title: Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study.
abstract: BACKGROUND
  One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response.
  
  
  METHODS
  A total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM).
  
  
  RESULTS
  At study end the cardiac output (10% HES200 143±48 ml/kgBW; 6% HES130 171±47 ml/kgBW; RAc 137±32 ml/kgBW; 4% gelatin 160±42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157±115 U/g creatinine; P<0.05) group compared to hydroxyethylstarch 130 (24±9 U/g creatinine), Ringer's acetate (2±3 U/g creatinine) and SHAM (21±15 U/g creatinine) at the study's end. Creatinine significantly increased by 87±84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845±1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492±604 pg/ml; RAc 874±363 pg/ml; 4% gelatin 1,623±1,242 pg/ml).
  
  
  CONCLUSIONS
  Despite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.
authors.affiliation: Department of Intensive Care and Intermediate Care, RWTH University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. tsimon@ukaachen.de
authors.forename: Tim Philipp
authors.initials: TP
authors.lastname: Simon
authors.forename: Tobias
authors.initials: T
authors.lastname: Schuerholz
authors.forename: Lars
authors.initials: L
authors.lastname: Hüter
authors.forename: Michael
authors.initials: M
authors.lastname: Sasse
authors.forename: Florian
authors.initials: F
authors.lastname: Heyder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfister
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
mesh_terms: D000818:Animals; D003102:Colloids / Q000627:therapeutic use / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects; D006895:Hydroxyethyl Starch Derivatives / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010952:Plasma Substitutes / Q000627:therapeutic use / Q000633:toxicity*; D011897:Random Allocation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000473:pathology; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology; D013552:Swine
chemical_list: D003102:Colloids; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; C517718:hydroxyethylstarch 200