DISCUSSION
The first trial, invigorated the possible role of high dose IV ascorbic acid in critically ill patients, was published by Marik. (38) Most trials evaluated the role of oral ascorbic acid in critically ill patients failed to show improved outcomes due to limited absorption, gut ischemia, impaired intestinal flora, and different distribution. (39) Animal models showed that the lungs are very susceptible to ascorbic acid deficiency. (40) Also, early reports showed that administration of ascorbic acid was associated with increased alveolar fluid clearance and decreased epithelial permeability. These effects were initiated via increased expression of Na+-K+-ATPase, aquaporin 5, and cystic fibrosis transmembrane conductance regulator. (41)
To our knowledge, this is the first RCT to investigate the role of high dose IV ascorbic acid in patients with TRALI in terms of oxidative stress, pro-inflammatory, and anti-inflammatory markers. Other trials are still running in patients with close entities for TRALI such as ARDS, sepsis-induced acute lung injury, and COVID-19 pulmonary complications.