Diuretic therapy for newborn infants with posthemorrhagic ventricular dilatation

Background: Intraventricular hemorrhage remains a serious complication of premature birth and post-hemorrhagic hydrocephalus still has no satisfactory treatment. Acetazolamide and furosemide, which both reduce the production of cerebrospinal fluid, have been suggested as non-invasive therapies to reduce hydrocephalus and the need for ventriculo-peritoneal (V-P) shunting. Objectives: To determine the effect of acetazolamide and furosemide on shunt dependence and other complications in infants developing post-hemorrhagic ventricular dilatation. Search methods: Searches were performed of electronic databases (MEDLINE from 1966, EMBASE from 1974 and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library). PubMed was searched on April 18, 2007 and Issue 2, 2007 of The Cochrane Library was searched. Selection criteria: Randomised, or quasi-randomised trials, of acetazolamide and/or furosemide compared with standard therapy in infants with IVH or post-hemorrhagic ventricular dilatation. Data collection and analysis: Data were extracted independently by each author and were analysed by the standard methods of the Cochrane Collaboration using relative risk (RR) and risk difference (RD), a fixed effect model and sensitivity analyses where appropriate. Main results: There were two eligible trials: one randomized 16 infants and the other 177 infants. Neither study showed a decreased risk for V-P shunt or for V-P shunt or death associated with acetazolamide and furosemide therapy. The larger trial showed that acetazolamide and furosemide treatment resulted in a borderline increase in the risk for motor impairment at one year (RR 1.27, 95% CI 1.02 - 1.58; RD 0.16, 95% CI 0.02 - 0.31), but did not significantly affect the risk for the combined outcome of delay, disability or motor impairment among survivors, or the risk of the combined outcome of death, delay, disability or impairment at one year. The larger trial showed that diuretic treatment increased the risk for nephrocalcinosis (RR 5.31, 95% CI 1.90 - 14.84; RD 0.19, 95% CI 0.09 - 0.29); meta-analysis confirmed this result. Authors' conclusions: Acetazolamide and furosemide therapy is neither effective nor safe in treating post-hemorrhagic ventricular dilatation. Acetazolamide and furosemide cannot be recommended as therapy for post hemorrhagic hydrocephalus.