Effect of fluid resuscitation on mortality and organ function in experimental sepsis models
- Equal contributors
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
Critical Care 2009, 13:R186 doi:10.1186/cc8179
See related commentary by Groeneveld, http://ccforum.com/content/14/1/101Published: 23 November 2009
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.
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.
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.
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.