Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia

Simon A W G Dello, Kostan W Reisinger, Ronald M van Dam, Marc H A Bemelmans, Toin H van Kuppevelt, Maartje A J van den Broek, Steven W M Olde Damink, Martijn Poeze, Wim A Buurman, Cornelis H C Dejong, Simon A W G Dello, Kostan W Reisinger, Ronald M van Dam, Marc H A Bemelmans, Toin H van Kuppevelt, Maartje A J van den Broek, Steven W M Olde Damink, Martijn Poeze, Wim A Buurman, Cornelis H C Dejong

Abstract

Objectives: The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM.

Methods: Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day.

Results: 24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed.

Conclusion: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery.

Trial registration: ClinicalTrials.gov NCT01099475.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Timeline of sample collection.
Figure 1. Timeline of sample collection.
Figure 2. Time course of I-FABP plasma…
Figure 2. Time course of I-FABP plasma levels and interorgan arterio-venous concentration differences.
2A For visual purposes data were plotted as mean and SEM. * p<0.005 compared to baseline of total-IPM (T = 0), p<0.01 compared to no-IPM on T = 5. 2B Mean (SEM) arterio-venous concentration gradients of I-FABP across the gut (portal venous minus arterial) and the hepatosplanchnic area (hepatic venous minus arterial). I-FABP was specifically released from the gut (*p<0.0001 vs. zero) and this resulted in a net I-FABP release from the hepatosplanchnic area (#p<0.005 vs. zero).
Figure 3. Values are median (range), pairwise…
Figure 3. Values are median (range), pairwise comparisons of EndoCAb at baseline (T = 0) and on post-operative day one (T = 6).
3A Total-IPM: two patients were excluded from this analysis because of missing samples on post-operative day 1. EndoCAb levels of one patient were undetectable and therefore the lower detection limit of the EndoCAb ELISA kit, corrected for dilution factor was used (12.5 GMU/ml). 3B No-IPM. 3C Sel-IPM: 1 patient was excluded from analysis because of missing samples on post-operative day 1.

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