Search

Unfractionated heparin (UFH) is a commonly used anticoagulant for pediatric patients undergoing extracorporeal membrane oxygenation (ECMO), but evidence is lacking on the ideal dosing. We aimed to (1) develop a population pharmacokinetic (PK) model for UFH, measured through anti-factor Xa assay; (2) optimize UFH starting infusions and dose titrations through simulations; and (3) explore UFH exposure-clinical outcomes relationship. Data from 218 patients admitted to Utah's Primary Children's Hospital were retrospectively collected. A 1-compartment PK model with time-varying clearance (CL) adequately described UFH PK. Weight on CL and volume of distribution and ECMO circuit change on CL were significant covariates. The typical estimates for initial CL and first-order rate constant to reach steady-state CL were 0.57 L/(h·10 kg) and 0.02/h. Comparable to non-ECMO patients, the typical steady-state CL was 0.81 L/(h·10 kg). Simulations showed that a 75 IU/kg UFH bolus dose followed by starting infusions of 25 and 20 IU/h/kg for patients aged younger than 6 years and 6 years or older, respectively, achieved the therapeutic target in 56.6% of all patients, whereas only 3.1% exceeded the target. The proposed UFH titration schemes achieved the target in more than 90% of patients while less than 0.63% were above the target after 24 and 48 hours of treatment. The median intensive care unit survival time in patients within and below the target at 24 hours was 136 and 66 hours, respectively. In conclusion, PK model of UFH was developed for pediatric patients on ECMO. The proposed UFH dosing scheme attained the anti-factor Xa target rapidly and safely., (© 2023, The American College of Clinical Pharmacology.)

Objective: Adult congenital heart disease (ACHD) patients who undergo cardiac surgery are at risk for poor outcomes, including extracorporeal membrane oxygenation support (ECMO) and death. Prior studies have demonstrated risk factors for mortality, but have not fully examined risk factors for ECMO or death without ECMO (DWE). We sought to identify risk factors for ECMO and DWE in adults undergoing congenital heart surgery in tertiary care children's hospitals., Design: All adults (≥18 years) undergoing congenital heart surgery in the Pediatric Health Information System (PHIS) database between 2003 and 2014 were included. Patients were classified into three groups: ECMO-free survival, requiring ECMO, and DWE. Univariate analyses were performed, and multinomial logistic regression models were constructed examining ECMO and DWE as independent outcomes., Setting: Tertiary care children's hospitals., Results: A total of 4665 adult patients underwent ACHD surgery in 39 children's hospitals with 51 (1.1%) patients requiring ECMO and 64 (1.4%) patients experiencing DWE. Of the 51 ECMO patients, 34 (67%) died. Increasing patient age, surgical complexity, diagnosis of single ventricle heart disease, preoperative hospitalization, and the presence of noncardiac complex chronic conditions (CCC) were risk factors for both outcomes. Additionally, low and medium hospital ACHD surgical volume was associated with an increased risk of DWE in comparison with ECMO., Conclusions: There are overlapping but separate risk factors for ECMO support and DWE among adults undergoing congenital heart surgery in pediatric hospitals., (© 2019 Wiley Periodicals, Inc.)

