Background & Aims
Recent data indicate that oxycodone is a feasible opioid for epidural analgesia [1]. After epidural administration, opioids agonists are assumed to diffuse first into cerebrospinal fluid and then into the superficial dorsal horn of the cord where opioids exert analgesic effect by binding to receptors. Ideally, drug concentrations would be measured at their site of action, but such data concerning epidural opioids can be obtained only in experimental studies. Epidural puncture is most easy and safe to perform at lumbar site, but, for efficient analgesia, drug concentration should be sufficient at appropriate dermatomal level. In this study we evaluated oxycodone spinal cord distribution after a single epidural administration in an experimental ewe model.
Methods
After approval of the study protocol by the National Animal Experiment Board of Finland (ESAVI/22032/2019, Sept 4, 2019) a total of 19 Aland landrace ewes at 137-142 gestational days (term 145 days) received in an open, random order a single oxycodone bolus 0.1 mg/kg either (i) epidurally (n=10), or (ii) intravenously (n=9). Before epidural puncture at presacral space the ewes had general anesthesia for cesarean section. 60 minutes after the oxycodone injection the animals were euthanized with an intravenous overdose of pentobarbital, and necropsy was performed immediately to obtain tissue samples of the ewe’s spinal cord at the epidural catheter tip area, 10 cm caudal and 10, 20 and 30 cm cranial to that. From the ewes in the intravenous group a single spinal cord sample was obtained from the upper lumbar region. Tissue samples oxycodone concentrations were analyzed with ultra-performance liquid chromatography-mass spectrometry [2].
Results
The mean of oxycodone concentration in ewes’ spinal cord was 200-fold higher after an epidural injection, 8823 (SD 3302) ng/g compared to intravenous injection, 43 (34) ng/g, respectively. After epidural injection the mean of spinal cord oxycodone concentration at the epidural catheter tip area was 10422 (2213) ng/g, at 10 cm caudal to that 9332 (2348) ng/g and 10753 (1515) ng/g at 10 cm and 8513 (3593) ng/g at 20 cm cranial to that. The mean of spinal cord oxycodone concentration was the lowest at 30 cm cranial to the epidural catheter tips site, 5095 (3305) ng/g (P = 0.003 and P = 0.002 compared to the tip site and + 10 cm, respectively, Kruskal-Wallis Test with the Bonferroni correction for multiple tests).
Conclusions
This experimental data indicated that the spinal cord oxycodone concentration at 60 min after a single bolus dose are 120-250 fold higher after epidural compared to intravenous administration. This data can be used in veterinary medicine, in pain management in animal species, and applied to human medicine also: most easy puncture site can be used to insert an epidural catheter for spinal oxycodone administration.