Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin

Objective: Acute severe pancreatitis is often associated with acute lung injury, including acute respiratory distress syndrome. Acute lung injury induced by phospholipase A2 (PLA2) or trypsin, a pancreatic enzyme, is an experimental model resembling acute respiratory distress syndrome. Neutrophils and platelets are thought to play a pivotal role in the pathogenesis of acute 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 FIO2 of 0.4, and thereafter, they were randomly assigned 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 lidocaine 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 saline infusion instead of the pancreatic enzymes. Measurements and Main Results: During the experimental period (4 hrs), arterial blood gases, lung mechanics, and peripheral neutrophil and platelet counts were measured. Immediately after killing, the wet weight/dry weight ratio of the lung was recorded. Light microscopic findings (lung injury score and number of neutrophils) were compared between the three groups. The combination of PLA2 and trypsin decreased PaO2, lung compliance, and peripheral counts of neutrophils and platelets and increased alveolar/arterial oxygen tension difference, lung resistance, wet weight/dry weight ratio, and the number of neutrophils in the lung. Lidocaine treatment attenuated these changes. The two pancreatic enzymes caused extensive morphologic lung damage, which was lessened by lidocaine. Conclusions: We conclude that pretreatment with intravenous lidocaine attenuated the lung injury induced by the pancreatic enzymes. However, further studies are required to determine whether this drug has a therapeutic effect once the lung injury has developed.