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Neuroleptic malignant syndrome
From WikEM
Contents
Background
- Life threatening neurologic emergency associated with the use of neuroleptic agents[1][2]
- Can occur with single dose, increasing dose, or same dose as usual [3]
- Most often seen with "typical" high potency antipsychotics (haloperidol), but also occurs with newer "atypicals" (risperidone, olanzapine) and antiemetics (metoclopramide, promethazine)
- May also occur with withdrawal of anti-Parkinson medication
- Develops over 1-3 days
- Majority of deaths occur from complications of muscle rigidity
Clinical Features
- Tetrad of:[4]
- Altered mental status - Agitated delirium progressing to stupor/coma
- Muscular Rigidity - Generalized, "lead pipe" rigidity
- Hyperthermia >38C (87%); >40C (40%)
- Autonomic Instability - Tachycardia, Hypertension, Diaphoresis
Differential Diagnosis
- Serotonin Syndrome
- More likely to have hyperreflexia, myoclonus, ataxis, nausea and vomiting, diarrhea
- Rigidity and hyperthermia, if present, is less severe than in NMS
- Malignant Hyperthermia
- Distinguish by clinical setting (use of inhalational anesthetics or sux)
- Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
- Anticholinergic Toxicity
- Diaphoresis, rigidity, elevated CK are absent
- Flushing, mydriasis, bladder distension are common
- Sympathomimetics
- Rigidity is not seen
Altered mental status and fever
- Infectious
- Sepsis
- Meningitis
- Encephalitis
- Cerebral malaria
- Other
- Neuroleptic malignant syndrome
- Serotonin syndrome
- Malignant hyperthermia
- Sympathomimetic toxicity (cocaine, amphetamine, ketamine)
- Anticholinergic toxicity
- Heat stroke
- Delirium tremens
- Hypothalamic stroke
- Pheochromocytoma
- Thyroid storm
Evaluation
Workup
- Total CK
- Typically >1000
- Correlates with degree of rigidity
- CBC
- WBC >10K is typical
- Chemistry
- May show hypocalcemia, hypomagnesemia, hyperkalemia, metabolic acidosis
- Urinalysis
- Myoglobinuria (from rhabdo)
- LFT
- Transaminitis
- CT/LP
- CSF may have mildly elevated protein
Serotonin syndrome vs Neuroleptic malignant syndrome
- History of a new serotonergic drug or a dose increase of a serotonergic drug are helpful
- Serotonin syndrome is usually much more acute in onset than NMS which may develop over days or weeks
- Presence of ‘lead pipe’ rigidity is typical of NMS, while serotonin syndrome typically manifests with tremor and hyperreflexia
- Elevations in CK, LFTs, and WBC, coupled with a low iron level, distinguishes NMS from serotonin syndrome among patients taking both neuroleptic and serotonin agonist medications simultaneously
Management
- The causative agent should be stopped
- If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient
Supportive Care
- Agitation should be controlled with Benzodiazepines
- Fluid resuscitation
- Cooling measures
Directed Medical Therapy[5]
Controversial with unclear and disputed efficacy
- Dantrolene (skeletal muscle relaxant) - Consider only in patients with severe rigidity
- May cause hepatotoxicity in patients with liver disease
- 0.25-2mg/kg IV q6-12hr
- Bromocriptine (dopamine agonist)
- 2.5mg PO q6-8hr
- Amantadine (alternative to bromocriptine)
- 100mg PO initially; titrate up as needed to max dose 200mg q12hr
Disposition
- Admit
Complications
- Dehydration
- Electrolyte imbalance
- Acute renal failure (rhabdomyolysis)
- Dysrhythmias
- ACS
- Respiratory failure
- DIC
- Seizure (hyperthermia, electrolyte derangements)
- Hepatic failure
- Sepsis
See Also
References
- ↑ 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
- ↑ Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92
- ↑ Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109
- ↑ Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013
- ↑ Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20
