Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs.
OBJECTIVE
To evaluate the efficacy of treating sepsis-induced adult respiratory distress syndrome (ARDS) by instillation of exogenous surfactant in a porcine endotoxin model.


METHODS
Prospective trial.


METHODS
Laboratory at a university medical center.


METHODS
Fifteen hybrid pigs, weighing 15 to 20 kg.


METHODS
Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into three groups: a control group (group I; n=4) that received sham Escherichia coli lipopolysaccharide (endotoxin); an endotoxin group (group II; n=6) that received endotoxin (25 micrograms/kg); and an endotoxin + surfactant (Infasurf, ONY, Amherst, NY) instillation group (group III; n=5) that received endotoxin (25 micrograms/kg) followed by surfactant (100 mg/kg) instillation; all groups were studied for 6 hrs after the start of endotoxin injection. At necropsy, lung water and surfactant function (Wilhelmy balance) were measured and the right middle lung lobe was fixed for histologic analysis. Surfactant function was expressed as the surface tension at the minimum trough area.


RESULTS
Surfactant treatment (group III) significantly (p<.05) decreased venous admixture (group III = 41.5 +/- 9.1%; group II = 61.6 +/- 4.7%), PaCO2 (group III = 46.6 +/- 1.3 torr [6.2 +/- 0.2 kPa]; group II = 54.4 +/- 2.6 torr [7.25 +/- 0.34 kPa], and surface tension minimum (group III = 8.8 +/- 1.8 dyne/cm; group II = 20.0 +/- dyne/cm), as compared with endotoxin without treatment (group II) 6 hrs after endotoxin infusion. However, surfactant instillation did not significantly improve PaO2 (group III = 62.8 +/- 6.8 torr [8.4 +/- 0.9 kPa2]; group II = 50.3 +/- 3.7 torr [6.7 +/- 0.49 kPa]) or reduce the amount of pulmonary edema (group III = 7.1 +/- 0.39 ratio; group II = 6.8 +/- 0.24 ratio) seen 6 hrs following endotoxin injection. Histologic analysis showed that endotoxin caused edema accumulation around airways and pulmonary vessels, and a large increase in the number of marginated leukocytes with or without surfactant treatment. Surfactant treatment significantly increased the total number of leukocytes in the pulmonary parenchyma.


CONCLUSIONS
We conclude that endotoxin caused lung injury typical of ARDS as demonstrated by pulmonary edema, an increase in PaCO2, and a decrease in PaO2, a decrease in static lung compliance and inhibition of surfactant function. Exogenous surfactant treatment effected only moderate improvements in lung function (i.e., reduced venous admixture and restored surfactant function) in this sepsis-induced ARDS model.
Nieman
G F
GF
Department of Surgery, SUNY Health Science Center at Syracuse, NY 13210, USA.
Gatto
L A
LA
Paskanik
A M
AM
Yang
B
B
Fluck
R
R
Picone
A
A
D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications; D006439:Hemodynamics; D008070:Lipopolysaccharides; D010101:Oxygen Consumption; D011446:Prospective Studies; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012772:Shock, Septic / Q000150:complications; D013501:Surface-Active Agents / Q000627:therapeutic use*; D013552:Swine
D008070:Lipopolysaccharides; D013501:Surface-Active Agents