Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity
Caroline Hartley, Ravi Poorun, Sezgi Goksan, Alan Worley, Stewart Boyd, Richard Rogers, Tariq Ali, Rebeccah Slater, Caroline Hartley, Ravi Poorun, Sezgi Goksan, Alan Worley, Stewart Boyd, Richard Rogers, Tariq Ali, Rebeccah Slater
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.
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References
- André M., Lamblin M.-D., d’Allest A.M., Curzi-Dascalova L., Moussalli-Salefranque F., S Nguyen The T., Vecchierini-Blineau M.-F., Wallois F., Walls-Esquivel E., Plouin P. Electroencephalography in premature and full-term infants. Developmental features and glossary. Neurophysiol Clin. 2010;40:59–124.
- Antognini J.F., Carstens E. Isoflurane blunts electroencephalographic and thalamic-reticular formation responses to noxious stimulation in goats. Anesthesiology. 1999;91:1770–1779.
- Bischoff P., Kochs E., Haferkorn D., Schulte am Esch J. Intraoperative EEG changes in relation to the surgical procedure during isoflurane–nitrous oxide anesthesia: hysterectomy versus mastectomy. J Clin Anesth. 1996;8:36–43.
- Bourgeois E., Sabourdin N., Louvet N., Donette F.X., Guye M.L., Constant I. Minimal alveolar concentration of sevoflurane inhibiting the reflex pupillary dilatation after noxious stimulation in children and young adults. Br J Anaesth. 2012;108:648–654.
- Constant I., Nghe M.-C., Boudet L., Berniere J., Schrayer S., Seeman R., Murat I. Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables. Br J Anaesth. 2006;96:614–619.
- Constant I., Sabourdin N. The EEG signal: a window on the cortical brain activity. Paediatr Anaesth. 2012;22:539–552.
- Cornelissen L., Fabrizi L., Patten D., Worley A., Meek J., Boyd S., Slater R., Fitzgerald M. Postnatal temporal, spatial and modality tuning of nociceptive cutaneous flexion reflexes in human infants. PLoS One. 2013;8:e76470.
- Drewes A.M., Nielsen K.D., Arendt-Nielsen L., Birket-Smith L., Hansen L.M. The effect of cutaneous and deep pain on the electroencephalogram during sleep—an experimental study. Sleep. 1997;20:632–640.
- Duggan L.V., 4th National Audit Project of the Royal College of Anaesthetists and The Difficult Airway Society (NAP4) Major complications of airway management in the United Kingdom. Can J Anaesth. 2011;58:1061–1062.
- Franks N.P. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci. 2008;9:370–386.
- Gasser T., Verleger R., Bächer P., Sroka L. Development of the EEG of school-age children and adolescents. I. Analysis of band power. Electroencephalogr Clin Neurophysiol. 1988;69:91–99.
- Hagihira S., Takashina M., Mori T., Ueyama H., Mashimo T. Electroencephalographic bicoherence is sensitive to noxious stimuli during isoflurane or sevoflurane anesthesia. Anesthesiology. 2004;100:818–825.
- Hartley C., Slater R. Neurophysiological measures of nociceptive brain activity in the newborn infant – the next steps. Acta Paediatr. 2014;103:238–242.
- Huttenlocher P.R., Dabholkar A.S. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol. 1997;387:167–178.
- Iannetti G.D., Baumgärtner U., Tracey I., Treede R.D., Magerl W. Pinprick-evoked brain potentials: a novel tool to assess central sensitization of nociceptive pathways in humans. J Neurophysiol. 2013;110:1107–1116.
- Kochs E., Bischoff P., Pichlmeier U., Schulte am Esch J. Surgical stimulation induces changes in brain electrical activity during isoflurane/nitrous oxide anesthesia. A topographic electroencephalographic analysis. Anesthesiology. 1994;80:1026–1034.
- Kox W.J., Heymann von C., Heinze J., Prichep L.S., John E.R., Rundshagen I. Electroencephalographic mapping during routine clinical practice: cortical arousal during tracheal intubation? Anesth Analg. 2006;102:825–831.
- Lerman J., Sikich N., Kleinman S., Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology. 1994;80:814–824.
- Lundy J.S. Balanced anesthesia. Minn Med. 1926:399–404.
- McCormick D.A., Bal T. Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci. 1997;20:185–215.
- Morimoto Y., Matsumoto A., Koizumi Y., Gohara T., Sakabe T., Hagihira S. Changes in the bispectral index during intraabdominal irrigation in patients anesthetized with nitrous oxide and sevoflurane. Anesth Analg. 2005;100:1370–1374.
- Ní Mhuircheartaigh R., Warnaby C., Rogers R., Jbabdi S., Tracey I. Slow-wave activity saturation and thalamocortical isolation during propofol anesthesia in humans. Sci Transl Med. 2013;5:208ra148.
- Otto K.A. EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery. Lab Anim. 2008;42:45–61.
- Otto K.A., Mally P. Noxious stimulation during orthopaedic surgery results in EEG ‘arousal’ or “paradoxical arousal” reaction in isoflurane-anaesthetised sheep. Res Vet Sci. 2003;75:103–112.
- Paus T., Collins D.L., Evans A.C., Leonard G., Pike B., Zijdenbos A. Maturation of white matter in the human brain: a review of magnetic resonance studies. Brain Res Bull. 2001;54:255–266.
- Prince D.A., Shanzer S. Effects of anesthetics upon the EEG response to reticular stimulation. Patterns of slow synchrony. Electroencephalogr Clin Neurophysiol. 1966;21:578–588.
- Schomer D.L., Lopes da Silva F., editors. Niedermeyer’s electroencephalography. Lippincott Williams & Wilkins; Philadelphia: 2011.
- Slater R., Cornelissen L., Fabrizi L., Patten D., Yoxen J., Worley A., Boyd S., Meek J., Fitzgerald M. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet. 2010;376:1225–1232.
- Slater R., Fabrizi L., Worley A., Meek J., Boyd S., Fitzgerald M. Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants. Neuroimage. 2010;52:583–589.
- Slater R., Worley A., Fabrizi L., Roberts S., Boyd S., Meek J., Fitzgerald M. Evoked potentials generated by noxious stimulation in the human infant brain. Eur J Pain. 2010;14:321–326.
- Sleigh J.W., Leslie K., Voss L. The effect of skin incision on the electroencephalogram during general anesthesia maintained with propofol or desflurane. J Clin Monit Comput. 2010;24:307–318.
- Steriade M., McCormick D.A., Sejnowski T.J. Thalamocortical oscillations in the sleeping and aroused brain. Science. 1993;262:679–685.
- Tracey I., Mantyh P.W. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377–391.
- Uhlhaas P.J., Pipa G., Lima B., Melloni L., Neuenschwander S., Nikolić D., Singer W. Neural synchrony in cortical networks: history, concept and current status. Front Integr Neurosci. 2009;3:17.
- Uhlhaas P.J., Roux F., Singer W., Haenschel C., Sireteanu R., Rodriguez E. The development of neural synchrony reflects late maturation and restructuring of functional networks in humans. Proc Natl Acad Sci USA. 2009;106:9866–9871.
- Worley A., Fabrizi L., Boyd S., Slater R. Multi-modal pain measurements in infants. J Neurosci Methods. 2012;205:252–257.
Source: PubMed