A phase II study of ramelteon for the prevention of postoperative delirium in elderly patients undergoing gastrectomy

Honda, Shinya; Furukawa, Katsunori; Makuuchi, Rie; Irino, Tomoyuki; Tokunaga, Masanori; Tanizawa, Yutaka; Bando, Etsuro; Kawamura, Taiichi; Shinsato, Kaori; Matsumoto, Teruaki; Terashima, Masanori

doi:10.1007/s00595-020-02073-9

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Hokuto et al ( 2020) reported that ramelt-eon, an agonist of the melatonin receptor, reduces the risk of POD after hepatectomy. Honda et al (2020) also reported that ramelteon is feasible for preventing POD in elderly patients after gastrectomy. In the future, such drugs may be used to prevent delirium in elderly patients after hepatectomy.…”

Section: Discussionmentioning

confidence: 94%

Usefulness of Preoperative Controlling Nutritional Status in Predicting Prolonged Hospitalization and Incidence of Postoperative Delirium for Elderly Hepatectomy with Hepatocellular Carcinoma

Fujio

Usuda

Hara

et al. 2022

Tohoku J. Exp. Med.

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The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing, but it remains unclear whether hepatectomy can be performed using the same criteria as in younger patients. Furthermore, the appropriate preoperative evaluation for hepatectomy in elderly patients is not yet clearly defined. Here, we investigated the applicability of preoperative assessment using the Controlling Nutritional Status (CONUT) score to help improve hepatectomy outcomes in elderly patients with HCC. This was a single-center retrospective analysis, and the study population comprised 64 consecutive patients who underwent hepatectomy for HCC between January 2012 and August 2016. We compared the preoperative assessment and perioperative outcomes between elderly (≥ 75 years old) and younger (< 75 years old) patients. A total of 61 patients were reviewed. Poor preoperative CONUT score was associated with a longer postoperative hospital stay in elderly patients undergoing hepatectomy for HCC. In addition, although elderly patients had similar perioperative outcomes to younger patients, the incidence of delirium was significantly higher, and univariate analysis confirmed that old age is a risk factor for delirium among the preoperative factors. Hepatectomy for HCC in the elderly can be safely performed with appropriate preoperative nutritional assessment using CONUT score and prevention of postoperative delirium. Preoperative nutritional assessment using the CONUT score was useful in predicting prolonged hospitalization for elderly hepatectomy with HCC.

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Section: Discussionmentioning

confidence: 94%

Usefulness of Preoperative Controlling Nutritional Status in Predicting Prolonged Hospitalization and Incidence of Postoperative Delirium for Elderly Hepatectomy with Hepatocellular Carcinoma

Fujio

Usuda

Hara

et al. 2022

Tohoku J. Exp. Med.

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“…Ramelteon, the only melatonin analog included in this meta-analysis, has a 6-fold higher affinity for melatonin 1 receptors and a 3-fold higher affinity for melatonin 2 receptors ( 44 ); ramelteon's higher affinity for melatonin receptors may contribute to its favorable benefits in delirium prevention, and previous RCTs reported that ramelteon can reduce POD after non-cardiac surgery in elderly patients ( 45 , 46 ). However, in this meta-analysis, results from an RCT and an observational study showed no evidence of a preventive effect of ramelteon 8 mg on POD in adults who underwent cardiac surgery.…”

Section: Discussionmentioning

confidence: 99%

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

Han

Tian

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe effectiveness of melatonin and its analogs in preventing postoperative delirium (POD) following cardiac surgery is controversial. The purpose of this systematic review and meta-analysis was to confirm the benefits of melatonin and its analogs on delirium prevention in adults who underwent cardiac surgery.MethodsWe systematically searched the PubMed, Cochrane Library, Web of Science, Embase, and EBSCOhost databases, the last search was performed in October 2021 and repeated before publication. The controlled studies were included if investigated the impact of melatonin and its analogs on POD in adults who underwent cardiac surgery. The primary outcome was the incidence of delirium. The Stata statistical software 17.0 was used to perform this study.ResultsThis meta-analysis included eight randomized controlled trials (RCTs) and two cohort studies with a total of 1,714 patients. The results showed that melatonin and ramelteon administration were associated with a significantly lower incidence of POD in adults who underwent cardiac surgery (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.29–0.74; P = 0.001). The subgroup analyses confirmed that melatonin 3 mg (OR, 0.37; 95% CI, 0.18–0.76; P = 0.007) and 5 mg (OR, 0.34; 95% CI, 0.21–0.56; P < 0.001) significantly reduced the incidence of POD.ConclusionMelatonin at dosages of 5 and 3 mg considerably decreased the risk of delirium in adults who underwent cardiac surgery, according to our results. Cautious interpretation of our results is important owing to the modest number of studies included in this meta-analysis and the heterogeneity among them.Systematic Review RegistrationPROSPERO registration number: CRD42021246984.

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“…Moreover, in a recent clinical study, ramelteon was found to be effective for the prevention of delirium in elderly patients undergoing gastrectomy. 2 Therefore, ramelteon represents an interesting synthetic target. However, ramelteon’s molecular structure consisting of a tricyclic 1,6,7,8-tetrahydro-2 H -indeno[5,4- b ]furan core containing a chiral substituent suggests that its concise and efficient asymmetric synthesis might be challenging.…”

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confidence: 99%

“…The ramelteon market value in 2019 accounted for $161 million (USD), which makes it a valuable drug in the category of medications for the treatment of sleeping disorders. Moreover, in a recent clinical study, ramelteon was found to be effective for the prevention of delirium in elderly patients undergoing gastrectomy . Therefore, ramelteon represents an interesting synthetic target.…”

mentioning

confidence: 99%

Concise Six-Step Asymmetric Approach to Ramelteon from an Acetophenone Derivative Using Ir, Rh, Cu, and Ni Catalysis

Jérôme¹,

Nettekoven²,

Kovačevič³

et al. 2021

J. Org. Chem.

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A concise six-step asymmetric synthesis of nearly enantiomerically pure ramelteon was developed from a monocyclic precursor with a 17% overall yield and a 97% ee in the asymmetric step. The synthetically challenging tricyclic 1,6,7,8-tetrahydro-2 H -indeno[5,4- b ]furan core of ramelteon was assembled by using Ir-catalyzed O -vinylation and Rh-catalyzed vinyl ether annulation through directed C–H bond activation, while the chirality was introduced with enantioselective reduction of an α,β-unsaturated nitrile moiety under hydrosilylation conditions using a Cu II /Walphos type catalyst. The presented methodology represents the shortest synthetic approach to ramelteon.

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A phase II study of ramelteon for the prevention of postoperative delirium in elderly patients undergoing gastrectomy

Cited by 6 publications

References 28 publications

Usefulness of Preoperative Controlling Nutritional Status in Predicting Prolonged Hospitalization and Incidence of Postoperative Delirium for Elderly Hepatectomy with Hepatocellular Carcinoma

Usefulness of Preoperative Controlling Nutritional Status in Predicting Prolonged Hospitalization and Incidence of Postoperative Delirium for Elderly Hepatectomy with Hepatocellular Carcinoma

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

Concise Six-Step Asymmetric Approach to Ramelteon from an Acetophenone Derivative Using Ir, Rh, Cu, and Ni Catalysis

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