Evaluation of the nociception level index in the pediatric population: An observational feasibility study.

The nociception level (NOL) index is a multiparametric noninvasive monitoring method that combines pulse rate, pulse rate variability, photoplethysmographic amplitude, skin conductance, and skin temperature in an algorithm that gives an index (0–100) that measures intraoperative nociception.1 The NOL index has not been extensively evaluated in the pediatric population.2 The primary objective of this study was to evaluate whether the NOL index is able to detect nociceptive stimuli in children undergoing surgery with general anesthesia. Secondary objectives were to evaluate the response of the NOL index to opioid administration and to evaluate the response of the NOL index in comparison with changes in mean arterial blood pressure (MAP), heart rate (HR), and respiratory rate (RR). We performed an observational feasibility study in the pediatric population during elective surgical procedures. This study was approved by the local ethics committee of the Radboud University Medical Center, Nijmegen, The Netherlands. Patients were enrolled between February 2021 and August 2021. Both male and female patients of 1 to 5 years of age scheduled to undergo elective surgery under general anesthesia were included after obtaining written parental informed consent. The routine anesthesia protocol was followed and anesthesia personnel was blinded toward the NOL monitor. General anesthesia was achieved by induction with a mixture of sevoflurane and oxygen. General anesthesia was maintained with sevoflurane targeting an endtidal sevoflurane concentration close to a minimum alveolar concentration (MAC) of 1. Patients that were intubated received fentanyl (2 mcg/kg) and rocuronium 0.3–0.7 mg/kg or suxamethonium 1 mg/kg as neuromuscular blocking agent. Muscle relaxation was not maintained during surgery after intubation. Appropriate locoregional anesthesia techniques were applied by the anesthesiologist when indicated. After induction, patients were connected to the NOL monitor. Before intubation and when intraoperative nociception was suspected by anesthesia personnel, boluses of intravenous fentanyl were administered. During surgery, data regarding first incision and intraoperative fentanyl administration were registered by a trained researcher. The intraoperative NOL index response was evaluated and compared to changes in HR, MAP, and RR during first incision and intraoperative fentanyl administration. All demographic data were reported as median and interquartile range with 25th to 75th percentile. All other data were reported as median with 95% confidence intervals (95% CI) around them. Change in variables between pre- and postnociceptive events were reported (NOL Δ, HR Δ, RR Δ, and MAP Δ). Prenociceptive event average measurements were compared to postnociceptive event average measurements using the one-tailed Wilcoxon signed-rank test. A p < 0.0125 was considered statistically significant after correcting for multiple testing with four variables with the Bonferroni correction. Twenty-one patients were included, of which 13 were male and eight were female. Performing a D'Agostino–Pearson test revealed that none of the demographic variables assessed in this study were normally distributed. Median age of included patients was 2 years.1-3 Ten patients underwent general surgery, nine patients underwent urologic surgery, and 2 patients underwent plastic surgery. Median weight in kilograms was 13.5 (11.3–19), and median length in centimeters was 85 (78.8–99.5). Data on length in three patients were missing. Median duration of general anesthesia was 84 min (64–126). Median duration of surgery was 44 min (36–83). The total perioperative fentanyl usage in micrograms was 20 (17.5–32.5). The NOL index significantly increased during first incision with NOL Δ 10 (95% CI 2–23, p = <0.0001) (Table 1) and significantly decreased following fentanyl administration (n = 11) with NOL Δ -11 (95% CI −25–1, p = 0.0054). HR, MAP, and RR did not change significantly during these events. The NOL index significantly detected physiological responses of the nociceptive system directly related to surgical incision or fentanyl administration. These responses are not registered by standard monitoring parameters HR, MAP, and RR. The algorithm the NOL index is based on was developed using data derived from adults.1 And, as children have a different physiology with higher base heart rates and different blood vessel distensibility with different photoplethysmography amplitudes than adults, it could have been possible that the current multiparametric algorithm that the NOL index is based on would not be suitable for use in children.3 However, this study demonstrates that NOL index with the current algorithm is able to detect reactions of the patients' nociceptive systems following skin incision. Future studies should investigate if NOL index-guided analgesia administration can influence relevant clinical outcomes such as a reduction in perioperative opioid usage or postoperative pain. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.