Rolan, Paul EdwardUpton, Richard N.MacIntyre, Pamela ElizabethAhmad, Muhammad Imran2014-07-312014-07-312014http://hdl.handle.net/2440/84137Pain is poorly managed in the opioid-maintained population. This study aimed to find safe and efficacious doses of fentanyl for acute pain management in the opioid-tolerant using experimental pain models and link that with the baseline morphine equivalent daily dose that the patients were taking. 9 patients were enrolled in the study from the Pain Management Unit at the Royal Adelaide Hospital. The study was an open label study using an infusion pump and STANPUMP software to rapidly achieve constant estimated effect compartment fentanyl concentrations. Fentanyl effect site concentrations of 2, 4, 6 and 8 ng/ml were targeted for the first visit and 4, 8, 12 and 16 ng/ml were targeted for patients on the second visit. The infusion involved four infusion steps lasting for 30 minutes each and during each step pharmacodynamic measures were taken that consisted of electroencephalography (EEG), saccadic eye movement test (SEM), pupillometry, morphine-benzedrine group scale (MBG) and cold pain test. The subjective opioid withdrawal scale tests (SOWS) were conducted once the infusion was stopped. Using PK/PD modelling techniques within R, the concentration-effect relationships were described using zero slope, linear, Emax [max subscript] and Sigmoid Emax [max subscript] models. Our study was not able to demonstrate that the baseline morphine equivalent daily dose predicted suitable doses of fentanyl in acute pain management of the opioid-tolerant. This was probably due to the fact that the study was of insufficient sample size to detect the effect of the covariate. However, we have demonstrated that the study design was safe, informative and suitable for it to be replicated with a larger number of subjects in the future.fentanyl; opioid-tolerant; opioid-dependent; acute pain; pain management; opioidThesis20140728123033