Neonatal Extracorporeal Membrane Oxygenation: Associations between Continuous Renal Replacement Therapy, Thrombocytopenia, and Outcomes.

INTRODUCTION: The incidence of thrombocytopenia in neonates receiving extracorporeal membrane oxygenation (ECMO) with and without concurrent continuous renal replacement therapy (CRRT) and associated complications have not been well described. The primary aims of the current study were to (1) characterize thrombocytopenia in neonates receiving ECMO (including treated concurrently with CRRT) and (2) evaluate risk factors (including CRRT utilization) associated with severe thrombocytopenia. In a planned exploratory secondary aim, we explored the association of severe thrombocytopenia with outcomes in neonates receiving ECMO. METHODS: We conducted a retrospective single-center chart review of neonates who received ECMO 07/01/14 - 03/01/20 and evaluated associations between CRRT, severe thrombocytopenia (platelet count <50,000/mm3), and outcomes (ECMO duration, length of stay, and survival). RESULTS: Fifty-two neonates received ECMO; 35 (67%) received concurrent CRRT. Severe thrombocytopenia occurred in 27 (52%) neonates overall and in 21 (60%) neonates who received concurrent CRRT. Underlying diagnosis, ECMO mode, care unit, and moderate/severe hemolysis differed between those who did and did not receive CRRT. CRRT-receivers experienced shorter hospital stays than CRRT non-receivers, but ECMO duration, length of intensive care unit (ICU) stay, and survival did not differ between groups. CRRT receipt was associated with severe thrombocytopenia. Exploratory classification and regression tree (CART) analysis suggests CRRT use, birthweight, and ICU location are all predictors of interest for severe thrombocytopenia. CONCLUSIONS: In our cohort, CRRT use during ECMO was associated with severe thrombocytopenia, and patients who received ECMO with CRRT experienced shorter hospital stays than those who did not receive CRRT. Exploratory CART analysis suggests CRRT use, birthweight, and ICU location are all predictors for severe thrombocytopenia and warrant further investigations in larger studies.

Systemic anticoagulation in ECMO.

While unfractionated heparin (UFH) remains the mainstay of anticoagulation during pediatric extracorporeal life support, direct thrombin inhibitors (DTIs) are increasingly used. In this article, we will review most recent evidence regarding utilization of both UFH and DTIs and compare their known advantages and disadvantages. We will present anticoagulation monitoring strategies during ECMO and outline the most recent Extracorporeal Life Support Organization's anticoagulation guidelines, however with the caveat that there are no true consensus recommendations for anticoagulation management in pediatric ECMO. With these updates, we will serve as the bedside clinician's refresher on common practices for anticoagulation during "routine" ECMO. We will additionally highlight special circumstances, including high risk surgical procedures during ECMO, in which adjustments in anticoagulation and/or addition of antifibrinolytic therapy might mitigate risk.

Complication accrual impacts pediatric extracorporeal life support mortality.

INTRODUCTION: This study tested the hypothesis that complication accrual during pediatric extracorporeal life support (ECLS) increases mortality irrespective of indication for support. METHODS: Prospectively collected Extracorporeal Life Support Organization (ELSO) registry data for all neonatal and pediatric patients cannulated for ECLS at our institution from 1/1/2015 to 12/31/2020 was stratified based on the presence or absence of complications. We excluded renal replacement therapy from complications, as this is frequently and empirically applied within our practice. RESULTS: Of 114 patients, overall survival to discharge was 66%. 62 patients (54%) had 149 total complications: 29% were mechanical (circuit related), and the rest were patient related. Age (neonatal versus pediatric), sex, race/ethnicity, support type, presence of pre-ECLS arrest, pre-ECLS pH and intubation-to-ECLS duration were not significantly associated with the development of complications. Patients with complications required longer ECLS duration (168 versus 86 median hours, p < 0.001) and were more likely to be decannulated due to death or poor prognosis (25% versus 8%, p = 0.022). One or more ECLS complications was associated with significantly decreased survival by Cox proportional hazard regression (p = 0.003). CONCLUSION: Complications on ECLS are associated with longer support duration and predict decreased survival independent of pre-ECLS variables, suggesting a multidisciplinary ECLS team target for improved outcomes.

Emanuel syndrome and congenital diaphragmatic hernia: A systematic review.

