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Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1429-1436

The Effect of Intensive Plasma Water Exchange by Hemofiltration on Hemodynamics and Soluble Mediators in Canine Endotoxemia

RINALDO BELLOMO, JOHN A. KELLUM, CHANDRASHEKHAR R. GANDHI, MICHAEL R. PINSKY, and Brian Ondulik,  with the Technical Assistance of 

Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh Medical Centre, Pittsburgh, Pennsylvania

High volume hemofiltration (HVHF) (200 ml/kg/h) improves hemodynamics in experimental septic shock but is difficult to apply clinically. Accordingly, we studied whether less intensive HVHF (80 ml/kg/h) can still improve hemodynamics in experimental septic shock. We also investigated its effect on the serum concentrations of several inflammatory mediators, including endothelin (ET-1), endotoxin (LPS), tumor necrosis factor-alpha (TNF-alpha ), and 6-keto prostaglandin F1alpha (6-kepto PGF1alpha ). Sixteen anesthetized dogs were connected to a continuous veno-venous hemofiltration (CVVH) (filtration: 80 ml/kg/h) or sham circuit and endotoxin (0.5 mg/kg) was infused intravenously over 5 min. Hemodynamic variables were measured at baseline and at 15, 45, 90, and 180 min. The major hemodynamic finding was that endotoxin-induced hypotension was significantly attenuated by intensive CVVH (p < 0.04). Changes in cardiac output and right ventricular ejection fraction were equal in both groups. ET-1 levels, but not LPS, TNF-alpha , or 6-keto PGF1alpha , were lower during CVVH (p = 0.042). Endotoxin or TNF-alpha were not found in the ultrafiltrate. Median clearances of ET-1 and 6-keto PGF1alpha during intensive CVVH were 8.8 and 25.9 ml/m, respectively. We conclude that intensive CVVH attenuates the early component of endotoxin-induced hypotension and reduces serum concentrations of endothelin-1. The effect of CVVH on blood pressure is not explained by convective clearance of the mediators in question.




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