Background: Hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. The effects of hypercapnic acidosis in the setting of established pulmonary sepsis are not known. The authors investigated whether hypercapnic acidosis-induced by adding carbon dioxide to inspired gas-would be beneficial or deleterious in established Escherichia coli pneumonia in an in vivo model, in the presence and absence of antibiotic therapy.Methods: Adult male Sprague-Dawley rats were anesthetized and ventilated. In the first set of experiments, rats were anesthetized, E coli (5-6.4 X 10(9)/ml colony-forming units) was instilled intratracheally, and the animals were allowed to recover. After 6 h, during which time a severe pneumonia developed, they were reanesthetized and randomly assigned to normocapnia (fraction of inspired carbon dioxide [FICO2] = 0-00, n = 10) or hypercapnic acidosis (FICO2 = 0.05, n = 10). The second set of experiments was performed in a manner identical to that of series 1, but all rats (n = 10 per group) were given intravenous ceftriaxone (30 mg/kg) at randomization. All animals received normocapnia or hypercapnic acidosis for 6 h, and the severity of lung injury was assessed.Results: in the absence of antibiotic therapy, hypercapnic acidosis reduced the pneumonia-induced increase in peak airway pressure and the decrease in static lung compliance compared with control conditions. in the presence of antibiotic therapy, which substantially reduced lung bacterial counts, hypercapnic acidosis significantly attenuated the extent of pneumonia-induced histologic injury.Conclusions: Hypercapnic acidosis reduced the magnitude of the lung injury induced by established E coli pneumonia.