Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery.

BACKGROUND: Children undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury. METHODS: We conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass. RESULTS: There were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different. CONCLUSIONS: There is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Applying the Hybrid Concept as a Bridge to Transplantation in Infants Without Hypoplastic Left Heart Syndrome.

Therapies to support small infants in decompensated heart failure that are failing medical management are limited. We have used the hybrid approach, classically reserved for high-risk infants with single ventricle physiology, in patients with biventricular physiology with left ventricular failure. This approach secures systemic circulation, relieves left atrial hypertension, protects the pulmonary vasculature, and allows the right ventricle to support cardiac output. This approach can be used as a bridge to transplantation in select individuals. Infants without single ventricle congenital heart disease who were treated with the hybrid approach between 2008 and 2021 were included in analysis. Eight patients were identified. At the time of hybrid procedure, the median weight was 3.2 kg (range 2.4-3.6 kg) and the median age was 18 days (range 1-153 days). Seventy five percent were mechanically ventilated and 88% were on inotropic support. The median duration from hybrid procedure to transplant was 63 days (range 4-116 days). All patients experienced a good outcome (delisted for improvement or transplanted). The hybrid procedure is an appropriate therapeutic bridge to transplantation in a carefully selected subset of critically ill infants without single ventricle congenital heart disease in whom alternate therapies may confer increased risk for morbidity and mortality.

Thrombosis in Extracorporeal Membrane Oxygenation (ECMO) Circuits.

Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.

2020 EACTS/ELSO/STS/AATS Expert Consensus on Post-Cardiotomy Extracorporeal Life Support in Adult Patients.

Post-cardiotomy extracorporeal life support (PC-ECLS) in adult patients has been used only rarely but recent data have shown a remarkable increase in its use, almost certainly due to improved technology, ease of management, growing familiarity with its capability and decreased costs. Trends in worldwide in-hospital survival, however, rather than improving, have shown a decline in some experiences, likely due to increased use in more complex, critically ill patients rather than to suboptimal management. Nevertheless, PC-ECLS is proving to be a valuable resource for temporary cardiocirculatory and respiratory support in patients who would otherwise most likely die. Because a comprehensive review of PC-ECLS might be of use for the practitioner, and possibly improve patient management in this setting, the authors have attempted to create a concise, comprehensive and relevant analysis of all aspects related to PC-ECLS, with a particular emphasis on indications, technique, management and avoidance of complications, appraisal of new approaches and ethics, education and training.

2020 EACTS/ELSO/STS/AATS expert consensus on post-cardiotomy extracorporeal life support in adult patients.

Post-cardiotomy extracorporeal life support (PC-ECLS) in adult patients has been used only rarely but recent data have shown a remarkable increase in its use, almost certainly due to improved technology, ease of management, growing familiarity with its capability and decreased costs. Trends in worldwide in-hospital survival, however, rather than improving, have shown a decline in some experiences, likely due to increased use in more complex, critically ill patients rather than to suboptimal management. Nevertheless, PC-ECLS is proving to be a valuable resource for temporary cardiocirculatory and respiratory support in patients who would otherwise most likely die. Because a comprehensive review of PC-ECLS might be of use for the practitioner, and possibly improve patient management in this setting, the authors have attempted to create a concise, comprehensive and relevant analysis of all aspects related to PC-ECLS, with a particular emphasis on indications, technique, management, and avoidance of complications, appraisal of new approaches and ethics, education, and training.

2020 EACTS/ELSO/STS/AATS expert consensus on post-cardiotomy extracorporeal life support in adult patients.

Post-cardiotomy extracorporeal life support (PC-ECLS) in adult patients has been used only rarely but recent data have shown a remarkable increase in its use, almost certainly due to improved technology, ease of management, growing familiarity with its capability and decreased costs. Trends in worldwide in-hospital survival, however, rather than improving, have shown a decline in some experiences, likely due to increased use in more complex, critically ill patients rather than to suboptimal management. Nevertheless, PC-ECLS is proving to be a valuable resource for temporary cardiocirculatory and respiratory support in patients who would otherwise most likely die. Because a comprehensive review of PC-ECLS might be of use for the practitioner, and possibly improve patient management in this setting, the authors have attempted to create a concise, comprehensive and relevant analysis of all aspects related to PC-ECLS, with a particular emphasis on indications, technique, management and avoidance of complications, appraisal of new approaches and ethics, education and training.

