Association of nociception level index‐guided intra‐operative analgesia with postoperative pain outcomes: a trial sequential analysis

We read with great interest the article by Bornemann-Cimenti et al. on the effect of nociception level index-guided intra-operative analgesia on early postoperative pain and opioid consumption [1]. The use of nociception level index monitoring resulted in statistically significant reductions in both self-reported postoperative pain scores (mean difference -0.46 on an 11-point scale) and opioid requirements (mean difference -1.04 mg intravenous morphine equivalent) in the early recovery period, without clinically meaningful benefits in terms of shortened post-anaesthesia care unit stay or reduction in postoperative nausea and vomiting. We believe that further analysis of this article is necessary. Although the primary outcome is statistically significant, it is crucial for readers to consider whether the evidence presented is adequate. Trial sequential analysis (TSA) [2] accounts for repeated significance testing when sparse data are accumulated in a cumulative meta-analysis. It controls the risk of random errors and calculates the required information size to detect or reject an a priori defined intervention effect. Trial sequential analysis can be particularly insightful in determining whether a meta-analysis includes sufficient trials or whether more research is needed. Based on the TSA graph, if the z-curve crosses the trial sequential monitoring boundary or required information size, sufficient evidence for the anticipated effect may have been obtained, and no further trials are needed. To address this gap, we utilised raw data from the original meta-analysis [1] to conduct TSA (TSA viewer version 0.9.5.10 Beta) [3], specifically focusing on two key parameters: pain scores and opioid consumption. We defined a type 1 error rate of 5% and aimed to achieve 80% statistical power. For the pain scores (Fig. 1), TSA showed that the Z-curve did not cross the trial sequential monitoring boundary or required information size. Similarly, for opioid consumption, the TSA results also showed that the Z-curve did not cross these boundaries. These findings suggest that the cumulative evidence is not sufficient to establish that nociception level index-guided anaesthesia reduces pain scores or opioid consumption. Further large, high-quality, randomised trials are needed to evaluate the clinical utility of this monitoring approach before it can be widely recommended.