Effects of Melatonin on Postoperative Delirium After PCI in Elderly Patients: A Randomized, Single-Center, Double-Blind, Placebo-Controlled Trial
Anti-delirium Effects of Melatonin
DOI:
https://doi.org/10.1532/hsf.4049Keywords:
Acute myocardial infarction, PCI, postoperative delirium, prognosisAbstract
Background: Experimental evidence has indicated the benefits of melatonin (Mel) for the treatment of delirium. Clinical trials had no definite conclusions concerning Mel on delirium after percutaneous transluminal coronary intervention (PCI) in elderly patients. The present study explored whether acute Mel treatment could reduce the incidence of delirium.
Methods: This trial enrolled patients over the age of 60, who were admitted to intensive care units (ICUs) after PCI. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive Mel (3 mg/day) or placebo once daily for up to 7 days. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method (CAM) during the first 7 postoperative days. Analyses were performed using intention-to-treat and safety populations.
Results: A total of 297 patients randomly were assigned to receive either placebo (N = 149) or Mel (N = 148). The incidence of postoperative delirium was significantly lower in the Mel group than in the placebo group (27.0% vs. 39.6%, respectively, P = 0.02). There was no significant difference between 30-day all-cause mortality (12.2% vs. 14.1%, P = 0.62) and drug reactions (0 vs. 2.0%, P = 0.25). The length of stay and hospitalization costs in the Mel group were significantly decreased compared with those in the placebo group (P > 0.05).
Conclusion: The current study suggests that Mel is safe and effective in the treatment of delirium after PCI. Further investigation is necessary to fully understand the potential usefulness of Mel in older patients via larger randomized, multicenter, double-blind, and placebo-controlled trials.
References
Abelha FJ, Luis C, Veiga D, Parente D, Fernandes V, Santos P, et al. 2013. Outcome and quality of life in patients with postoperative delirium during an ICU stay following major surgery. Critical Care. 17(5).
Al Tmimi L, Verbrugghe P, Van de Velde M, Meuris B, Meyfroidt G, Milisen K, et al. 2020. Intraoperative xenon for prevention of delirium after on-pump cardiac surgery: a randomised, observer-blind, controlled clinical trial. British Journal of Anaesthesia. 124(4):454-62.
Baumgartner L, Lam K, Lai J, Barnett M, Thompson A, Gross K, et al. 2019. Effectiveness of Melatonin for the Prevention of Intensive Care Unit Delirium. Pharmacotherapy. 39(3):280-7.
Chen J, Chen G, Li J, Qian C, Mo H, Gu C, 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. 57(3):340-7.
Chen J, Wang Y, Hu X, Li M, Xiong K, Zhang Z, et al. 2020. The role of statins in the management of delirium: Recent advances. CNS Neurol Disord Drug Targets.
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.
Dong Y, Fan C, Hu W, Jiang S, Ma Z, Yan X, et al. 2016. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling. Journal of Pineal Research. 60(3):253-62.
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. 2001. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). Jama. 286(21):2703-10.
Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, et al. 2010. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Critical Care Medicine. 38(7):1513-20.
Gleason LJ, Schmitt EM, Kosar CM, Tabloski P, Saczynski JS, Robinson T, et al. 2015. Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults. Jama Surgery. 150(12):1134-40.
Han YY, Wu J, Qin ZS, Fu WJ, Zhao BC, Li X, et al. 2020. Melatonin and its analogues for the prevention of postoperative delirium: A systematic review and meta-analysis. Journal of Pineal Research.
Li S, Zhang XH, Zhou GD, Wang JF. 2019. Delirium after primary percutaneous coronary intervention in aged individuals with acute ST-segment elevation myocardial infarction: A retrospective study. Exp Ther Med. 17(5):3807-13.
Liu J-C, Li L, Yan H-C, Zhang T, Zhang P, Sun Z-Y, 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. 67(1).
Mather JF, Corradi JP, Waszynski C, Noyes A, Duan Y, Grady J, et al. 2017. Statin and Its Association With Delirium in the Medical ICU. Critical Care Medicine. 45(9):1515-22.
Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, et al. 2004. Costs associated with delirium in mechanically ventilated patients. Critical Care Medicine. 32(4):955-62.
Pandharipande PP, Girard TD, Ely EW. 2014. Long-Term Cognitive Impairment after Critical Illness REPLY. New England Journal of Medicine. 370(2):185-6.
R E, E L-H. 2020. Elimination of the causes of poor sleep underlying delirium is a basic strategy to prevent delirium. Current molecular pharmacology.
Redelmeier DA, Manzoor F, Thiruchelvam D. 2019. Association Between Statin Use and Risk of Dementia After a Concussion. Jama Neurology. 76(8):887-96.
Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, et al. 2012. Cognitive trajectories after postoperative delirium. N Engl J Med. 367(1):30-9.
SJ J, AD V, AJ H, H A, A A, NH K, et al. 2019. Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy. Critical care medicine. 47(12):1751-8.
SJ J, TJ M, NE W, DY K, J S, S G, et al. 2018. Melatonin and Sleep in Preventing Hospitalized Delirium: A Randomized Clinical Trial. The American journal of medicine. 131(9):1110-7.e4.
van den Boogaard M, Slooter AJC, Bruggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, et al. 2018. Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium The REDUCE Randomized Clinical Trial. Jama-Journal of the American Medical Association. 319(7):680-90.
Xuan Y, Fan R, Chen JH, Wang YH, Wu JY, Yang JJ, et al. 2018. Effects of dexmedetomidine for postoperative delirium after joint replacement in elderly patients: a randomized, double-blind, and placebo-controlled trial. International Journal of Clinical and Experimental Medicine. 11(12):13147-57.
