Venovenous Extracorporeal Membrane Oxygenation Initiation for Pediatric Acute Respiratory Distress Syndrome With Cardiovascular Instability is Associated With an Immediate and Sustained Decrease in Vasoactive-Inotropic Scores.

OBJECTIVE: To determine the association of venovenous extracorporeal membrane oxygenation (VV-ECMO) initiation with changes in vasoactive-inotropic scores (VISs) in children with pediatric acute respiratory distress syndrome (PARDS) and cardiovascular instability. DESIGN: Retrospective cohort study. SETTING: Single academic pediatric ECMO center. PATIENTS: Children (1 mo to 18 yr) treated with VV-ECMO (2009-2019) for PARDS with need for vasopressor or inotropic support at ECMO initiation. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas values, VIS, mean airway pressure (mPaw), and oxygen saturation (Sp o2 ) values were recorded hourly relative to the start of ECMO flow for 24 hours pre-VV-ECMO and post-VV-ECMO cannulation. A sharp kink discontinuity regression analysis clustered by patient tested the difference in VISs and regression line slopes immediately surrounding cannulation. Thirty-two patients met inclusion criteria: median age 6.6 years (interquartile range [IQR] 1.5-11.7), 22% immunocompromised, and 75% had pneumonia or sepsis as the cause of PARDS. Pre-ECMO characteristics included: median oxygenation index 45 (IQR 35-58), mPaw 32 cm H 2o (IQR 30-34), 97% on inhaled nitric oxide, and 81% on an advanced mode of ventilation. Median VIS immediately before VV-ECMO cannulation was 13 (IQR 8-25) with an overall increasing VIS trajectory over the hours before cannulation. VISs decreased and the slope of the regression line reversed immediately surrounding the time of cannulation (robust p < 0.0001). There were pre-ECMO to post-ECMO cannulation decreases in mPaw (32 vs 20 cm H 2o , p < 0.001) and arterial P co2 (64.1 vs 50.1 mm Hg, p = 0.007) and increases in arterial pH (7.26 vs 7.38, p = 0.001), arterial base excess (2.5 vs 5.2, p = 0.013), and SpO 2 (91% vs 95%, p = 0.013). CONCLUSIONS: Initiation of VV-ECMO was associated with an immediate and sustained reduction in VIS in PARDS patients with cardiovascular instability. This VIS reduction was associated with decreased mPaw and reduced respiratory and/or metabolic acidosis as well as improved oxygenation.

Extracorporeal Membrane Oxygenation for Neonates With Congenital Diaphragmatic Hernia: Prevalence of Seizures and Outcomes.

OBJECTIVES: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective, descriptive case series. SETTING: Neonatal ICU (NICU) in a quaternary care institution. PATIENTS: All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074). CONCLUSIONS: Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population.

Survival and Developmental Outcomes of Neonates Treated with Extracorporeal Membrane Oxygenation: A 10-Year Single-Center Experience.

OBJECTIVE: To evaluate the associations between the primary indication for extracorporeal membrane oxygenation (ECMO) in neonates and neurodevelopmental outcomes at 12 and 24 months of age. STUDY DESIGN: This is a retrospective cohort study of neonates treated with ECMO between January 2006 and January 2016 in the Children's Hospital of Philadelphia newborn/infant intensive care unit. Primary indication for ECMO was classified as medical (eg, meconium aspiration syndrome) or surgical (eg, congenital diaphragmatic hernia). Primary study endpoints were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Groups were compared with standard bivariate testing and multivariable regression. RESULTS: A total of 191 neonates met the study's inclusion criteria, including 96 with a medical indication and 95 with a surgical indication. Survival to discharge was 71%, with significantly higher survival in the medical group (82% vs 60%; P = .001). Survivors had high rates of developmental therapies and neurosensory abnormalities. Developmental outcomes were available for 66% at 12 months and 70% at 24 months. Average performance on the Bayley-III was significantly below expected population normative values. Surgical patients had modestly lower the Bayley-III scores over time; most notably, 15% of medical infants and 49% of surgical infants had motor delay at 24 months (P = .03). CONCLUSIONS: In this single-center cohort, surgical patients had lower survival rates and higher incidence of motor delays. Strategies to reduce barriers to follow-up and improve rates of postdischarge developmental surveillance and intervention in this high-risk population are needed.

Hospital-Acquired Infection in Pediatric Subjects With Congenital Heart Disease Postcardiotomy Supported on Extracorporeal Membrane Oxygenation.

OBJECTIVE: To determine prevalence of and risk factors for infection in pediatric subjects with congenital heart disease status postcardiotomy supported on extracorporeal membrane oxygenation, as well as outcomes of these subjects. DESIGN: Retrospective cohort from the Extracorporeal Life Support Organization. SETTING: U.S. and international medical centers providing care to children with congenital heart disease status postcardiotomy. PATIENTS: Critically ill pediatric subjects less than 8 years old admitted to medical centers between January 1, 2013, and December 31, 2015, who underwent cardiac surgery for congenital heart disease and required extracorporeal membrane oxygenation support within the first 14 postoperative days. Subjects were excluded if they underwent orthotopic heart transplantation, required preoperative extracorporeal membrane oxygenation, and had more than one postoperative extracorporeal membrane oxygenation run. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,314 extracorporeal membrane oxygenation subject encounters in the Extracorporeal Life Support Organization registry met inclusion criteria. Neonates comprised 53% (n = 696) of the cohort, whereas infants made up 33% (n = 435). Of the 994 subjects with Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery categorizable surgery, 33% (n = 325) were in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 and 23% (n = 231) in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 5. While on extracorporeal membrane oxygenation, 229 subjects (17%) acquired one or more extracorporeal membrane oxygenation-related infections, which represents an occurrence rate of 67 infections per 1,000 extracorporeal membrane oxygenation days. Gram-negative (62%) and Gram-positive (42%) infections occurred most commonly. Forty percent had positive blood cultures. Infants and children were at higher infection risk compared with neonatal subjects; subjects undergoing less complex surgery had higher infection rates. Unadjusted survival to hospital discharge was lower in infected subjects compared with noninfected subjects (43% vs 51%; p = 0.01). After adjusting for confounders via propensity matching, we identified no significant mortality difference between infected and noninfected subjects. CONCLUSIONS: Neonatal and pediatric subjects in this study have a high rate of acquired infection. Infants and children were at higher infection risk compared with neonatal subjects. There was not, however, a significant association between extracorporeal membrane oxygenation-related infection and survival to hospital discharge after propensity matching.

