Influence of anastomoses on intestine ischemia and cefuroxime concentrations: Evaluated in the ileum and colon in a porcine model

Abstract

BACKGROUND Anastomotic leakage is a serious complication following gastrointestinal surgery and is associated with increased morbidity and mortality. The incidence of anastomotic leakage is determined by anatomy and is reported to be between 4%-33% for colon anastomosis and 1%-3% for small intestine anastomosis. The etiology of anastomotic leakage of the intestine has been divided into three main factors: healing disturbances, communication between intra- and extra-luminal compartments, and infection. All three factors interact, and one factor will inevitably lead to the other two factors resulting in tissue ischemia, tissue necrosis, and anastomotic leakage. AIM To evaluate ischemic metabolites and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon in a porcine model. METHODS Eight healthy female pigs (Danish Landrace breed, weight 58-62 kg) were included in this study. Microdialysis catheters were placed for sampling of ischemic metabolites (glucose, lactate, glycerol, and pyruvate) and cefuroxime concentrations in both anastomosis and non-anastomosis ileum and colon. Cefuroxime 1.5 g was administered as an intravenous infusion over 15 min. Subsequently, dialysates and blood samples were collected over 8 h and the ischemic metabolites and cefuroxime concentrations were quantified in all samples. The concentrations of glucose, lactate, glycerol and pyruvate were determined using the CMA 600 Microdialysis Analyzer with Reagent Set A (M Dialysis AB, Sweden), and the concentrations of cefuroxime and meropenem were quantified using a validated ultra-high-performance liquid chromatography assay. RESULTS Only the colon anastomosis induced mean ischemic lactate/pyruvate ratios above 25 (ischemic cut-off) throughout the entire sampling interval, and simultaneously decreased glucose concentrations. The mean time for which cefuroxime concentrations were maintained above the clinical breakpoint minimal inhibitory concentration for Escherichia coli (8 µg/mL) ranged between 116-128 min across all the investigated compartments, and was similar between the anastomosis and non-anastomosis ileum and colon. For all pigs and in all the investigated compartments, a cefuroxime concentration of 8 µg/mL was reached within 10 min after administration. When comparing the pharmacokinetic parameters between the anastomosis and non-anastomosis sites for both ileum and colon, only colon T max and half-life differed between anastomosis and non-anastomosis ( P < 0.03). Incomplete tissue penetrations were found in all tissues except for the non-anastomosis colon. CONCLUSION Administering 1.5 g cefuroxime 10 min prior to intestine surgery seems sufficient, and effective concentrations are sustained for approximately 2 h. Only colon anastomosis was locally vulnerable to ischemia.