Ronald W. Day

Randomized controlled study of inhaled nitric oxide after operation for congenital heart disease

BACKGROUND Inhaled nitric oxide selectively decreases pulmonary vascular resistance. This study was performed to determine whether inhaled nitric oxide decreases the incidence of pulmonary hypertensive crises after corrective procedures for congenital heart disease. METHODS Patients with a systolic pulmonary arterial pressure of 50% or more of the systolic systemic arterial pressure during the early postoperative period were randomized to receive 20 parts per million inhaled nitric oxide (n = 20) or conventional therapy alone (n = 20). Acute hemodynamic and blood gas measurements were performed at the onset of therapy. The efficacy of sustained therapy was determined by comparing the number of patients in each group who experienced a pulmonary hypertensive crisis. RESULTS In comparison to controls, there were no significant differences in the baseline and 1-hour measurements of patients who were treated with nitric oxide. Four patients in the control group and 3 patients in the nitric oxide group experienced a pulmonary hypertensive crisis. CONCLUSIONS Nitric oxide did not substantially improve pulmonary hemodynamics and gas exchange immediately after operation for congenital heart disease. Nitric oxide also failed to significantly decrease the incidence of pulmonary hypertensive crises.

Inhaled nitric oxide in children with severe lung disease: Results of acute and prolonged therapy with two concentrations

OBJECTIVES To evaluate the acute effects of 11 and 60 parts per million (ppm) inhaled nitric oxide on the pulmonary vascular resistance and systemic oxygenation of children with severe lung disease, and to compare the outcome of prolonged therapy with approximately 10 and 40 ppm inhaled nitric oxide. DESIGN Prospective, randomized study. SETTING A 26-bed pediatric intensive care unit in a tertiary childrens hospital. PATIENTS Nineteen patients (median age 11 yrs, range 7 months to 16 yrs) with acute bilateral lung disease requiring a positive end-expiratory pressure (PEEP) of > 6 cm H2O and an FIO2 of > 0.5 for > 12 hrs were treated with inhaled nitric oxide. One patient was treated twice during the same hospitalization. INTERVENTIONS Acute hemodynamic and blood gas effects of 11 and 60 ppm inhaled nitric oxide were studied, while delivering these concentrations in random order for intervals of 20 to 30 mins. Each interval was preceded by an interval of 20 to 30 mins without nitric oxide. Patients were then randomized and treated for a prolonged period with approximately 10 or 40 ppm inhaled nitric oxide independent of their initial acute responses to 11 and 60 ppm. Nitric oxide was discontinued when ventilatory support was decreased to a PEEP of < or = 6 cm H2O and an FIO2 of < or = 0.5. MEASUREMENTS AND MAIN RESULTS Inhaled nitric oxide selectively decreased pulmonary vascular resistance and improved systemic oxygenation. Acute hemodynamic and blood gas effects of 11 and 60 ppm nitric oxide were similar. Systemic oxygenation improved to a greater extent in patients with radiographic evidence of residual aerated lung regions than in patients with diffuse bilateral lung disease. Maximum methemoglobin concentrations were greater in patients treated for a prolonged period with 40 ppm nitric oxide. The mortality and duration of therapy were similar for patients treated with 10 and 40 ppm inhaled nitric oxide. CONCLUSIONS Pulmonary vascular resistance and systemic oxygenation are acutely improved to a similar extent by 11 and 60 ppm inhaled nitric oxide, and concentrations in excess of 10 ppm are probably not needed for prolonged therapy of children with severe lung disease.

Pulmonary vasodilatory effects of 12 and 60 parts per million inhaled nitric oxide in children with ventricular septal defect

Abstract In conclusion, inhaled nitric oxide selectively decreased pulmonary vascular resistance of children with VSD and moderate pulmonary hypertension. During 7-minute intervals, pulmonary vascular resistance was selectively decreased to a similar extent by 12 and 60 ppm inhaled nitric oxide while breathing air or supplemental oxygen. Pulmonary vascular resistance was also decreased by supplemental oxygen alone; however, there was a concomitant increase in systemic vascular resistance. Pulmonary vascular resistance decreased to a greater extent with oxygen and inhaled nitric oxide than with either nitric oxide or oxygen alone.

