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 (Fio₂), 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 H₂O, frequency 20 breaths min⁻¹). The Fio₂ was varied: group 1, Fio₂ 0.30 (228 mm Hg) throughout; group 2, Fio₂ 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fio₂ 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fio₂ 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fio₂ 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.

Keywords::

• Administration
• inhalation
• animals
• chemical warefare agents
• phosgene
• oxygen
• pulmonary edema
• treatment

Acknowledgements

The authors would like to acknowledge the expert technical assistance given by Dr. R. Chilcott, Mr. S. Rutter, Mr. C. Dalton, and Mr. I. Hattersley, and the inhalation team.

Declaration of interest

The authors report no conflicts of interest.