Effect of fluid resuscitation on mortality and organ function in experimental sepsis models.
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.
Brandt
Sebastian
S
Department of Anaesthesia and Pain Therapy, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland. Sebastian.Brandt@insel.ch
Regueira
Tomas
T
Bracht
Hendrik
H
Porta
Francesca
F
Djafarzadeh
Siamak
S
Takala
Jukka
J
Gorrasi
José
J
Borotto
Erika
E
Krejci
Vladimir
V
Hiltebrand
Luzius B
LB
Bruegger
Lukas E
LE
Beldi
Guido
G
Wilkens
Ludwig
L
Lepper
Philipp M
PM
Kessler
Ulf
U
Jakob
Stephan M
SM
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
D007773:Lactates; D010100:Oxygen