Dopamine versus no treatment to prevent renal dysfunction in indomethacin-treated preterm newborn infants

Indomethacin therapy for closure of patent ductus arteriosus frequently causes oliguria, and occasionally more serious renal dysfunction. Low dose dopamine has been suggested as a means for preventing this side effect.

To determine whether dopamine therapy may prevent indomethacin-mediated deterioration in renal function in the preterm newborn infant without serious adverse effects.

To assess the effects of dopamine on the above variables in two subgroups: (1) patients given indomethacin as prophylaxis of intraventricular hemorrhage, and (2) patients given indomethacin as treatment of patent ductus arteriosus

Standard methods of the Cochrane Neonatal Review Group (CNRG) were used. We searched MEDLINE (1966-2001) using PubMed as the search engine, EMBASE (1974-2001) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (Issue 3, 2001). In addition we contacted the principal investigators if necessary to ascertain the required information.

Randomized or quasi-randomized studies of the effects of dopamine on urine output, glomerular filtration rate, fluid balance or incidence of renal failure, in preterm newborn infants receiving indomethacin. The comparison group should have received no dopamine.

We used the standard methods of the Cochrane Collaboration and those of the CNRG. The primary outcomes of interest were: mortality before discharge; intraventricular hemorrhage, grade three or four; cystic periventricular leukomalacia; renal failure (either oliguria, defined as a urine output less than 1 ml/kg/hour or an elevation in creatinine by more than 40 micromoles/L); failure to close the ductus arteriosus; need for surgical PDA ligation. For categorical outcomes, we calculated typical estimates for relative risk and risk difference. For continuous outcomes the weighted mean difference (WMD) was calculated. Fixed effect models were assumed for meta-analysis.

Three studies were found (total number randomized patients, 75) which fulfilled the entry criteria for this review. All were single center trials which enrolled NICU patients receiving indomethacin for symptomatic patent ductus arteriosus. There are no (or only partial) results for effects of dopamine on several of the primary outcomes, including death before discharge, serious intraventricular hemorrhage, cystic periventricular leukomalacia, or renal failure. There has been inadequate investigation of the effects of dopamine on cerebral perfusion or cardiac output, or GI complications, or endocrine toxicity. Dopamine improved urine output [WMD 0.68 ml/kg/hour (95% CI 0.22, 1.44)], but there was no evidence of effect on serum creatinine (WMD 2.04 micromoles/liter, CI -17.90, 21.97) or the incidence of oliguria (urine output < 1 ml/kg/hour) (RR 0.73, CI 0.35, 1.54). There was no evidence of effect of dopamine on the frequency of failure to close the ductus arteriosus (RR 1.11, CI 0.56, 2.19).

There is no evidence from randomized trials to support the use of dopamine to prevent renal dysfunction in indomethacin-treated preterm infants.