Staged Single-Ventricle Palliation in an Infant with Hemoglobin SC Disease

Abstract

Staged single-ventricle palliation is used to treat many cyanotic congenital heart diseases. Hemoglobin sickle cell disease is associated with anemia and significant vascular sickling sequelae, which increase the risk associated with single-ventricle palliation. To our knowledge, there are no reports in the English-language medical literature of single-ventricle palliation having been performed on a patient who had either sickle cell anemia or sickle cell–hemoglobin C disease. Herein, we discuss our clinical and surgical management of an infant with tricuspid atresia type IA and hemoglobin sickle cell disease who survived single-ventricle palliative procedures through the 2nd stage of a bidirectional Glenn anastomosis.

Sickle cell anemia (HbS) and sickle cell–hemoglobin C (HbSC) disease are associated with anemia and with vascular sequelae, which include painful vaso-occlusive crisis, acute chest syndrome, and cerebral infarction.^1,2 Patients with HbSC disease usually experience a milder clinical course and longer survival than do patients who have HbS disease³; however, patients with HbSC disease remain at risk for serious sequelae, which are often initiated or exacerbated by stress, surgery, dehydration, acidosis, and hypoxemia.^1,2,4

At our institution, staged single-ventricle palliation often begins with the placement of a systemic-to-pulmonary artery shunt when the patient is a neonate, followed by a bidirectional superior cavopulmonary (bidirectional Glenn) anastomosis when the infant is approximately 5 to 8 months old. When the child is 3 to 4 years of age, the palliation is completed by means of a Fontan procedure. Although the overall outcomes of single-ventricle palliation are favorable, morbidity may ensue from multiple surgeries, cardiopulmonary bypass (CPB), hypoxemia, embolic disease, and stagnant or passive blood flow through the pulmonary vascular bed.^5,6 In addition, many patients become susceptible to dehydration when they are treated with diuretics in order to avoid heart failure symptoms. These factors increase the risk of red-blood-cell sickling in patients who have HbSC disease.^1,2

We report our management of a child with HbSC disease who underwent single-ventricle palliation via systemic-to-pulmonary artery stenting and a subsequent bidirectional Glenn anastomosis.

Case Report

In February 2005, a female neonate was born at 39 weeks' gestation after her mother's uncomplicated pregnancy. Shortly after birth, the newborn was noted to be cyanotic during feeding. Treatment with oxygen and prostaglandin E was initiated due to the concern of congenital heart disease. An echocardiogram revealed tricuspid atresia type IA with a hypoplastic right ventricle and a small apical ventricular septal defect. She also had significant hypoplasia of the proximal left pulmonary artery. Of note, her hemoglobin concentration was 14.4 g/dL after birth (normal cord blood range, 13.5–19.5 g/dL).

At 10 days of age, the neonate underwent placement of a right-sided 3.5-mm gore-tex® modified Blalock-Taussig shunt (W.L. Gore & Associates, Inc.; Flagstaff, Ariz), division of the patent ductus arteriosus, and pericardial patch augmentation of the left pulmonary artery. These procedures were performed via median sternotomy without CPB. The immediate postoperative course was complicated by severe hypotension, hypoxemia, and bradycardia, which resulted in cardiac arrest. After attempts at cardiopulmonary resuscitation led to no hemodynamic improvement, the patient's chest was emergently re-explored. The shunt was patent. When internal cardiac compressions and further medical intervention failed to restore a cardiac rhythm capable of perfusion, the right atrium and ascending aorta were cannulated, and the patient was placed on extracorporeal membrane oxygenation (ECMO) support. She received multiple packed red-blood-cell transfusions while on ECMO. Substantial improvement occurred over the next 48 hours; she was decannulated from ECMO on postoperative day 3, and her sternum was closed 2 days later. She was extubated and placed on oxygen on the 8th postoperative day, and her subsequent course in the cardiovascular intensive care unit was uncomplicated.

Before her discharge from intensive care, her newborn screening yielded the diagnosis of HbSC disease, which was confirmed by hemoglobin electrophoresis. Because newborns with HbSC disease are rarely anemic, and because vaso-occlusive crises are prevented at ages younger than 3 months by the protective effects of fetal hemoglobin,^3,7 the diagnosis of HbSC disease had not been suspected before the results of the newborn screening became available. Our hospital's hematology service was consulted, and the neonate was started on folic acid and prophylactic penicillin (for Streptococcus pneumoniae). The patient remained hospitalized for the next 2 weeks, during which time she was weaned from oxygen and her oral intake improved. Cephalic ultrasonography and computed tomography revealed no neurologic complications. The patient was discharged from the hospital on a medical regimen that included folic acid, penicillin, furosemide 3 times daily, a methadone taper, and aspirin for routine anticoagulation. Her oxygen saturation levels on room air were in the low 80% range.

