Indian Journal of Critical Care Medicine
Volume 28 | Issue 2 | Year 2024

Post-cardiac Surgery Delirium: When the Details Matter!

Varun Suresh1https://orcid.org/0000-0003-2521-1149, Rohan Magoon2https://orcid.org/0000-0003-4633-8851

1Department of Anesthesia and Intensive Care, Jaber Al Ahmad Al Sabah Hospital, Kuwait, Arabian Gulf

2Department of Cardiac-Anaesthesia, Atal Bihari Vajpayee Institute of Medical Sciences (ABVIMS) and Dr. Ram Manohar Lohia Hospital, New Delhi, India

Corresponding Author: Varun Suresh, Department of Anesthesia and Intensive Care, Jaber Al Ahmad Al Sabah Hospital, Kuwait, Arabian Gulf, Phone: +0091 9041426743, e-mail: varunsureshpgi@gmail.com

How to cite this article: Suresh V, Magoon R. Post-cardiac Surgery Delirium: When the Details Matter! Indian J Crit Care Med 2024;28(2):185–187.

Source of support: Nil

Conflict of interest: None

Keywords: Cardiac surgery, Cognition, Delirium, Melatonin.

Dear Editor,

The meta-analysis by Niyogi et al. suggests a protective role of melatonin-melatonin agonists on post-cardiac surgery delirium, which surfaces at a particularly important time given a heightened recent focus on the pharmacological prevention of postoperative delirium (POD) in peculiarly predisposed settings such as cardiac surgery.13 Having included seven studies (six randomized trials and a non-randomized trial), the authors attribute a pooled odds ratio (OR) of 0.44 [95% confidence interval (CI): 0.27–0.71, p = 0.04] supporting a favorable impact of melatonin-melatonin agonists on POD, in a total of 1,179 cardiac surgical patients.1 The research group concurrently elucidates a low overall level of evidence amidst the prevailing risk of bias and/or heterogeneity in their analysis, where we have additional observations to discuss in the matter.

In a meta-analysis involving 13,286 patients, Chen et al. outline the importance of preoperative depression and mild cognitive impairment in determining the risk of POD following cardiac surgery (OR; 95% CI: 3.29; 2.18–4.96, I2 = 0% and 5.40; 2.68–10.89, I2 = 39%, respectively).4 Considering Niyogi et al. do not present the details on the former, we re-evaluated their seven studies focusing on the differences amongst the individual researchers with regards to the preoperative risk assessment.1 For the benefit of the readership, Table 1 enlists how the POD risk factors were accounted for in the seven component studies, with a special emphasis on the objective documentation of the baseline neurocognition. Of note, a 2021 meta-analysis by Li et al. studying the role of dexmedetomidine in preventing post-cardiac surgery delirium formally excluded the existing trials which failed to objectively document the preoperative cognitive status with mini-mental state examination (MMSE) score or other relevant tools.2,3

