TBI - Mahmoud (Fall 2024) - Handout PDF

TRAUMATIC BRAIN INJURY Sherif Mahmoud, B S c ( P h a r m ) , M S c , P h D , F N C S Clinical Professor and Associate Dean, Academic Faculty of Pharmacy and Pharmaceutical Sciences Copyrighted material contained...

TRAUMATIC BRAIN INJURY Sherif Mahmoud, B S c ( P h a r m ) , M S c , P h D , F N C S Clinical Professor and Associate Dean, Academic Faculty of Pharmacy and Pharmaceutical Sciences Copyrighted material contained herein is reproduced under ss. 29- University of Alberta 29.4 of the Canadian Copyright [email protected] Act. This document is available for your individual use; further distribution may infringe copyright  OBJECTIVES Students will be able to:  Describe the etiology and pathophysiology of traumatic brain injury (TBI)  Describe the epidemiology of TBI  Describe the severity and prognosis of TBI  Describe the work-up of TBI  Describe the acute management of TBI  Discuss the role of the pharmacist in acute TBI management  OUTLINE  Definition  Severity  Etiology  Epidemiology  Pathophysiology  Presentation and Work-up  Prognosis  Acute Management  Role of the pharmacist  TBI DEFINITION  Brain insult secondary to external mechanical force  CDC definition: “Disruption in the normal function of the brain that can be caused by a bump, blow, or jolt to the head or a penetrating head injury” Centers for Disease Control and Prevention. (2014). Report to Congress on Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation. National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention. Atlanta, GA  SEVERITY Centers for Disease Control and Prevention. (2014). Report to Congress on Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation. National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention. Atlanta, GA  GLASGOW COMA SCORE (GCS) Eye Response Verbal Response Motor Response 1. No eye opening 1. No verbal response 1. No motor response 2. Eye opening to pain 2. Incomprehensible 2. Extension to pain sounds 3. Eye opening to 3. Inappropriate words 3. Flexion to pain verbal command 4. Eyes open 4. Confused 4. Withdrawal from spontaneously pain 5. Orientated 5. Localizing to pain 6. Obeys commands Teasdale et al. Lancet. 1974: 2(7872);81-84.  ETIOLOGY - CDC Source: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Division of unintentional injury prevention http://www.cdc.gov/traumaticbraininjury/get_the_facts.html  EPIDEMIOLOGY  The leading cause of death and disability in children and young adults  Canada 1 , 2  Incidence  Severe TBI ~12 per 100,000  Mild TBI can reach up to ~ 600 per 100,000  United States - brain trauma foundation  Incidence  ~ 1.7 million per year  Severe TBI ~13 per 100,000  ~ 1.5 million emergency room visits per year  ~ 52,000 deaths per year from TBI  Males are twice more likely to experience a TBI than females 1. D. A. Zygun et al., “Severe Traumatic Brain Injury in a Large Canadian Health Region,” The Canadian Journal of Neurological Sciences 32 (2005): pp. 87–92. 2. J. D. Cassidy et al., “Incidence, Risk Factors and Prevention of Mild Traumatic Brain Injury: Results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury,” Journal of Rehabilitation Medicine 43 Suppl (2004): pp. 28–6  PATHOPHYSIOLOGY  Primary Injury  At the time of the insult  Mechanism  Contact  Impact e.g. hitting the head with an object  Penetrating e.g. gun shot  Sudden acceleration/deceleration  Types of injuries  Focal – ICH, SDH, SAH, contusions, skull fractures  Diffuse – Diffuse axonal injury  Mixed  Can be severe enough leading to death  Secondary Injury  Minutes to days following primary injury  PRESENTATION AND WORK-UP  GCS score  Presence of:  Seizures  Headache, dizziness  Nausea, vomiting  Focal neurological symptoms  Hemodynamic instability  Labs  Electrolytes  ABG  ETOH level, drug screening  Imaging  CT head  PROGNOSIS  Prognosis ranges from complete resolution of symptoms to partial or permanent disability to death  Predictors of poor outcome  Increasing Age  Low GCS score  Abnormal pupillary reactivity  Systemic hypotension  CT scan  Presence of hematoma  Presence of SAH  Midline shift  Absent/compressed cisterns ACUTE MANAGEMENT Severe TBI  GOALS OF THERAPY Minimize morbidity and mortality Short-term goals Minimize secondary injury Avoid medical complications  CRITICAL CARE MANAGEMENT  Hemodynamic support and ventilation  Surgical interventions  Sedation  Control ICP  Seizure prophylaxis  Correct electrolyte disturbances  DVT prophylaxis  Inf ection prophylaxis  Stress ulcer prophylaxis  Temperature control  Glycemic control  Nutrition  HEMODYNAMIC SUPPORT AND VENTILATION  Goal is to avoid systemic hypotension and