Neuroleptic Agent Toxicity Workup

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

Laboratory Studies

  • Perform laboratory tests depending on the nature of the presentation; patients with simple dystonia may require no tests, and patients with neuroleptic malignant syndrome may require multiple tests.
  • Qualitative assays for detection of antipsychotics are not widely available. In addition, serum drug levels for major tranquilizers do not correlate well with the clinical severity of the overdose and are not useful in acute treatment.
  • Because patients with major tranquilizer ingestion are often prescribed other medications, such as tricyclic antidepressants, benzodiazepines, or lithium, appropriate toxicology screening for these substances and for drugs of abuse is indicated. Serum toxicologic panels must always include a serum acetaminophen level.
  • Routine electrolytes, blood urea nitrogen, creatinine, glucose, and bicarbonate are useful in determining hydration status, renal function, acid base status, and in excluding hypoglycemia as the cause for the alteration in sensorium.
  • Pulse oximetry or arterial blood gas (ABG) sampling is indicated for patients in coma or with depressed gag reflex and diminished respiratory drive.
  • Patients with neuroleptic malignant syndrome are critically ill and frequently sustain end-organ damage to the brain, liver, heart, lungs, and kidneys. Consequently, appropriate laboratory tests to monitor such damage are indicated.
  • Creatinine kinase level
    • Continuous muscle contraction often produces muscle breakdown that is reflected by an increase in potassium, uric acid, and creatine kinase-MM.
    • Massive elevation of CK levels into the 100,000 range may occur and portends a significant risk of renal injury. Elevation of total CK higher than 3 times normal levels occurs in 50-100% of cases.
  • Urinalysis
    • Muscle breakdown products (eg, myoglobin) precipitate in the kidney, and tubular dysfunction may occur. Dehydration promotes this precipitation.
    • The urinalysis may reveal a moderate-to-strong reaction on the dipstick for occult blood. Microscopic analysis typically reveals very few RBCs, which is indirect evidence for the presence of myoglobinuria. In advanced myoglobinuria, the urine is dark brown.
    • Urine specific gravity and hourly output can guide rehydration efforts. Myoglobin assays can be performed to confirm the diagnosis but are usually not required.
  • Liver function tests: Severe sustained hyperthermia can result in hepatic necrosis, which is reflected in significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), and glutamic-pyruvic transaminase (GPT) liver enzymes.
  • Coagulation profile
    • Patients with NMS are prone to develop a coagulopathy or disseminated intravascular coagulation (DIC).
    • Establish baseline levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), platelets, and fibrinogen.
  • Various infections and septic shock may resemble NMS. Obtain a lactate level and blood, urine, and sputum cultures and perform a lumbar puncture to obtain cerebrospinal fluid (CSF) after a head CT for examination and culture.
  • Consider thyroid function tests (TFTs) because thyrotoxicosis can present with many features similar to NMS.
Next

Imaging Studies

No specific radiographs are routinely required; however, if appropriate, the patient's individual condition may require the following radiographs:

  • Chest radiographs are important in patients requiring intubation and in those with any respiratory distress. Comatose patients are at risk for aspiration, and chest radiographs are routinely obtained for this reason.
  • Kidney-ureter-bladder (KUB) radiographs may be helpful because phenothiazines are radio-opaque and are often observed on a plain film of the abdomen. This may be of some use if the ingestion is unknown and may help quantify the number of pills taken if the study is performed soon after ingestion. If obtained, KUB radiographs should be performed before administration of activated charcoal because it may hinder radiographic visualization. KUB radiographs cannot be used to rule out phenothiazine exposure.
  • CT scans of the head without contrast are indicated in some cases. Although not all patients with major tranquilizer ingestion require a CT scan of the head, it may be useful in comatose patients, those with seizures or status epilepticus, and in patients with focal neurologic deficits.
Previous
Next

