Utility of Frontal Electroencephalography in the Evaluation of Nociception in Patients submitted to General Anesthesia using Neural Networks

In this study bilateral frontal EEG was studied in conjunction with autonomic variables, to assess their relation to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision); patients were randomized to receive remifentanil 2.0, 3.0 or 4.0 ng/ml. BIS bilateral sensor was used to collect frontal EEG; features extracted include: normalized energy distribution (δ 0-4 Hz, θ 4-8 Hz, ɑ 5-15 Hz, β 15-30 Hz and Ɣ 30-44 Hz), Slow Wave Activity (SWA, 0,5-1,5 Hz), total energy, spectral entropy, and total and spectral bands coherence (FP7 or 8-FPZ). Other variables include HR, BP, PPG amplitude (PPGA), BIS and BIS EMG. These were compared between study groups and stimuli (Wilcoxon signed ranks, and Kruskal-Wallis tests, P<0,05). Extracted features were used to feed a pattern neural network (NN, 70-15-15) to classify pre and post events (LOC, Laringoscopy, Intubation, Tetanic, Incision), using as inputs the EEG features, frontal EEG bilateral coherence, and cardiovascular and BIS indexes. Following institutional approval and informed consent, thirty four patients were enrolled in the study; 28 in the final dataset. Extracted features presented more pronounced responses to laringoscopy: significant differences in EEG coherence were observed in all frequency bands as well as in PPGA. A decrease in total coherence was observed for all stimuli, except tetanic. HR was significantly different pre and post-stimulation except for incision. BP was significantly different for the incision. Considering LOC, a statistical significant difference was found between EEG energy distribution in all frequency bands, as well as in the entropy and EEG energy pre and post-LOC. HR, BP, PPGA, BIS, and EEG coherence (SWA, δ and ɑ bands) were also significantly different pre and post-LOC. NN best classification results were obtained for the identification of LOC using EEG features. NN for all stimuli results were poor, nonetheless laringoscopy detection presented a 78,7% accuracy in the test dataset, using bilateral EEG coherence features. Limitations of the study include the reduced number of patients in each group and NN testing datasets, and the analysis of responses under different analgesic doses, which may block noxious activation. Preliminary results seem to point that there may be useful information on bilateral frontal EEG not only for the hypnosis monitoring during anethesia, but also to assess the nociception-antinociception balance. vi BP is one of the signal used to assess the adequacy of analgesia during anesthesia. Recent studies have shown that hypotension lasting for short periods of time, as brief as five minutes, negatively impact on outcome, however continuous monitoring of BP is not used unless for specific higher risk cases. The same dataset was used for estimation of BP through noninvasive signal containing beat to beat information on the cardiovascular system (ECG and PPG). Blood pressure was monitored non-invasively using a cuff-based monitor at 1 to 5 minute intervals before and during anesthesia induction; following an arterial catheter was placed for continuous beat to beat BP monitoring. A NN was trained and adjusted to individual datasets using beat to beat RR interval (RRI) and PPGA as inputs; data were divided in training (30%), validation (20%), and testing (50%) datasets; random and block data selection for training were used. Thirty one patients composed the final dataset for BP estimation. Results show that the best performance was obtained with Bayesian regulation NN, using feedback of SBP at 5 minutes intervals (MAE 5,13±1,65 mmHg, ME 0,01±0,18 mmHg and ρ 0,89±0,04). The use of training data in block deteriorates the results, although it represents the likely scenario for its applicability. NN for the estimation of BP temporal series presented satisfactory preliminary results, with errors close to the recommended targets (5 mmHg). Future work includes assessing the impact of different drug combinations, and noxious stimulation during general anesthesia, and to explore other characteristics of the signals, such as PPG wave slope as described in the literature.