Abstract

BackgroundThe osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, particularly when the ability to measure serum concentrations of the substances is not available. The objectives of this study were: 1) to measure the diagnostic accuracy of the osmole gap for screening for ethylene glycol and methanol exposure, and 2) to identify whether a recently proposed modification of the ethanol coefficient affects the diagnostic accuracy.MethodsElectronic laboratory records from two tertiary-care hospitals were searched to identify all patients for whom a serum ethylene glycol and methanol measurement was ordered between January 1, 1996 and March 31, 2002. Cases were eligible for analysis if serum sodium, blood urea nitrogen, glucose, ethanol, ethylene glycol, methanol, and osmolality were measured simultaneously. Serum molarity was calculated using the Smithline and Gardner equation and ethanol coefficients of 1 and 1.25 mOsm/mM. The diagnostic accuracy of the osmole gap was evaluated for identifying patients with toxic alcohol levels above the recommended threshold for antidotal therapy and hemodialysis using receiver-operator characteristic curves, likelihood ratios, and positive and negative predictive values.ResultsOne hundred and thirty-one patients were included in the analysis, 20 of whom had ethylene glycol or methanol serum concentrations above the threshold for antidotal therapy. The use of an ethanol coefficient of 1.25 mOsm/mM yielded higher specificities and positive predictive values, without affecting sensitivity and negative predictive values. Employing an osmole gap threshold of 10 for the identification of patients requiring antidotal therapy resulted in a sensitivity of 0.9 and 0.85, and a specificity of 0.22 and 0. 5, with equations 1 and 2 respectively. The sensitivity increased to 1 for both equations for the identification of patients requiring dialysis.ConclusionIn this sample, an osmole gap threshold of 10 has a sensitivity and negative predictive value of 1 for identifying patients for whom hemodialysis is recommended, independent of the ethanol coefficient applied. In patients potentially requiring antidotal therapy, applying an ethanol coefficient of 1.25 resulted in a higher specificity and positive predictive value without compromising the sensitivity.

Highlights

  • The osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, when the ability to measure serum concentrations of the substances is not available

  • Selection of Study Subjects Cases were only eligible for inclusion in the analysis if serum sodium, blood urea nitrogen, glucose, ethanol, ethylene glycol, methanol, and serum osmolality measured using freezing point depression were measured on blood drawn at the same time

  • Characteristics of Study Subjects We identified 235 patients with 240 hospital visits during which serum ethylene glycol and methanol levels were measured by gas chromatography within 24 hours of their first laboratory results (Figure 1)

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Summary

Introduction

The osmole gap is used routinely as a screening test for the presence of exogenous osmotically active substances, such as the toxic alcohols ethylene glycol and methanol, when the ability to measure serum concentrations of the substances is not available. The objectives of this study were: 1) to measure the diagnostic accuracy of the osmole gap for screening for ethylene glycol and methanol exposure, and 2) to identify whether a recently proposed modification of the ethanol coefficient affects the diagnostic accuracy. The osmole gap is routinely used to screen patients for the presence of other exogenous osmotically active substances such as ethylene glycol and methanol, when the ability to measure the serum concentrations of these substances is not available. Toxic alcohol exposure meets these criteria given that serious toxicity is preventable with early diagnosis and initiation of antidotal therapy. The rapid and accurate diagnosis of toxic alcohol poisoning is crucial to prevent serious adverse outcomes

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