Inhaled nitric oxide and heparin for infantile primary pulmonary hypertension.
Explore the source record for details and available documents.
Drug Therapy, Combination↗
Biomedical subjects
D L Wessel
Publications and source records attributed to D L Wessel.
Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest.
INTRODUCTION: We have recently used extracorporeal membrane oxygenation as a means of rapidly resuscitating pediatric patients with heart disease after cardiopulmonary arrest, in whom conventional resuscitation measures have failed. METHODS: We developed a fully portable extracorporeal membrane oxygenation circuit that is maintained vacuum and carbon dioxide-primed at all times. When needed, the circuit is crystalloid-primed and can be ready for use within 15 minutes. Since February 1996, we have used this rapid-deployment circuit to resuscitate 11 pediatric patients in full cardiopulmonary arrest. RESULTS: The median age of the 11 patients was 120 days (2 days to 4.6 years). Nine patients had a cardiac arrest after cardiac surgery. One patient had a cardiac arrest during cardiac catheterization and one patient had a cardiac arrest before cardiac surgery. Median duration of cardiopulmonary resuscitation was 55 minutes (range 20 to 103 minutes), with no difference in the duration of cardiopulmonary resuscitation between survivors and nonsurvivors. Ten of 11 patients (91%) were weaned from extracorporeal membrane oxygenation and seven (64%) survived to hospital discharge. Six patients are long-term survivors, five of whom are in New York Heart Association class I; one survivor is in class II. Seven patients resuscitated with extracorporeal membrane oxygenation before the use of this rapid-deployment circuit had a median duration of cardiopulmonary resuscitation of 90 minutes, with two (28.6%) survivors. CONCLUSIONS: The use of rapid-deployment extracorporeal membrane oxygenation results in shorter resuscitation times and improved survival in pediatric patients with heart disease after cardiopulmonary arrest.
Cardiac Surgical Procedures↗
Inhaled nitric oxide does not affect adenosine 5'-diphosphate-dependent platelet activation in infants with persistent pulmonary hypertension of the newborn.
OBJECTIVE: To investigate the effect of inhaled nitric oxide (NO) treatment in newborns with persistent pulmonary hypertension on adenosine 5'-diphosphate (ADP)-dependent platelet activation. METHODS: After parental informed consent, infants with persistent pulmonary hypertension of the newborn were randomly assigned to receive conventional treatment (control group) or treatment with 40 parts per million of inhaled NO. Platelet activation was measured at time of entry and 30 minutes later by surface expression of P-selectin in response to increasing concentrations of the agonist ADP (0, 2, 5, 10, and 20 microM) using fluorescence-activated flow cytometry. RESULTS: We examined 11 infants in the inhaled NO group and 13 in the control group. P-selectin expression, quantified as mean fluorescence, was not significantly different in the two groups of patients at baseline. Median percent change from baseline fluorescence was assessed using the Wilcoxon matched-pairs signed-rank test. At 30 minutes after enrollment there were no statistically significant changes from baseline fluorescence in either group of patients and at all ADP concentrations. CONCLUSION: Thirty minutes of exposure to 40 ppm of inhaled NO does not inhibit ADP-dependent platelet activation as measured by surface expression of P-selectin in infants with persistent pulmonary hypertension of the newborn.
Adenosine Diphosphate↗
Effect of inhaled nitric oxide on endothelin-1 and cyclic guanosine 5'-monophosphate plasma concentrations in newborn infants with persistent pulmonary hypertension.
