P01 The effect of intraoperative N-acetylcysteine on hepatocellular injury during laparoscopic bariatric surgery: a randomised controlled trial

Abstract

IntroductionThe combination of pneumoperitoneum and intraoperative retraction of the left lobe of the liver leads to hepatocellular injury during laparoscopic oesophago-gastric surgery, with often more than a sixfold rise in serum transaminases. Fatty livers are more susceptible to ischaemic insults and increased oxidative stress. AimThe aim of the study was to investigate whether the antioxidant N-acetylcysteine (NAC) could reduce liver injury during laparoscopic sleeve gastrectomy. MethodPatients undergoing laparoscopic sleeve gastrectomy were allocated to receive intraoperative NAC infusion or standard anaesthetic treatment in a single blind randomised controlled trial. Blood samples were taken before and at the end of surgery and on post-operative days 1-4. Primary endpoints included serum aminotransferases and clinical outcomes. Secondary measures were markers of oxidative stress (superoxide dismutase, lipid peroxidation (TBARS) and liver injury (cytokeratin-18 M30 and M65) and plasma TRAIL and FasL for apoptosis. Results20 patients (14 females, median age 44 (27-64) years, median BMI 62 (39-83) kg/m2) were recruited; NAC n=10, control n=10. Demographic parameters and baseline liver function were similar [pre-op ALT NAC median 25 U/ml (IQR 24-42) vs control 30.5 (29-44)]. The peak rise in liver enzymes was on day 1, but the levels were not significantly different between the groups? ALT: NAC median 126 (IQR 73-627) vs control 136 (107-239); AST: NAC 130 IU/l (68-504) vs Control 124 (72-237). There were no significant differences in day 1 superoxide dismutase (NAC 0.48 pg/ml vs Control 0.66), TBARS (NAC 8.84 nmol/ml vs Control 12.47), CK18-M30 (NAC 340U/l vs 471) and CK18-M65 (NAC 803.5 U/l vs 878). There was a significant reduction in TRAIL and FasL after POD1 (TRAIL pre-op 100.6 pg/ml day 1_ 38.8, p<0.01; FasL pre-op 94.6 pg/ml vs POD1 67.5, p<0.01), but there were no significant differences between the treatment groups. Rates of complications and length of stay were not significantly different. ConclusionNAC was not shown reduce intraoperative liver injury in this small number of patients. The heterogenous nature of the bariatric patient population, with differences in comorbidities, body mass index and intra-abdominal anatomy, makes this difficult. Significant hepatocyte injury does occur through both necrosis and apoptosis, which does not appear to be mediated by TRAIL or FasL.