Implementing a Pediatric Pulmonary Embolism Response Team Model: An Institutional Experience.

Pulmonary embolism is increasing in prevalence among pediatric patients; although still rare, it can create a significant risk for morbidity and death within the pediatric patient population. Pulmonary embolism presents in various ways depending on the patient, the size of the embolism, and the comorbidities. Treatment decisions are often driven by the severity of the presentation and hemodynamic effects; severe presentations require more invasive and aggressive treatment. We describe the development and implementation of a pediatric pulmonary embolism response team designed to facilitate rapid, multidisciplinary, data-driven treatment decisions and management.

Acute Compartment Syndrome in Pediatric Patients on Extracorporeal Membrane Oxygenation Support.

BACKGROUND: When acute compartment syndrome (ACS) occurs in pediatric patients requiring venoarterial extracorporeal membrane oxygen (VA ECMO) support, there is little data to guide surgeons on appropriate management. The purpose of this study is to characterize the presentation, diagnosis, timeline, and outcomes of patients who developed this complication. METHODS: This is a single-center retrospective case series of children below 19 years old on VA ECMO support who subsequently developed extremity ACS between January 2016 and December 2022. Outcomes included fasciotomy findings, amputation, mortality, and documented function at the last follow-up. RESULTS: Of 343 patients on VA ECMO support, 18 (5.2%) were diagnosed with ACS a median 29 hours after starting ECMO. Initial cannulation sites included 8 femoral, 6 neck, and 4 central. Femoral artery cannulation was associated with an increased risk of ACS [odds ratio=6.0 (CI: 2.2 to 15), P <0.0001]. In the hospital, the mortality rate was 56% (10/18). Fourteen (78%) patients received fasciotomies a median of 1.2 hours after ACS diagnosis. Only 4 (29%) patients had all healthy muscles at initial fasciotomy, while 9 (64%) had poor muscular findings in at least 1 compartment. Patients with worse findings at fasciotomy had a significantly longer duration between ischemia onset and ACS diagnosis. Patients required a median of 1.5 additional procedures after fasciotomy, and only 1 (7%) developed a surgical site infection. Of the 7 surviving fasciotomy patients, 2 required amputations, 3 developed an equinus contracture, 1 developed foot drop, and 3 had no ACS-related deficits. Four patients did not receive fasciotomies: 3 were deemed too ill and later died, and 1 was diagnosed too late to benefit. The only surviving nonfasciotomy patient required bilateral amputations. CONCLUSIONS: Pediatric ECMO-associated ACS is not exclusive to patients with femoral artery cannulation. The majority of fasciotomy patients were diagnosed with ACS after muscle necrosis had already started. We were unable to definitively conclude whether fasciotomies provide better outcomes. There is a need for increased awareness and earlier recognition of this rare yet potentially devastating complication. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Outcomes of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest Among Children With Noncardiac Illness Categories.

OBJECTIVES: The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years. DESIGN: Retrospective multicenter cohort study. SETTING: Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021. PATIENTS: Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 [interquartile range: 0.2-7.0] year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 [35-63] minutes. ECPR use increased over time ( p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis ( p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 [95% CI, 0.84-2.40; p = 0.19]). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge. CONCLUSIONS: ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).

Atrial septal defect closure is associated with improved clinical status in patients ≤ 10 kg with bronchopulmonary dysplasia.

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post-ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD-ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD-ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre- to 8 weeks post-intervention, and pre- and post-intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre- versus post-intervention slope with the most score drop the first week post-intervention (-2.1 + /- 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope -0.8 + /- 0.8, p = 0.013) and 4 (slope -1.0 + /- 0.5, p = 0.001) post-intervention. There was a significant difference in pre- and post-intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO2 need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD-ASD score, diuretic need, and respiratory status after ASD closure in BPD-ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single-center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non-intervention infants.

Corrigendum: Case report: Selexipag in pediatric pulmonary hypertension: initiation, transition, and titration.

[This corrects the article DOI: 10.3389/fped.2023.1050508.].

Pulmonary Hypertension in Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.

Hereditary pulmonary arterial hypertension burden in pediatrics: A single referral center experience.

Introduction: Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center. Methods: Children with PAH panel administered by the John Welsh Cardiovascular Diagnostic Laboratory at Texas Children's Hospital and Baylor College of Medicine in Houston, Texas between October 2012 to August 2021 were included into this study. Medical records were retrospectively reviewed for clinical correlation. Results: Sixty-six children with PAH underwent PAH genetic testing. Among those, 9 (14%) children were found to have pathogenic mutations, 16 (24%) children with variant of unknown significance and 41 (62%) children with polymorphism (classified as likely benign and benign). BMPR2 mutation was the most common pathogenic mutation, seen in 6 of the 9 children with detected mutations. Hemodynamic studies showed higher pulmonary vascular resistance among those with pathogenic mutations than those without (17.4 vs. 4.6 Wood units). All children with pathogenic mutations had severe PAH requiring triple therapy. There were tendencies for higher lung transplantation rate but lower mortality among those with pathogenic mutations. Conclusions: Abnormalities on genetic testing are not uncommon among children with PAH, although majority are of unclear significance. However, children with pathogenic mutations tended to present with more severe PAH requiring aggressive medical and surgical therapies. Genetic testing should be routinely considered due to consequences for treatment and prognostic implications. Larger scale population studies and registries are warranted to characterize the burden of HPAH in the pediatric population specifically.

Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

INTRODUCTION: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). METHODS: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. RESULTS: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008-0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01-0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31-47.04; p = 0.024). CONCLUSION: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

Use of Berlin EXCOR cannulas in both venovenous and venoarterial central extracorporeal membrane oxygenation configurations overcomes the problem of cannula instability while bridging infants and young children to lung transplant.

Objectives: Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant. Methods: We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between 2019 and 2021. Results: Six patients, 2 with pulmonary veno-occlusive disease (15-month-old male and 8-month-old male), 1 with ABCA3 mutation (2-month-old female), 1 with surfactant protein B deficiency (2-month-old female), 1 with pulmonary arterial hypertension in the setting of D-transposition of the great arteries after repair as a neonate (13-year-old male), and 1 with cystic fibrosis and end-stage lung disease, were supported for a median of 56.3 days on extracorporeal membrane oxygenation while awaiting transplantation. All patients were extubated after initiation of extracorporeal membrane oxygenation, participating in rehabilitation until transplant. No complications due to central cannulation and use of the Berlin Heart EXCOR cannulas were observed. One patient with cystic fibrosis developed fungal mediastinitis and osteomyelitis resulting in discontinuation of mechanical support and death. Conclusions: Novel use of Berlin Heart EXCOR cannulas for central cannulation eliminates the problem of cannula instability allowing extubation, rehabilitation, and bridge to lung transplant for infants and young children.

Case Report: Selexipag in pediatric pulmonary hypertension: Initiation, transition, and titration.

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient's and caregiver's quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited to case reports in older adolescent patients and selexipag is not approved for use in the pediatric pulmonary hypertension population, many pediatric centers are expanding the use of this therapy to this population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children under 10 years of age, between 10 and 30 kg. Seven patients were initiated on selexipag therapy including de novo initiation and transition from intravenous treprostinil to oral selexipag. All patients were on stable background therapy with phosphodiesterase-5 inhibitor and endothelin receptor antagonist therapies at baseline. All patients reached their planned goal selexipag dose during admission without the need for changes to the titration schedule and without hemodynamic deterioration. In our experience, oral selexipag is safe and well-tolerated in young pediatric patients with pulmonary hypertension. Based on our favorable experience, we developed an institution-specific selexipag process algorithm for continued successful use in the pediatric population.

Computer simulation of surgical interventions for the treatment of refractory pulmonary hypertension.

This paper describes computer models of three interventions used for treating refractory pulmonary hypertension (RPH). These procedures create either an atrial septal defect, a ventricular septal defect or, in the case of a Potts shunt, a patent ductus arteriosus. The aim in all three cases is to generate a right-to-left shunt, allowing for either pressure or volume unloading of the right side of the heart in the setting of right ventricular failure, while maintaining cardiac output. These shunts are created, however, at the expense of introducing de-oxygenated blood into the systemic circulation, thereby lowering the systemic arterial oxygen saturation. The models developed in this paper are based on compartmental descriptions of human hemodynamics and oxygen transport. An important parameter included in our models is the cross-sectional area of the surgically created defect. Numerical simulations are performed to compare different interventions and various shunt sizes and to assess their impact on hemodynamic variables and oxygen saturations. We also create a model for exercise and use it to study exercise tolerance in simulated pre-intervention and post-intervention RPH patients.

Risk Stratification by Percent Liver Herniation in Congenital Diaphragmatic Hernia.

INTRODUCTION: Congenital diaphragmatic hernia is associated with pulmonary hypoplasia, pulmonary hypertension, and significant neonatal morbidity. Although intrathoracic liver herniation (LH) >20% is associated with adverse outcomes, the relationship between LH <20% and outcomes is poorly characterized. METHODS: A single-center retrospective cohort study was performed from 2011 to 2020 of 80 fetuses with left-sided congenital diaphragmatic hernia that were delivered and repaired at our institution. Perinatal, perioperative, and postoperative data were collected. We evaluated the association of %LH with outcomes as a stratified ordinal variable (0%-10% LH, 10%-19% LH, and >20% LH) and as a continuous variable. Data were analyzed by analysis of variance with Bonferroni post hoc analysis, chi-square analyses, and univariate logistic regression. RESULTS: Extracorporeal membrane oxygenation (ECMO) (P < 0.001), repair on ECMO (P = 0.002), repair with patch (P < 0.001), length of stay (P = 0.002), inhaled nitric oxide use (P < 0.001), and sildenafil use at discharge (P < 0.001), showed significant differences among LH groups. There were no differences among the groups concerning survival (at discharge, 6 mo, and 1 y) and tracheostomy. On further analysis there was no difference between 10% and 19% LH and ≥20% LH patients concerning ECMO (P = 0.55), repair on ECMO (P = 0.54), repair with patch (P = 1.00), length of stay (P = 1.00), and inhaled nitric oxide use (P = 0.33). Logistic regression analysis displayed a significant association with LH and ECMO, repair on ECMO, repair with patch, inhaled nitric oxide use, and sildenafil use. CONCLUSIONS: Our analysis displays no significant difference in perinatal management between patients with 10%-19% and ≥20% LH. These findings suggest that the historical cutoff of ≥20% LH may not be sufficient alone to guide perinatal counseling and decision-making.

