Intermittent infusion of dobutamine in the therapy of severe congestive heart failure--long-term effects and lack of tolerance.
Twenty patients with refractory heart failure NYHA class IV were randomly assigned to infusion therapy with 9.25 micrograms/kg/min dobutamine over 24 hours or placebo. Eight infusions over a 4-week period were performed in the hospital; between infusions breaks of 3 days were scheduled. A dose titration was performed before study during which dobutamine was infused at 2.5 micrograms/kg/min and increased by 2.5 micrograms/kg/min steps every 15 minutes up to a maximum dosage of 10 micrograms/kg/min. After dobutamine, exercise duration on the treadmill stress test increased from 177 +/- 110 seconds to 251 +/- 120 seconds (p less than 0.05). The heart-rate response to exercise increased (91 +/- 20 to 116 +/- 26 beats/min at baseline, 88 +/- 17 to 132 +/- 26 beats/min after therapy). Body weight decreased from 70.9 +/- 15.5 to 68.9 +/- 14.2 kg (p less than 0.03). On placebo, no significant changes were evident. Systolic time intervals and hemodynamic parameters showed only minor and not significant changes in both groups. No excess mortality emerged during intermittent dobutamine therapy. No clinical or hemodynamic signs of tolerance development were evident during control assessment 3 days after the last infusion. Intermittent therapy with dobutamine seems to be a promising concept in the management of refractory severe heart failure.