Early clinical features associated with severe valproic acid poisoning: a toxicology investigators consortium core registry study

Abstract

Severe acute Valproic Acid (VPA) ingestions may require intensive care, intubation, or Extracorporeal Treatments (ECTRs), but early predictors are poorly defined. In this study we aimed to identify presentation features associated with Intensive Care Unit (ICU)-level care, intubation, and ECTRs after VPA exposure. We analyzed 164 VPA cases reported to the Toxicology Investigators Consortium Core Registry from January 1, 2012, through December 31, 2025. Candidate predictors were selected a priori from severe VPA toxicity features. Associations were assessed using Fisher exact tests and Odds Ratios (ORs). Median age was 34.5 years; 144/164 exposures (87.8%) were intentional. ICU-level care occurred in 49/164 cases (29.9%), intubation in 23/164 (14.0%), and ECTRs in 5/164 (3.0%). ICU-level care was associated with respiratory depression (OR 30.0), metabolic acidosis (OR 15.9), hypotension (OR 4.63), central nervous system depression (OR 4.23), and co-ingestion (OR 3.25). Therapeutic-use cases were less likely to require ICU-level care or intubation. Respiratory depression, metabolic acidosis, hypotension, central nervous system depression, and co-ingestion identify VPA exposures at higher risk for ICU-level care.