Pharmacology and Reversal Agents: Onset, Offset, and Why Reversal Is Not Discharge
This domain tests drug selection by onset and offset, mechanism, weight-based dosing, and reversal, including why reversal does not end monitoring. Items commonly combine a dose history with an unexpected level of consciousness.
Sedative-hypnotics
- Midazolam: onset 2-3 minutes IV, duration 20-60 minutes, half-life 2-6 hours; the active metabolite accumulates in renal impairment and the elderly. Titrate 0.5-2 mg.
- Propofol: 1-2 mg/kg bolus; rapid redistribution, no reversal agent; dose-related hypotension and apnea.
- Ketamine: 1-2 mg/kg IV dissociative; preserves airway tone and respiration; increases secretions, heart rate and blood pressure; emergence reactions occur.
- Dexmedetomidine: alpha-2 agonist; load 0.5-1 mcg/kg over 10 minutes, infuse 0.2-0.7 mcg/kg/h; causes bradycardia and hypotension; no reversal agent.
- Etomidate: 0.3 mg/kg, hemodynamically neutral, associated with myoclonus and adrenal suppression.
Opioids and reversal
- Fentanyl: onset 2-3 minutes, peak 3-5 minutes; rapid high doses can cause chest wall rigidity.
- Naloxone: 0.04-0.4 mg IV titrated to respiration; half-life 30-90 minutes, shorter than most opioids, so renarcotization requires at least two hours of observation.
- Flumazenil: 0.2 mg IV increments to a maximum of 1 mg in standard reversal, up to 3 mg in overdose; risks include resedation, withdrawal seizures in benzodiazepine-dependent patients, and arrhythmia when tricyclics are co-ingested.
Neuromuscular blockade
- Sugammadex: 2 mg/kg at a train-of-four count of at least 2, 4 mg/kg at a post-tetanic count of 1-2, 16 mg/kg for immediate rescue; it encapsulates rocuronium and vecuronium.
- Neostigmine 0.03-0.07 mg/kg with an antimuscarinic; it has a ceiling effect and is ineffective at deep block.
Worked example
A 70-kg patient received midazolam 6 mg and fentanyl 100 mcg and is unresponsive with a respiratory rate of 8. Reasoning: reverse the opioid first with naloxone 0.04-0.08 mg increments, then titrate flumazenil 0.2 mg to respiration, and observe at least two hours because naloxone's half-life is shorter than fentanyl's clinical effect.
Traps that cost marks
- Giving full reversal doses and precipitating withdrawal, seizures or severe pain.
- Discharging immediately after reversal without a resedation observation period.
- Using neostigmine for deep block or without train-of-four confirmation.