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PURPOSE: To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD, it was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. CONCLUSION: This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality.
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Insuficiência Cardíaca , Coração Auxiliar , Miocardite , Criança , Humanos , Miocardite/diagnóstico , Miocardite/terapia , Miocardite/complicações , Insuficiência Cardíaca/terapia , Estado Terminal , Estudos Retrospectivos , CoraçãoRESUMO
Our objective was to assess the effect of nitric oxide added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) in infants on platelet count, platelet function, clinical outcomes, and safety. A randomized, double-blinded, placebo-controlled clinical trial in infants less than a year of age undergoing cardiac surgery requiring CPB was undertaken. Nitric oxide at a dose of 20 ppm was added to the sweep gas in the treatment group. Blood was collected at baseline and prior to separation from CPB to measure platelet count and function as determined by responsiveness to specific agonists. Clinical outcomes were observed through hospital discharge. Methemoglobin levels were measured preoperatively, at the conclusion of CPB, and upon admission to the ICU. Forty patients consented and were randomized in the trial. Eighteen patients were randomized to the treatment group and 22 were included in the placebo group. The groups were similar in terms of age, weight, gender, and surgical complexity. No significant differences were found in measures of platelet count, platelet response to agonist, or clinical outcomes. Patients in the treatment group had higher methemoglobin levels after receiving nitric oxide, but no levels approached toxicity (maximum 2.4%). Nitric oxide added to the sweep gas of the oxygenator during CPB in infants did not have an appreciable effect on the preservation of platelet count, platelet responsiveness to agonist, or clinical outcomes. Methemoglobin levels were increased after receiving nitric oxide but were far below a toxic level of 15%.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Óxido Nítrico/administração & dosagem , Oxigenadores/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/instrumentação , Ponte Cardiopulmonar/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metemoglobina/análise , Projetos Piloto , Testes de Função Plaquetária , Resultado do TratamentoRESUMO
We aim to describe the clinical course of a series of patients with hypoplastic left heart syndrome and refractory systolic heart failure supported with a HeartWare ventricular assist device (HVAD) following Fontan palliation. This is a retrospective review of three consecutive patients supported with a HVAD following Fontan palliation through February 2016. Data include patient characteristics, operative variables, postimplantation hemodynamic/device parameters, event outcomes, and duration of HVAD support. Patient ages were 11.7, 13.5, and 17.5 years, respectively, at the time of HVAD implant. The duration of HVAD support was 148, 272, and 271 days, respectively, of which 86, 222, and 211 were outpatient days. Inflow cannula position was the morphologic right ventricle with depth adjustment and manipulation of the tricuspid subvalvar apparatus to ensure good inflow. Echocardiographic, hemodynamic, and noninvasive oximetric monitoring resulted in high RPM settings for all patients. Despite various complications, all patients were successfully transplanted and discharged home alive. We present three patients bridged to transplantation using the HVAD following Fontan palliation. We demonstrate potential for durable support with transition to outpatient care while awaiting heart transplantation in a subset of patients status post Fontan surgery.
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Técnica de Fontan , Ventrículos do Coração/cirurgia , Coração Auxiliar , Implantação de Prótese , Adolescente , Anticoagulantes/uso terapêutico , Criança , Ecocardiografia , Técnica de Fontan/efeitos adversos , Coração Auxiliar/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Implantação de Prótese/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Because of the inadequacies inherent to a circulation supported by a single ventricle, many Fontan patients will experience failure of their circulation. To date, there is no medical regimen that reliably and consistently restores circulatory function in these patients. Because of the shortage of donor organs and the fact that many of these patients present with features that either preclude or render heart transplantation a high risk, there is an intense need to better understand how mechanical circulatory support (MCS) may benefit these patients. In this report, we share our experience of successful MCS and transplantation of three patients. Our experience and that of others is very encouraging, but also preliminary. In general, a systemic ventricular assist device, with or without a Fontan fenestration, is a reasonable consideration for a patient presenting with predominantly systolic dysfunction. A pulmonary/systemic venous assist device may be sufficient for the patient with preserved systolic function and failure of the systemic venous/lymphatic system; however, this remains speculative. The more comprehensive approach of a total artificial heart or bilateral support is attractive in theory, but beset by the need for a more complex operation. In all scenarios, early referral, before organ failure, is paramount to successful MCS.
