Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial

Introduction Postoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored.Methods and analysis This multicentre, randomised, placebo-controlled, quadruple-blinded trial will include 900 older (>60 years) cardiac surgical patients requiring CPB. Patients meeting the inclusion criteria and not meeting any exclusion criteria will be enrolled at seven centres across the USA with Beth Israel Deaconess Medical Center (BIDMC), Boston, as the central coordinating centre. Additional sites may be included to broaden or speed accrual. The primary outcome measure is the incidence of in-hospital delirium till day 30. Secondary outcomes include the duration and severity of in-hospital delirium, hospital and ICU lengths of stay, postoperative pain scores, postoperative rescue analgesic consumption, postoperative cognitive function and chronic sternal pain. Creation of a biorepository and the use of intraoperative-blinded electroencephalogram (EEG) and cerebral oximetry data will support exploratory endpoints to determine mechanistic predictors of postoperative delirium.Ethics and dissemination This trial is approved and centrally facilitated by the Institutional Review Board at BIDMC. An independent Data Safety and Monitoring Board is responsible for maintaining safety oversight. Protocol # 2019 P00075, V.1.4 (dated 20 October 2020).Trial registration number NCT04093219

CONSORT checklist.

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Intraoperative anesthetics administered by group.

Intraoperative anesthetics administered by group.</p

Original master protocol.

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Protocol explanation letter.

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Preoperative characteristics.

Preoperative characteristics.</p

Data export.

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Postoperative outcomes.

Postoperative outcomes.</p

Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Consolidated Standards of Reporting Trials (CONSORT) flow diagram.</p

Fig 2 -

A) Image of a study patient using the VR equipment. B) Screenshot of a typical immersive environment with an example of text communication from study personnel. The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish this image.</p