Delayed low-dose supplemental oxygen improves survival following phosgene-induced acute lung injury

Abstract

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces life-threatening pulmonary edema within hours of exposure; no antidote exists. This study examines pathophysiological changes seen following treatment with elevated inspired oxygen concentrations (Fi(O2)), in a model of phosgene-induced acute lung injury. Anesthetized pigs were exposed to phosgene (Ct 2500 mg min m(-3)) and ventilated (intermittent positive pressure ventilation, tidal volume 10 ml kg(-1), positive end-expiratory pressure 3 cm H(2)O, frequency 20 breaths min(-1)). The Fi(O2) was varied: group 1, Fi(O2) 0.30 (228 mm Hg) throughout; group 2, Fi(O2) 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fi(O2) 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 at 12 h post exposure. The current results demonstrate that oxygen is beneficial, with improved survival, arterial oxygen saturation, shunt fraction, and reduced lung wet weight to body weight ratio in all treatment groups, and improved arterial oxygen partial pressure in groups 2 and 3, compared to phosgene controls (group 1) animals. The authors recommend that treatment of phosgene-induced acute lung injury with inspired oxygen is delayed until signs or symptoms of hypoxia are present or arterial blood oxygenation falls. The lowest concentration of oxygen that maintains normal arterial oxygen saturation and absence of clinical signs of hypoxia is recommended.

Phosgene Exposure: A Case of Accidental Industrial Exposure

“…Oxygen therapy has been widely advocated since World War I; however, early high-dose oxygen could be potentially harmful through the production of reactive oxygen species. Improved survival has been demonstrated with the use of low-oxygen concentration (<40 %) and delayed oxygen therapy until signs and symptoms of phosgene inhalation have become apparent [25].…”

The injured lung: clinical issues and experimental models

“…when to give supplemental oxygen (early versus late). We demonstrated the benefits of a protective ventilation strategy (low tidal volume, high positive end expiratory pressure-acute respiratory distress network [7,23]) and supplemental inspired oxygen therapy against CG injury [24].…”

“…Oxygen supplementation also significantly improved survival and arterial blood oxygenation at 24 h even when given at low flow (40% versus 80%) and delayed onset (started 12 h postexposure) [24]. Use of a protective ventilation strategy and oxygen therapy is currently recommended to treat CG-induced lung injury.…”

Management of phosgene-induced acute lung injury

“…[3][4][5] Recently, several important studies have been published which have yet to be incorporated into clinical advice. [6][7][8][9][10] In addition, previous guidance has generally focused on the immediate treatment of individuals or small numbers of people definitely exposed to phosgene in an industrial environment. There is currently no guidance on the 498 C. Grainge and P. Rice management of mass casualties following a large, and possibly deliberate, release in an urban situation where inhaled doses are likely to be unknown and where there will be a large medical and logistic burden from the worried well.…”

“…Multiple regression analysis in large animal models suggests that LWW:BW is related to 24 h survival, so this may be an appropriate surrogate marker. 7 In small animals, it is extremely difficult to measure intrapulmonary shunt fraction, which has also been shown by logistic regression to be related to survival. 7 The best animal studies for treatment options following phosgene exposure would involve large numbers of large animals followed over significant time periods examining survival as a primary end point, with markers of morbidity in surviving animals.…”