Pharmacodynamic interaction of nitrous oxide with sevoflurane, desflurane, isoflurane and enflurane in surgical patients: measurements by effects on EEG median power frequency

Background and objective This study investigates the interaction of sevoflurane and nitrous oxide on EEG median power frequency of 2.5 Hz during surgery. Methods Sevoflurane concentrations required for electroencephalographic median power frequency between 2 and 3 Hz were measured in 25 patients during gynaecological laparotomies. Nitrous oxide was randomly administered at 0, 20, 40, 60 and 75 vol%, subsequently two different concentrations in each patient. The data were analysed using isobolographic analysis together with previously published data on nitrous oxide–isoflurane, –enflurane, or –desflurane interaction. Results The interaction is described by the equation: C volatile anaesthetic/C0 volatile anaesthetic + C N2O/C0 N2O=1 (C is the concentrations for a drug combination to achieve the desired effect; C0 is the concentration for single drug use). The parameters are C0 isoflurane=1.11 vol% (95% CI 1.03–1.19), C0 enflurane=1.64 (1.52–1.77), C0 desflurane=5.31 (4.92–5.73), C0 sevoflurane=2.12 (1.96–2.29), C0 N2O=174 (153–202). These parameters decrease by 6% (2.5–10) for every 10 years of patients’ age > 40 years. Conclusions The interaction is compatible with additivity. The potency of nitrous oxide to substitute the volatile anaesthetics is less than anticipated from previously reported MAC values.

[1]  A Matsuki,et al.  Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl. , 1999, European journal of anaesthesiology.

[2]  E. Eger,et al.  Determination and applications of MAC. , 1980, Anesthesiology.

[3]  E. Eger,et al.  Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. , 1992, Anesthesiology.

[4]  H. Schwilden,et al.  Interaction of Isoflurane and Nitrous Oxide Combinations Similar for Median Electroencephalographic Frequency and Clinical Anesthesia , 1996, Anesthesiology.

[5]  Joseph Berkson,et al.  Approximation of Chi-Square by “Probits” and by “Logits” , 1946 .

[6]  U Finsterer,et al.  Power spectral analysis of the electroencephalogram during increasing end‐expiratory concentrations of isoflurane, desflurane and sevoflurane , 1998, Anaesthesia.

[7]  Chiharu Negishi,et al.  Bispectral EEG Index during Nitrous Oxide Administration , 1998, Anesthesiology.

[8]  S. Loewe The problem of synergism and antagonism of combined drugs. , 1953, Arzneimittel-Forschung.

[9]  K. Ikeda,et al.  Electroencephalographic Derivatives as a Tool for Predicting the Depth of Sedation and Anesthesia Induced by Sevoflurane , 1998, Anesthesiology.

[10]  E. Eger,et al.  Does Nitrous Oxide Antagonize Isoflurane‐induced Suppression of Learning? , 1993, Anesthesiology.

[11]  H Schwilden,et al.  Quantitative EEG analysis during anaesthesia with isoflurane in nitrous oxide at 1.3 and 1.5 MAC. , 1987, British journal of anaesthesia.

[12]  I J Rampil,et al.  Anesthetic Potency (MAC) Is Independent of Forebrain Structures in the Rat , 1993, Anesthesiology.

[13]  J. Antognini,et al.  Exaggerated Anesthetic Requirements in the Preferentially Anesthetized Brain , 1993, Anesthesiology.

[14]  E. Tassonyi,et al.  MAC-awake of isoflurane, enflurane and halothane evaluated by slow and fast alveolar washout. , 1992, British journal of anaesthesia.

[15]  K. Ikeda,et al.  Cerebral Awakening Concentration of Sevoflurane and Isoflurane Predicted During Slow and Fast Alveolar Washout , 1993, Anesthesia and analgesia.

[16]  E. Eger,et al.  Kinetics and Potency of Desflurane (I‐653) in Volunteers , 1990, Anesthesia and analgesia.

[17]  E. Bradley,et al.  Isobolographic Analysis of Propofol-thiopental Hypnotic Interaction in Surgical Patients , 1999 .

[18]  R. Dutton,et al.  Concentrations of Desflurane and Propofol That Suppress Response to Command in Humans , 1995, Anesthesia and analgesia.

[19]  W W Mapleson,et al.  Effect of age on MAC in humans: a meta-analysis. , 1996, British journal of anaesthesia.

[20]  H Schwilden,et al.  Closed-loop feedback controlled administration of alfentanil during alfentanil-nitrous oxide anaesthesia. , 1993, British journal of anaesthesia.

[21]  Berenbaum Mc What is synergy? , 1989, Pharmacological reviews.

[22]  I J Rampil,et al.  Anesthetic Potency Is Not Altered after Hypothermic Spinal Cord Transection in Rats , 1994, Anesthesiology.

[23]  H Ishihara,et al.  The effects of nitrous oxide and ketamine on the bispectral index and 95% spectral edge frequency during propofol-fentanyl anaesthesia. , 1999, European journal of anaesthesiology.

[24]  I. Rampil A Primer for EEG Signal Processing in Anesthesia , 1998, Anesthesiology.

[25]  K. Ikeda,et al.  Does nitrous oxide antagonize sevoflurane-induced hypnosis? , 1997, British journal of anaesthesia.

[26]  M. Berenbaum What is synergy? , 1989, Pharmacological reviews.

[27]  T. Yamamura,et al.  Fast Oscillatory EEG Activity Induced by Analgesic Concentrations of Nitrous Oxide in Man , 1981, Anesthesia and analgesia.

[28]  E. Tassonyi,et al.  MAC-AWAKE OF ISOFLURANE, ENFLURANE AND HALOTHANE EVALUATED BY SLOW AND FAST ALVEOLAR WASHOUT , 1992 .

[29]  E Olofsen,et al.  The dynamic relationship between end-tidal sevoflurane and isoflurane concentrations and bispectral index and spectral edge frequency of the electroencephalogram. , 1999, Anesthesiology.

[30]  L. L. Cam,et al.  Maximum likelihood : an introduction , 1990 .

[31]  E. Eger,et al.  Clinical Pharmacology of Nitrous Oxide: An Argument for Its Continued Use , 1990, Anesthesia and analgesia.

[32]  I J Rampil,et al.  Volatile Anesthetics Depress Spinal Motor Neurons , 1996, Anesthesiology.

[33]  J. Jakobsson,et al.  Nitrous oxide does not alter bispectral index: study with nitrous oxide as sole agent and as an adjunct to i.v. anaesthesia. , 1999, British journal of anaesthesia.