2020 EACTS/ELSO/STS/AATS Expert Consensus on Post-cardiotomy Extracorporeal Life Support in Adult Patients.

Post-cardiotomy extracorporeal life support (PC-ECLS) in adult patients has been used only rarely but recent data have shown a remarkable increase in its use, almost certainly due to improved technology, ease of management, growing familiarity with its capability and decreased costs. Trends in worldwide in-hospital survival, however, rather than improving, have shown a decline in some experiences, likely due to increased use in more complex, critically ill patients rather than to suboptimal management. Nevertheless, PC-ECLS is proving to be a valuable resource for temporary cardiocirculatory and respiratory support in patients who would otherwise most likely die. Because a comprehensive review of PC-ECLS might be of use for the practitioner, and possibly improve patient management in this setting, the authors have attempted to create a concise, comprehensive and relevant analysis of all aspects related to PC-ECLS, with a particular emphasis on indications, technique, management and avoidance of complications, appraisal of new approaches and ethics, education and training.

Monitoring Hemostasis During Extracorporeal Life Support.

To balance the risk of bleeding versus circuit thrombosis during extracorporeal life support (ECLS), it is important to monitor anticoagulants and hemostasis. We evaluated the prothrombin time (PT), partial thromboplastin time (PTT), activated clotting time (ACT), and antifactor Xa heparin activity (aXa) correlation with changes in coagulation factor and heparin levels using in vitro and in vivo samples. aXa correlated with heparin (r = 0.97) and antithrombin (r = 0.98) but was unaffected by other parameters. PT correlated with coagulation factors (r = 0.88) but was minimally affected by heparin or other parameters. When single parameters were changed, ACT was insensitive to <0.5 U/ml heparin, correlated with coagulation factors (r = 0.99), and was affected by factor XII and platelets. When multiple parameters changed in vitro and in vivo, ACT was not correlated with heparin or coagulation factors. PTT correlated with heparin and coagulation factors individually but had low correlation when multiple parameters changed in vitro and in vivo. In conclusion, aXa is the most specific for heparin levels, and PT is most specific for coagulation factor levels making these assays well suited to monitor anticoagulation and hemostasis for patients on ECLS. PTT is highly variable when multiple parameters are changing in vitro and in vivo, but may be useful when aXa cannot be used because of interference. ACT is too insensitive to heparin, sensitive to too many other factors, and too imprecise to be useful for monitoring hemostasis during ECLS.

Increased Stroke Risk in Children and Young Adults on Extracorporeal Life Support with Carotid Cannulation.

Patients on extracorporeal life support (ECLS) are at risk for central nervous system (CNS) injury. One potentially modifiable risk factor is site of arterial cannulation in venoarterial (VA) ECLS, as in most cases one can choose the femoral or carotid artery. There is acute alteration in cerebral blood flow with carotid cannulation, potentially increasing the risk of stroke. Children may have lower risk of stroke with carotid cannulation compared with adults because of impaired cerebral circulation with aging. Our objective was to evaluate risk of stroke with carotid versus femoral cannulation and determine whether this differs between children and adults. Using the Extracorporeal Life Support Organization Registry, we evaluated patients 6-40 years old on VA ECLS during 2000-2012. We used multivariable logistic regression to estimate the relationship between location of arterial cannulation and stroke. We included an interaction term to assess whether this was modified by age. One thousand five hundred eighteen patients were included in the analysis. There was a fourfold increased odds of CNS infarct (odds ratio [OR]: 4.03; 95% CI: 2.17-7.46) with carotid cannulation. This estimate was not modified by age. There is increased likelihood of stroke with carotid cannulation in patients 6-40 years old in comparison with femoral cannulation during VA ECLS.

Early Cardiac Catheterization Leads to Shortened Pediatric Extracorporeal Membrane Oxygenation Run Duration.

OBJECTIVE: Cardiac catheterization in patients receiving extracorporeal life support (ECLS) has previously been shown to be safe and, in many cases, therapeutic. However, the influence of cardiac catheterization on clinical outcomes in this patient population has not been clearly defined. METHODS: A single institution, retrospective review of all pediatric cardiac ECLS patients who underwent cardiac catheterization between January 2006 and September 2015 was performed. RESULTS: Eighty-two interventional cardiac catheterization procedures were performed on 74 patients. Catheterization findings directly led to catheterization-based or surgical intervention in 54 (73%) patients. One (1.2%) catheterization-related complication occurred (pulmonary artery rupture), which ultimately resulted in death. Patients who underwent early catheterization (≤72 hours of ECLS initiation) required shorter total duration of ECLS than patients who underwent catheterization >72 hours after ECLS initiation (136 hours vs. 227 hours, P < 0.01). The groups experienced similar rates of interventions based on catheterization findings (72% early cath vs. 74% late cath, P = 0.81). Survival to hospital discharge was higher in the early catheterization group (74% vs. 51%, P = 0.04). In multivariate models adjusting for covariates, early catheterization was associated with a reduction in ECLS duration by approximately 150 hours (P < 0.01). CONCLUSIONS: Cardiac catheterization is safe in pediatric ECLS patients and an earlier catheterization is associated with shorter duration of ECLS and improved hospital survival. Diagnostic cardiac catheterization should be considered in patients who remain dependent on ECLS after several days of support.

