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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

Neuroleptic Malignant Syndrome

Recognition, Risk factors and Management

pathophysiology
Pathophysiology
  • Relative lack of dopamine
    • dopamine receptor blockade
    • inadequate dopamine production
pathophysiology1
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
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 features1
Clinical features
  • Major (all within 24 h)
    • fever > 37.5oC (no other cause)
    • autonomic dysfunction
    • extrapyramidal features
autonomic dysfunction
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
Extrapyramidal features
  • 2 or more of
    • bradykinesia
    • lead-pipe or cogwheel rigidity
    • resting tremor
    • sialorrhoea
    • dysphagia
    • dysarthria/mutism
minor features
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
Risk factors
  • Incidence 1% (0.02–3.23)
  • Pre-NMS
    • psychomotor agitation
    • dehydration
risk factors1
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
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
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
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