Dobutamine Tachyphylaxis
Yes, dobutamine infusion exhibits tachyphylaxis, with tolerance developing after 24-48 hours of continuous infusion, resulting in partial loss of hemodynamic effects. 1
Mechanism and Timeline of Tolerance
Prolonged dobutamine infusion beyond 24-48 hours is associated with tolerance and partial loss of hemodynamic effects, requiring either dose escalation or alternative strategies. 1, 2
The FDA label confirms that most clinical experience with dobutamine is short-term (not more than several hours), and in limited patients studied for 24-72 hours, cardiac output returned toward baseline values in some patients while remaining elevated in others. 3
Drug tolerance has been documented in clinical practice during outpatient continuous infusion therapy, though the exact mechanism remains incompletely understood. 4
Clinical Implications
Dobutamine should be withdrawn as soon as adequate organ perfusion is restored and/or congestion is reduced to minimize the development of tolerance and avoid complications. 2
When tachyphylaxis develops, consider switching to phosphodiesterase inhibitors (milrinone or enoximone), which work distal to beta-adrenergic receptors and may maintain efficacy when dobutamine loses effectiveness. 1, 2
The combination of phosphodiesterase inhibitors and dobutamine produces additive inotropic effects greater than either drug alone, which may be useful when tolerance develops. 1
Weaning Strategy to Manage Tolerance
Gradual tapering is essential when discontinuing dobutamine: decrease dosage by steps of 2 μg/kg/min every other day while optimizing oral vasodilator therapy (hydralazine and/or ACE-inhibitors). 1, 2, 5
Weaning may be difficult due to recurrence of hypotension, congestion, or renal insufficiency, and it may be necessary to tolerate some degree of renal insufficiency or hypotension during this phase. 1
Evidence Quality Considerations
The 1977 Circulation study by Leier et al. found no tachyphylaxis during 72-hour infusions at 10-15 μg/kg/min, with sustained improvements in contractile performance throughout the infusion period. 6
However, the European Society of Cardiology guidelines (2005) clearly state that prolonged infusion is associated with tolerance, representing the consensus expert opinion that supersedes older individual studies. 1
Clinical experience with outpatient dobutamine therapy has documented instances of drug tolerance requiring therapy adjustments or discontinuation. 4, 7