Objective Inhaled nitric oxide (iNO) has revolutionized the treatment of hypoxemic respiratory failure caused by persistent pulmonary hypertension of newborn (PPHN). However, analysis of large randomized trials proving the efficacy of iNO has shown that it is effective in approximately 60% of the infants. The reason for this variable response is unknown. Prostanoids, thromboxane and prostacyclin have been implicated in the pathophysiology of PPHN. But their role in failure of iNO therapy has not been studied. This study was designed to test the hypothesis that newborns with PPHN not responding to iNO have higher blood levels of thromboxane and prostacyclin compared to those who do not respond to iNO. We also examined the ratio of thromboxane (vasoconstrictor) to prostacyclin (vasodilator) in these groups.
Methods Infants > 34 weeks gestation with PPHN on mechanical ventilation and with hypoxemic respiratory failure were enrolled. Blood samples for thromboxane and prostacyclin were obtained just prior to and 4 hours after starting iNO. Based on the response to iNO, infants were divided in two groups: responders (increase in PaO2 by > 20% and decrease in oxygenation index by 20%) or nonresponders. Serum levels of thromboxane and prostacyclin were measured using commercially available ELISA assays.
Results We have enrolled 9 patients so far; 5 of them were responders and 4 were nonresponders. Mean gestational age in responders and nonresponders was 38 weeks and 37 weeks respectively. Mean birth weight in responders and nonresponders was 3.8 kg and 3.3 kg respectively. Analysis of the samples shows that thromboxane levels were higher in nonresponders as compared to responders (responders: mean: 78.74 pg/mL SD ± 50.17 pg/mL, nonresponders: mean 4,870.94 pg/mL, SD ± 7451 pg/mL). In addition, we found that thromboxane to prostacyclin ratios were lower in responders in comparison to nonresponders (responders: mean 0.34, SD ± 0.18, nonresponders: mean 93.97, SD ± 137.61).
Conclusion This preliminary study suggests that thromboxane may play a role in determining the response to iNO therapy in hypoxemic respiratory failure. Furthermore, the balance between vasoconstrictors (like thromboxane) and vasodilators (such as prostacyclin) may also be involved.
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