The use of dopamine for the prevention of the renal side effects of indomethacin in premature infants with patent ductus arteriosus. Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study. Effect of dopamine on failure of indomethacin to close the patent ductus arteriosus.
To determine if dopamine would prevent the renal side effects of indomethacin, fifteen preterm infants were randomized into two groups: seven received indomethacin alone, and eight received indomethacin together with low dose dopamine infusion. Infants who received indomethacin together with dopamine had significantly higher UV (p less than 0.005), CNa (p less than 0.005), Cosm (p less than 0.005) and FENA (p less than 0.005) than those of infants who received indomethacin alone. There was, however, no significant difference in Ccr and FNa between the groups. These data indicate that dopamine overcomes indomethacins renal side effects of tubular origin, but it cannot prevent the renal vasoconstrictive action of vasoconstrictor hormones following the inhibition of prostaglandin synthesis by indomethacin. Considering that RBF and GFR turn to normal approximately 12 hours after the last dose of indomethacin, and that with the use of dopamine systemic blood pressure and peripheral circulation can also be normalized and to some extent myocardiac contractility improved, low doses of dopamine can be used instead of furosemide in the sick preterm infant with PDA when indomethacin therapy is indicated. Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy.
                33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study.
                15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose.
                Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups.
                The additional use of dopamine does not reduce the renal side effects of indomethacin. To test the hypotheses that administering dopamine before and concurrently with indomethacin therapy would (1) increase successful ductal closure rate, (2) act by maintaining a diuresis, and (3) prevent oliguria or high serum creatinine concentrations, we conducted a randomized, controlled trial in infants whose gestational age was <36 weeks and who had hemodynamically significant ductus arteriosus. Thirty-six infants were selected to receive a continuous infusion of either placebo or dopamine at either a low dosage of 2 micrograms/kg per minute or a higher dosage of 5 micrograms/kg per minute, beginning 6 hours before the use of indomethacin and continuing until 12 hours after the third dose of indomethacin. A total of 12 patients were selected to receive placebo, 14 were selected to receive "low dopamine," and 10 were selected to receive "high dopamine." The three groups were similar in their initial characteristics. Serum creatinine concentrations, urine output, and fractional excretion of sodium were not different in the three groups after indomethacin treatment. Two patients receiving placebo required a second course of indomethacin compared with four patients in the low-dopamine group and one in the high-dopamine group. The proportion of failures of medical treatment was not statistically different among the three groups. We conclude that concomitant dopamine therapy neither decreases the failure rate in indomethacin-treated infants nor reduces the magnitude of the indomethacin-induced oliguria.
There is no evidence from randomized trials to support the use of dopamine to prevent renal dysfunction in indomethacin-treated preterm infants.