BACKGROUND: Emanuel Syndrome (ES), a rare chromosomal disorder caused by a supernumerary chromosome 22 derivative (der(22)t(11;22)), was identified in a fetus with congenital diaphragmatic hernia (CDH) at our fetal center. We aimed to identify a precedent for clinical care and patient outcomes to guide family decision-making. METHODS: This non-funded and non-registered study queried the entire CDH Registry (CDHR) including >10,000 patients since 1995 and conducted a systematic literature review for patients with concomitant ES and CDH. RESULTS: Literature review captured 12 citations and identified 9 patients with CDH+ES from over 400 known ES cases. Given the rarity of the disease and to reduce bias, there were no exclusion criteria aside from non-English language. Of these 9, two underwent surgical CDH repair with neither surviving. The CDHR identified 6 patients with ES, all reported after 2013 and prenatally diagnosed. Median estimated gestational age was 39 weeks (range 37-40) and median birth weight was 2.72 kg (range 2.4-3.4 kg). 3 patients died within the first few postnatal days; surgical repair was not offered due to "anomalies" and "pulmonary hypertension" in two and one family chose comfort measures. The other 3 patients underwent surgical repair, and 2 were supported with ECMO. Two patients survived to discharge, incurring surgical comorbidities associated with severe CDH including gastrostomy dependence, tracheostomy, and CDH recurrence. CONCLUSIONS: ES patients with CDH have potential to tolerate repair and survive to discharge, however with significant additional morbidity combined with severe challenges inherent to ES. This represents the largest series of patients with CDH and ES to date. LEVEL OF EVIDENCE: IV (Case series with no comparison group).

Keto-Bezoar: Adverse Event Related to Initiation of Ketogenic Diet in an Infant.

The ketogenic diet is frequently used as part of the treatment regimen for pediatric patients with refractory epilepsy. This diet is generally well tolerated, with constipation being the most described side effect. This case highlights a previously undocumented severe complication of a "keto-bezoar" formation related to the initiation of the ketogenic diet in a young infant.

Long term follow-up in congenital diaphragmatic hernia.

Survivorship of patients with congenital diaphragmatic hernia (CDH) has created a unique cohort of children, adolescents and adults with complex medical and surgical needs. Morbidities specific to this disease benefit from multi-specialty care, and the long term follow up of these patients offers a tremendous opportunity for research and collaboration. Herein we aim to offer an overview of the challenges that modern CDH survivors face, and include a risk-stratified algorithm as a general guideline for a multi-specialty follow up program.

Aggressive Surgical Management of Congenital Diaphragmatic Hernia: Worth the Effort?: A Multicenter, Prospective, Cohort Study.

OBJECTIVE: The objectives of this study were (i) to evaluate infants with congenital diaphragmatic hernia (CDH) that do not undergo repair, (ii) to identify nonrepair rate by institution, and (iii) to compare institutional outcomes based on nonrepair rate. BACKGROUND: Approximately 20% of infants with CDH go unrepaired and the threshold to offer surgical repair is variable. METHODS: Data were abstracted from a multicenter, prospectively collected database. Standard clinical variables, including repair (or nonrepair), and outcome were analyzed. Institutions were grouped based on volume and rate of nonrepair. Preoperative mortality predictors were identified using logistic regression, expected mortality for each center was calculated, and observed /expected (O/E) ratios were computed for center groups and compared by Kruskal-Wallis ANOVA. RESULTS: A total of 3965 infants with CDH were identified and 691 infants (17.5%) were not repaired. Nonrepaired patients had lower Apgar scores (P < 0.05) and increased incidence of anomalies (P < 0.0001). Low-volume centers ("Lo", n=44 total, < 10 CDH pts/yr) and high-volume centers ("Hi", n = 21) had median nonrepair rates of 19.8% (range 0%-66.7%) and 16.7% (5.1%-38.5%), respectively. High-volume centers were further dichotomized by rate of nonrepair (HiLo = 5.1-16.7% and HiHi = 17.6-38.5%), leaving 3 groups: HiLo, HiHi, and Lo. Predictors of mortality were lower birth weight, lower Apgar scores, prenatal diagnosis, and presence of congenital anomalies. O/E ratios for mortality in the HiLo, HiHi, and Lo groups were 0.81, 0.94, and 1.21, respectively (P < 0.0001). For every 100 CDH patients, HiLo centers have 2.73 (2.4-3.1, 95% confidence interval) survivors beyond expectation. CONCLUSIONS: There are significant differences between repaired and nonrepaired CDH infants and significant center variation in rate of nonrepair exists. Aggressive surgical management, leading to a low rate of nonrepair, is associated with improved risk-adjusted mortality.

Long-term follow-up of congenital diaphragmatic hernia.

