Effects of Melatonin for Delirium in Elderly Acute Heart Failure Patients: A Randomized, Single-Center, Double-Blind, and Placebo-Controlled Trial
DOI:
https://doi.org/10.1532/hsf.4325Keywords:
melatonin, acute heart failure, deliriumAbstract
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.
References
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.
