INTERNATIONAL RANDOMIZED CONTROLLED TRIAL OF ACETAZOLAMIDE AND FUROSEMIDE IN POSTHEMORRHAGIC VENTRICULAR DILATATION IN INFANCY

Background Furosemide and acetazolamide are widely used in the treatme nt of posthaemorrhagic ventricular dilatation (PHVD) in the hope of av oiding the need for surgical management, but this approach has not bee n evaluated in a controlled trial. This multicentre randomised control led trial tested the hypothesis that these drugs would reduce the rate of shunt placement and increase disability-free survival at 1 year of age. Methods Between 1992 and 1996, 177 infants aged less than 3 mont hs past term, and with ventricular width more than 4 mm above 97th cen tile after intraventricular haemorrhage, were randomly assigned standa rd therapy alone or standard therapy plus treatment with acetazolamide (100 mg/kg daily) and furosemide (1 mg/kg daily). A minimisation algo rithm ensured balance between groups with respect to both referral cen tre and the presence of a cerebral parenchymal lesion on cerebral ultr asonography at enrolment. The trial was stopped in September, 1996, be cause the data showed a clear advantage with standard therapy. Finding s We report outcomes for 151 infants whose expected date of delivery w as before the end of 1995, with complete information at 1 year for 129 infants. The median gestational age was 28 weeks, mean birthweight 12 99 g, and mean postnatal age at enrolment 25 days. 44% had a parenchym al lesion at randomisation. Death or shunt placement occurred in 49 of 75 infants allocated drugs plus standard therapy, compared with 35 of 76 allocated to standard therapy alone. The relative risk was 1.42 (9 5% CI 1.06-1.90; p=0.026), which is equivalent to one extra death or s hunt placement for every five infants allocated drug therapy. 84% (52/ 62) of infants assigned drug therapy had died or were disabled or impa ired at 1 year, compared with 60% (40/67) of those assigned standard t herapy (relative risk 1.40 [1.12-1.76]; p=0.012). Interpretation These preliminary results suggest that the use of acetazolamide and furosem ide in preterm infants with PHVD is associated with a higher rate of s hunt placement and increased neurological morbidity, and so cannot be recommended.