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Neuroleptic Malignant Syndrome. Recognition, Risk factors and Management. Pathophysiology. Relative lack of dopamine dopamine receptor blockade inadequate dopamine production. Pathophysiology. Supporting evidence neuroleptic drugs block dopamine receptors
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Neuroleptic Malignant Syndrome Recognition, Risk factors and Management
Pathophysiology • Relative lack of dopamine • dopamine receptor blockade • inadequate dopamine production
Pathophysiology • Supporting evidence • neuroleptic drugs block dopamine receptors • occurs with other dopamine blocking drugs • occurs on sudden withdrawal of antiparkinsonian therapy • responds to dopamine agonists
Clinical features • Essential • recent or current therapy with dopamine blocking drug • neuroleptic • other drug eg metoclopramide • recently stopped a dopamine agonist eg L-dopa
Clinical features • Major (all within 24 h) • fever > 37.5oC (no other cause) • autonomic dysfunction • extrapyramidal features
Autonomic dysfunction • 2 or more of • hypertension or labile BP • systolic > 30 mmHg above baseline or • diastolic > 20 mmHg above baseline • variability of > 30 mmHg systolic or >20 mmHg diastolic between readings • tachycardia (pulse > 30 bpm above baseline) • diaphoresis (intense) • incontinence • tachypnoea (> 25 breaths/min)
Extrapyramidal features • 2 or more of • bradykinesia • lead-pipe or cogwheel rigidity • resting tremor • sialorrhoea • dysphagia • dysarthria/mutism
Minor features • Support but are not required for diagnosis • rise in creatinine kinase • altered sensorium/delirium • leucocytosis > 15,000x109/L • low serum iron • Help confirm diagnosis • therapeutic response to dopamine agonist
Risk factors • Incidence 1% (0.02–3.23) • Pre-NMS • psychomotor agitation • dehydration
Risk factors • Related to treatment • neuroleptic dose in first 24h > 600 mg of chlorpromazine • maximum dose in any 24h > 600 mg of chlorpromazine • required restraint or seclusion • Associated • past ECT
Management • High risk patients • monitor temperature tds • monitor blood pressure tds • record episodes of diaphoresis • On suspicion • assess for other medical illness • FBC, MBA, CK, serum iron • On diagnosis • withdraw all dopamine blocking drugs
Drug therapy • Bromocriptine • 2.5 mg q8h up to 5 mg q4h • continue for 7–10 days after resolution then taper over 1–2 weeks (except depot preparations) • Dantrolene • 2–3 mg/kg • extreme rigidity, very high fever (> 40oC), unable to tolerate oral treatment
Other therapy • Benzodiazepines • to control agitation/delirium • ECT • refractory to adequate trial of dopamine agonist/supportive care • after resolution of acute features • remain catatonic or • develop ECT-responsive psychotic features • suspected acute lethal catatonia