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Insuficiência Cardíaca/terapia , Coração Auxiliar , Síndrome do Coração Esquerdo Hipoplásico/terapia , Adolescente , Criança , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/complicações , Síndrome do Coração Esquerdo Hipoplásico/fisiopatologia , MasculinoRESUMO
Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed. Four patients were supported with an EXCOR Pediatric (Berlin Heart Inc., The Woodlands, TX, USA) following SCPA for a median duration of 10.5 days (range 9-312 days). Selective excision of trabeculae and chords facilitated apical cannulation in all patients without inflow obstruction. There were two pump exchanges in the one patient supported for 312 days. Two patients were evaluated by cardiac catheterization while supported. Three of four patients were successfully bridged to transplantation. One patient died while supported. All patients had significant bleeding at the time of transplantation, and one required posttransplant extracorporeal membrane oxygenation with subsequent full recovery. VAD support can provide a successful bridge to transplantation in patients with single-ventricle circulation following SCPA. A thorough understanding of the challenges encountered during this support is necessary for successful outcomes.
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Derivação Cardíaca Direita , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Coração Auxiliar , Pré-Escolar , Oxigenação por Membrana Extracorpórea , Feminino , Derivação Cardíaca Direita/métodos , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy.
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Anticoagulantes/administração & dosagem , Antitrombina III/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar , Cardiopatias Congênitas/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Anticoagulantes/efeitos adversos , Anticoagulantes/sangue , Antitrombina III/efeitos adversos , Testes de Coagulação Sanguínea , Ponte Cardiopulmonar/efeitos adversos , Método Duplo-Cego , Estudos de Viabilidade , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico , Heparina/administração & dosagem , Humanos , Recém-Nascido , Projetos Piloto , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/etiologia , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , WisconsinRESUMO
BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. METHODS AND RESULTS: This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.
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Transplante de Coração , Coração Auxiliar , Tamanho Corporal , Causas de Morte , Criança , Pré-Escolar , Comorbidade , Ensaios de Uso Compassivo , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Cardiopatias/sangue , Cardiopatias/cirurgia , Transplante de Coração/estatística & dados numéricos , Hemorragia/epidemiologia , Humanos , Hiperbilirrubinemia/epidemiologia , Lactente , Nefropatias/epidemiologia , Hepatopatias/epidemiologia , Masculino , Mortalidade , Insuficiência de Múltiplos Órgãos/epidemiologia , Modelos de Riscos Proporcionais , Risco , Acidente Vascular Cerebral/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento , Listas de EsperaRESUMO
OBJECTIVE: To empirically derive the optimal measure of pharmacologic cardiovascular support in infants undergoing cardiac surgery with bypass and to assess the association between this score and clinical outcomes in a multi-institutional cohort. DESIGN: Prospective, multi-institutional cohort study. SETTING: Cardiac ICUs at four academic children's hospitals participating in the Pediatric Cardiac Critical Care Consortium during the study period. PATIENTS: Children younger than 1 year at the time of surgery treated postoperatively in the cardiac ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-one infants undergoing surgery with bypass were enrolled consecutively from November 2011 to April 2012. Hourly doses of all vasoactive agents were recorded for the first 48 hours after cardiac ICU admission. Multiple derivations of an inotropic score were tested, and maximum vasoactive-inotropic score in the first 24 hours was further analyzed for association with clinical outcomes. The primary composite "poor outcome" variable included at least one of mortality, mechanical circulatory support, cardiac arrest, renal replacement therapy, or neurologic injury. High vasoactive-inotropic score was empirically defined as more than or equal to 20. Multivariable logistic regression was performed controlling for center and patient characteristics. Patients with high vasoactive-inotropic score had significantly greater odds of a poor outcome (odds ratio, 6.5; 95% CI, 2.9-14.6), mortality (odds ratio, 13.2; 95% CI, 3.7-47.6), and prolonged time to first extubation and cardiac ICU length of stay compared with patients with low vasoactive-inotropic score. Stratified analyses by age (neonate vs infant) and surgical complexity (low vs high) showed similar associations with increased morbidity and mortality for patients with high vasoactive-inotropic score. CONCLUSIONS: Maximum vasoactive-inotropic score calculated in the first 24 hours after cardiac ICU admission was strongly and significantly associated with morbidity and mortality in this multi-institutional cohort of infants undergoing cardiac surgery. Maximum vasoactive-inotropic score more than or equal to 20 predicts an increased likelihood of a poor composite clinical outcome. The findings were consistent in stratified analyses by age and surgical complexity.
