Timothy F. Feltes

Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease

OBJECTIVES To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD). STUDY DESIGN A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization. RESULTS Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups. CONCLUSIONS Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.

Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient

Objective: Hyperglycemia in critical care populations has been shown to be a risk factor for increased morbidity and mortality. Minimal data exist in postoperative pediatric cardiac patients. The goal of this study was to determine whether hyperglycemia in the postoperative period was associated with increased morbidity or mortality. Design: Retrospective chart review. Setting: Tertiary care, free-standing pediatric medical center with a dedicated cardiac intensive care unit. Patients: We included 184 patients <1 yr of age who underwent cardiac surgery requiring cardiopulmonary bypass from October 2002 to August 2004. Patients with a weight <2 kg, a preoperative diagnosis of diabetes, preoperative extracorporeal membrane oxygenation support, solid organ transplant recipients, and preoperative renal or liver insufficiency were excluded. Interventions: None. Measurements and Main Results: Age was 4.3 ± 3.2 months and weight was 4.9 ± 1.7 kg at surgery. Duration of hyperglycemia was significantly longer in patients with renal insufficiency (p = .029), liver insufficiency (p = .006), infection (p < .002), central nervous system event (p = .038), extracorporeal membrane oxygenation use (p < .001), and death (p < .002). Duration of hyperglycemia was also significantly associated with increased intensive care (p < .001) and hospital (p < .001) stay and longer ventilator use (p < .001). Peak glucose levels were significantly different in patients with renal insufficiency (p < .001), infection (p = .002), central nervous system event (p = .01), and mortality (p < .001). Conclusions: Hyperglycemia in the postoperative period was associated with increased morbidity and mortality in postoperative pediatric cardiac patient. Strict glycemic control may improve outcomes in this patient population.

Early initiation of peritoneal dialysis after surgical repair of congenital heart disease

Abstract The mortality rate of infants who require renal replacement therapy after surgical repair of congenital heart disease has been reported to be 30%–79%. We report our experience with early initiation of continuous manual peritoneal dialysis (CPD) to treat fluid overload in 20 consecutive critically ill children who underwent CPD post cardiotomy. CPD catheters were inserted at the discretion of the cardiothoracic surgeon. CPD was started for evidence of total body fluid overload with inadequate urine output, and stopped when negative fluid balance was achieved and urine output improved. Median age was 10 days (range 3–186 days), mean time to start CPD post-operatively was 22 h (range 5–40 h), and mean duration of CPD was 50 h (range 13–92 h). CPD resulted in mean ultrafiltration of 93 ml/kg per day (range 43–233 ml/kg per day). Net negative fluid balance was 106 ml/kg per day (range 49–273 ml/kg per day). During CPD, the mean number of inotropes decreased from 2.2 to 1.6 (P<0.05) and urine output increased from 2.2 to 3.9 ml/kg per hour (P<0.01). No patient died during CPD or had CPD discontinued due to adverse hemodynamic effects. The overall mortality rate was 20%. We conclude that early initiation of CPD can safely and effectively promote fluid removal in infants after repair of congenital heart disease, with a lower mortality rate than has previously been reported.

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease A Scientific Statement From the American Heart Association

Thrombosis has long been recognized as a potentially life-threatening complication in children with congenital heart disease (CHD), children with acquired heart disease, and in adults with CHD. High-risk groups include patients with shunt- dependent single ventricles (shunt thrombosis, 8%–12%; 4%

Transesophageal echocardiographic detection of atrial thrombi in patients with nonfibrillation atrial tachyarrhythmias and congenital heart disease

