69(1):15-23 [MEDLINE]
Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011;39:2743–2751 [MEDLINE]
Sedation in traumatic brain injury. Emerg Med Int. 2012; vol 2012; article ID 637171, pp 1–11 [MEDLINE]
Hemodynamic Management
SAFE Study. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247–2256 [MEDLINE]
Hemostatic Therapy
rFVIIa Traumatic ICH Study Group. Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial. Neurosurgery. 2008 Apr;62(4):776-86; discussion 786-8 [MEDLINE]
Utility of platelet transfusion in adult patients with traumatic intracranial hemorrhage and preinjury antiplatelet use: a systematic review. J Trauma Acute Care Surg. 2012 Jun;72(6):1658-63 [MEDLINE]
Corticosteroids
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(9442):1321 [MEDLINE]
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(9475):1957 [MEDLINE]
Guidelines for the management of severe traumatic brain injury. XV. Steroids. J Neurotrauma. 2007;24 Suppl 1:S91-5 [MEDLINE]
Management of Increased Intracranial Pressure
Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991 Nov;75(5):731-9 [MEDLINE]
Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma. 1998;44(1):50 [MEDLINE]
Cerebral tissue PO2 and SjvO2 changes during moderate hyperventilation in patients with severe traumatic brain injury. J Neurosurg. 2002 Jan;96(1):97-102 [MEDLINE]
Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates. Crit Care Med. 2002 Sep;30(9):1950-9 [MEDLINE]
Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery. 2005;57(4):727 [MEDLINE]
Effect of intracranial pressure monitoring and targeted intensive care on functional outcome after severe head injury. Crit Care Med. 2005 Oct;33(10):2207-13 [MEDLINE]
Refractory intracranial hypertension and “second-tier” therapies in traumatic brain injury. Intensive Care Med. 2008;34:461–467 [MEDLINE]
Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. Crit Care Med. 2011 Dec;39(12):2743-51 [MEDLINE]
Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011;364(16):1493 [MEDLINE]
Hyperosmolar therapy for raised intracranial pressure. N Engl J Med. 2012;367:746–752 [MEDLINE]
High-osmolarity saline in neurocritical care: systematic review and meta-analysis. Crit Care Med 2013;41:1353–1360. doi: 10.1097/CCM.0b013e31827ca4b3 [MEDLINE]
The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014 Aug;21(1):163-73. doi: 10.1007/s12028-013-9950-y [MEDLINE]
Brain Tissue Oxygen Monitoring and the Intersection of Brain and Lung: A Comprehensive Review. Respir Care. 2016 Jul 19. pii: respcare.04962 [MEDLINE]
A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients. Biomed Res Int. 2015;2015:529580. doi: 10.1155/2015/529580. Epub 2015 Aug 27 [MEDLINE]
Management of Seizures
Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Cochrane Database Syst Rev. 2001;(4):CD000173 [MEDLINE]
Management of Serum Glucose
Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg. 1991;75(4):545 [MEDLINE]
The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery. 2000;46(2):335 [MEDLINE]
The impact of hyperglycemia on patients with severe brain injury. J Trauma. 2005;58(1):47 [MEDLINE]
Management of Body Temperature
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(2):326 [MEDLINE]
Therapeutic Hypothermia
Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556 [MEDLINE]
Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008;371:1955 [MEDLINE]
Hypothermia for traumatic head injury. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD001048. DOI: 10.1002/ 14651858.CD001048.pub4 [MEDLINE]
Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review. CJEM 2010; 12:355-364 [MEDLINE]
Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011; 10:131-139 [MEDLINE]
Therapeutic hypothermia for the management of intracranial hypertension in severe traumatic brain injury: a systematic review. Brain Inj 2012; 26:899-908 [MEDLINE]
Therapeutic hypothermia for acute brain injuries. Scand J Trauma Resusc Emerg Med. 2015 Jun 5;23:42. doi: 10.1186/s13049-015-0121-3 [MEDLINE]
Surgery
Surgery of cerebral trauma and associated critical care. Neurosurgery. 2007 Jul;61(1 Suppl):203-20; discussion 220-1. doi: 10.1227/01.NEU.0000255497.26440.01 [MEDLINE]
