Benzodiazepine and z-drug prescribing in critical care survivors and the risk of rehospitalisation or death due to falls/trauma and due to any cause: a retrospective matched cohort study using the UK Clinical Practice Research Datalink.

Purpose: Benzodiazepines and z-drugs are often prescribed to critical care survivors due to high prevalence of mental health problems and insomnia. However, their safety has not been studied in this population.

Methods: Retrospective cohort study of 28,678 adult critical care survivors hospitalised in 2010 and 2018: 4844 prescribed benzodiazepines or z-drugs, matched to 23,834 unexposed survivors using UK Clinical Practice Research Datalink linked datasets. Multivariable stratified Cox regression was used to estimate the adjusted hazards ratio (adjHR) with 95% confidence intervals (CI) of community benzodiazepine/z-drug prescribing and falls/trauma-related events, as well as all-cause 30-day rehospitalisation or death. We performed subgroup analyses on patients without pre-critical care admission prescription of benzodiazepines/z-drugs ('treatment-naïve'), and sensitivity analyses excluding patients receiving palliative care after discharge.

Results: Prescription of benzodiazepines or z-drugs showed no conclusive evidence of increased risk of falls/trauma-related events in the whole cohort (adjHR 1.27; 95%CI 0.76-2.14) or in treatment-naïve individuals (adjHR 1.79; 95%CI 0.61-5.26), because estimates lacked precision due to low event rates. For all-cause rehospitalisation or death, benzodiazepines/z-drugs were associated with increased risk (whole cohort adjHR 1.24, 95%CI 1.14-1.36; treatment-naïve adjHR 1.66, 95%CI 1.49-1.86). However, after excluding patients treated for palliative care, the association persisted only in treatment-naïve individuals (whole cohort adjHR 1.08, 95%CI 0.98-1.19; treatment-naïve adjHR 1.42, 95%CI1.25-1.62).

Conclusions: Community benzodiazepine and z-drug prescribing was associated with increased risk of all-cause, but not falls/trauma-related, rehospitalisations and deaths in critical care survivors who had not been prescribed these before hospitalisation. Clinicians should balance the possible benefits with the likely harms of prescribing these drugs in this potentially vulnerable patient group.