High-dose furosemide alters gas exchange in a model of acute lung injury.
OBJECTIVE
Furosemide is often used to reduce edema in patients with acute respiratory distress syndrome (ARDS). It was hypothesized that furosemide would reduce lung water and improve gas exchange in a phorbol-myristate acetate (PMA) model of acute lung injury.


METHODS
Two groups of mongrel dogs received PMA (25 to 30 micrograms/kg) and continuous saline at 10 mL/kg/h; one group received PMA plus two 1-mg/kg doses of furosemide at 1 and 2 hours after PMA. Arterial blood gases on F1O2 = 1.0 and double-dilution lung water were measured at intervals over 7 hours.


RESULTS
In dogs receiving PMA+furosemide, AaDO2 and shunt fraction increased compared with dogs receiving PMA only (AaDO2, P = .014; shunt, P = .017). There were no significant differences between the groups in lung water (P = .34) during the experiment or in wet/dry weight postmortem. Urine flow was markedly reduced in both groups; the kidneys appeared unresponsive to the diuretic effects of furosemide. Significant elevations in hematocrit and pulmonary vascular resistance were seen in furosemide-treated compared with PMA-only dogs.


CONCLUSIONS
In this model of ARDS, which results in the absence of effective kidney function and multiple organ failure, furosemide compromises alveolar-capillary gas exchange and fails to influence the time course of lung water accumulation. The results suggest that the nondiuretic affects of furosemide cannot explain its purported clinical utility in ARDS.
Waugh
J B
JB
Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus, USA.
Op't Holt
T B
TB
Gadek
J E
JE
Clanton
T L
TL
D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004285:Dogs; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate; D014655:Vascular Resistance / Q000187:drug effects
D005665:Furosemide; D013755:Tetradecanoylphorbol Acetate