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Traumatic Brain Injury: Changes in Management Across the Spectrum of Age and Time Omaha 2018 Trauma Symposium June 15, 2018 Gail T. Tominaga, M.D., F.A.C.S. Scripps Memorial Hospital La Jolla Outline Background Basic principles of TBI management Brain Trauma Foundation 2016 Pediatric Traumatic Brain Injury Guidelines 2012

Traumatic Brain Injury Leading cause of death in Americans < 45 years of age Leading cause of death & acquired disability in childhood 75% have other significant injuries https://www.cdc.gov

https://www.cdc.gov/traumaticbraininjury//rates_hosp_byage.html https://www.cdc.gov/traumaticbraininjury//dist_death.html

Survey of 219 hospital intensive care units in 45 states that treated patients with severe head injury. Centers % Routine ICP monitoring (more in high volume centers) 28 Hyperventilation and osmotic diuretics routinely used 83 Aiming for PaCO 2 < 25 mm Hg 29 Corticosteroids use more than half the time 64 Crit Care Med 23: 560 567, 1995

Findings ICP monitoring used infrequently Severe hyperventilation Use of steroids currently not indicated Wide variability in practice Brain Injury PRIMARY Immediate damage Can lead to cell death and worsening damage to the brain SECONDARY Indirect injury Delayed Due to: Inadequate blood flow Inadequate substrate delivery

Controlling Secondary Brain Injury Operable Lesions Subdural hematoma Depressed skull fractures Controlling Secondary Brain Injury Hypotension

Controlling Secondary Brain Injury Hypotension SBP < 90 mmhg TCDB, 717 pts: mortality 27% to 50%* Mortality increased: 34 to 75%** Bad outcome (dead, disabled, pvs) increased: 24 to 88%*** *Chestnut. JOT. 34(2), 1997. **Gentleman. Lancet. 2:853, 1981. ***Kohi et al. Injury. 16:25, 1984. Controlling Secondary Brain Injury Hypotension AVOID Hypotension Adequate fluid resuscitation EUVOLEMIA Preferred: Normal saline (308 mosm) Others: LR (273 mosm) Consider: 3% saline

Controlling Secondary Brain Injury Hypoxia Hypoxemia po 2 < 60mmHg: 23 46% Increases mortality from 34 to 59% Poor outcome increases from 28 to 71% Controlling Secondary Brain Injury Elevated ICP Brain -- CSF -- Blood Creates pressure gradients within the skull (herniation) Compromises cerebral perfusion pressure ischemia (esp end vessels)

Controlling Secondary Brain Injury Cerebral Perfusion Pressure CPP = MAP ICP Normal Adequate Ischemic 70 100 mmhg 50 60 mm Hg 30 40 mmhg Treatment of Elevated ICP Elevate HOB Oxygenation Hyperventilation (mild) Sedation Neuromuscular blockade Osmotic diuretics Seizure control Mild hypothermia CSF drainage Barbiturate coma Decompressive Craniectomy

Brain Trauma Foundation Guidelines for Severe TBI Date Title Comment 2007 Guidelines for Prehospital Management of TBI, 2 nd ed Rec in 7 topic areas; based mostly on Class III evidence 2006 Guidelines for Surgical Management of Severe TBI 2007 Guidelines for Management of Severe TBI, 3 rd edition* Rec for 15 clinical areas, ranking from Level I to III. 2006 Guidelines for the Prehospital Management of TBI, 2 nd edition Pediatric sections added 2000 Early Indicators of Prognosis in Severe TBI 1999 Guidelines for Management of Severe TBI, 2 nd edition 1995 Guidelines for Management of Severe TBI, 1 st edition * Endorsed by principal neurosurgery organizations Controlling Secondary Brain Injury Barbiturate Coma Decompressive Craniectomy CSF drainage Osmotic diuresis Mild Hypothermia Neuromuscular blockade Mild hyperventilation Elevate HOB; Sedation Seizure control and prophylaxis Avoid hyperthermia AVOID HYPOTENSION (Adequate fluid resuscitation) AVOID HYPOXIA (Early airway, oxygen)

