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An Evaluation of the Osmole Gap as a Screening Test for Toxic Alcohol Poisoning

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Case Reports

An Evaluation of the Osmole Gap as a Screening Test for Toxic Alcohol Poisoning

Larry D Lynd et al. BMC Emerg Med.

Abstract

Background: 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, 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.

Methods: Electronic 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.

Results: One 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.

Conclusion: In 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.

Figures

Figure 1
Figure 1
Flow diagram outlining the derivation of the final study sample. Shaded boxes represent patients considered to be 'exposed' (i.e. ethylene glycol or methanol serum concentrations exceeding the threshold for antidotal therapy). Legend: All concentrations expressed as mmol/l. EG = ethylene glycol ME = methanol
Figure 2
Figure 2
Receiver Operator Characteristics curves for the two equations when used to identify patients with serum concentrations of ethylene glycol and methanol that exceed the threshold at which antidotal therapy is recommended - - - - osmole gap derived using equation 1 (ethanol coefficient of 1) ------ osmole gap derived using equation 2 (ethanol coefficient of 1.25). The points delineated by ● and ■ indicate the cut-off of 10 derived using equations 1 and 2, respectively. The points delineated by ○ and □ indicate the cut-off of 20 derived using equations 1 and 2, respectively.
Figure 3
Figure 3
Receiver Operator Characteristics curves for the two equations when used to identify patients with serum concentrations of ethylene glycol and methanol that exceed the threshold at which hemodialysis is recommended - - - - osmole gap derived using equation 1 (ethanol coefficient of 1) ----- osmole gap derived using equation 2 (ethanol coefficient of 1.25). The points delineated by ● and ■ indicate an osmole gap cut-off of 10 derived using equations 1 and 2, respectively. The points delineated by ○ and □ indicate an osmole gap cut-off of 20 derived using equations 1 and 2, respectively.
Figure 4
Figure 4
The Positive Predictive Value and Negative Predictive Value of osmole gap values ranging between -10 and 30 to identify toxic alcohol concentrations exceeding the antidotal therapy (Panel a) and hemodialysis (Panel b) thresholds Black lines represent the positive predictive value. Grey lines represent the negative predictive value. - - - - osmole gap derived using equation 1 (ethanol coefficient of 1) ----- osmole gap derived using equation 2 (ethanol coefficient of 1.25)

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