Objectives: Previous studies demonstrate racial and ethnic disparities among children undergoing congenital heart surgery. Extracorporeal membrane oxygenation (ECMO) is used to support critically ill children after congenital heart surgery and improve survival. Thus, racial or ethnic variations in postoperative ECMO use following congenital heart surgery may be associated with racial/ethnic disparities in hospital survival., Methods: All children in the Pediatric Health Information Systems dataset undergoing congenital heart surgery from 2004 to 2015 were examined. Multivariable, multinomial regression models examining hospital survival without ECMO use, survival after ECMO, death after ECMO, and death without ECMO support were constructed., Results: Of 130,860 congenital cardiac surgery patients, 95.4% survived to hospital discharge without requiring ECMO support, whereas 1.3% survived after ECMO support, 1.3% died after ECMO support, and 1.9% died without receiving ECMO support. After adjustment for other covariates, black patients (odds ratio, 1.22; 95% confidence interval [CI], 1.05-1.42) and patients of other race (odds ratio, 1.36; 95% CI, 1.17-1.58) were at increased odds of mortality compared with white patients. In multivariable multinomial models, black patients had increased risk of death without ECMO support (relative risk, 1.31; 95% CI, 1.11-1.56). Patients of other race (relative risk, 1.37; 95% CI, 1.10-1.69) and governmental insurance (relative risk, 1.24; 95% CI, 1.12-1.37) were also at increased risk of death without ECMO., Conclusions: Black children and children of other race are at increased odds of mortality after congenital heart surgery. These disparities can be traced to variations in ECMO utilization across racial/ethnic groups., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Centers with higher surgical and extracorporeal membrane oxygenation (ECMO) volumes have improved survival for children undergoing pediatric cardiac surgery and ECMO, respectively. We examined the relationship between both cardiac surgical and cardiac ECMO volumes, with survival. Using data from the Pediatric Health Information System, we reviewed patients who underwent ECMO during the hospitalization for cardiac surgery or heart transplantation from January 2003 to June 2014. Among 106,967 patients in 43 centers undergoing a Risk Adjustment for Congenital Heart Surgery-1 1-6 procedure (n = 104,951) or cardiac transplantation (n = 2,016), 2.9% (n = 3,069) underwent ECMO support. Centers were categorized into volume quartiles based on annual ECMO and cardiac surgical volumes. Multivariable logistic regression models controlling for clustering by center and adjusting for factors associated with mortality were constructed. Although mortality was lower in ECMO centers that performed ≥7 ECMO runs (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.22-0.88)] and centers performing ≥158 cardiac surgical cases (OR: 0.37, 95% CI: 0.22-0.63), surgical volume was more strongly associated with ECMO mortality. Centers with higher cardiac surgical volume had fewer ECMO complications. Cardiac surgical volume, compared with ECMO volume, is more strongly associated with cardiac ECMO survival.

Objective: Congenital heart disease is commonly a manifestation of genetic conditions. Surgery and/or extracorporeal membrane oxygenation were withheld in the past from some patients with genetic conditions. We hypothesized that surgical care of children with genetic conditions has increased over the last decade, but their cardiac extracorporeal membrane oxygenation use remains lower and mortality greater., Design: Retrospective cohort study., Setting: Patients admitted to the Pediatric Health Information System database 18 years old or younger with cardiac surgery during 2003-2014. Genetic conditions identified by International Classification of Diseases, 9th Edition codes were grouped as follows: trisomy 21, trisomy 13 or 18, 22q11 deletion, and all "other" genetic conditions and compared with patients without genetic condition., Patients: A total of 95,253 patients met study criteria, no genetic conditions (85%), trisomy 21 (10%), trisomy 13 or 18 (0.2%), 22q11 deletion (1%), and others (5%)., Interventions: None., Measurements and Main Results: Annual surgical cases did not vary over time. Compared to patients without genetic conditions, trisomy 21 patients, extracorporeal membrane oxygenation use was just over half (odds ratio, 0.54), but mortality with and without extracorporeal membrane oxygenation were similar. In trisomy 13 or 18 patients, extracorporeal membrane oxygenation use was similar to those without genetic condition, but all five treated with extracorporeal membrane oxygenation died. 22q11 patients compared with those without genetic condition had similar extracorporeal membrane oxygenation use, but greater odds of extracorporeal membrane oxygenation mortality (odds ratio, 3.44). Other genetic conditions had significantly greater extracorporeal membrane oxygenation use (odds ratio, 1.22), mortality with extracorporeal membrane oxygenation (odds ratio, 1.42), and even greater mortality odds without (odds ratio, 2.62)., Conclusions: The proportion of children undergoing cardiac surgery who have genetic conditions did not increase during the study. Excluding trisomy 13 or 18, all groups of genetic conditions received and benefited from extracorporeal membrane oxygenation, although extracorporeal membrane oxygenation mortality was greater for those with 22q11 deletion and other genetic conditions.