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Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Cardiotônicos/administração & dosagem , Cuidados Pós-Operatórios , Índice de Gravidade de Doença , Vasoconstritores/administração & dosagem , Extubação , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/mortalidade , Cuidados Críticos , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo , Resultado do TratamentoRESUMO
Pediatric patients supported on ventricular assist devices (VADs) require systemic anticoagulation and are at risk for intracranial hemorrhage (ICH). Little is known about the incidence or outcomes of pediatric patients with ICH while supported on a VAD. A retrospective chart review of all patients receiving VAD support was completed. Patients diagnosed with ICH while supported on a VAD were identified. Significant factors prior to diagnosis of ICH, medical/surgical treatment of ICH, and patient outcomes were assessed. Five of 30 (17%) patients supported on a VAD from January 2000 to November 2012 were diagnosed with an ICH. Four patients had an identified cerebral thromboembolic injury prior to the ICH. Four patients required interruption in their anticoagulation regimen due to other bleeding concerns prior to ICH. Neurosurgical intervention consisted of evacuation of hemorrhage in one, whereas two others required management of hydrocephalus with external ventricular drainage. Three of the five patients died on VAD support. Two deaths were directly related to ICH, whereas the third was unrelated. Two patients were successfully transplanted; one remains with a significant neurological impairment, and the other has recovered with minimal residual impairment following neurosurgical evacuation of a large subdural hematoma. ICH is a devastating complication of VAD support. Prior ischemic infarcts and interruptions to anticoagulation may put a patient at risk for ICH. Prompt neurosurgical evaluation/intervention can result in positive outcomes.
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Coração Auxiliar/efeitos adversos , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/terapia , Adolescente , Adulto , Anticoagulantes/uso terapêutico , Criança , Humanos , Incidência , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Direct thrombin inhibitor (DTI) use has been associated with decreased stroke and death rates in children on ventricular assist devices (VADs). Most information about DTI use for children on VADs has focused on bivalirudin with limited data on argatroban. We hypothesized that, compared to unfractionated heparin (UFH), argatroban would be associated with decreased bleeding, stroke, and death rates in children on VADs. We retrospectively collected data from patients <18 years old on paracorporeal VADs at Children's Wisconsin between January 1, 2010 and July 1, 2021. We divided patients into cohorts based on anticoagulation strategy with heparin or argatroban. Definitions of bleeding and neurologic events were the same as in other published reports on this population. We compared categorical variables with the χ 2 or Fisher's exact test, and continuous variables with the Mann-Whitney U test. Nineteen children were anticoagulated with argatroban, and 16 with heparin. Demographics between groups were not significantly different. Stroke, bleeding, and death rates did not differ between patients treated with UFH versus argatroban. The study population was complex with a high rate of extracorporeal membrane oxygenation (ECMO) use before VAD support, which likely impacted our findings. Our study does not support argatroban as a superior alternative anticoagulant compared to UFH in children requiring VADs.
