Interpretive Reference Ranges for Plasma Drug Concentrations in Acute Recreational Drug Toxicity: A Short...

Acute recreational drug toxicity (ARDT) is a frequent cause of emergency department presentations; however, clinicians lack guidance for interpreting drug concentrations. Existing terminology ("therapeutic," "toxic," and "lethal") does not reflect the variability observed in ARDT, where tolerance, interindividual differences, and polydrug exposure influence clinical features. This study aimed to develop a descriptive, clinician-oriented framework to categorize illicit and prescription drug concentrations into meaningful interpretive bands.

A literature search identified studies reporting antemortem plasma concentrations in adults. Twenty-four analytes (parent drugs and metabolites) commonly detected in ARDT were included. Concentrations were standardized to ng/mL. For illicit drugs, skewness, histograms, and robust z-scores (median absolute deviation-based; threshold ±3.5) were used to identify and remove outliers. Interquartile- or tertile-based interpretive bands (low, moderate, and high) were assigned according to data set characteristics. Gamma-hydroxybutyrate concentrations were classified using endogenous cutoff values. Prescription medicines were categorized as within or above the therapeutic range based on established reference ranges.

Thousand two hundred sixteen plasma concentrations from 79 studies met the inclusion criteria. Illicit drug ranges included analytes with narrow (ketamine, 53-86 ng/mL) and broad (cocaine, 65-193 ng/mL) concentration-effect variability. The endogenous cutoff for gamma-hydroxybutyrate was 5000 ng/mL. Prescription medicine ranges reflected expected therapeutic patterns.

This study proposes a reproducible, percentile-based framework for interpreting plasma drug concentrations in ARDT. The framework provides clinically intuitive, data-driven reference bands to support clinical interpretation, enhance communication between laboratories and clinicians, and offer a scalable foundation for future guideline development.