title: Pharmacokinetic model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia.
abstract: OBJECTIVE
  To evaluate the prospective predictive accuracy and the quality of anesthesia of pharmacokinetic model-driven infusion of sufentanil and midazolam designed to establish and maintain a plasma level of drug during cardiac surgery.
  
  
  METHODS
  Prospective analysis.
  
  
  METHODS
  Operating room at a university hospital.
  
  
  METHODS
  Twenty adult patients younger than 75 years old scheduled for valvular or coronary artery bypass graft surgery.
  
  
  METHODS
  Patients were anesthetized using a variable predicted concentration of sufentanil (1 to 10 ng/mL) combined with a stable predicted concentration of midazolam (100 ng/mL).
  
  
  RESULTS
  For each patient, arterial samples were taken before (6 samples), during (2 samples), and after (2 samples) cardiopulmonary bypass (CPB). Plasma sufentanil and midazolam concentrations were measured by specific radioimmunoassay and high-performance liquid chromatography techniques. Predicted sufentanil and midazolam concentrations were derived using the data sets of Gepts et al and Maitre et al. The predictive performance, the percentage prediction error (PE), and the absolute percentage error were calculated for each sample. The bias, inaccuracy, and dispersion were assessed by determining the median of the individual medians of the prediction errors (MDPE), the median of the individual median of the absolute prediction errors (MDAPE), and the 10th and 90th percentiles of PE. For midazolam, the inaccuracy was low (MDAPE < 21%), but CPB was associated with a dilution of the measured concentration associated with a negative bias. For sufentanil, the inaccuracy was also low before CPB (MDAPE = 18%) but increased during and after CPB (MDAPE > 40%). During the whole procedure, the hemodynamic control necessitated only a few interventions.
  
  
  CONCLUSIONS
  Pharmacokinetic model-driven infusion of sufentanil and midazolam using the pharmacokinetic sets of Gepts et al and Maitre et al is a safe and accurate anesthetic technique before CPB in adult patients undergoing cardiac surgery when high sufentanil (1 to 10 ng/mL) and low midazolam (100 ng/mL) predicted plasma concentrations are targeted.
authors.affiliation: Department of Anesthesiology, Erasmus Hospital, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Barvais
authors.forename: D
authors.initials: D
authors.lastname: Heitz
authors.forename: D
authors.initials: D
authors.lastname: Schmartz
authors.forename: V
authors.initials: V
authors.lastname: Maes
authors.forename: E
authors.initials: E
authors.lastname: Coussaert
authors.forename: F
authors.initials: F
authors.lastname: Cantraine
authors.forename: A
authors.initials: A
authors.lastname: d'Hollander
mesh_terms: D000328:Adult; D000368:Aged; D000758:Anesthesia; D019162:Anesthetics, Combined / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002315:Cardiopulmonary Bypass; D002851:Chromatography, High Pressure Liquid; D001026:Coronary Artery Bypass; D005260:Female; D006351:Heart Valves / Q000601:surgery*; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D011446:Prospective Studies; D011863:Radioimmunoassay; D017409:Sufentanil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013813:Therapy, Computer-Assisted
chemical_list: D019162:Anesthetics, Combined; D018686:Anesthetics, Intravenous; D017409:Sufentanil; D008874:Midazolam