see also: [[Toxidromes]] > [!Key Points] > > - **risk dose:** > - Causes:: haloperidol, any anti-psychotic/ dopamine antagonist > - Tetrad symptoms: [[Hot and bothered|fever]], Rigidity, Mental status changes, Dysautonomia > - Antidote:: bromocriptine # Risk assessment - can occur after a single dose of a drug - OR - after treatment with the same agent at the same dose for many years usually start within 10 days of either starting a drug or increasing dosage sx generally progress over 1-3 days recovery ~2 weeks after ceasing the offending drug # Toxic Mechanism ## drugs - haloperidol - fluphenazine every class of dopamine antagonist has been implicated, including atypical agents - closapine - rispiridone - olanzapine ## mechanism # Clinical features > Most patients have a typical course of mental status changes first, followed by rigidity, hyperthermia, and autonomic dysfunction. similar to [[Serotonin Syndrome]] - **hyperthermia 38.5** (without other cause, may take 24 h to develop) - thought due to sustained muscle contraction and hypothalamic effect - extrapyramidal effects: - muscular rigidity ("lead pipe"), generalised, can be extream - parkinsonism: bradykinesia, akinesia, tremor - dystonias, abnormal posturing - altered mental status - autonomic instability - tachycardia, tachyponea, labile or high BP, diaphoresis, arrhythmias - May get myoglobulinuria/[[rhabdomyolysis]] may have **elevated CK** and **hyperkalemia** > usually moderate CK ~1000 (consensus suggest 3x upper limit of normal is required for dx) - Negative work-up for infectious, toxic, metabolic, or neurological causes ## DSM-5 criteria must have all 3 of: - exposure to dopamine blocker - muscle rigidity - hyperthermia AND at least 2 of: - diaphoresis - tremor - altered level of consciousness - labile BP - tachycardia - elevated CK - leukocytosis - mutism ## differences from serotonin syndrome table - **onset** (serotonin syndrome is <12 hours, NMS usually days) - **reflexes** (serotonin syndrome increased, NMS decreased) - **tone** (serotonin increased tone lower limbs > upper limbs and CLONUS, NMS lead pipe rigidity) - **pupils** (serotonin syndrome dilated pupils, NMS does not) - **mental state** (serotonin agitation or coma, NMS bradykinease, mutism) - **bowel sounds** (serotonin increased, NMS may have ileus) Important differences between serotonin syndrome and neuroleptic malignant syndrome: - NMS is a idiosyncratic reaction after prolonged exposure to neuroleptics or after withdrawal of a dopamine receptor agonist. - NMS usually develops over days or weeks - NMS usually accompanied by hyperthermia, severe muscle rigidity and rhabdomyolysis (not mydriasis, diarrhoea, hyperreflexia, myoclonus) - NMS frequently associated with multi-organ failure Both conditions are associated with increase in HR, BP,RR and raise in temperature. # DDx - infection - malignant hyperthermia - serotonin syndrome - anticholinergic syndrome - sympathomimetic syndrome - heat stroke - thyrotoxic storm # Treatment - active cooling (note antipyretics don't work) - benzos as needed - tx hyperkalemia - tx HTN with [[GTN]] ## Bromocriptine dopamine agonist 2.5mg orally (or NGT) Q8H endpoint for treatment is lowering temperature and improving muscle rigidity ## Dantrolene - hypothetical - # Difference from serotonin syndrome - **onset** (serotonin syndrome is <12 hours, NMS usually days) - **reflexes** (serotonin syndrome increased, NMS decreased) - **tone** (serotonin increased tone lower limbs > upper limbs and CLONUS, NMS lead pipe rigidity) - **pupils** (serotonin syndrome dilated pupils, NMS does not) - **mental state** (serotonin agitation or coma, NMS bradykinease, mutism) - **bowel sounds** (serotonin increased, NMS may have ileus)