Objectives: Only a small fraction of pediatric cardiac surgical patients are supported with extracorporeal membrane oxygenation following cardiac surgery, but extracorporeal membrane oxygenation use is more common among those undergoing higher complexity surgery. We evaluated extracorporeal membrane oxygenation metrics indexed to annual cardiac surgical volume to better understand extracorporeal membrane oxygenation use among U.S. cardiac surgical programs., Design: Retrospective analysis SETTING:: Forty-three U.S. Children's Hospitals in the Pediatric Health Information System that performed cardiac surgery and used extracorporeal membrane oxygenation., Patients: All patients (< 19 yr) undergoing cardiac surgery during January 2003 to July 2014., Interventions: None., Measurements and Main Results: Both extracorporeal membrane oxygenation use and surgical mortality were risk adjusted using Risk Adjustment for Congenital Heart Surgery 1. Extracorporeal membrane oxygenation metrics indexed to annual cardiac surgery cases were calculated for each hospital and the metric values divided into quintiles for comparison across hospitals. Among 131,786 cardiac surgical patients, 3,782 (2.9%) received extracorporeal membrane oxygenation. Median case mix adjusted rate of extracorporeal membrane oxygenation use was 2.8% (interquartile range, 1.6-3.4%). Median pediatric cardiac case mix adjusted surgical mortality was 3.5%. Extracorporeal membrane oxygenation-associated surgical mortality was 1.3% (interquartile range, 0.7-1.6%); without extracorporeal membrane oxygenation, median case mix adjusted surgical mortality would increase from 3.5% to 5.0%. Among patients who died, 36.7% (median) were supported with extracorporeal membrane oxygenation. The median reduction in case mix adjusted surgical mortality from extracorporeal membrane oxygenation surgical survival was 30.1%. The median extracorporeal membrane oxygenation free surgical survival was 95% (interquartile range, 94-96%). Centers with less than 150 annual surgical cases had significantly lower median extracorporeal membrane oxygenation use (0.78%) than centers with greater than 275 cases (≥ 2.8% extracorporeal membrane oxygenation use). Extracorporeal membrane oxygenation use and mortality varied within quintiles and across quintiles of center annual surgical case volume., Conclusions: Risk adjusted extracorporeal membrane oxygenation metrics indexed to annual surgical volume provide potential for benchmarking as well as a greater understanding of extracorporeal membrane oxygenation utilization, efficacy, and impact on cardiac surgery mortality.

Objective: Our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. Preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families., Design: Multivariable logistic regression of a large international cohort of pediatric extracorporeal membrane oxygenation patients., Setting: Multi-institutional data., Patients: Prognostic score development: A total of 4,352 children more than 7 days to less than 18 years old, with an initial extracorporeal membrane oxygenation run for respiratory failure reported to the Extracorporeal Life Support Organization's data registry during 2001-2013 were used for derivation (70%) and validation (30%). Bidirectional stepwise logistic regression was used to identify factors associated with mortality. Retained variables were assigned a score based on the odds of mortality with higher scores indicating greater mortality. External validation was accomplished using 2,007 patients from the Pediatric Health Information System dataset., Interventions: None., Measurements and Main Results: The Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction score included mode of extracorporeal membrane oxygenation; preextracorporeal membrane oxygenation mechanical ventilation more than 14 days; preextracorporeal membrane oxygenation severity of hypoxia; primary pulmonary diagnostic categories including, asthma, aspiration, respiratory syncytial virus, sepsis-induced respiratory failure, pertussis, and "other"; and preextracorporeal membrane oxygenation comorbid conditions of cardiac arrest, cancer, renal and liver dysfunction. The area under the receiver operating characteristic curve for internal and external validation datasets were 0.69 (95% CI, 0.67-0.71) and 0.66 (95% CI, 0.63-0.69)., Conclusions: Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction is a validated tool for predicting in-hospital mortality among children with respiratory failure receiving extracorporeal membrane oxygenation support.

