To inhale or to nebulize: treating the pulmonary vascular bed post-operatively in children with congenital heart disease.

Article p. 387 Controlling the pulmonary vascular bed is key to the early management of infants with congenital heart disease (CHD) who have potential for excessive pulmonary blood flow or obstruction to blood egress from the lungs. Timing of surgical management has evolved to ensure that the hemodynamic consequences of excessive pulmonary blood flow or pulmonary venous hypertension do not translate into irreversible elevation of pulmonary vascular resistance through remodeling of the pulmonary vascular bed, characterized by smooth muscle cell hypertrophy, pulmonary vasoconstriction and impaired endothelium-dependent pulmonary vasodi-lation. However, even with appropriately timed surgery, the pulmonary vascular bed remains reac-tive to cardiopulmonary bypass, which precipitates activation of a systemic inflammatory response with associated endothelial cell injury and inhibition of nitric oxide (NO) production and increase in endo-thelin levels [1]. The post-operative response may vary from clinically irrelevant elevation in right ventricular pressures to pulmonary hypertensive (PH) crises characterized by abrupt pulmonary vas-oconstriction leading to hypotension, hypoxia and associated with increased mortality [2]. High-risk pre-operative anatomic subtypes as well as preventative post-operative strategies for those at risk have been defined [2], and as a consequence the incidence of PH crises have declined significantly from over 30% in the 1980's to less than 1% in contemporary series [3], although this may vary depending on the definitions and treatment protocols used. Mortality, however associated with severe post-operative PH remains high at approximately 10% [3]. Inhaled NO (iNO), mediates selective pulmonary vasodilation by stimulating production of cGMP and both retrospective [4], and randomized trials [5] have demonstrated fewer post-operative pulmonary hypertensive crises and significant decreases in mortality, although these results have not been substantiated by a systematic review [6]. Nearly all studies however have demonstrated efficacy in reducing elevated pulmonary artery pressures in the post-operative infant undergoing surgery for CHD and consequently iNO has become the standard therapy for post-operative PH in this setting. Timing of introduction of iNO may vary between institutions with some employing an early post-operative " prophylactic " approach in those at risk and others reserving iNO for those with proven severe post-operative PH. Concerns have been raised however regarding potential for oxidation of hemoglobin to methemoglobin by iNO. This may lead to reduced oxygen carrying capacity of hemo-globin as methemoglobin in unable to reversibly bind oxygen and levels over 10% in infants have been associated with cyanosis. Rebound PH has also been described with rapid weaning due to a …