Inhaled nitric oxide only leads to a transient improvement of oxygenation in patients with acute hypoxemic respiratory failure

Acute hypoxemic respiratory failure (AHRF) is a key feature of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Flori et al. have reported that the initial severity of hypoxemia has predictive value for identifying children at high risk of prolonged mechanical ventilation and death. Management of AHRF is focused on supporting the recovery from hypoxemic respiratory failure, while applying lung protective modes of ventilation to avoid further exacerbation of lung injury. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator with a very short half-life used to improve ventilation–perfusion mismatch in ventilated areas of the lung. By increasing perfusion to ventilated areas of the lung, there is an improvement in alveolar deadspace and thus increased oxygenation. This may also result in improvement of pulmonary hypertension caused by local vasoconstriction. As iNO has significant effects in well-recruited lung regions, an aggressive lungrecruitment strategy such as HFOV may maximize the beneficial effects of iNO as compared to conventional mechanical ventilation (CMV). Recent reviews have suggested that iNO is widely used in critical care settings, justifying further investigation into the potential benefits of this therapy. The use of iNO has not shown to improve mortality in patients with ARDS. A meta-analysis in 2007 by Adhikari et al. showed an initial improvement in oxygenation with iNO, but the improvement was transient, there was no change in overall mortality and there was concern for potential adverse effects and high cost of therapy. A recent Cochrane Review of data from 14 trials involving both adults and children from 1997 to 2004 showed no statistically significant effect of iNO on mortality. The authors found a statistically significant but transient improvement in oxygenation in the first 24 hr, expressed as the P/Fratio (partial pressure of oxygen to fraction of inspired oxygen) and the oxygenation index (OI). An aggressive lung recruitment strategy that is also lung protective may enhance iNO delivery while maximizing lung protection. HFOV is a modality that may have potential benefit in AHRF. HFOV has been shown to result in initial improvement in oxygenation in pediatric patients with ARDS. However, most studies have demonstrated similar outcomes to CMV and have failed to show a reduction of mortality when comparing HFOV to CMV in the context of AHRF. In contrast to those publications, a recently published meta-analysis of eight randomized control trials in both adults and children from 1994 to 2007 has suggested that HFOV may decrease mortality and has a lower incidence of treatment failure. The combined treatment of HFOV plus iNO improved oxygenation as compared to treatment with CMV alone or CMV plus iNO in a retrospective analysis by Dobyns et al. These effects were observed acutely and at 72 hr. This data indicates that the acute and sustained benefits of iNO therapy are, at least in part, dependent on the mode of ventilation. In this issue of Pediatric Pulmonology, Fioretto et al. compare the use of 5 ppm (parts per million) of iNO combined with either conventional ventilation or HFOV in children with AHRF. A total of 28 patients were studied, 14 in each group, and the general characteristics of each group were well matched with pneumonia as the primary cause of respiratory failure in all