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Toxicity, Neuroleptic Agents: Differential Diagnoses & Workup

Author: Kathryn Ruth Challoner, MD, FACEP, MPH, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Keck School of Medicine, University of Southern California.
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
Contributor Information and Disclosures

Updated: Sep 15, 2009

Differential Diagnoses

Delirium Tremens
Toxicity, Cocaine
Heat Exhaustion and Heatstroke
Toxicity, Lithium
Neuroleptic Malignant Syndrome
Toxicity, Methamphetamine
Rhabdomyolysis
Toxicity, Salicylate
Status Epilepticus
Toxicity, Selective Serotonin Reuptake Inhibitor
Torsade de Pointes
Withdrawal Syndromes
Toxicity, Anticholinergic
Toxicity, Antidepressant
Toxicity, Antihistamine

Other Problems to Be Considered

Malignant hyperthermia
Malignant catatonia
Serotonin syndrome
Thyrotoxicosis
Ecstasy toxicity

Workup

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 are available in most hospitals and are useful in identifying unknown ingestions. However, serum drug levels for major tranquilizers do not correlate well with the clinical severity of the overdose and are not useful.
  • 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.

Imaging Studies

  • No specific radiographs are routinely required; however, if appropriate, the patient's individual condition may require the following radiographs:
    • Chest x-rays are important in patients requiring intubation and in those with any respiratory distress. Comatose patients are at risk for aspiration and chest x-rays are routinely obtained for this reason.
    • Kidney-ureter-bladder (KUB) x-rays 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 x-rays should be performed before administration of activated charcoal because it may hinder radiographic visualization.
    • 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.

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 tests may be indicated as a qualitative screening tool to detect the presence of phenothiazines in either the serum or urine. Given the ready availability and reliability of qualitative colorimetric tests, bedside tests of limited accuracy are rarely indicated.

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).

More on Toxicity, Neuroleptic Agents

Overview: Toxicity, Neuroleptic Agents
Differential Diagnoses & Workup: Toxicity, Neuroleptic Agents
Treatment & Medication: Toxicity, Neuroleptic Agents
Follow-up: Toxicity, Neuroleptic Agents
References
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Further Reading

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Keywords

neuroleptic agent toxicity, neuroleptic poisoning, major tranquilizers, antipsychotic drugs, phenothiazines, aliphatics, piperidines, piperazines, thioxanthenes, butyrophenones, dibenzoxazepines, dihydroindolone, diphenylbutylpiperidine, benzisoxazole, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, NMS, seizures, hypothermia, arrhythmias, respiratory depression, involuntary movement disorders, dystonia, torticollis, oculogyric crisis, opisthotonus, dysrhythmia, acute dystonia, parkinsonism, akathisia, tardive dyskinesia, dantrolene, tardive dyskinesia

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Contributor Information and Disclosures

Author

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

Medical Editor

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 Health Sciences Center
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.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & 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.

Managing Editor

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of Emergency Medicine, Director of Medical Toxicology - Allegheny General Hospital, Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine
Disclosure: Nothing to disclose.

CME Editor

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, Department of Surgery, Section 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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