Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). Design: Cross-sectional electronic survey. Setting: Email-based Research Electronic Data Capture survey. Patients: Neonates undergoing ECMO for respiratory failure at level IV NICUs. Interventions: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children\u27s Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. Measurements and main results: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). Conclusions: The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity

Presumed Systemic Inflammatory Response Syndrome in the Pediatric Emergency Department.

OBJECTIVE: The aim of this study was to examine the incidence and outcomes of patients presenting with systemic inflammatory response syndrome (SIRS) in the pediatric emergency department (PED). METHODS: This was a descriptive, retrospective cohort study of all patients from birth to 18 years presenting to the PED of a single center on 16 days distributed over 1 year. The presence of presumed SIRS (pSIRS, defined as noncore temperature measurement and cell count when clinically indicated) and sepsis was determined for all study patients. Patients were followed up for 1 week. RESULTS: The incidence of pSIRS was 15.3% (216/1416). Suspected or proven infection was present in 37.1% (n = 525) of the study population and 76.4% (n = 165) with pSIRS, with no cases of severe sepsis or septic shock. Sensitivity and specificity of pSIRS for predicting infection were 31.4% (95% confidence interval [CI], 27.5%-35.6%) and 94.3% (95% CI, 92.5%-95.7%), respectively. Although patients with pSIRS had a relative risk of 2.4 (95% CI, 1.6-3.5; P \u3c 0.0001) for admission, 74% were discharged home with no subsequent PED visits. Of defined sepsis cases, 75% were discharged home without return. CONCLUSIONS: Presumed SIRS and sepsis are relatively common in the PED. Use of pSIRS to screen for sepsis risks missing infection, whereas using pSIRS in the current sepsis definition results in overinclusion of nonsevere illness

Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease

Amyloid β-peptide (Aβ) appears to play a key pathogenic role in Alzheimer disease (AD). Immune therapy in mouse models of AD via Aβ immunization or passive administration of Aβ antibodies markedly reduces Aβ levels and reverses behavioral impairment. However, a human trial of Aβ immunization led to meningoencephalitis in some patients and was discontinued. Here we show that nasal vaccination with a proteosome-based adjuvant that is well tolerated in humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat multiple sclerosis, potently decreases Aβ plaques in an AD mouse model. This effect did not require the presence of antibody, as it was observed in B cell–deficient (Ig μ–null) mice. Vaccinated animals developed activated microglia that colocalized with Aβ fibrils, and the extent of microglial activation correlated strongly with the decrease in Aβ fibrils. Activation of microglia and clearing of Aβ occurred with the adjuvant alone, although to a lesser degree. Our results identify a novel approach to immune therapy for AD that involves clearing of Aβ through the utilization of compounds that have been safely tested on or are currently in use in humans