Traditionally, the management of perioperative analgesia has depended on hemodynamic parameters such as heart rate and blood pressure to assess whether the patient is receiving adequate analgesia. However, these parameters can be unreliable, as they are also influenced by other perioperative factors, including the depth of anesthesia, the use of vasoactive medications, and the patient’s underlying physiological state. Inadequate titration of analgesia during surgery can lead to adverse outcomes, ranging from intraoperative awareness and sympathetic surges to opioid-induced hyperalgesia, delayed extubation, and increased postoperative complications. In order to optimize patient outcomes, several tools and metrics have been designed to measure intraoperative nociception.
One of the most widely investigated tools is the Surgical Pleth Index (SPI), which calculates a score based on normalized heartbeat intervals and photoplethysmographic pulse wave amplitudes. While SPI offers a continuous measure of surgical stress, its accuracy can be compromised by peripheral vascular tone, arrhythmias, and circulating catecholamines.
Another approach is the use of infrared pupillometry to monitor the pupillary dilation reflex (PDR). PDR is a sensitive measure of nociception that occurs when noxious stimuli inhibit the Edinger–Westphal nucleus, leading to pupillary dilation even in the intraoperative setting under general anesthesia. Unlike SPI, the PDR is largely independent of systemic sympathetic activation and peripheral vascular resistance, though it can be dose-dependently suppressed by high-dose opioids.
Additional indicators include the Analgesia Nociception Index (ANI), which utilizes heart rate variability to assess parasympathetic activity, and the Nociception Level (NOL) index, which integrates multiple physiological signals such as skin conductance, temperature, and pulse wave amplitude.
Clinical evidence supports the utility of these monitors in optimizing opioid delivery. A comprehensive meta-analysis of randomized controlled trials found that the use of nociception monitors significantly reduces intraoperative opioid administration compared to standard clinical practice. Specifically, monitors like pupillometry and the NOL index have shown a high degree of effectiveness in guiding opioid titration.
In a prospective randomized study comparing pupillometry to SPI during laparoscopic surgery, patients in the pupillometry group required significantly less intraoperative remifentanil and reported lower peak postoperative pain scores. This reduction in intraoperative opioid consumption is clinically significant, as it is associated with a shorter time to extubation and a decreased incidence of postoperative nausea and vomiting (PONV). However, research on NOL has also found that patients may experience greater surgical stress, suggesting that the metric may need to be refined to optimize pain management without negatively impacting other elements of the patient’s surgical experience.
The application of nociception monitors requires careful consideration of the clinical context. For instance, the advantage of these tools appears more pronounced in major surgeries compared to minor procedures, likely because they eliminate subjective over-dosing by the clinician. Furthermore, the reference ranges for these indices may not be uniform across all age groups—children may require different target values than adults for tools like the SPI.
Some studies have also observed that very low remifentanil doses guided by these monitors can be associated with an increase in stress hormone levels, such as cortisol and ACTH, suggesting that current threshold values may require further validation. The impact of the use of these metrics on long-term postoperative pain remains a subject of ongoing study. Nevertheless, the development and integration of tools to monitor intraoperative nociception represents an important step toward personalized anesthesia.
References
- Kim, J. H. et al. Comparison of Pupillometry With Surgical Pleth Index Monitoring on Perioperative Opioid Consumption and Nociception During Propofol–Remifentanil Anesthesia: A Prospective Randomized Controlled Trial. Anesth. Analg. 131, 1589–1598 (2020). https://doi.org/10.1213/ANE.0000000000004958
- Ma, D. et al. Nociception monitors vs. standard practice for titration of opioid administration in general anesthesia: A meta-analysis of randomized controlled trials. Front. Med. 9, 963185 (2022). https://doi.org/10.3389/fmed.2022.963185
- Jiao, Y. et al. Intraoperative monitoring of nociception for opioid administration: a meta-analysis of randomized controlled trials. Minerva Anestesiol. 85, 522–530 (2019). https://doi.org/10.23736/S0375-9393.19.13151-3
- Funcke, S. et al. Nociception level-guided opioid administration in radical retropubic prostatectomy: a randomised controlled trial. Br. J. Anaesth. 126, 516–524 (2021). https://doi.org/10.1016/j.bja.2020.09.051