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Effect of fluid resuscitation on mortality and organ function in experimental sepsis models

Sebastian Brandt1, Tomas Regueira2, Hendrik Bracht2, Francesca Porta2, Siamak Djafarzadeh2, Jukka Takala2, José Gorrasi2, Erika Borotto2, Vladimir Krejci1, Luzius B Hiltebrand1, Lukas E Bruegger3, Guido Beldi3, Ludwig Wilkens5, Philipp M Lepper2, Ulf Kessler4 and Stephan M Jakob2*

Author Affiliations

1 Department of Anaesthesia and Pain Therapy, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland

2 Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland

3 Department of Visceral and Transplant Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland

4 Department of Pediatric Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerl

5 Institute of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern, Switzerland

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Critical Care 2009, 13:R186  doi:10.1186/cc8179


See related commentary by Groeneveld, http://ccforum.com/content/14/1/101

Published: 23 November 2009

Abstract

Introduction

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.