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Toxic alcohols and glycols are easy to find in most households, harmful if ingested, and difficult to identify in poisoned patients. The latest issue of Clinical & Forensic Toxicology News (CFTN) discusses the specific properties of these toxins, the analytical methods and challenges of testing, and how clinical labs can leverage certain tests such as the osmolal gap to assist clinicians in diagnosing ingestions of these compounds.
CFTN is a quarterly AACC/College of American Pathologists (CAP) educational newsletter for toxicology laboratories and individuals with an interest in toxicology. Each issue highlights topics of interest to the clinical and forensic toxicology fields.
Compounds such as ethylene glycol, isopropanol, and methanol “are easily obtained from widely available and inexpensive household and industrial products. Similar to ethanol, the toxic alcohols and glycols can cause central nervous system (CNS) and respiratory depression that may be particularly dangerous when combined with other CNS depressants, such as benzodiazepines and opioids,” wrote Heather R. Greene and Matthew D. Krasowski, MD, PhD. Clinicians struggle to make a diagnosis of ingestion because the symptoms associated with these substances are so nonspecific. Getting an accurate patient history of ingestion is also a challenge. Quick diagnosis, however, is critical, “particularly when [patients have ingested] methanol or ethylene glycol, because the efficacy of treatment depends on how much time has elapsed,” wrote the authors, who described the properties of specific toxins, their metabolic pathways, and their potential repercussions to human health.
Greene and Krasowski also described the strengths and limitations of current tests available to diagnose these conditions. While gas chromatography alone or with mass spectrometry (GC/MS) is the current gold standard for identifying and measuring toxic alcohols and glycols in blood samples, this method is time- and labor-intensive, which means that not many labs conduct it in-house. Yet sending out samples for GC/MS analysis produces too long a turnaround time, which could delay time-sensitive diagnoses or treatments, wrote Greene and Krasowski. “This may lead to use of antidote and/or hemodialysis as empiric therapy in cases for which ingestion is not certain based on initial history and clinical signs or to missing the diagnosis altogether when severe toxicity may still be preventable,” they added.
Enzymatic assays that run on standard clinical chemistry analyzers have emerged to assess quantitative ethylene glycol concentrations. However, structurally related compounds in patient specimens such as propylene glycol and 2,3-butanediol can interfere with their performance. “A limited number of clinical laboratories have adapted veterinary ethylene glycol enzymatic assays for analysis of human samples, and method validation for these assays on multiple chemistry platforms has been reported in the published literature,” the authors reported. But to their knowledge, the U.S. Food and Drug Administration has yet to approve this type of assay, posing a barrier for more widespread adoption.
Labs can assist in diagnosis by knowing the limitations and strengths of osmolal gap (OG), anion gap, blood gas analysis, and other laboratory testing used in diagnosing and managing toxic alcohol and glycol ingestions, Greene and Krasowski suggested. Measuring the OG, for example, can help determine and monitor ethylene glycol, isopropanol, or methanol in serum or plasma.
“Ethylene glycol and methanol can have a classic pattern in which they first produce an increased OG (‘early’ ingestion). An anion gap, metabolic acidosis develops later if no treatment is initiated (‘late’ ingestion). There may be an intermediate period during which an increased OG and anion gap are both present,” the authors explained. Some ingestions might not increase OG or anion gap, however, cautioned Greene and Krasowski.
CFTN is an educational service of the Forensic Urine Drug Testing Accreditation Program co-sponsored by AACC and CAP. Individual subscriptions are also available; the regular price is $65, and AACC members pay $45. Subscribers are eligible to receive four ACCENT continuing education credits per year, one credit per quarterly issue.