Randomized controlled trial of the effect of hyperinsulinemic normoglycemia during liver resection on postoperative hepatic function and surgical site infection

BACKGROUND: While avoidance of preoperative fasting followed by hyperinsulinemic-normoglycemic clamp (HNC) reduced postoperative hepatic dysfunction and surgical site infection (SSI), the effect of HNC restricted to the intraoperative period is unknown. This study examined whether HNC restricted to the intraoperative period has similar effects in patients undergoing elective liver resections. METHODS: This study is a post hoc exploratory analysis of a randomized-controlled trial in patients undergoing hepatobiliary surgery and receiving the HNC as a potential preventative intervention to reduce infectious morbidity postoperatively. Patients (>18 years old) undergoing elective transabdominal resection of liver malignancy were enrolled. We implemented the random allocation by labelling cards. Consenting patients were randomly assigned to receive the HNC during surgery or standard metabolic care. The HNC was initiated by insulin (2 mU/kg/min) followed by 20% dextrose infusion titrated to keep blood glucose between 4.0 and 6.0 mmol/L until the end of surgery. In the control group, glycemia >10.0 mmol/L prompted insulin treatment according to a standardized sliding scale. The primary outcome was hepatic function on postoperative day (POD) one, assessed by Schindl score. Secondary outcome was the incidence of SSIs within 30 days after surgery. The Schindl score was analyzed by Mann-Whitney U test and the incidence of SSIs was analyzed by Fisher’s exact test. Two-sided P values <0.05 were considered statistically significant. RESULTS: From October 2018 to May 2022, 32 patients in the control group and 34 patients in the HNC group were analyzed. Patient characteristics were similar in the two groups. There was no significant difference in the mean Schindl score on POD1 between the HNC group and the control group (0.8±0.9 vs. 1.2±1.6, P=0.61). However, the incidence of SSIs in the HNC group was significantly lower than in the control group (6% vs. 31%, P=0.01). CONCLUSIONS: The HNC restricted to the intraoperative period did not improve postoperative hepatic function but reduced SSIs. Preoperative carbohydrate loading may contribute to the preservation of hepatic function. TRIAL REGISTRATION: ClinicalTrials.gov NCT01528189.