The infant did well as an outpatient. She was weaned from methadone, and the penicillin was changed to amoxicillin. At her 2-week follow up visit, the furosemide dosage was decreased to once daily, in order to prevent substantial dehydration. Without transfusion, her hemoglobin remained greater than 12.0 g/dL, a level deemed sufficient for oxygen delivery. Her hemoglobin S fraction rose from 17.7% to 29.8%; and her hemoglo-bin C fraction, from 16.6% to 28.2%. The remaining hemoglobin profile consisted of hemoglobin A (range, 18.6%–47.9%, from blood transfusions after her surgery) and hemoglobin F (range, 17.8%–23.4%).

In preparation for the planned bidirectional Glenn shunting procedure, the infant underwent cardiac catheterization at 3 months of age. No blood transfusion was required. Her pulmonary arteriolar resistance was low (0.4 Wood units), and her branch pulmonary arteries were of adequate size. On angiography and echocardiography, her left ventricular function appeared normal and without significant mitral regurgitation. The patient was therefore considered a good candidate to undergo a bidirectional Glenn anastomosis.

Before this 2nd surgical procedure, the child had a hemoglobin S fraction of 27.6% and a hemoglobin C fraction of 26.1%. She underwent a successful bidirectional Glenn anastomosis at the age of 5 months. In accordance with recommendations in the medical literature regarding the management of sickle cell disease and CPB,^8–11 she had a complete exchange transfusion before CPB was initiated. She was extubated in the operating room after surgery. The postoperative course was uneventful, and she was discharged from the hospital on postoperative day 6 with acceptable oxygen saturations (upper 80% range). Her hemoglobin S fraction was 3.2% and her hemoglobin C fraction was 3.0%.

The subsequent clinical course was uncomplicated. The patient was weaned from furosemide over 1 month; her ongoing medical regimen included aspirin, enalapril, amoxicillin, and folic acid. Three months postoperatively, her hemoglobin S fraction was 37% and her hemoglobin C fraction was 35%. As of October 2007, she exhibited normal growth and development, and her oxygen saturation levels remained well above 80%. Moreover, under this management, she experienced no infectious sequelae, neurologic symptoms, vaso-occlusive crises, or acute chest syndrome.

Discussion

This is the 1st report of an infant with HbSC disease who has undergone single-ventricle palliation with a Blalock-Taussig shunt and subsequent bidirectional Glenn anastomosis. To our knowledge, the management of combined HbSC and single-ventricle congenital heart disease has not been previously reported.

Hemoglobin SC disease is associated with anemia, vaso-occlusive crises, and acute chest syndrome—sequelae often initiated or exacerbated by stress, hypoxemia, dehydration, acidosis, and surgery.^1,2 Vaso-occlusive crises may occur with increased frequency in cyanotic patients who have HbSC disease, because they are often on diuretics, are at increased risk of infection, and undergo multiple surgeries. Furthermore, until these children undergo a Fontan procedure, their oxygen saturation levels will remain low, which increases the risks of red-blood-cell sickling and systemic embolization. Recurrent acute chest syndrome can also lead to chronic lung disease and increased pulmonary vascular resistance.¹² Avoiding these sequelae is integral to the bidirectional Glenn and Fontan procedures, because the postoperative physiology of each relies on passive pulmonary blood flow and low pulmonary vascular resistance.

Often, the 1st stage of a single-ventricle palliation is performed before the results of a newborn screen become available; however, it is unlikely that the 1st surgery will be complicated by red-blood-cell sickling, due to the protective presence of fetal hemoglobin until the age of at least 3 months. More vigilant newborn screening would unlikely aid in management during this initial neonatal palliation. Thereafter, fetal hemoglobin levels substantially decrease and fractions of hemoglo-bin S and C increase.

Our management approach was to maintain our patient's hemoglobin S fraction at approximately 35% or less before the addition of any substantial stress. Because our patient was acyanotic with sickle cell disease, we performed a complete exchange transfusion at the time of surgery involving CPB, in order to reduce the fraction of hemoglobin S.^8–11 Also, to prevent dehydration in our patient, we rapidly decreased the dosages of diuretics after her discharge from the hospital. To lower the risk of worsening hypoxemia as the infant grew in relation to the size of the Blalock-Taussig shunt, we performed the bidirectional Glenn anastomosis at a relatively early point. Ideally, the child will undergo an unfenestrated Fontan procedure at around 2½ to 3 years of age, thereby reducing the risks of hypoxemia and systemic emboli that are associated with nonseptated circulation.

We have described a unique combination of HbSC disease and tricuspid atresia type IA. To our knowledge, this is the 1st report of a patient with either HbSC or HbS disease who survived palliation of a single ventricle. This case illustrates that a multidisciplinary approach and close follow-up can result in a successful single-ventricle palliation in a patient who has HbSC.