Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: A pragmatic, randomised, double blind, placebo- controlled trial

Abstract

Abstract Background After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality in ICU. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. Methods Randomized, pragmatic, multicentre, double blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8PM to 8AM and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. Results A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 26, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. In as-treated population, sleep quality assessed by numerical scale was significantly higher in the patients receiving dexmedetomidine (5.7 vs. 5; p = 0.01), as was the evaluation with the Leeds sleep evaluation questionnaire (-4.0 vs. -7.3; p = 0.02). Conclusion In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration: This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018)