EEG responses to standardised noxious stimulation during clinical anaesthesia: a pilot study

Abstract

Background: During clinical anaesthesia, the administration of analgesics mostly relies on empirical knowledge and observation of the patient's reactions to noxious stimuli. Previous studies in healthy volunteers under controlled conditions revealed EEG activity in response to standardised nociceptive stimuli even at high doses of remifentanil and propofol. This pilot study aims to investigate the feasibility of using these standardised nociceptive stimuli in routine clinical practice.

Methods: We studied 17 patients undergoing orthopaedic trauma surgery under general anaesthesia. We evaluated if the EEG could track standardised noxious phase-locked electrical stimulation and tetanic stimulation, a time-locked surrogate for incisional pain, before, during, and after the induction of general anaesthesia. Subsequently, we analysed the effect of tetanic stimulation on the surgical pleth index as a peripheral, vegetative, nociceptive marker.

Results: We found that the phase-locked evoked potentials after noxious electrical stimulation vanished after the administration of propofol, but not at low concentrations of remifentanil. After noxious tetanic stimulation under general anaesthesia, there were no consistent spectral changes in the EEG, but the vegetative response in the surgical pleth index was statistically significant (Hedges' g effect size 0.32 [95% confidence interval 0.12-0.77], P=0.035).

Conclusion: Our standardised nociceptive stimuli are not optimised for obtaining consistent EEG responses in patients during clinical anaesthesia. To validate and sufficiently reproduce EEG-based standardised stimulation as a marker for nociception in clinical anaesthesia, other pain models or stimulation settings might be required to transfer preclinical studies into clinical practice.

Clinical trial registration: DRKS00017829.

Keywords: EEG; general anaesthesia; nociception; pain; pain-related evoked potentials; pilot study; tetanic stimulation.

Fig. 1

Study flow. Phase-locked stimuli were applied (1) in awake patients, (2) at induction with propofol alone or with remifentanil alone, and (3) at steady state with a combination of propofol and remifentanil. Tetanic stimulation was performed in our patients during stable anaesthesia. LOR, loss of responsiveness; VAS, visual analogue scale; NMB, neuro muscular block.

Fig. 2

Evoked response after painful noxious electrical stimulation in awake and sedated patients. The top row (a) shows Group R (i.e. the group that started the induction of anaesthesia with remifentanil). The middle row (b) shows Group P (i.e. the group that started the induction of anaesthesia with propofol). The bottom row (c) shows all patients of Groups R and P combined in an awake state and after the administration of both propofol and remifentanil later in time after a steady state of general anaesthesia was achieved. The right-hand side column shows the statistical comparison between the left and middle columns, whereas a red box indicates a statistically significant difference in at least three adjoined points in time. The blue arrow indicates the N-wave, the black arrow indicates the P-wave. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Event-related spectral perturbation (ERSP) and statistical comparison including area under the receiver operating characteristic (AUROC) curve effect sizes of the event-related data of all patients during the awake state and general anaesthesia. The panel shows the event-related spectral changes after the phase-locked noxious stimulation. The graph on the right shows the statistical comparison; a pixel is only coloured red or blue according to the colour bar if the difference is statistically significant. The colour then depicts the value of the AUROC effect size. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Spectral changes before, during, and after tetanic stimulation in absolute terms. The upper panel shows the changes in the absolute power in density spectral array (DSA) for electrode Cz across time averaged from seven patients, and the middle panel shows the absolute power in DSA averaged for the frontal electrodes Fp2, Fp2, and F4 from 17 patients. The black lines in all three panels indicate the start and end of the tetanic stimulation.

Fig. 5

The spectral power changes either with or without neuromuscular block after tetanic stimulation. Panel (a) shows the mean power spectrum of seven patients within 10 s before (blue) and within 10 s after (grey) tetanic stimulation before neuromuscular block. Panel (b) is the same for 10 patients with complete neuromuscular block. Statistics are shown in the lower panel. AUC is calculated as individual absolute change between the prestimulation (pre) and poststimulation (post). Black dots indicate AUC effect size >0.75, grey AUC effect size <0.75. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6

The average SPI during tetanic stimulation changes in patients without neuromuscular block. The lines indicate the average SPI or BIS values across time, while the shading indicates one standard deviation. The black bars indicate the start and end of the tetanic stimulation. As there are no absolute target values established for the SPI, normalised values are shown. Panel (a) shows SPI response of 7 stimulations before neuromuscular block, panel (b) the same of 10 stimulations at full neuromuscular block and panel (c) the average BIS of all 17 patients. BIS, bispectral index; SPI, surgical pleth index.