Biomedical subjects
Publications and source records attributed to Thomas L Spray.
This article discusses the necessity for standards for reasonable expectations and outcomes for neonatal treatment of congenital heart disease and the databases that allow such standards to be measured and to be compared among treatment centers.
OBJECTIVE: To explore whether prenatal diagnosis of congenital heart disease is associated with lower levels of parental distress and greater satisfaction with decisions about cardiothoracic surgery when compared to postnatal diagnosis. METHODOLOGY: A combined quantitative-qualitative design was used. Participants included the parents of 31 neonates (30 mothers and 22 fathers) admitted to the cardiac intensive care unit between 1 November 2001 and 1 May 2002 for repair of congenital cardiac malformations. Participants completed self-report measures of anxiety, optimism, and life events pre-operatively, and semi-structured qualitative interviews assessing satisfaction with decision-making within 1 week of the operation. RESULTS: At the time of surgery, mothers of neonates receiving the diagnosis prenatally did not differ from mothers of neonates receiving the diagnosis postnatally on measures of anxiety, optimism, and life events. Fathers of neonates receiving the diagnosis prenatally, however, reported more optimism, lower state and trait anxiety, and fewer negative life events than fathers of neonates receiving the diagnosis postnatally. When we analyzed the interviews, we found that, regardless of the timing of the diagnosis, parents felt as though they made a genuine choice for their baby to have surgery. CONCLUSIONS: In this pilot study, fathers who learned prenatally that their child had a congenital cardiac malformation were less distressed than those who discovered this fact only postnatally. From the parental perspective, nonetheless, distress and urgency do not impair their ability to make decisions about neonatal cardiac surgery.
The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6 year's age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482 ml kg(-1) and was independent of age. Clearance was a linear function of age given by Cl = 2.42 ml kg(-1) min(-1) [1 + 0.396*age].
OBJECTIVE: To identify factors associated with mortality in children with heart disease managed with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective chart review. SETTING: Tertiary care university-affiliated children's hospital. PATIENTS: All pediatric cardiac intensive care unit patients managed with ECMO between January 1, 1995, and June 30, 2001. INTERVENTIONS: None. RESULTS: During the study period, 137 patients were managed with ECMO in the pediatric cardiac intensive care unit. Of the 137 patients, 80 (58%) survived > or =24 hrs after decannulation, and 53 (39%) survived to hospital discharge. Patients managed with ECMO following cardiac surgery were analyzed separately from patients not in the postoperative period. Factors associated with an increased probability of mortality in the postoperative patients were age <1 month, male gender, longer duration of mechanical ventilation before ECMO, and development of renal or hepatic dysfunction while on ECMO. Single ventricle physiology and failure to separate from cardiopulmonary bypass were not associated with an increased risk of mortality. Cardiac physiology and indication for ECMO were not associated with mortality rate. Although longer duration of ECMO was not associated with increased mortality risk, patients with longer duration of ECMO were less likely to survive without heart transplantation. CONCLUSIONS: In a series of 137 patients managed with ECMO in a pediatric cardiac intensive care unit, survival to hospital discharge was 39%. In postoperative patients only, mortality risk was increased in males, patients <1 month old, patients with a longer duration of mechanical ventilation before initiation of ECMO, and patients who developed renal or hepatic failure while on ECMO.
OBJECTIVE: To report an influenza B infection with associated myocarditis and severe skeletal myositis. DESIGN: Case report. SETTING: Cardiac intensive care unit in a university-affiliated children's hospital. PATIENT: A 4-yr-old girl. RESULTS: The patient was successfully supported with extracorporeal membrane oxygenation for profound myocardial dysfunction and a combination of plasmapheresis and continuous venovenous hemodialysis for rhabdomyolysis and acute renal failure. CONCLUSIONS: This case provides a reminder that patients presenting with viral illness or myoglobinuria accompanied by renal failure, with or without associated myocarditis, may be demonstrating symptoms of influenza B.
