Antioxidants
Because ALI is an inflammatory process, antioxidant therapies have been used in an attempt to modulate the underlying pathophysiology. N-acetylcysteine is a precursor of the pulmonary antioxidant glutathione, levels of which are reduced in ALI. Supplementation with this agent can replenish glutathione and reduce markers of pulmonary oxidative damage. N-acetylcysteine has been investigated in several small, randomized, placebo-controlled studies, but with mixed results.
Although pentoxyfylline, and the related compound lisofylline, are antioxidant and immunomodulatory, neither has been successful in modifying ALI. A small study in six ARDS patients treated with pentoxyfylline failed to demonstrate pulmonary or circulatory improvements, whereas a large phase 3 study of lisofylline in 235 patients was stopped early for futility (Lisofylline and Respiratory Management of Acute Lung Injury [LARMA] trial). No effect was seen in either organ failure or 28-day mortality (31.9% in the lisofylline group, versus 24.7% in the placebo group, p = 0.215).