Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial*

Nishikimi, Mitsuaki; Numaguchi, Atsushi; Takahashi, Kunihiko; Miyagawa, Yasuhiro; Matsui, Kazumi; Higashi, Michiko; Makishi, Go; Matsui, Shigeyuki; Matsuda, Naoyuki

doi:10.1097/ccm.0000000000003132

Cited by 102 publications

(104 citation statements)

References 24 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar to melatonin, few adverse events are reported with the medication, but sleep promotion was not proven and the cost is higher than that of melatonin. One recent single-center, double-blind, placebo-controlled RCT, also not included in this analysis, found that the administration of 8 mg of ramelteon at 20:00 hours each day to critically ill adults without delirium was associated with significant reduction in delirium occurrence (521).…”

Section: Melatoninmentioning

confidence: 99%

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Devlin

Skrobik

Gélinas

et al. 2018

Critical Care Medicine

2,477

2,938

View full text Add to dashboard Cite

We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

show abstract

Section: Melatoninmentioning

confidence: 99%

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Devlin

Skrobik

Gélinas

et al. 2018

Critical Care Medicine

2,477

2,938

View full text Add to dashboard Cite

show abstract

“…Another group analyzed melatonin levels in general medicine vs ICU patients and found that ICU patients have a blunted release of nightly melatonin compared to non‐ICU patients . One of the only studies to date examining the use of a melatonin agonist (ramelteon) in ICU patients was recently published . The primary outcome of the study, ICU length of stay, was not found to be significantly reduced in the ramelteon group; however, a secondary finding of occurrence of ICU delirium was significantly lower (24.4% in the ramelteon group vs 46.5% in the placebo group, p = 0.044).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that the administration of nightly low‐dose exogenous melatonin to elderly patients in hospital wards resulted in a lower incidence of delirium . In addition, a recent study found that administration of ramelteon, a melatonin receptor agonist, decreased patients’ ICU length of stay . The optimal melatonin dosage and impact on the incidence of delirium in critically ill patients, however, remains unknown.…”

mentioning

confidence: 99%

“…19 In addition, a recent study found that administration of ramelteon, a melatonin receptor agonist, decreased patients' ICU length of stay. 20 The optimal melatonin dosage and impact on the incidence of delirium in critically ill patients, however, remains unknown. Thus, the purpose of this study was to evaluate the effectiveness of melatonin on the prevention of ICU delirium in adult critically ill adults.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of Melatonin for the Prevention of Intensive Care Unit Delirium

et al. 2019

View full text Add to dashboard Cite

Study Objective Intensive care unit (ICU) delirium is an acute brain dysfunction that has been associated with increased mortality, prolonged ICU and hospital lengths of stay, and development of post‐ICU cognitive impairment. Melatonin may help to restore sleep and reduce the occurrence of ICU delirium. The purpose of this study was to evaluate the effectiveness of melatonin for the prevention of ICU delirium in critically ill adults. Design Retrospective, observational cohort study. Setting Large academic medical center. Patients A total of 232 adults were included who were admitted to the medical‐surgical or cardiac ICUs between 2013 and 2017 who had a negative Confusion Assessment Method for the ICU (CAM‐ICU). Of those, patients who received melatonin for at least 48 hours were included in the melatonin group (n=117). Patients were included in the control group if they were admitted to the ICU for at least 4 days (average time of melatonin initiation) and did not receive melatonin or antipsychotics within the first 4 days of their ICU stay (n=115). Measurements and Main Results The primary outcome was development of delirium, which was assessed by using the CAM‐ICU twice daily by nursing staff. The development of delirium was significantly lower in the melatonin group: 9 (7.7%) versus 28 (24.3%) patients (p = 0.001). This finding remained significant in multivariate logistic models controlling for age, sex, history of hypertension, need for emergent surgery, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, ICU length of stay, dexmedetomidine use, and benzodiazepine use. For those patients who developed delirium, patients in the control group had, on average, 20.9 delirium‐free days without coma in 28 days compared with 19.9 days in the melatonin group (p = 0.72). In the melatonin group, melatonin was used for a mean ± SD of 6.3 ± 7.9 days, with a median dose of 3.5 mg/night (range: 1–10 mg). Conclusion The development of ICU delirium was significantly lower in the melatonin group compared with that in the control group. To our knowledge, this is one of the only studies that has examined the use of melatonin for the prevention of ICU delirium. Melatonin may be a promising agent for the prevention of ICU delirium; however, a randomized study is needed to further validate its efficacy.

show abstract

“…Previously, studies evaluating the benefit of pharmacological agents to promote sleep with an impact on clinical outcomes have been lacking. In the past year, studies using dexmedetomidine and ramelteon have suggested a great role for pharmacological promotion of sleep as a way to reduce the risk for delirium and improvement in other related clinical outcomes such as length of stay, while studies with propofol have not suggested a similar benefit consistently . Given this growing body of literature, the ICU pharmacist will take a greater role promoting sleep in the ICU and serving as the pharmacotherapy expert within this realm.…”

Section: Discussionmentioning

confidence: 99%

Survey of clinical pharmacist perceptions and practices in promoting sleep in intensive care unit patients

Heavner

Nguyen

Knauert

et al. 2018

J Am Coll Clin Pharm

View full text Add to dashboard Cite

Objectives Sleep deprivation is associated with significant patient morbidity in the intensive care unit (ICU) and must be addressed through a systematic, interdisciplinary approach. The objectives of this study were to describe pharmacists' perceptions and practices regarding sleep in the ICU. We also assessed the prevalence and characteristics of systematic processes to promote sleep in ICU patients. Methods We administered an international, cross‐sectional survey to 1723 pharmacists via a member distribution list through the American College of Clinical Pharmacy Critical Care Practice and Research Network. The survey included questions about pharmacists' demographics, practice sites, and individual and site‐specific perceptions of sleep promotion practices. Results Two hundred fifty‐five (15%) pharmacists initiated the survey and 195 were completed and included for analysis. Respondents most commonly had less than 5 years of experience in ICU practice, completed a Critical Care Pharmacy Residency, and worked in a Medical or Surgical ICU. All participants responded that the assessment of sleep quality is important in the ICU. Most respondents reported that they recommend both non‐pharmacological (81%) and pharmacological (93%) interventions to optimize sleep in their ICU patients. Pharmacists reported most commonly recommending to adjust non‐sleep‐related medications to avoid nighttime administration (41.4%) and initiating melatonin receptor agonists (33.7%). A low number of respondents (9%) reported the presence of a sleep protocol in their ICU. Within this subset, 59% reported that less than half of their ICU patients actually receive the protocol and 41% indicated low protocol compliance. Conclusions Critical care pharmacists value sleep, and most recommend interventions to optimize sleep in their patients. However, sleep protocols in ICUs are uncommon, and overall protocol use and compliance are perceived to be low. Pharmacists can improve protocol use and compliance and potentially impact sleep, delirium incidence, or other ICU patient outcomes. This impact should be evaluated in future studies.

show abstract

Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial*

Abstract: Supplemental Digital Content is available in the text.

Cited by 102 publications

References 24 publications

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Effectiveness of Melatonin for the Prevention of Intensive Care Unit Delirium

Survey of clinical pharmacist perceptions and practices in promoting sleep in intensive care unit patients

Contact Info

Product

Resources

About