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 pancreatitic 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 Ringers 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.


CONCLUSIONS
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.
Homma
Hiroshi
H
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103-1709, USA.
Deitch
Edwin A
EA
Feketeova
Elenora
E
Lu
Qi
Q
Berezina
Tamara L
TL
Zaets
Sergey B
SB
Machiedo
George W
GW
Xu
Da-Zhong
DZ
D000818:Animals; D001550:Benzamidines; D004396:Coloring Agents; D004359:Drug Therapy, Combination; D004907:Erythrocyte Deformability / Q000187:drug effects*; D005070:Evans Blue; D006146:Guanidines / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000473:pathology; D007552:Isotonic Solutions / Q000627:therapeutic use*; D008297:Male; D009102:Multiple Organ Failure / Q000517:prevention & control; D018375:Neutrophil Activation / Q000187:drug effects; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000473:pathology
D001550:Benzamidines; D004396:Coloring Agents; D006146:Guanidines; D007552:Isotonic Solutions; D011480:Protease Inhibitors; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; D005070:Evans Blue; C032855:nafamostat