Cut-Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients

Abstract

Background Although alcohol misuse is associated with deleterious outcomes in critically ill patients, its detection by either self-report or examination of biomarkers is difficult to obtain consistently. Phosphatidylethanol (PEth) is a direct alcohol biomarker that can characterize alcohol consumption patterns; however, its diagnostic accuracy in identifying misuse in critically ill patients is unknown. Methods PEth values were obtained in a mixed cohort comprised of 122 individuals from medical and burn intensive care units (n=33), alcohol detoxification unit (n=51), and healthy volunteers (n=38). Any alcohol misuse and severe misuse were referenced by AUDIT and AUDIT-C scores separately. Mixed effects logistic regression analysis was performed and the discrimination of PEth was evaluated using the area under the receiver operating characteristic (ROC) curve. Results The area under the ROC curve for PEth was 0.927 (95% CI: 0.877, 0.977) for any misuse and 0.906 (95% CI: 0.850, 0.962) for severe misuse defined by AUDIT. By AUDIT-C, the area under the ROC curves were 0.948 (95% CI: 0.910, 0.956) for any misuse and 0.913 (95% CI: 0.856, 0.971) for severe misuse. The PEth cut-points of ≥ 250 ng/mL and ≥ 400 ng/mL provided optimal discrimination for any misuse and severe misuse, respectively. The positive predictive value for ≥ 250 ng/mL was 88.7% (95% CI: 77.5%, 95.0%) and negative predictive value was 86.7% (95% CI: 74.9%, 93.7%). PEth ≥ 400 ng/mL achieved similar values and similar results were shown for AUDIT-C. In a subgroup analysis of critically ill patients only, test characteristics were similar to the mixed cohort. Conclusions PEth is a strong predictor and has good discrimination for any and severe alcohol misuse in a mixed cohort that includes critically ill patients. Cut-points at 250 ng/mL for any, and 400 ng/mL for severe, are favorable. External validation will be required to establish these cut-points in critically ill patients.

Inter Individual Variation and Factors Regulating the Formation of Phosphatidylethanol

“…PEth is formed from PC present in the erythrocyte cell membrane, and previous studies have shown a positive correlation between reported alcohol consumption and PEth concentration in blood (Aradottir et al., ; Stewart et al., ; Walther et al., ). Likewise, drinking studies in volunteer subjects with single or several intakes of alcohol sometimes aiming at specified targets of blood alcohol concentration have shown a correlation between PEth and consumed amounts of alcohol (Gnann et al., ; Kechagias et al., ; Schrock et al., ) but with significant interindividual differences in PEth values in relation to alcohol consumption (Afshar et al., ; Aradottir et al., ; Gnann et al., ; Kechagias et al., ; Schrock et al., ; Walther et al., ). Possible reasons for the observed between‐individual variability (e.g., variation in PC concentration, in PLD activity, or in the formation and elimination of PEth, and a possible lack of reliability in reported consumption) have been discussed in a previously published paper (Hahn et al., ).…”

Letter to the Editor Regarding Afshar et al. (2017): Cut‐Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients

“…However, when compared to a critically ill patient with lower Hb (100 g/l) and Hct (0.3), a typical male adult can have a significantly different red cell profile with this difference being potentially up to 50% (Hb g/l: 154/100 = 1.54 [+54%]; Hct: 0.455/0.3 = 1.52 [+52%]). Hence, in the context of Afshar and colleagues' () study, the impact of reduced red cell volume in critically ill patients can affect the PEth values.…”

“…In this letter, we briefly discuss the findings by Afshar and colleagues () regarding the use of the alcohol biomarker phosphatidylethanol (PEth) to identify alcohol misuse in a mixed cohort of individuals, particularly in critically ill patients from an intensive care unit (ICU). This particular patient group as highlighted by the authors is a difficult cohort to test for the presence of an alcohol use disorder and has therefore been underresearched.…”

“…In this study by Afshar and colleagues (), a cohort of 122 individuals was recruited. This included: 38 healthy volunteers, 51 patients undergoing alcohol detoxification, and 38 patients from the ICU.…”

“…Afshar and colleagues () analyzed PEth from dried whole blood spot samples. While consistency can be applied with good laboratory techniques to the volume during dried blood spotting, there is a high probability that the whole blood samples contain a degree of variation among patient groups for their red cell volume.…”