OBJECTIVE: To examine the role of endogenous nitric oxide (NO) and endothelin-1 (ET-1) in the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) and to determine whether inhaled NO, currently under investigation as a new therapy for PPHN, affects plasma concentrations of these vasoactive mediators. METHODS: Circulating ET-1 and cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay in 15 healthy term newborn infants and 46 newborn infants with PPHN enrolled in a randomized, controlled trial of inhaled NO. These concentrations were followed up longitudinally and compared between the NO and the conventionally treated group. RESULTS: Concentrations of ET-1 were significantly higher and cGMP concentrations significantly lower in infants with PPHN compared with healthy newborn infants (median ET-1, 28 vs 11 pmol/L; p = 0.0001; median cGMP, 35 vs 61 pmol/ml; p = 0.0001, respectively). ET-1 concentrations showed an upward trend at 1 and 24 hours of treatment and a subsequent decline at recovery in both subgroups of patients, with the most pronounced decrease in the NO group. cGMP concentrations increased significantly only in the NO group, with a peak at 1 hour of treatment (median, 61 pmol/ml). As the dose of NO decreased, cGMP concentrations declined. In contrast, conventionally treated infants manifested no change in cGMP concentrations from baseline until recovery, when a significant decrease was noted (median decrease of 13 pmol/ml; p = 0.002). We did not find a significant difference between ET-1 and cGMP concentrations in infants who required extracorporeal membrane oxygenation compared with those who did not. CONCLUSIONS: PPHN is associated with increased ET-1 and decreased cGMP plasma concentrations, which may contribute to the pathogenesis of the disease. Inhaled NO appears to modulate these mediators during the disease process, suggesting an interaction between ET-1 and NO in vivo.
Administration, Inhalation↗
Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.
OBJECTIVES: In a randomized, single-center trial, we compared perioperative outcomes in infants undergoing cardiac operations after use of the alpha-stat versus pH-stat strategy during deep hypothermic cardiopulmonary bypass. METHODS: Admission criteria included reparative cardiac surgery, age less than 9 months, birth weight 2.25 kg or more, and absence of associated congenital or acquired extracardiac disorders. RESULTS: Among the 182 infants in the study, diagnoses included D-transposition of the great arteries (n = 92), tetralogy of Fallot (n = 50), tetralogy of Fallot with pulmonary atresia (n = 6), ventricular septal defect (n = 20), truncus arteriosus (n = 8), complete atrioventricular canal (n = 4), and total anomalous pulmonary venous return (n = 2). Ninety patients were assigned to alpha-stat and 92 to pH-stat strategy. Early death occurred in four infants (2%), all in the alpha-stat group (p = 0.058). Postoperative electroencephalographic seizures occurred in five of 57 patients (9%) assigned to alpha-stat and one of 59 patients (2%) assigned to pH-stat strategy (p = 0.11). Clinical seizures occurred in four infants in the alpha-stat group (4%) and two infants in the pH-stat group (2%) (p = 0.44). First electroencephalographic activity returned sooner among infants randomized to pH-stat strategy (p = 0.03). Within the homogeneous D-transposition subgroup, those assigned to pH-stat tended to have a higher cardiac index despite a lower requirement for inotropic agents; less frequent postoperative acidosis (p = 0.02) and hypotension (p = 0.05); and shorter duration of mechanical ventilation (p = 0.01) and intensive care unit stay (p = 0.01). CONCLUSIONS: Use of the pH-stat strategy in infants undergoing deep hypothermic cardiopulmonary bypass was associated with lower postoperative morbidity, shorter recovery time to first electroencephalographic activity, and, in patients with D-transposition, shorter duration of intubation and intensive care unit stay. These data challenge the notion that alpha-stat management is a superior strategy for organ protection during reparative operations in infants using deep hypothermic cardiopulmonary bypass.
Acid-Base Equilibrium↗
Delayed sternal closure after cardiac operations in a pediatric population.
