Cause:Neuroleptic drugs (major tranquilizers) including phenothiazines, butyrophenones, thioxanthenes, loxapine, and rarely clozapine (Nejm 1991;324:746)
Pathophys:Diminished CNS dopamine
~0.2-0.5% of patients given these drugs will develop; unrelated to dose; 96% of cases occur within 30 d of starting the drug; 30% of those who have had before will get again if reexposed. Incidence is increased with exhaustion, dehydration, organic brain syndrome, and depot phenothiazines
Sx:1-3 d onset, up to 5-10 d after drug stopped, or 10-30 d after im depot types
Si:Fever (>38°C/100.4°F in 87%), rigidity and hypertonia ("lead pipe") (97%), changes in mental status (97%), autonomic instability (pallor, diaphoresis, BP changes, tachycardia, arrhythmias), akinesia, involuntary movements, tremor
Precipitated by dopamine agonists like metaclopramide (Reglan), or amoxapine (Asendin) sometimes
Respiratory failure, myoglobinuric renal failure, cardiovascular collapse, arrhythmias, pulmonary embolus
r/o malignant hyperthermia (Malignant Hyperthermia), idiopathicACUTE LETHAL CATATONIA, drug interactions with MAO inhibitors, central anticholinergic crisis, which responds to iv physostigmine, tetanus, stiff man syndrome (Tetanus, Lockjaw), myotonia, meningitis or encephalitis, thyroid storm, cocaine OD (Cocaine Use)
Lab:
Chem:CPK elevated, may be >16000 IU; aldolase elevated; elevated LFTs (due to pyrexia induced fatty changes?)
Hem:Wbc 15000-30000 with L shift
Urine:Myoglobinuria (67%)
Rx:
Stop neuroleptics then give
Nitroprusside iv/minoxidil po worked in 1 patient when dantrolene failed, controlled fever and BP (Ann IM 1986;104:56)
Prevent myoglobinuric ATN by iv fluids, mannitol infusion, and NaHCO3 iv to alkalinize the urine