Late Results and Reintervention After Aortic Valvotomy for Critical Aortic Stenosis in Neonates and Infants

BACKGROUND Many centers have adopted balloon valvuloplasty for treatment of infants with critical aortic stenosis because of historically poor early results and a lack of long-term results with surgical valvotomy. We evaluated our results with open aortic valvotomy over the past decade, specifically examining factors influencing survival and reintervention in the current era. METHODS From 1986 to 1996, 37 infants in the first 3 months of life underwent open aortic valvotomy for critical aortic stenosis. All patients underwent cardiopulmonary bypass, valvotomy, and valve debridement under direct vision with standard techniques. RESULTS Early mortality was 11% (4 of 37, 70% confidence limit 7% to 20%) and all early deaths were in neonates less than 2 weeks of age. Late death occurred in 6 patients a mean of 10 +/- 12 months (range, 2 to 36 months) after valvotomy. Actuarial survival, including operative deaths was 92% +/- 6% at 1 month, 78% +/- 9% at 1 year, and 73.4% +/- 10% at 10 years. In a multifactorial regression analysis, the best predictors of death were the presence of endocardial fibroelastosis and small body surface area and the best predictor of the need for late reintervention was preoperative aortic annular size. Thirteen patients required reintervention: repeat operation in 7 patients, balloon valvuloplasty in 3 patients, and both balloon valvuloplasty and reoperation in 3 patients. Actuarial freedom from reintervention postoperatively is 97% +/- 3% at 1 month, 73% +/- 9% at 1 year, and 55% +/- 11% at 10 years. Reintervention was for recurrent left ventricular outflow obstruction in 9 patients and mixed aortic stenosis and aortic insufficiency in 4. Echocardiography 4.3 +/- 2.5 years after aortic valvotomy in survivors who have not required reintervention (n = 20) revealed a Doppler peak instantaneous systolic gradient of 37 +/- 14 mm Hg and mild or less aortic regurgitation in 16 patients and moderate aortic regurgitation in 4 patients. CONCLUSIONS Current surgical results with critical aortic stenosis in the neonate and young infant are acceptable in terms of both late survival, reintervention, and functional results in the majority of patients. Newer interventions, such as balloon valvuloplasty, should be carefully evaluated for long-term results and should be compared more appropriately to current surgical results to determine the best treatment modality for the neonate and infant with critical aortic stenosis.

Doppler Evaluation of Aortic Regurgitation in Children

Doppler indexes have been used successfully to determine the severity of aortic regurgitation (AR) in adults but have not been evaluated systematically in children. To evaluate the accuracy of specific Doppler echocardiographic indexes in assessing the degree of AR in children, 30 children underwent 2-dimensional and Doppler echocardiography within 24 hours of angiography. Patients were divided into 4 groups based on the degree of angiographic AR. Color Doppler jet width, short-axis jet area, jet length, and maximum jet area were measured. AR slope was measured using continuous-wave Doppler. Flow in the abdominal aorta was evaluated using pulsed Doppler. Doppler indexes were compared with the angiographic grade of AR. Jet width and short-axis jet area were significantly different between groups and showed strong correlation with the angiographic grade. Holodiastolic flow reversal in the abdominal aorta separated 1+ to 2+ from 3+ to 4+ AR (100% sensitivity and 100% negative predictive value for 3+ to 4+ AR). Jet length, maximum jet area, and the ratio of reverse to forward abdominal aortic velocity time integrals correlated with angiography but showed little difference between groups that differed by only 1 angiographic grade. AR slope did not correlate with the angiographic grade. We conclude that in children, color Doppler jet width, short-axis jet area, and holodiastolic abdominal aortic flow reversal are the best predictors of angiographic severity. Use of these indexes may obviate the need for angiography to determine the degree of AR in children.

