Drug exposure during oxycodone-S-ketamine patient-controlled analgesia reflects pain-related dosing behaviour after lumbar fusion surgery
- 1Department of Anaesthesiology and Intensive Care, University of Turku, and Division of Perioperative Services, Intensive Care Medicine and Pain Management; Turk
Abstract
BackgroundOpioids remain the cornerstone of acute postoperative pain management but are associated with potentially serious adverse effects. We aimed to investigate the effect of oxycodone patient-controlled analgesia with adjunctive S-ketamine on pain after lumbar fusion surgery.
MethodsIn this secondary analysis, we examined oxycodone and S-ketamine exposure and PCA behaviour during the first 24 h. We assessed current pain versus subsequent PCA activity and whether the association between plasma oxycodone and adequate analgesia changed with postoperative time.
ResultsPlasma concentrations of administered drugs rose rapidly after PCA initiation, but variation was large. Metabolite concentrations accumulated over time. PCA attempt and delivered-dose rates decreased over postoperative time (RR 0.965 and 0.966 per hour, respectively; both P<0.001). Older age was associated with a lower delivered-dose rate (RR 0.905 per 10 years, 95% CI 0.829-0.987). Each 1-point higher current pain score was associated with more subsequent PCA attempts (RR 1.09, 95% CI 1.04-1.14) and delivered doses (RR 1.07, 95% CI 1.03-1.11). The oxycodone-analgesia association weakened over time [interaction P <0.001; odds ratios (Ors) per 10 ng/mL 1.16, 1.13, and 1.00 at 1, 4, and 24 h, respectively]. In active S-ketamine groups, including S-ketamine, norketamine, and 6-hydroxynorketamine concentrations left the pain-PCA association unchanged (RR 1.09 and 1.07) and preserved the time-dependent oxycodone association (ORs 1.30, 1.26, and 1.02).
ConclusionsDuring PCA, drug exposure develops from patient-generated dosing histories while pain and recovery change. Current pain was associated with subsequent PCA activity, and the oxycodone-analgesia association was time-dependent.
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BibTeX
@misc{virtanen2026drug,
title = {{Drug exposure during oxycodone-S-ketamine patient-controlled analgesia reflects pain-related dosing behaviour after lumbar fusion surgery}},
author = {T. Virtanen and E. C. V. Brinck and M. Engstrom and M. J. Kurkela and P. Tarkkila and J. Backman and A. Tornio and V. Kontinen and M. Peltoniemi and T. I. Saari},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.26365979},
url = {https://www.medrxiv.org/content/10.64898/2026.10.20.26365979v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Drug exposure during oxycodone-S-ketamine patient-controlled analgesia reflects pain-related dosing behaviour after lumbar fusion surgery
AU - T. Virtanen
AU - E. C. V. Brinck
AU - M. Engstrom
AU - M. J. Kurkela
AU - P. Tarkkila
AU - J. Backman
AU - A. Tornio
AU - V. Kontinen
AU - M. Peltoniemi
AU - T. I. Saari
PY - 2026
DA - 2026/10/20
PB - medRxiv
DO - 10.64898/2026.10.20.26365979
UR - https://www.medrxiv.org/content/10.64898/2026.10.20.26365979v1
AB - BackgroundOpioids remain the cornerstone of acute postoperative pain management but are associated with potentially serious adverse effects. We aimed to investigate the effect of oxycodone patient-controlled analgesia with adjunctive S-ketamine on pain after lumbar fusion surgery. MethodsIn this secondary analysis, we examined oxycodone and S-ketamine exposure and PCA behaviour during the first 24 h. We assessed current pain versus subsequent PCA activity and whether the association between plasma oxycodone and adequate analgesia changed with postoperative time. ResultsPlasma concentrations of administered drugs rose rapidly after PCA initiation, but variation was large. Metabolite concentrations accumulated over time. PCA attempt and delivered-dose rates decreased over postoperative time (RR 0.965 and 0.966 per hour, respectively; both P<0.001). Older age was associated with a lower delivered-dose rate (RR 0.905 per 10 years, 95% CI 0.829-0.987). Each 1-point higher current pain score was associated with more subsequent PCA attempts (RR 1.09, 95% CI 1.04-1.14) and delivered doses (RR 1.07, 95% CI 1.03-1.11). The oxycodone-analgesia association weakened over time [interaction P <0.001; odds ratios (Ors) per 10 ng/mL 1.16, 1.13, and 1.00 at 1, 4, and 24 h, respectively]. In active S-ketamine groups, including S-ketamine, norketamine, and 6-hydroxynorketamine concentrations left the pain-PCA association unchanged (RR 1.09 and 1.07) and preserved the time-dependent oxycodone association (ORs 1.30, 1.26, and 1.02). ConclusionsDuring PCA, drug exposure develops from patient-generated dosing histories while pain and recovery change. Current pain was associated with subsequent PCA activity, and the oxycodone-analgesia association was time-dependent.
ER -