Postoperative delirium after pharyngolaryngectomy with esophagectomy: a role for ramelteon and suvorexant

Abstract

BackgroundPostoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping medications and postoperative delirium after pharyngolaryngectomy with esophagectomy.MethodsWe performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016. All data were assessed by two psychiatrists, and univariate and multivariate analyses were performed.ResultsPostoperative delirium developed in 9 (13.8%) patients, with most cases (77.8%) occurring between postoperative day (POD) 1 and POD 3. Of the 24 patients taking a minor tranquilizer after surgery, 8 (33.3%) became delirious, but, of the remaining 41 patients taking ramelteon with or without suvorexant, only one (2.4%) became delirious after surgery. Moreover, of the 16 patients taking both ramelteon and suvorexant, no postoperative delirium was observed. Ramelteon with or without suvorexant was significantly associated with a decreased rate of postoperative delirium compared with minor tranquilizer use (p = 0.001). Multivariate analysis confirmed that the use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium (odds ratio 0.060, p = 0.013).ConclusionThe use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium after pharyngolaryngectomy with esophagectomy. However, using minor tranquilizers was associated with postoperative delirium. We recommend ramelteon with or without suvorexant for preventing postoperative delirium after pharyngolaryngectomy with esophagectomy.

Melatonin and its analogues for the prevention of postoperative delirium: A systematic review and meta‐analysis

“…Melatonin dose was 3 mg in 4 studies, 27‐29,31 5 mg in 2 studies 30,33 and 50 mg/kg in 1 study 32 . Ramelteon dose was 8 mg in the remaining 2 studies 34,35 . The diagnostic tools for delirium were different among these studies.…”

“…From these, 10 records were excluded due to the following reasons: 9 for conference abstracts and 1 for reporting tryptophan supplementation with no difference in the postoperative serum melatonin levels 26 . Finally, 6 randomized controlled trials, 27‐32 2 cohort studies 33,34 and 1 case‐control study 35 were included in the meta‐analysis.…”

“…Six studies compared the effect of melatonin with that of a placebo, 27,29‐33 1 study compared the effect of melatonin with that of oxazepam, 28 and 2 studies compared the effect of ramelteon with that of a placebo 34 or a tranquilizer 35 . Four studies were associated with patients undergoing cardiac surgery, 28‐29,31,33 while the remaining studies were associated with hip surgery, 27,30 liver resection, 32 pulmonary resection 34 and pharyngolaryngectomy with esophagectomy 35 . Melatonin dose was 3 mg in 4 studies, 27‐29,31 5 mg in 2 studies 30,33 and 50 mg/kg in 1 study 32 .…”

Suvorexant is associated with a low incidence of delirium in critically ill patients: a retrospective cohort study

“…However, the majority of study subjects were patients in acute care general wards (64%), while a minority (36%) of patients were in the ICU . A single‐centre retrospective observational study by Booka et al, showed that the use of suvorexant combined with ramelteon was associated with a decrease in postoperative delirium, but the only patients included in the study were those who had undergone pharyngolaryngectomy with esophagectomy . Another randomized control study by Hatta et al, showed that suvorexant had protective effects against delirium in acute care wards and ICU, but all intubated patients were excluded .…”

“…5 A single-centre retrospective observational study by Booka et al, showed that the use of suvorexant combined with ramelteon was associated with a decrease in postoperative delirium, but the only patients included in the study were those who had undergone pharyngolaryngectomy with esophagectomy. 9 Another randomized control study by Hatta et al, showed that suvorexant had protective effects against delirium in acute care wards and ICU, but all intubated patients were excluded. 10 In contrast to these studies, the present study was conducted only in an ICU, almost exclusively with intubated patients (Table 2).…”