Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.

BACKGROUND: The molecular basis of heterotaxy and congenital heart malformations associated with disruption of left-right asymmetry is broad and heterogenous, with over 25 genes implicated in its pathogenesis thus far. OBJECTIVE: We sought to elucidate the molecular basis of laterality disorders and associated congenital heart defects in a cohort of 30 unrelated probands of Arab-Muslim descent, using next-generation sequencing techniques. METHODS: Detailed clinical phenotyping followed by whole-exome sequencing (WES) was pursued for each of the probands and their parents (when available). Sanger sequencing was used for segregation analysis of disease-causing mutations in the families. RESULTS: Using WES, we reached a molecular diagnosis for 17 of the 30 probands (56.7%). Genes known to be associated with heterotaxy and/or primary ciliary dyskinesia, in which homozygous pathogenic or likely pathogenic variants were detected, included CFAP53 (CCDC11), CFAP298 (C21orf59), CFAP300, LRRC6, GDF1, DNAAF1, DNAH5, CCDC39, CCDC40, PKD1L1 and TTC25. Additionally, we detected a homozygous disease causing mutation in DAND5, as a novel recessive monogenic cause for heterotaxy in humans. Three additional probands were found to harbour variants of uncertain significance. These included variants in DNAH6, HYDIN, CELSR1 and CFAP46. CONCLUSIONS: Our findings contribute to the current knowledge regarding monogenic causes of heterotaxy and its associated congenital heart defects and underscore the role of next-generation sequencing techniques in the diagnostic workup of such patients, and especially among consanguineous families.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients.

Brain injury is a major source of patient morbidity after cardiac surgery in children. New early accurate biomarkers are needed for the diagnosis of patients at risk for cerebral postoperative damage. Specific circulating miRNAs have been found as suitable biomarkers for many diseases. We tested whether miRNA-124a reflects neurological injury in pediatric patients following heart surgery. Serum samples were obtained from 34 patients before and six hours after heart surgery. MiRNAs-124a was quantified by RQ-PCR. MiRNA-124a levels six hours after heart surgery correlated with the neurological outcome of the patients. In children with neurological deficits, miRNA-124a levels increased while in those with no neurological deficits the levels decreased. MiRNA-124a was able, at six hours after the operation, to identify patients who are at risk for the appearance of neurological deficits. Circulating miRNA-124a is a potential biomarker for the appearance of neurological deficits in pediatric patients following heart surgery. Graphical Abstract.

Inappropriate Shocks and Power Delivery Using Adult Automatic External Defibrillator Pads in a Pediatric Patient.

ABSTRACT: The use of automatic external defibrillators (AEDs) during pulseless resuscitations is considered safe and reliable, and was established as part of the guidelines in out-of-hospital events. Based on extensive studies, the use of the standard AED is now indicated in every age group with a preference of pediatric pad application for small children and babies. If unavailable, adult pads are recommended. We report a case of 2 inappropriate AED shocks that were delivered to a neonate during a pulseless resuscitation after application of adult pads. The 3.6-kg patient received 2 shocks, over 200 J each, for sinus bradycardia that was not detected by the device. Although treated inappropriately with high voltage, no cardiac or skin sequelae were detected, and the patient had normal cardiac and neurological development later on.

Immune and TRG repertoire signature of the thymus in Down syndrome patients.

