Attenuation of sepsis-related immunoparalysis by continuous venovenous hemofiltration in experimental porcine pancreatitis

Objectives: In light of evidence suggesting that hemofiltration favorably i nfluences septic diseases by removing sepsis mediators, the impact of diffe rent modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated . Design:Randomized, controlled intervention trial, Subjects: Forty-eight minipigs of either sex, Interventions: Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW), A nimals were allocated either to untreated controls-group 1-or to one of thr ee treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of he mofilters; group 3: law-volume CVVH, filters changed every 12 hrs; and grou p 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Surviva l represented the major parameter of the study. Serum cytokine levels, seps is-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were fur ther parameters evaluated in the study. Measurements and Main Results: High-volume CVVH combined with periodic fibe r change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-t erm survival (> 60 hrs) was found in 67% of group 4 and 33% of group 3 anim als (p < .05), whereas in controls and group 2 no animal survived. CVVH ame liorated the initial serum tumor necrosis factor-a! response and prevented sepsis-induced in vivo endotoxin hyporesponsiveness. Down-regulation of maj or histocompatibility complex II and CD14 expression on monocytes was signi ficantly improved by CVVH, improved oxidative burst and phagocytosis capaci ty in polymorphonuclear leukocytes suggested that leukocyte function was st abilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia, Conclusions: Hemofiltration reversed sepsis-induced immuno-paralysis in a p orcine model of bile acid-induced pancreatitis. Implications for human panc reatitis must be validated in prospective, clinical protocols.