Elizabeth M. Shaffer

Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn

We studied the effects of inhaled nitric oxide (NO) in 9 newborn infants with severe persistent pulmonary hypertension (PPHN) who were candidates for extracorporeal membrane oxygenation treatment. With low doses of NO (10-20 ppm) all showed rapid improvement in oxygenation without reduction of systemic blood pressure. In 6 infants treated with inhaled NO for 24 h, clinical improvement was sustained at 6 ppm.

Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide

We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.

Arterial oxygenation and pulmonary arterial pressure in healthy neonates and infants at high altitude

We sought to document arterial oxygen saturation relative to changes in the right ventricular pressure/left ventricular pressure ratio (RVP/LVP ratio), an index of pulmonary arterial pressure, in infants born at high altitude. We performed pulse oximetry and echocardiography in 15 healthy infants born in Leadville, Colo. (3100 m), at 6 to 24 hours, 24 to 48 hours, 1 week, 2 months, and 4 months of age. Pulse oximetry was done under conditions of wakefulness, feeding, and active and quiet sleep. All infants received supplemental O2 at delivery and during postnatal transition; all oximetry measurements were performed with infants breathing room air. The mean arterial O2 saturation ranged from 80.6% +/- 5.3% to 91.1% +/- 1.7% during the 4 months. Values fell during the first week after birth and then rose gradually to attain near-birth values at 2 and 4 months of age. Arterial O2 saturation was uniform among behavioral states at 6 to 24 hours and 24 to 48 hours of age. After 1 week of age, values were highest during wakefulness, intermediate during feeding and active sleep, and lowest during quiet sleep. The RVP/LVP ratio remained in the normal or mildly elevated range throughout the study period. We conclude that the RVP/LVP ratio promptly becomes normal at high altitude, and despite low arterial O2 saturation in the first weeks to months after birth, healthy newborn infants at 3100 m show little evidence of acute pulmonary hypertension.

Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary vasculature in children with pulmonary hypertension

We sought to describe the morphologic characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in children with and without pulmonary hypertension to compare these anatomic findings with those of pulmonary wedge angiography, and to determine the relation between these structural findings and functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary vascular structure in children with pulmonary hypertension with current imaging techniques has been limited and little is known about the relation between structural and functional characteristics of the pulmonary vasculature. In 23 children undergoing cardiac catheterization (15 with pulmonary hypertension and 8 controls) we performed IVUS and pulmonary wedge angiography of the distal pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15 children with pulmonary hypertension. Baseline pulmonary vascular resistance (PVR) was greater in the 15 children with pulmonary hypertension than in the 8 controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary hypertension showed a thicker middle layer, wall thickness ratio, and diminished pulsatility than did those in controls (p <0.05). The inner layer was not visualized by IVUS in any control patient, but was seen in 9 of 15 patients with pulmonary hypertension. Pulmonary artery wedge angiography correlated with baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of wall thickness ratio and inner layer thickness. The inner layer was not visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity to NO and oxygen did not correlate with structural assessment of the pulmonary vasculature by IVUS. Structural changes in the pulmonary arteries in children with pulmonary hypertension can be directly visualized by IVUS, but are not predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary arteries may complement current techniques utilized in the evaluation of children with pulmonary hypertension.

Maximal voluntary work and cardiorespiratory fitness in patients who have had Kawasaki syndrome

To assess the natural history of Kawasaki syndrome and its effect on maximal voluntary work and cardiorespiratory fitness, we performed cycle ergometry testing in 47 patients who had had the syndrome. Forty-one patients performed maximal effort as judged by achievement of 95% predicted heart rate response. Oxygen consumption, carbon dioxide production, and minute ventilation were performed in 23 patients. There was no difference in maximal voluntary work (total work, mean power) or maximal oxygen consumption between case subjects and control subjects. There were no differences between patients with and those without aneurysms. Serial exercise studies were performed in 10 patients; of these, two with initially normal exercise study findings had decreased maximal voluntary work and oxygen consumption with ischemic changes, and both were at high risk for the development of stenotic or occlusive coronary arteries. The other eight patients had normal cardiorespiratory reserve and no ischemic changes with serial studies. These results suggest that patients have normal cardiorespiratory fitness after Kawasaki syndrome. With the development of ischemic heart disease, they may have decreased cardiorespiratory reserve. Serial evaluation of cardiorespiratory fitness may demonstrate ischemic heart disease.

Prenatal Diagnosis of Total Anomalous Pulmnonary Venous Connection

Total anomalous pulmonary venous connection remains a difficult diagnosis to make prenatally. The absence of normal pulmonary veins entering the left atrium may provide an indication of an abnormality. The authors discuss a case of total anomalous pulmonary venous connection in conjunction with hypoplastic left heart syndrome that was diagnosed in utero.

Prenatal Diagnosis of Pulmonary Atresia With Intact Ventricular Septum

Pulmonary atresia with intact ventricular septum is a rare and complicated congenital cardiac anomaly. Pulmonary outflow is obstructed, which results in hypertrophy and hypoplasia of the right ventricle. The fetal echocardiographic findings include a small pulmonary artery with an atretic pulmonary valve, right ventricular hypertrophy, dilated right atrium, and absent flow in the pulmonary artery on Doppler interrogation. The left ventricle, left atrium, and aortic root also may be enlarged. Nonimmune hydrops may develop in utero, which is the result of poor left ventricular function. Surgical treatments vary, depending on the presence of associated cardiovascular anomalies, but generally include a systemic-to-pulmonary artery anastomosis and a pulmonary valvulotomy.