Ischemic preconditioning prior to intermittent Pringle maneuver in liver resections

Abstract

Background/Purpose Continuous inflow vascular occlusion during liver resections causes less severe ischemia and reperfusion injury (IRI) if it is preceded by ischemic preconditioning (IP) or if intermittent inflow occlusion is used during the resection. No previous clinical trial has studied the effects of adding IP to intermittent inflow occlusion. Methods Consecutive patients (n = 32) with suspicion of malignant liver disease had liver resections (minimum 2 segments) performed with inflow occlusion (intermittent clamping in a manner of 15 min of ischemia and 5 min of reperfusion repetitively; 15/5). Half of the patients were randomized to receive IP (10 min of ischemia and 10 min of reperfusion before parenchymal transection; 10/10). The patients were stratified according to volume of resection and none had chronic liver disease. The patients were followed for 5 days with microdialysis (μD). Results All patients completed the study and there were no deaths. No differences were seen between the groups regarding demographics or perioperative parameters (bleeding, duration of ischemia, resection volume, complications, and serum laboratory tests). There were no differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or prothrombin time (PT)‐INR levels, but μD revealed lower levels of lactate, pyruvate, and glucose in the IP group having major liver resections (analysis of variance; ANOVA). Nitrite and nitrate levels in μD decreased postoperatively, but no differences were seen between the groups. In one patient an elevated μD–glycerol curve was seen before the diagnosis of a stroke was made. Conclusions IP before intermittent vascular occlusion does not reduce the serum parameters used to assess IRI. IP seems to improve aerobic glucose metabolism, as the levels of glucose, pyruvate, and lactate locally in the liver were reduced, compared to controls, in patients having >3 segments resected. μD may be used to monitor metabolism locally.

Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine

“…A study in healthy humans showed that low dose NAC given intravenously (0.5 mg kg À1 ) stimulates peripheral glucose uptake and storage, at high dose (4 mg kg À1 ), it has no effect (Ammon et al, 1992). Other works suggest, conversely, that NAC active glycogenolysis and enhances the intracellular glucose metabolism in ischemic rats (Winbladh et al, 2012).…”

Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: A randomized clinical trial

“…18,33 All these factors should be considered in the setting of liver resection using INT. Recently, clinical studies 34,35 have shown that pretreatment by IPC in major liver resections with INT did not modify postoperative liver enzymes or patient outcomes. In the present study, the 2 preconditioned groups showed no differences in the kinetics of liver enzymes and HA, apoptotic index, liver histology, and clinical outcome compared with patients factors (age, baseline AST, ALT, bilirubin, steatosis, chemotherapy, total warm ischemia time, and type of resection; P = .052).…”

Ischemic preconditioning may reduce hyperglycemia associated with intermittent Pringle maneuver in hepatic resection

“…In both experimental [2] and clinical [3] studies using the Pringle maneuver, we found that hyperglycemia was caused by hepatic ischemia–reperfusion injury (IRI). During hepatic resection, blood glucose concentrations decreased marginally during clamping using the intermittent Pringle maneuver, but increased rapidly after unclamping [3].…”

“…In both experimental [2] and clinical [3] studies using the Pringle maneuver, we found that hyperglycemia was caused by hepatic ischemia–reperfusion injury (IRI). During hepatic resection, blood glucose concentrations decreased marginally during clamping using the intermittent Pringle maneuver, but increased rapidly after unclamping [3]. Specifically, a rapid and profound transition to hyperglycemia was observed after unclamping when the intermittent Pringle maneuver was used during hepatectomy, and this transition may have involved glycogen breakdown within the hepatocytes due to hypoxia [3].…”

“…Okabayashi et al [4] reported that not only was perioperative tight glycemic control (TGC) using an artificial pancreas (AP) to prevent hyperglycemia in hepatectomized patients more effective in reducing surgical site infection (SSI) than conventional glycemic control, but that it also had cost benefits by reducing the duration of the hospital stay. In the study of Winbladh et al [1], IP significantly decreased postoperative hyperglycemia on postoperative day (POD) 2 in patients who either had two to three or more than three segments resected compared with the respective control groups. IP protects against hepatic IRI because it reduces endothelial cell apoptosis and ATP degradation in the immediate postischemic period [1].…”