Monitoring the nociception level: A multi-parameter approach

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: NoL_linear, based on an ordinary linear regression, and NoL_non-linear, based on a non-linear Random Forest regression. NoL_linear and NoL_non-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). NoL _non-linear better ranked the level of nociception compared with NoL_linear (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.