Hypercapnic acidosis and mortality in acute lung injury*

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Abstract
We tested the hypothesis that hypercapnic acidosis is associated with reduced mortality rate in patients with acute lung injury independent of changes in mechanical ventilation. Secondary analysis of randomized clinical trial data using hypothesis-driven multivariate logistic regression. Randomized, multiple-center trial (n = 861) comparing 12 mL/kg to 6 mL/kg predicted body weight tidal volumes previously published by the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network. Acute lung injury patients enrolled in a randomized, multiple-center trial (n = 861). None. The adjusted odds ratio and 95% confidence intervals (CI) for 28-day mortality rate associated with hypercapnic acidosis defined as day 1 pH 45 mm Hg were 0.14 (95% CI 0.03–0.70, p = .016) in the 12 mL/kg predicted body weight tidal volume group and 1.18 (95% CI 0.59–2.35, p = .639) in the 6 mL/kg predicted body weight tidal volume group. Other definitions of hypercapnic acidosis spanning a range of magnitudes suggest a dose-response association between hypercapnic acidosis and 28-day mortality in the 12 mL/kg predicted body weight tidal volume group. None of our definitions of hypercapnic acidosis were associated with reduction in 28-day mortality in the 6 mL/kg predicted body weight tidal volume group. Hypercapnic acidosis was associated with reduced 28-day mortality in the 12 mL/kg predicted body weight tidal volume group after controlling for comorbidities and severity of lung injury. These results are consistent with a protective effect of hypercapnic acidosis against ventilator-associated lung injury that was not found when the further ongoing injury was reduced by 6 mL/kg predicted body weight tidal volumes.