LAUSR

Epidural anesthesia attenuates the hyperglycemic response to surgery, most likely a consequence of improved whole body insulin sensitivity. Insulin sensitivity during abdominal surgery, however, has never been quantified in the presence of epidural anesthesia. The hyperinsulinemic-normoglycemic clamp (HNC) is the gold standard method to measure insulin sensitivity in humans [1]. Here, we report insulin sensitivity as assessed by HNC during liver resections in patients receiving combined general/epidural anesthesia or general anesthesia alone. This study is a post hoc exploratory analysis of the first 130 patients participating in a randomized-controlled trial in patients undergoing hepatobiliary procedures and receiving HNC (ClinicalTrials.gov NCT01528189; registered on 7 February, 2012) at the Royal Victoria Hospital (McGill University Health Centre, Montreal, Quebec, Canada). Following approval from the institutional ethics review board, written informed consent was obtained from patients scheduled for elective transabdominal resections of liver cancer. Patients < 18 years, with diabetes mellitus, liver disease (Child–Pugh grade B or C) or on dialysis and administered steroid intraoperatively were not eligible. All patients kept fasting from midnight, except for water and medications. In the epidural anesthesia (EDA) group, epidural catheters were inserted at a thoracic level between Th7 and Th10. Epidural anesthesia during surgery was maintained by intermittent boluses of 0.25% bupivacaine. General anesthesia in both groups was maintained by volatile anesthetics supplemented with fentanyl and rocuronium. The HNC was initiated by insulin infused at rate of 2 mU/kg/min followed by dextrose (20%) infusion titrated to maintain blood glucose between 4.0 and 6.0 mmol/L. Blood glucose levels were measured at 5–30 min intervals (StatStrip® Glucose Hospital Meter System, Nova Biomedical, Waltham, MA, USA) to establish and maintain normoglycemia. The average of three consecutive infusion rates during steady state (coefficient of variation of the dextrose infusion rate < 5%), typically after 90–120 min, was used as a measure of insulin sensitivity. Sample size calculation was based on insulin sensitivity data obtained in our previous studies using the HNC in nondiabetic patients undergoing liver resections (2.0 ± 0.6 mg/ kg/min, SD) [2]. To achieve 80% power to detect a 40% difference in insulin sensitivity and an alpha error of 5%, at least seven subjects were required in the GA group and 14 subjects in the EDA group. Continuous data were analyzed by the unpaired t test, Mann–Whitney U test or Wilcoxon test and proportions were analyzed by Fisher’s exact test. Two-sided P values < 0.05 were considered statistically significant. Patient characteristics are shown in Table 1. The reasons for not inserting epidural catheters in the GA group were the following: patient refusal (n = 1), coagulation disorder (n = 1), accidental intravascular placement (n = 1), and technical difficulties (n = 4). Fifteen patients comprised the EDA group. Biometric and surgical data in the GA group and in the EDA group were similar. Mean insulin sensitivity in the EDA group (2.2 ± 1.0 mg/kg/min) was almost three times higher than in the GA group (0.8 ± 0.6 mg/kg/ min, P = 0.003, Table 1). The mean insulin sensitivity was measured before the cancer was resected and in patients who received the Pringle maneuver before this intervention. This is, to our best knowledge, the first study quantifying intraoperative insulin sensitivity using HNC in patients undergoing upper abdominal surgery with or without epidural anesthesia. Only one previous study had applied an HNC technique to measure insulin sensitivity one day after open gastrectomies or cholecystectomies performed under combined epidural/general anesthesia or general anesthesia alone [3]. Another report using the lower homeostatic model * Keisuke Omiya [email protected]