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. Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction? Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Furosemide prevents the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus. Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. Renal dose dopamine in open heart surgery. Does it protect renal tubular function? Response to dobutamine and dopamine in the hypotensive very preterm infant.
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. We aimed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction. The latter included older patients or those with pre-existing renal disease, elevated preoperative serum creatinine (Cr), poor ventricular function, hypertension, diabetes mellitus and unstable angina requiring intravenous therapy.
                Fifty patients undergoing cardiopulmonary bypass (CPB) who fulfilled the entry criteria were prospectively randomized into two groups: Group 1 received a 'renal-dose' (3 microg kg(-1) min(-1)) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2. The anaesthetic and CPB regimes were standardized. Urinary excretion of retinol binding protein (RBP) indexed to Cr, an accurate and sensitive marker of early renal tubular damage, was assessed daily for 6 days. Additional outcome measures included daily fluid balance, blood urea and serum Cr. Statistical comparisons were made using ANOVA and Mann-Whitney U-test.
                No significant difference was found between the groups in their age, gender, preoperative NYHA class, ejection fraction, baseline serum Cr and duration of CPB and aortic cross-clamping. Renal replacement therapy was not required in any instance. Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period. Dopamine-treated patients achieved more negative average fluid balance than those on placebo (5 vs. 229 ml, P<0.05).
                Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB. Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (< 1 ml/kg per h) during treatment (P = 0.017).
                Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment. To determine if furosemide would prevent the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus, 19 premature infants were randomized into two groups: nine received indomethacin alone, and ten received indomethacin followed immediately by furosemide. There was no significant difference between the groups in birth weight, gestational age, postnatal age, and in cardiopulmonary or renal status at the time of study. Infants who received indomethacin and furosemide had significantly higher urine output (P less than 0.05), higher FENa and FECl (P less than 0.01), and higher glomerular filtration rate (P less than 0.05) than those of infants who received indomethacin alone. Seven infants in each group responded to indomethacin therapy with disappearance of PDA murmur and improvement of cardiovascular status. The results of this study suggest that furosemide may prevent the renal side effects of indomethacin therapy and yet not affect the efficacy of indomethacin in the closure of a PDA. Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine (D) and dopamine-nitroprusside (DN) on renal function during cardiopulmonary bypass (CPB). No differences from the control group (C) were found in creatinine clearance, fractional sodium excretion, osmolarity and free-water clearance. Sodium output/intake ratio during CPB was higher in group D than in groups C and DN (P less than 0.05); water output/intake ratio was higher in group D than in group C (P less than 0.05). Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups, suggesting ischemic tubular cell damage. No patients showed acute postoperative renal failure or a worsening of their renal dysfunction. The data suggest an increased water and sodium excretion during CPB with a dopamine infusion, possibly resulting from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration. This prospective, randomized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting.
                Two groups of patients with normal preoperative renal function were randomly divided into a dopamine group (n=11), who received dopamine in a dose of 2 mg/kg x min, and a control group (n=11), who received no treatment. Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively. Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st, 3rd, and 7th postoperative days. Urinary excretion of b2-Microglobulin (b2-M), considered a sensitive means for diagnosing proximal tubular damage, was measured during the early (day 3) and late (day 7) postoperative period.
                There were no significant differences respect to the clearances of creatinine, osmotic, and free-water in the dopamine group compared with the control group (p>0.05). Urine microalbumin levels significantly increased on postoperative day 3 in both groups. During the early postoperative period, excretion of urine b2-M was significantly greater in the dopamine group than in the control group (p<0.05).
                Consequently, in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting, renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period. A randomised double blind study was designed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks' gestation. Neonates initially received dopamine or dobutamine 5 micrograms/kg/min. If mean arterial pressure (MAP) remained below 31 mm Hg, the infusion rate was increased in increments of 5 micrograms/kg/min. If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg, it was discontinued and the other drug was administered at the same infusion rate. Left ventricular output (LVO) was measured by pulsed Doppler echocardiography. Mean (SE) MAP increased significantly from 24.4 (1.0) to 32.0 (1.4) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 (1.2) to 37.7 (1.5) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min. The percentage LVO increase was +21 (7)% with dobutamine compared with -14 (8)% with dopamine. Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10, whereas dopamine succeeded in all 10 infants. Six switches from dobutamine to dopamine were thus performed, providing a rise in MAP (29.2 (0.5) to 41.2 (2.0) mm Hg) and drop in LVO (356 (40) to 263 (36) ml/kg/min). These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg; however dopamine does not increase LVO.
There is no evidence from randomized trials to support the use of dopamine to prevent renal dysfunction in indomethacin-treated preterm infants.