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Arginina/análogos & derivados , Coração Auxiliar , Ácidos Pipecólicos , Acidente Vascular Cerebral , Sulfonamidas , Humanos , Criança , Adolescente , Heparina/efeitos adversos , Estudos Retrospectivos , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Hemorragia/induzido quimicamenteRESUMO
Ventricular assist devices (VADs) have been increasingly implanted in pediatric patients. Paracorporeal VADs are generally chosen when intracorporeal continuous (IC) devices are too large. Superiority between IC and paracorporeal pulsatile (PP) devices remains unclear in smaller pediatric patients. Our study analyzes outcomes of IC and PP VADs in pediatric patients who could be considered for either of these options. Using the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) database, we identified children between 10 and 30 kg who received a VAD between June 2018 and September 2021. Survival and stroke outcomes were analyzed based on VAD type. There were 41 patients in the IC group and 54 patients in the PP group. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile at the time of implant was higher in the PP cohort ( p < 0.02). The PP cohort was younger ( p < 0.001) and smaller ( p < 0.001) than the IC cohort. The diagnosis was similar between cohorts. Overall survival was similar between groups. Stroke was more common in the PP cohort, but did not reach statistical significance ( p = 0.07). Discharge was possible only in the IC group, but the discharge rate was low (9.5%). Direct comparisons remain challenging given differences in INTERMACS profiles, age, and size.
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Coração Auxiliar , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Resultado do Tratamento , Estudos Retrospectivos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Criança , Acidente Vascular Cerebral , Sistema de Registros/estatística & dados numéricos , Peso CorporalRESUMO
Ventricular assist devices (VADs) have been increasingly implanted in pediatric patients. Paracorporeal VADs are generally chosen when intracorporeal continuous (IC) devices are too large. Superiority between IC and paracorporeal pulsatile (PP) devices remains unclear in smaller pediatric patients. Our study analyzes outcomes of IC and PP VADs in pediatric patients who could be considered for either of these options. Using the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) database, we identified children between 10 and 30 kg who received a VAD between June 2018 and September 2021. Survival and stroke outcomes were analyzed based on VAD type. There were 41 patients in the IC group and 54 patients in the PP group. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile at the time of implant was higher in the PP cohort ( p < 0.02). The PP cohort was younger ( p < 0.001) and smaller ( p < 0.001) than the IC cohort. The diagnosis was similar between cohorts. Overall survival was similar between groups. Stroke was more common in the PP cohort, but did not reach statistical significance ( p = 0.07). Discharge was possible only in the IC group, but the discharge rate was low (9.5%). Direct comparisons remain challenging given differences in INTERMACS profiles, age, and size.
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Coração Auxiliar , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Resultado do Tratamento , Estudos Retrospectivos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Criança , Acidente Vascular Cerebral , Sistema de Registros/estatística & dados numéricos , Peso CorporalRESUMO
We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.
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OBJECTIVE: This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children. DESIGN/METHODS: This is a retrospective chart review of a single institution comprising patients aged 0 to 18 years old with congenital heart disease. Patients must have received either PCC or rFVIIa after coming off CPB. Our primary efficacy endpoint is time in the operating room from off-CPB to pediatric intensive care unit admission. Our primary safety endpoint is thrombosis through 30 days. RESULTS: Our primary efficacy outcome was significantly shorter in the PCC group compared with the rFVIIa group (P < .0001). Similarly, secondary efficacy outcomes of packed red blood cell administration, chest tube output, and transfusion exposures all significantly favored PCC administration. However, CPB time was significantly longer, and body temperatures were significantly lower, in the rFVIIa group. Safety outcomes, including our primary safety outcome of thrombosis through 30 days, were similar between the two groups. CONCLUSION: This study questions whether PCC could be favored over rFVIIa for hemostasis in children with congenital heart disease following CPB surgery. In addition, this study has found no difference when comparing PCC and rFVIIa in terms of safety outcomes, particularly thrombosis events. There are several limitations to this study due to the retrospective nature of the design and the differences between the two study groups. Despite the limitations, this study suggests that relatively early administration of PCC could be favored over delayed administration of rFVIIa to control recalcitrant post-CPB bleeding in the operating room.