BACKGROUND: Patients with Down syndrome (DS) are at increased risk for infections and autoimmune disorders. Although several immunological abnormalities were previously found, differences in T cell receptor repertoire have never been shown. Thus we compared the T cell receptor gamma (TRG) repertoire in DS and non-syndromic pediatric patients by next-generation sequencing, in addition to other immunological markers. METHODS: Genomic DNA was extracted from thymuses of pediatric patients who underwent heart surgery, where six were with DS and six were non-syndromic patients. Peripheral blood counts, T cell subpopulations, thymus TCR excision circles (TRECs), spectratyping, and next-generation sequencing for TRG were analyzed. RESULTS: The mean age of the patients was 7 months and the mean lymphocyte count was slightly lower in patients with DS, whereas thymus TREC results were similar to non-syndromic patients (p = 0.197). The TRG repertoire analysis showed that patients with DS had a significantly larger number of unique TRG sequences, together with decreased clonal expansion. Lastly, the V and J gene usages in the thymus were similar in DS and non-syndromic patients. CONCLUSIONS: Patients with DS showed increased TRG repertoire diversity with decreased clonal expansion compared to non-syndromic patients. IMPACT: Alterations in T cell receptor gamma repertoire were found in patients with Down syndrome using next-generation sequencing (NGS) technique. Patients showed increased repertoire diversity and decreased clonal expansion compared to controls. These findings add to previous reports on abnormalities of other immune system components in patients with Down syndrome. NGS technique may point out differences not seen by previous methods. Repertoire abnormalities may contribute to those patients' predisposition to infections and autoimmune diseases.

A founder truncating variant in GDF1 causes autosomal-recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds.

The genetic basis of congenital heart malformations associated with disruption of left-right (L-R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left-right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab-Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left-right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.

Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery.

Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.

The Bilateral Bidirectional Glenn Operation as a Risk Factor Prior to Fontan Completion in Complex Congenital Heart Disease Patients.

INTRODUCTION: The Glenn procedure is generally performed as a second-stage palliative procedure toward the completion of Fontan circulation in patients with a functionally univentricular heart. Safe Fontan completion requires normal ventricular function, competent atrioventricular valves, normal pulmonary arteries anatomy, and low pulmonary vascular resistances (PVRs), which is merely an estimation that considers both lungs as a single unit. Clinical observations revealed that patients who previously underwent bilateral bidirectional cavopulmonary anastomosis (b-BCPA) had a stormier postoperative course in respect to other patients with previous unilateral BCPA (u-BCPA) postoperatively after Fontan completion. This retrospective study was designed to compare and analyze the outcomes of patients following Fontan completion with previous u-BCPA versus b-BCPA. PATIENTS AND METHODS: A total of 98 patients were divided into two groups based on the presence or absence of bilateral superior vena cava (SVC). Group 1 included 80 patients with unilateral SVC, and group 2 included 18 patients with bilateral SVC. Univariate and multivariate (SPSS) analyses were performed with regard to mortality and failure. P value of <.05 was considered as significant. RESULTS: Prior to the total cavopulmonary anastomosis operation, the G1 and G2 had similar demographic and physiological findings, ages and weights were 4.3 ± 1.72 years and 15.0 ± 3.71 kg in G1 and 4.8 ± 3.21 years and 17.5 ± 9.76 kg in G2. Mean end-diastolic ventricular pressures (in mm Hg) were 10.50 ± 2.86 in G1 and 10.28 ± 3.07 in G2 and the mean PVRs (in Woods units) were 1.66 ± 1.29 in G1 and 1.49 ± 0.82 in G2. The Stormy postoperative course, Fontan failure, and early mortality were all significantly higher in G2 in respect to G1 ( P value <.05). G1 mortality rate was 3.7%, 3 patients of 80, while in G2, the mortality rate was 22%, 4 patients of 18. Late Fontan failure rates were 6% for G1 patients where two patients developed pulmonary hypertension, two patients developed heart failure, and one patient had protein losing enteropathy (PLE), and 22% for the G2 patients of which two patients developed heart failure, one patient had PLE, and one patient had persistent low systemic venous saturation. CONCLUSIONS: Our results have demonstrated that patients after b-BCPA might have a tendency for worse outcomes upon Fontan completion. The b-BCPA is associated with pulmonary artery bifurcation stenosis and presents multiple sources of pulmonary blood flow where conventional PVR calculation might be imprecise and misleading since it considers the lungs as a single unit. Therefore, b-BCPA engenders correction of the conventional PVR calculation to consider each lung separately. Furthermore, the surgical approach for patients with persistent left SVC and univentricular heart should be modified.

