Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease

Background Nitric oxide (NO) is a prevalent molecule in the human body responsible for many physiologic activities including pulmonary vasodilation. An exogenous, inhaled form (iNO) exists that mimics this action without directly affecting systemic blood pressure. This therapy has been implemented in the treatment of pulmonary hypertension. This review examines the efficacy of iNO in the postoperative management of infants and children with congenital heart disease. Objectives To compare the effects of postoperative iNO versus placebo and/or conventional management on infants and children with congenital heart disease. The primary outcome was mortality, while secondary outcomes included length of hospital stay, assessment of neurodevelopmental disability, number of pulmonary hypertensive crises (PHTC), changes in haemodynamics including mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and heart rate (HR), changes in oxygenation measured as the ratio PaO(2): FiO(2), and measurement of maximum methaemoglobin level as a marker of toxicity. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2004), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We included abstracts and all languages. Selection criteria We included randomized and quasi-randomized controlled trials comparing iNO with placebo and conventional management, or both. Trials included only children with congenital heart disease requiring surgery and complicated by pulmonary hypertension. Data collection and analysis Data were collected on mortality, number of PHTC, changes in MPAP, MAP, HR, and PaO(2): FiO(2), and maximum methaemoglobin level, while data on long-term mortality, neurodevelopmental disability, and length of hospital stay were unavailable. We performed subgroup analysis by age and method of control. We performed sensitivity analysis using studies of highest methodologic quality. Main results We included four randomized trials. We observed no differences between groups with respect to mortality (P = 0.50), PHTC (P = 0.79), change in MPAP (P = 0.16), MAP (P = 0.40), HR (P = 1.00), or PaO2: FiO(2) (P = 0.46). There was a significant reduction in MPAP in the subgroup of patients from birth to three months (P = 0.005), although this finding was based on a small number of patients (N = 23). Authors' conclusions We observed no differences with the use of iNO as compared with control in the majority of outcomes reviewed. No data were available for analysis with respect to several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions because of concerns regarding methodologic quality, bias, sample size, and heterogeneity.