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.

Unilateral pediatric "do not attempt resuscitation" orders: the pros, the cons, and a proposed approach.

A unilateral do not attempt resuscitation (DNAR) order is written by a physician without permission or assent from the patient or the patient's surrogate decision-maker. Potential justifications for the use of DNAR orders in pediatrics include the belief that attempted resuscitation offers no benefit to the patient or that the burdens would far outweigh the potential benefits. Another consideration is the patient's right to mercy, not to be made to undergo potentially painful interventions very unlikely to benefit the patient, and the physician's parallel obligation not to perform such interventions. Unilateral DNAR orders might be motivated in part by the moral distress caregivers sometimes experience when feeling forced by parents to participate in interventions that they believe are useless or cruel. Furthermore, some physicians believe that making these decisions without parental approval could spare parents needless additional emotional pain or a sense of guilt from making such a decision, particularly when imminent death is unavoidable. There are, however, several risks inherent in unilateral DNAR orders, such as overestimating one's ability to prognosticate or giving undue weight to the physician's values over those of parents, particularly with regard to predicted disability and quality of life. The law on the question of unilateral DNAR varies among states, and readers are encouraged to learn the law where they practice. Arguments in favor of, and opposed to, the use of unilateral DNAR orders are presented. In some settings, particularly when death is imminent regardless of whether resuscitation is attempted, unilateral DNAR orders should be viewed as an ethically permissible approach.

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.

Effects of hormones on fetal lung development.

Endogenous hormones, such as glucocorticoids, play a major role in the development of the fetal lung. Considerable effort has been devoted to defining the underlying physiology and the clinical effects of administration of antenatal glucocorticoids to women who are at risk of premature delivery. Antenatal glucocorticoids have significant therapeutic benefits to the neonate with respect to the respiratory distress syndrome, intraventricular hemorrhage, and mortality. Current controversies relate to the choice of glucocorticoid, optimal dosing regime, number of courses of therapy that should be administered, and, most importantly, potential toxicities.

Rest-activity patterns of premature infants are regulated by cycled lighting.

OBJECTIVES: Many hospitalized premature infants are exposed to continuous dim lighting rather than to cycled lighting. However, we do not know whether dim lighting or low-intensity cycled lighting is more conducive to the development of rest-activity patterns that are in phase with the solar light-dark cycle. Thus, we examined the effects of nursery lighting conditions on the development of activity patterns in premature infants. METHODS: Premature infants who were born at <32 weeks' postmenstrual age and were medically stable in neonatal intensive care unit rooms were randomly assigned between 32 and 34 weeks' postmenstrual age to either continuous dim lighting (<25 lux; duration 24 days; control group; n = 29) or cycled lighting (239 +/- 29 lux, 7:00 AM to 7:00 PM; <25 lux, 7:00 PM to 7:00 AM; duration: 25 days; experimental group; n = 33). Activity was continuously monitored from enrollment until approximately 1 month after discharge from the hospital. Weight and head circumference were also assessed up to 6 months after discharge from the hospital. RESULTS: Over the first 10 days at home, distinct day-night differences in activity were not seen in control subjects (D day-night: N 1.07 +/- 0.02), but experimental group infants were more active during the day than at night (day-night: 1.25 +/- 0.03). It was not until 21 to 30 days after discharge that day-night activity ratios in control infants matched those seen in experimental group infants shortly after discharge, yet even at this age, experimental group infants (day-night: 2.13 +/- 0.19) were considerably more active during the day than at night as compared with control subjects (day-night: 1.43 +/- 0.09). CONCLUSION: Exposure of premature infants to low-intensity cycled lighting in the hospital nursery induces distinct patterns of rest-activity that are apparent within 1 week after discharge. In comparison, the appearance of distinct patterns of rest and activity are delayed in infants who are exposed to continuous dim lighting in the hospital. These observations show that day-night rhythms in activity patterns can be detected shortly after discharge to home in premature infants and that the circadian clock of developing infants is entrained by cycled lighting.