MiRNA-208a as a Sensitive Early Biomarker for the Postoperative Course Following Congenital Heart Defect Surgery.

Current clinical risk assessment strategies have poor accuracy for identifying patients who will suffer adverse perioperative events. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome after pediatric heart surgery. We tested the hypothesis that miRNAs-208a, -208b, and -499 can serve as noninvasive biomarkers for the extent of myocardial damage and the postoperative clinical course of pediatric patients with congenital heart defects (CHDs) at an early time point following surgery. Serum samples were obtained from 79 pediatric patients before and 6, 12, and 24 h after surgery. MiRNAs-208a, -208b, and -499 were quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Our results show that the levels of the three miRNAs were elevated at 6 h after surgery, remained high at 12 h and declined at 24 h after the operation. The amount of all three miRNAs at 6 h after surgery correlated with surgical and laboratory parameters. Their amount at 12 h after surgery correlated with the length of stay at the hospital. Expression levels of miRNA-208a at 6 h were related to the appearance of cardiac complications, and could predict whether a patient will sustain complications or will be ventilated for more than 48 h after surgery. Circulating miRNA-208a is a predictor for the risk of developing cardiac complications during the postoperative course as early as 6 h after heart surgery for CHD in pediatric patients.

The Utilization of an Insertable Cardiac Monitor in a Child With Pallid Breath-Holding Spells.

BACKGROUND: Pacing can be a successful treatment for pallid breath-holding spells, primarily in individuals with severe bradycardia. PATIENT DESCRIPTION: We describe an 18-month-old girl experiencing severe pallid breath-holding spells in whom repeated electrocardiographic, Holter, and electroencephalographic monitoring tests were all normal. RESULTS: Using a subcutaneous insertable cardiac monitor, severe bradycardia was detected during one of this girl's episodes. This finding led to a pacemaker implantation. Subsequently, her breath-holding spells completely resolved. CONCLUSION: This child illustrates the ability of the insertable cardiac monitor to help and diagnose arrhythmias in children with unresolved clinical findings. The ability to implant it with a minimal scar makes it ideal for uncooperative individuals with relative few and unexpected episodes that are hard to diagnose.

Micro-RNA-208a, -208b, and -499 as Biomarkers for Myocardial Damage After Cardiac Surgery in Children.

OBJECTIVES: To test the hypothesis that cardiac-enriched micro-RNAs can serve as accurate biomarkers that reflect myocardial injury and to predict the postoperative course following pediatric cardiac surgery. Micro-RNAs have emerged as plasma biomarkers for many pathologic states. We aimed to quantify preoperative and postoperative plasma levels of cardiac-enriched micro-RNA-208a, -208b, and -499 in children undergoing cardiac surgery and to evaluate correlations between their levels, the extent of myocardial damage, and the postoperative clinical course. DESIGN: PICU. PATIENTS: Thirty pediatric patients that underwent open heart surgery for the correction of congenital heart defects between January 2012 to July 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At 12 hours post surgery, the plasma levels of the micro-RNAs increased by 300- to 4,000-fold. At 24 hours, their levels decreased but remained significantly higher than before surgery. Micro-RNA levels were associated with troponin levels, longer cardiopulmonary bypass and aortic crossclamp times, maximal postoperative aspartate aminotransferase levels, and delayed hospital discharge. CONCLUSIONS: Circulating micro-RNA-208a, -208b, and -499 are detectable in the plasma of children undergoing cardiac surgery and may serve as novel biomarkers for monitoring and forecasting postoperative myocardial injury and recovery.

Insight into normal thymic activity by assessment of peripheral blood samples.

The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.

The role of cardiac computed tomography in infants with congenital heart disease.

