Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (B-Free Pilot): a pilot, multicentre, randomised, cluster crossover trial

Abstract

Background: Delirium is common after cardiac surgery and is associated with adverse outcomes. Perioperative benzodiazepine use is associated with delirium and is common during cardiac surgery, which may increase the risk of postoperative delirium. We undertook a pilot study to inform the feasibility of a large randomised cluster crossover trial examining whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared with liberal administration) would reduce delirium. Methods: We conducted a two-centre, pilot, randomised cluster crossover trial with four 4 week crossover periods. Each centre was randomised to a policy of restricted or liberal use, and then alternated between the two policies during the remaining three periods. Our feasibility outcomes were adherence to each policy (goal !80%) and outcome assessment (one delirium assessment per day in the ICU in !90% of participants). We also evaluated the incidence of intraoperative awareness in one site using serial Brice questionnaires. Results: Of 800 patients undergoing cardiac surgery during the trial period, 127/800 (15.9%) had delirium. Of these, 355/ 389 (91.3%) received benzodiazepines during the liberal benzodiazepine periods and 363/411 (88.3%) did not receive benzodiazepines during the restricted benzodiazepine periods. Amongst the 800 patients, 740 (92.5%) had !1 postoperative delirium assessment per day in the ICU. Of 521 patients screened for intraoperative awareness, one patient (0.2%), managed during the restricted benzodiazepine period (but who received benzodiazepine), experienced intraoperative awareness.

The use of dexmedetomidine to prevent delirium after major cardiac and non‐cardiac surgery

“…Examples of peri‐operative care bundles have included: the Hospital Elder Life Program (orientation, nutritional support, early mobilisation) after abdominal surgery [4]; and a multidisciplinary approach to hip fracture surgery (fascia iliaca blocks, rationalising prescribing practices and avoidance of triggers) [5]. Investigations of single interventions have included: benzodiazepine restriction [6]; intra‐operative use of the inhalational anaesthetic agent, xenon [7]; depth of anaesthesia monitoring [8]; and dexmedetomidine given at various time‐points in the peri‐operative period [9].…”

Evaluating interventions to reduce the risk of postoperative delirium

“…A pilot trial is an important early step in this process. 18 In this issue of the British Journal of Anaesthesia, Spence and colleagues 19 present their results of a pilot randomised cluster crossover trial evaluating intraoperative benzodiazepine restriction for cardiac surgery. They included four, 4-week crossover periods in their design, requiring clinicians to crossover three times between treatment periods, meaning that each of the two hospitals involved in the study would be obliged to use a 'liberal' and 'restricted' approach to intraoperative benzodiazepine administration on two occasions.…”

“…Their primary goal was to test the feasibility (treatment adherence, reliable detection of postoperative delirium in a setting of routine care) of a future large-scale trial, and to determine the incidence of intraoperative awareness during the restricted benzodiazepine periods. 19 Most key methodological features of the study design, and its reporting on a publicly accessible trial registration website, 20 were according to best practice. All process (except intraoperative drug administration data) and outcome data were obtained from electronic medical records; this enhanced the efficiency of the trial, but to some extent limited the quality of the data.…”

“…Spence and colleagues 19 enrolled 800 cardiac surgical patients of which they detected 127 patients (15.9%) with delirium. Most (91%) had received intraoperative benzodiazepines during their standard care (liberal) periods, and this was reduced to 12% during the restricted benzodiazepine periods.…”

“…Spence and colleagues 19 had, importantly, predetermined their feasibility criteria. 18 The two key criteria were to show that at least 80% of patients would receive care that complied with the assigned benzodiazepine administration policy, and at least 95% of patients would have at least one delirium assessment completed in the ICU during the study period.…”