Purpose: Low tidal volume ventilation and permissive hypercapnia are required in patients with sepsis complicated by ARDS. The effects of hypercapnia on tissue oxidative metabolism in this setting are unknown. We therefore determined the effects of moderate hypercapnia on markers of systemic and splanchnic oxidative metabolism in an animal model of endotoxemia. Methods: Anesthetized rats maintained at a PaCO2 of 30, 40 or 60mmHg were challenged with endotoxin. A control group (PaCO2 40mmHg) received isotonic saline. Hemodynamic variables, arterial lactate, pyruvate, and ketone bodies were measured at baseline and after 4h. Tissue adenosine triphosphate (ATP) and lactate were measured in the small intestine and the liver after 4h. Results: Endotoxin resulted in low cardiac output, increased lactate/pyruvate ratio and decreased ketone body ratio. These changes were not influenced by hypercapnia, but were more severe with hypocapnia. In the liver, ATP decreased and lactate increased independently from PaCO2 after endotoxin. In contrast, the drop of ATP and the rise in lactate triggered by endotoxin in the intestine were prevented by hypercapnia. Conclusions: During endotoxemia in rats, moderate hypercapnia prevents the deterioration of tissue energetics in the intestin
