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.

Outcomes of Adults with Congenital Heart Disease Supported with Extracorporeal Life Support After Cardiac Surgery.

Patients with adult congenital heart disease (ACHD) who undergo cardiac surgery may require extracorporeal life support (ECLS) for cardiopulmonary support, but outcomes after ECLS support have not been well described. This study aimed to identify risk factors for ECLS mortality in this population. We identified 368 ACHD patients who received ECLS after cardiac surgery between 1994 and 2016 in the Extracorporeal Life Support Organization (ELSO) database, a multicenter international registry of ECLS centers. Risk factors for mortality were assessed using multivariate logistic regression. Overall mortality was 61%. In a multivariate model using precannulation characteristics, Fontan physiology (odds ratio [OR]: 5.7; 95% CI: 1.6-20.0), weight over 100 kg (OR: 2.6; 95% CI: 1.3-5.4), female gender (OR: 1.6; 95% CI: 1.001-2.6), delayed ECLS cannulation (OR: 2.0; 95% CI: 1.2-3.2), and neuromuscular blockade (OR: 1.9; 95% CI: 1.1-3.3) were associated with increased mortality. Adding postcannulation characteristics to the model, renal complications (OR: 3.0; 95% CI: 1.7-5.2), neurologic complications (OR, 4.7; 95% CI: 1.5-15.2), and pulmonary hemorrhage (OR: 6.4; 95% CI: 1.3-33.2) were associated with increased mortality, whereas Fontan physiology was no longer associated, suggesting the association of Fontan physiology with mortality may be mediated by complications. Fontan physiology was also a risk factor for neurologic complications (OR: 8.2; 95% CI: 3.3-20.9). Given the rapid increase in ECLS use, understanding risk factors for ACHD patients receiving ECLS after cardiac surgery will aid clinicians in decision-making and preoperative planning.

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.

Long-term outcomes after transplantation after support with a pulsatile pediatric ventricular assist device.

BACKGROUND: There has been increasing use of durable ventricular assist devices (VAD) in children as a bridge to transplantation (BTT). The Berlin Heart investigational device exemption (IDE) trial was the first pediatric VAD trial to demonstrate excellent survival outcomes as a BTT. OBJECTIVES: Our aim was to compare the expanded post-transplant outcomes for children enrolled in the Berlin Heart IDE trial to a matched Pediatric Heart Transplant Study (PHTS) cohort not requiring mechanical circulatory support (MCS). SETTING: University Hospitals. METHODS: This was a retrospective review of linked PHTS and Berlin Heart IDE databases for pediatric (≤18 years) recipients transplanted from 2007-2011. Subjects with <5 years of follow up were excluded. VAD supported patients were matched 1:2 to non-VAD supported controls from the PHTS database. RESULTS: Among 109 Berlin Heart IDE study enrollees, 83 were merged with the PHTS database and matched to 166 non-MCS supported patients. There was no difference in diagnosis, status at listing, and age between groups with the expected difference in inotrope use in the non-MCS supported patients. Compared to their matched cohort, there was no statistical difference in 5-year patient survival between VAD and non-VAD patients (81% vs 88%; p = 0.09) nor was there a difference in freedom from rejection or infection. CONCLUSIONS: This data suggests that children supported with a Berlin Heart VAD had similar survival, infection and rejection rates compared to those not requiring MCS support. Continued surveillance of the Berlin Heart IDE trial population post heart transplantation is warranted.

Surgical Atrioventricular Valve Replacement With Melody Valve in Infants and Children.

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes <15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P<0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.

Indications and outcomes of extracorporeal life support in trauma patients.

