N-Acetylcysteine Enhances Recovery From Acute Lung Injury in Man – Discussion

Despite major improvements in patient care, ARDS still remains a formidable clinical challenge and carries a high mortality rate. Recent clinical studies suggest that patients with ARDS undergo relevant oxidative stress. Toxic oxygen products cause cellular and subcellular damage and activate epithelial cells, macrophages, or endothelial cells. Oxygen radicals are also recognized as mediators between primary and secondary effectors, either directly or via cytokine release {ie, tumor necrosis factor) with subsequent formation of reactive oxygen. Thus, oxygen-free radicals are important proinflammatory agents and it seems desirable to control their activity in states of overshooting inflammation. Endogenous antioxidants and particularly glutathione (GSH) normally constitute an effective control of toxic oxygen. Glutathione is detected in high concentrations in the extracellular epithelial lining fluid of the lower respiratory tract of normal subjects and could act as a first-time scavenger of toxic oxygen intermediates and protect against lung cell damage and injury. Patients with severe acute lung injury of the ARDS type have a marked decrease of GSH in epithelial lining fluid, plasma, and blood cells.’ Glutathione depletion in plasma and granulocytes in ARDS is reversible by NAC-mediated glutathione rescue.
The present trial examines the effects of NAC in patients presenting with mild-to-moderate acute lung injury. At ICU admission, our two groups were similar for severity of illness and lung injury score. We were unable to find a preventive effect of NAC on the progression to ARDS. Survival had a tendency to be higher in the NAC group. N-acetylcysteine may have positive hemodynamic effects in critically ill patients, ie, improvement in cardiac output, systemic oxygen transport, and consumption. The mechanisms involved in these changes are not entirely clear. N-acetylcysteine possibly restores the decreased activity of endothelium-derived relaxing factor, thereby improving microcirculation. The most interesting finding of our study is the improvement seen in oxygenation index and LIS, which are sensitive markers of the severity of acute respiratory failure and prognosis. Fewer patients in the NAC group were receiving mechanical ventilatory support at day 2 and 3 and this group had a tendency to have a shorter ICU stay (median 7 days vs 10 days for the placebo group).
In conclusion, the present study suggests that early intravenous administration of NAC in patients with mild-to-moderate acute lung injury improves pulmonary gas exchange and may reduce the duration of mechanical ventilatory support. However, the number of patients included is small and the causes of acute lung injury is heterogeneous. Further and larger trials have to be done to define if this therapy can prevent ARDS and improve outcome.

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