Epidural Oxycodone for Acute Pain.

Epidural analgesia is commonly used in labour analgesia and in postoperative pain after major surgery. It is highly effective in severe acute pain, has minimal effects on foetus and newborn, may reduce postoperative complications, and enhance patient satisfaction. In epidural analgesia, low concentrations of local anaesthetics are combined with opioids. Two opioids, morphine and sufentanil, have been approved for epidural use, but there is an interest in evaluating other opioids as well. Oxycodone is one of the most commonly used opioids in acute pain management. However, data on its use in epidural analgesia are sparse. In this narrative review, we describe the preclinical and clinical data on epidural oxycodone. Early data from the 1990s suggested that the epidural administration of oxycodone may not offer any meaningful benefits over intravenous administration, but more recent clinical data show that oxycodone has advantageous pharmacokinetics after epidural administration and that epidural administration is more efficacious than intravenous administration. Further studies are needed on the safety and efficacy of continuous epidural oxycodone administration and its use in epidural admixture.

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.

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.

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone.

Global oxycodone consumption has increased sharply during the last two decades, and, in 2008, oxycodone consumption surpassed that of morphine. As oxycodone was synthesized in 1916 and taken to clinical use a year later, it has not undergone the same approval process required by today's standards. Most of the basic oxycodone pharmacokinetic (PK) data are from the 1990s and from academic research; however, a lot of additional data have been published over the last 10 years. In this review, we describe the latest oxycodone data on special populations, including neonates, children, pregnant and lactating women, and the elderly. A lot of important drug interaction data have been published that must also be taken into account when oxycodone is used concomitantly with cytochrome P450 (CYP) 3A inducers and inhibitors and/or CYP2D6 inhibitors. In addition, we gathered data on abuse-deterrent oxycodone formulations, and the PK of alternate administration routes, i.e. transmucosal and epidural, are also described.

The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double-blind, double-dummy comparison with intravenous administration.

AIM: The aim of the present study was to compare the analgesic efficacy of epidural and intravenous (i.v.) oxycodone at the same dose. METHODS: In this randomized, double-blind, double-dummy clinical trial, 30 women, aged 24-67 years, undergoing elective gynaecological laparotomy, were administrated either i.v. saline and epidural oxycodone 0.1 mg·kg-1 (EPI group; n = 15) or i.v. oxycodone 0.1 mg·kg-1 and epidural saline (IV group; n = 15). For multimodal analgesia, patients received i.v. paracetamol and dexketoprofen, and a triple-mixture epidural infusion after the first 4 h postoperatively. The primary outcome was the total dose of i.v. fentanyl for rescue analgesia during the first 4 h postoperatively. RESULTS: All patients required fentanyl during the first 4 h. The median number of fentanyl doses were three (quartiles 1, 8) in the EPI group and seven (6, 9) in the IV group (mean difference 3.1; 95% confidence interval 0.9, 5.2; P = 0.01). After the first 4 h, the two groups needed a similar total dose of epidural infusion. Patient satisfaction was similarly high in both groups, and both administration routes were well tolerated. CONCLUSIONS: The data support the superiority of epidural oxycodone compared with that of i.v. administration in pain management after laparotomy.