Diphenhydramine dose–response: a novel approach to determine triage thresholds

Context. It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose–response studies have had conflicting results. Objective. We sought to evaluate DPH dose–response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. Methods. We retrospectively analyzed APAP/DPH-only exposures in patients 2–80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating cha...