Impact of different modalities of continuous venovenous hemofiltration on sepsis-induced alterations in experimental pancreatitis

Abstract

Continuous venovenous hemofiltration (CVVH) is assumed to attenuate systemic complications in septic diseases. The impact of different treatment intensities of CVVH on immunologic and systemic alterations in experimental pancreatitis was evaluated. Eighty-four minipigs were allocated either to an untreated control group (group 1) or to one of six treatment groups (groups 2 to 7) that underwent CVVH in different modalities: (1): "late" CVVH, started after a decline of total peripheral resistance of 30% versus "prophylactic" CVVH started immediately after the induction of pancreatitis; (2) no change of hemofilters versus a periodic change of filters every 12 hours; (3) low-volume CVVH with a filtrate turnover of 20 mL/kg body weight (BW)/h versus high-volume CVVH (100 mL/kg/h). Pancreatitis was induced by intraductal injection of sodium-taurocholate (3%, 1 mL/kg BW) and enterokinase (2 U/kg BW). We focused on the occurrence of sepsis, serum cytokines, down-regulation of major histocompatibility complex II (MHC II) and the endotoxin receptor CD14 expression, bacterial translocation/endotoxemia, and pulmonary and renal histologic alterations. CVVH delayed or definitively prevented the occurrence of sepsis. Pancreatitis was associated with a tremendous initial tumor necrosis factor-alpha (TNF-alpha) response prior to a return to near baseline levels in the late course of sepsis. Endotoxin hyporesponsiveness, suggested by the dissociation of decreasing TNF-alpha levels and increasing endotoxemia in end-stage sepsis, was favorably influenced by CVVH. Down-regulation of MHC II and CD14 expression was prevented in non-septic animals. CVVH-related sepsis-protection led to a significant attenuation of histological injury in lungs and kidneys. "Prophylactic" CVVH prevented histological changes more effectively than "late" CVVH. CVVH offers a therapeutic option for supportive treatment in severe pancreatitis. The efficiency of CVVH is associated with the duration of filter use and cumulative plasma turnover. Since CVVH may lead to sepsis-protection and long-term survival, further evaluation in controlled, clinical trials is warranted.