Near-fatal neonatal coronary ischaemia associated with intermittent aortic regurgitation: successful surgical treatment.

An infant presented with features suggestive of an anomalous left coronary artery was found to have normal origins of both coronary arteries. Echocardiography during episodes of ischaemia showed marked aortic regurgitation with retrograde coronary flow. The left coronary leaflet was mildly hypoplastic. Surgical re-suspension of this leaflet prevented aortic regurgitation and the patient had no further symptoms and recovered cardiac function.

ABO blood group antibody levels in infants exposed to mechanical circulatory support.

ABO sensitization is a barrier to ABO-incompatible heart transplantation in infants. We investigate the development of ABO antibodies in infants with and without mechanical circulatory support (MCS) during their waiting period. Although the proportion of patients with antibodies was similar between the groups, the median age at antibody detection was only 9 days (6-198) for MCS vs. 223 days (28-367) for non-MCS patients (P = 0.028), suggesting MCS is associated with earlier ABO antibody detection.

Human leukocyte antigen sensitization in pediatric patients exposed to mechanical circulatory support.

Human leukocyte antigen (HLA) sensitization of pediatric heart recipients increases their risk of rejection and graft loss. As more children are placed on mechanical circulatory support (MCS) as a bridge to transplant, the risk factors for development of sensitization warrant further study. A single-center retrospective review of 36 children who received MCS identified 22 patients supported with either extracorporeal membrane oxygenation (ECMO) (n = 15) or ECMO-ventricular assist device (VAD) (n = 7) with paired (pre-MCS/post-MCS) panel reactive antibodies (PRA) or only negative post-MCS PRAs. Four patients (18%) became sensitized post-MCS (one ECMO-only patient, three ECMO-VAD patients). No difference was found between sensitized and nonsensitized patients in terms of congenital heart disease versus primary cardiomyopathy (p = 0.096), duration of MCS (38 days vs. 14 days, p = 0.233), or volume of blood product transfusions (358.6 ml/kg vs. 612.7 ml/kg, p = not significant). By multivariable analysis, the association of sensitization with older age at MCS (p = 0.076) and history of homograft (p = 0.064) approached significance. Pediatric patients supported with MCS are at low risk of developing HLA sensitization. Diagnosis, MCS duration, and volume of transfused blood products do not appear to be associated with HLA sensitization, but there is a suggestion of an association with older age at MCS and history of a homograft.

Downsized Contegra graft as a right ventricle-to-pulmonary artery conduit in the setting of mediastinitis.

Polytetrafluoroethylene (PTFE) grafts are commonly used for construction of the right ventricle-to-pulmonary artery conduit in the modified Norwood procedure. Dehiscence of a PTFE conduit in the setting of purulent mediastinitis presents a challenging clinical problem because of limited availability of appropriately sized replacement vascular homografts. The Contegra bovine jugular vein graft is an alternative to placing another PTFE graft in an infected space when a homograft of appropriate size is not available. We describe the use of a downsized Contegra conduit to replace an infected PTFE right ventricle-to-pulmonary artery graft in a neonate with life-threatening purulent mediastinitis.

Association of thymectomy with infection following congenital heart surgery.

BACKGROUND: Congenital absence of the thymus can lead to profound immunodeficiency, suggesting that thymic function during fetal development is essential to normal lymphocyte development. How vital the thymus after birth is to human immune competence and regulation is not known. Routine thymectomy, especially at an early age, may influence immunity, and therefore the risk of infection, autoimmunity, or malignancy. METHODS: A retrospective review of cardiac surgery patients followed at Seattle Children's Hospital was performed. The primary outcome was rate of serious infections requiring hospitalization. Secondary analyses included age, type of infection, cardiac diagnosis, surgical procedure, and comorbidities. RESULTS: Patients fell into 2 groups: 60 with complete thymectomy and 35 with partial or no thymectomy. There was no statistical difference between groups in the overall prevalence of serious infections (16.7% vs 17.2%, P = 1.0). There was a nonsignificant trend toward reduced time between surgery and onset of first infection in patients in the total thymectomy group versus those without thymectomy (1.7 years vs 4.6 years, P = .07). Total thymectomy before 6 months of age also tended to increase infection rate, but the effect was not significant (0.09/year vs 0.02, P = .14). Gastroesophageal reflux in patients with total thymectomy increased the risk of infection (P = .013), suggesting a cumulative effect. CONCLUSIONS: Though infections occurred frequently in the childhood cardiac surgery population, total thymectomy was not associated with increased risk of serious infection. Comorbid conditions may be more important contributing factors increasing the risk of infection in this complex and vulnerable population.