Effect of early targeted indomethacin on the ductus arteriosus and blood flow to the upper body and brain in the preterm infant.
OBJECTIVE
To determine if indomethacin given to preterm infants with a large ductus arteriosus (DA) in the first hours of life results in maintained or improved brain and upper body blood (superior vena cava (SVC)) flow.


METHODS
A randomised, double blind trial of indomethacin v placebo. Echocardiography was performed on 111 infants born at < 30 weeks gestation at 3 and/or 10 hours after birth. Infants were eligible if the DA diameter was > 1.6 mm. Infants were randomised to receive indomethacin 0.2 mg/kg or placebo. Crossover occurred if the DA was still > 1.6 mm. Echocardiography was performed one hour after each treatment.


RESULTS
Seventy (63%) infants had a DA > 1.6 mm, with 35 randomised to receive indomethacin and 35 to receive placebo. At one hour there was no difference in DA constriction (indomethacin -20% v placebo -15%), change in SVC flow (-1% v -9%), for right ventricular output (RVO). Two hours after indomethacin, 62 infants had uncontrolled observations, at which time significant ductal constriction had occurred. At this time, infants of > or = 27 weeks gestation had significantly greater increases in SVC flow and RVO than infants of < 27 weeks gestation. Infants with failed ductal constriction had significantly lower initial SVC flow and developed more late grade 3/4 peri/intraventricular haemorrhage (P/IVH). Initial SVC flow, but not ductal constriction, was a significant predictor of late grade 3/4 P/IVH in adjusted analysis.


CONCLUSIONS
Indomethacin had minimal effect on ductal constriction and blood flow at one hour compared with placebo. Failure of ductal constriction is associated with low SVC flow and subsequent late severe P/IVH.
Osborn
D A
DA
Department of Neonatal Medicine, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW, Australia. david.osborn@email.cs.nsw.gov.au
Evans
N
N
Kluckow
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy* / Q000503:physiopathology; D004452:Echocardiography / Q000379:methods; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin