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

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Contributed by Olivier Huet, MD, PhD, Université de Bretagne Occidentale, Brest, France.

Background

Postoperative delirium is acknowledged to have a significant negative impact on patient outcome after cardiac surgery including long-term cognitive decline. To date, there is no specific treatment for postoperative delirium 1. Prevention of postoperative delirium primarily relies on patient re-orientation, mobility and avoidance of deliriogenic medications 2. The use of nonpharmacologic interventions to improve sleep quality and maintain circadian entrainment have been suggested as approaches to reduce postoperative delirium after cardiac surgery 3.

Dexmedetomidine is an α-2A adrenergic receptor agonist that has been shown to help normalize sleep architecture, give it produces spindle and slow-delta oscillations patterns close to N2 sleep stage. However, recent trials evaluating the use of dexmedetomidine to reduce postoperative delirium have demonstrated conflicting results that can be explained, in part, by study heterogeneity and a failure to consistently use proven postoperative nonpharmacologic delirium reduction interventions and delirium assessment approaches 4-6.

Methods

We conducted a pragmatic, randomized, double blind, parallel group, placebo-controlled trial to determine whether a repeated nocturnal infusion of low-dose of dexmedetomidine prevents the onset of postoperative delirium in older adults after an elective cardiac surgery. Patient’s aged 65 years or older who underwent cardiac surgery with or without cardiopulmonary bypass were included. Patients with dementia, 2nd or 3rd degree heart block, uncontrolled hypertension, hepatic failure, acute stroke or receiving clonidine were excluded.

For all participants, a nocturnal continuous infusion of dexmedetomidine or matching placebo (from 8 pm to 8 am) was started the night after surgery while the patient remained in the ICU for up to 7 nights. The infusion was initiated at a dose of 0.1 µg/kg/h and was titrated by the bedside nurse or clinician by 0.1 µg/kg/h every hour to maintain a Richmond Agitation and Sedation Scale (RASS) of -1 to +1.

Delirium was assesed twice daily with the CAM-ICU, patient-perceved sleep quality was evaluated each morning using the Leeds Sleep Evaluation Questionnaire (LSEQ) and at 3 months, quality of life was evaluated using the Short-Form 36 (SF-36), PTSD was evaluated using the PCL-5, and cognitive function was evaluated using the Cognitive Failure Questionnaire (CFQ). Secondary safety outcomes included bradycardia, hypotension, and arrthymias.

Results

A total of 331 patients were randomized and analyzed. The incidence of postoperative delirium was not significantly different between the dexmedetomidine (vs. placebo) groups (12.6% vs. 12.4%, p = 0.97). In the as-treated population, the median (IQR) LSEQ sleep quality was significantly improved in the dexmedetomidine (vs. placebo) group [5.7 (4.0-7.0) vs 5.0 (3.0-3.0-6.8); p = 0.01]. However, patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, the SF-36, PCL-5 and CFQ assessments were not different between the two groups.

Conclusions and Future Directions

We report that overnight infusions of dexmedetomidine did not prevent the onset of postoperative delirium after elective cardiac surgery. In our study, sleep quality was improved but more episodes of hypotension were reported in the dexmedetomidine-treated patients.

We believe that the results of our study and the DECADE study (where dexmedetomidine, initiated at anesthetic induction before cardiac surgery and continued for 24 hours, did not decrease postoperative delirium) are complementary as we tested a similar population but postulated a different mechanism of action 4. In addition, we confirmed the results of the DECADE study demonstrating postoperative dexmedetomidine use after cardiac surgery is not associated with greater arrythmia occurrence 4.

On the other hand, our study is the third randomized trial reporting a significant increase of hypotensive events among patients administered infusions of dexmedetomidine to reduce postoperative delirium. Therefore, the risks and benefits of using dexmedetomidine for delirium reduction or sleep improvement after cardiac surgery should be carefully considered.

In our study, dexmedetomidine improved patients sleep quality without decreasing the occurrence of postoperative delirium. Further studies should focus on the potential mechanisms, including circadian improvement, of the relationship between postoperative delirium and disturbed sleep. The benefit of sleep quality improvement on postoperative functional and cognitive outcomes should be investigated.

Reference

  1. Burry L, Hutton B, Williamson DR et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev. 2019;9(9):CD011749. doi: 10.1002/14651858.CD011749.pub2
  2. Burton JK, Craig LE, Yong SQ et al. Non-pharmacological interventions for preventing delirium in hospitalized non-ICU patients. Cochrane Database Syst Rev. 2021;7(7):CD013307. doi: 10.1002/14651858.CD013307.pub2
  3. Wang H, Zhang L, Luo Q, Li Y, Yan F. Effect of Sleep Disorder on Delirium in Post-Cardiac Surgery Patients. Can J Neurol Sci. 2020;47(5):627-633. doi: 10.1017/cjn.2020.62
  4. Turan A, Duncan A, Leung S et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomized placebo-controlled trial. Lancet. 2020;396(10245):177-185. doi: 10.1016/S0140-6736(20)30631-0
  5. Qu JZ, Mueller A, McKay TB et al. Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): A single-center, parallel-arm, randomized, placebo-controlled superiority trial. EClinicalMedicine. 2023;56:101796. doi: 10.1016/j.eclinm.2022.101796
  6. Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018;197(9):1147-1156. doi: 10.1164/rccm.201710-1995OC

Suggested Citation

Huet, Olivier. Prevention of postoperative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: A pragmatic, randomized, double blind, placebo-controlled trial; September 2024, Available at: https://deliriumnetwork.org/prevention-of-postoperative-delirium-overnight-dexmedetomidine-infusion/ (accessed today’s date)

Posted in Delirium Research.

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