OBJECTIVE: The purpose of this study was to assess morbidity and mortality associated with delayed sternal closure after pediatric cardiac operations. METHODS: Hospital records were reviewed of all patients with an open sternum after a cardiac operation at Children's Hospital, Boston, from January 1992 to December 1995. RESULTS: A total of 178 patients had delayed sternal closure with an overall mortality rate of 19%. The most common diagnosis of patients with delayed sternal closure was hypoplastic left heart syndrome (29%). Although myocardial distention or chest wall edema (n = 47) was a common indication to delay sternal closure, in many patients (n = 47) the sternum was left open electively to avoid postoperative cardiac or respiratory compromise. Successful sternal closure was achieved in 158 patients (89%) at a mean of 3.4 +/- 1.8 days after opening. There were significant increases in left atrial pressure (7.7 +/- 3.4 to 9.8 +/- 4.1 mm Hg, p = 0.00001) and right atrial pressure (8 +/- 3.2 to 10.1 +/- 3.3 mm Hg, p = 0.00001) with sternal closure. There was a small but statistically significant drop in pH (7.44 +/- 0.05 to 7.41 +/- 0.08, p < 0.0001) during sternal closure. The peak inspiratory pressure, delivered breaths per minute, and fraction of inspired oxygen all significantly increased during sternal closure. Clinical evidence of surgical site infection occurred in 12 (6.7%) of the patients with delayed sternal closure; mediastinitis developed in 7 (3.9%) patients. CONCLUSIONS: Although delayed sternal closure after complex operations for congenital heart disease is often necessary in the operating room because of edema, unstable hemodynamic conditions, or bleeding, it can also be used electively to aid in hemodynamic and respiratory stability in the initial postoperative period. Our review supports a low morbidity associated with delayed sternal closure in a pediatric population.
Bandages↗
Inhaled nitric oxide in the neonate with cardiac disease.
As a selective pulmonary vasodilator, inhaled nitric oxide is an important diagnostic and therapeutic agent for the treatment of pulmonary hypertension in patients with congenital heart disease. Among 400 patients treated in our center with nitric oxide, 37% were newborns. Hemodynamic benefit was shown in newborns with total anomalous pulmonary venous connection, in those with congenital mitral stenosis, and in postoperative patients with preexisting left to right shunts and other lesions. It can be used to help discriminate anatomic obstruction to pulmonary blood flow from pulmonary vasoconstriction, and it may be used in the treatment or prevention of pulmonary hypertensive crises after cardiopulmonary bypass. However, none of the purported benefits of inhaled nitric oxide in children with congenital heart disease have been studied in a randomized, placebo-controlled manner.
Administration, Inhalation↗
Evaluation of a staged treatment protocol for rapid automatic junctional tachycardia after operation for congenital heart disease.
OBJECTIVES: This study sought to 1) develop an efficient treatment protocol for postoperative automatic junctional tachycardia (JT) using conventional drugs and techniques, and 2) identify clinical features associated with this disorder by analyzing a large study group. BACKGROUND: Postoperative JT is a transient arrhythmia that may be fatal after operation for congenital cardiac defects. Its precise cause is unknown. A variety of palliative treatments have evolved, but because of a low incidence of JT, large studies of the most efficient therapeutic sequence are lacking. METHODS: A protocol for rapid JT (>170 beats/min) was adopted in 1986, and was tested in 71 children between 1986 and 1994. Staged therapy involved 1) a reduction of catecholamines; 2) correction of fever; 3) atrial pacing to restore synchrony; 4) digoxin; 5) phenytoin or propranolol or verapamil; 6) procainamide or hypothermia; and 7) combined procainamide and hypothermia. Effective therapy was defined as a sustained reduction of JT rate <170 beats/min within 2 h. Clinical profiles of the study group were contrasted with all patients without JT from this same era to identify features associated with JT. RESULTS: Of the multiple treatment stages, only correction of fever and combined procainamide and hypothermia appeared to be efficacious. By refining the protocol to eliminate nonproductive stages, the time to JT control was significantly shortened for the last 30 patients. Treatment was ultimately successful in 70 of 71 children. Postoperative JT was strongly associated with young age, transient atrioventricular block and operations involving ventricular septal defect closure. CONCLUSIONS: A staged approach to therapy, with emphasis on combined hypothermia and procainamide in difficult cases, appears to be an effective management strategy for postoperative JT. These results may also serve as comparison data for evaluation of newer and promising JT options, such as intravenous amiodarone. Trauma to conduction tissue may play a central role in the etiology of this disorder.
Adolescent↗
Inhaled nitric oxide in sickle cell disease with acute chest syndrome.
Explore the source record for details and available documents.
Administration, Inhalation↗
Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn.
