title: Effect of fluid resuscitation on mortality and organ function in experimental sepsis models.
abstract: BACKGROUND
  Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models.
  
  
  METHODS
  48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis.
  
  
  RESULTS
  Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals.
  
  
  CONCLUSIONS
  High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.
authors.affiliation: Department of Anaesthesia and Pain Therapy, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland. Sebastian.Brandt@insel.ch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandt
authors.forename: Tomas
authors.initials: T
authors.lastname: Regueira
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
authors.forename: Francesca
authors.initials: F
authors.lastname: Porta
authors.forename: Siamak
authors.initials: S
authors.lastname: Djafarzadeh
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
authors.forename: José
authors.initials: J
authors.lastname: Gorrasi
authors.forename: Erika
authors.initials: E
authors.lastname: Borotto
authors.forename: Vladimir
authors.initials: V
authors.lastname: Krejci
authors.forename: Luzius B
authors.initials: LB
authors.lastname: Hiltebrand
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Bruegger
authors.forename: Guido
authors.initials: G
authors.lastname: Beldi
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wilkens
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Lepper
authors.forename: Ulf
authors.initials: U
authors.lastname: Kessler
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002302:Cardiac Output; D004195:Disease Models, Animal; D004231:Diuresis; D005440:Fluid Therapy / Q000379:methods*; D006339:Heart Rate; D007773:Lactates / Q000097:blood; D010100:Oxygen / Q000097:blood; D010538:Peritonitis / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D011651:Pulmonary Artery / Q000503:physiopathology; D012077:Renal Artery / Q000503:physiopathology; D012151:Resuscitation / Q000379:methods*; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D013318:Stroke Volume; D013552:Swine
chemical_list: D007773:Lactates; D010100:Oxygen