BACKGROUND: Patients with complex congenital heart disease (CHD) have a high incidence of extracardiac vascular and non-vascular malformations. Those additional abnormalities may have an impact on the precise planning of surgical or non-surgical treatment. OBJECTIVES: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings. METHODS: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan. RESULTS: Median age was 28 +/- 88 days and mean weight 3.7 +/- 1.5 kg. Diagnostic quality was good or excellent (visual image score 3-4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information on extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 +/- 0.07 mSv (range 1.014-2.3 mSv). CONCLUSIONS: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE with regard to extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose.

Increased RNA editing in children with cyanotic congenital heart disease.

PURPOSE: To test the hypothesis that RNA editing is altered in pediatric patients with cyanotic congenital heart disease (CHD) and to determine whether A-to-I RNA editing is associated with the postoperative course following cardiac surgery. Cyanotic CHD is associated with a unique pathophysiology caused by chronic hypoxia. The perioperative course of cyanotic infants is partly dictated by the degree of expression of inflammatory and cardiac genes, some of which undergo A-to-I RNA editing. METHODS: RNA was extracted pre- and postoperatively from blood samples of cyanotic and acyanotic patients. Each sample was analyzed for A-to-I RNA editing using automatic DNA sequencing of an intronic segment of the MED13 gene. RNA expression levels of adenosine deaminase acting on RNA (ADAR) enzymes responsible for RNA editing were examined by quantitative reverse-transcriptase polymerase chain reaction. RESULTS: A-to-I RNA editing in MED13 was significantly higher among cyanotic patients (n = 19) than acyanotic ones (n = 18) both pre- and postoperatively, as manifested by average editing at seven highly edited sites (27.4 ± 8.5% versus 20.8 ± 10.2%; P = 0.038) and editing at specific sites, e.g., position 14 (20.2 ± 5.1% versus 14.5 ± 5.2%; P = 0.002). Cyanotic patients exhibited a more complicated postoperative course than acyanotic patients. ADAR2 RNA levels were significantly lower among cyanotic patients. CONCLUSIONS: Cyanotic children manifest significantly higher rates of A-to-I RNA editing than acyanotic children as well as a more complicated surgical course. Posttranscriptional RNA changes may affect cellular and metabolic pathways and influence the perioperative course following hypoxia.

Delta chemokine (fractalkine)--a novel mediator of pulmonary arterial hypertension in children undergoing cardiac surgery.

BACKGROUND: Fractalkine (FKN), a unique chemokine associated with pulmonary hypertension, may be involved in the acute stress response that regulates inflammation after cardiopulmonary bypass (CPB) surgery. We characterized FKN levels and correlated them with clinical parameters in children undergoing cardiac surgery involving CPB. METHODS: Twenty-seven consecutive patients, aged 30 days to 11.5 years, who underwent surgery for correction of congenital heart defects, were prospectively studied. Serial blood samples were collected preoperatively, upon termination of CPB, and at six points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70° C until assayed. Clinical and laboratory data were collected. RESULTS: Baseline FKN levels were skewed between patients. Patients with low FKN levels showed significantly higher levels of oxygen saturation in room air compared to patients with high FKN levels (p<0.05). Moreover, there was a positive correlation between preoperative pulmonary arterial hypertension and FKN levels (p<0.05). Surprisingly, FKN elevation from preoperative to postoperative levels displayed no discernible pattern. CONCLUSIONS: FKN levels significantly correlate with preoperative hypoxemia and PAH, suggesting that FKN may be up-regulated during hypoxemia. CPB is not associated with acute changes in circulating FKN levels. The role of FKN in the postoperative course should be further investigated.

Blood lactate levels differ significantly between surviving and nonsurviving patients within the same risk-adjusted Classification for Congenital Heart Surgery (RACHS-1) group after pediatric cardiac surgery.

