It should also be noted that the majority of respondents reported they did not know the oxygenation index level at which iNO should be initiated; those who did know reported that the appropriate level for iNO initiation is an oxygenation index of more than 25. Indeed, traditional practice has been to initiate iNO at an oxygenation index of 25 or more, based on criteria used in clinical studies of iNO that were conducted during the 1990s.27,28 However, later studies have shown that earlier initiation of iNO may be more beneficial for improvement in oxygenation and attenuating progression to severe hypoxic respiratory failure than later initiation, and patients with lower oxygenation index levels at iNO initiation may be more likely to have a complete response to iNO (Table 2).29,33–35 Given that premature infants are particularly susceptible to oxygen toxicity,36,37 and the known risks of toxicity associated with overreliance on the use of supplemental oxygen,5,38,39 consideration of early initiation of iNO (ie, before patients reach moderate to severe hypoxic respiratory failure) may help balance supplemental oxygen needs and improve patient outcomes.
To further deepen the understanding of the role of oxygen therapy and vasodilators in the treatment of PPHN, a more formal education process for the bedside clinician and NNPs can include discussions of the body's NO pathway, mechanism of action of iNO and its selective pulmonary vasodilation properties, and effects of reactive oxygen species on major organs. Use of iNO causes pulmonary vasodilation by the entrance of inspired air into the alveoli.42 The NO molecule is diffused into the vascular smooth muscle adjacent to the pulmonary arterioles, where it activates soluble guanylate cyclase.42 The vasodilatory effects of iNO are limited to the arterioles adjacent to the alveoli, where it penetrates and selectively dilates the pulmonary vasculature.42
In addition to echocardiographic findings, calculating the oxygenation index at the bedside is a quick, easy, and widely accepted tool (Oxygenation index = FIO2 × Mean arterial pressure × 100, divided by PaO2) to look at severity of the disease process (mild: 0-15; moderate: 15-25; severe: 25-40; very severe: >40).33 Diseases commonly associated with oxygen supplementation and oxidative stress are outlined in the study by Kayton et al.43
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