Deliberate induction of prophylactic hypercapnic acidosis protects against lung injury after in vivo ischemia-reperfusion and ventilation-induced lung injury. However, the efficacy of hypercapnic acidosis in sepsis, the commonest cause of clinical acute respiratory distress syndrome, is not known. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would be protective against endotoxin-induced lung injury in an in vivo rat model. Prophylactic institution of hypercapnic acidosis (i.e., induction before endotoxin instillation) attenuated the decrement in arterial oxygenation, improved lung compliance, and attenuated alveolar neutrophil infiltration compared with control conditions. Therapeutic institution of hypercapnic acidosis, that is, induction after endotoxin instillation, attenuated the decrement in oxygenation, improved lung compliance, and reduced alveolar neutrophil infiltration and histologic indices of lung injury. Therapeutic hypercapnic acidosis attenuated the endotoxin-induced increase in the higher oxides of nitrogen and nitrosothiols in the lung tissue and epithelial lining fluid. Lung epithelial lining fluid nitrotyrosine concentrations were increased with hypercapnic acidosis. We conclude that hypercapnic acidosis attenuates acute endotoxin-induced lung injury, and is efficacious both prophylactically and therapeutically. The beneficial actions of hypercapnic acidosis were not mediated by inhibition of peroxynitrite-induced nitration within proteins.

3 Fisher QA, Shaffner DH, Yaster M. Detection of intravascular injection of regional anaesthetics in children. Can J Anesth 1997; 44: 592-598. 4. Giaufre E, Dalens B, Combert A. Epidemiology and morbidity of regional anesthesia in children: a one-year prospective survey of the French-language society of pediatric anesthesiologists. Anesth Analg 1996; 83: 904-912. 5. Tanaka M, Nishikawa T. The efficacy of a simulated intravascular test dose in sevoflurane-anesthetized children: a dose-response study. Anesth Analg 1999; 89: 632-637. 6. Sethna NF, Sullivan L, Retik A et al. Efficacy of simulated epinephrine-containing epidural test dose after intravenous atropine during isoflurane anesthesia in children. Reg Anest Pain Med 2000; 25: 566-572. 7. Tanaka M, Nishikawa T. Simulation of an epidural test dose with intravenous epinephrine in sevoflurane-anesthetized children. Anesth Analg 1998; 86: 952-957.