A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7 days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Simulation-Based Training in High-Quality Cardiopulmonary Resuscitation Among Neonatal Intensive Care Unit Providers.

Introduction: American Heart Association guidelines recommend the use of feedback devices for CPR provider resuscitation training. There is paucity of published literature regarding the utility of these devices especially in neonates and infants. We sought to evaluate if simulation-based education and debriefing using a CPR feedback device would improve CPR performance on an infant manikin in a cohort of NICU nurses as evaluated by CPR feedback device. Methods: We conducted a prospective, observational simulation study to assess the quality of chest compressions by NICU nurses before and after debriefing using CPR quality data captured by an accelerometer-based device. Chest compression (CC) depth, rate, recoil, CC fraction and nursing confidence level related to performing a high-quality CPR were compared before and after debriefing using paired t-test and Wilcoxon rank sum test. Results: A total of 62 NICU nurses participated in the study and all of them were Neonatal Resuscitation Program (NRP) certified. There was a significant improvement in CC depth and CC fraction [mean + SD values = 0.79 in + 0.17 (pre-debrief), 0.86 in + 0.21 (post-debrief) (p = 0.034) and 56.8% + 17.7 (pre-debrief), 70.8% + 18.4 (post-debrief) (0.0014), respectively]. There was no difference in CC rate (p = 0.36) and recoil (p = 0.25) between pre and post structured debriefing. The confidence level of nurses in all CPR dynamics (appropriate CC rate, CC depth, team communication, minimizing interruption in CC and coordinating CC with ventilation) was significantly higher after simulation and structured debriefing. All the nurses used 3:1 compression: ventilation ratio of NRP despite the patient being a 4 month old premature baby in the NICU. Conclusions: Simulation training and debriefing of NICU nurses using CPR feedback device improved their chest compression quality on an infant mannequin and their confidence level for performing high-quality CPR. NICU providers tend to use NRP protocol of 3:1 compression: ventilation ratio during CPR in the NICU irrespective of age of the infant.

Understanding increased ferritin levels in pediatric ECMO patients.

Abnormally high serum ferritin levels have been reported during pediatric ECMO, attributed to frequent red blood cell transfusion and suggestive of iron overload. However, the utility of ferritin for diagnosing iron overload is complicated by its response as an acute-phase reactant. In this study, we aimed to assess the utility of ferritin for diagnosing ECMO-related iron overload, with secondary aims of understanding its relationship with inflammation and erythropoiesis. Ferritin was elevated in all pediatric ECMO runs (median 459 ng/ml, IQR = 327.3-694.4). While intermittent elevations in serum iron were observed, all normalized prior to decannulation. Unreported previously, erythropoietin (EPO) remained well above normative values prior to and throughout ECMO runs, despite frequent transfusion and exposure to hyperoxia. Ferritin correlated poorly with serum iron [r(80) = 0.05, p = 0.65], but correlated well with IL-6 [r(76) = 0.48, p < 0.001] and EPO [r(81) = 0.55, p < 0.001]. We suggest that serum ferritin is a poor biomarker of iron overload in ECMO patients, and that future investigation into its relationship with EPO is warranted.

Endotracheal tube manipulation during cardiopulmonary resuscitation in the neonatal intensive care unit.

OBJECTIVES: We sought to describe the approach to and impact of endotracheal tube (ETT) placement for cardiopulmonary resuscitation (CPR) occurring in the neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective review of in-NICU CPR from 2012 to 2017 across ten NICUs in San Antonio, Texas. RESULTS: Of 209 CPR events, 22 (10.5%) patients required ETT placement at CPR onset, 23 (11%) had an existing ETT removed and replaced, and 8 (3.4%) both. We found no association between time without an ETT tube during CPR and time to return of spontaneous circulation (ROSC) or rate of ROSC. We found no documented use of a laryngeal mask airway during in-NICU CPR. CONCLUSIONS: For CPR occurring in the NICU, the achievement of ROSC or time to ROSC is not impacted by the need to place an initial AA at the onset of CPR in this contemporary cohort.

The Characteristics and Outcomes of Cardiopulmonary Resuscitation within the Neonatal Intensive Care Unit Based on Gestational Age and Unit Level of Care.

OBJECTIVES: This study aimed to describe the variation of in-neonatal intensive care unit (NICU) cardiopulmonary resuscitation (CPR) characteristics and outcomes across different gestational ages and levels of NICU care. STUDY DESIGN: This is a retrospective cohort study of in-NICU CPR events across 10 NICUs in San Antonio, TX from 2012 through 2017. RESULTS: We identified 140 patients experiencing a total of 210 in-NICU CPR events. CPR was performed in 0.23% of Level III and 0.85% of Level IV NICU admissions. Gestational age was inversely related to CPR incidence. The median age at in-NICU CPR was lower for preterm versus term infants (6 vs. 28 days, p = 0.002). With regression modeling, each added minute of chest compression decreased the odds of return to spontaneous circulation by 11%. CONCLUSION: In-NICU CPR incidence rises with decreasing gestational age and increasing level of NICU care. The rate of return of spontaneous circulation decreases significantly with increasing duration of chest compressions. Further study is needed to identify patient factors associated with adverse outcome.

LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel ∼35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.

Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide.

OBJECTIVES: Evaluate the short-term effects of IV epoprostenol in neonates with persistent pulmonary hypertension (PPHN) of the newborn. STUDY DESIGN: We reviewed 36 patients with inhaled nitric oxide (iNO) refractory PPHN placed on IV epoprostenol from 2010 to 2015. Patients were categorized as responders or non-responders (who either died or required extracorporeal membranous oxygenation). RESULTS: There were 15 responders and 21 non-responders. Pulmonary hypoplasia was the etiology of PPHN for 57% of non-responders vs. 13% of responders. Median oxygenation index (OI) was similar at baseline (41.8 non-responders vs. 36.5 responders, p = 0.41) with responders having a significantly lower OI by 4 h of treatment (42.3 vs. 23.1, p = 0.002). Epoprostenol responders had a median OI decrease of 11.6 within 4 h (p = 0.017) with a significant response persisting through 24 h. CONCLUSION: In infants with iNO-refractory PPHN, initiation of IV epoprostenol was associated with a significant and rapid OI reduction among responders.