The effect of steroid treatment with inhaled budesonide or intravenous methylprednisolone on phosgene-induced acute lung injury in a porcine model.
Toxic industrial chemicals e.g., phosgene, are widely used as reactive intermediates in industrial processes. Inhalation exposure to these chemicals can result in life-threatening acute lung injury (ALI), to which no specific antidote exists. This study aimed to assess the potential benefit of steroids in treating phosgene induced ALI. Anesthetized pigs were instrumented, exposed to phosgene Ct 2000 mg.min.m(-3) (Ct is the product of concentration [mg.m(-3)] x time [min]), and ventilated with intermittent positive pressure ventilation before being randomized to study part 1: treatment with intravenous glucose saline (20 mL) or methylprednisolone (12.5 mg.kg(-1) in 20 mL) 6 h postexposure or study part 2: treatment with inhaled glucose saline (2 mL) or budesonide (2 mL of 0.5 mg.mL(-1) solution) at 1, 6, 12, and 18 h postexposure. Biochemical parameters and animal physiology were monitored to 24 h postexposure. The results show no change in mortality, lung edema, or shunt fraction; however, some beneficial effects on cardiac parameters e.g., stroke volume, left ventricular stroke work, were noted. Steroids were neither beneficial nor detrimental in the treatment of phosgene induced ALI. This study does not support the use of steroids alone as a treatment, but their use in a combined therapy strategy should be investigated.
Smith
Adam
A
Biomedical Sciences Department, Defence Science and Technology Laboratory, UK.
Brown
Roger
R
Jugg
Bronwen
B
Platt
Janet
J
Mann
Thomas
T
Masey
Charles
C
Jenner
John
J
Rice
Paul
P
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D018893:Bronchoalveolar Lavage; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005260:Female; D018836:Inflammation Mediators / Q000097:blood; D007275:Injections, Intravenous; D007385:Intermittent Positive-Pressure Ventilation; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D010705:Phosgene / Q000633:toxicity*; D011897:Random Allocation; D013552:Swine
D002619:Chemical Warfare Agents; D018836:Inflammation Mediators; D010705:Phosgene; D019819:Budesonide; D008775:Methylprednisolone