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Fator VIIa , Trombose , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Fator VIIa/uso terapêutico , Ponte Cardiopulmonar/efeitos adversos , Estudos Retrospectivos , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Preoperative risk stratification in cardiac surgery includes patient and procedure factors that are used in clinical decision-making. Despite these tools, unidentified factors contribute to variation in outcomes. Identification of latent physiologic risk factors may strengthen predictive models. Nuclear cell-free DNA (ncfDNA) increases with tissue injury and drops to baseline levels rapidly. The goal of this investigation is to measure and to observe ncfDNA kinetics in children undergoing heart operations with cardiopulmonary bypass (CPB), linking biomarkers, organ dysfunction, and outcomes. METHODS: This is a prospective observational study of 116 children <18 years and >3 kg undergoing operations with CPB. Plasma ncfDNA samples were collected and processed in a stepwise manner at predefined perioperative time points. The primary outcome measure was occurrence of postoperative cardiac arrest or extracorporeal membrane oxygenation. RESULTS: Data were available in 116 patients (median age, 0.9 years [range, 0-17.4 years]; median weight, 7.8 kg [range, 3.2-98 kg]). The primary outcome was met in 6 of 116 (5.2%). Risk of primary outcome was 2% with ncfDNA <20 ng/mL and 33% with ncfDNA >20 ng/mL (odds ratio, 25; CI, 3.96-158; P = .001). Elevated ncfDNA was associated with fewer hospital-free days (P < .01). CONCLUSIONS: This study analyzes ncfDNA kinetics in children undergoing operations with CPB for congenital heart disease. Elevated preoperative ncfDNA is strongly associated with postoperative arrest and extracorporeal membrane oxygenation. Further studies are needed to validate this technology as a tool to predict morbidity in children after cardiac surgical procedures.
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Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Criança , Humanos , Lactente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/etiologia , Ponte Cardiopulmonar/efeitos adversos , Estudos Prospectivos , Fatores de RiscoRESUMO
Bivalirudin offers several important advantages of relevance to the management of extracorporeal membrane oxygenation (ECMO) patients. This multicenter retrospective analysis evaluated the bivalirudin dosing in pediatric ECMO and correlated these doses with the severity of renal dysfunction. A total of 75 patients were included in this analyses: estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m 2 (n = 29), eGFR 30-60 (n = 18), eGFR < 30 (n = 28), and of those 23 were on renal replacement therapy (RRT). The initial bivalirudin dose used to reach therapeutic anticoagulation in patients with eGFR > 60 was significantly higher than the dose required in those with renal impairment (0.25 mg/kg/hr in patients with eGFR > 60 and 0.19 mg/kg/hr in patients on RRT, 0.18 mg/kg/hr in patients with eGFR 30-60 and 0.13 mg/kg/hr in patients with eGFR < 30 with no RRT). Progressive dose escalations (two to threefold increase) were required to maintain therapeutic range over the initial 4 days of ECMO that coincided with improving renal creatinine clearance during that same time period. Establishing an initial starting dose of bivalirudin contingent upon eGFR is essential for the rapid achievement of target anticoagulation intensity. Further dose adjustments guided by laboratory monitoring is necessary given the dynamic changes in creatinine clearance following ECMO initiation.
