Acute Responses To Phosgene Inhalation and Selected Corrective Measures (Including Surfactant)

We exposed 22 mongrel dogs to 94 ppm phosgene for 20 min from a non-rebreathing system. We expressed exposure to phosgene as ppm. _I ·min.kg ₁, i.e., the amount of gas containing a known phosgene concentration that was actually inhaled per min standardized to body weight, the "exposure index" (EI). In contrast, the conventional expression of exposure, i.e., ppm·min, fails to take volume inhaled (V_I) and body weight into account.

Five dogs received no intervention and served as controls. Fourteen dogs received basic therapy of oral cortisone (40 mg/kg) and NaHCO₃ (3 mEq/kg) plus 100% O ₂ (FiO₂ = 1.0)for 30 min after the exposure period. These animals were further divided according to the following selected additional therapies, which were started 30 min after exposure: (1) Theophylline, 5 mg/kg iv for 20 min followed by 1 mg/kg/hr for 70 min (n = 5). Three dogs of this group were given a trial of 5 cm H20 expiratory resistance during the period of basic therapy. Because of the untoward response, expiratory resistance was discontinued and not used in other experiments. (2) PGE₂-hi, [1 μg/kg/min] iv for 90 min (n = 3). (3) PGE₁-lo, [0.04 μg/kg/min]iv for 90 min (n = 3). (4) Atropine, 0.5 mg/kg iv at 30 and 50 min after exposure (n = 3). Three dogs [group 5] received oral cortisone and NaHCO₃ plus inhaled supplementary surfactant, 2.7 mg/min ultrasonically nebulized (FiO₂ = 0.5; phosphate buffer), for 30 min after exposure. All treated dogs, groups [1] through [4] and the surfactant group [5], received cortisone (40 mg/kg/hr iv), NaHC03 to correct base deficit, and O₂ to correct hypoxemia from 30 min to 120 min after exposure. Because of its clearly beneficial effect in group [1], theophylline was also given to all other treatment groups during this period. At the end of the study, all lungs were excised, examined and prepared for light microscopy.

We found that EI, which varied among subjects because of spontaneous variations of _I during exposure, correlated significantly with the changes in base deficit induced by phosgene inhalation. We also found that the change in minute ventilation, Δ _I·kg^-1, correlated significantly with changes in lung compliance, peak flow and base deficit.

Evaluation of the various therapeutic modalities revealed the following: Immediate therapy with 02 is vital and and FiO₂ of 0.4 to 0.5 is sufficient. NaHCO₃ iv corrects base deficit and should be given as soon as possible. Theophylline improves cardiovascular function but has little effect on expiratory flow. Supplemental surfactant improves compliance and seems to minimize the alveolar response to phosgene. There was no apparent acute benefit from oral cortisone and NaHC03. Expiratory resistance is contraindicated and PGE₁-hi is not recommended. We found no evidence that either PGE₁-lo or atropine produced any effect.