Analgesia nociception index for intra‐operative remifentanil dose and pain after gynaecological laparotomy: a reply

We appreciate the comments from Hickey et al. [1] regarding our article [2]. They raise important concerns regarding the analgesic protocol used in our study and the potential effects of ephedrine on analgesia nociception index values. Unfortunately, due to limited hospital resources, we were unable to provide multimodal analgesia, such as surgical wound infiltration, regional analgesic techniques or opioid-sparing postoperative analgesia, as recommended in the recent guideline on enhanced recovery after surgery [3]. We acknowledge that these deviations from the current standard of multimodal analgesia may have introduced some bias in our study and it is, therefore, crucial to approach the interpretation of our results with caution. We completely agree with the concerns about the opioid crisis, a pressing global issue, and we strongly support the judicious prescribing of opioids during the peri-operative period, actively striving to reduce opioid consumption [4]. To address these challenges, we have recently initiated a change in our postoperative analgesic protocol, transitioning from the previous opioid-based postoperative analgesia to a regimen centred around non-opioid analgesics, such as regular postoperative administration of non-steroidal anti-inflammatory drugs and paracetamol. We are also developing a collaborative plan by establishing a multidisciplinary team to enhance our postoperative management protocol. We hope these changes, aimed at aligning our peri-operative care with current standards, will promote progress in our peri-operative care of patients. The calculation of the analgesia nociception index relies on heart rate variability [5]. However, it is important to note that heart rate variability can be influenced by the administration of drugs that affect the autonomic nervous system [6]. Consequently, the use of these medications may potentially affect the accuracy or reliability of the analgesia nociception index. In our study, although we recorded the dose of ephedrine administered, with no significant differences between the two groups, we did not record the exact timing of ephedrine administration, nor did we evaluate its effects on changes in the analgesia nociception index. Therefore, we acknowledge that this may also introduce bias and interfere with the accurate management of the remifentanil infusion. In conclusion, we agree that the analgesic protocol used in our study differed from the current standard of multimodal analgesia, and the effects of ephedrine on analgesia nociception index values were not adequately evaluated. Further studies are required to gain a better understanding of these issues.