Association between benzodiazepine premedication and 30-day mortality rate: A propensity-score weighted analysis of the Peri-interventional Outcome Study in the Elderly (POSE)

Abstract

Background: Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence.

Objective: We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality.

Design: We used propensity score methods to perform a confounder-adjusted time-to-event analysis of the association between benzodiazepine premedication and 30-day mortality of the POSE study.

Setting: POSE was conducted as a European multicentre prospective cohort study.

Patients: Adults aged 80 years or older scheduled for surgical or nonsurgical intervention under anaesthesia.

Results: A total of 9497 patients were analysed. One thousand five hundred and twenty-one patients received benzodiazepine premedication, 7936 patients received no benzodiazepine premedication, 30 received clonidine and 10 had missing premedication data. Inverse propensity-score-weighted log-rank analysis did not provide unambiguous evidence for an association between benzodiazepine premedication and 30-day mortality; median [range] P = 0.048 [0.044 to 0.078], estimated 30-day mortality rates 3.21% and 4.45% in benzodiazepine-premedicated and nonbenzodiazepine-premedicated patients, respectively. Inverse propensity-score-weighted Cox regression resulted in a hazard ratio of 0.71 (95% CI 0.49 to 1.04), pointing at a possible reduction of 30-day mortality in the benzodiazepine premedication group. Sensitivity analyses, which constituted subgroup, matched-pairs, and subclassification analyses, resulted in similar findings.

Conclusion: This secondary analysis of the POSE data did not find evidence for an unambiguous association between benzodiazepine premedication and 30-day mortality. Point estimates indicated a reduction of 30-day mortality in benzodiazepine-premedicated patients. The results presented here might be affected by unmeasured confounding factors, which could be addressed in a randomised trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03152734.

Fig. 1

Standardised differences of the covariates included in the propensity score model

Fig. 2

Distribution of the propensity score values

Fig. 3

Estimated survival probabilities in the benzodiazepine-premedicated and nonbenzodiazepine-premedicated patients