Impact of Pre-ICU benzodiazepine and Z-Drug exposure on mortality in critically ill Adults: A nationwide retrospective cohort study: A nationwide retrospective cohort study.

OBJECTIVES

Outpatient use of benzodiazepines and Z-drugs (BZRA) is common, yet its impact on mortality after intensive care unit (ICU) admission remains unclear. We therefore aimed to determine whether outpatient BZRA use within 30 days before ICU admission is independently associated with 30- and 90-day mortality.

METHODS

Using South Korea's National Health Insurance Service database, we retrospectively identified adults (≥18 years) with first ICU admissions from 2020 to 2023 and defined pre-ICU BZRA exposure as ≥ 1 prescription within 30 days before admission. We performed 1:1 propensity-score matching on demographic, clinical (including Charlson Comorbidity Index and acute organ dysfunction), socioeconomic, functional, institutional, and temporal variables, then estimated 30- and 90-day mortality associations via conditional logistic regression and Kaplan-Meier survival analysis.

RESULTS

Among 1,189,042 unique adult ICU admissions, 115,821 (9.7 %) had pre-ICU BZRA exposure. After matching, 115,820 exposed and 115,820 unexposed patients had excellent covariate balance (all ASDs < 0.10). BZRA exposure was associated with higher 30-day mortality (23.8 % vs 16.6 %; odds ratio [OR] 1.57; 95 % confidence interval [CI] 1.54-1.60; P < 0.001) and higher 90-day mortality (36.8 % vs 27.3 %; OR 1.56; 95 % CI 1.53-1.58; P < 0.001). Kaplan-Meier analysis confirmed reduced cumulative survival (log-rank P < 0.001). Notably, combined benzodiazepine + Z-drug users exhibited the greatest risk: OR 2.46 (95 % CI 2.35-2.58) for 30-day death and OR 2.61 (95 % CI 2.50-2.72) for 90-day death versus non-exposed patients.

CONCLUSIONS

Outpatient BZRA use within 30 days before ICU admission is independently associated with higher 30- and 90-day mortality, with combination exposure conferring an even greater risk.

IMPLICATIONS FOR CLINICAL PRACTICE: Recent outpatient BZRA prescriptions are an easily obtainable risk marker that clinicians should incorporate into pre-ICU assessment and triage; where clinically appropriate, medication review and targeted deprescribing may reduce early ICU morbidity and mortality.