Neuroleptic Agent Toxicity Treatment & Management

  • Author: Kathryn Ruth Challoner, MD, MPH, FACEP; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Jun 23, 2010
 

Prehospital Care

Be aware that patients with an antipsychotic (neuroleptic) overdose are at risk of rapid deterioration with coma, seizures, hypotension, or dysrhythmias. They all require transport to a hospital facility because the severity of overdose cannot be ascertained immediately after ingestion.

  • Prehospital treatment with activated charcoal, 1 g/kg, is indicated as soon as possible. This can be administered in the field if permitted by local protocol and if there is no risk of aspiration due to altered mental status.
  • Establish a large-bore IV line of isotonic sodium chloride solution in anticipation of possible hypotension or the need to administer medications.
  • Seizure activity usually responds to diazepam in the usual anticonvulsant doses.
  • Treat ventricular dysrhythmias with standard advanced cardiac life support (ACLS) pharmaceutical agents.
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Emergency Department Care

ED care varies, depending on the patient's condition and on the care already provided in the field.

  • No specific antidote for any of the neuroleptics exists.
  • The standard approach to resuscitation (airway, breathing, circulation, drugs, and environment [ABCDE]) is employed as indicated by the patient's condition. Active airway management is indicated for patients who are in shock, status epilepticus, coma, or cardiac arrest.
  • Placement of a Foley catheter may be necessary in comatose patients or those with shock or severe dehydration to monitor urine output and to obtain urine specimens in patients who may have urinary retention from the anticholinergic effects of the overdose.
  • Gastrointestinal decontamination
    • If used within an hour of ingestion, gastric lavage may be useful in decreasing the absorption of neuroleptics. Protect the patient's airway before lavage if an altered level of consciousness is present. Many toxicologists now advise against lavage and recommend administering activated charcoal orally or by nasogastric tube.
    • Activated charcoal with a saline cathartic remains the GI decontamination method of choice. Neuroleptics are generally well bound by activated charcoal and should be administered in standard doses as soon as possible postingestion.
    • Multiple dose activated charcoal is of limited benefit and cannot be used if an ileus is present.
  • Ipecac syrup is never recommended.
  • Hemoperfusion, hemodialysis, and forced diuresis are not effective.
  • Seizures are treated in a step-wise fashion, beginning with benzodiazepines (eg, diazepam, lorazepam) and followed by barbiturates (eg, phenobarbital, pentobarbital).
  • The combination of peripheral alpha-blockade and dehydration may result in severe hypotension during major tranquilizer overdose. Initial treatment involves administration of a volume challenge with isotonic sodium chloride solution. If the patient remains hypotensive after fluid challenge or manifests signs of cardiogenic shock, pressor agents may be required.
    • Norepinephrine is the preferred pressor agent in this circumstance because it has direct agonist effects.
    • Paradoxically, epinephrine or dopamine may lower the blood pressure because alpha-blockade from major tranquilizer causes unopposed beta-agonist peripheral vasodilation.
  • For patients manifesting NMS with worsening hyperthermia, immediate cooling measures, such as fans, wet cloths, ice packs in groin and axilla, and rectal acetaminophen, are indicated. Severe hyperthermia should be treated in aggressive and rapid manner with the ice bath immersion.
  • Dantrolene sodium (1-10 mg/kg) is recommended as adjunctive therapy for patients manifesting severe hyperthermia (rectal temperatures >105°F) and significant muscle rigidity.
    • Dantrolene is incompatible with acidic solutions and is mixed with sterile water for injection. It must be given directly by slow IV push or by intravenous piggyback into a large-bore IV near the needle with the IV fluid shut off. Great care must be taken to avoid extravasation into the tissues.
    • Dantrolene is given by 1-2 mg/kg doses until a maximum dose of 10 mg/kg or until the rectal temperature breaks.
    • Dantrolene may be effective in malignant hyperthermia by acting in dissociating the excitation-contraction coupling of skeletal muscles. While the precise mechanism of action and molecular targets are still incompletely known, dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. In the April 2004 issue of Anesthesia, Krause et al stated that studies have identified the ryanodine receptor (the major calcium release channel of the skeletal muscle sarcoplasmic reticulum) as a dantrolene-binding site.[5] A direct or indirect inhibition of the ryanodine receptor is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene acts primarily peripherally and has no effect on the cardiovascular or respiratory systems in this acute setting.
    • Some studies have questioned the efficacy of dantrolene[6] , but anecdotal reports still advocate for its use. Dantrolene should not be used as monotherapy.
  • Bromocriptine and amantadine are central dopaminergic agonists that may be effective in reversing the dopaminergic blockade caused by the neuroleptics. They have been reported as effective in treating NMS but work slowly (eg, over several days). They are given orally or by nasogastric tube, and they should be tapered gradually to avoid precipitation of another episode of NMS.
  • Oral levodopa, with or without carbidopa, and intravenous levodopa are therapies used more commonly in patients with Parkinson disease who develop NMS on sudden withdrawal of their dopaminergic therapy. Steroid pulse therapy may be useful in NMS for reducing the illness duration and improving symptoms in patients with Parkinson disease.
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Consultations

  • Notification of the regional poison control center is indicated.
  • In complex or severe cases, consult with the regional poison control center or a medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.
  • A psychiatric assessment is indicated once the patient's medical condition has stabilized to determine any suicidal intent.
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Contributor Information and Disclosures
Author

Kathryn Ruth Challoner, MD, MPH, FACEP  Clinical Professor of Emergency Medicine, Department of Emergency Medicine, Keck School of Medicine of the University of Southern California

Kathryn Ruth Challoner, MD, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Edward J Newton, MD, FACEP, FRCPC  Professor of Clinical Emergency Medicine, Chairman, Department of Emergency Medicine, University of Southern California Keck School of Medicine

Edward J Newton, MD, FACEP, FRCPC is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Royal College of Physicians and Surgeons of Canada, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Peter MC DeBlieux, MD  Professor of Clinical Medicine and Pediatrics, Section of Pulmonary and Critical Care Medicine, Program Director, Department of Emergency Medicine, Louisiana State University School of Medicine in New Orleans

Peter MC DeBlieux, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Radiological Society of North America, and Society of Critical Care Medicine

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.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP  Director of Medical Toxicology, Allegheny General Hospital

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.

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