Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit

Abstract

IntroductionInsomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.Methods and analysisIn this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.Ethics and disseminationEthics approval was obtained through the ‘Committee on Clinical Investigations’ at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.Trial registration numberThis trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study

“…[4][5][6] Awareness regarding risk factors, prevention, and diagnosis of postoperative delirium has grown substantially in recent years. [7][8][9] There are equivocal data on the association between intraoperative blood pressure management and the incidence of postoperative delirium. [10][11][12][13] A critical decrease in cerebral perfusion pressure, for example, during cardiac arrest is an independent risk factor for delirium.…”

A Rapid Systematic Review of Pharmacologic Sleep Promotion Modalities in the Intensive Care Unit

“…[18][19][20]25,26,29,31,32 Suvorexant and other orexin receptor antagonists are also important candidates for ICU sleep research given they have been found to be beneficial for chronic insomnia, may help prevent delirium, and have a relatively benign safety profile. 47,48…”

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement

“…However, the study of pharmacologic options to promote nighttime sleepiness is limited by small trial sizes, the failure to enroll mechanically ventilated adults with a high severity of illness, and an overreliance on delirium reduction and/or patient-reported sleep quality to define efficacy. In addition, RCTs to date have involved prescribing of pharmacologic agents upon ICU admission or timed in relation to specific clinical events (e.g., surgical procedure) ( 222 – 224 ). However, in practice, clinicians are frequently seeking options to promote sleep after patients report sleep disruption or have already presented with delirium.…”