Efficacy of Orexin Receptor Antagonist for Delirium after Coronary Artery Bypass Grafting Compared with Melatonin Receptor Agonist

Abstract

Postoperative delirium (POD) represents a disturbance in attention, awareness, and cognition that develops over the postoperative period. The prevalence of POD after coronary artery bypass grafting (CABG) is reported from 37 to 52% 1,2) . Because POD increases postoperative complications and prolongs intensive care unit and hospital stay 3) , patient's outcomes could have been worse. Some medicines were reported to reduce the incidence of POD. Ramelteon, as a melatonin receptor agonist, regulates the sleep cycle and improves subjective sleep quality of patients with chronic insomnia 4) . Ramelteon also is reported to reduce the occurrence of delirium in patients admitted to the intensive care unit (ICU) 5) .Recently, Suvorexant, as a new type of sleep medication as an orexin receptor antagonist, is noted for subjective measures of sleep onset and maintenance 6) . The orexin neuropeptide signal system supports wakefulness, but Suvorexant inhibits the bind-ing of orexin neuropeptides to receptors and suppresses the wake drives. Recently, a few studies reported the effect of Suvorexant for delirium [7][8][9] .The purposes of this study were to investigate the availability of Suvorexant for POD after CABG and to evaluate the effect of Suvorexant for the operative outcome. II. Patients and methods Thisretrospective study was approved by the institutional review board of Soka municipal hospital. Cardiac surgery has started since February 2013 in our institution. In a total of 175 consecutive patients who underwent elective CABG from February 2013 to May 2019. We investigated the patients weaned ventilator support at the first postoperative day (under 24 hours after operation), excluded patients with a mental disorder, sleep disorder and dementia patient. And the patients with emergency operations were excluded. Because benzodiazepine could induce POD, patients with benzodiazepine sedative-hypnotic agent for insomnia after CABG were excluded, too. So, 138 patients (29 women, mean age 69.7 ± 3.4 years) were intended.Induction and maintenance of operative anesthesia were similar for all patients and consisted of weight-related doses of fentanyl, midazolam, and pancuronium bromide.

Melatonin and Its Analogs for Prevention of Post-cardiac Surgery Delirium: A Systematic Review and Meta-Analysis

“…After analyzing the titles and abstracts, we determined that 26 full-text publications were possibly acceptable for inclusion, whereas 102 studies were excluded. Finally, eight RCTs ( 19 – 22 , 29 – 32 ) and two observational studies ( 33 , 34 ) were included based on the aforementioned eligibility criteria.…”

“…Ten studies ( 19 – 22 , 29 – 34 ) (1,714 patients) were published in English between 2015 and 2021. The sample size ranged from 50 to 500, and the participants were mainly elderly inpatients.…”

“…The interventions used included ramelteon 8 mg in two studies ( 31 , 34 ) and melatonin 3 mg or 5 mg in eight studies ( 19 – 22 , 29 , 30 , 32 , 33 ). Nine studies ( 19 – 21 , 29 – 34 ) included 1,417 patients who underwent cardiothoracic surgery, such as coronary artery bypass graft surgery, aortic valve replacement, mitral valve replacement, and elective pulmonary thromboendarterectomy. A total of 297 patients underwent percutaneous transluminal coronary intervention ( 22 ).…”

“…A total of 297 patients underwent percutaneous transluminal coronary intervention ( 22 ). As diagnostic methods for POD, the Intensive Care Delirium Screening Checklist (ICDSC) ( 32 , 34 ), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) ( 19 – 22 , 30 , 31 , 33 ), and clinical observations ( 29 ) were employed. Table 1 presents the characteristics of the included studies.…”

“…The other study was also classified as being associated with “some concern” owing to deviations from intended interventions and outcome measurements ( 29 ) ( Supplementary Table 2 ). The NOS scores in the two non-randomized observational studies were 8 ( 33 ) and 9 ( 34 ), respectively ( Supplementary Table 3 ).…”