Cardiac critical care, Melatonin, Postoperative delirium
Citation Information :
Niyogi SG, Naskar C, Singh A, Kumar B, Grover S. Melatonin and Melatonin Agonists for Prevention of Delirium in the Cardiac Surgical ICU: A Meta-analysis. Indian J Crit Care Med 2023; 27 (11):837-844.
Aim and Background: Delirium is highly prevalent in the immediate postoperative period following cardiac surgery and adversely impacts outcomes. Melatonin has been increasingly used in pharmacological prevention of delirium. We aimed to synthesize the available evidence concerning the role of melatonin and melatonin agonists in preventing delirium in patients after cardiac surgery.
Materials and methods: PubMed, Google Scholar, and Web of Science databases were searched for relevant randomized and non-randomized trials in adults undergoing cardiac surgery investigating melatonin agonists to prevent delirium. Studies incorporating transplants, preoperative organ support, prophylactic antipsychotics, or children were excluded. Risk-of-bias was assessed using Cochrane ROB 2.0 and ROBINS-I tools. A systematic review and meta-analysis were conducted, calculating pooled odds ratio (OR) for the incidence of postoperative delirium using a random effects model with the Mantel–Haenszel method with restricted maximum-likelihood estimator. Trial sequential analysis was also carried out for the primary outcome.
Results: Six randomized trials and one non-randomized trial involving 1,179 patients were included. Incidence of delirium was 16.7 and 29.6% in the intervention and comparator groups respectively, indicating a pooled OR of 0.44 [95% confidence interval (CI) 0.27 – 0.71, p = 0.04] favoring melatonin. Two studies had a high risk of bias, and I2 statistics indicated significant heterogeneity. However, publication bias was insignificant, and trial sequential analysis indicated the significance of the attained effect size.
Conclusion: Based on available studies, perioperative melatonin use significantly decreases postoperative incidence of delirium after adult cardiac surgery. However, the available quality of evidence is low, and larger trials with standardization of nonpharmacological delirium prevention interventions, in high-risk cohorts, and exploring various dosages and regimens should be carried out.
Evans A, Weiner M, Arora R, Chung I, Deshpande R, Varghese R, et al. Current approach to diagnosis and treatment of delirium after cardiac surgery. Ann Card Anaesth 2016;19(2):328–337. DOI: 10.4103/0971-9784.179634.
Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: A meta-analysis. J Cardiothorac Surg 2021;16(1):113. DOI: 10.1186/s13019-021-01496-w.
Junior MM, Kumar A, Kumar P, Gupta P. Assessment of delirium as an independent predictor of outcome among critically ill patients in intensive care unit: A prospective study. Indian J Crit Care Med 2022;26:676–681. DOI: 10.5005/jp-journals-10071-23907.
Balasubramanian V, Suri JC, Ish P, Gupta N, Behera D, Gupta P, et al. Neurocognitive and quality-of-life outcomes following intensive care admission: A prospective 6-month follow-up study. Indian J Crit Care Med 2021;24(10):932–937. DOI: 10.5005/jp-journals- 10071-23576.
Grover S, Avasthi A. Clinical practice guidelines for management of delirium in elderly. Indian J Psychiatry 2018;60(Suppl. 3):S329–S340. DOI: 10.4103/0019-5545.224473.
Bellapart J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth 2012;108(4):572–580. DOI: 10.1093/bja/aes035.
Wang CM, Zhou LY. Melatonin and melatonergic agents for the prevention of postoperative delirium: A meta-analysis of randomized placebo-controlled trials. Asian J Surg 2022;45(1):27–32. DOI: 10.1016/j.asjsur.2021.04.041.
Han Y, Wu J, Qin Z, Fu W, Zhao B, Li X, et al. Melatonin and its analogues for the prevention of postoperative delirium: A systematic review and meta-analysis. J Pineal Res 2020;68:68(4):e12644. DOI: 10.1111/jpi.12644.
Khaing K, Nair BR. Melatonin for delirium prevention in hospitalized patients: A systematic review and meta-analysis. J Psychiatr Res 2021;133:181–190. DOI: 10.1016/j.jpsychires.2020.12.020.
Zhang Q, Gao F, Zhang S, Sun W, Li Z. Prophylactic use of exogenous melatonin and melatonin receptor agonists to improve sleep and delirium in the intensive care units: A systematic review and meta- analysis of randomized controlled trials. Sleep Breath 2019; 23(4):1059–1070. DOI: 10.1007/s11325-019-01831-5.
Han Y, Tian Y, Wu J, Zhu X, Wang W, Zeng Z, et al. Melatonin and its analogs for prevention of post-cardiac surgery delirium: A systematic review and meta-analysis. Front Cardiovasc Med 2022;9:888211. DOI: 10.3389/fcvm.2022.888211.
Reeves BC, Deeks JJ, Higgins JPT, Shea B, Tugwell P, Wells GA. Including non-randomized studies on intervention effects. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane, 2022.
