Impact of perioperative esketamine on the perioperative neurocognitive dysfunction: a systematic review and meta-analysis of randomised controlled studies

Abstract

Objectives: The effect of esketamine on perioperative neurocognitive dysfunction (PND) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of perioperative esketamine administration on PND.

Design: Systematic review and meta-analysis.

Data sources: PubMed, EMBASE, Web of Science and Cochrane Library were searched from their inception to 25 April 2024.

Eligibility criteria for selecting studies: We included the randomised controlled trials (RCTs) that compared single or continuous intravenous infusion of esketamine to saline among adult surgical patients without pre-existing neurocognitive disorders.

Data extraction and synthesis: Two reviewers independently extracted pertinent information from the included studies. Risk of bias was assessed using Cochrane's risk of bias criteria. Risk ratios (RRs) and their corresponding 95% CIs were synthesised using a random-effects model. The overall evidence quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results: 10 RCTs were included in our meta-analysis, involving 854 surgical patients. Perioperative esketamine was associated with a reduced risk of postoperative delirium (POD) (relative risk (RR): 0.46, 95% CI: 0.30 to 0.71, p<0.001) and delayed neurocognitive recovery (dNCR) (RR: 0.41, 95% CI: 0.21 to 0.78, p<0.001). However, no statistically significant difference was found in the risk of postoperative neurocognitive disorder (post-NCD) at 3 months postsurgery between the esketamine and control groups (RR: 0.57, 95% CI: 0.19 to 1.73, p=0.40). Additionally, pain severity was reduced on postoperative day 1, with no difference in the risk of adverse events or length of hospital stay.

Conclusion: Perioperative esketamine reduces the risk of short-term PND, including POD and dNCR, without significantly affecting the incidence of adverse events or length of hospital stay. However, no significant differences were observed in the risk of post-NCD at 3 months following surgery. This systematic review and meta-analysis offers valuable data for PND research and clinical drug intervention strategies.

Prospero registration number: CRD42024538438.

Keywords: Adult anaesthesia; Meta-Analysis; Systematic Review.

Figure 1. Flow diagram of study selection.

Figure 2. (A) Forest plot showing the effect of perioperative esketamine on the perioperative neurocognitive dysfunction (PND) and subgroup analysis of postoperative delirium (POD) and delayed neurocognitive recovery (dNCR) within 7 days postoperatively. The relative risk (RR) was calculated by pooling six randomised controlled trials (RCTs) compared with two groups. (B) Forest plot showing the effect of perioperative esketamine on the PND and subgroup of POD and dNCR within 7 days postoperatively. The RR was calculated by pooling six RCTs compared with two groups and two RCTs compared with three groups.

Figure 3. (A) Forest plot showing the effect of perioperative esketamine on the perioperative neurocognitive dysfunction (PND) and subgroup of postoperative delirium (POD) and delayed neurocognitive recovery (dNCR) at 24 hours postoperatively. (B) Forest plot showing the effect of perioperative esketamine on the PND and subgroup of POD and dNCR at 72 hours postoperatively. (C) Forest plot showing the effect of perioperative esketamine on the postoperative neurocognitive disorder (post-NCD) at 3 months postoperatively.

Figure 4. (A) Forest plot showing the effect of perioperative esketamine on the postoperative nightmare. (B) Forest plot showing the effect of perioperative esketamine on the PONV.

Figure 5. (A) Forest plot showing the effect of perioperative esketamine on the postoperative cardiovascular adverse events and subgroup. Analysis of hypotension, hypertension, tachycardia and bradycardia. (B) Forest plot showing the effect of perioperative esketamine on hallucination. (C) Forest plot showing the effect of perioperative esketamine on length of hospital stay.

Figure 6. Forest plot showing the effect of perioperative esketamine on the postoperative pain and subgroup analysis of Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS) scales. (A) At postoperative day 1. (B) At postoperative day 2. (C) At postoperative day 3.