The hemodynamic effects of Cremophor-EL

A problem associated with parenteral cyclosporine has been the increased incidence of renal toxicity. Cremophor-EL, the vehicle for parenteral cyclosporine has been associated with massive histamine release and anaphylaxis in certain animal models. We investigated the effects of Cremophor-EL on the cardiac output (CO); mean arterial pressure (MAP); and hepatic, renal and pancreatic blood flow in the anesthesized canine model. Doppler flow probes were utilized to calculate individual organ blood flow. Profound adverse affects were noted on the CO, MAP, and hepatic blood flow. There were negative trends noted in the renal and splenic arterial flow that did not reach statistical significance. It was noted that the changes in organ blood flow were partially independent on MAP and the total dose of Cremophor-EL. We therefore conclude that it is prudent to consider the possible adverse hemodynamic role of Cremophor-EL in canine allograft dysfunction.