Pharmacology Review

Abstract

Listen

Translate article

After completing this article, readers should be able to: 1. Describe the primary cardiovascular effects of dobutamine in neonates. 2. Delineate the monitoring that is required in neonates to whom dobutamine is administered. Dobutamine was introduced for the management of neonatal cardiovascular compromise 2 decades ago in an attempt to provide an alternative to dopamine and improve outcomes in preterm and term neonates presenting with hypotension. However, as with dopamine, dobutamine was introduced in neonatal intensive care without appropriately designed clinical trials. Furthermore, most of the randomized studies have investigated the effectiveness of the agent in treating hypotension; organ blood flow changes and tissue perfusion have become the primary outcome measures only in more recent studies. Finally, because there is virtually no information from prospective, randomized trials on the impact of treating neonatal hypotension on mortality and neurodevelopmental outcome, evidence that use of dobutamine or the other sympathomimetic amines (dopamine, epinephrine, norepinephrine) improves neonatal mortality or morbidity is only suggestive and indirect. Dobutamine, an analog of isoproterenol, is a synthetic sympathomimetic amine originally developed for the treatment of congestive heart failure. Unlike dopamine, dobutamine is a relatively cardioselective agent, with significant cardiac alpha1- and beta1/beta2-adrenoreceptor-mediated direct inotropic effects and limited chronotropic actions. Because dobutamine contains an asymmetric carbon atom, there are two enantiomers of the drug. The available preparation is a 1:1 racemic mixture of the (−)- and (+)-enantiomers. However, the adrenoreceptor affinity of the two optical isomers differs substantially. The (−)-dobutamine is a highly selective alpha1-adrenoreceptor agonist, and the (+)-dobutamine exerts a potent and selective beta1- and beta2-adrenoreceptor stimulatory effect. In addition, (+)-3-O-methyldobutamine, the (+) optical isomer of the major dobutamine metabolite, is a relatively potent and highly selective alpha1-adrenoreceptor blocker. Thus, the interaction of the two …