Enhancing the evidence for opioid-free anaesthesia in the elderly: a call for methodological clarity

Enhancing the evidence for opioid-free anaesthesia in the elderly: a call for methodological clarity Dear EditorWe read with great interest the randomized controlled trial by Wei et al. comparing opioid-free (OFA) versus opioid-based total intravenous anaesthesia in elderly patients undergoing short-duration surgery [1].The authors report clinically meaningful reductions in postoperative hypoxaemia and PONV with OFA, offering valuable insights for perioperative care in this vulnerable population.However, two methodological aspects warrant further discussion to strengthen the interpretation and generalizability of these findings.First, while outcome assessors were blinded, the attending anaesthesiologists were not.This may introduce performance bias, particularly in analgesic titration guided by the Surgical Pleth Index (SPI).A recent randomized trial demonstrated that dexmedetomidine significantly attenuates SPI responses to noxious stimuli compared to opioids [2].Specifically, blunted SPI responses may cause discrepant analgesic titration between groups, altering intraoperative hemodynamics and postoperative recovery trajectories [2].This pharmacodynamic interaction suggests SPI-guided analgesia may be systematically confounded when dexmedetomidine is used exclusively in one arm, potentially leading to asymmetrical intraoperative management.Clarification on concurrent depth-of-anaesthesia monitoring (e.g.BIS) would help assess the robustness of these findings.Second, the primary outcome of hypoxaemia-SpO 2 <95% requiring oxygen-is liberal and clinician-dependent.A global meta-analysis reported wide variation in hypoxaemia diagnostic thresholds, with the 95% threshold exceeding commonly used standards (e.g.<90% or <92%) [3,4].The requirement for supplemental oxygen introduces subjectivity; without standardized oxygen-weaning policies and blinded decision-making, the 17% absolute reduction in hypoxaemia could be partially attributable to observer and management bias.Continuous monitoring can detect otherwise missed SpO 2 <90% desaturation events [5].For a sensitivity analysis-not a proposed change to the original primary outcome-we suggest reporting the frequency and cumulative duration of SpO 2 <90% within 24h postoperatively, regardless of oxygen supplementation, to enhance confidence in this key finding.We commend the authors for addressing this critical clinical question in a rigorous RCT framework.Addressing these points would further solidify the evidence supporting OFA as a viable alternative in elderly surgical patients.We warmly invite the original authors to respond to these methodological considerations.