Neuroleptic Malignant Syndrome Emergency Management

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal idiosyncratic reaction to dopamine D2 receptor antagonists with mortality of 5-20%. It develops within 24 hours to 4 weeks of drug initiation, dose escalation, or addition of another dopamine antagonist. The pathophysiology involves central dopaminergic blockade in the hypothalamus, basal ganglia, and corticospinal tracts.

Triggering medications include first-generation antipsychotics (haloperidol, fluphenazine, chlorpromazine), second-generation antipsychotics (olanzapine, risperidone, quetiapine, paliperidone), antiemetics (metoclopramide, prochlorperazine, droperidol), tetrabenazine, and abrupt withdrawal of dopaminergic agents in Parkinson disease. Risk factors include rapid dose titration, IM depot administration, dehydration, agitation, restraint use, and previous NMS episode.

Clinical tetrad includes hyperthermia (>38 degrees C, often >40), severe lead-pipe muscle rigidity with bradykinesia, autonomic instability (labile blood pressure, tachycardia, diaphoresis, sialorrhea), and altered mental status (delirium to coma). Laboratory findings include creatine kinase elevation (often >1000), leukocytosis, elevated liver enzymes, metabolic acidosis, and acute kidney injury from rhabdomyolysis. Management includes immediate discontinuation of triggering agent, ICU admission, aggressive cooling, IV fluids targeting urine output 200-300 mL/h, electrolyte correction, dantrolene 1-2.5 mg/kg IV every 6 hours for severe cases, bromocriptine 2.5 mg every 6-8 hours, benzodiazepines for agitation, and treatment of complications (renal failure, DIC, aspiration). Restart antipsychotics cautiously after 2 weeks if needed, preferring lower-potency or different class.