Dr. Josh Farkas of PulmCrit explains why the osmolal gap is not useful for the diagnosis of toxic alcohol ingestion in his post PulmCrit- Toxicology dogmalysis: the osmolal gap
August 14, 2017.
Dr. Farkas post is an excellent update on the [lack of] usefulness of the osmolal gap.
Since these are my study notes, I went ahead and reviewed Resources (3) to (9) for the different toxic alcohol ingestions and and differential diagnoses.
This post contains some excerpts from Dr. Farkas’ post.
Reminder: Anyone who an acute mental status change or who appears to be intoxicated needs a stat finger stick blood sugar. And every apparently intoxicated or altered mental status patient needs to be considered for occult brain trauma and the usual other causes.
Basically, if you have a significant pretest probability of toxic alcohol ingestion, you need to go ahead and consider giving fomepazole (3).
Dr. Farkas points out the problem with current screening tests – it is the low pretest probability of toxic alcohol ingestion in the routine patient who appears intoxicated:
Screening of the undifferentiated intoxicated patient
Imagine a patient presenting with undifferentiated intoxication, without any history suggestive of a toxic alcohol ingestion. The likelihood that this patient has a toxic alcohol ingestion is low. Krawsowski 2012 detected a toxic alcohol in 0.3% of these patients (~1/300), which is consistent with large-scale toxicology data (Watson 2004).
Dr. Farkas quotes from Goldfrank’s 10th edition (1):
The negative and positive predictive values of the osmol gap are too poor to recommend this test to routinely screen for xenobiotic ingestion.
Dr. Farkas also quotes Lepetre et al (2):
A “normal” osmolal gap does not exclude toxic alcohol exposure and extreme caution is required when interpreting a “normal” osmolal gap (even <5) when there are clues to such an exposure such as history of ingestion, classic symptoms, or elevated anion gap.
There are, however, useful tests currently available in veterinary medicine which may become available for human medical testing, Dr. Farkas states:
There are a variety of innovative tests under development to detect methanol, ethylene glycol, or their toxic metabolites. For example, one promising assay evaluates ethylene glycol based on its reaction with a bacterial enzyme, glycerol dehydrogenase. Quantitative and qualitative point-of-care versions of this test are currently available for veterinary use (Rooney 2016, Robson 2017).
Although serum osmolal gap is a poor test for toxic alcohol ingestion, the disease itself is uncommon. Therefore, our diagnostic failure rate is low (perhaps ~1/1,000 intoxicated patients). Missed diagnosis may be devastating for an individual patient. However, a low error rate among a marginalized patient population won’t gain much attention (1). Thus, it’s possible that veterinarians will continue to out-perform us on this diagnosis.
(1) Goldfranks Toxicologic Emergencies Edition 10, 2014, by Robert S. Hoffman, Mary Ann Howland, Neal A. Lewin, Lewis S. Nelson, Lewis R. Goldfrank
(2) Formulas for Calculated Osmolarity and Osmolal Gap: A Study of Diagnostic Accuracy [PubMed Abstract]. Am J Kidney Dis. 2017 May 31. pii: S0272-6386(17)30670-4. doi: 10.1053/j.ajkd.2017.03.023. [Epub ahead of print]
Although any alcohol can be toxic if ingested in large enough quantities, the term toxic alcohol has traditionally referred to isopropanol, methanol, and ethylene glycol.  Prompt recognition and treatment of patients intoxicated with these substances can reduce the morbidity and mortality associated with these alcohols.
This article discusses not only the three toxic alcohols but also ethanol. For discussion of the individual agents, see Methanol Toxicity and Ethylene Glycol Toxicity; for discussion of pediatric ethanol ingestion, see Ethanol Toxicity. Ethanol withdrawal is a serious and potentially life-threatening problem, which is discussed in Withdrawal Syndromes.