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Excitatory effects of fentanyl upon the rat electroencephalogram and auditory-evoked potential responses during anaesthesia

Published online by Cambridge University Press:  11 July 2005

L. M. Antunes
Affiliation:
Comparative Biology Centre, Medical School, Newcastle-upon-Tyne, UK ICETA-UTAD, Patologia e Clinicas Veterinárias, Vila Real, Portugal
J. V. Roughan
Affiliation:
Comparative Biology Centre, Medical School, Newcastle-upon-Tyne, UK
P. A. Flecknell
Affiliation:
Comparative Biology Centre, Medical School, Newcastle-upon-Tyne, UK
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Summary

Background and objective: Previous studies have shown existence of inconsistent data concerning the use of auditory-evoked potential (AEP) and electroencephalogram (EEG) changes to measure the depth of anaesthesia in regimens involving the use of opioids. The present studies characterize the effects of fentanyl on those responses in rats.

Methods: The effects of a bolus of fentanyl (6–10 μg kg−1 intravenously) alone or following naloxone (100 μg kg−1 intravenously) were examined using brain responses in rats during light anaesthesia with either propofol (20–30 mg kg−1 h−1) or isoflurane (0.8%). Electrophysiological data were recorded using silver ball electrodes. The rats' tracheas were intubated and a femoral artery cannula was inserted to monitor blood pressure. Body temperature, respiratory and pulse rate, and pedal withdrawal data were also collected. Parameters measured before and following administration of naloxone and fentanyl or of fentanyl alone were compared using repeated-measures ANOVA.

Results: Fentanyl significantly increased the latency of the major peak from the AEP during propofol and isoflurane anaesthesia (F = 13.2 and 13.5, respectively; P < 0.05) and the amplitude differential between two waveform complexes, and the second differential index (F = 28.3 and 57.2, respectively; P < 0.01). The spectral edge frequency and median frequency from the EEG tended to increase. These effects were abolished by the prior administration of naloxone.

Conclusions: These excitatory effects were inconsistent with the classical concept of brain activity depression indicating a deepening of anaesthesia.