Pulmonary Vascular Resistance of Children Treated With Nitrogen During Early Infancy

BACKGROUND We have empirically used supplemental nitrogen in newborns with a functional single ventricle and ductal-dependent systemic perfusion to prevent pulmonary vasodilation and deliver a greater proportion of flow to the systemic circulation. Thus, we reviewed patient outcome to determine whether adverse pulmonary vascular effects may be associated with this therapy. METHODS From December 1991 to December 1995, the fraction of inspired oxygen was adjusted, with supplemental nitrogen if necessary, to maintain an oxygen saturation near 75% in 20 newborns awaiting heart transplantation. Medical records were reviewed to evaluate (1) the duration of nitrogen therapy, (2) pulmonary vascular histology, (3) postoperative pulmonary hemodynamics, and (4) survival. RESULTS Thirteen patients underwent heart transplantation, 4 patients died without surgical intervention, and 3 patients underwent late aortic reconstruction. Supplemental nitrogen was used without exceeding a fraction of inspired oxygen of 0.21 for 38 +/- 6 days. One patient had evidence of changes of potentially irreversible pulmonary vascular disease. Pulmonary vascular resistance was not increased long-term in surviving patients. CONCLUSIONS Supplemental nitrogen can be used to maintain a systemic oxygen saturation near 75% for an extended period in newborns with ductal-dependent systemic perfusion with no long-term adverse effect on pulmonary vascular resistance.

Early and intermediate results of the fontan procedure at moderately high altitude

At higher elevations, alveolar hypoxia increases pulmonary vascular resistance and may limit the cardiac output of individuals without a subpulmonary ventricle. Thus, we reviewed the outcome of definitive palliation for tricuspid atresia and other forms of single ventricle in 60 consecutive Fontan patients living at a mean elevation of 1,370 m (range, 910 to 2,130 m). There were four early deaths (6.7%; 70% confidence limits, 4.1% to 10.7%) and six late deaths. Kaplan-Meier actuarial survival (+/- standard error) is 79.6% +/- 8.2% at 5 years. Survival was significantly decreased in patients with a preoperative mean pulmonary arterial pressure greater than or equal to 15 mm Hg unless the Fontan procedure was performed with a residual fenestration. Exercise tolerance was significantly worse at higher elevations in a subgroup of patients who have traveled to altitudes of 1,680 to 3,350 m. We conclude that the early and intermediate results of the Fontan procedure at moderately high altitude are similar to results reported at sea level. However, exercise tolerance may be impaired at higher elevations in many patients.

Growth of children with a functionally single ventricle following palliation at moderately increased altitude

The bidirectional Glenn and Fontan procedures are empirically performed as interim and definitive procedures in children with a functionally single ventricle. The optimal stage of palliation, nonetheless, remains unknown. During childhood, growth is a fundamental measure of response to therapy. Growth may be influenced by the degree of cyanosis, the volume load on the ventricle, and cardiac performance. Thus, the weight and stature of children with a functionally single ventricle who underwent a bidirectional Glenn procedure or a Fontan procedure were studied to determine the effect of each intervention on growth. Z scores for weight and stature were retrospectively determined prior to palliation, at yearly intervals for 4 years, and from long-term measurements until 18 years of age in all patients with at least 2 years of observation following palliation. Growth was evaluated in 54 patients with a bidirectional Glenn procedure, and 65 patients with a Fontan procedure. The Z scores for weight were improved after each method of surgical palliation. Stature, however, was improved only following the bidirectional Glenn procedure. Growth was impaired in patients who developed protein losing enteropathy. Weight improved only during the initial 2 years after the Fontan procedure in patients who had a surgical fenestration. Over the long-term, patients who underwent a Fontan procedure were more likely to have a Z score less than -2.0 for weight and stature than patients who underwent only a bidirectional Glenn procedure. Late mortality and the incidence of heart transplantation were increased in patients who experienced a decrease in their rate of growth, defined as a negative change of more than one Z score in weight or stature, following the Fontan procedure. In conclusion, at moderately increased altitude, children with a functionally single ventricle grow more appropriately following the bidirectional Glenn procedure than following the Fontan procedure. A decrease in the rate of growth is associated with a poor prognosis following the Fontan procedure.

