Spontaneous high systemic oxygen delivery increases survival rate in awake sheep during sustained endotoxemia

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Abstract
Objective: To study the natural evolution of systemic oxygen delivery (ḊO2) and oxygen consumption (V̇O2) in sheep infused with low or high doses of endotoxin. Design: Prospective, controlled experimental study. Setting: Animal research laboratory at a medical university. Subjects: Twenty-nine chronically instrumented awake sheep (25-35 kg). Interventions: Awake animals were continuously infused with saline (n = 8) or two doses ofEscherichia coliendotoxin (20 or 40 ng/kg/min; n = 21) for 72 hrs. No attempt was made to increase ḊO2, but respiratory failure was treated by mechanical ventilation and metabolic acidosis was corrected. Measurements and Main Results: The mortality rate was 25% in the group infused with the low dose and 89% in the group infused with the high dose of endotoxin. During the first 12 hrs of endotoxemia, both surviving (S group; n = 10) and nonsurviving (NS group; n = 11) sheep developed similar pulmonary hypertension, left ventricular failure, and hypotension with low systemic vascular resistance. However, S sheep had less interstitial lung edema (pulmonary lymph protein clearance at 8 hrs was 13 ± 3 mL/hr vs. 27 ± 6 mL/hr in the NS group and 4 ± 1 mL/hr in the control group). During this early phase of endotoxemia, ḊO2, V̇O2, and oxygen extraction ratio did not change significantly in any group. After this phase, animals that ultimately survived had a persistent hyperdynamic syndrome with high cardiac output and hypotension. In this group, the ḊO2 increase was greater than the ḊO2 measured in controls and remained steady up to 48 hrs after the start of the endotoxin infusion. Because systemic V̇O2 did not change significantly, oxygen extraction ratio decreased progressively to values less than those measured in controls. In contrast, animals that ultimately died had a hypotensive and normokinetic syndrome associated with pulmonary hypertension, persistent depressed left ventricular function, hypothermia, and a progressive deterioration of gas exchange. Systemic ḊO2 was not significantly different from that in the control group. In contrast, V̇O2 decreased progressively to values significantly lower than those measured in controls and remained low until death. Conclusions: Our results indicate that in the absence of treatment such as fluid challenge or inotropic drugs in sheep infused with endotoxin, the occurrence of spontaneous hyperdynamic syndrome and high ḊO2 improves the survival rate.