Analgesic efficacy and pharmacokinetics of epidural oxycodone in pain management after gynaecological laparoscopy—A randomised, double blind, active control, double‐dummy clinical comparison with intravenous administration

Abstract

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 gynaecological laparoscopy. Methods: Women (n = 60), aged 23-71 years, undergoing elective gynaecological laparoscopy, were administrated either epidural oxycodone 0.1 mg kg −1 and intravenous (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 cerebrospinal fluid (CSF) concentrations obtained in these patients and data of 2 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 = .021. The median (interquartile range) 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 = .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 to be based on enhanced permeation into the central nervous system after epidural administration.

Postoperative Effects of Continuous Dexmedetomidine Infusion During Gynecological Laparoscopy: A Randomized, Placebo-Controlled, Double-Blind, Single Center Clinical Trial

“…Differences were not significant between groups regarding to demographic and perioperative data (Table 1) [4,5] in group N, and the differences were significant(P<0.05). NRS scores were similar at the second postoperative hour and after ( Table 2).…”

“…Laparoscopy has been confirmed to provide fewer postoperative complications and shorter hospitalization while the oncologic outcomes are not affected [1,2]. General anesthesia is currently most commonly used for laparoscopic surgery [3][4][5], which helps eliminate the discomfort caused by the increased intraabdominal pressure and peritoneal irritation during artificial pneumoperitoneum and special position [6]. Opioid-based general anesthesia is a classical anesthetic method to facilitate tracheal intubation and mechanical ventilation.…”

Bioavailability of oxycodone by mouth in coronary artery bypass surgery patients – a randomized trial

“…Use of a 2-compartment model allowed comparison with estimates published by others. [17][18][19] Cardiac surgery is associated with profound changes to physiology (e.g. altered volume of distribution and changes in plasma protein concentrations), changes in gut, renal and hepatic activity; these factors can alter perioperative drug PK.…”

“…The absorption lag-time was used to quantify the delay in oxycodone-naloxone controlled-release tablet absorption after cardiac surgery. Data were pooled with those available in patients given the intravenous formulation after laparotomy 17 and urological procedures 18 , 19 to make an estimate of the relative oral bioavailability (F). Parameter estimates were scaled using theory based allometry to a 70 kg total body weight individual.…”

Implementation of a 23-h surgery model in a tertiary care hospital: a safe and feasible model with high patient satisfaction

“…The extension of surgery, substantial risk of a serious postoperative complication and need for parenteral opioid analgesics in the early phase of postoperative recovery are the main indicators for the 23‐h surgical model. Proposed procedures for this model are, for example, cholecystectomy in chronic cholecystitis, extended shoulder or wrist surgery, anterior cruciate ligament reconstruction and hysterectomy, all shown to be associated with moderate or severe early postoperative pain. Procedures where postoperative bleeding can have devastating complications, such as thyroid surgery, cervical discectomy and prostate surgery, are eligible for the 23‐h model.…”