Index of nociception: A potential complementary parameter for the control of analgesia during general anesthesia

Background: Today monitors for the level of hypnosis and muscle relaxation during general anesthesia are available, but such a measurement for the level of analgesia is missing. In search of a suitable measure to control the analgesic component to a desired clinical set point, both predictive characteristics of the opioid drug effect and responses to surgical stimulation need to be taken into account. Multi-parameter approaches have been suggested to accomplish a clinically meaningful and useable numeric measure of adequate analgesia. Methods: Our goal was first to find and recognize the patterns in the commonly available physiological monitoring parameters that are specific and sensitive to the level of nociception, and secondly to develop an optimal combination of these patterns to produce a measure of nociception tailored for the control of analgesia during general anesthesia and surgery. We studied 55 female patients anaesthetised with propofol and remifentanil, and paralysed with rocuronium. Remifentanil target site concentration was adjusted to 1, 3, or 5 ng/ml during surgery. The patterns in the photoplethysmographic waveform amplitude (PPGA) and heart rate (HR) were first analysed for specificity and sensitivity to remifentanil level and stimulation at the incision, electric tetanic stimuli and some recognized painful surgical events. The best combination of the parameter patterns was found by linear or non-linear regression against the combined effect of the assessed stimulation severity and remifentanil level. A State Index of Nociception (SN) was developed as the best performing level indicator of the adequacy of analgesia and a Response Index of Nociception (RN) for the best fast indicator of the responses to nociception. For SN the median of correlation coefficients was calculated over the patients and the significance of the median, compared to zero, was evaluated using Wilcoxon sign rank test. For RN the response amplitudes were analysed for significance using the Kruskal-Wallis H test. Results: SN correlated positively with stimulation level (median r=0.42, P<0.0001) and negatively with remifentanil level (median r=-0.33, P<0.0001). Median correlation with their difference was 0.50 (P<0.0001). A RN was significantly higher in the low doses of remifentanil as compared to the higher doses for both tetanic stimulus (p=0.00005) and skin incision (p=0.00003). Discussion: SN appears to be sensitive to insufficient remifentanil levels during surgery and provides information of the adequacy of analgesia during propofol-remifentanil anaesthesia. SN may hence be suitable to adjust the level of analgesia. RN provides fast quantification of nociceptive responses and can identify abrupt changes of stimulation during the surgery. References: Seitsonen E. Anesthesiology 2002: 97: A-582.