The aim of the present study was to develop and validate an objective index for nociception level (NoL) of patients under general anesthesia, based on a combination of multiple physiological parameters. Twenty-five patients scheduled for elective surgery were enrolled. For clinical reference of NoL, the combined index of stimulus and analgesia was defined as a composite of the surgical stimulus level and a scaled effect-site concentration of opioid. The physiological parameters heart rate, heart rate variability (0.15–0.4 Hz band power), plethysmograph wave amplitude, skin conductance level, number of skin conductance fluctuations, and their time derivatives, were extracted. Two techniques to incorporate these parameters into a single index representing the NoL have been proposed: NoLlinear, based on an ordinary linear regression, and NoLnon-linear, based on a non-linear Random Forest regression. NoLlinear and NoLnon-linear significantly increased after moderate to severe noxious stimuli (Wilcoxon rank test, p < 0.01), while the individual parameters only partially responded. Receiver operating curve analysis showed that NoL index based on both techniques better discriminated noxious and non-noxious surgical events [area under curve (AUC) = 0.97] compared with individual parameters (AUC = 0.56–0.74). NoLnon-linear better ranked the level of nociception compared with NoLlinear (R = 0.88 vs. 0.77, p < 0.01). These results demonstrate the superiority of multi-parametric approach over any individual parameter in the evaluation of nociceptive response. In addition, advanced non-linear technique may have an advantage over ordinary linear regression for computing NoL index. Further research will define the usability of the NoL index as a clinical tool to assess the level of nociception during general anesthesia.
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Declaration of interest
The study was funded by Medasense Biometrics Ltd. N.B., M.K., and G.Z. are employees of Medasense Biometrics. Y.K. serves on the advisory board of Medasense Biometrics Ltd.
All authors jointly designed the study; R.E. and Y.K. recruited the patients, coordinated and supervised administration of anesthesia during operations; R.E., N.B., and G.Z. collected and annotated the data; N.B., M.K., and G.Z. developed NoL index and CISA score and wrote MATLAB code; N.B. and M.K. designed and performed the statistical analysis; N.B., M.K., and R.E. wrote the manuscript; G.Z. and Y.K. edited the manuscript. All authors read and approved the final manuscript.
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Ben-Israel, N., Kliger, M., Zuckerman, G. et al. Monitoring the nociception level: a multi-parameter approach. J Clin Monit Comput 27, 659–668 (2013). https://doi.org/10.1007/s10877-013-9487-9
- Autonomic response
- Pain monitoring
- General anesthesia