provide adequate tissue oxygenation  Target SBP > 90, MAP > 60 mmHg  Fluid resuscitation  Vasopressors if fluids fail  Target oxygen saturation > 90% and PaO2 > 60 mmHg  Mechanical ventilation  SURGICAL INTERVENTIONS  External ventricular drainage (EVD)  ICP monitoring  Control of hydrocephalus  Surgical evacuation of intracranial hematomas  Surgical removal of foreign bodies e.g bullets  Decompressive craniectomy  For refractory intracranial hypertension  SEDATION  To control agitation and pain and facilitate mechanical ventilation  Reduce ICP  Reduce brain oxygen consumption  Agents  Opioids: Fentanyl  Propofol (see next slide)  Anxiolytics: Midazolam  Neuromuscular blockers  Limited to elevated ICP resistant to first line agents  PROPOFOL  Rapid acting sedative-hypnotic  Mechanism: GABA-A receptor agonist  Onset: minutes  Duration: minutes – continuous infusion needed for sustained effects  Easy titration, rapid offset of action  Antiseizure properties  Possible neuroprotective properties  Concern: propofol infusion syndrome, hemodynamic instability, respiratory depression  Formulation: Lipid emulsion for IV administration  CONTROL ICP  Target cerebral perfusion pressure (CPP) > 60 mmHg  CPP is a function of MAP and ICP (CPP = MAP – ICP)  Target ICP < 20 mmHg  Sedation, analgesia  CSF drainage (EVD)  Hyperventilation  Acute reduction in PaCO2 causes cerebral vasoconstriction  For temporary relief of ICP  Hyperosmolar agents  Mannitol  Hypertonic saline  Neuromuscular blockers  CONTROL ICP  Decompressive surgery  Pentobarbital coma  Dose: 10 mg/kg over 30 min then 15 mg/kg over 3 h then infusion 1-2 mg/kg/h to target ICP60 and EEG burst suppression  Requires continuous EEG, ECG, mechanical ventilation and hemodynamic support  Aim to reduce brain metabolic demand  Adverse effects: hypotension, decreased GI motility  Other therapies  Hypothermia ≈ - NEJM Oct 2015  High dose corticosteroids  Not recommended  Associated with increased mortality - Lancet 2004;364:1321–1328  MANNITOL Dosing 0.25 – 1 g/kg iv q4h or less frequent Side effects Hypotension, ARF Mechanism 1. Increase osmotic gradient causing water to come out of intracellular compartment relieving cerebral edema 2. Plasma expansion and reduction of blood viscosity with resulting increased cerebral blood flow Comments Onset: within minutes Duration: 1.5-6 h Monitoring: Hold if sodium > 155, serum osmolality > 320 More recently hold if osmole gap > 20 (better reflection of mannitol concentration) to avoid ARF  HYPERTONIC SALINE Dosing 3% saline is generally used Used as boluses (1-2 ml/kg) or continuous infusion Other institutions might use concentrations up to 23.4% Mechanism Increase osmotic gradient causing water to come out intracellular compartment relieving cerebral edema Comments Superior to mannitol?  SEIZURE PROPHYLAXIS  All TBI patients presenting with seizures should be treated  If the patient did not seize:  Phenytoin (or levetiracetam) x 7 days is recommended  Reduce early post-traumatic seizures in high risk patients but no effect on late post-traumatic epilepsy  Risk factors for early seizures:  GCS < 10  Penetrating head injury  Depressed skull fracture  Presence of ICH, SDH, cerebral contusion  OTHER TREATMENT MODALITIES  Correct electrolyte disturbances  DVT prophylaxis  Pneumatics initially  Pharmacological DVT prophylaxis if not contraindicated  LMWH  Unfractionated heparin  Infection prophylaxis  Suggested for penetrating head trauma. Duration not clear.  Treatment of infection complications is recommended  Stress ulcer prophylaxis  H2 receptor antagonists vs PPIs  OTHER TREATMENT MODALITIES  Temperature control  Noromothermia must be achieved  Acetaminophen, ibuprofen, cooling blankets, intravascular cooling  Glycemic control  Avoid hyper and hypoglycemia  Suggested target glucose 6-10  Nutrition  Early initiation of feeding might be associated with better outcome  ROLE OF THE PHARMACIST IN CRITICAL CARE MANAGEMENT OF TBI  Pharmacists play an important role in the medical management of TBI patients  Identify DRPs related to PmHx and medication history  Monitor  Hyperosmolar therapy  Infection complications  Seizure control  Temperature and glycemic control  ADRs of medications including sedation  Make sure that patient has proper  Stress ulcer prophylaxis  DVT prophylaxis  Seizure prophylaxis  AUGMENTED RENAL CLEARANCE  Enhanced renal function seen in critically ill  Definition: creatinine clearance > 130 ml/min/1.73m2  Risk Factors: Young, Male, Trauma  Pathophysiology: not fully known  Impact: Enhanced clearance of renally eliminated drugs  Examples: β-lactam antimicrobials, vancomycin, aminoglycosides, levetiracetam