Protective ventilation strategies in the management of phosgene-induced acute lung injury.
Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20 breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O; frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.
Parkhouse
Duncan A
DA
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, SP4 OJQ, UK.
Brown
Roger F
RF
Jugg
Bronwen J
BJ
Harban
Fraser M
FM
Platt
Jan
J
Kenward
Christopher E
CE
Jenner
John
J
Rice
Paul
P
Smith
Adam J
AJ
D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005260:Female; D007385:Intermittent Positive-Pressure Ventilation; D023421:Models, Animal; D010705:Phosgene / Q000633:toxicity*; D011175:Positive-Pressure Respiration; D012123:Pulmonary Ventilation / Q000502:physiology; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D013990:Tidal Volume / Q000502:physiology
D002619:Chemical Warfare Agents; D010705:Phosgene