PURINE METABOLISM AND INHIBITION OF XANTHINE-OXIDASE IN SEVERELY HYPOXIC NEONATES GOING ONTO EXTRACORPOREAL MEMBRANE-OXYGENATION

The effect of allopurinol to inhibit purine metabolism via the xanthin e oxidase pathway in neonates with severe, progressive hypoxemia durin g rescue and reperfusion with extracorporeal membrane oxygenation (ECM O) was examined. Twenty-five term infants meeting ECMO criteria were r andomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after m eeting criteria and before cannulation, in addition to a 20-mg/kg prim ing dose to the ECMO circuit. Infant plasma samples before cannulation , and at 15, 30, 60, and 90 min, and 3, 6, 9, and 12 h on bypass were analyzed (HPLC) for allopurinol, oxypurinol, hypoxanthine, xanthine, a nd uric acid concentrations. Urine samples were similarly evaluated fo r purine excretion. Hypoxanthine concentrations in isolated blood-prim ed ECMO circuits were separately measured. Hypoxanthine, xanthine, and uric acid levels were similar in both groups before ECMO. Hypoxanthin e was higher in allopurinol-treated infants during the time of bypass studied (p = 0.022). Xanthine was also elevated (p < 0.001), and uric acid was decreased (p = 0.005) in infants receiving allopurinol. Simil arly, urinary elimination of xanthine increased (p < 0.001), and of ur ic acid decreased (p = 0.04) in treated infants. No allopurinol toxici ty was observed. Hypoxanthine concentrations were significantly higher in isolated ECMO circuits and increased over time during bypass (p < 0.001). This study demonstrates that allopurinol given before cannulat ion for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free rad icals during reoxygenation and reperfusion of hypoxic neonates recover ed on bypass.