Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial

Abstract

Background: Postoperative delirium is common in elderly cardiac surgery patients. It is multifactorial and is influenced by the patient's baseline status and the nature of the medical and surgical interventions that the patient receives. Some of these factors are potentially modifiable, including postoperative sedation and analgesia protocols. This study has been designed to evaluate the effectiveness of postoperative intravenous acetaminophen in conjunction with either dexmedetomidine or propofol in decreasing the incidence of delirium.

Methods: This is a prospective, randomized, placebo-controlled, double-blinded, factorial trial that includes patients who are at least 60 years old and who are undergoing cardiac surgeries involving cardiopulmonary bypass, including coronary artery bypass graft (CABG) and combined CABG/valve surgeries. Patients are randomly assigned to receive one of four postoperative analgesic-sedation regimens: (1) acetaminophen and dexmedetomidine, (2) acetaminophen and propofol, (3) dexmedetomidine and placebo, or (4) propofol and placebo. The primary outcome, incidence of delirium, will be assessed with the Confusion Assessment Method (CAM or CAM-ICU). The secondary outcome, postoperative cognitive decline, will be assessed with the Montreal Cognitive Assessment. Additional secondary outcomes, including duration of delirium, postoperative analgesic requirement, length of stay, and incidence of adverse events, will also be reported. Data will be analyzed in 120 randomly assigned patients who received at least one dose of the study medication(s) on a modified intention-to-treat basis.

Discussion: This study has been approved by the institutional review board at Beth Israel Deaconess Medical Center, and the trial is currently recruiting. This study will systematically examine the implications of modification in postoperative sedative/analgesic protocols after cardiac surgery, specifically for short- and long-term cognitive outcomes. Any positive outcomes from this study could direct simple yet effective practice changes aimed to reduce morbidity.

Trial registration: ClinicalTrials.gov Identifier: NCT02546765 , registered January 13, 2015.

Keywords: Acetaminophen; Cardiac surgery; Confusion Assessment Method; Coronary artery bypass grafting; Dexmedetomidine; Montreal Cognitive Assessment; Neurocognition; Postoperative delirium; Propofol.

Conflict of interest statement

Ethics approval and consent to participate

This study has been approved by the Committee on Clinical Investigations Institutional Review Board at Beth Israel Deaconess Medical Center (Protocol 2014-P-000413). Written informed consent will be obtained from all subjects prior to initiation of study procedures by a trained study staff member. This will include discussion about all the aspects of the study, including drug intervention, assessments, follow-up, and acquisition and storage of blood samples.

Consent for publication

Not applicable.

Competing interests

The principal investigator is supported by National Institutes of Health Research Project Grant GM 098406. The authors declare that they have no competing interests.

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Figures

Fig. 1

Study schema

Fig. 2

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure: The schedule of enrollment, interventions, and assessments in the study