Neuroleptic Malignant Syndrome in Emergency Medicine 

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

Background

The neuroleptic malignant syndrome (NMS) is a rare, but life-threatening, idiosyncratic reaction to a neuroleptic medication. The syndrome is characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction.

Although potent neuroleptics (eg, haloperidol, fluphenazine) are more frequently associated with NMS, all antipsychotic agents, typical or atypical, may precipitate the syndrome. For example, these agents have been associated with NMS: prochlorperazine (Compazine), promethazine (Phenergan), clozapine (Clozaril), and risperidone (Risperdal). NMS has also been associated with non-neuroleptic agents that block central dopamine pathways such as metoclopramide (Reglan), amoxapine (Ascendin), and lithium.[1]

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Pathophysiology

All medications implicated in NMS have dopamine D2-receptor antagonist properties. NMS has been noted following withdrawal of anti-Parkinson medication. The clinical syndrome is thought to be secondary to decreased dopamine activity in the central nervous system (CNS) either from blockade of dopamine D2-receptors or from decreased availability of dopamine itself, and NMS shares similarities with malignant hyperthermia and the serotonin syndrome. Blockade of dopamine neurotransmission in the nigrostriatum and hypothalamus results in muscular rigidity and altered thermoregulation, respectively. Sympathetic nervous system activation or dysfunction may play a significant role in the pathogenesis of NMS.[2, 3]

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Epidemiology

Frequency

United States

Incidence is uncommon, with rates ranging from 0.02-12.2% of patients treated with a neuroleptic medication. Prospective studies and pooled data from the literature report an incidence of 0.07-0.2%. Because of increased awareness of this syndrome and efforts at prevention, the incidence is probably less now than in the past.[1]

Mortality/Morbidity

The incidence of mortality, once reported at 20-30% is now estimated at 5-11.6%. Death usually results from respiratory failure, cardiovascular collapse, myoglobinuric renal failure, arrhythmias, or diffuse intravascular coagulation (DIC).

Morbidity from NMS includes rhabdomyolysis, pneumonia, renal failure, seizures, arrhythmias, DIC, and respiratory failure.

Sex

NMS has been reported to be more common in males, most likely because of increased use of neuroleptics in males. The male-to-female ratio is 2:1.

Age

No age predilection for NMS exists. NMS may occur in patients of any age who are receiving neuroleptics or other precipitating medications.

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Proceed to Clinical Presentation
 
 
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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  20. Reulbach U, Dütsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care. 2007;11(1):R4. [Medline].

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