Isotopic evidence for anthropogenic lead exposure on a 17th/18th century Barbadian plantation.

OBJECTIVES: To identify and characterize anthropogenic lead sources on a 17th/18th century Barbadian plantation and to test if lead isotope analyses can be used to identify the geographic origins of first-generation African captives. MATERIALS AND METHODS: We carried out lead (Pb) isotope analyses on dental enamel samples from 24 individuals from the Newton Plantation Cemetery in Barbados, which had previously been analyzed for strontium (Sr) and oxygen (O) isotope composition (Schroeder et al., American Journal of Physical Anthropology, 2009, 139:547-557) and Pb concentrations (Schroeder et al., American Journal of Physical Anthropology, 2013, 150:203-209. RESULTS: We are able to identify British Pb sources, and more specifically Bristol/Mendips Pb, as the most likely source of anthropogenic Pb on the plantation, highlighting the impact of the British Atlantic economy on the lives of enslaved peoples in Barbados during the period of plantation slavery. Furthermore, we find that there is only one clear outlier among seven individuals who had previously been identified as African-born based on their enamel Sr isotope composition (Schroeder et al., American Journal of Physical Anthropology, 2009, 139:547-557). All other individuals present a very homogenous Pb isotope composition, which overlaps with that of British Pb sources. CONCLUSION: Our results indicate that while Pb isotope analyses can help identify and further characterize the sources of anthropogenic Pb in plantation settings, they might not be suited for identifying the origins of African-born individuals in diasporic contexts.

Short-Term Neurodevelopmental Outcome in Congenital Diaphragmatic Hernia: The Impact of Extracorporeal Membrane Oxygenation and Timing of Repair.

OBJECTIVES: The purpose of this study was to assess the need and timing of extracorporeal membrane oxygenation in relation to congenital diaphragmatic hernia repair as modifiers of short-term neurodevelopmental outcomes. DESIGN: Retrospective study. SETTING: A specialized tertiary care center. PATIENTS: Between June 2004 and February 2016, a total of 212 congenital diaphragmatic hernia survivors enrolled in our follow-up program. Neurodevelopmental outcome was assessed at a median age of 22 months (range, 5-37) using the Bayley Scales of Infant Development, third edition. Fifty patients (24%) required extracorporeal membrane oxygenation support. Four patients (8%) were repaired prior to cannulation, 25 (50%) were repaired on extracorporeal membrane oxygenation, and 21 (42%) were repaired after decannulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children with congenital diaphragmatic hernia, who required extracorporeal membrane oxygenation scored on average 4.6 points lower on cognitive composite (p = 0.031) and 9.2 points lower on the motor composite (p < 0.001). Language scores were similar between groups. Mean scores for children with congenital diaphragmatic hernia repaired on extracorporeal membrane oxygenation were significantly lower for cognition (p = 0.021) and motor (p = 0.0005) outcome. Language scores were also lower, but did not reach significance. A total of 40% of children repaired on extracorporeal membrane oxygenation scored below average in all composites, whereas only 9% of the non-extracorporeal membrane oxygenation, 4% of the repaired post-extracorporeal membrane oxygenation, and 25% of the repaired pre-extracorporeal membrane oxygenation patients scored below average across all domains. Only 20% of congenital diaphragmatic hernia survivors repaired on extracorporeal membrane oxygenation support scored within the average range for all composite domains. Duration of extracorporeal membrane oxygenation support was not associated with a higher likelihood of adverse cognitive (p = 0.641), language (p = 0.147), or motor (p = 0.720) outcome. CONCLUSIONS: Need for extracorporeal membrane oxygenation in congenital diaphragmatic hernia survivors is associated with worse neurocognitive and neuromotor outcome. Need for congenital diaphragmatic hernia repair while on extracorporeal membrane oxygenation is associated with deficits in multiple domains. Overall time on extracorporeal membrane oxygenation did not impact neurodevelopmental outcome.

Special equipment considerations for neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) for neonates is applied routinely at major children's hospitals around the world. While the practice seems routine, the peculiar physiology of the small human imposes particular constraints on selection of equipment, performance of the circuit, and risks to the child. The physiology of small patients and physics of circuit elements leave many areas opaque and far from optimal, but still allow assembly of a set of useful heuristics for good practice. Here, we examine individual mechanical components of the ECMO circuit with attention to selection, pitfalls, and peculiarities of each when applied to the neonate.

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection (P = .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/µL, CD8 < 50 cells/µL, CD45RA < 10%, or a restricted Vß T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913.