Acid-Base Phenotypes in Sedative Toxidrome: Characterisation, Agent-Specific Patterns and Clinical Associations

Acid-base patterns and their association with clinical outcomes have not been characterised using venous-specific reference ranges in a sedative-specific cohort. We aimed to characterise acid-base phenotypes in sedative toxidrome using venous-specific thresholds, examine agent-specific associations and evaluate relationships to adverse outcomes.

Retrospective cohort study of 374 consecutive patients referred to a toxicology service with sedative poisoning between November 2022 and November 2023. VBG data (pH, pCO₂, HCO₃ and lactate) were classified into acid-base phenotypes using venous-specific reference ranges (venous respiratory acidosis: pH < 7.31, pCO₂ > 51 mmHg; hypercapnia with preserved pH: pH 7.31-7.41, pCO₂ > 51 mmHg). Outcomes of interest were endotracheal intubation, ICU admission and in-hospital complications. Associations were assessed using chi-squared tests, Mann-Whitney U tests and ROC curve analysis.

VBG was obtained in 330 of 374 patients (88.2%). Venous respiratory acidosis occurred in 54 patients (16.4%), hypercapnia with preserved pH in 81 (24.5%) and normal venous pH in 153 (46.4%). Opioid exposures had the highest hypercapnic burden (59%) compared with anti-psychotic exposures (20%; p < 0.001). Venous respiratory acidosis was associated with ICU admission (40.7% vs. 17.0%, p = 0.001) and complications (64.8% vs. 32.7%, p < 0.001). Among hypercapnic patients, pCO₂ ≥ 65 mmHg was associated with ICU admission in 50.0%. Venous pH had the strongest discriminative performance across outcomes (AUC 0.631-0.683).

Venous respiratory acidosis identifies a high-risk subgroup. Hypercapnic burden varies substantially by agent class. These findings support routine early VBG measurement in sedative overdose and highlight the importance of venous-specific thresholds when interpreting point-of-care acid-base results.