Table 1.

Differential Diagnosis of Serotonin Syndrome

	Serotonin Syndrome	Neuroleptic Malignant Syndrome	Malignant Hyperthermia
Triggering agents	MAOIs, SSRIs, TCAs, SNRIs, amphetamines, serotonin antagonists, St. John’s Wort	Atypical antipsychotics, Typical antipsychotics, or dopamine antagonist	Volatile anesthetics or depolarizing neuromuscular blocking agent
Clinical Presentation	Hyperthermia (temperature >41.1°C suggest a severe case), progressive respiratory failure, altered mental status(agitation, akathisia, confusion), peripheral (especially lower extremities) hypertonicity, truncal rigidity, clonus, hyperreflexia Hunter’s Diagnostic Criteria Use of serotonergic agent and 1 of the following: • spontaneous clonus, • inducible clonus plus agitation or diaphoresis, • ocular clonus plus agitation or diaphoresis, • tremor and hyperreflexia, hypertonia • temperature above 38°C plus ocular or inducible clonus	Labile blood pressure, hyperventilation, tachycardia, hyperthermia, skin pallor, muscle rigidity, tremor, chorea, akinesia, dystonic movement, autonomic instability, seizures, mutism, abnormal reflexes, metabolic acidosis, elevated creatinine phosphokinase, rhabdomyolysis, leukocytosis, renal failure, sialorrhea	Early: Tachycardia, hyperventilation, a rapid increase in end-tidal CO2, hypoxia, hypertension (early), masseter spasm, generalized muscular rigidity, Late: hyperthermia, rhabdomyolysis, metabolic acidosis, acute renal failure, hyperkalemia, increased creatine phosphokinase, myoglobinuria, hypotension, arrhythmias, circulatory collapse
Treatment	Stop triggering agent, supportive care: cooling, hemodynamic support, benzodiazepines, cardiac monitoring, and prevention of neurological sequelae. Severe cases: Serotonin antagonist (Cyproheptadine and Olanzapine), sedation and paralysis with a non-depolarizing muscle relaxant, admission to a critical care unit	Stop triggering agent, supportive care: aggressive hydration, cooling, hemodynamic management, and prevention of neurologic sequelae. Severe cases: Benzodiazepine (Lorazepam 1 to 2 mg parenterally). Bromocriptine orally or via nasogastric tube (2.5mg 2 or 3 times daily for a hypodopaminergic state), Dantrolene IV (1 to 2.5mg/kg every 6 hours; max. of 10 mg/kg/day). Electroconvulsive therapy (ECT) may be used in refractory catatonic cases.	Stop triggering agent (maintain with non-triggering agents if surgery must continue), notify surgeon, call for help, supportive care: hyperventilate with 100% oxygen, hemodynamic management (avoid calcium channel blockers), hydration (diuresis to >1ml/kg/hr), manage acid-base status, dantrolene IV (2.5–10 mg/kg until decrease in ETCO2), charcoal filters, cool patient to <38°C, treat hyperkalemia, admission to critical care unit