BACKGROUND: The use of extracorporeal life support (ECLS) in the trauma population remains controversial and has been reported only in small cohort studies. Recent ECLS technical advances have increased its use as an advanced critical care option in trauma. Given the degree of resource utilization, costs, and expertise required to provide ECLS support in trauma patients, we sought to perform a multi-institutional study to assess the indications and outcomes of ECLS in trauma. METHODS: A retrospective review of adult (≥16 years) trauma patients receiving ECLS support in the Extracorporeal Life Support Organization (ELSO) registry (1989-2016) was performed. Standardized data from the contributing ELSO centers includes patient demographics, diagnoses, and ECLS technique and procedures. Additionally, baseline characteristics, precannulation and postcannulation physiologic data, complications, and outcomes were recorded. Survival was categorized both by transition off ECLS support and survival to hospital discharge. RESULTS: Two hundred seventy-nine trauma patients were identified (0.92% of 30,273 adult ECLS patients). Extracorporeal life support increased significantly in the last 5 years (173 in 2011-2016, 62%) compared with 106 in the prior 18 years. Trauma patients were predominantly male (78%), with a mean age of 34.8 ± 15.4 years (range, 16-88 years). Thoracic injury was the most common diagnosis; acute respiratory distress syndrome was the most common indication. Extracorporeal life support was venovenous for respiratory failure (89%), VA for cardiac failure (7%), and VA for ECLS-assisted cardiopulmonary resuscitation (CPR) (E-CPR) (4%). Extracorporeal life support duration was 8.8 ± 9.5 days (longest 83 days), and was longer for respiratory support (9.3 ± 9.3 days) vs. cardiac support (4.1 ± 4.5 days) and E-CPR (6.5 ± 16.8 days). Overall survival from ECLS was 70% and survival to hospital discharge was 61% in the total cohort (63% respiratory, 50% cardiac, 25% E-CPR), similar to survival rates in other ELSO registry cohorts. More than 80% of patients had a reported complication during ECLS support. The most common complication was cardiovascular (51%) followed by a bleeding complication (29%). Multiple organ failure was the most common cause of death (15.4%). CONCLUSION: Data from the largest registry of critically ill trauma patients receiving ECLS support demonstrates reasonable survival. With growing experience and improved safety profile, trauma should not be considered a contraindication for ECLS. Further analysis of the ELSO registry regarding trauma-specific risk factors and ECLS-specific practices may identify best candidates and improve trauma ECLS outcomes. LEVEL OF EVIDENCE: Therapeutic study, level III.

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.

Extracorporeal cardiopulmonary resuscitation.

Extracorporeal life support (ECLS) is used for patients in isolated or combined cardiopulmonary failures. The use of ECLS to rescue patients with cardiac arrest that is refractory to conventional cardiopulmonary resuscitation has been shown to improve survival in many patient populations. Increasing recognition of the survival benefit associated with extracorporeal cardiopulmonary resuscitation (ECPR) has led to increased use of ECPR during the past decade. This review provides an overview of ECPR utilization; population-based clinical outcomes, resource utilization and costs associated this advanced form of life support therapy.

Racial and Ethnic Variation in Pediatric Cardiac Extracorporeal Life Support Survival.

OBJECTIVES: Previous studies have suggested an association between nonwhite race and poor outcomes in small subsets of cardiac surgery patients who require extracorporeal life support. This study aims to examine the association of race/ethnicity with mortality in pediatric patients who receive extracorporeal life support for cardiac support. DESIGN: Retrospective analysis of registry data. SETTING: Prospectively collected multi-institutional registry data. SUBJECTS: Data from all North American pediatric patients in the Extracorporeal Life Support International Registry who received extracorporeal life support for cardiac support between 1998 and 2012 were analyzed. Multivariate regression models were constructed to examine the association between race/ethnicity and hospital mortality, adjusting for demographics, diagnosis, pre-extracorporeal life support care, extracorporeal life support variables, and extracorporeal life support-related complications. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 7,106 patients undergoing cardiac extracorporeal life support, the majority of patients were of white race (56.9%) with black race (16.7%), Hispanic ethnicity (15.8%), and Asian race (2.8%) comprising the other major race/ethnic groups. The mortality rate was 53.9% (n = 3,831). After adjusting for covariates, multivariate analysis identified black race (relative risk = 1.10; 95% CI, 1.04-1.16) and Hispanic ethnicity (relative risk = 1.08; 95% CI, 1.02-1.14) as independent risk factors for mortality. CONCLUSIONS: Black race and Hispanic ethnicity are independently associated with mortality in children who require cardiac extracorporeal life support.