OBJECTIVES: We sought to assess the prevalence and progression of neo-aortic root dilation and valvar regurgitation after staged reconstruction for hypoplastic left heart syndrome (HLHS). BACKGROUND: In HLHS, the pulmonary valve functions as the neo-aortic valve. Neo-aortic valve dysfunction has been observed after arterial switch operation and the Ross procedure. METHODS: Patients with HLHS born before January 1995 who had the Fontan operation and had serial echocardiograms were included. Echocardiograms were reviewed preoperatively, after each surgical reconstruction, and at most recent follow-up for neo-aortic root size and severity of neo-aortic regurgitation (AR). Potential risk factors for neo-aortic valve dysfunction were assessed. RESULTS: Fifty-three patients met inclusion criteria. Bidirectional superior cavopulmonary anastomosis as an interim procedure was performed in 39 patients (74%). Median duration of follow-up was 9.2 (range 5.1 to 21) years. During follow-up, the neo-aortic root progressively dilated out of proportion to body size over time, with 52 patients (98%) having a Z-score >2 at most recent follow-up. Neo-AR was present in 61% of patients at most recent follow-up, with progression over time in 26 patients (49%). However, neo-AR was more than mild in only three patients. Significantly larger neo-aortic root Z-scores were observed in patients with any degree of neo-AR at most recent follow-up. No other anatomic or clinical variables correlated with severity of neo-AR or root dilation. CONCLUSIONS: After staged reconstruction for HLHS, neo-aortic root dilation and neo-AR progress over time. Early volume unloading does not have a beneficial impact on dilation of the neo-aortic root. These findings raise concerns about neo-aortic valve function into adulthood.
BACKGROUND: Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. METHODS AND RESULTS: The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25- microg/kg bolus over 60 minutes followed by a 0.25- microg/kg per min infusion for 35 hours; high dose, 75- microg/kg bolus followed by a 0.75- microg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P=0.023) in 238 treated patients and 64% (P=0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049). CONCLUSIONS: The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.
BACKGROUND: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. METHODS: A single-institution prospective study of patients <or=6 months of age undergoing cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction. Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development. RESULTS: One-year evaluation was performed in 244 patients. After adjustment for preoperative and postoperative covariates-including gestational age, age at operation, sex, race, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development (P =.036). Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index. CONCLUSIONS: Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery. The effect was independent of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest. An effect of the apolipoprotein E epsilon4 allele was not detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery.
OBJECTIVE: The Fontan procedure is utilized as a final reconstructive procedure for patients with functional single ventricle. Short- and long-term outcomes have improved significantly, however, some patients require additional cardiac procedures following the Fontan operation. The outcomes for these reinterventions are not known. METHODS: Cardiac Surgery and Cardiac Intensive Care Unit databases at The Children's Hospital of Philadelphia were reviewed to identify all patients who underwent cardiac surgery after a previous Fontan operation between January 1, 1995 and December 31, 2001. RESULTS: During the study period, 123 procedures were performed in 71 patients. The median time from Fontan to reoperation was 3.6 years (range 0.1-20 years). Indications for reintervention included arrhythmia, cyanosis, 'failing' Fontan circulation or exercise intolerance, protein losing enteropathy, atrioventricular valve (AVV) regurgitation, and other indications. Procedures included pacemaker insertion or revision (n = 59, 48%), reinclusion of previously excluded hepatic veins (n = 16, 13%), revision to either a lateral tunnel or extra-cardiac conduit Fontan (n = 13, 11%), cardiac transplantation (n = 9, 7%), enlargement or creation of a baffle fenestration (n = 6, 5%), isolated AVV repair or replacement (n = 2, 2%), and other procedures (n = 18, 14%). There were five early and five late deaths. Hospital mortality was greatest for patients undergoing cardiac transplantation (4/9, 44%), accounting for 80% of the early deaths. CONCLUSIONS: Surgical reinterventions following the Fontan procedure may be necessary for multiple indications which result in impairment of the Fontan circulation. Most reinterventions can be performed with minimal morbidity and mortality. Survival for patients requiring cardiac transplantation following the Fontan procedure remains poor.
OBJECTIVE: Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. METHODS: Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). RESULTS: There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. CONCLUSIONS: Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.
