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 humans that is responsible for many physiologic activities including pulmonary vasodilation. An exogenous, inhaled form (iNO) exists that mimics this action without 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 (CHD). The original review was published in 2005, updated in 2008 and again in 2014. OBJECTIVES: To compare the effects of postoperative administration of iNO versus placebo or conventional management, or both, on infants and children with CHD and pulmonary hypertension. The primary outcome was mortality. Secondary outcomes included length of hospital stay; neurodevelopmental disability; number of pulmonary hypertensive crises (PHTC); changes in mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and heart rate (HR); changes in oxygenation measured as the ratio of arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2); and measurement of maximum methaemoglobin level as a marker of toxicity. SEARCH METHODS: In this updated version we extended the CENTRAL search to 2013, Issue 12 of The Cochrane Library, and MEDLINE and EMBASE through to 1 December 2013. The original search was performed in July 2004 and again in November 2007. We included abstracts and all languages. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing iNO with placebo or conventional management, or both. Trials included only children with CHD requiring surgery complicated by pulmonary hypertension. DATA COLLECTION AND ANALYSIS: Two authors extracted data. Data were collected on mortality; number of PHTC; changes in MPAP, MAP, HR, and PaO2:FiO2; and maximum methaemoglobin level. Data on long-term mortality, neurodevelopmental disability, and length of hospital stay were unavailable. We performed subgroup analysis by method of control (placebo or conventional management). MAIN RESULTS: We reran the searches to December 2013 and identified three new studies. These three studies did not fulfil our inclusion criteria. Therefore, no new studies were included in this updated review. In total four randomized trials involving 210 participants were included in this review. We observed no differences in mortality (OR 1.67, 95% CI 0.38 to 7.30; P = 0.50); PHTC (OR 0.80, 95% CI 0.15 to 4.18; P = 0.79); changes in MPAP (treatment effect -2.94 mm Hg, 95% CI -9.28 to 3.40; P = 0.36), MAP (treatment effect -3.55 mm Hg, 95% CI -11.86 to 4.76; P = 0.40), HR (treatment effect 0.02 bpm, 95% CI -8.13 to 8.18; P = 1.00), or PaO2:FiO2 (mean difference 17.18, 95% CI -28.21 to 62.57; P = 0.46). There was a significant increase in the methaemoglobin level (mean difference 0.30%, 95% CI 0.24 to 0.36; P < 0.00001) in patients treated with iNO, although levels did not reach toxicity levels. Data from long-term mortality, neurodevelopmental disability, and length of stay were not available. Two trials had a low risk of bias. Very low quality of the evidence was observed considering grading of the outcomes. AUTHORS' CONCLUSIONS: We observed no differences with the use of iNO in the outcomes reviewed. No data were available for several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions given concerns regarding methodologic quality, sample size, and heterogeneity.

Circulating stem cells in extremely preterm neonates.

AIM: To measure circulating CD34+ cell levels in premature neonates and to correlate the initial CD34+ counts with measures of pulmonary function and neonatal morbidity. METHODS: CD34+ cell counts were measured in the peripheral blood of preterm neonates (gestational ages 24-32 weeks) ventilated for respiratory disease at <48 h of life, and at the start of the 2nd, 3rd and 4th weeks of life. Data pertaining to neonatal demographics and short-term outcomes were collected. Pulmonary function tests were performed to coincide with CD34+ sampling. RESULTS: Thirty preterm neonates with median gestational age of 24 weeks and birth weight of 641 g were analysed. A mean of 99.4 CD34+ cells per microliter was observed in the 1st week of life with a decline to 54.4 cells per microliter by the 4th week. An inverse correlation between initial CD34+ count and gestational age (p=0.01) was observed. No significant correlations were observed with measures of pulmonary function or neonatal morbidities. CONCLUSIONS: Extremely premature neonates have remarkably high levels of CD34+ cells in their peripheral blood at birth. Umbilical cord blood from this population may potentially provide an abundant source of hematopoietic stem and progenitor cells for therapeutic purposes.