ABSTRACT
Cytochrome P450 2D6 (CYP2D6) gene polymorphisms influence the exposure to tramadol (T) and its pharmacologically active metabolite, O-demethyl tramadol (O-dT). Tramadol has been considered as a candidate probe drug for CYP2D6 phenotyping. The objective of the CYTRAM study was to investigate the value of plasma O-dT/T ratio for CYP2D6 phenotyping. European adult patients who received IV tramadol after surgery were included. CYP2D6 genotyping was performed and subjects were classified as extensive (EM), intermediate (IM), poor (PM), or ultra-rapid (UM) CYP2D6 metabolizers. Plasma concentrations of tramadol and O-dT were determined at 24 h and 48 h. The relationship between O-dT/T ratio and CYP2D6 phenotype was examined in both a learning and a validation group. Genotype data were obtained in 301 patients, including 23 PM (8%), 117 IM (39%), 154 EM (51%), and 7 UM (2%). Tramadol trough concentrations at 24 h were available in 297 patients. Mean value of O-dT/T ratio was significantly lower in PM than in non-PM individuals (0.061 ± 0.031 versus 0.178 ± 0.09, p < 0.01). However, large overlap was observed in the distributions of O-dT/T ratio between groups. Statistical models based on O-dT/T ratio failed to identify CYP2D6 phenotype with acceptable sensitivity and specificity. Those results suggest that tramadol is not an adequate probe drug for CYP2D6 phenotyping.
ABSTRACT
BACKGROUND: The aim of this study was to investigate whether the implementation of enhanced recovery after surgery (ERAS) guidelines according to Thorell and co. in our tertiary referral bariatric center might improve post-operative outcomes. METHODS: ERAS program was introduced in our center since January 1, 2017. Retrospective review of a prospectively collected database identified patients who underwent laparoscopic primary and revisional bariatric surgeries from October 2005 to January 2018. Patients exposed to ERAS program ("ERAS group") were matched in a 1:1 ratio with patients exposed to conventional care (control group) using a propensity score based on age, gender, preoperative body mass index (BMI), diabetes mellitus, and the type of procedures. The primary outcome was total hospital length of stay (LOS) and the secondary outcomes included the post-operative complications and readmission rates. RESULTS: During the study period, 464 patients were included, 232 in each group. Implementation of the ERAS protocol was significantly associated with a reduction of LOS (2.47 ± 1.7 vs 5.39 ± 1.9 days, p < 0.00001). One-third of patients was discharged (77/232, 33%) on the first postoperative day (POD) and more than three quarter of patients on POD 2 (182/232, 77%). At the opposite, no patients of the control group were discharged on POD 2. Overall 30-day and 90-day morbidity and readmission rates were the same in both groups. There was no death in each group. CONCLUSIONS: This large case-matched study using a propensity score analysis suggests that implementation of ERAS program significantly reduced length of hospital stay without significant increases on overall morbidity, and readmission rates.
