Drug exposure during oxycodone patient-controlled analgesia with adjuvant dexmedetomidine after lumbar spinal fusion

Abstract Background We characterized dexmedetomidine and oxycodone exposure during postoperative patient-controlled analgesia (PCA). Two additional analyses addressed the relationships between current pain and subsequent oxycodone administration and between measured oxycodone concentration and analgesia at the time of sampling. Methods This analysis included 98 patients from a randomized, double-blind, placebo-controlled dose-response trial after lumbar spinal fusion. PCA contained oxycodone 1 mg/mL alone or with dexmedetomidine 2.5, 5, or 10 µg/mL. Plasma dexmedetomidine, oxycodone, and major metabolite concentrations were characterized over 24 h with high-performance liquid chromatography tandem mass spectrometry. Associations of resting pain with subsequent PCA-administered oxycodone and of measured oxycodone concentration with adequate analgesia (numerical rating scale at rest ≤ 4) were analysed using linear and logistic mixed-effects models, respectively. Results Oxycodone concentrations showed marked between-patient variability, while noroxycodone and noroxymorphone increased progressively and oxymorphone remained lower. Dexmedetomidine concentrations separated clearly according to randomized dose. Higher current resting pain was associated with greater subsequent oxycodone administration (P < 0.001). A 3-point higher resting NRS was associated with approximately 1.1–1.2 mg greater oxycodone administration over the following 3–4 h and 5.2 mg over the subsequent 16 h. Higher measured oxycodone concentration was associated with lower odds of adequate analgesia (odds ratio 0.377 per concentration doubling; 95% CI 0.24–0.59; P < 0.001). Conclusions During postoperative PCA, higher current pain was associated with greater subsequent oxycodone administration. The association between measured oxycodone concentration and analgesia cannot be interpreted as a simple pharmacological concentration–effect relationship. Trial registration ClinicalTrials.gov, NCT02454881 (https//clinicaltrials.gov/study/NCT02454881) EudraCT 201400325231.