Provider Perceptions for Withdrawing Life Sustaining Therapies at a Large Pediatric Hospital.

CONTEXT: More than 74% of pediatric deaths occur in an intensive care unit (ICU), with 40% occurring after withdrawal of life-sustaining therapies (WOLST). No needs assessment has described provider needs or suggestions for improving the WOLST process in pediatrics. OBJECTIVES: This study aims to describe interdisciplinary provider self-reported confidence, needs, and suggestions for improving the WOLST process. METHODS: A convergent parallel mixed-methods design was used. An online survey was distributed to providers involved in WOLSTs in a quaternary children's hospital between January and December 2018. The survey assessed providers' self-reported confidence in their role, in providing guidance to families about the WOLST, experiences with the WOLST process, areas for improvement, and symptom management. Kruskal-Wallis testing was used for quantitative data analysis with P values <0.05 considered significant. Analysis was performed with SPSS v27. Qualitative data were thematically analyzed using Atlas.ti.8 and NVivo. RESULTS: A total of 297 surveys were received (48% survey completion) that consisted of multiple choice, Likert-type, and yes/no questions with options for open-ended responses. Mean provider self-rated confidence was high and varied significantly between disciplines. Qualitative analysis identified four areas for refining communication: 1) between the primary team and family, 2) within the primary team, 3) between the primary team and consulting providers, and 4) logistical challenges. CONCLUSIONS: While participants' self-rated confidence was high, it varied between disciplines. Participants identified opportunities for improved communication and planning before a WOLST. Future work includes development and implementation of a best practice guideline to address gaps and standardize care delivery.

Extracorporeal Membrane Oxygenation Support for Antineutrophil Cytoplasmic Antibody-associated Vasculitides: An ELSO Registry Analysis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides with pulmonary involvement include granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, and can present with life-threatening pulmonary hemorrhage in up to 40% of patients. Mortality in those patients who require intubation and mechanical ventilation can reach 77%. Extracorporeal membrane oxygenation (ECMO) can be used to support these patients through definitive diagnosis and treatment, although minimizing the risk of ventilator-induced lung injury. We aimed to determine factors associated with favorable outcomes in patients with (ANCA)-associated vasculitides supported on ECMO. We performed a retrospective observational study using the Extracorporeal Life Support Organization registry of pediatric and adult patients with ANCA-associated vasculitis supported on ECMO from 2010 to 2020. One hundred thirty-five patients were included for analysis. Many patients had renal involvement (39%) in addition to pulmonary involvement (93%). Survival was 73% in AAV patients supported on ECMO. The presence of pulmonary hemorrhage was not associated with worse outcomes in our cohort. Older age, the use of venoarterial ECMO, ECMO-cardiopulmonary resuscitation, or sustaining a cardiac arrest before ECMO was associated with decreased survival. In conclusion, venovenous ECMO should be considered as a supportive bridge to definitive diagnosis and treatment in (ANCA)-associated vasculitides, regardless if pulmonary hemorrhage is present.

Outcomes of COVID-19 infection in pediatric pulmonary hypertension: A single-center experience.

BACKGROUND: The global COVID-19 pandemic was particularly concerning for the pediatric pulmonary hypertension (PH) population due to immature immune systems and developmental comorbidities. This study aims to describe a single-center experience of pediatric PH patients diagnosed with COVID-19 disease. METHODS: A retrospective cohort study of all pediatric patients followed by the PH Center at Texas Children's Hospital diagnosed with COVID-19 infection from April 2020 to February 2021. RESULTS: We identified 23 patients with a median age of 58 months (interquartile range [IQR]: 25-75th, 21-132 months), 48% being Hispanics. Eight patients (35%) required hospitalization; median length of stay was 6 days (IQR: 25-75th, 5-8 days). Only three of these eight patients required increased respiratory support. Targeted PH therapy was escalated in four patients (two in dual and two in triple therapy). There was one mortality in a patient with failing Fontan physiology. Ninety-one percent of patients have had post-COVID outpatient follow-up, median of 101 days (IQR: 25-75th, 50-159 days) from diagnosis. Of the five patients with 6 min walk test (6MWT) data, three (60%) children walked less distance, median of -12 m (IQR: 25-75th, -12 to +49 m) compared to pre-COVID testing. Postinfection pulmonary function testing (PFT) was notable for decrease in predicted forced vital capacity (FVC; median -6%, range -11% to +6%) and forced expiratory volume in one second (FEV1; median -14%, range -12% to -18%) in 75% of the patients with PFT data. CONCLUSION: In our institution, COVID-19 was found more frequently in Hispanics and associated with low mortality.

Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension.

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease. OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure. METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States. RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001). CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure.