Lidocaine attenuates acute lung injury induced by a combination of phospholipase A(2) and trypsin

Objective: Acute severe pancreatitis is often associated with acute lung in jury, including acute respiratory distress syndrome. Acute lung injury indu ced by phospholipase A(2) (PLA2) or trypsin, a pancreatic enzyme, is an exp erimental model resembling acute respiratory distress syndrome. Neutrophils and platelets are thought to play a pivotal role in the pathogenesis of ac ute respiratory failure. Lidocaine inhibits some aspects of neutrophil and platelet functions. We conducted the current study to assess the effects of pretreatment with lidocaine on acute lung injury induced by a combination of PLA2 and trypsin, Design: Prospective, randomized animal study. Setting: University research laboratory. Subjects: Twenty-one adult male Japanese White rabbits (weight range, 2.0-2 .4 kg), Interventions: The animals were mechanically ventilated with a tidal volume of 10 mL/kg and an F-IO2 of 0.4, and thereafter, they were randomly assign ed to three groups. Acute lung injury was induced by a combination of PLA2 (1000 units/kg/hr) and trypsin (5000 units/kg/hr) infused intravenously for 4 hrs, Immediately before induction of the acute lung injury, the lidocain e treatment group received intravenous lidocaine (2 mg/kg bolus followed by 2 mg/kg/hr) until they were killed. In the nontreatment group, saline was given instead of lidocaine. Rabbits in the nonlung- injury group received s aline infusion instead of the pancreatic enzymes. Measurements and Main Results: During the experimental period (4 hrs), arte rial blood gases, lung mechanics, and peripheral neutrophil and platelet co unts were measured. Immediately after killing, the wet weight/dry weight ra tio of the lung was recorded. Light microscopic findings (lung injury score and number of neutrophils) were compared between the three groups. The com bination of PLA2 and trypsin decreased paO(2), lung compliance, and periphe ral counts of neutrophils and platelets and increased alveolar/arterial oxy gen tension difference, lung resistance, wet weight/dry weight ratio, and t he number of neutrophils in the lung. Lidocaine treatment attenuated these changes. The two pancreatic enzymes caused extensive morphologic lung damag e, which was lessened by lidocaine, Conclusions: We conclude that pretreatment with intravenous lidocaine atten uated the lung injury induced by the pancreatic enzymes. However, further s tudies are required to determine whether this drug has a therapeutic effect once the lung injury has developed.