OBJECTIVE: To determine the effect of inhaled nitric oxide (NO) on clinical outcome in newborns with persistent pulmonary hypertension (PPHN). DESIGN: A prospective, randomized trial of patients referred to a level 3 nursery in a single large center. Clinicians were not masked to group assignment. Crossover of patients from control to NO treatment was not permitted. METHODS: We randomized 49 mechanically ventilated newborns, transferred to our center with clinical and echocardiographic evidence of severe PPHN (arterial oxygen tension [PaO2] <100; fractional inspired oxygen = 1) to treatment with or without NO. Patients with gestational age <34 weeks or with congenital heart disease or diaphragmatic hernia were excluded. High-frequency oscillatory ventilation was used but not allowed concomitantly with NO. Primary outcome variables were oxygenation, mortality, and use of extracorporeal membrane oxygenation (ECMO). RESULTS: Meconium aspiration syndrome and isolated PPHN were the most common diagnoses (32/49) and were distributed equally between groups. The median age at the time of entry into the study was similar between groups, 25 hours for control patients and 18 hours for NO patients. Median baseline oxygenation index (OI) was similar in 23 control (OI = 29) and 26 NO (OI = 30) patients. Mortality (8%), use of ECMO (33%), median days on mechanical ventilation (9 days), and duration of supplemental oxygen (13 days) were not different between treatment groups. PaO2, oxygen saturation, and OI improved in the NO group compared with baseline and to control patients at 15 minutes. The median percent change in OI (-31%) in the NO group was significantly different from baseline and from the control group. The difference in oxygenation between treatment groups was still apparent 12 hours after baseline. Before cannulation for ECMO, oxygenation was better in the NO group compared with control patients. Among patients who were placed on ECMO, the median time from baseline to ECMO cannulation was 2.4 hours (range, 1 to 12 hours) among control patients and 3.3 hours (range, 2 to 68 hours) for those randomized to receive NO. There was a tendency to observe fewer adverse neurologic events (seizure and intracranial hemorrhage) in the NO group (4/26 vs 8/23). One child with alveolar capillary dysplasia confirmed by postmortem examination could not be weaned from 80 parts per million of NO and transiently developed methemoglobinemia (peak methemoglobin level = 17%). No other side effects were observed. CONCLUSIONS: Although mortality and ECMO use were similar for both treatment groups using this study size and design, sustained improvement in oxygenation with NO and better oxygenation at initiation of ECMO may have important clinical benefits. We speculate that modification of treatment to include specific lung expansion strategies with NO treatment and recognition that early improvement of oxygenation may be sustained with NO may lead to reduced use of ECMO in NO treated patients compared with controls.
Administration, Inhalation↗
Outcome of patients with ectopia cordis and significant intracardiac defects.
BACKGROUND: Previous reports suggest a poor prognosis for patients with ectopia cordis and significant congenital heart disease. METHODS AND RESULTS: To determine the outcome of affected patients in a recent medical and surgical era, we reviewed the clinical course, echocardiograms, catheterization data, and operative reports of all patients with ectopia cordis and significant heart disease encountered at Children's Hospital from 1982 to the present. We identified 13 patients with conotruncal defects and either thoracic (TEC, n = 4) or thoracoabdominal (TAEC, n = 9) ectopia cordis. Diagnosis was established in utero in 6, with termination of pregnancy in 2 and death before transfer to Children's Hospital in 1. Of 10 patients postnatally managed at Children's Hospital, 4 of 8 with TAEC and 1 of 2 with TEC survived beyond infancy, with an age at most recent follow-up of 3.5 to 9.8 years. All 5 survivors had procedures as neonates to provide skin coverage over the midline defect and heart, with concomitant repair of a small omphalocele in 4. Three underwent successful surgical repair of the cardiac defect, including ventricular septal defect closure for double-outlet right ventricle (9 months), repair of tetralogy of Fallot with pulmonary atresia (2.6 years), and repair of double-outlet right ventricle, pulmonary stenosis, and total anomalous pulmonary venous connection to the coronary sinus (3.3 years). Two other patients with TAEC, conoventricular defects, and hypoplastic left ventricle underwent single-ventricle palliation. One patient, at 4 years of age underwent a right cavopulmonary anastomosis and intra-atrial coronary sinus-to-right superior vena cava baffle. The second patient had a modified Fontan procedure. None of the 5 survivors had significant extrathoracic defects, whereas all 3 who died by 3 weeks of age had both a large omphalocele and pulmonary hypoplasia. Two infants with pentalogy of Cantrell, 1 with a large omphalocele, died of fungal sepsis by 5 weeks of age, and 1 other died intraoperatively after repair of pulmonary venous confluence obstruction and right Blalock-Taussig shunt placement. CONCLUSIONS: Our experience indicates that patients with TEC and TAEC and significant intracardiac defects, in the absence of significant extracardiac defects, can survive beyond early infancy and undergo successful cardiac repair or more definitive palliation for single-ventricle physiology.
