Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery.

Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017-March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann-Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0-7 (ß = 9.52, 95% CI 1.30-17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.

Resting energy expenditure and nutritional status in patients undergoing transthoracic esophagectomy for esophageal cancer.

This study was to assess the resting energy expenditure of patients with esophageal cancer using indirect calorimetry. Eight male patients with esophageal cancer and eight male healthy controls were enrolled in this study. All patients underwent transthoracic esophagectomy with lymph nodes dissections. The resting energy expenditure was measured preoperatively, and on postoperative day 7 and 14 using indirect calorimetry. Preoperatively, the measured resting energy expenditure/body weight in these patients was significantly higher than that of the controls (23.3 ± 2.1 kcal/kg/day vs 20.4 ± 1.6 kcal/kg/day), whereas the measured/predicted energy expenditure from the Harris-Benedict equation ratio was 1.01 ± 0.09, which did not differ significantly from the control values. The measured resting energy expenditure/body weight was 27.3 ± 3.5 kcal/kg/day on postoperative day 7, and 23.7 ± 5.07 kcal/kg/day on postoperative day 14. Significant increases in the measured resting energy expenditure were observed on postoperative day 7, and the measured/predicted energy expenditure ratio was 1.17 ± 0.15. In conclusion, patients with operable esophageal cancers were almost normometabolic before surgery. On the other hand, the patients showed a hyper-metabolic status after esophagectomy. We recommended that nutritional management based on 33 kcal/body weight/day (calculated by the measured resting energy expenditure × active factor 1.2-1.3) may be optimal for patients undergoing esophagectomy.