Type
Original Article
Copyright
© 2003 European Society of Anaesthesiology

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References

Thornton C, Konieczko KM, Knight AB, et al. Effect of propofol on the auditory evoked response and oesophageal contractility. Br J Anaesth 1989; 63: 411417.Google Scholar
Hung OR, Varvel JR, Shafer SL, Stanski DR. Thiopental pharmacodynamics II: Quantitation of clinical and electroencephalographic depth of anesthesia. Anesthesiology 1992; 77: 237244.Google Scholar
Dwyer RC, Rampil IJ, Eger EI, II, Bennett HL. The electroencephalogram does not predict depth of isoflurane anesthesia. Anesthesiology 1994; 81: 403409.Google Scholar
Fox SS, O'Brian JH. Duplication of evoked potential waveform by curve of probability of firing of a single cell. Science 1965; 147: 888890.Google Scholar
Samra SK, Lilly DJ, Rush NL, Kirsh MM. Fentanyl anesthesia and human brain-stem auditory evoked potentials. Anesthesiology 1984; 61: 261265.Google Scholar
Velasco M, Velasco F, Castaneda R, Sanchez R. Effect of fentanyl and naloxone on somatic and auditory evoked potentials in man. Proc West Pharmacol Soc 1983; 26: 291294.Google Scholar
Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantification of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology 1991; 74: 3442.Google Scholar
Gilron I, Plourde G, Marcantoni W, Varin F. 40 Hz auditory steady-state response and EEG spectral edge frequency during sufentanil anaesthesia. Can J Anaesth 1998; 45: 115121.Google Scholar
Cox EH, Langemeijer MW, Gubbens-Stibbe JM, Muir KT, Danhof M. The comparative pharmacodynamics of remifentanil and its metabolite, GR90291, in a rat electroencephalographic model. Anesthesiology 1999; 90: 535544.Google Scholar
Haberham ZL, van de Brom WE, Haagen AJ, de Groof HN, Baumans V, Hellebrekers LJ. Differential monitoring of hypnosis and anti-nociception during fentanyl anaesthesia using spontaneous and evoked electroencephalography in the rat. In: Haberham ZL, ed. Development and Evaluation of Methods for Assessment of Quality of Anaesthesia in the Rat. Utrecht, The Netherlands: University of Utrecht, 2000; 77101.
Hoffman WE, Cunningham F, James MK, Baughman VL, Albrecht RF. Effects of remifentanil, a new short-acting opioid, on cerebral blood flow, brain electrical activity, and intracranial pressure in dogs anesthetized with isoflurane and nitrous oxide. Anesthesiology 1993; 79: 107113.Google Scholar
Johnson CB, Taylor PM. Effects of alfentanil on the equine electroencephalogram during anaesthesia with halothane in oxygen. Res Vet Sci 1997; 62: 159163.Google Scholar
Antunes LM, Roughan JV, Flecknell PA. Evaluation of auditory evoked potentials to predict depth of anaesthesia during fentanyl/fluanisone – midazolam anaesthesia in rats. Vet Anaesth Analg 2001; 28: 196203.Google Scholar
Jordan C. Auditory Evoked Response Program AVG Manual. Harrow, UK: Academic Department of Anaesthesia, Northwick Park Hospital. 1994.
Wauquier A, De Ryck M, Van den Broeck W, Van Loon J, Melis W, Janssen P. Relationships between quantitative EEG measures and pharmacodynamics of alfentanil in dogs. Electroencephalogr Clin Neurophysiol 1988; 69: 550560.Google Scholar
Vaughan DJ, Shinner G, Thornton C, Brunner MD. Effect of tramadol on electroencephalographic and auditory-evoked response variables during light anaesthesia. Br J Anaesth 2000; 85: 705707.Google Scholar
Crabb I, Thornton C, Konieczko KM, et al. Remifentanil reduces auditory and somatosensory evoked responses during isoflurane anaesthesia in a dose-dependent manner. Br J Anaesth 1996; 76: 795801.Google Scholar
Shinner G, Sharpe RM, Thornton C, Dore CJ, Brunner MD. Effect of bolus doses of alfentanil on the arousal response to intubation, as assessed by the auditory evoked response. Br J Anaesth 1999; 82: 925928.Google Scholar
Schwender D, Rimkus T, Haessler R, Klasing S, Poppel E, Peter K. Effects of increasing doses of alfentanil, fentanyl and morphine on mid-latency auditory evoked potentials. Br J Anaesth 1993; 71: 622628.Google Scholar
Mi WD, Sakai T, Singh H, Kudo T, Kudo M, Matsuki A. Hypnotic endpoints versus the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl. Eur J Anaesthesiol 1999; 16: 4752.Google Scholar
Barr G, Anderson RE, Owall A, Jakobsson JG. Effects on the bispectral index during medium–high dose fentanyl induction with or without propofol supplement. Acta Anaesthesiol Scand 2000; 44: 807811.Google Scholar
