Early prediction of pulmonary outcomes in preterm infants using electrical impedance tomography.

Introduction: Electrical impedance tomography (EIT) allows assessment of ventilation and aeration homogeneity which may be associated with respiratory outcomes in preterm infants. Methods: This was a secondary analysis to a recent randomized controlled trial in very preterm infants in the delivery room (DR). The predictive value of various EIT parameters assessed 30 min after birth on important respiratory outcomes (early intubation <24 h after birth, oxygen dependency at 28 days after birth, and moderate/severe bronchopulmonary dysplasia; BPD) was assessed. Results: Thirty-two infants were analyzed. A lower percentage of aerated lung volume [OR (95% CI) = 0.8 (0.66-0.98), p = 0.027] as well as a higher aeration homogeneity ratio (i.e., more aeration in the non-gravity-dependent lung) predicted the need for supplemental oxygen at 28 days after birth [9.58 (5.16-17.78), p = 0.0028]. Both variables together had a similar predictive value to a model using known clinical contributors. There was no association with intubation or BPD, where numbers were small. Discussion: In very preterm infants, EIT markers of aeration at 30 min after birth accurately predicted the need for supplemental oxygen at 28 days after birth but not BPD. EIT-guided individualized optimization of respiratory support in the DR may be possible.

Tidal volumes during delivery room stabilization of (near) term infants.

BACKGROUND: We sought to assess tidal volumes in (near) term infants during delivery room stabilization. METHODS: Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH2O and positive end-expiratory airway pressure of 5 cmH2O. Expired tidal volumes (Vt) were measured with a respiratory function monitor. Target range for Vt was defined to be 4 - 8 ml/kg. RESULTS: Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 - 39.0) weeks received 1828 inflations with a median Vt of 4.6 (3.3 - 6.2) ml/kg. Median Vt was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25-27) % of the inflations were in the target rage over the duration of PPV while 42 (25 - 65) % and 10 (3 - 33) % were above and below target range. CONCLUSIONS: Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. TRIAL REGISTRATION: This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493).

Nasal Intermittent Positive Pressure Ventilation for Neonatal Respiratory Distress Syndrome.

Nasal or noninvaisve intermittent positive pressure ventilation (NIPPV) refers to well-established noninvasive respiratory support strategies combining a continuous distending pressure with intermittent pressure increases. Uncertainty remains regarding the benefits provided by the various devices and techniques used to generate NIPPV. Our included meta-analyses of trials comparing NIPPV with continuous positive airway pressure (CPAP) in preterm infants demonstrate that both primary and postextubation NIPPV are superior to CPAP to prevent respiratory failure leading to additional ventilatory support. This short-term benefit is associated with a reduction in bronchopulmonary dysplasia, but not with mortality. Benefits are greatest when ventilator-generated, synchronized NIPPV is used.

Does surfactant nebulization prevent early intubation in preterm infants? A protocol for a systematic review and meta-analysis.

BACKGROUND: Respiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered intratracheally. However, this requires airway instrumentation and subsequent fluid instillation which may be harmful. Surfactant nebulization (SN) may offer a safe and effective alternative for surfactant administration, but the clinical efficacy is not yet established. Thus, this systematic review and meta-analysis of randomized controlled trials will summarize the available evidence to determine the effectiveness and safety of SN for the prevention of intubation and subsequent mechanical ventilation at 72 h after birth. METHODS: A systematic literature search in Medline, Embase, and The Cochrane Library will be performed, and all randomized controlled trials (RCTs) and quasi-RCTs from published articles, presentations, and trial registries will be included in this meta-analysis. Titles and abstracts of all records identified in the search will be screened by two reviewers independently. Data on preterm infants (≤ 37 weeks) receiving nebulized surfactant in the first 72 h after birth for the treatment or prevention of RDS will be evaluated. Primary outcome is the intubation rate by 72 h after birth, and secondary outcomes include peridosing safety effects as well as major neonatal morbidities. Risk of bias will be assessed using the revised Cochrane ROB tool, and subgroup analyses will be performed to evaluate potential confounding factors. Publication bias will be assessed by examining a funnel plot. The meta-analysis will be performed using a fixed-effects model. DISCUSSION: This review will provide an evidence-based tool for information about surfactant nebulization, illustrating the current knowledge and hopefully revealing potential novel avenues for researchers and clinicians alike. SYSTEMATIC REVIEW REGISTRATION: This review is registered with the publicly available resource PROSPERO ( CRD42020175625 ).

Regional ventilation characteristics during non-invasive respiratory support in preterm infants.

