A Bayesian multilevel joint model for predicting neonatal head circumference and body mass index: a case study in Dalahu County, Iran.

While opioids have historically been indispensable for surgical anesthesia via central nervous system receptor binding (μ, δ, and κ), their use carries significant dose-dependent risks. These include respiratory depression, postoperative nausea and vomiting (PONV), pruritus, urinary retention, and postoperative delirium. Furthermore, the global opioid abuse crisis has elevated perioperative opioid exposure to a serious public health concern, driving efforts to mitigate these risks and associated economic burdens [, ]. Consequently, Enhanced Recovery After Surgery (ERAS) protocols increasingly advocate minimizing or avoiding perioperative opioids [–]. This shift has catalyzed the development of opioid-free anesthesia (OFA), which employs multimodal non-opioid adjuvants—such as dexmedetomidine, clonidine, ketamine, and lidocaine—to achieve analgesia. Evidence indicates that these multimodal combinations can significantly curtail opioid-related adverse effects []. Esketamine, the S-enantiomer of ketamine, is an N-Methyl-D-Aspartate (NMDA) receptor antagonist with a stronger receptor affinity, enabling effective analgesia at lower doses. It was specifically developed to reduce adverse effects such as psychosis and addiction []. Indeed, systematic reviews in psychiatric settings suggest esketamine possesses a more favorable safety and tolerability profile compared to intravenous racemic ketamine [, ]. Despite these potential advantages and its increasing perioperative utilization [], its specific role and safety in diverse surgical populations remain debated. While previous meta-analyses have extensively evaluated the broad concept of OFA, they have predominantly pooled diverse non-opioid agents into generalized intervention groups. Consequently, the distinct clinical contribution and psychomimetic safety profile of esketamine within these complex regimens remain obscured. Clinical trials evaluating esketamine have yielded inconsistent results regarding its analgesic efficacy compared to traditional regimens. To our knowledge, no systematic review has specifically isolated and synthesized the evidence to address this critical gap.