A Systematic Review and Meta Analysis of Postmortem Ethanol Determination: Influencing Factors, Alternative Biomarkers, and Interpretation of Fatal Intoxication

Postmortem ethanol determination is a long-standing challenge in forensic toxicology, as measured postmortem ethanol concentrations (PMEC) may be influenced by multiple preanalytical and analytical factors, including postmortem ethanol production, specimen type, storage conditions, and postmortem interval (PMI). These factors can complicate the differentiation between antemortem alcohol consumption and postmortem ethanol formation, particularly in cases involving decomposition or delayed sampling. This study is designed as a systematic review and meta-analysis to comprehensively evaluate existing evidence on postmortem ethanol determination in medicolegal contexts. The review will focus on three interrelated components. First, it will examine factors that influence PMEC, including microbial ethanol production after death, variability across biological specimens (e.g., blood, urine, vitreous humor, cerebrospinal fluid), and the effects of storage conditions and PMI on ethanol stability and measurement reliability. Second, the review will assess alternative and complementary biomarkers of alcohol exposure that may assist in interpreting postmortem ethanol findings when direct ethanol measurement is unreliable. These biomarkers include ethyl glucuronide (EtG), ethyl sulfate (EtS), fatty acid ethyl esters (FAEEs), and protein carbonyl content (PCC). The analysis will summarize reported detection windows, specimen-specific performance, and proposed cutoff values, as well as their reported associations with antemortem alcohol consumption. Third, the review will synthesize evidence related to the interpretation of fatal ethanol intoxication, integrating PMEC data with biomarker findings and contextual information reported in forensic case series and epidemiological studies. This includes consideration of co-intoxicants, pathological findings, and circumstances of death that are relevant to medicolegal determinations. By systematically synthesizing data from experimental studies, clinical investigations, and forensic case reports, this review aims to clarify current evidence, identify methodological heterogeneity, and highlight areas where further research is needed to improve the interpretation of postmortem ethanol findings in forensic practice.