OBJECTIVE: This study was undertaken to determine the demographic, anatomic, institutional, and surgical risk factors associated with outcomes after the Norwood operation. METHODS: A total of 710 of 985 neonates with critical aortic stenosis or atresia enrolled in a prospective 29-institution study between 1994 and 2000 underwent the Norwood operation. Admission echocardiograms were independently reviewed for 64% of neonates. Competing risks analyses were constructed for outcomes after Norwood operation and after cavopulmonary shunt. Incremental risk factors for outcome events were sought. RESULTS: Overall survivals after the Norwood operation were 72%, 60%, and 54% at 1 month, 1 year, and 5 years, respectively. According to competing risks analysis, 97% of neonates reached a subsequent transition state by 18 months after Norwood operation, consisting of death (37%), cavopulmonary shunt (58%), or other state (2%, cardiac transplantation, biventricular repair, or Fontan operation). Risk factors for death occurring before subsequent transition included patient-specific variables (lower birth weight, smaller ascending aorta, older age at Norwood operation), institutional variables (institutions enrolling < or =10 neonates, two institutions enrolling >/=40 neonates), and procedural variables (shunt originating from aorta, longer circulatory arrest time, and management of the ascending aorta). Of neonates undergoing cavopulmonary shunt, 91% had reached a subsequent transition state by 6 years after cavopulmonary shunt, consisting of Fontan operation (79%), death (9%), or cardiac transplantation (3%). Risk factors for death occurring before subsequent transition included younger age at cavopulmonary shunt and need for right atrioventricular valve repair. CONCLUSIONS: Competing risks analysis defines the prevalence of the various outcomes after Norwood operation and predicts improved outcomes with successful modification of controllable risk factors.
OBJECTIVE: To identify pre- and intraoperative variables associated with postoperative acute neurologic events (ANEs), including seizures and coma, in newborn survivors of congenital heart surgery undergoing deep hypothermic circulatory arrest (DHCA), and to risk-stratify this population on the basis of preoperative risk variables for the purpose of designing future neuroprotection trials. METHODS: Survivors of newborn heart surgery who were enrolled in a neuroprotection trial provided a comprehensive database for the evaluation of pre- and intraoperative variables that influence the postoperative occurrence of ANEs (seizures or coma). Patients with hypoplastic heart syndrome were excluded. After characterization of the study population, stepwise logistic regression, combined with clinical judgment, was used to identify variables that were most likely to be associated with an increased risk of seizures in the study sample and that were most likely to be generalized to other populations. RESULTS: Data were available on 164 nonhypoplastic left heart syndrome survivors who underwent newborn heart surgery using DHCA. ANEs occurred in 31 (18.9%) including "seizures alone" (n = 28), "coma alone" (n = 2) or "seizures and coma" (n = 1). A preoperative risk model was constructed demonstrating that infants with a genetic condition and aortic arch obstruction had a 47.8% risk of ANEs compared with all other remaining infants, who had a 9.9% risk. It was also found that prolonged DHCA time (>or=60 minutes) can be a significant risk for infants who have a preexisting genetic condition; however, infants who have genetic conditions and do not undergo prolonged DHCA time or have an aortic arch obstruction are not at increased risk of ANEs. CONCLUSIONS: This study provides new information about the occurrence of ANEs after newborn heart surgery. Seizures or coma, which appeared in approximately 19% of all non-hypoplastic left heart syndrome survivors, were not random events but were significantly associated with specific types of congenital heart disease, the presence of genetic conditions, and prolonged DHCA time. The 3 identified variables permitted individual cases to be assigned to low-, intermediate-, or high-risk categories. Because neonatal seizures are a good surrogate marker of long-term neurologic outcome, these models provide useful information to stratify individual patients for risk of seizures in future neuroprotection trials.
