Guidelines and Beyond: Traumatic Brain Injury

Transcription

1 Guidelines and Beyond: Traumatic Brain Injury Aimee Gowler, PharmD, BCCCP, BCPS Neuromedicine Critical Care Clinical Pharmacy Specialist UF Health Shands Disclosures I have no financial interests to disclose. Objectives Discuss early, short-term prophylactic hypothermia in traumatic brain injury. Examine deep vein thrombosis prophylaxis literature in traumatic brain injury. Evaluate the evidence regarding prophylaxis of early post-traumatic seizures in traumatic brain injury. Traumatic Brain Injury (TBI) in the United States 2013 Statistics Total of 2.5 million ED visits More than 282,00 hospitalizations Contribute ~30% of all injury deaths in the United States ED: Emergency department Taylor et al. CDC MMWR 2017 Brain Trauma Foundation (BTF) 4 th Edition of BTF Guidelines for Severe TBI released online in 2016 Initiated within 24 hours of injury Recommendation Levels Level I: based on high-quality body of evidence Level IIA: based on moderate-quality body of evidence Level IIB and III: based on low-quality body of evidence Goal temperature from C Proposed benefit Decrease intracranial pressure Neuroprotectant 1

2 Proposed Hypothermia Benefits Prevent Increase in NO Synthesis Preserve Brain ATP Supply Decrease Cerebral Metabolic Rate Neuroprotection Improve Brain Glucose Utilization BTF Guidelines for Level IIB Early (within 2.5 hours), short-term (48 hour post-injury), prophylactic hypothermia is not recommended to improve outcomes in patients with diffuse injury. Reduce Glutamate Release Suppress NMDA Receptor Phosphorylation NMDA: non-n-methyl-d-aspartic acid ATP: adenosine triphosphate Karnatovskaia et al. Neurohospitalist 2014 Duration Abiki Jiang Liu 2006 Marion day Qiu (average) Target ( C) Rewarming Rate 1 C per day 1 C per 4 hrs 0.5 C per 2 hrs 0.5 C per 2 hrs 1 C per hr Natural rewarming 1 C per hr Natural rewarming Results ± ± - Futile + + ± + Neurocritcal Care Society (NCS) Guidelines for Targeted Temperature Management (TTM) Conditional recommendation, moderate quality evidence We suggest longer duration TTM for severe TBI patients should ICP control be the goal. Strong recommendation, moderate quality evidence We recommend using controlled normothermia to reduce fever burden with fever refractory to conventional therapy. Madden et al. Neurocrit Care 2017 Hypothermia/TTM Clinical Pearls Prophylactic hypothermia has not been shown to improve outcomes. Fever should be treated in TBI and consideration of use of TTM interventions to maintain hypo- or normothermia should take place after fever control is unable to be obtained. Deep Vein Thrombosis (DVT) in TBI TBI induces early activation of coagulation Incidence Up to 54% without prophylaxis 25% in isolated TBI with sequential compression devices Increased Risk Injury Severity Score Subarachnoid hemorrhage Age Extremity injury Nekludov et al. J Neurotrauma 2007 Geerts et al. NEJM 1994 Denson et al. Am J Surg 2007 Ekeh et a. J Trauma 2010 Getty images 2

3 BTF Guidelines for DVT Prophylaxis Level III LMWH or low-dose UFH may be used in combination with mechanical prophylaxis. However, there is an increased risk for expansion of intracranial hemorrhage. In addition to compression stockings, pharmacologic prophylaxis may be considered if the brain injury is stable and the benefit is considered to outweigh the risk of increased intracranial hemorrhage. There is insufficient evidence to support recommendations regarding the preferred agent, dose, or timing of pharmacologic prophylaxis for deep vein thrombosis. LMWH: low molecular weight heparin UFH: unfractionated heparin Intervention Protocol Medication Farooqi, 2013 Nickele, 2013 Kim, 2002 Pre-post protocol: 24 hrs post-repeat CT with stable ICH Enoxaparin 30 mg BID or 0.5 mg/kg BID or UFH 5000 units TID Pre-post protocol: 24 hrs postrepeat CT with stable ICH Dalteparin 5000 units daily or UFH 5000 units TID Initiation 159 hrs vs 60.8 hrs (average) 4.9 vs 3.4 (average) %with prophylaxis Outcome N/A UFH 5000 units BID <72 hrs vs >72 hrs 59.8% vs 64.3% 45.8% vs 72.4% N/A DVT: 5.61% vs 0%, p=0.008 PE: 3.74% vs 0.78%, p=0.18 Increased ICH: 2.8% vs 0.7%, p=0.33 DVT: 4.2% vs 6.9% PE: 4.2% vs 5.75% CT: computed tomography BID: twice daily PE: pulmonary embolism ICH: intracranial hemorrhage TID: three times daily DVT: 4% vs 6% PE: 4% vs 0% NCS Guidelines for DVT Prophylaxis Weak recommendation and low-quality evidence We recommend initiating IPC for VTE prophylaxis within 24 hours of presentation of TBI or within 24 hours after completion of craniotomy as supported by evidence in ischemic stroke and postoperative craniotomy We recommend initiating LMWH or UFH for VTE prophylaxis within hours of presentation in patients with TBI and ICH, or 24 hours after craniotomy. We recommend using mechanical devices such as IPC for VTE prophylaxis in patients with TBI, based on data from other Neurological injuries such as ischemic stroke. BTF and NCS Comparison BTF NCC Mechanical Compression stockings IPC Drug UFH/LMWH UFH/LMWH Dose?? Timing? Post craniotomy: Within 24 hours post-operative TBI and ICH: Within hours TBI: Within 24 hours IPC: Intermittant pneumatic compression Nyquist et al. Neurocrit Care 2016 Nyquist et al. Neurocrit Care 2016 Unanswered Questions for TBI DVT Prophylaxis When should pharmacologic prophylaxis be initiated? Which medication and dose should be used? DVT Prophylaxis Clinical Pearls Assess TBI patients daily for initiation of DVT prophylaxis No definitive difference between LMWH and UFH but dose may play a role Ensure appropriate LMWH dosing for renal function 3

4 Post-traumatic Seizures (PTS) Onset post injury Early: within 7 Late: after 7 Incidence Clinical seizures in up to 12% Subclinical seizures up to 20-25% Risk Factors for Early Posttraumatic Seizures (PTS) GCS 10 Immediate seizures Cortical contusion Linear or depressed skull fracture Age > 65 years old Penetrating head injury GCS: Glasgow Coma Score Subdural, epidural, or intracerebral hematoma More than 30 minutes post-traumatic amnesia Chronic alcoholism Torbic et al. Am J Health Syst Pharm 2013 BTF Guidelines for Post-traumatic Seizure (PTS) Prophylaxis Level IIA Prophylactic use of phenytoin or valproate is not recommended for preventing late PTS Phenytoin is recommended to decrease incidence of early PTS (within 7 of injury), when the overall benefit is thought to outweigh the complications associated with such treatment. However, early PTS have not been associated with worse outcomes. At the present time there is insufficient evidence to recommend levetiracetam compared with phenytoin regarding efficacy in preventing early post-traumatic seizures and toxicity. Unanswered Questions for TBI Seizure Prophylaxis Which medication and dose should be used? What is the optimal duration? Levetiracetam vs Phenytoin LEV dose PHT dose Duration PHT Levels Outcomes Prospective: Inaba, mg BID 20 mg/kg load and 5 mg/kg/day 7 Daily Seizure: 1.5% vs 1.5%, p=0.997 Mortality: 5.4% vs 3.7%, p=0.236 Retrospective: Caballero, mg BID ± 1000 mg load 4 mg/kg/day ± 13 m/kg load LEV 9 vs PHT 14 5 levels/patient (median) Seizure: 28% vs 29%, p=0.99 Prospective: Szaflarski, mg/kg load mg BID 20 mg/kg load + 5 mg/kg/day Prospective vs Historical: Jones, mg BID Not defined 7 7 Day 2 and 6 Seizure: 14.7% vs 16.7%, p=1 Not defined Abnormal EEG: 53.3% vs 0%, p=0.003 Seizure: 3.1% vs 0%, p=0.556 LEV: levetiracetam PHT: phenytoin mg: milligram kg: kilogram BID: twice daily EEG: electroencephalogram Post-traumatic Seizure Prophylaxis Clinical Pearls Levetiracetam is an acceptable alternative to phenytoin If using phenytoin for PTS prophylaxis, include loading dose and follow levels for dose adjustments and mini-loads Be compliant with early PTS prophylaxis 4

5 Guidelines and Beyond: Traumatic Brain Injury Aimee Gowler, PharmD, BCCCP, BCPS Neuromedicine Critical Care Clinical Pharmacy Specialist UF Health Shands 5