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Oxigenação por Membrana Extracorpórea , Insuficiência Renal , Humanos , Criança , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos Retrospectivos , Creatinina , Anticoagulantes/efeitos adversos , Fragmentos de Peptídeos/uso terapêutico , Terapia de Substituição Renal , Insuficiência Renal/tratamento farmacológico , Proteínas RecombinantesRESUMO
OBJECTIVES: Mortality rates following pediatric cardiac surgery with cardiopulmonary bypass have declined over decades, but have plateaued in recent years. This is in part attributable to persistent issues with postoperative global inflammation and myocardial dysfunction, commonly manifested by systemic inflammatory response syndrome and low cardiac output syndrome, respectively. Quantified cell-free DNA (cfDNA), of nuclear or mitochondrial origin, has emerged as a biomarker for both inflammation and myocardial injury. Recent data suggest that nuclear cfDNA (ncfDNA) may quantify inflammation, whereas mitochondrial cfDNA (mcfDNA) may correlate with the degree of myocardial injury. We hypothesize that threshold levels of ncfDNA and mcfDNA can be established that are sensitive and specific for postoperative mortality mediated through independent pathways, and that association will be enhanced with combined analysis. METHODS: Prospective observational study of infants younger than age 1 year undergoing planned surgery with cardiopulmonary bypass. The study received institutional review board approval. Samples were drawn before skin incision, immediately after completion of cardiopulmonary bypass, and subsequently at predetermined intervals postoperatively. Association of early postoperative ncfDNA and mcfDNA levels with mortality were assessed by logistic regression with cut-points chosen by receiving operating characteristic curve exploration. RESULTS: Data were available in 59 patients. Median age and weight were 122 days (interquartile range, 63-154 days) and 4.9 kg (interquartile range, 3.9-6.2 kg). Median STAT category was 3 (interquartile range, 1-4). The primary outcome of death was met in 3 out of 59 (5%). Combined analysis of ncfDNA and mcfDNA levels at 12 hours after the initiation of cardiopulmonary bypass with death at a threshold of 50 ng/mL ncfDNA and 17 copies/µL mcfDNA yielded 100% sensitivity and negative predictive value. The specificity (91%) and positive predictive value (38%) increased through combined analysis compared with univariate analysis. Combined analysis exhibited high specificity (93%) and negative predictive value (78%) for prolonged (>30 postoperative days) hospitalization. CONCLUSIONS: Combined analysis of early postoperative ncfDNA and mcfDNA can stratify risk of mortality and prolonged hospitalization following infant cardiac surgery. Evaluation of both ncfDNA and mcfDNA to identify states of generalized inflammation and myocardial injury may allow for targeted interventions and improved outcomes.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Ácidos Nucleicos Livres , Baixo Débito Cardíaco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ponte Cardiopulmonar/efeitos adversos , DNA Mitocondrial , Humanos , Lactente , Inflamação , Complicações Pós-Operatórias/etiologia , Estudos ProspectivosRESUMO
Heparin remains the predominant anticoagulant during extracorporeal membrane oxygenation (ECMO). Heparin acts by potentiating the anticoagulant effect of antithrombin (ATIII). Acquired ATIII deficiency, common in pediatric patients requiring ECMO, may result in ineffective anticoagulation with heparin. ATIII replacement may result in increased bleeding. Our objective is to determine ATIII's effect on anticoagulation and blood loss during ECMO. A retrospective chart review was performed of all patients at Children's Hospital of Wisconsin who received ATIII while supported on ECMO in 2009. ATIII activity levels, heparin drip rate, and activated clotting times (ACT) were compared before, 4, 8, and 24 h after ATIII administration. Chest tube output and packed red blood cell (pRBC) transfusion volume were compared from 24 h before ATIII administration to 24 h after. Twenty-eight patients received ATIII as a bolus dose during the course of 31 separate times on ECMO support. The median age of these patients was 0.3 years (range 1 day-19.5 years). ATIII activity increased significantly at 8 and 24 h after administration. No significant difference was noted in heparin drip rate, ACT levels, chest tube output, or pRBC transfusion volume. ATIII administration resulted in higher ATIII activity levels for 24 h without a significant effect on heparin dose, ACT, or measures of bleeding.
Assuntos
Anticoagulantes/uso terapêutico , Antitrombina III/uso terapêutico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemorragia/etiologia , Heparina/uso terapêutico , Adolescente , Anticoagulantes/farmacologia , Antitrombina III/farmacologia , Criança , Pré-Escolar , Hemorragia/diagnóstico , Heparina/farmacologia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Adulto JovemRESUMO
Aortic insufficiency (AI) is generally regarded as a contraindication for mechanical circulatory support in children. In the current Berlin EXCOR trial, moderate to severe AI is an exclusion criterion. There are reports in the literature of successful mechanical circulatory support (MCS) in adult patients with significant AI via "aortic exclusion" or bioprosthetic aortic valve replacement. We report the first case of aortic exclusion in an infant with moderate to severe aortic insufficiency in need of MCS.