OBJECTIVES We hypothesized an association between atrial thrombi and nonfibrillation atrial tachyarrhythmias in patients with congenital heart disease. BACKGROUND We observed a fatal thromboembolus after direct current cardioversion in an adolescent with atrial flutter and repaired tetralogy of Fallot. METHODS Using transesophageal echocardiography, we prospectively studied 19 consecutive patients with congenital heart disease with nonfibrillation atrial tachyarrhythmia (atrial flutter in 18, primary atrial tachycardia in 1) undergoing electrophysiologic procedures (median age 19.6 years, range 7.0 to 53.8; 11 male, 8 female). Transthoracic echocardiograms were available for 17 patients. RESULTS All transesophageal examinations were performed without incident. No atrial thrombi were detected in 11 patients who subsequently had uncomplicated direct current cardioversion. Eight solitary atrial thrombi were detected (incidence 42%). Six thrombi were located in the right atrium (Fontan repair in four patients, Ebsteins malformation repair in two), and two were noted in the left atrium (congenital hypertrophic cardiomyopathy and atrial septal defect repair in one patient each). Transthoracic echocardiograms were available in seven of eight patients with thrombus detected by transesophageal echocardiography, with only one study conclusive for an atrial thrombus. Cardioversion was deferred in six of eight patients with thrombus, and anticoagulation therapy was initiated. Uncomplicated electrophysiologic procedures were conducted in two patients at the time of detection of right atrial thrombus (atrioventricular node ablation in one patient, direct current cardioversion in the other). CONCLUSIONS Prothrombin conditions exist in patients with congenital heart disease with nonfibrillation atrial tachyarrhythmias, as indicated by a significant incidence of transesophageally detected atrial thrombi. The need for prophylactic anticoagulation and the safety of pharmacologic or direct current cardioversion are issues that remain unresolved.

Quantitated left ventricular systolic mechanics in children with septic shock utilizing noninvasive wall-stress analysis

Objective: To quantitate ventricular systolic mechanics in septic children. Design: Prospective wall‐stress analysis was compared to standard ejection phase indices. Setting: University‐based pediatric intensive care unit. Patients: Fifteen children with sepsis (hemodynamically stable, n = 5; in shock, n = 10). Measurements and Main Results: Left ventricular ejection phase indices: shortening fraction (shortening) and corrected mean velocity of circumferential shortening (velocity) were adjusted for end‐systolic wall stress (stress). Ejection phase, performance (stress‐shortening relation), contractility (stress‐velocity relation), and afterload (stress) were indexed to age‐corrected normal means, with variance of ≥2 sd regarded as significant. Preload index represented variance between performance and contractility indices. All hemodynamically stable septic patients had normal performance, contractility, and preload. Afterload was increased in three of five patients. Of the patients with septic shock, six often had decreased performance (decreased contractility and increased afterload, n = 4; decreased afterload, n = 1; and severe preload deficit, n = 1). Despite aggressive volume resuscitation, six of ten children in septic shock had evidence of diminished preload. Follow‐up studies in the septic shock patients demonstrated reversal of depressed ventricular contractility within 3 to 6 days in all four patients initially affected (p < .05). One patient developed late decreased performance and contractility in association with multiple organ failure. Ventricular loading abnormalities persisted in a follow‐up study of these patients including a preload deficit in five of ten patients in shock. Conclusions: The frequency rate (40%) of reversible impaired ventricular contractility in children with septic shock is significant. Afterload is normal or increased in the majority of septic subjects, possibly due to acute ventricular dilation. Decreased preload contributes to altered ventricular performance in the majority of children with septic shock, persisting days after the initiation of therapy. Wall‐stress analysis provided detailed information regarding ventricular mechanics that was not otherwise obtainable by standard ejection phase indices. (Crit Care Med 1994; 22:1647–1658)

Mediastinitis after pediatric cardiac surgery: a 15-year experience at a single institution