Increased survival of patients with congenital diaphragmatic hernia has created a unique cohort of children, adolescent, and adult survivors with complex medical and surgical needs. Disease-specific morbidities offer the opportunity for multiple disciplines to unite together to provide long-term comprehensive follow-up, as well as an opportunity for research regarding late outcomes. These children can exhibit impaired pulmonary function, altered neurodevelopmental outcomes, nutritional insufficiency, musculoskeletal changes, and specialized surgical needs that benefit from regular monitoring and intervention, particularly in patients with increased disease severity. Below we aim to characterize the specific challenges that these survivors face as well as present an algorithm for a multidisciplinary long-term follow-up program.

A risk-stratified analysis of delayed congenital diaphragmatic hernia repair: does timing of operation matter?

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns and, despite improved outcomes with multimodality therapies, optimal timing of repair remains undefined. We sought to evaluate the influence of surgical timing on patient outcomes and hypothesized that delayed repair does not improve survival in CDH. METHODS: Prospectively collected data from 1,385 CDH Registry infants without preoperative extracorporeal membrane oxygen therapy (ECMO) were evaluated. Patients were stratified by timing of repair: Day of life (DOL) 0-3 (group 1), 4-7 (group 2), or >8 (group 3), and the effect of surgical timing on mortality was determined by logistic regression and risk-adjusted for severity of illness. RESULTS: The unadjusted odds ratio (OR) for mortality increased significantly with delayed repair (group 2, 1.73 [95% CI, 1.00-2.98; group 3, 3.42 [95% CI, 1.97-5.96]). However, when adjusted for severity of illness, delay in repair did not predict increased mortality (group 2, 1.2 [95% CI, 0.7-2.2]; group 3, 1.4 [95% CI, 0.8-2.6]), nor did it portend an increased need for postoperative ECMO (group 2, 1.1 [95% CI, 0.5-2.4]; group 3, 0.5 [95% CI, 0.2-1.4]). CONCLUSION: After adjustment for known risk factors, the timing of CDH repair in low-risk infants does not seem to influence mortality. However, specific clinical parameters guiding timing of elective CDH repair remain unknown.

Endocarditis with left ventricular cutaneous fistula after aortic root replacement with a valved conduit.

Infection after aortic root replacement is uncommon, and it can be fatal. Herein, we present the case of a patient who underwent aortic root replacement with a valved conduit and coronary reimplantation. Prosthetic valve endocarditis and left ventricular cutaneous fistula ensued. Either condition alone could have been fatal. The fistula coursed from the valved conduit through the left ventricular outflow tract, behind the left main coronary artery, and to the skin at the upper sternum. Safe surgical entry into the chest was crucial, due to the free communication between the left ventricle, mediastinum, and skin. We discuss our surgical approach to this unusual combination of conditions, and the postoperative treatment of the patient.

Microscopic minimally invasive approach to nonsyndromic craniosynostosis.

PURPOSE: The purpose of this retrospective study was to present the results of the authors' microscopic minimally invasive approach in the treatment of nonsyndromic craniosynostosis. METHODS: From 2001 to 2007, the authors treated a cohort of 67 infants with nonsyndromic sagittal, unicoronal, bicoronal, and metopic craniosynostosis, either with the microscopic (n = 40) or the open (n = 27) approach. In the microscopic approach, incisions were placed over the premature suture, and using a surgical microscope, the appropriate synostectomy was performed. The open approach used a traditional coronal incision with cranial vault reconstruction. Both groups of patients had postoperative molding helmet therapy. Finally, anthropometric measurements were used to evaluate the treatment results. The measurement used for the patients with sagittal and bicoronal craniosynostoses was the divergence from the norm of the age-adjusted cephalic index. The (FZr-EUl/FZl-EUr) and (FZr-EUr)/(FZl-EUl) were used for the patients with unicoronal craniosynostosis. The divergence from the norm of age-adjusted (FTr-FTl)/(Tr-Tl) was used for the patients with metopic craniosynostosis. (FZr = right frontozygomaticus, EUl = left eurion, FZl = left frontozygomaticus, Eur = right eurion, FTr = right frontotemporale, FTl = left frontotemporale, Tr = tragion, Tl = left tragion). RESULTS: The median surgical times for microscopic and open approaches were 108 and 210 minutes, the volumes of blood loss were 75 and 220 mL, the durations of hospital stay were 2 and 4 days, the numbers of helmet were 2 and 1, and the durations of helmet therapy were 10.5 and 8 weeks, respectively. The analysis of variance for repeated measures showed that there was no statistically significant difference between the 2 groups in any of the craniosynostoses. CONCLUSIONS: The treatment outcomes from the microscopic minimally invasive approach to craniosynostosis are equal to those seen with the open approach. The microscopic approach results in less operative time, blood loss, and hospitalization.