Neuroleptic Malignant Syndrome in Emergency Medicine Clinical Presentation

  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Sep 1, 2010
 

History

Neuroleptic malignant syndrome (NMS) is more likely to develop following initiation of neuroleptic therapy or an increase in the dose. The onset can be within hours, but, on average, it is 4-14 days after initiation of therapy. However, NMS can occur at any time during neuroleptic use, even years after initiating therapy. Of those patients who develop NMS, 90% of them do so within 10 days.

NMS is a heterogeneous syndrome that spans a broad severity continuum. The diagnosis is made on clinical grounds based on the presence of certain historical, physical, and laboratory findings. The diagnosis is confirmed, but not necessarily excluded, by the presence of the following 5 criteria:

  • Recent treatment with neuroleptics within past 1-4 weeks
  • Hyperthermia (temperature above 38°C)
  • Muscular rigidity
  • At least 5 of the following:
    • Change in mental status
    • Tachycardia
    • Hypertension or hypotension
    • Diaphoresis or sialorrhea
    • Tremor
    • Incontinence
    • Increased creatinine phosphokinase (CPK) or urinary myoglobin level
    • Leukocytosis
    • Metabolic acidosis
    • Autonomic instability
  • Exclusion of other drug-induced, systemic, or neuropsychiatric illness
  • Clinical signs
    • Hyperthermia
    • Profuse diaphoresis
    • Generalized rigidity (lead pipe)
    • Mental status changes
  • Atypical NMS[4]
    • Patients with NMS may present with atypical features that do not include muscle rigidity or hyperthermia at the onset.
    • Hyperthermia and muscle rigidity may develop over time or not at all.
    • Atypical presentation of NMS may be more common after treatment with the atypical class of antipsychotics.
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Physical

Signs of neuroleptic malignant syndrome may include the following:

  • Hyperthermia
  • Diaphoresis
  • Generalized muscular rigidity (lead pipe)
  • Tachycardia
  • Hypertension or hypotension
  • Tremor
  • Incontinence
  • Altered mental status
  • Tachypnea
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Causes

All classes of neuroleptics (dopamine D2-receptor antagonists) are associated with NMS, and dopamine receptor blockade is considered the cause of NMS.

  • Experimental blockade of dopamine in the striatum can cause rigidity, tremor, and rhabdomyolysis.
  • Blockade of dopamine in the hypothalamus can cause impaired temperature regulation and hyperthermia.
  • This theory does not explain why only some patients develop NMS. It also does not explain why patients rechallenged with neuroleptics do not always redevelop NMS.

Risk factors for developing NMS include the following:

  • Increased ambient temperature
  • Dehydration
  • Patient agitation or catatonia
  • Rapid initiation or dose escalation of neuroleptic
  • Withdrawal of anti-Parkinson medication
  • Use of high-potency agents and depot intramuscular preparations
  • History of organic brain syndrome or affective disorder
  • History of NMS
  • Concomitant use of predisposing drugs (eg, lithium, anticholinergic agents)
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Contributor Information and Disclosures
Author

Theodore I Benzer, MD, PhD  Assistant Professor in Medicine, Harvard Medical School; Director of Clinical Operations, Director of Toxicology, Chair of Quality and Safety, Department of Emergency Medicine, Massachusetts General Hospital

Theodore I Benzer, MD, PhD is a member of the following medical societies: Alpha Omega Alpha and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Mark S Slabinski, MD, FACEP, FAAEM  Vice President, EMP Medical Group

Mark S Slabinski, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Ohio State Medical Association

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD  Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD  Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

References

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