Effects of Melatonin for Delirium in Elderly Acute Heart Failure Patients: A Randomized, Single-Center, Double-Blind, and Placebo-Controlled Trial
Keywords:melatonin, acute heart failure, delirium
Background: Delirium is a common, life-threatening, typical clinical syndrome with the main clinical manifestations of temporary organic mental disorder without specific drug treatment. The aim of the study was to explore the benefits of melatonin for the treatment of delirium after acute heart failure in elderly patients.
Methods: This was a randomized, double-blind, and placebo-controlled trial. This study enrolled patients aged more than 60 years after acute heart failure. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either melatonin (3 mg/day, 7 days) or placebos. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 days. Analyses were performed by intention-to-treat and safety populations.
Results: Between October 2015 and October 2019, 584 patients were assessed. A total of 497 patients randomly were assigned to receive either placebo (N = 249) or melatonin (N = 248). The incidence of delirium was significantly lower in the melatonin group than in the placebo group (27.0% vs. 36.9%, P = 0.021). Regarding safety, the occurrence of rhabdomyolysis and abnormal hepatic function did not differ between the two groups.
Conclusion: The current study (clinical trial registered number: CHWX-904-201511) suggests that acute melatonin treatment can reduce the incidence of delirium for elderly acute heart failure. It also can reduce the time of hospital stays and hospitalization costs. The therapy was safe and worth spreading.
Chen J, Chen G, Li J, et al. 2014. Melatonin attenuates inflammatory response-induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of pro-inflammatory cytokines. Journal of Pineal Research. Oct;57(3):340-347.
Chen J, Wang Y, Hu X, et al. 2020. The role of statins in the management of delirium: Recent advances. CNS Neurol Disord Drug Targets. Jul 19.
CP Y, PT T, J P-CC, H S, SK S, KP S. 2020. Melatonergic agents in the prevention of delirium: A network meta-analysis of randomized controlled trials. Sleep medicine reviews. 50:101235.
Gleason LJ, Schmitt EM, Kosar CM, et al. 2015. Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults. Jama Surgery. Dec; 150(12):1134-1140.
Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. 2019. Lancet Neurol. May;18(5):439-458.
Han YY, Wu J, Qin ZS, et al. 2020. Melatonin and its analogues for the prevention of postoperative delirium: A systematic review and meta-analysis. Journal of Pineal Research. e12644.
Hokuto D, Nomi T, Yoshikawa T, Matsuo Y, Kamitani N, Sho M. 2020. Preventative effects of ramelteon against postoperative delirium after elective liver resection. PLoS One. 15(11):e0241673.
Iwata E, Kondo T, Kato T, et al. 2020. Prognostic Value of Delirium in Patients With Acute Heart Failure in the Intensive Care Unit. Can J Cardiol. Oct;36(10):1649-1657.
Kwak MJ, Avritscher E, Holmes HM, et al. 2021. Delirium Among Hospitalized Older Adults With Acute Heart Failure Exacerbation. J Card Fail. Apr;27(4):453-459.
Liu J-C, Li L, Yan H-C, et al. 2019. Identification of oxidative stress-related Xdh gene as a di(2-ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP-induced impairments in newborn mouse ovaries. Journal of Pineal Research. Aug;67(1)e12577.
Mather JF, Corradi JP, Waszynski C, et al. 2017. Statin and Its Association With Delirium in the Medical ICU. Critical Care Medicine. Sep;45(9):1515-1522.
Odinokova I, Baburina Y, Kruglov A, et al. 2018. Effect of Melatonin on Rat Heart Mitochondria in Acute Heart Failure in Aged Rats. Int J Mol Sci. May 23; 19(6).
Pak M, Hara M, Miura S, et al. 2020. Delirium is associated with high mortality in older adult patients with acute decompensated heart failure. BMC Geriatr. Dec 3;20(1):524.
Saczynski JS, Marcantonio ER, Quach L, et al. 2012. Cognitive trajectories after postoperative delirium. N Engl J Med. Jul 5;367(1):30-9.
SJ J, AD V, AJ H, et al. 2019. Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy. Critical care medicine. 47(12):1751-1758.
SJ J, TJ M, NE W, et al. 2018. Melatonin and Sleep in Preventing Hospitalized Delirium: A Randomized Clinical Trial. The American journal of medicine. 131(9):1110-1117.e4.
Wang J, Toan S, Li R, Zhou H. 2020. Melatonin fine-tunes intracellular calcium signals and eliminates myocardial damage through the IP3R/MCU pathways in cardiorenal syndrome type 3. Biochem Pharmacol. Apr;174:113832.
How to Cite
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).