Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity

Abstract

More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations.

Keywords: Anaesthetics; EEG; Paediatrics.

Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Recruitment flow chart. LA, local anaesthetic.

Fig. 2

Summary of experimental protocol. Anaesthetic induction was performed following routine practice, with sevoflurane and nitrous oxide. A laryngeal mask airway (LMA) was then inserted and the end-tidal (ET) concentration of sevoflurane was set to 2.5% and nitrous oxide

Fig. 3

Electroencephalography (EEG) time-locking. Example shots show the video recordings. Experimental tactile stimuli (row A) were time-locked to recordings through an event detection interface. Experimental noxious stimuli (row B) and cannulation (row C) were time-locked to the EEG recording using high-speed video recordings. t = 0 ms refers to the time when the stimuli first came into contact with the skin. The times shown in ms in the frames refer to these particular examples.

Fig. 4

Power-spectra for background electroencephalogram (EEG). (A) Average power spectrum of the background EEG across all channels (Naïve group; n = 28). The spectrum was divided into 4 frequency bands: delta (0–3 Hz, red), theta (3–8 Hz, blue), alpha (8–12 Hz, yellow), and beta (12–30 Hz, green). (B) Comparison of the power in the background EEG in each frequency band. (C) The delta power in the background EEG at each of the EEG channels. Error bars indicate SEM.

Fig. 5

Change in delta band power in response to cannulation. The change in delta band power between cannulation and background activity, compared with the change between 2 background periods at Cz and CPz in (A) the naïve group, and (B) the local anaesthetic (LA) group. Cannulation evoked a significant increase in delta power in the naïve group (∗P < 0.05), which was not seen in the LA group. (C) Change in delta power between cannulation and background activity at each of the electroencephalogram (EEG) channels (ordered according to mean response). Error bars indicate SEM.

Fig. 6

Changes in electromyogram (EMG) and electroencephalogram (ECG) in response to cannulation. (A) Average EMG trace 5 seconds before and after cannulation (across all subjects). (B) Average root mean square (RMS) of EMG activity in response to cannulation and in the background. (C) Average heart rate 5 seconds before and after cannulation (across all subjects). (D) Average heart rate in response to cannulation and in the background. Error bars indicate SEM.

Fig. 7

Change in infra-slow and high-delta activity in response to cannulation. To determine whether the delta power response to cannulation was related to infra-slow or higher frequency delta activity, the delta band was split into infra-slow-delta (0–0.5 Hz) and high-delta (0.5–3 Hz) components. (A) Infra-slow-delta increased with cannulation compared with background periods, but this increase was not significant (P = 0.13). (B) High-delta significantly increased in response to cannulation (P = 0.031). Error bars indicate SEM.

Fig. 8

Change in delta power in response to experimental noxious and tactile stimuli. The change in delta band power (poststimulus minus prestimulus) for all experimental tactile and noxious stimulation (∗P < 0.05, significant difference from 0) compared with the change between sequential prestimulus (baseline) periods. Error bars indicate SEM.

Supplementary Fig. 1

Change in delta power in individual subjects. Individual subjects were ranked according to change in delta power between cannulation and background. Dashed lines indicate the mean ± SD of the change in delta power between the background periods.