Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial

Oh, Esther S.; Leoutsakos, Jeannie Marie S.; Rosenberg, Paul B.; Pletnikova, Alexandra; Khanuja, Harpal S.; Sterling, Robert S.; Oni, Julius K.; Sieber, Frederick E.; Fedarko, Neal S.; Akhlaghi, Narjes; Neufeld, Karin J.

doi:10.1016/j.jagp.2020.05.006

Cited by 33 publications

(40 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Six of 59 (10%) had CAM-positive delirium following surgery. This delirium incidence is in line with other cohorts of elective orthopedic procedures 30,31 and probably relates to use of spinal anesthesia and/or improvements in post-operative delirium prevention. Individuals who were ATN biomarker-positive (any pattern), compared with those who were ATN biomarker-negative, experienced a higher rate of delirium, but this difference did not achieve statistical significance (23% vs 7%, P = 0.10).…”

Section: The Relationship With Delirium Incidence and Severitysupporting

confidence: 82%

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults

Fong

Vasunilashorn

Gou

et al. 2021

A&D Transl Res & Clin Interv

Self Cite

View full text Add to dashboard Cite

Introduction The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. Methods Participants ( n = 59) were free of clinical dementia, age 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme‐linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were A = amyloid beta (Aβ) 42 <175 pg/mL or Aβ 42/40 ratio <0.07; T = p‐tau >80 pg/mL; and N = t‐tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM‐Severity (CAM‐S) were rated daily post‐operatively for delirium and delirium severity, respectively. Results Aβ 42 , tau, and p‐tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM‐S [mean difference (95% confidence interval)] was 1.48 points higher (0.29‐2.67), P = 0.02 among the ATN positive. Delirium in the ATN‐positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM‐S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM‐S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM‐S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM‐S scores. Discussion The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre‐clinical phase, in delirium.

show abstract

Section: The Relationship With Delirium Incidence and Severitysupporting

confidence: 82%

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults

Fong

Vasunilashorn

Gou

et al. 2021

A&D Transl Res & Clin Interv

Self Cite

View full text Add to dashboard Cite

show abstract

“…A study, with 80 patients, investigating the effect of ramelteon on the prevention of postoperative delirium in older patients undergoing orthopedic surgery indicated 9% delirium incidence during the 2 days following surgery. [ 12 ] Referring to the results of this study, it is expected that the effect of melatonin agonists will be similar in patients with ASD with existing sleep disorders. Assuming that the incidence of postoperative sleep disorders is 50% in the Rozerem non-additional administration group, it will be about 80 cases when calculated with the ratio of α = 0.05, power = 0.8.…”

Section: Methodsmentioning

confidence: 83%

Study on the preventive effect of ramelteon on the onset of sleep disorder after general anesthesia in patients with autism spectrum disorder

Ayuse¹,

Ozaki-Honda

Kurata

et al. 2020

Medicine

View full text Add to dashboard Cite

Background: The persistent loss of consciousness caused by general anesthesia without the existence of repeated 90-minute cycles of non-REM and REM sleep might significantly disturb and suppress the cycle of normal physiological sleep in postoperative periods after general anesthesia. Patients with autism spectrum disorders (ASD) with existing circadian rhythm disorder are reported to rapidly deteriorate due to acute sleep disorder during the perioperative period after general anesthesia. A melatonin receptor agonist, ramelteon (Rozerem), which is a sleep cycle regulator, is used as a therapeutic drug for patients with sleep disorders, but there are no studies on the prevention of postoperative sleep disorder after general anesthesia. In this study, we investigate whether prophylactic administration of a sleep-inducing substance, a melatonin receptor agonist, is effective against sleep disorder after general anesthesia in patients with ASD. Methods/design: This study is intended for patients with ASD aged 12 years and above who undergo treatment at Nagasaki University Hospital, Isahaya General Hospital Dentistry, and Sasebo City General Medical Center Dentistry and undergo dental treatment under general anesthesia. A melatonin receptor agonist (Rozerem) will be taken 7 days prior and 7 days postsurgery in patients diagnosed with insomnia. A randomized comparison will be made between 2 groups: an experimental group that is additionally administered Rozerem and a control group. The primary endpoint is the incidence of NREM-REM sleep disorders that occur within 3 to 5 days after general anesthesia. The secondary endpoint is the incidence of circadian rhythm sleep disorders (rate of occurrence of sleep-retardation syndrome with drowsiness and strong fatigue). Discussion: Postoperative sleep disorders after general anesthesia has been reported in patients with ASD; however, effective preventive pharmacological treatments have not been established. A sleep cycle regulator, ramelteon (Rozerem), is used as a therapeutic drug for patients with sleep disorders by decreasing the difficulty of falling asleep in insomnia. If sleep disorder can be prevented after the administration of general anesthesia in patients with ASD, we can support social participation while maintaining their quality of life. Trial registration: The study was registered with the jRCT1071200030.

show abstract

“…[101][102][103] Although some of the results from these trials have been positive, the findings were not sufficiently robust (e.g., lack of validated tools to detect delirium) to recommend melatonergic drugs for the management of delirium. 101,104,105 Other pharmacological treatments There is insufficient evidence to recommend the following medications for delirium prevention and treatment: ketamine, cholinesterase inhibitors, statins, Z-hypnotics (e.g., zolpidem, zopiclone), NMDA receptor blocking agents (amantadine and memantine), methylphenidate, and gabapentin, based on efficacy. [106][107][108][109][110][111] Additionally, some of these medications are associated with a substantial risk of adverse events, including hallucinations (ketamine) and seizures (Z-drugs), which further discourages their prescription in patients with delirium.…”

Section: Melatonin and Melatonin Agonistsmentioning

confidence: 99%

Delirium in older adults

Garcez

Avelino‐Silva

Castro

et al. 2021

Geriatr Gerontol Aging

View full text Add to dashboard Cite

This narrative review provides a broad examination of the most current concepts on the etiopathogenesis, diagnosis, prevention, and treatment of delirium, an acute neuropsychiatric syndrome characterized by fluctuating changes in cognition and consciousness. With the interaction of underlying vulnerability and severity of acute insults, delirium can occur at any age but is particularly frequent in hospitalized older adults. Delirium is also associated with numerous adverse outcomes, including functional impairment, cognitive decline, increased healthcare costs, and death. Its diagnosis is based on clinical and cognitive assessments, preferably following systematized detection instruments, such as the Confusion Assessment Method (CAM). Delirium and its consequences are most effectively fought using multicomponent preventive interventions, like those proposed by the Hospital Elder Life Program (HELP). When prevention fails, delirium management is primarily based on the identification and reversal of precipitating factors and the non-pharmacological control of delirium symptoms. Pharmacological interventions in delirium should be restricted to cases of dangerous agitation or severe psychotic symptoms.

show abstract

Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial

Cited by 33 publications

References 44 publications

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults

Study on the preventive effect of ramelteon on the onset of sleep disorder after general anesthesia in patients with autism spectrum disorder

Delirium in older adults

Contact Info

Product

Resources

About