Small volume resuscitation with hypertonic saline is more effective in ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation and red blood cell dysfunction than pancreatic protease inhibition

Background: Recognition of the limitations of standard crystalloid resuscitation has led to the search for alternative resuscitation strategies that might better limit the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone, and in combination, with those of standard resuscitation with Ringer's lactate (RL). The two strategies were small volume resuscitation with hypertonic saline (HTS) and intraluminal inhibition of pancreatic proteases with the serine protease inhibitor nafamostat. Methods: Male rats were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with RL, HTS, nafamostat, or the combination of HTS and nafamostat. The T/HS model consisted of a laparotomy plus 90 minutes of shock (MAP 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, pulmonary neutrophil sequestration, neutrophil activation, red blood cell deformability, and gut injury were assessed. Results: Both HTS and nafamostat reduced T/HS-induced pulmonary permeability and neutrophil sequestration, as well as neutrophil activation as compared with resuscitation with RL. However, HTs was more effective than nafamostat in reducing T/HS-induced acute lung injury and neutrophil activation. Additionally, HTS, but not nafamostat, reduced T/HS-induced RBC rigidification. Lastly, gut injury after T/HS was reduced to the greatest extent by the combination of HTS plus nafamostat. Conclusion: Small volume resuscitation with HTS is more effective than RL and nafamostat in limiting T/HS-induced acute lung injury, neutrophil activation and red blood cell injury.