Critical Decision Support
Liquid chromatography-tandem mass spectrometry has a pivotal role in diagnosing intoxicated patients
Imagine your lab receives a call from an emergency physician regarding a patient who has just presented to your hospital. A witnessed seizure prompted the patient’s visit to the emergency department, but the patient has no reported history of seizures. Their mental status is altered, though, and they are becoming increasingly agitated. The patient’s friends say that they take citalopram for anxiety and occasionally smoke marijuana. The emergency physician wants a comprehensive drug screen to determine if the patient’s condition is the result of an ingestion. But what sort of testing would you recommend?
Comprehensive drug screening, as requested by the physician in the vignette, can take many forms. It should include as many relevant compounds as possible, and in the case of an acutely poisoned patient, the results should be available quickly.
In most laboratories, a comprehensive drug screen would involve running a patient’s urine sample through a battery of immunoassays, which are attractive because they are fast and compatible with automated analyzers. However, immunoassays have two limitations when assessing poisoned patients. First, they’re only available for a small fraction of toxicologically relevant compounds. Second, most immunoassays are designed for urine samples, and although urine is the specimen of choice for monitoring drug use, it has a more limited utility for assessing acute intoxication.
One of the most promising alternatives is liquid chromatography-tandem mass spectrometry (LC-MS/MS). The technique has a lengthy history in the clinical laboratory, and is often used as the gold standard method for quantitative analyses. Many laboratorians will be familiar with LC-MS/MS as a confirmatory technique for urine toxicology testing, but it can also be used to measure a wide variety of clinically relevant substances. LC-MS/MS methods are typically laboratory-developed tests, which allow the laboratory to include as many compounds as desired and to establish which sample type(s) to accept. The disadvantages of LC-MS/MS are that most methods involve manual sample preparation and somewhat complex data processing, both of which require experienced personnel and can prolong turnaround time.
Despite these disadvantages, the technique has several features that make it attractive for comprehensive drug screening. One is the ability to analyze serum or plasma samples, which can provide more useful information on acute intoxication than a urine sample. Another is the ability to include many different types of drugs. This means the laboratory can customize the comprehensive screen based on regional drug use, and can include over-the-counter and “designer” drugs that would not be detected by immunoassays. Turnaround time can be reduced to approximately three hours by choosing a minimalist sample preparation protocol, having well-trained staff, and having a dedicated LC-MS/MS available for testing.
Returning to the opening vignette… imagine your laboratory could perform comprehensive drug screening using both immunoassays and LC-MS/MS. So you recommended that the clinician order both types of testing. Results from the immunoassays performed on the patient’s urine were made available to the treating team in under an hour, and were negative. Although this is valuable information, it doesn’t explain the patient’s condition. Results from the LC-MS/MS screen were available in three hours, and showed diphenhydramine in the patient’s serum and urine samples. This over-the-counter antihistamine has anticholinergic effects and can cause seizures at high doses, so the team decided to administer a cholinergic agent, and the patient’s clinical picture improved immediately.
As illustrated here, an effective comprehensive drug screening program can provide critical decision support for a hospital’s emergency department and improve patient care. Thoughtfully designed, LC-MS/MS-based tests can provide valuable information in a clinically relevant timeframe, and when used in conjunction with immunoassays, serve as an all-round solution for rapid toxicology screening.
Jennifer Colby is Assistant Professor of Pathology, Microbiology and Immunology and Associate Director of Clinical Chemistry at Vanderbilt University Medical Center, Nashville, Tennessee, USA