Artemiou P, Bily B, Bilecova–Rabajdova M, Sabol F, Torok P, Kolarcik P, et al. Melatonin treatment in the prevention of postoperative delirium in cardiac surgery patients. Kardiochir Torakochirurgia Pol 2015;12(2):126–133. DOI: 10.5114/kitp.2015.52853.
Jaiswal SJ, Vyas AD, Heisel AJ, Ackula H, Aggarwal A, Kim NH, et al. Ramelteon for prevention of postoperative delirium: A randomized controlled trial in patients undergoing elective pulmonary thromboendarterectomy. Crit Care Med 2019;47(12):1751–1758. DOI: 10.1097/CCM.0000000000004004.
Ford AH, Flicker L, Kelly R, Patel H, Passage J, Wibrow B, et al. The healthy heart–mind trial: Randomized controlled trial of melatonin for prevention of delirium. J Am Geriatr Soc 2020;68:112–119. DOI: 10.1111/jgs.16162.
Sharaf SI, Nasr El-Din DA, Mahran MG, Nawar DFA, El-Naggar DI. A study of the prophylactic and curative effect of melatonin on postoperative delirium after coronary artery bypass grafting surgery in elderly patients. Egypt J Hosp Med 2018;72:4919–4926. DOI: 10.21608/EJHM.2018.10174.
Mahrose R, ElSerwi H, Maurice A, Elsersi M. Postoperative delirium after coronary artery bypass graft surgery: Dexmedetomidine infusion alone or with the addition of oral melatonin. Egypt J Anaesth 2021;37:62–68. DOI: 10.1080/11101849.2021.1885956.
Kasnavieh FH, Rezaeipandari H, Hadadzadeh M, Vakili M, Biouki FH. Effect of melatonin on incidence rate of delirium in elderly patients undergoing open-heart surgery without a pump: A clinical trial. Elder Health J 2019;5:32–39. DOI: 10.18502/ehj.v5i1.1197.
Zadeh FJ, Janatmakan F, Shafaeebejestan E, Jorairahmadi S. Effect of melatonin on delirium after on-pump coronary artery bypass graft surgery: A randomized clinical trial. Iran J Med Sci 2021;46(2):120–127. DOI: 10.30476/ijms.2020.82860.1146.
Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive function after cardiac surgery. Anesthesiology 2018;129(4):829–851. DOI: 10.1097/ALN.0000000000002194.
Maldonado JR. Neuropathogenesis of delirium: Review of current etiologic theories and common pathways. Am J Geriatric Psychiatry 2013;21(12):1190–1222. DOI: 10.1016/j.jagp.2013.09.005.
Weinhouse GL, Schwab RJ, Watson PL, Patil N, Vaccaro B, Pandharipande P, et al. Bench-to-bedside review: Delirium in ICU patients: Importance of sleep deprivation. Crit Care 2009;13(6):234. DOI: 10.1186/cc8131.
Stahl SM, Muntner N. Stahl's essential psychopharmacology: Neuroscientific basis and practical application, 4th edition. Cambridge University Press: New York, 2013.
Randhawa PK, Gupta MK. Melatonin as a protective agent in cardiac ischemia–reperfusion injury: Vision/illusion? Eur J Pharmacol 2020;885:173506. DOI: 10.1016/j.ejphar.2020.173506.
Grover S, Dua D, Sahoo S, Chakrabarti S, Avasthi A. Effectiveness of melatonin in the management of delirium: A retrospective study. J Mental Health Human Behav 2019;24(2):78–84. DOI: 10.4103/jmhhb.jmhhb_56_19.
Shi Y. Effects of melatonin on postoperative delirium after PCI in elderly patients: A randomized, single-center, double-blind, placebo-controlled trial. Heart Surg Forum 2021;24(5):E893–E897. DOI: 10.1532/hsf.4049.
Gusmao–Flores D, Salluh JIF, Chalhub R, Quarantini LC. The confusion assessment method for the intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC) for the diagnosis of delirium: A systematic review and meta-analysis of clinical studies. Crit Care 2012;16(4):R115. DOI: 10.1186/cc11407.
Kumar AK, Jayant A, Arya V, Magoon R, Sharma R. Delirium after cardiac surgery: A pilot study from a single tertiary referral center. Ann Card Anaesth 2017;20(1):76–82. DOI: 10.4103/0971-9784.197841.
van Eijk MMJ, van Marum RJ, Klijn IAM, de Wit N, Kesecioglu J, Slooter AJC. Comparison of delirium assessment tools in a mixed intensive care unit. Crit Care Med 2009;37(6):1881–1885. DOI: 10.1097/CCM.0b013e3181a00118.
Abad VC, Guilleminault C. Insomnia in elderly patients: Recommendations for pharmacological management. Drugs Aging 2018;35(9):791–817. DOI: 10.1007/s40266-018-0569-8.
Cupka JS, Hashemighouchani H, Lipori J, Ruppert MM, Bhaskar R, Ozrazgat–Baslanti T, et al. The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: A systematic review. F1000Res 2021;9:1178. DOI: 10.12688/f1000research.25769.2.