INTRODUCTION: Persistent patent ductus arteriosus (PDA) often produces hemodynamic and respiratory derangement necessitating use of inotropic drugs and escalating ventilatory support in premature infants. When medical therapy fails, surgical ligation is indicated. Because of the risks of transferring unstable neonates to the operating room, ductal ligation is routinely performed at the neonatal intensive care unit (NICU) bedside. Some patients, however, require transfer from hospitals without pediatric cardiac surgical teams. In an attempt to eliminate the risks associated with transfer, a surgical team from our institution offered to perform duct ligation in the NICUs of referring institutions. This experienced team consisted of a pediatric cardiac attending anesthesiologist and certified registered nurse anesthetist, cardiac operating room nurses, an attending cardiothoracic surgeon, and a cardiothoracic surgery fellow. We retrospectively reviewed our experience. METHODS: After approval from the Committee for the Protection of Human Subjects, the charts of premature neonates who underwent PDA ligation in the NICU at the Children's Hospital of Philadelphia NICU or in a network NICU between January 1996 and April 2002 were reviewed. Data abstracted included institution, gender, gestational age, birth weight, weight at surgery, and number of courses of indomethacin. Mean arterial blood pressure and use of inotropic drugs and ventilatory parameters (fraction of inspired oxygen, peak inspiratory pressure) were recorded at the time of surgery and 96 hours postoperatively. Perioperative complications were recorded. RESULTS: Seventy-two patients met the criteria for inclusion. PDA ligation was performed in the Children's Hospital of Philadelphia NICU in 38 of 72 patients, 53% (group 1). The remainder, 34 of 72 (47%) underwent PDA ligation in the NICU at 1 of 6 referring institutions (group 2). There were no significant differences between groups with respect to demographics, number of courses of indomethacin, or use of inotropic drugs or ventilatory support. The incidence of perioperative complications did not differ between groups: 3 in group 1 (bleeding, chylothorax, and pleural effusion) and 3 in group 2 (pneumothorax [3]). There were no anesthetic-related complications. Seven patients died (4 in group 1 and 3 in group 2), none within 96 hours of surgery and none secondary to the procedure. DISCUSSION: The data demonstrate that an experienced team can perform PDA ligation safely in NICUs of hospitals without on-site pediatric cardiac surgical capabilities in critically ill neonates without incurring the risks inherent in patient transport. Most importantly, patient care is continued by the neonatology team most familiar with the infant's medical and social history, and the patient's family is minimally inconvenienced.
BACKGROUND: Neurological deficits are observed in patients with congenital heart disease (CHD) before and after neonatal surgery, the etiology being multifactorial. To understand the impact of preoperative events and to characterize the evaluation of neurological injury, we performed serial magnetic resonance imaging (MRI) studies of the brain in a cohort of neonates undergoing open-heart surgery. METHODS AND RESULTS: Twenty-four term neonates with CHD were studied prospectively with brain MRI: before surgery, within 2 weeks of surgery, and several months after surgery. Preoperative MRI examinations showed periventricular leukomalacia (PVL) in 4 patients (16%) and infarct in 2 subjects (8%). MR spectroscopy was performed in 19 subjects preoperatively and revealed elevated brain lactate in 53%. An early postoperative MRI (n=21) identified new PVL in 48%, new infarct in 19%, and new parenchymal hemorrhage in 33%. New lesions or worsening of preoperative lesions occurred in 67% of subjects. No patient- or procedure-related factors for the development of early postoperative lesions were identified. A late postoperative MRI (n=17) demonstrated resolution of early lesions in 8 and mild cerebral atrophy in 2. CONCLUSIONS: Mild ischemic lesions, primarily in the form of PVL, occur in a number of neonates with CHD before surgery and >50% of patients postoperatively. Resolution of these lesions is common 4 to 6 months after surgery. Longer-term follow-up is needed to determine the significance of perioperative ischemic lesions on functional outcome.
BACKGROUND: Early outcomes after repair of total anomalous pulmonary venous connection continue to improve; however, little information is available concerning long-term functional status and quality of life. METHODS: One hundred patients underwent isolated total anomalous pulmonary venous connection repair at The Children's Hospital of Philadelphia between 1983 and 2001. Medical records were reviewed and a standardized questionnaire was administered to guardians of survivors. RESULTS: Median age at repair was 15.5 days (range, 1 to 563 days). Overall hospital mortality was 14%, decreasing from 19% before 1995 to 5% after 1995. At 15 years after repair, actuarial survival was 84% and freedom from late death or reintervention for hospital survivors was 85%. At a median follow-up of 5.9 years (range, 0 to 17.7 years) 64% of guardians described their child's overall health as excellent, 27% good, 9% fair, and 0% poor. With regard to school performance, 40% of children were characterized as above average, 29% average, 4% below average, and 27% were in special education classes or had repeated grades. By multivariable logistic regression, the presence of associated chromosomal or noncardiac syndromes and pulmonary venous obstruction were found to be significant factors with regard to parental assessment of both overall health and school performance. CONCLUSIONS: The majority of children who undergo isolated total anomalous pulmonary venous connection repair can expect an excellent long-term functional outcome. Factors present before operation, such as pulmonary venous obstruction and associated anomalies, can influence overall health and school performance in the long term.
