About 160,000 people survive critical illness in the UK each year and with advances in critical care, this number is expected to grow. Reportedly, over half of critical care survivors have anxiety, post-traumatic stress disorder (PTSD), and sleep disturbances within the first months after hospital discharge which is frequently associated with decreased quality of life. Anxiety and PTSD can contribute to problems with sleeping and vice versa. Whether prescribed anxiety medications or sleeping tablets such as benzodiazepines and “z-drugs” (such as zopiclone, zolpidem) are safe in critical care survivors has not been previously researched.
This study will examine prescribing and safety of benzodiazepines and z-drugs in survivors of critical illness. Specifically:
1. We will examine factors associated with new benzodiazepine and z-drug prescribing after critical care hospitalisation.
2. We will investigate whether benzodiazepine and z-drug prescribing after hospital discharge in critical care survivors increases the chance of outcomes such as emergency hospital readmission and death.
3. We will factor in other medications prescribed at the same time that may be associated with such adverse outcomes (for example, opioids and other sedating medications) and assess if certain groups of patients (e.g., elderly) are at higher risk of adverse events with benzodiazepine and z-drugs.
We will share our findings to ensure that prescribers are aware of the results to reduce harms associated with these medications, to enable safer prescribing.
Mental health issues and insomnia affect about one of every two critical care survivors within a year of hospital discharge. Such conditions contribute to increased morbidity and mortality in medically unwell patients. Few studies have shown that anxiolytics and hypnotics such as benzodiazepines and z-drugs are commonly prescribed after discharge in adult survivors of critical illness. However, these patients may be more vulnerable to known adverse outcomes such as falls, fractures, motor vehicle accidents, and death. The safety of these medications in this population has not been previously investigated.
Our retrospective cohort study aims to investigate community prescribing in survivors of critical illness to: 1) identify risk factors for incident primary care prescribing of benzodiazepines and z-drug hypnotics within 90 days of index hospital discharge; 2) estimate the risk of adverse outcomes such as emergency hospital readmissions and death in patients exposed to benzodiazepines or z-drugs compared to unexposed patients; and 3) conduct subgroup analyses to understand if subpopulations of critical illness survivors have heterogeneous risk of adverse outcomes (e.g., those with multimorbidity or those co-prescribed sedating medications). We will leverage CPRD Aurum linked to Hospital Episode Statistics Admitted Patient Care (HES APC) for adults with a critical care stay. Outcomes of subsequent hospitalisation and death including diagnosis codes will be extracted from HES APC and ONS death registration. Community prescribing data will be extracted from CPRD Aurum. The association between benzodiazepine and z-drugs and outcomes will be estimated using a stratified Cox regression model to calculate hazard ratios and 95% confidence intervals while accounting for confounders and competing risks.
We will publish and disseminate our findings to ensure we reach multiple audiences to enable the safest prescribing possible.
Hospitalisations or deaths from falls, fractures, motor vehicle accidents, and drug overdose; All-cause hospitalisation; All-cause mortality.
Nazir Lone - Chief Investigator - University of Edinburgh
Elizabeth Mansi - Corresponding Applicant - University of Edinburgh
Bruce Guthrie - Collaborator - University of Edinburgh
Christopher Rentsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation