A new randomized trial finds that the dual orexin receptor antagonist suvorexant, given nightly to patients recovering from cardiac surgery, did not improve objective sleep measures or reduce postoperative delirium compared with placebo.
The findings challenge the assumption that blocking orexin signaling can rescue sleep in the uniquely hostile environment of the intensive care unit, where noise, light, pain, and disrupted circadian rhythms create a near-perfect obstacle to restorative rest.
What they found
The multicenter, double-blind trial enrolled 100 adults who had undergone cardiac surgery with cardiopulmonary bypass at two academic medical centers. Patients received either suvorexant 20 mg or placebo once nightly, starting the first night after extubation and continuing until hospital discharge or up to seven days.
The primary outcome was wakefulness after sleep onset (WASO), measured objectively by EEG using the SedLine system from Masimo. The results were unambiguous. Patients in the suvorexant group spent an average of 200.7 minutes awake after initially falling asleep, compared with 184.2 minutes in the placebo group. The difference was not statistically significant (p = 0.33). Total sleep time followed the same pattern: 224 minutes for suvorexant versus 253 minutes for placebo (p = 0.92).
Secondary outcomes also showed no benefit. There was no difference in the use of rescue sleep medications, no improvement in subjective sleep quality as rated by patients, and no reduction in the incidence of postoperative delirium or in delirium-free days.
The study was funded by Merck, the manufacturer of suvorexant. One of the investigators, Matthias Eikermann, has served on an advisory board for the drug and received research funding from Merck for this trial.
Why it matters
Suvorexant is approved for the treatment of insomnia and works by blocking orexin, a neuropeptide that promotes wakefulness. The drug has shown promise for improving sleep in older adults with insomnia and, in smaller studies, for reducing delirium risk in hospitalized patients. Its use in the ICU has been growing, driven by the intuition that a targeted orexin antagonist might improve sleep more effectively than benzodiazepines or other sedatives with less cognitive side effects.
This trial suggests that intuition may be wrong in the acute postoperative context. The ICU is not the bedroom. Patients recovering from cardiac surgery face a storm of factors that fragment sleep: pain from sternotomy and chest tubes, mechanical ventilation, frequent nursing interventions, alarms, and the lingering effects of anesthesia and cardiopulmonary bypass. Under these conditions, simply blocking orexin may not be enough. The sleep drive may be overwhelmed by nociception, inflammation, and environmental disruption.
The negative result is particularly notable because the trial used objective EEG monitoring rather than subjective reports. Subjective sleep assessments often overestimate improvement in ICU patients, who may be amnestic for periods of wakefulness. The EEG data here provide a more reliable picture, and the picture is clear: suvorexant did not meaningfully change sleep architecture in this setting.
Limits
The trial has important limitations. It was relatively small at 100 patients, and it enrolled a specific population of cardiac surgery patients. The results may not generalize to other ICU populations or to patients receiving different surgical procedures. The study was conducted at only two centers, both in the United States. The funding source is also worth noting: industry-sponsored trials of a manufacturer’s own drug raise the possibility of publication bias, though in this case the negative result was published in full, which is itself a meaningful contribution.
The SedLine EEG system captures frontal leads only, which may not capture all aspects of sleep architecture, particularly rapid eye movement sleep originating from posterior regions. And the dosing regimen (20 mg nightly, started the first night after extubation) may not represent the optimal timing or dose for this population.
Bottom line
Suvorexant did not improve sleep quality or reduce delirium in patients recovering from cardiac surgery in the ICU, despite objective EEG measurement and a rigorous randomized design. The drug may still have a role in other settings or patient populations, but these data do not support its routine use for sleep management after cardiac surgery. Further research is needed to identify which ICU patients, if any, might benefit from orexin antagonism and whether alternative approaches to ICU sleep hygiene or pharmacotherapy can produce meaningful improvements.
Source
Eikermann M, et al. Effect of the orexin receptor antagonist, suvorexant, on sleep architecture in the early postoperative period following cardiac surgery: a randomized controlled trial. Critical Care. 2026 Jun 23. doi: 10.1186/s13054-026-06151-1. PMID: 42337809.