Other Tests

  • A 12-lead electrocardiogram (ECG) and cardiac monitoring are indicated to look for potentially serious lengthening of the QT interval, AV block, or dysrhythmias. Symptoms generally present within 6 hours of ingestion; thus, monitoring patients for at least 6 hours is wise.
  • Ferric chloride or Phenistix test results can be positive with very high concentrations of phenothiazines in urine; however, due to lack of sensitivity and specificity, their use as bedside tests is rarely indicated.
Previous
Next

Procedures

  • A lumbar puncture (LP) is indicated, usually following CT scan of the brain, because meningitis may present in a manner similar to NMS (high fever, altered mental status).
Previous
Proceed to Treatment & Management
 
 
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.

References

  1. DeSilva P, Fenton M, Rathbone J. Zotepine for schizophrenia. Cochrane Database Syst Rev. Oct 18 2006;CD001948. [Medline].

  2. Haddad PM, Dursun SM. Neurological complications of psychiatric drugs: clinical features and management. Hum Psychopharmacol. Jan 2008;23 Suppl 1:15-26. [Medline].

  3. DE Hert M, Schreurs V, Vancampfort D, VAN Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry. Feb 2009;8(1):15-22. [Medline].

  4. Shirzadi AA, Ghaemi SN. Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome. Harv Rev Psychiatry. May-Jun 2006;14(3):152-64. [Medline].

  5. Krause T, Gerbershagen MU, Fiege M, et al. Dantrolene--a review of its pharmacology, therapeutic use and new developments. Anaesthesia. Apr 2004;59(4):364-73. [Medline].

  6. Reulbach U, Dutsch 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].

  7. Ananth J, Parameswaran S, Gunatilake S. Side effects of atypical antipsychotic drugs. Curr Pharm Des. 2004;10(18):2219-29. [Medline].

  8. Ananth J, Parameswaran S, Gunatilake S, et al. Neuroleptic malignant syndrome and atypical antipsychotic drugs. J Clin Psychiatry. Apr 2004;65(4):464-70. [Medline].

  9. Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin. May 2004;22(2):389-411. [Medline].

  10. Brady WA. Life threatening syndromes presenting with altered mentation and muscular rigidity. Emerg Med Rep. 1999;20:5160.

  11. Capel MM, Colbridge MG, Henry JA. Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol. Mar 2000;3(1):51-54. [Medline].

  12. Carbone JR. The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am. May 2000;18(2):317-25, x. [Medline].

  13. Correll CU, Penzner JB, Parikh UH, Mughal T, Javed T, Carbon M. Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child Adolesc Psychiatr Clin N Am. Jan 2006;15(1):177-206. [Medline].

  14. Dubois D. Toxicology and overdose of atypical antipsychotic medications in children: does newer necessarily mean safer?. Curr Opin Pediatr. Apr 2005;17(2):227-33. [Medline].

  15. Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotonergic disorders. Pain Med. Mar 2003;4(1):63-74. [Medline].

  16. Ferrando SJ, Eisendrath SJ. Adverse neuropsychiatric effects of dopamine antagonist medications. Misdiagnosis in the medical setting. Psychosomatics. 1991;32(4):426-32. [Medline].

  17. Fleishman SB, Lavin MR, Sattler M, Szarka H. Antiemetic-induced akathisia in cancer patients receiving chemotherapy. Am J Psychiatry. May 1994;151(5):763-5. [Medline].

  18. Gareri P, De Fazio P, De Fazio S, Marigliano N, Ferreri Ibbadu G, De Sarro G. Adverse effects of atypical antipsychotics in the elderly: a review. Drugs Aging. 2006;23(12):937-56. [Medline].

  19. Gil-ad I, Shtaif B, Shiloh R, Weizman A. Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms. Cell Mol Neurobiol. Dec 2001;21(6):705-16. [Medline].

  20. Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry. Aug 1998;155(8):1113-6. [Medline].