Brain Trauma Foundation Guidelines for Severe TBI Date Title Comment 2016 Guidelines for the Management of Severe TBI, 4 th ed* Rec in 28 topics; based on 5 Class I studies, 46 Class 2, 136 Class III, 2 meta-analyses 2012 Guidelines for Severe TBI in Infants, Children, & Adolescents, 2nd ed* Rec for 8 topic areas; based on Class II and III evidence * Endorsed by principal neurosurgery organizations Guidelines for Management of Severe TBI Systematic evidence review and synthesis Screened for scientific and statistical validity Classified: Class Qualification 1 Good quality randomized trials 2 Moderate quality randomized trials, good quality cohort or case-control studies 3 Low quality randomized controlled trials, mod-low quality cohort or case-control studies, case series

Guidelines for Severe TBI in Infants, Children, & Adolescents, 2nd ed Systematic evidence review and synthesis Screened for scientific and statistical validity Classified: Class Qualification 1 Good quality randomized trials 2 Moderate quality randomized trials, good quality cohort or case-control studies 3 Low quality randomized controlled trials, mod-low quality cohort or case-control studies, case series Guidelines for Management of Severe TBI, 4 th ed Level of Recommendations Level I IIA IIB III Qualification High quality body of evidence Moderate quality body of evidence Body of evidence with Class 2 studies that provided direct evidence but were of overall poor quality Body of evidence with Class 3 studies or Class 2 studies providing only indirect evidence

Guidelines for Management of Severe TBI, 4 th ed Studies: 5 Class 1, 46 Class 2, 136 Class 3, 2 meta analysis TREATMENTS MONITORING THRESHOLDS Decompressive Craniectomy ICP BP Prophylactic Hypothermia CPP ICP Hyperosmolar tx Advanced cerebral monitoring CPP CSF drainage Advanced cerebral monitoring Ventilator therapies Anesthestics, Analgesia, Sedation Steroids Nutrition Infection Prophylaxis DVT Prophylaxis Seizure Prophylaxis Guidelines for Management of Severe TBI, 4 th ed DECOMPRESSIVE CRANIOTOMY Level I Level IIA PEDIATRIC GUIDELINES Bifrontal DC is not recommended to improve outcomes ( GOS-E at 6 months post-injury) Reduces ICP and minimizes ICU LOS Large F-T-P DC ( > 12 x 15 cm) recommended DC with duraplasty, leaving the bone flap out, may be considered for pediatric patients with TBI who are showing early signs of neurologic deterioration or herniation or are developing intracranial HTN refractory to medical management during the early stages of their treatment

Decompressive Craniectomy Decompressive Craniectomy Are there Prospective Randomized Studies? DECRA: Decompressive Craniectomy in Diffuse Traumatic Brain Injury RESCUEicp: Randomized Evaluation of Surgery with Craniectomy for Uncontrolled Elevated Intracranial Pressure

Dec 2002 April 2010 N = 155; age 15 59 yrs; GCS 3 8; 72 hrs Severe diffuse TBI and intracranial HTN refractory to first tier therapies Bifrontotemporoparietal DC vs Standard Care Intracranial Pressure before and after Randomization Cooper DJ et al. N Engl J Med 2011;364:1493 1502

Cumulative Proportions of Results on the Extended Glasgow Outcome Scale Cooper DJ et al. N Engl J Med 2011;364:1493-1502 DECRA In adults with severe diffuse TBI and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and length of stay in the ICU but was associated with more unfavorable outcomes.

2004 2014; 40 centers in 17 countries 408 patients; ge 10 65 years Severe diffuse TBI and intracranial HTN (> 25 mm Hg) refractory to first and second tier therapies DC vs Medical Treatment

DC in Pediatric TBI Taylor Pediatric Single center RCT N = 27, 1991 1998 Age 1.8 15 years ICP > 20 mm Hg in first 24 hrs or evidence of herniation F/U 6 months 57% favorable outcome in DC vs 14% in medical group Decompressive Craniectomy Decreases ICP Increases CPP Improves PbtO2 More unfavorable outcomes

