Response to letter regarding enhancing the evidence for opioid-free anaesthesia in the elderly: a call for methodological clarity

Response to letter regarding the evidence for opioid-free anaesthesia in the elderly: a call for methodological clarityDear Editor We are grateful to Guo et al. for their insightful critique of our study [1].We appreciate the opportunity to address their methodological considerations, which are highly valuable for the ongoing refinement of anaesthetic research.Regarding performance bias, we agree that it is difficult to blind the anesthesiologists providing care in this type of trial.To address this, we followed a standardized anesthesia protocol for all patients.Furthermore, the team members who collected the main outcomes were blinded to the group assignments, which helps make our findings more reliable.The authors correctly point out that dexmedetomidine, which was used in the OFA group, can affect the Surgical Pleth Index (SPI).We agree this is an important point to consider.To manage this, we aimed to keep the SPI between 20 and 50 in both groups.As shown in Table 1 of our original article [2], the time patients stayed within this target range was high and very similar between the OFA (89.23%) and OBA (90.83%) groups.This suggests that the anesthesia management during surgery was consistent for both groups.In addition, we chose to use SPI rather than the Bispectral Index (BIS) because esketamine, another drug in our OFA group, is known to affect BIS readings [3].Using BIS could have made it harder to accurately judge the depth of anesthesia.Regarding the definition of hypoxemia (SpO 2 <95%), we truly appreciate the suggestion to test a stricter cutoff.To look into this, we ran an additional analysis using SpO 2 <90%.Even with this tighter rule, the benefit of OFA was still clear.The main combined outcome happened in 22.5% of the OFA group compared to 38.0% of the OBA group (OR 0.47; 95% CI 0.31-0.73;p < 0.001).Likewise, postoperative hypoxemia (SpO 2 <90%) occurred in 12.5% of the OFA group and 26.5% of the OBA group (OR 0.40; 95% CI 0.23-0.67;p < 0.001).These results show that our findings are stable and do not just rely on the first cutoff we chose.For more details, please see Table 1 below.We thank the authors for their constructive comments, which highlight the importance of methodological clarity in opioid-free anaesthesia research.