  21. Haupt DW. Differential metabolic effects of antipsychotic treatments. Eur Neuropsychopharmacol. Sep 2006;16 Suppl 3:S149-55. [Medline].

  22. Heiman-Patterson TD. Neuroleptic malignant syndrome and malignant hyperthermia. Important issues for the medical consultant. Med Clin North Am. Mar 1993;77(2):477-92. [Medline].

  23. Herrmann N, Lanctot KL. Do atypical antipsychotics cause stroke?. CNS Drugs. 2005;19(2):91-103. [Medline].

  24. Isbister GK, Balit CR, Kilham HA. Antipsychotic poisoning in young children: a systematic review. Drug Saf. 2005;28(11):1029-44. [Medline].

  25. Knight ME, Roberts RJ. Phenothiazine and butyrophenone intoxication in children. Pediatr Clin North Am. Apr 1986;33(2):299-309. [Medline].

  26. Le Blaye I, Donatini B, Hall M. Acute overdosage with clozapine: A review of the available clinical experience. Pharm Med. 1992;6:169.

  27. Le Blaye I, Donatini B, Hall M, Krupp P. Acute overdosage with thioridazine: a review of the available clinical exposure. Vet Hum Toxicol. Apr 1993;35(2):147-50. [Medline].

  28. Lee SH, Yang YY. Reversible neurotoxicity induced by a combination of clozapine and lithium: a case report. Zhonghua Yi Xue Za Zhi (Taipei). Mar 1999;62(3):184-7. [Medline].

  29. Love JN, Smith JA, Simmons R. Are one or two dangerous? Phenothiazine exposure in toddlers. J Emerg Med. Jul 2006;31(1):53-9. [Medline].

  30. McCarron MM, Boettger ML, Peck JJ. A case of neuroleptic malignant syndrome successfully treated with amantadine. J Clin Psychiatry. Sep 1982;43(9):381-2. [Medline].

  31. Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry. Jul 2006;51(8):480-91. [Medline].

  32. Nicholson D, Chiu W. Neuroleptic malignant syndrome. Geriatrics. Aug 2004;59(8):36, 38-40. [Medline].

  33. Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?. Curr Pharm Des. 2004;10(20):2463-75. [Medline].

  34. Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv. Sep 1998;49(9):1163-72. [Medline].

  35. Pierre JM. Extrapyramidal symptoms with atypical antipsychotics : incidence, prevention and management. Drug Saf. 2005;28(3):191-208. [Medline].

  36. Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. Aug 1997;154(8):1156-8. [Medline].

  37. Sakkas P, Davis JM, Janicak PG, Wang ZY. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull. 1991;27(3):381-4. [Medline].

  38. Sato Y, Asoh T, Metoki N, Satoh K. Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson's disease. J Neurol Neurosurg Psychiatry. May 2003;74(5):574-6. [Medline].

  39. Schneider SM. Neuroleptic malignant syndrome: controversies in treatment. Am J Emerg Med. Jul 1991;9(4):360-2. [Medline].

  40. Titier K, Canal M, Deridet E, et al. Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice. Toxicol Appl Pharmacol. Aug 15 2004;199(1):52-60. [Medline].

  41. Trenton A, Currier G, Zwemer F. Fatalities associated with therapeutic use and overdose of atypical antipsychotics. CNS Drugs. 2003;17(5):307-24. [Medline].

  42. Viejo LF, Morales V, Punal P, et al. Risk factors in neuroleptic malignant syndrome. A case-control study. Acta Psychiatr Scand. Jan 2003;107(1):45-9. [Medline].

  43. Wilt JL, Minnema AM, Johnson RF, Rosenblum AM. Torsade de pointes associated with the use of intravenous haloperidol. Ann Intern Med. Sep 1 1993;119(5):391-4. [Medline].

  44. Zetin M. Psychopharmacohazardology: major hazards of the new generation of psychotherapeutic drugs. Int J Clin Pract. Jan 2004;58(1):58-68. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.