Antunes LM. The use of the electroencephalogram and auditory evoked potentials to assess the depth of anaesthesia and effects of anaesthetic agents in the laboratory rat (Rattus norvegicus). PhD thesis, University of Newcastle upon Tyne, UK, 2001.
Barbanoj MJ, Antonijoan RM, Morte A, Riba J, Jane F. Study of human psychotropic drug interactions by means of q-EEG, In: Saletu B, ed. Electrophysiological Brain Research in Preclinical and Clinical Pharmacology and Related Fields – An Update. Vienna, Austria: International Pharmaco-EEG Group (IPEG) Meeting, 2000: 164172.
Kuizenga K, Kalkman CJ, Hennis PJ. Quantitative electroencephalographic analysis of the biphasic concentration– effect relationship of propofol in surgical patients during extradural analgesia. Br J Anaesth 1998; 80: 725732.Google Scholar
Gustafsson LL, Ebling WF, Osaki E, Stanski DR. Quantitation of depth of thiopental anesthesia in the rat. Anesthesiology 1996; 84: 415427.Google Scholar
Dutta S, Matsumoto Y, Gothgen NU, Ebling WF. Concentration–EEG effect relationship of propofol in rats. J Pharm Sci 1997; 86: 37 – 43.Google Scholar
Dafny N. Neurophysiological approach as a tool to study the effects of drugs on the central nervous system: dose effect of pentobarbital. Exp Neurol 1978; 59: 263274.Google Scholar
Borbely AA, Hall RD. Effects of pentobarbitone and chlorpromazine on acoustically evoked potentials in the rat. Neuropharmacology 1970; 9: 575586.Google Scholar
Castaneda R, Velasco M, Sanchez R, Davila A. Effect of fentanyl and naloxone on early and late components of the auditory evoked potentials. Arch Invest Med (Mex) 1987; 18: 5167.Google Scholar
Angel A. Processing of sensory information. Prog Neurobiol 1977; 9: 1122.Google Scholar
Church MW, Gritzke R. Effects of ketamine anesthesia on the rat brain-stem auditory evoked potential as a function of dose and stimulus intensity. Electroencephalogr Clin Neurophysiol 1987; 67: 570583.Google Scholar
Gahwiler BH. Excitatory action of opioid peptides and opiates on cultured hippocampal pyramidal cells. Brain Res 1980; 194: 193203.Google Scholar
Nicoll RA, Siggins GR, Ling N, Bloom FE, Guillemin R. Neuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study. Proc Natl Acad Sci USA 1977; 74: 25842588.Google Scholar
Henriksen SJ, Bloom FE, McCoy F, Ling N, Guillemin R. Beta-endorphin induces nonconvulsive limbic seizures. Proc Natl Acad Sci USA 1978; 75: 52215225.Google Scholar
Zieglgansberger W, French ED, Siggins GR, Bloom FE. Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science 1979; 205: 415417.Google Scholar
Lupica CR, Dunwiddie TV. Differential effects of mu- and delta-receptor selective opioid agonists on feedforward and feedback GABAergic inhibition in hippocampal brain slices. Synapse 1991; 8: 237248.Google Scholar
Werz MA, Macdonald RL. Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action. Brain Res 1982; 236: 107119.Google Scholar
Kofke WA, Garman RH, Tom WC, Rose ME, Hawkins RA. Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain. Anesth Analg 1992; 75: 953964.Google Scholar
Sinz EH, Kofke WA, Garman RH. Phenytoin, midazolam, and naloxone protect against fentanyl-induced brain damage in rats. Anesth Analg 2000; 91: 14431449.Google Scholar
Short CE. Pain, analgesics, and related medications. In: Short CE, ed. Principles and Practice of Veterinary Anesthesia. Baltimore, USA: Williams & Wilkins, 1987: 2846.
Smith NT, Benthuysen JL, Bickford RG, et al. Seizures during opioid anesthetic induction – are they opioid-induced rigidity? Anesthesiology 1989; 71: 852862.Google Scholar
Sprung J, Schedewie HK. Apparent focal motor seizure with a Jacksonian march induced by fentanyl: a case report and review of the literature. J Clin Anesth 1992; 4: 139143.Google Scholar
Da Silva O, Alexandrou D, Knoppert D, Young GB. Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion. J Perinatol 1999; 19: 120123.Google Scholar
Benthuysen JL, Smith NT, Sanford TJ, Head N, Dec-Silver H. Physiology of alfentanil-induced rigidity. Anesthesiology 1986; 64: 440446.Google Scholar
Lai S, Lui P. Inhibition by neuropeptide Y of fentanyl-induced muscular rigidity at the locus coeruleus in rats. Neurosci Lett 2000; 280: 203206.Google Scholar
Miyazato H, Skinner RD, Cobb M, Andersen B, Garcia-Rill E. Midlatency auditory-evoked potentials in the rat: effects of interventions that modulate arousal. Brain Res Bull 1999; 48: 545553.Google Scholar