title: Impact of different modalities of continuous venovenous hemofiltration on sepsis-induced alterations in experimental pancreatitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University Hospital Eppendorf, Hamburg, Germany. yekebas@uke.uni-hamburg.de
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
authors.forename: Tim
authors.initials: T
authors.lastname: Strate
authors.forename: Sharam
authors.initials: S
authors.lastname: Zolmajd
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Armin
authors.initials: A
authors.lastname: Saalmüller
authors.forename: Katharina
authors.initials: K
authors.lastname: Steffani
authors.forename: Christoph
authors.initials: C
authors.lastname: Busch
authors.forename: Holger-Andreas
authors.initials: HA
authors.lastname: Elsner
authors.forename: Madelaine
authors.initials: M
authors.lastname: Engelhardt
authors.forename: Andrea
authors.initials: A
authors.lastname: Gillesen
authors.forename: Jan
authors.initials: J
authors.lastname: Meins
authors.forename: Marcel
authors.initials: M
authors.lastname: The
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D000818:Animals; D001201:Ascites / Q000401:mortality / Q000503:physiopathology; D016470:Bacteremia / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D006439:Hemodynamics; D006440:Hemofiltration; D016130:Immunophenotyping; D007668:Kidney / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D009842:Oligopeptides / Q000097:blood; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*; D018805:Sepsis / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D013556:Swine, Miniature
chemical_list: D016207:Cytokines; D009842:Oligopeptides; C080396:trypsinogen activation peptide; D002097:C-Reactive Protein