Guidelines for Management of Severe TBI, 4 th ed PROPHYLACTIC HYPOTHERMIA Level I Level IIA Level IIB PEDIATRIC GUIDELINES Early (within 2.5 hrs), short term (48 hrs), prophylactic hypothermia is NOT recommended (II) Avoid mod hypothermia (32-33 o C) beginning early after severe TBI for only 24 hours (II) Consider mod hypothermia beginning within 8 hrs after severe TBI for up to 48 hrs duration to reduce ICP (II) If hypothermia is induced, rewarming at a rate of > 0.5 o C per hour should be avoided 4 th edition 3 rd edition Guidelines for Management of Severe TBI, 4 th ed HYPEROSMOLAR THERAPY Level I Level IIA Level IIB PEDAITRIC GUIDELINES (II) Hypertonic saline should be considered for tx of severe TBI with elevated ICP (6.5-10 ml/kg) (III) HTS should be considered for tx of severe pediatric TBI with elevated ICP 9dose 3% saline continuous dose 0.1-1.0 ml/kg/hr to maintain ICP < 20 mmhg & serum osm < 300 mosm/l Level I Level II Level III Mannitol effective for control of elevated ICP (0.25 mg/kg 1 g/kg); avoid SBP < 90 mm Hg Restrict use prior to ICP monitoring to patients with signs of transtentorial herniation or progressive neurologic deterioration

Guidelines for Management of Severe TBI, 4 th ed CSF DRAINAGE Level I Level IIA Level III PEDIATRIC GUIDELINES EVD system zeroed at midbrain with continuous drainage may be considered to lower ICP Use of CSF drainage to lower ICP in pts with initial GCS < 6 during the 1 st 12 hrs after injury may be considered (III) CSF drainage via an EVD may be considered in the management of increased ICP in children with severe TBI. (III) Addition of a lumbar drain may be considered in the case of refractory intracranial HTN with a functioning EVD, open basal cisterns, and no evidence of a mass lesion or shift on imaging studies. 4 th edition 3 rd edition Guidelines for Management of Severe TBI, 4 th ed VENTILATION THERAPIES Level I Level IIA Level IIB PEDIATRIC GUIDELINES Insufficie nt Prolonged prophylactic hyperventilation with PaCO 2 < 25 is NOT recommended (III) Avoid prophylactic severe hyperventilation (paco2 < 30 mm Hg may be considered in initial 48 hrs after surgery (III) If hyperventilation is used to manage refractory intracranial HTN, advanced neuro monitoring for cerebral ischemia may be considered Level I Level II Level 3 Prophylactic hyperventilation Hyperventilation recommended as a temporizing NOT recommended measure to reduce elevated ICP Hyperventilation should be avoided during the 1 st 24 hrs after injury

Guidelines for Management of Severe TBI, 4 th ed ANESTHETICS, ANALGESICS, SEDATIVES Level I Level IIA Level IIB PEDIATRIC GUIDELINES Barbiturates to induce burst suppression (EEG) is NOT recommended as prophylaxis against development of intracranial HTN High-dose barbiturates is recommended to control elevated ICP refractory to maximum standard medical and surgical tx. Propofol is recommended for the control of ICP but is not recommended for improvement in mortality or 6 month outcome. Caution required as high-dose propofol can produce significant morbidity (III) Etomidate may be considered to control severe intracranial HTN (III) Thiopental may be considered to control intracranial HTN Guidelines for Management of Severe TBI, 4 th ed STEROIDS Level I Level IIA PEDIATRIC GUIDELINES Use of steroids NOT (II) Use of steroids not recommended recommended

Guidelines for Management of Severe TBI, 4 th ed NUTRITION Level I Level IIA Level IIB PEDIATRIC GUIDELINES Attain basal caloric replacement at least by 5 th day and at most 7 th days post injury (to decrease mortality) Transgastric jejunal feeding is recommended to reduce the incidence of VAP (II) Evidence does not support the use of immunemodulating diet for the tx of severe TBI to improve outcome Guidelines for Management of Severe TBI, 4 th ed DVT Level I Level IIA Level III LMWH or low dose fractionated heparin may be used in combination with mechanical prophylaxis (increased risk for expansion of ICH) evidence of support recommendation of preferred agent, dosing, or timing of pharmacologic agent.

Guidelines for Management of Severe TBI, 4 th ed SEIZURE PROPHYLAXIS Level I Level IIA Level III PEDIATRIC GUIDELINES Prophylactic use of phenytoin or valproate is NOT recommended for late PTS Phenytoin is recommended to decrease the incidence of early PTS (within 7 days) evidence to recommend levetiracetam compared with phenytoin regarding efficacy in preventing early PTS and toxicity (III) Prophylactic tx with phenytoin may be considered to reduce the incidence of early PTS Guidelines for Management of Severe TBI, 4 th ed INFECTION Level I Level IIA Level III Early tracheostomy is recommended to reduce mechanical ventilator days when the overall benefit is thought to outweigh the complications. There is no evidence that Antimicrobial impregnated catheters may be considered to prevent catheter-related infection during external ventricular drainage early tracheostomy reduces mortality rate or rate of nosocomial infection. The use of providone-iodine is NOT recommended to reduce VAP and may cause an increase risk of ARDS.

