In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function.
OBJECTIVE
The adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what dose of surfactant is required for treatment of these syndromes.


METHODS
The purpose of this study was to investigate the amount of exogenous surfactant needed to overcome the inhibitory components in human plasma. Male adult rats suffering from respiratory failure due to surfactant depletion after whole-lung lavage received human plasma (4 ml/kg body weight) mixed with surfactant at different concentrations, intratracheally. Rats receiving surfactant only at different concentrations served as controls. Blood gas analysis was performed.


RESULTS
It was demonstrated that plasma (4 ml/kg-273 mg plasma proteins/kg) mixed with surfactant at 300 mg/kg was able to increase and maintain PaO2 at normal values. Plasma mixed with surfactant at 100 mg/kg, after initial restoration of blood gases, showed deterioration of PaO2 values. Plasma mixed with surfactant at a dose of 50 mg/kg did not improve PaO2 whereas surfactant at 50 mg/kg, without plasma, restored blood gases to pre-lavage values.


CONCLUSIONS
It is concluded that approximately 1 mg surfactant phospholipids is required to overcome the inhibitory effect of approximately 1 mg plasma proteins. For clinical practice this means that an excess of surfactant should be given, or repeatedly be substituted ("titrated") at low concentrations, until blood gases improve.
Lachmann
B
B
Department of Anesthesiology, Erasmus University, Rotterdam, The Netherlands.
Eijking
E P
EP
So
K L
KL
Gommers
D
D
D000818:Animals; D001798:Blood Proteins / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000097:blood / Q000188:drug therapy
D001798:Blood Proteins; D011663:Pulmonary Surfactants; D002245:Carbon Dioxide; D010100:Oxygen