TITLE:
Should Propofol and Alfentanil Be Combined in Patient-Controlled Sedation? A Randomised Controlled Trial Using Pharmacokinetic Simulation
AUTHORS:
Andreas Nilsson, Lena Nilsson, Thomas Schnider, Eva Uustal, Folke Sjöberg
KEYWORDS:
Anaesthetics, Intravenous, Propofol, Analgesics, Opioids, Alfentanil, Sedation
JOURNAL NAME:
Open Journal of Anesthesiology,
Vol.5 No.6,
June
24,
2015
ABSTRACT: Background: Patient-controlled sedation (PCS) is increasingly used for moderate sedation. Detailed understanding is essential for maintaining safety and giving the most benefit. We wanted to explore the associations between patients’ characteristics, perioperative pain and anxiety, the procedure, and the calculated concentrations at the effect site (Ce) of propofol. We also wanted to analyse the pharmacokinetic profiles of propofol and alfentanil during PCS, and their association with respiratory complications. Methods: 155 patients were double-blinded and randomised to have propofol or propofol and alfentanil for PCS during gynaecological surgery. Pharmacokinetic simulation of Ce and multiple regressions aided the search for correlations between explanatory variables and concentrations of drugs. Results: In group propofol, treatment for incontinence, anterior repair, and the patient’s weight correlated the best (B-coef = 0.20, 0.20 and 0.01; r = 0.69; r² = 0.48). When alfentanil was added, alfentanil and the patient’s weight were associated with Ce of propofol (B-coef = ǂ.40 and 0.01; r = 0.70; r² = 0.43). Logistic regression indicated that age and Ce of drugs were related to ten cases of respiratory complications. Conclusions: Patients’ weights and the type of surgery performed were associated with the Ce of propofol; this knowledge could be used for refinement of the doses given during PCS. Because the pharmacokinetic profiles of propofol and alfentanil are different, the alfentanil effect becomes predominant during the time course of sedation. In order to reduce the risk of early and late respiratory depression, alfentanil should not be added to propofol in the same syringe.