Risk Factors Associated with Deterioration in Sedative Drug Overdose

Background: Sedative overdoses, particularly involving opioids, γ-hydroxybutyrate (GHB), and benzodiazepines, are an increasing contributor to toxicology admissions and intensive care unit (ICU) utilisation in Australia. While pharmacological mechanisms are well characterised, identifying which patients will deteriorate remains challenging. Existing risk stratification tools, such as the Glasgow Coma Scale (GCS), lack toxicology-specific nuance and may not adequately account for early physiological derangement, highlighting the need for improved, patient-centred risk assessment. Aims: To evaluate clinical and exposure-related features associated with ICU admission, endotracheal intubation, and in-hospital complications following sedative overdose. Methods: This retrospective cohort study included patients referred to a district toxicology service with suspected sedative overdose between November 2022 and November 2023. Data extracted from electronic medical records included demographics, ingestion characteristics, clinical course, and investigation results. Sedatives were defined by central nervous system depressant effects. Outcomes were ICU admission, endotracheal intubation, and in-hospital complications. Associations were examined using univariable analyses and multivariable logistic regression; venous pH was modelled separately using penalised logistic regression. Results: A total of 374 patients were included. Common agents were benzodiazepines (32.1%), opioids (29.1%), and GHB (20.6%). In-hospital complications occurred in 35.8% of patients, ICU admission in 17.9%, and intubation in 13.6%. After adjustment, ICU admission was independently associated with lower venous pH and non-benzodiazepine GABA-ergic agent ingestion (e.g. pregabalin and Z-drugs) (adjusted OR 3.35, p = 0.04). Lower venous pH was consistently associated with all adverse outcomes. The model-estimated probability of intubation increased non-linearly with worsening acidaemia, rising from 8% at pH 7.35 to 66% at pH 7.20. In-hospital complications were independently associated with opioid ingestion (adjusted OR 3.81, p < 0.001) and lower GCS, while intubation was associated with lower GCS and lower venous pH. GHB ingestion was inversely associated with intubation. Conclusion: Lower GCS, reduced venous pH, and ingestion of high-risk sedative agents—particularly opioids and non-benzodiazepine GABA-ergic ingestion —were key features associated with clinical deterioration in sedative overdose. These findings support multifactorial, toxicology-specific risk stratification incorporating early physiological and pharmacological markers, with prospective validation required before clinical implementation.