OBJECTIVES: To determine the regional ventilation characteristics during non-invasive ventilation (NIV) in stable preterm infants. The secondary aim was to explore the relationship between indicators of ventilation homogeneity and other clinical measures of respiratory status. DESIGN: Prospective observational study. SETTING: Two tertiary neonatal intensive care units. PATIENTS: Forty stable preterm infants born <30 weeks of gestation receiving either continuous positive airway pressure (n=32) or high-flow nasal cannulae (n=8) at least 24 hours after extubation at time of study. INTERVENTIONS: Continuous electrical impedance tomography imaging of regional ventilation during 60 min of quiet breathing on clinician-determined non-invasive settings. MAIN OUTCOME MEASURES: Gravity-dependent and right-left centre of ventilation (CoV), percentage of whole lung tidal volume (VT) by lung region and percentage of lung unventilated were determined for 120 artefact-free breaths/infant (4770 breaths included). Oxygen saturation, heart and respiratory rates were also measured. RESULTS: Ventilation was greater in the right lung (mean 69.1 (SD 14.9)%) total VT and the gravity-non-dependent (ND) lung; ideal-actual CoV 1.4 (4.5)%. The central third of the lung received the most VT, followed by the non-dependent and dependent regions (p<0.0001 repeated-measure analysis of variance). Ventilation inhomogeneity was associated with worse peripheral capillary oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (p=0.031, r2 0.12; linear regression). In those infants that later developed bronchopulmonary dysplasia (n=25), SpO2/FiO2 was worse and non-dependent ventilation inhomogeneity was greater than in those that did not (both p<0.05, t-test Welch correction). CONCLUSIONS: There is high breath-by-breath variability in regional ventilation patterns during NIV in preterm infants. Ventilation favoured the ND lung, with ventilation inhomogeneity associated with worse oxygenation.

Alternatives to systemic postnatal corticosteroids: Inhaled, nebulized and intratracheal.

Concern about adverse outcomes with the use of systemic postnatal corticosteroids (PCS) for bronchopulmonary dysplasia (BPD) have led to the widespread use of alternative methods of administration in research and clinical care. Theoretically, administration of topical (directly to the lung) corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable side effects compared with systemic administration. Current evidence suggests that inhaled corticosteroids may be an effective therapy in the management of developing BPD in preterm infants, but questions about their safety remain. An alternative to inhalation is the intratracheal administration of corticosteroids using surfactant as a vehicle, but this approach has only been studied in a limited number of infants. We review the evidence for the short-term clinical efficacy and safety of inhaled, nebulized and intratracheal PCS for the prevention and treatment of BPD.

The Pediatric Index of Mortality as a Trigger Tool for the Detection of Serious Errors and Adverse Events.

OBJECTIVES: To test the hypothesis that patients who die in a PICU despite a low predicted mortality at PICU admission are affected by serious errors and adverse events. DESIGN: Retrospective cross-sectional review of medical records for serious errors and adverse events. SETTING: Tertiary interdisciplinary neonatal PICU. PATIENTS: All admissions to our PICU who died despite a low expected mortality (Pediatric Index of Mortality) of less than 10% (trigger-positive admissions). They were compared with a random sample of 100 PICU admissions with a Pediatric Index of Mortality of less than 10% who survived (trigger-negative admissions). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 7,383 admissions (91%) with a Pediatric Index of Mortality 2 below 10%. Seventy-two trigger-positive admissions and 100 trigger-negative admissions met the criteria for detailed chart review. Forty-five serious errors and adverse events were identified, 0.47 per trigger-positive admission and 0.11 per trigger-negative admission (p < 0.001). Nineteen serious errors and adverse events (42%) were related to clinical sepsis acquired during the PICU stay, 17 (89%) in trigger-positive admissions and two (11%) in trigger-negative admissions (p < 0.001). A further 18 serious errors and adverse events (40%) were intervention related, nine (50%) in trigger-positive admissions and nine (50%) in trigger-negative admissions (p = 0.46). Eight serious errors and adverse events (18%) were associated with medication use, all of which occurred in trigger-positive admissions (p = 0.001). The median (interquartile range) age for admissions with and without serious errors and adverse events was 0.3 months (0.0-4.6 mo) and 7.4 months (0.4-58.4 mo) (p < 0.001), and their median (interquartile range) duration of invasive ventilation was 140 hours (50-451 hr) and 2 hours (0-41 hr) (p < 0.001), respectively. CONCLUSIONS: The records of PICU patients with a low expected mortality at admission and death in PICU should be reviewed routinely and/or discussed at morbidity and mortality meetings. These patients may have experienced more in-hospital safety-related events compared with PICU patients with a low Pediatric Index of Mortality who survived. Such adverse events may be amenable to system changes, thus improving patient care.

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380.

Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?

BACKGROUND: Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. CASE PRESENTATION: We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. CONCLUSION: Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.