Pediatric research
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Randomized Controlled Trial Clinical Trial
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 xanthine oxidase pathway in neonates with severe, progressive hypoxemia during rescue and reperfusion with extracorporeal membrane oxygenation (ECMO) was examined. Twenty-five term infants meeting ECMO criteria were randomized in a double-blinded, placebo-controlled trial. Fourteen did not receive allopurinol, whereas 11 were treated with 10 mg/kg after meeting criteria and before cannulation, in addition to a 20-mg/kg priming dose to the ECMO circuit. ⋯ No allopurinol toxicity 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 cannulation for and during ECMO significantly inhibits purine degradation and uric acid production, and may reduce the production of oxygen free radicals during reoxygenation and reperfusion of hypoxic neonates recovered on bypass.
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The purpose of this study was to determine whether mild hypothermia after a moderate hypoxic-ischemic insult reduces the extent of brain damage. Hypoxia was achieved in newborn piglets (n = 24; age, 14-72 h) by abrupt reduction of the inspired oxygen concentration (FiO2) to the maximum concentration (approximately 6%) giving low amplitude (< 7.0 microV) EEG. FiO2 was temporarily increased if heart rate, blood pressure, or end expiratory partial pressure of alveolar CO2 (PAco2) were markedly reduced. ⋯ It was concluded that there was no general beneficial effect of postinsult hypothermia. However, when controlling for the duration of the insult and occurrence of seizures, hypothermia reduced the severity of brain damage. This indicates a significant neuroprotective effect of 3 h of mild hypothermia on moderate, but not severe, hypoxic-ischemic insults.