Endocrine effects of dopamine and dobutamine in very low birthweight infants

About 20% of very low birthweight (VLBW) infants in neonatal intensive care units become hypotensive within 24 h of admission. This condition is a major risk factor for periventricular-intraventricular haemorrhage and poor long-term neurodevelopmental outcome, probably because of the low cerebral perfusion pressure and blood flow. Therefore hypotension is usually treated with volume expansion and inotropic agents, such as dopamine and dobutamine. It has been suggested that dopamine therapy is more successful than dobutamine.

However, dopamine suppresses anterior pituitary function in VLBW infants and treatment is associated with some side effects as hypothyroxinaemia of prematurity and low levels of prolactin (PRL). In adults, dobutamine has been shown to induce a small but important decrease in levels of thyroid stimulating hormone (TSH). It is currently not known whether dobutamine has similar effects in VLBW infants. Such hormonal suppression would be of great relevance because decreased thyroid function and hypoprolactinaemia are associated with worse neurodevelopmental and clinical outcomes, respectively.

On these basis, an Italian group conducted an open-label, randomised prospective trial to compare the endocrine effects of dopamine and dobutamine in hypotensive VLBW infants in a tertiary care unit. In total, 35 hypotensive VLBW infants who did not respond to volume loading, were assigned to receive dopamine or dobutamine, starting from 4 µg/kg/min to a maximum dose of 20 µg/kg/min. Haemodynamic variables and serum levels of TSH, total thyroxine (T4), PRL and growth hormone were assessed during the first 72 h of treatment and the first 72 h after stopping treatment.

Results show that mean drug doses and maximum infusion required to normalise blood pressure were significantly higher in the dobutamine than in the dopamine group (p<0.01). Both drugs determined an increase in blood pressure; however, dopamine was associated to better results. Suppression of TSH, T4 and PRL was observed in dopamine-treated newborns from 12 h of treatment onwards, whereas levels of growth hormone reduced significantly only at 12 h and 36 h of treatment (p<0.01). TSH, T4 and PRL rebound was observed from the first day onwards after stopping dopamine. On the other hand, dobutamine administration did not alter the profile of any of the hormones and no rebound was observed after stopping treatment.

These data may confirm that dopamine and dobutamine are both effective for treating volume loading refractory hypotension in VLBW preterm infants. In contrast with dobutamine, dopamine significantly reduces the levels of TSH, T4 and PRL. On the basis of the rapid reversal that occurred after dopamine was stopped, it is possible to speculate that the iatrogenic pituitary suppression that is induced for a short time with dopamine infusion will probably not cause long-term injury. However, this may be further investigated with long-term clinical studies. Meanwhile, caution is required mainly if dopamine is administered for a long time.

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