Guidelines for Management of Severe TBI, 4 th ed BLOOD PRESSURE THRESHOLDS Level I Level IIA Level IIB Level III Age 15-29 yrs: maintain SBP > 110 mm Hg Age 50-69 yrs: maintain SBP > 100 mmhg Age > 70 yrs: maintain SBP > 110 mmhg Guidelines for Management of Severe TBI, 4 th ed ICP MONITORING & THRESHOLDS Type of Level I Level IIA Level IIB Level III PEDIATRIC GUIDELINES Monitoring ICP Management of severe TBI using information from ICP monitoring is RECOMMENDED to reduce in-hospital and 2- week post-injury mortality NO LONGER SUPPORTED Use in pts with GCS 3-6 after resuscitation and abnormal CT Use in pts with severe TBI with normal CT scan with > 2 of the following: age > 40 yrs, motor posturing, or SBP < 90 mmhg (III) Consider use in pediatric pt with severe TBI ICP threshold Treat ICP > 22 mm Hg (increased mortality associated with ICP > 22) Combination of ICP, clinical an brain CT findings may be used to make management decisions (III) Treatment ICP threshold of 20 mm Hg.

Guidelines for Management of Severe TBI, 4 th ed CPP MONITORING & THRESHOLDS Type of Monitoring CPP Level I Level IIA Level IIB Level III PEDIATRIC GUIDELINES Management of severe TBI patients using guidelinesbased recommendations for CPP monitoring is recommended to decrease 2-wk mortality CPP threshold Recommended target CPP for survival and favorable outcomes is 60-70 mmhg (depends on autoregulatory status of the patient) Avoid aggressive attempts to maintain CPP > 70 mm Hg with fluids and pressors (risk of ARDS) (Level III): Minimum CPP 40 mmhg Guidelines for Management of Severe TBI, 4 th ed ADVANCED CEREBRAL MONITORING & THRESHOLDS Type of Level I Level IIA Level IIB Level III PEDIATRIC GUIDELINES Monitoring Advanced cerebral monitoring Jugular bulb monitoring of AVDO 2 as a source of information for management decisions may be considered to reduce mortality and improve outcomes at 3 and 6 months post injury Advanced cerebral monitoring threshold Jugular venous saturation of < 50% may be a threshold to avoid (III) If brain oxygenation monitoring is used, maintenance of partial pressure of brain tissue oxygen (PbtO 2 )10 mm Hg may be considered.

Revised Treatment Scheme Decompressive Craniectomy +Barbiturates Mild Hyperventilation* ICP Monitoring Hyperosmolar therapy *PaCO 2 35; Titrate to avoid SjvO 2 < 60 or PbtO 2 <15 ICP Monitoring CSF Drainage Elevate HOB; Sedation Seizure control/prophylaxis; Nutrition; Avoid hyperthermia AVOID HYPOTENSION (Adequate fluid resuscitation) AVOID HYPOXIA (Early airway, Oxygen) If refractory intracranial hypertension despite medical intervention Head CT without contrast STAT (If no head CT since ICP elevation

Significant Mortality and Morbidity Reductions Rapid transport to a trauma care facility Prompt resuscitation CT scanning Prompt evacuation of significant intracranial hematomas ICP monitoring and treatment Summary Avoid Secondary Brain Injury EARLY evacuation of mass lesions AVOID HYPOTENSION AVOID HYPOXIA Initial Assessment / Management ABCD; Early intubation Avoid excessive hyperventilation Fluid resuscitation Look for other injuries

Summary Coagulopathy Correct to decrease chance of lesion evolution Metabolic issues Avoid dextose & hypotonic fluids Avoid hyponatremia Fevers are bad for ICP Early nutrition Summary ICP & CPP Elevate HOB Maintain SBP > 100 110 mm Hg Maintain ICP < 22; CPP > 60 Do not hyperventilate Short acting sedatives Mannitol intermittent bolus dosing