This study aimed to examine the association between lactate levels in the first hours after surgery for congenital heart defects and the results of Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) scoring and to evaluate serial lactate levels over time to determine whether they can serve as a supplementary tool for postoperative assessment within the same RACHS-1 group of patients. A retrospective cohort study was performed using data retrieved from a clinical database of 255 children who had surgery for congenital heart defects between 1999 and 2001 at Sheba Medical Center. Lactate levels were measured postoperatively four times (mg/dL units). The last sample was taken at the end of the surgical procedure, and lactate levels were measured at admission to the pediatrics critical care unit, then 6 and 12 h after admission. The lactate level was measured via arterial blood gases. A total of 27 deaths occurred, yielding a mortality rate of 7.4% when Norwood operations were excluded and 10.16% when they were included. The mean initial postoperative lactate level was significantly lower for survivors (42.2 ± 32.0 mg/dL) than for nonsurvivors (85.4 ± 54.1 mg/dL) (p < 0.01). The serial mean lactate levels decreased progressively for all surviving patients (r (2) = 0.96) compared with nonsurvivors (r (2) = 0.02). The lactate levels correlated with the RACHS-1 subgroups at each time point (r (2) > 0.96 for all). The Pearson correlations between postoperative lactate levels (last lactate measurement taken in the operating room) and cardiopulmonary bypass (CPB) duration (r = 0.549), clamp duration (r = 0.586), and the inotropic score (r = 0.466) (p < 0.001 for all) were significantly positive. The correlations between the maximum lactate levels (during the first 12 postoperative hours) and CPB duration (r = 0.496), clamp duration (r = 0.509), and the inotropic score (r = 0.633) (p < 0.001 for all) were extremely positive. The early elevation of lactate levels in RACHS-1 subgroups 1 to 3 were highly correlated with poor prognosis and death (p < 0.03). In addition, the lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. The survivors in RACHS-1 subgroups 1 to 3 had lower mean lactate levels than the nonsurvivors in this group (P = 0.011), and this also held true for the survivors and nonsurvivors in RACHS-1 subgroups 4 to 6 (P = 0.026). Lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. This combination allows the targeting of appropriately intensive interventions and therapies toward the sickest patients.

Terlipressin for children with extremely low cardiac output after open heart surgery.

BACKGROUND: Terlipressin, a long-acting analog of vasopressin, has been used successfully in patients with extremely low cardiac output, but its application in children following open heart surgery is limited. OBJECTIVE: To describe our experience using terlipressin in children with extremely low cardiac output after open heart surgery. METHODS: Records were reviewed of all pediatric patients between January 2003 and December 2005 who had undergone open heart surgery, experienced extremely low cardiac output, and were treated with terlipressin as rescue therapy. Mean arterial blood pressure, heart rate, urine output, and lactate and oxygenation index values were retrieved and analyzed when available. RESULTS: Twenty-nine children who were considered gravely ill despite conventional vasoactive agents received terlipressin as rescue therapy, which rapidly yielded significant improvements in all measured hemodynamic and respiratory indices. Mean +/- SD arterial blood pressure increased significantly, from 49 +/- 17 to 57 +/- 16 mm Hg after 10 minutes (p = 0.004) and to 64 +/- 15 mm Hg 24 hours after treatment onset (p = 0.001). Twenty-four hours following terlipressin administration, urine output increased from 1.5 +/- 2.1 to 3.0 +/- 2.3 mL/kg/h (p = 0.001), the oxygenation index decreased from 16.5 +/- 27.9 to 9.5 +/- 16.7 in the survivors (p = 0.023), and the inotropic score decreased from 41.9 +/- 19.9 to 32.6 +/- 18.8 (p = 0.009). CONCLUSIONS: Terlipressin caused significant improvement in hemodynamic, respiratory, and renal indices in children with extremely low cardiac output after open heart surgery. Further controlled studies are needed to confirm the drug's safety and efficacy in this population.

The metabolic effects of fresh versus old stored blood in the priming of cardiopulmonary bypass solution for pediatric patients.