Child↗
Inhaled nitric oxide in children with pulmonary hypertension and congenital mitral stenosis.
We demonstrated selective pulmonary vasodilation in patients with congenital mitral stenosis with inhaled NO, and used NO as prolonged therapy to stabilize the postintervention course of these children. The pulmonary vasoreactivity was greater than that previously reported in adults and may be due to particular sensitivity of pulmonary veins to inhaled NO when pulmonary venous hypertension has been present since birth.
Administration, Inhalation↗
Rebound pulmonary hypertension after inhalation of nitric oxide.
BACKGROUND: We describe the hemodynamic response to initiation and withdrawal of inhaled nitric oxide (NO) in infants with pulmonary hypertension after surgical repair of total anomalous pulmonary venous connection. METHODS: Between January 1, 1992, and January 1, 1995, 20 patients underwent repair of total anomalous pulmonary venous connection. Nine patients had postoperative pulmonary hypertension and received a 15-minute trial of inhaled NO at 80 parts per million. Five of these patients received prolonged treatment with NO at 20 parts per million or less. RESULTS: Mean pulmonary artery pressure decreased from 35.6 +/- 2.4 to 23.7 +/- 2.0 mm Hg (mean +/- standard error of the mean) (p = 0.008), and pulmonary vascular resistance decreased from 11.5 +/- 2.0 to 6.4 +/- 1.0 U.m2 (p = 0.03). After prolonged treatment with NO, pulmonary artery pressure increased transiently in all patients when NO was discontinued. CONCLUSIONS: After operative repair of total anomalous pulmonary venous connection, inhaled NO selectively vasodilated all patients with pulmonary hypertension. Withdrawal of NO after prolonged inhalation was associated with transient rebound pulmonary hypertension that dissipated within 60 minutes. Appreciation of rebound pulmonary hypertension may have important implications for patients with pulmonary hypertensive disorders when interruption of NO inhalation is necessary or when withdrawal of NO is planned.
Administration, Inhalation↗
Commentary: simple gases and complex single ventricles.
Explore the source record for details and available documents.
Animals↗
Diagnostic use of inhaled nitric oxide after neonatal cardiac operations.
Explore the source record for details and available documents.
Cardiac Surgical Procedures↗
Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest.
BACKGROUND: The neurological morbidity associated with prolonged periods of circulatory arrest has led some cardiac surgical teams to promote continuous low-flow cardiopulmonary bypass as an alternative strategy. The nonneurological postoperative effects of both techniques have been previously studied only in a limited fashion. METHODS AND RESULTS: We compared the hemodynamic profile (cardiac index and systemic and pulmonary vascular resistances), intraoperative and postoperative fluid balance, and perioperative course after deep hypothermia and support consisting predominantly of total circulatory arrest or low-flow cardiopulmonary bypass in a randomized, single-center trial. Eligibility criteria included a diagnosis of transposition of the great arteries and a planned arterial switch operation before the age of 3 months. Of the 171 patients, 129 (66 assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had an associated ventricular septal defect. There were 3 (1.8%) hospital deaths. Patients assigned to low-flow bypass had significantly greater weight gain and positive fluid balance compared with patients assigned to circulatory arrest. Despite the increased weight gain in the infants assigned to low-flow bypass, the duration of mechanical ventilation, stay in the intensive care unit, and hospital stay were similar in both groups. Hemodynamic measurements were made in 122 patients. During the first postoperative night, the cardiac index decreased (32.1 +/- 15.4%, mean +/- SD), while pulmonary and systemic vascular resistance increased. The measured cardiac index was < 2.0 L.min-1.m-2 in 23.8% of the patients, with the lowest measurement typically occurring 9 to 12 hours after surgery. Perfusion strategy assignment was not associated with postoperative hemodynamics or other nonneurological postoperative events. CONCLUSIONS: After heart surgery in neonates and infants, both low-flow bypass and circulatory arrest perfusion strategies have comparable effects on the nonneurological postoperative course and hemodynamic profile.
