Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients

• Published in: Intensive care medicine 2003-11, Vol.29 (11), p.1916-1920
• Main Authors: ETHUIN, Frédéric, BOUDAOUD, Said, LEBLANC, Isabelle, TROJE, Christian, MARIE, Olivier, LEVRON, Jean-Claude, LE MOING, Jean-Pierre, ASSOUNE, Patrice, EURIN, Benoit, JACOB, Laurent
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - blood; Analgesics, Opioid - pharmacokinetics; APACHE; Biological and medical sciences; Conscious Sedation - methods; Critical Care - methods; Drug Monitoring; Drug Therapy, Combination; Half-Life; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - pharmacokinetics; Hypnotics. Sedatives; Infusions, Intravenous; Injections, Intravenous; Long-Term Care; Male; Medical sciences; Metabolic Clearance Rate; Midazolam - administration & dosage; Midazolam - pharmacokinetics; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Radioimmunoassay; Respiration, Artificial; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Distress Syndrome, Adult - therapy; Sufentanil - administration & dosage; Sufentanil - blood; Sufentanil - pharmacokinetics; Time Factors; Tissue Distribution
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-003-1920-y

To determine the pharmacokinetics of long-term infusion of sufentanil in ICU patients. Open-label study in a surgical intensive care unit. Ten consecutive patients without renal or hepatic failure requiring mechanical ventilation for at least 6 days. Patients received sufentanil (initial bolus 0.5 micro g/kg and continuous infusion rate of 0.5 micro g/kg per hour) and midazolam (initial bolus 0.08 mg/kg and continuous infusion 0.05 mg/kg per hour). Sedation was adjusted according to the Ramsay scale (score >3). Blood samples were taken during and up to 72 h after the infusion, and plasma concentrations were measured using a sensitive radioimmunoassay method. Plasma concentration-time profiles of sufentanil and pharmacokinetic parameters such as initial postinfusion half-life (t(1/2alpha)), elimination half-life (t(1/2beta)), total clearance (Cl), volume of distribution (Vdbeta), and time required to obtain a 50% decrease in plasma concentration (tcp(0/2)). The mean duration of sedation was 12+/-7 days. The initial half-life t(1/2alpha) was 1.33+/-1.15 h. The observed prolonged elimination half-life (t(1/2beta)=25.5+/-9.4 h) was related to the large volume of distribution (Vdbeta=22.6+/-9.4 l/kg). The mean total clearance was 13.4+/-7.0 ml/kg per minute. The mean time required to obtain a 50% decrease in plasma concentration was short (tcp(0/2=)4.7+/-3.7 h). The pharmacokinetic analysis of sufentanil for ICU sedation revealed increased volume of distribution and elimination half-life. Nevertheless the rapid distribution and elimination processes suggest that the rapid reversibility of sedation with sufentanil is maintained after long duration of infusion. Further studies should be carried out to evaluate the clinical relevance of these results.