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

Abstract

IntroductionSeveral 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.Methods48 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.ResultsMortality 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.ConclusionsHigh-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.

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

“…Edema, positive fluid balance, and/or high central venous pressure have been shown in human and/or experimental models to have a negative impact on biological processes, including microvascular perfusion, renal perfusion, sodium and water excretion, intraabdominal pressure, cardiac function, and pulmonary gas exchange (31)(32)(33)(34)(35)(36). Intestinal edema and edema of the skin may contribute to impaired epithelial integrity and risk of bacterial translocation and/or infection (37).…”

Fluid Therapy in Trauma

“…Therefore, the net driving force (NDF) for movement of fluids in acapillary bed can berepresented as: [12]. Hypoperfusion with decreased oxygen delivery causes uncoupling of normal metabolic pathways with lactate production, and metabolic acidosis [13].…”

“…Large volumes of sodium-containing fluids given for resuscitation aggravate the retention [2]. Excessive fluid and electrolyte retention and interstitial oedema are an independent risk factor for SIR syndrome and multiple organ dysfunction, and failure [13]. Results of randomized controlled prospective clinical studies suggest that limiting the sodium and chloride input and optimal use of colloids.…”

Pulse pressure variation to predict fluid responsiveness in spontaneously breathing patients: tidal vs forced inspiratory breathing

“…Fluid administration is usually the first line therapy for hypotension during anaesthesia. Although fluid administration usually improves cardiac output and blood pressure, excessive fluid therapy leads to interstitial oedema, which may worsen the patient outcome [1,2].…”