Analgesic efficacy and pharmacokinetics of epidural oxycodone in pain management after gynaecologic laparoscopy - a randomised, double blind, active control, double-dummy clinical comparison with intravenous administration.

AIMS: Early pain after laparoscopy is often severe. Oxycodone is a feasible analgesic option after laparoscopy, but there are sparse data on epidural administration. The aim was to evaluate the analgesic efficacy and pharmacokinetics of a single dose of epidural oxycodone as a part of multimodal analgesia after gynaecologic laparoscopy.

METHODS: Women (n=60), aged 23-71 years, undergoing elective gynaecologic laparoscopy, were administrated either epidural oxycodone 0.1 mg·kg-1 and i.v. saline (EPI-group n=31) or epidural saline and i.v. oxycodone 0.1 mg·kg-1 (IV-group=29) in a randomised, double blind, active control, double dummy clinical trial. A pharmacokinetic-model was developed using population modelling of plasma and CSF concentrations obtained in these patients and data of two published studies. The primary outcome was the amount of i.v. fentanyl for rescue analgesia during the first 4 hours.

RESULTS: Twenty of the 31 patients in the EPI-group and 26 of the 29 patients in the IV-group needed i.v. fentanyl for rescue analgesia, p=0.021. The median (IQR) number of fentanyl doses were 1.0 (1.0, 3.0) in the EPI-group and 2.5 (1.0, 4.0) doses in the IV-group, p=0.008. Plasma concentrations were similar, but CSF concentrations were 100-fold higher in the EPI-group. The population model indicated that 60% of oxycodone injected into the epidural space enters into CSF and 40% is absorbed into the systemic circulation.

CONCLUSIONS: The data support superiority of epidural administration of oxycodone compared to i.v. administration during the first hours after laparoscopic surgery. This is likely based on enhanced permeation into the CNS after epidural administration.