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Modelling the pharmacodynamic interaction between remifentanil and propofol by EEG-controlled dosing

Published online by Cambridge University Press:  30 June 2005

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

Summary

Background and objective: Knowledge of the pharmacodynamic interaction between remifentanil and propofol is important to permit optimal dosage strategies. We studied this pharmacodynamic interaction using the median power frequency of the processed electroencephalogram as a control parameter for feedback-controlled dosing of propofol.

Methods: Twenty-one patients were given total intravenous anaesthesia with remifentanil and propofol. During three target-controlled infusion regimens, the target concentrations of remifentanil (5, 10, 15 ng mL−1) and propofol dosing were automatically adjusted to keep the median power frequency in the range 2 ± 0.5 Hz. In each patient and during each remifentanil target concentration, four arterial propofol/remifentanil concentration pairs were measured. The type of interaction was tested using the relative distance from the line of additivity and the isobole was modelled using Bernstein splines.

Results: The results from 13 patients were used for data analysis. The measured remifentanil concentrations during the three targets were (mean ± SD): 3.6 ± 0.9, 8.1 ± 2.5 and 12.4 ± 2.8 ng mL−1. The corresponding propofol concentrations were 2.64 ± 0.86, 2.13 ± 0.58 and 2.09 ± 0.58 μg mL−1. The data were best described with an additive type of interaction and the isobole was estimated using:

Conclusions: Within the studied concentration range, remifentanil and propofol showed an additive type of pharmacodynamic interaction on the electroencephalogram.

Keywords

ANAESTHETICS, INTRAVENOUS, propofol, remifentanilDIAGNOSTIC TECHNIQUES AND PROCEDURES, electrodiagnosis, electroencephalographyDRUG INTERACTIONSMONITORING, PHYSIOLOGICAL, drug monitoring
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 5 , May 2003 , pp. 373 - 379
Copyright
2003 European Society of Anaesthesiology

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References

Sneyd JR, Whaley A, Dimpel HL, Andrews CJ. An open, randomized comparison of alfentanil, remifentanil and alfentanil followed by remifentanil in anaesthesia for craniotomy. Br J Anaesth 1998; 81: 361–364.Google Scholar
Schuttler J, Albrecht S, Breivik H, et al. A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery. Anaesthesia 1997; 52: 307–317.Google Scholar
Larsen B, Seitz A, Larsen R. Recovery of cognitive function after remifentanil–propofol anesthesia: a comparison with desflurane and sevoflurane anesthesia. Anesth Analg 2000; 90: 168–174.Google Scholar
Park GR, Evans TN, Hutchins J, et al. Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil. Eur J Anaesthesiol 2000; 17: 111–119.Google Scholar
Ogilvy AJ. Awareness during total intravenous anaesthesia with propofol and remifentanil. Anaesthesia 1998; 53: 308.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
Vuyk J. Drug interactions in anaesthesia. Minerva Anestesiol 1999; 65: 215–218.Google Scholar
Kissin I. A concept for assessing interactions of general anesthetics. Anesth Analg 1997; 85: 204–210.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; discussion 26A.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, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology 1991; 74: 34–42.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
Schwilden H, Schuttler J, Stoeckel H. Quantitation of the EEG and pharmacodynamic modelling of hypnotic drugs: etomidate as an example. Eur J Anaesthesiol 1985; 2: 121–131.Google Scholar
Egan TD, Minto CF, Hermann DJ, et al. Remifentanil versus alfentanil: comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology 1996; 84: 821–833.Google Scholar
Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997; 86: 10–23.Google Scholar
Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology 1997; 86: 24–33.Google Scholar
Schuttler J. Pharmakokinetik und -dynamik des intravenösen Anaesthetikums Propofol (Disoprivan).Berlin, Germany: Springer, 1990.
Schuttler J, Stoeckel H, Schwilden H. Pharmacokinetic and pharmacodynamic modelling of propofol (‘Diprivan’) in volunteers and surgical patients. Postgrad Med J 1985; 61: 53–54.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
Albrecht S, Ihmsen H, Suchodolski K, Frenkel C, Schuttler J. Analgo-sedation in intensive care: a quantitative, EEG-based trial with propofol 1% and 2%. Anaesthesist 1999; 48: 794–801.Google Scholar
Schwilden H, Stoeckel H. Closed-loop feedback controlled administration of alfentanil during alfentanil-nitrous oxide anaesthesia. Br J Anaesth 1993; 70: 389–393.Google Scholar
Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusions in humans. Anesth Analg 1987; 66: 1256–1263.Google Scholar
Plummer GF. Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987; 421: 171–176.Google Scholar
Bender J, van den Elshout J, Selinger K, et al. Determination of remifentanil in human heparinised whole blood by tandem mass spectrometry with short-column separation. J Pharm Biomed Anal 1999; 21: 559–567.Google Scholar
Gessner PK, Shakarjian MP. Interactions of paraldehyde with ethanol and chloral hydrate. J Pharmacol Exp Ther 1985; 235: 32–36.Google Scholar
Schuttler J, Ihmsen H. Population pharmacokinetics of propofol: a multicenter study. Anesthesiology 2000; 92: 727–738.Google Scholar
Egan TD, Lemmens HJ, Fiset P, et al. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology 1993; 79: 881–892.Google Scholar
Schwilden H, Fechner J, Albrecht S, Hering W, Ihmsen H, Schüttler J. Testing and modelling the interaction of alfentanil and propofol on the EEG. Eur J Anaesthesiol 2003; 20: 363–372.Google Scholar
Forrest FC, Tooley MA, Saunders PR, Prys-Roberts C. Propofol infusion and the suppression of consciousness: the EEG and dose requirements. Br J Anaesth 1994; 72: 35–41.Google Scholar
Drover DR, Lemmens HJ. Population pharmacodynamics and pharmacokinetics of remifentanil as a supplement to nitrous oxide anesthesia for elective abdominal surgery. Anesthesiology 1998; 89: 869–877.Google Scholar
Høymork SC, Raeder J, Grimsmo B, Steen PA. Bispectral index, predicted and measured drug levels of target-controlled infusions of remifentanil and propofol during laparoscopic cholecystectomy and emergence. Acta Anaesthesiol Scand 2000; 44: 1138–1144.Google Scholar
Dershwitz M, Randel GI, Rosow CE, et al. Initial clinical experience with remifentanil, a new opioid metabolized by esterases. Anesth Analg 1995; 81: 619–623.Google Scholar
Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M. The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg 2000; 90: 161–167.Google Scholar
Röpcke H, Konen-Bergmann M, Cuhls M, Bouillon T, Hoeft A. Propofol and remifentanil pharmacodynamic interaction during orthopedic surgical procedures as measured by effects on bispectral index. J Clin Anesth 2001; 13: 198–207.Google Scholar
Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther 1997; 281: 226–232.Google Scholar
Lang E, Kapila A, Shlugman D, et al. Reduction of iso-flurane minimal alveolar concentration by remifentanil. Anesthesiology 1996; 85: 721–728.Google Scholar