Acute Vasodilator Response in Pediatric Pulmonary Arterial Hypertension: Current Clinical Practice From the TOPP Registry

BACKGROUND In pulmonary arterial hypertension (PAH), acute vasodilator response testing (AVT) is considered important to identify adult patients with favorable prognosis using calcium-channel blocker (CCB) therapy. However, in pediatric PAH, criteria used to identify acute responders and CCB use are insufficiently studied. OBJECTIVES This study sought to describe current clinical practice of AVT and subsequent treatment decisions in pediatric PAH. METHODS From January 2008 to May 2013, 529 consecutive children with confirmed pulmonary hypertension were enrolled in an international registry. We analyzed those children with evaluable AVT. RESULTS Of 382 children with evaluable AVT, 212 had idiopathic/familial PAH (IPAH/FPAH) and 105 had PAH associated with congenital heart disease (PAH-CHD). In 70% of the patients, AVT was performed using inhaled nitric oxide; other agents were used in the remaining patients. In IPAH/FPAH patients, 78 (37%) patients were acute responders according to their physician, 62 (30%) according to REVEAL (Registry-to-Evaluate-Early-And-Long-term PAH disease management)-pediatric criteria, and 32 (15%) according to Sitbon criteria. For PAH-CHD patients, the numbers of AVT responders were 38 (36%), 14 (13%), and 7 (7%) respectively. Correlation between AVT responder status as judged by the treating physician and by published response criteria was poor. Moreover, of the IPAH/FPAH patients judged by the treating physician as acute responders, only 23% were treated with CCB without additional PAH-targeted therapy. The Sitbon criteria selected patients with better prognosis who had excellent outcome when treated with CCB. CONCLUSIONS The current practice of identifying responders to AVT and subsequent treatment with CCB therapy demonstrated large discrepancies with current international guidelines. Also, in pediatric IPAH, the Sitbon criteria are the criteria of choice to identify patients with excellent survival when treated with CCB therapy.

Living at altitude adversely affects survival among patients with a fontan procedure

OBJECTIVES This study sought to determine whether survival in this cohort of patients was adversely affected by increased residential altitude. BACKGROUND The success of the Fontan procedure depends in large part on low pulmonary vascular resistance (PVR). Factors that increase PVR, including an increase in residential altitude, may adversely affect long-term outcome. Higher altitude has been shown to affect functional well-being in patients with a Fontan circulation. METHODS Databases from a tertiary cardiac care center in the Intermountain West (elevation 5,000 feet) were analyzed for patients born with single-ventricle anatomy who would now be of adult age. Complete data were then collected on all identified patients who subsequently underwent the Fontan operation. Correlates of, and time to, adverse outcome, defined as death, cardiac transplantation, or clinical decompensation requiring a move to sea level, were determined. RESULTS Of 149 patients with single-ventricle anatomy, 103 underwent the Fontan procedure, with 70 surviving to adulthood at moderate altitude. Adverse outcome occurred in 55, with death in 24 (23%), cardiac transplantation in 18 (17%), and clinical decompensation requiring move to sea level in 13 (13%). There was no relationship between type, age at, or era of Fontan procedure and long-term outcome. Correlates of long-term, transplant-free survival at moderate altitude included lower residential altitude (4,296 vs. 4,637 feet, p < 0.001), and lower pulmonary artery pressures before the Fontan procedure (13 vs. 15 mm Hg, p = 0.01), and after (14 vs. 18 mm Hg, p = 0.01). CONCLUSIONS Long-term outcome after the Fontan procedure is adversely impacted by higher residential altitude.