Background Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure, Methods Infants born after a gestation of greater than or equal to 34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas, Results The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The nitric oxide group had significantly greater improvement in PaO2 (mean [+/-SD] increase, 58.2+/-85.2 mm Hg, vs. 9.7+/-51.7 mm Hg in the controls; P Conclusions Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality, in critically ill infants with hypoxic respiratory failure. (C) 1997, Massachusetts Medical Society.

Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure

Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: Dose response

Inhibition of pulmonary surfactant function by meconium

Ligation of the ductus arteriosus in utero produces pulmonary hypertension and vascular remodeling in fetal and newborn lambs. However, the mechanisms producing these vascular changes are not well defined. Because reactive oxygen species (ROS) have been implicated as mediators of smooth muscle cell proliferation, we hypothesized that increased formation of ROS may be involved in the pathophysiology of pulmonary hypertension after in utero ductal ligation. Using ethidium fluorescence, we demonstrated an increase in superoxide levels after 9 days of ductal ligation compared with control lungs (P<0.05) that was localized to the adventitia and smooth muscle cells of hypertensive vessels. SOD-1 and SOD-2 protein levels and activities in lung, vein, and artery of hypertensive lambs were unchanged relative to controls after 2 days of ductal ligation. However, after 9 days, superoxide dismutase (SOD) activity was significantly decreased in arteries from ligated lambs without associated changes in SOD protein expr...

Increased Superoxide Generation Is Associated With Pulmonary Hypertension in Fetal Lambs. A Role for NADPH Oxidase

The evidence from randomized controlled trials (RCTs) is widely regarded as supplying the ‘gold standard’ in medicine—we may sometimes have to settle for other forms of evidence, but this is always epistemically second-best. But how well justified is the epistemic claim about the superiority of RCTs? This paper adds to my earlier (predominantly negative) analyses of the claims produced in favour of the idea that randomization plays a uniquely privileged epistemic role, by closely inspecting three related arguments from leading contributors to the burgeoning field of probabilistic causality—Papineau, Cartwright and Pearl. It concludes that none of these further arguments supplies any practical reason for thinking of randomization as having unique epistemic power.1Introduction2Why the issue is of great practical importance—the ECMO case3Papineau on the ‘virtues of randomization’4Cartwright on causality and the ‘ideal’ randomized experiment5Pearl on randomization, nets and causes6Conclusion

Why There's No Cause to Randomize

Extracorporeal membrane oxygenation for respiratory and cardiac failure in infants and children.

A correlation of pulmonary hypoplasia, mean airway pressure, and survival in congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation*

Persistent Pulmonary Hypertension in the Neonate

Extracorporeal membrane oxygenation for newborn respiratory failure.

Posterolateral congenital diaphragmatic hernia (Bochdalek's hernia, CDH) that presents in the neonatal period is often manifest as life-threatening respiratory distress due to mechanical compression of the cardiopulmonary system by herniated viscera. Most patients can be supported through surgical reduction and repair with standard neonatal techniques. Postoperatively, many develop severe, refractory persistent pulmonary hypertension of the newborn (PPHN) after a variable period of adequate oxygenation. Despite aggressive ventilatory and pharmacologic maneuvers, a significant number of these infants develop fatal hypoxia and acidosis. At our institution, extracorporeal membrane oxygenation (ECMO) has been used as a therapy of last resort in 12 moribund infants with PPHN and respiratory failure after repair of CDH. There were 7 survivors. All long-term survivors [6] were totally weaned from ventilatory support; all met the criteria for nonsurvival as defined by Bohn et al. [2]. Eight patients (4 survivors) had no PaO2 greater than 100 torr postoperatively. ECMO can relieve the hypoxic and metabolic stimuli that aggravate pulmonary hypertension and provide cardiopulmonary support. It is the treatment of choice for infants who are deteriorating in the face of maximum conventional therapy after surgical correction. Lesions that were formerly denoted nonsurvivable can be effectively treated. It is urged that this therapy be used whenever necessary to sustain the life of an infant who has survived operation, regardless of whether the patient has demonstrated a “honeymoon” period, PaO2 greater than 100 torr, or any other factor conventionally thought to delineate survivable from nonsurvivable lesions. Such practices may exclude patients with survivable lesions from life-saving therapy.

Ernest D. Graves

Papers

Extracorporeal membrane oxygenation for respiratory and cardiac failure in infants and children.

A correlation of pulmonary hypoplasia, mean airway pressure, and survival in congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation*

Persistent Pulmonary Hypertension in the Neonate

Extracorporeal membrane oxygenation for newborn respiratory failure.

Congenital diaphragmatic hernia. Improving survival with extracorporeal membrane oxygenation