Cardiopulmonary Bypass↗
Inhaled nitric oxide for children with congenital heart disease and pulmonary hypertension.
BACKGROUND: Endothelium-derived nitric oxide (NO) is a potent vasodilator and a major mediator of pulmonary vascular tone. METHODS: Five infants underwent a trial of inhaled NO with hemodynamic monitoring in the operating room after atrioventricular canal repair. An additional 15 patients with congenital heart disease and refractory pulmonary hypertension were treated with inhaled NO for 1 day to 10 days postoperatively. RESULTS: In the 5 infants with atrioventricular canal, corrective surgical intervention and conventional therapy (hyperventilation, inspired oxygen fraction of 0.80, and inotropic agents) lowered mean pulmonary artery pressure from 49.5 +/- 10.5 to 20.0 +/- 2.2 mm Hg (p < 0.001). Adding inhaled NO further decreased mean pulmonary artery pressure to 18.0 +/- 2.8 mm Hg (p = not significant). Inhaled NO had no effect on ventricular function curves (inflow occlusion) in this group. In the 15 patients with refractory postoperative pulmonary hypertension, 11 had a favorable response to inhaled NO, with a decrease in mean pulmonary artery pressure from 30.9 +/- 5.8 to 23.1 +/- 5.4 mm Hg (p < 0.01) in 8 patients with pulmonary artery catheters. CONCLUSIONS: These studies demonstrate that inhaled NO has minimal beneficial effect on pulmonary artery pressure or cardiac output in infants after repair of atrioventricular canal. Inhaled NO is effective in decreasing PAP postoperatively in select patients with congenital heart disease and pulmonary hypertension refractory to conventional therapeutic modalities.
Administration, Inhalation↗
Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation.
OBJECTIVES: We investigated the effect of inhaled nitric oxide and infused acetylcholine in patients with pulmonary hypertension undergoing cardiac catheterization before cardiopulmonary transplantation. BACKGROUND: The fate of patients under consideration for transplantation of the heart or lungs, or both, is influenced by the evaluation of their pulmonary vascular reactivity. METHODS: We evaluated 11 patients who were classified into two groups on the basis of mean left atrial pressure > 15 mm Hg (group I, n = 6) or < or = 15 mm Hg (group II, n = 5). All patients inhaled nitric oxide at 80 ppm. This was preceded by an infusion of 10(-6) mol/liter of acetylcholine in seven consecutive patients (n = 3 in group I, n = 4 in group II). RESULTS: In group I, inhaled nitric oxide decreased pulmonary artery pressure from (mean +/- SE) 71 +/- 13 to 59 +/- 10 mm Hg (p < 0.05), pulmonary vascular resistance from 14.9 +/- 3.8 to 7.6 +/- 1.7 Um2 (p < 0.05) and intrapulmonary shunt fraction from 17.8 +/- 3.6% to 12.7 +/- 2.1% (p < 0.05). Left atrial pressure tended to increase from 27 +/- 4 to 32 +/- 5 mm Hg (p = 0.07). In group II pulmonary vascular resistance decreased in response to nitric oxide from 36.4 +/- 9.0 to 31.1 +/- 7.9 Um2 (p < 0.05). Cardiac index, systemic pressure and resistance did not change in either group. Seven patients who received acetylcholine had no significant alteration in pulmonary hemodynamic variables. CONCLUSIONS: These preliminary observations suggest that nitric oxide is a potent pulmonary vasodilator with minimal systemic effects. It may be useful in discriminating patients needing combined heart and lung transplantation from those requiring exchange of the heart alone.
Acetylcholine↗