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Testing and modelling the interaction of alfentanil and propofol on the EEG

Published online by Cambridge University Press:  30 June 2005

H. Schwilden ,
J. Fechner ,
S. Albrecht ,
W. Hering ,
H. Ihmsen  and
J. Schüttler
H. Schwilden
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
J. Fechner
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
S. Albrecht
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
W. Hering
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
H. Ihmsen
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
J. Schüttler
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Anaesthesiology, Erlangen, Germany
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Extract

Summary

Background and objective: For total intravenous anaesthesia an opioid is often combined with a hypnotic. A supra-additive interaction has been reported for clinical signs such as loss of consciousness or loss of the eyelash reflex. This study investigated the type of interaction of alfentanil and propofol on the electroencephalogram.

Methods: Twenty patients scheduled for abdominal surgery were enrolled in the study. Anaesthesia was induced and maintained with alfentanil and propofol. Each patient received a target-controlled infusion of alfentanil. Three target concentrations of 150, 225 and 300 ng mL−1 were applied to each patient in random order. Propofol was added to the alfentanil infusion by a feedback system. The set point was the range of 1.5–2.5 Hz median frequency of the electroencephalogram. Four arterial blood samples were taken within the last 20 min of each period. The mean drug concentrations were used to determine the type of interaction and an isobole was estimated by fitting Bernstein spline functions to the data.

Results: In 17 patients, all three alfentanil target concentrations could be administered. The test for supra-additivity as well as the isobole construction resulted in an additive type of interaction. The line of additivity cA/cA0 + cP/cP0 = 1 was best fitted for the values (standard deviation) cA0 = 1240 (51) ng mL−1 and cP0 = 5.21 (0.36) μg mL−1.

Conclusions: The type of interaction between alfentanil and propofol on the electroencephalogram in the investigated dose range is additive. This gives the freedom and need to select the appropriate dosing ratio of alfentanil and propofol by other considerations.

Keywords

ANAESTHESIA, INTRAVENOUSANAESTHETICS, INTRAVENOUS, propofolCHEMICAL AND PHARMACOLOGICAL PHENOMENA, drug interactions, drug synergismNARCOTICS, alfentanil
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 5 , May 2003 , pp. 363 - 372
Copyright
2003 European Society of Anaesthesiology

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References

Iselin-Chaves IA, Flaishon R, Sebel PS, et al. The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index. Anesth Analg 1998; 87: 949–955.Google Scholar
Kazama T, Ikeda K, Morita K, Katoh T, Kikura M. Propofol concentration required for endotracheal intubation with a laryngoscope or fiberscope and its interaction with fentanyl. Anesth Analg 1998; 86: 872–879.Google Scholar
Smith C, McEwan AI, Jhaveri R, et al. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology 1994; 81: 820–828.Google Scholar
Vuyk J, Lim T, Engbers FH, Burm AG, Vletter AA, Bovill JG. The pharmacodynamic interaction of propofol and alfentanil during lower abdominal surgery in women. Anesthesiology 1995; 83: 8–22.Google Scholar
Vuyk J, Engbers FH, Burm AGL, et al. Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia. Anesthesiology 1996; 84: 288–299.Google Scholar
Vuyk J. Pharmacokinetic and pharmacodynamic interactions between opioids and propofol. J Clin Anesth 1997; 9: 23S–26S.Google Scholar
Vuyk J, Mertens MJ, Olofsen E, Burm AG, Bovill JG. Propofol anesthesia and rational opioid selection: determination of optimal EC50–EC95 propofol–opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology 1997; 87: 1549–1562.Google Scholar
Maitre PO, Vozeh S, Heykants J, Thomson DA, Stanski DR. Population pharmacokinetics of alfentanil: the average dose–plasma concentration relationship and interindividual variability in patients. Anesthesiology 1987; 66: 3–12.Google Scholar
Schwilden H, Schuttler J, Stoeckel H. Closed-loop feedback control of methohexital anesthesia by quantitative EEG analysis in humans. Anesthesiology 1987; 67: 341–347.Google Scholar
Schwilden H, Stoeckel H, Schuttler J. Closed-loop feedback control of propofol anaesthesia by quantitative EEG analysis in humans. Br J Anaesth 1989; 62: 290–296.Google Scholar
Ihmsen H, Tzabazis A, Schywalski M, Schwilden H. Propofol in rats: testing for nonlinear pharmacokinetics and modelling acute tolerance to EEG effects. Eur J Anaesthesiol 2002; 19: 177–188.Google Scholar
Schraag S, Mohl U, Bothner U, Georgieff M. Interaction modeling of propofol and sufentanil on loss of consciousness. J Clin Anesth 1999; 11: 391–396.Google Scholar
Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology 1985; 62: 234–241.Google Scholar
Eger EI. Does 1 + 1 = 2? Anesth Analg 1989; 68: 551–552.Google Scholar
Berenbaum MC. What is synergy? Pharmacol Rev 1989; 41: 93–141.Google Scholar
Ihmsen H, Albrecht S, Fechner J, Hering W, Schüttler J. The elimination of alfentanil is decreased by propofol. Anesthesiology 2000; 93: A531.Google Scholar
Coderre TJ, Katz J, Vaccarino AL, Melzack R. Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence. Pain 1993; 52: 259–285.Google Scholar
Katz J, Kavanagh BP, Sandler AN, et al. Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain. Anesthesiology 1992; 77: 439–446.Google Scholar
Celerier E, Rivat C, Jun Y, et al. Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology 2000; 92: 465–472.Google Scholar
Eisenach JC. Preemptive hyperalgesia, not analgesia? Anesthesiology 2000; 92: 308–309.Google Scholar
Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology 2000; 93: 409–417.Google Scholar
Dierkcx P. Curve and Surface Fitting with Splines.New York, USA: Oxford University Press, 1993.