BACKGROUND: Junctional ectopic tachycardia (JET) occurs commonly after pediatric cardiac operation. The cause of JET is thought to be the result of an injury to the conduction system during the procedure and may be perpetuated by hemodynamic disturbances or postoperative electrolyte disturbances, namely hypomagnesemia. The purpose of this study was to determine perioperative risk factors for the development of JET. METHODS: Telemetry for each patient admitted to the cardiac intensive care unit from December 1997 through November 1998 for postoperative cardiac surgical care was examined daily for postoperative JET. A nested case-cohort analysis of 33 patients who experienced JET from 594 consecutively monitored patients who underwent cardiac operation was performed. Univariate and multivariate analyses were conducted to determine factors associated with the occurrence of JET. RESULTS: The age range of patients with JET was 1 day to 10.5 years (median, 1.8 months). Univariate analysis revealed that dopamine or milrinone use postoperatively, longer cardiopulmonary bypass times, and younger age were associated with JET. Multivariate modeling elicited that dopamine use postoperatively (odds ratio, 6.2; p = 0.01) and age less than 6 months (odds ratio, 4.0; p = 0.02) were associated with JET. Only 13 (39%) of the patients with JET received therapeutic interventions. CONCLUSIONS: Junctional ectopic tachycardia occurred in 33 (5.6%) of 594 patients who underwent cardiac operation during the study period. Postoperative dopamine use and younger age were associated with JET. It may be speculated that dopamine should be discontinued in the presence of postoperative JET.
OBJECTIVES: Recent studies have suggested that survival following the Norwood procedure is influenced by anatomy and is worse for patients with hypoplastic left heart syndrome (HLHS), particularly aortic atresia (AA), as compared to other forms of functional single ventricle and systemic outflow tract obstruction. The current study was undertaken to evaluate our recent experience with the Norwood procedure and to evaluate potential predictors of operative and 1-year mortality. METHODS: A retrospective study of risk factors for operative and 1-year mortality in 158 patients undergoing the Norwood procedure between January 1, 1998 and June 30, 2001. RESULTS: HLHS was present in 102 patients (70 with AA) and other forms of functional single ventricle with systemic outflow tract obstruction in the remaining 56. Operative survival was 77% (122/158), 78% for patients with HLHS and 75% for patients with other diagnoses. Multivariable analysis identified birth weight (odds ratio (OR) 0.18/kg, 95% confidence limit (CL) 0.08-0.42, P<0.001), associated cardiac anomalies (OR 4.45, 95% CL 1.50-13.2, P=0.001), total support time (OR 1.02/min, 95% CL 1.01-1.03, P=0.004), and extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) support (OR 17.8, 95% CL 4.40-71.0, P<0.001) as predictors of operative mortality. The anatomic diagnosis (HLHS versus non-HLHS) was not a predictor of mortality, P=0.6). The Kaplan-Meier survival estimate at 1 year was 66% (95% CL 58-73%) and was not different for patients with HLHS compared to non-HLHS, P=0.5. For patients who have survived the Norwood procedure, survival to 1 year was 86% (95% CL 78-91%). Presence of an extra-cardiac anomaly or genetic syndrome (OR 2.70, 95% CL 0.98-7.41%, P=0.05) and presence of an additional cardiac defect (OR 3.99, 95% CL 1.67-9.57, P=0.002) were predictors of worse survival in the first year of life. CONCLUSIONS: The Norwood procedure is currently being applied to a heterogeneous group of patients. Operative and 1-year survival are equivalent for patients with HLHS and those with other cardiac defects. The presence of additional cardiac or extra-cardiac anomalies are predictors of poor outcome.