BACKGROUND The spectrum of sternal wound infections after cardiac surgery ranges from superficial infections to a deep sternal infection known as mediastinitis. Mediastinitis is a rare but clinically relevant source of postoperative morbidity and mortality in adult and pediatric patients after cardiac surgery. METHODS We retrospectively identified all patients diagnosed with mediastinitis after cardiac surgery from January 1987 to December 2002 (17 patients/7,616 surgeries = 0.2%). Demographic data, cardiac diagnosis, cardiac surgery, hospital length of stay, associated medical diagnosis, and surgical treatment for mediastinitis were collected. RESULTS Fifteen pediatric patients (age < 18 years) were diagnosed with mediastinitis (mean age at diagnosis 37.5 months, range 21 days to 17 years. The median postoperative day of diagnosis was 14 days (6 to 50 days). The most common organism was Staphylococcus species (n = 9). Six patients had an associated bacteremia. The median hospital length of stay for all patients was 42.5 days (range 16 to 163 days). The hospital mortality was 1 of 15 (6%). Each patient was treated with intravenous antibiotics; sternal debridement; and rectus abdominus flap reconstruction (n = 7), pectoralis muscle flap reconstruction (n = 3), omentum reconstruction (n = 1), or primary sternal closure (n = 4). Three patients have undergone redo-sternotomy with orthotopic heart transplantation, bidirectional cavopulmonary anastomosis, and replacement of a right ventricle to pulmonary artery homograft. CONCLUSIONS Timely diagnosis, aggressive sternal debridement, and liberal use of rotational muscle flaps can potentially minimize the morbidity and mortality in pediatric postoperative cardiac patients. Subsequent redo-sternotomy has not been problematic.

The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE The aim of this study was to determine the effect of prophylactic immune suppression on the incidence and severity ofpostpericardiotomy syndrome (PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND Prophylactic suppression of the inflammatory response has an unknown effect on the incidence and severity of PPS in children undergoing surgery with CPB. METHODS This randomized double-blind placebo controlled trial included two study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg) plus four additional intravenous doses over 24 h, and Group B received intravenous saline placebo at identical intervals. Data included patient demographics, cardiac diagnosis/operation, CPB time, incidence and severity of PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub, patient irritability, small pericardial +/- pleural effusion. Complicated PPS--noncomplicated PPS plus hospital readmission +/- pericardiocentesis or thoracentesis. RESULTS We randomized 266 children: 20 exclusions (6 perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n = 126) and Group B (n = 120). There were no significant group differences in gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and was treated as a covariate with no substantive outcome effect. In total, 39/246 children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There was no inter-group difference in overall PPS incidence (p = 0.73). However, Group A had a marginally significant increase in complicated PPS (p = 0.05). CONCLUSIONS Intravenous methylprednisolone at a standard anti-inflammatory dose administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in children. Short-term pre-CPB and post-CPB methylprednisolone treatment may complicate PPS.

A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease.

Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34–1.59 and RR: 0.49; 95% CI, 0.10–1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD.

Identification, imaging, functional assessment and management of congenital coronary arterial abnormalities in children

The coronary arteries, the vessels through which both substrate and oxygen are provided to the cardiac muscle, normally arise from paired stems, right and left, each arising from a separate and distinct sinus of the aortic valve. The right coronary artery runs through the right atrioventricular groove, terminating in the majority of instances in the inferior interventricular groove. The main stem of the left coronary artery bifurcates into the anterior descending, or interventricular, and the circumflex branches. Origin of the anterior descending and circumflex arteries from separate orifices from the left sinus of Valsalva occurs in about 1% of the population, while it is also frequent to find the infundibular artery arising as a separate branch from the right sinus of Valsalva. Anomalies of the coronary arteries can result from rudimentary persistence of an embryologic coronary arterial structure, failure of normal development or normal atrophy as part of development, or misplacement of connection of a an otherwise normal coronary artery. Anomalies, therefore, can be summarized in terms of abnormal origin or course, abnormal number of coronary arteries, lack of patency of the orifice of coronary artery, or abnormal connections of the arteries. Anomalous origin of the left coronary artery from the pulmonary trunk occurs with an incidence of approximately 1 in 300,000 children. The degree of left ventricular dysfunction produced likely relates to the development of collateral vessels that arise from the right coronary artery, and provide flow into the left system. Anomalous origin of either the right or the left coronary artery from the opposite sinus of Valsalva can be relatively innocuous, but if the anomalous artery takes an interarterial course between the pulmonary trunk and the aorta, this can underlie sudden death, almost invariably during or immediately following strenuous exercise or competitive sporting events. Distal anomalies of the coronary arteries most commonly involve abnormal connections, or fistulas, between the right or left coronary arterial systems and a chamber or vessel. We discuss the current techniques available for imaging these various lesions, along with their functional assessment, concluding with a summary of current strategies for management.