Neuroleptic malignant syndrome

Background

  • Life threatening neurologic emergency associated with the use of neuroleptic agents[1]
    • Can occur with single dose, increasing dose, or same dose as usual
    • May also occur with withdrawal of anti-Parkinson medication or use of antiemetics
  • Develops over 1-3 days
  • Majority of deaths occur from complications of muscle rigidity

Clinical Features

  • Tetrad of:
  1. Altered Mental Status
    1. Agitated delirium progressing to stupor/coma
  2. Muscular Rigidity
    1. Generalized, "lead pipe" rigidity
  3. Hyperthermia
    1. >38C (87%)
    2. >40C (40%)
  4. Autonomic Instability
    1. Tachycardia
    2. Hypertension
    3. Diaphoresis

DDX

  1. Serotonin Syndrome
    1. More likely to have hyperreflexia, myoclonus, ataxis, N/V, diarrhea
    2. Rigidity and hyperthermia, if present, is less severe than in NMS
  2. Malignant Hyperthermia
    1. Distinguish by clinical setting (use of inhalational anesthetics or sux)
    2. Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
  3. Anticholinergic Toxidrome
    1. Diaphoresis, rigidity, elevated CK are absent
    2. Flushing, mydriasis, bladder distension are common
  4. Sympathomimetics
    1. Rigidity is not seen
  5. Meningitis/encephalitis
  6. Delirium Tremens
  7. Heat Stroke

Work-Up

  1. Total CK
    1. Typically >1000
    2. Correlates with degree of rigidity
  2. CBC
    1. WBC >10K is typical
  3. Chemistry
    1. May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
  4. UA
    1. Myoglobinuria (from rhabdo)
  5. LFT
    1. Transaminitis
  6. CT/LP
    1. CSF may have mildly elevated protein

Treatment

  1. Stop causative agent
    1. If precipitant is discontinuation of dopaminergic therapy, it should be restarted
  2. Supportive Care
    1. Fluid resuscitation
    2. Cooling measures
      1. Consider paralysis with nondepolarizing agents
    3. Agitation control with benzos
    4. Blood pressure control with clonidine or nitroprusside
  3. Medical therapy[2]
    1. Controversial; efficacy is unclear and disputed
      1. Dantrolene
        1. Skeletal muscle relaxant; may cause hepatotoxicity in pts w/ liver disease
        2. Consider only in pts with severe rigidity
        3. Give 0.25-2mg/kg IV q6-12hr
      2. Bromocriptine
        1. Dopamine agonist
        2. Give 2.5mg NG q6-8hr
      3. Amantadine
        1. Alternative to bromocriptine
        2. Give 100mg PO/NG initially; titrate up as needed to max dose 200mg q12hr
      4. ECT

Complications

  1. Dehydration
  2. Electrolyte imbalance
  3. ARF (rhabdo)
  4. Dysrhythmias
  5. ACS
  6. Respiratory failure
    1. Chest wall rigidity, aspiration PNA, PE
  7. DIC
  8. Seizure (hyperthermia, electrolyte derangements)
  9. Hepatic failure
  10. Sepsis

Source

<references>

  1. Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013
  2. Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20