Diuretic therapy for newborn infants with posthemorrhagic ventricular dilatation: Cochrane systematic review


Assessed as up to date: 2007/04/22


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.


To determine the effect of acetazolamide and furosemide on shunt dependence and other complications in infants developing post-hemorrhagic ventricular dilatation.

Search strategy

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.


Whitelaw Andrew, Brion Luc P, Kennedy Colin R, Odd David


Diuretic therapy for newborn infants with posthemorrhagic ventricular dilatation

Bleeding (hemorrhage) into the fluid-producing cavities (ventricles) of the brain is a serious complication of premature birth. Large hemorrhages may result in fluid building up under pressure, progressively enlarging the brain and head. Current treatment approaches, including the insertion of a valve drainage system (shunt) are fraught with problems. Acetazolamide and furosemide, two drugs with diuretic action, reduce the production of fluid in the ventricles of the brain and have been proposed as safe treatments to treat dilatation of the ventricles after intraventricular hemorrhage in newborn infants. When compared with standard treatment, diuretic therapy was found not to reduce the need for shunt surgery. Diuretic drugs are neither safe nor effective in treating ventricular dilatation in infants with intraventricular hemorrhage.

Reviewer's Conclusions

Implications for practice

Acetazolamide and furosemide therapy is neither effective (no reduction in the risk for V-P shunt) nor safe (risk for nephrocalcinosis and biochemical anomalies and borderline increased risk for motor developmental anomalies at one year) in infants with post-hemorrhagic ventricular dilatation. Thus acetazolamide and furosemide cannot be recommended for these infants.

Implications for research

In view of the lack of efficacy in reducing need for V-P shunt and in view of evidence for increased risk for motor developmental anomalies and nephrocalcinosis in the drug treated group in a large trial, it seems unlikely that another large trial of this therapy would receive funding, ethical approval or informed parental consent. Although the proportion of premature infants suffering IVH has declined, post-hemorrhagic hydrocephalus is still a serious complication for which we do not have a satisfactory treatment. Research must focus more on the mechanisms of hydrocephalus and radically new therapeutic approaches will have to be considered. These new treatments will first need to be evaluated in animal models of post-hemorrhagic hydrocephalus.

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