Objectives: Recent analyses show higher mortality at low-volume centers providing extracorporeal membrane oxygenation. We sought to identify factors associated with center volume and mortality to explain survival differences and identify areas for improvement., Design: Retrospective cohort study., Setting: Patients admitted to children's hospitals in the Pediatric Health Information System database and supported with extracorporeal membrane oxygenation for respiratory failure from 2003 to 2014., Patients: A total of 5,303 patients aged 0-18 years old met inclusion criteria: 3,349 neonates and 1,954 children., Interventions: None., Measurements and Main Results: Low center volume was defined as less than 20, medium 20-49, and large greater than or equal to 50 cases per year. Center volume was also assessed as a continuous integer. Among neonates, clinical factors including intraventricular hemorrhage (relative risk, 1.4; 95% CI, 1.24-1.56) and acute renal failure (relative risk, 1.38; 95% CI, 1.20-1.60) were more common at low-volume compared to larger centers and were associated with in-hospital death. After adjustment for differences in demographic factors and primary pulmonary conditions, mild prematurity, acute renal failure, intraventricular hemorrhage, and receipt of dialysis remained independently associated with mortality, as did center volume measured as a continuous number. Among children, the risk of acute renal failure was almost 20% greater (relative risk, 1.18; 95% CI, 1.02-1.38) in small compared to large centers, but dialysis and bronchoscopy were used significantly less but were associated with mortality. After adjustment for differences in demographic factors and primary pulmonary conditions, acute renal failure, acute liver necrosis, acute pancreatitis, and receipt of bronchoscopy remained independently associated with mortality. Center volume measurement was not associated with mortality given these factors., Conclusions: Among neonates, investigation for intraventricular hemorrhage prior to extracorporeal membrane oxygenation and preservation of renal function are important factors for improvement. Earlier initiation of extracorporeal membrane oxygenation and careful attention to preservation of organ function are important to improve survival for children.

Objective: Extracorporeal membrane oxygenation, an accepted rescue therapy for refractory cardiopulmonary failure, requires a complex multidisciplinary approach and advanced technology. Little is known about the relationship between a center's case volume and patient mortality. The purpose of this study was to analyze the relationship between hospital extracorporeal membrane oxygenation annual volume and in-hospital mortality and assess if a minimum hospital volume could be recommended., Design: Retrospective cohort study., Setting: A retrospective cohort admitted to children's hospitals in the Pediatric Health Information System database from 2004 to 2011 supported with extracorporeal membrane oxygenation was identified. Indications were assigned based on patient age (neonatal vs pediatric), diagnosis, and procedure codes. Average hospital annual volume was defined as 0-19, 20-49, or greater than or equal to 50 cases per year. Maximum likelihood estimates were used to assess minimum annual case volume., Patients: A total of 7,322 pediatric patients aged 0-18 were supported with extracorporeal membrane oxygenation and had an indication assigned., Interventions: None., Measurements and Main Results: Average hospital extracorporeal membrane oxygenation volume ranged from 1 to 58 cases per year. Overall mortality was 43% but differed significantly by indication. After adjustment for case-mix, complexity of cardiac surgery, and year of treatment, patients treated at medium-volume centers (odds ratio, 0.86; 95% CI, 0.75-0.98) and high-volume centers (odds ratio, 0.75; 95% CI, 0.63-0.89) had significantly lower odds of death compared with those treated at low-volume centers. The minimum annual case load most significantly associated with lower mortality was 22 (95% CI, 22-28)., Conclusions: Pediatric centers with low extracorporeal membrane oxygenation average annual case volume had significantly higher mortality and a minimum volume of 22 cases per year was associated with improved mortality. We suggest that this threshold should be evaluated by additional study.