Table 1: Preoperative cognitive assessment, psychometric tools used and potential confounders evaluated in the candidate studies analyzed by Niyogi et al.1 in their meta-analysis
S. No. Reference study in the Niyogi et al.1 meta-analysis Inclusion Preoperative or baseline assessment Psychometric tool used to assess delirium and sedation Other potential confounders evaluated Main results
Cognition Delirium
1 Reference 13 (Artemiou et al.) 500 patients undergoing elective cardiac surgery, also including off-pump cases No; preexisting psychiatric diseases were only noted No CAM-ICU and RASS score • EuroSCORE II
• Total BZD, sufentanil consumption
CPB, aortic cross clamp time
Melatonin reduced the incidence of POD
2 Reference 14 (Jaiswal et al.) Patients undergoing elective pulmonary thrombo-endarterectomy No No CAM-ICU score for assessing delirium and RASS score for sedation • Dose and duration of BZD, opiates and, antipsychotics in ICU
• SOFA score
• MV and LOS
Ramelteon did neither prevent delirium nor cause sedation in the authors’ homogenous cohort of 120 cases
3 Reference 15 (Ford et al.) 210 adult patients undergoing elective cardiac surgery (CABG or valve surgery) Yes, patients with dementia as per TICS-M score were excluded (score ≤19) Patients with preoperative scores ≥15 on alcohol use disorders identification test were excluded CAM-ICU, MDAS, HADS, TICS-M, RASS scores • Education, smoking, history of stroke, depression
• Mood and anxiety disorders
Melatonin did not reduce the incidence, duration or severity of delirium in the study cohort
4 Reference 16 (Sharaf et al.) 50 patients undergoing elective CABG Yes, patients with low MMSE scores were excluded (score ≤24) No ICDSC • Renal impairment, liver function
• CPB time, aortic cross clamp time
• Total fentanyl consumption
Melatonin reduced the incidence of POD
5 Reference 17 (Mahrose et al.) 110 patients above 60 years of age, undergoing elective CABG Patients with mental disorders excluded, however lacking objective assessment Yes, CAM score estimated as a preoperative baseline CAM-ICU, RASS • CPB time, aortic cross clamp time
• Blood transfusion, renal impairment
• Atrial fibrillation
Dexmedetomidine use with melatonin reduced the incidence and duration of POD
6 Reference 18 (Kasnavieh et al.) 140 patients exclusively undergoing elective off-pump CABG No No, first CAM-ICU assessment was done on the day of surgery, postoperatively CAM-ICU score and RASS score • Education, sleep disorders
• Potassium, sodium, AST, and creatinine
Reduced incidence of delirium found in the melatonin group
7 Reference 19 (Zadeh et al.) 60 patients undergoing elective CABG No No CAM-ICU score for the incidence and MDAS for the severity of delirium • Smoking, alcohol consumption and opioid addiction
• Aortic cross-clamp and CPB times
Melatonin reduced the incidence and severity of POD after CABG
AST, aspartate aminotransferase; BZD, benzodiazepines; CABG, coronary artery bypass graft; CAM-ICU, confusion assessment method in intensive care unit; CPB, cardiopulmonary bypass; EuroSCORE, European system for cardiac operative risk evaluation; HADS, hospital anxiety depression scale; ICDSC, intensive care delirium screening checklist; ICU, intensive care unit; LOS, length of stay; MDAS, memorial delirium assessment scale; MMSE, mini mental state examination; MV, mechanical ventilation; POD, postoperative delirium; RASS, Richmond agitation and sedation scale; SOFA, sequential organ failure assessment; TICS-M, modified telephone interview for cognitive status

Meanwhile, Niyogi et al. declare that the optimal timing of melatonin-melatonin agonists for pharmacological neuroprotection is yet to be explored, it remains to be first highlighted that one of their studies also included patients operated on an off-pump basis with another study exclusively including off-pump coronary artery revascularization (Table 1) which becomes particularly important in the purview of POD, given independent researchers associate the use of cardiopulmonary bypass and its’ duration with post-cardiac surgery delirium.1,5


Varun Suresh https://orcid.org/0000-0003-2521-1149

Rohan Magoon https://orcid.org/0000-0003-4633-8851


1. 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. DOI: 10.5005/jp-journals-10071-24571.

2. Magoon R, Mahajan S, Jose J. DEX, Delirium and Dilemma. Braz J Cardiovasc Surg 2023;38(2):305–308. DOI: 10.21470/1678-9741-2022-0002.

3. Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: A meta-analysis of randomized controlled trials. BMC Anesthesiol 2021;21(1):153. DOI: https://doi.org/10.1186/s12871-021-01370-1.

4. 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: https://doi.org/10.1186/s13019-021-01496-w.

5. O’Neal JB, Billings FT 4th, Liu X, Shotwell MS, Liang Y, Shah AS, et al. Risk factors for delirium after cardiac surgery: A historical cohort study outlining the influence of cardiopulmonary bypass. Can J Anaesth 2017;64(11):1129–1137. DOI: 10.1007/s12630-017-0938-5.

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