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Neuroleptic malignant syndrome (Differential diagnosis (Serotonin syndrome…
Neuroleptic malignant syndrome
Idiosynchratic response to antipsychotic agents, not dose related
Differential diagnosis
Serotonin syndrome
MH
CNS infection
Thyroid storm
Dystonic reaction
Cerebral masses
Tetanus
Heat stress
Drug toxicities (lithium, atropine, MAOIs)
Lethal catatonia
Risk factors
Organic brain disease
Functional psychoses
Dehydration
Rapid loading of antipsychotics
Pathogenesis
Unclear
Neuroleptic induced perturbation of central thermo and neuroregulatory mechanisms
Abnormal reaction of skeletal muscle
Hypothalamic thermoregulation involves: noradrenaline, serotonin, cholinergic, central dopaminergic (D2) receptors
Basal ganglia involvement - Dopamine: muscle hypertonicity and contraction, further heat production
Abnormal reaction of predisposed skeletal muscle - Neuroleptic meds induce abnormal calcium activity (like MH)
Implicated drugs
Antiemetics: metoclopramide, droperidol, prochlorperazine, promethazine
Discontinuation of anti Parkinson's drugs
Typical antipsychotics: Chlorpromazine, Haloperidol, Perphenazine
Atypical antipsychotics: Clozapine, Risperidone, Quetiapine, Olanzapine
Features
Typically evolves rapidly over hours and manifests as tremor, hyperreflexia and clonus
Males>females
CNS
Encephalopathy, delirium, agitation, coma
Muscle rigidity
Extrapyramidal symptoms: chorea
Seizures
CVS
Autonomic instability
Renal / musculoskeletal
Rigidity (lead-pipe)
Rhabdomyelysis and elevated CK
Hyperkalaemia and ARF
Respiratory
Hypoventilation from chest wall rigidity
Other
Hyperthermia
Sweating
Investigations
CK, Leukocytosis, electrolyte disturbance, elevated hepatic enzymes, proteinuria, myoglobinuria, EEG (diffuse slowing)
Management
Mild to life threatening manifestations
Early recognition
Withdrawal of all neuroleptic, dopamine-depleting or dopamine-antagonist meds
Consider cessation of all psychotropic drugs
Supportive therapy
Fluid and electrolyte monitoring and optimisation
Acid-base monitoring and replacement
Renal protection strategies: rehydrate with crystalloid, alkalinise urine with sodium bicarb, consider diuretics (controversial), haemodialysis if refractory electrolyte imbalance/fluid overload (wont clear drugs)
Active cooling if hyperthermia
Benzos for agitation
Specific therapy
Bromocriptine (5mg oral QID) - Dopamine agonist: well tolerated, effective within 24hrs, reduces rigidity followed by temp reduction
Dantrolene 2mg/kg/day - to max 10mg/kg: More rapid resolution
Complications
Acute renal failure (rhabdo)
Resp failure, hypovent, aspiration
CVS collapse
Irreversible neurological injury (from extreme temps)
Prognosis
Renal failure increases mort rate up to ~ 50%
Prognosis good for survivors