Association Between Early Perioperative Fentanyl Exposure and Dose-Normalized Tacrolimus Exposure After Kidney Transplantation

Introduction Tacrolimus exposure varies early after kidney transplantation, and perioperative factors may complicate therapeutic drug monitoring. Fentanyl is commonly used perioperatively, but its association with dose-normalized tacrolimus exposure is unclear. Project Aims or Questions: This study evaluated whether early perioperative fentanyl exposure was associated with dose-normalized tacrolimus exposure during the first week after kidney transplantation. Design This single-center retrospective program evaluation included 43 adult living-donor kidney transplant recipients who received perioperative fentanyl and had evaluable tacrolimus trough concentrations and corresponding oral daily doses. Cumulative fentanyl dose was the conventional exposure measure; body surface area-normalized and patient-controlled analgesia-administered volume measures were exploratory. The outcome was the log-transformed tacrolimus trough concentration divided by the daily tacrolimus dose. Repeated measurements were analyzed using linear mixed models adjusted for clinical covariates. Results The conventional cumulative fentanyl dose through postoperative day 1 was associated with 22.7% higher dose-normalized tacrolimus exposure per 1 standard deviation increase, 95% confidence interval 4.4% to 44.1%, P = .013. In exploratory analyses, body surface area-normalized cumulative exposure through postoperative day 1 had the strongest association, a 24.9% increase, 95% confidence interval 7.3% to 45.4%, P = .004. Exposure through postoperative day 2 showed weaker, nonsignificant associations. Conclusion Early perioperative fentanyl exposure, particularly cumulative exposure through postoperative day 1, was associated with higher dose-normalized tacrolimus exposure during the first postoperative week after kidney transplantation. These findings support contextual interpretation of early tacrolimus monitoring while recognizing confounding by clinical status and the exploratory nature of body surface area-normalized findings.