Fluid resuscitation is necessary in sepsis, but positive fluid balance may increase the risk of mortality. We tested the hypothesis that a volume resuscitation strategy may modify liver mitochondrial function and outcome.
Methods
Twenty-nine anesthetized pigs received for 24 hours either endotoxin or placebo, and either Ringer's lactate 10 ml/kg/hour or 15 ml/kg/hour + 5 ml/hour HES. Systemic and regional hemodynamics were measured. Liver mitochondrial state 3 and state 4 oxygen consumption were determined.
Results
Hepatosplanchnic oxygen delivery was similar in endotoxic pigs with high (2.97 ± 1.58 ml/min/kg) vs moderate volume administration (3.06 ± 0.6 ml/min/kg), but hepatosplanchnic VO2 was lower in animals with high (1.32 ± 0.4 ml/min/kg) vs moderate volume administration (1.75 ± 0.3 ml/min/kg, P = 0.019). Endotoxin high-volume pigs exhibited a decrease in state 3 respiration for complex I and complex II (not significant) in comparison with control high-volume and with endotoxin low-volume pigs (Figure 1). They also had an increased mortality rate during the 24-hour study period (60% vs 0% in controls).
Figure 1
(abstract P29)
Conclusion
A prolonged high-volume resuscitation approach during endotoxemia may be associated with impaired hepatosplanchnic oxygen consumption, liver mitochondrial dysfunction and high mortality. The impact of aggressive and prolonged volume administration on hepatosplanchnic oxygenation and mitochondrial function in human sepsis should be determined.
