Pain management is critical for burn care. Unfortunately, interindividual variation in pharmacokinetics (PK) due to burn hypermetabolism and genetic polymorphisms can lead to treatment failures in this at-risk population. Analgesics may be affected by genetic polymorphisms affecting cytochrome P450 (CYP) drug metabolizing enzymes. Fentanyl is a common opiate primarily metabolized by CYP3A4 subtypes. Recent studies demonstrate CYP2D6 variants, affecting fentanyl PK. Functional CYP polymorphisms can significantly alter opiate levels resulting in inadequate analgesia or life-threatening toxicity. The goal of our study was to evaluate fentanyl PK and assess associations with CYP polymorphisms. We obtained samples from the previously banked blood of 13 patients (eight males and five females) with >20% TBSA burns. Mean (SD) patient age was 41.7 (14.5) years, and mean burn size was 25.8 (15.3) %TBSA. Plasma fentanyl was quantified, and CYP genotyping was performed. Pharmacokinetic analysis was performed using Monolix software (Lixsoft, France) with a two-compartment population model best-representing fentanyl profiles. Three CYP slow-metabolizing genotypes were identified, which included CYP2D6*9, CYP2D6*29, and CYP3A4*1B. All three patients with variant polymorphisms had increased serum fentanyl concentrations due to impaired clearance. This pilot study supports the need for further research in this topic, and CYP genotyping of individual patients prior to receiving opiate analgesics to inform precision-guided decisions, improve therapeutic efficacy, and, most importantly, increase patient well-being and safety.

Background  Flexor tendon injury is a rare but serious complication of distal radius volar plating. Purpose  This study aims to determine whether the design of distal radius volar plates impacts the amount of force exerted on the flexor digitorum profundus (FDP) and flexor pollicis longus (FPL) tendons when the plates are placed proximal and distal to the watershed line. Methods  Three commercially available plates were applied to 10 fresh, matched-pair upper extremity specimens. Cyclical loading was applied to the tendons, and the force generated between tendon and plate was measured. Linear mixed effect models were used to evaluate differences in maximum and mean forces by plate position, plate design, and the interaction between position and design. Results  Forces on the tendons differed significantly by position but not plate design. For the FPL tendon, the average maximum force with a plate in Soong's grade 2 was 4.50 (95% confidence interval [CI]: 2.8-7.3) times higher than when the plate was in a Soong's grade 0 placement, and 4.63 (95% CI: 2.82-7.61) times higher for the FDP tendon. While not statistically significant, lower observed force values with thinner plates when plates were placed distal to the watershed line suggest that that plate thickness could also be a critical plate characteristic for distally placed plates. Conclusion  Despite differences in plate design, the main determinant of plate prominence and therefore flexor tendon injury potential is placement in relation to the watershed line. Clinical Relevance  This study may help to guide surgeon implant selection and volar plate design.