OBJECTIVES: Pediatric cardiopulmonary bypass involves the creation of a large obligatory priming reservoir. Packed red blood cells are an essential part of the cardiopulmonary bypass priming solution in children. The storage media in packed red blood cells might cause significant acid-base, glucose, and electrolyte imbalances, which have been associated with severe complications. The purpose of the present study was to evaluate the metabolic effects of fresh (< or =5 days) versus old (>5 days) stored packed red blood cells added to the priming solutions of pediatric patients undergoing cardiac surgery. METHODS: Blood samples were drawn from cardiopulmonary bypass priming of 30 consecutive pediatric patients undergoing cardiac surgery. Patients were divided into 2 groups. Fresh (< or =5 days old) stored packed red blood cells were added to the priming solution in group 1, and old (>5 days old) stored packed red blood cells were added to the priming solution in group 2. In each group blood samples were drawn from the packed red blood cells on arrival to the operating room and from the priming solution immediately after packed red blood cells were added and after 20 minutes of prime circulation. Samples were also collected at the beginning of cardiopulmonary bypass and after 30 minutes. The last sample was collected on arrival to the pediatric intensive care unit. The levels of potassium, glucose, and lactate and the acid-base balance were analyzed in each sample. RESULTS: There was a linear increase in potassium levels in packed red blood cell samples with increasing packed red blood cell age, ranging from 5.4 to 18.4 mEq/L. Significant differences in the concentrations of potassium, glucose, and lactate and the acid-base balance were found when comparing old and fresh packed red blood cells in samples taken during the packed red blood cell and early prime time. Those differences resolved after 20 minutes of reconstitution of the priming solution. The age of the packed red blood cells had no effect on the samples taken during bypass and those taken in the pediatric intensive care unit. CONCLUSION: The significantly higher concentration of potassium and lactate and lower pH in old stored packed red blood cells has a minimal effect on the final constitution of priming solution before and during cardiopulmonary bypass in children undergoing corrective cardiac surgery.

[ECMO--extra corporeal membrane oxygenation as a bridge to recovery, following surgery for complex congenital cardiac anomalies, in children and neonates].

BACKGROUND: ECMO is used as a method for mechanical life support in the face of extreme cardiopulmonary failure. Most children and neonates that require ECMO do so because of respiratory failure unresponsive to conventional supportive measures. Less then 16% of the patients require ECMO support for the failing heart. The Sheba Medical Center, is one of two centers in Israel authorized by the Ministry of Health to use ECMO technique and is the only center that also performs pediatric cardiac surgery. OBJECTIVES: To present our experience with ECMO support in patients with low cardiac output syndromes following open-heart surgery for congenital cardiac anomalies as compared to international experience. METHODS: The charts of all pediatric and neonatal patients requiring ECMO support following cardiac surgery for complex congenital cardiac anomalies were reviewed. Patient and ECMO characteristics were compared, as well as the success rates. RESULTS: Between 1995 and 2001, sixteen neonates and children were treated at our institution by ECMO for low cardiac output syndromes following heart surgery. Twelve were operated on at our institution, and four were referred to the ECMO unit of our pediatric critical care ward from other hospitals. ECMO support resulted in full recovery in seven of the sixteen patients, cardiac function returned to normal and the patients were discharged home in good condition, nine patients died. CONCLUSIONS: Our experience is in accord with the reported international experience. Following cardiac surgery for congenital cardiac anomalies, low cardiac output, unresponsive to maximal conventional medical support, is a rare but life threatening condition. Extracorporeal membrane oxygenation serves as a rescue mechanical support for these patients and due to improved and sophisticated intensive care, can serve as a bridge to recovery. The availability of ECMO provides an extra margin of safety in the very complex cases of open-heart surgery.

Compression of the pulmonary artery during transesophageal echocardiography in a pediatric cardiac patient.

IMPLICATIONS: Hemodynamic compromise caused by the insertion of the probe for transesophageal echocardiography in a patient with severe stenosis of the main pulmonary artery is reported for the first time. The first symptom of the impending problem was a rapid decrease of end-tidal CO(2).