Neuroleptic Agent Toxicity Workup

Updated: May 11, 2022
  • Author: Jay T Melton, MD; Chief Editor: Michael A Miller, MD  more...
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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 (NMS) may require multiple tests.

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.

Because patients with major tranquilizer ingestion are often prescribed other medications, such as tricyclic antidepressants, benzodiazepines, or lithium, [17] appropriate toxicology screening for these substances and for drugs of abuse is indicated. A serum acetaminophen concentration should always be obtained in cases of ingestions with suicidal intent.

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.

The creatine kinase level should be checked. Continuous muscle contraction often produces muscle breakdown that is reflected by an increase in potassium, uric acid, and creatine kinase–MM. Massive elevation of creatine kinase levels into the 100,000 U/L range may occur and portends a significant risk of renal injury. Elevation of total creatine kinase higher than 3 times normal levels occurs in 50-100% of cases.

Urinalysis should be performed. Muscle breakdown products (eg, myoglobin) precipitate in the kidney, and tubular dysfunction may occur. Dehydration promotes this precipitation. Urinalysis may reveal a moderate-to-strong reaction on the dipstick for occult blood. Microscopic analysis typically reveals very few red blood cells, 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 usually are not required.

Liver enzyme levels may be altered. 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 changes may occur in patients with NMS, who 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.

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.


Imaging Studies

No specific imaging studies are routinely required; however, if appropriate, the patient's individual condition may require imaging.

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 radiopaque and are often observed on a plain film of the abdomen. This may be useful 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.


Other Tests

A 12-lead 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 recommended.

Ferric chloride or Phenistix test results can be positive with very high concentrations of phenothiazines in the urine; however, owing to a lack of sensitivity and specificity, their use as bedside tests is rarely indicated.



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