PEDIATRIC ORIGINAL Adaptive mechanical backup ventilation for preterm infants on respiratory assist modes -a pilot study

Abstract Background: Mechanical respiratory-assist modes, such as assist/control, low-rate intermittent mandatory ventilation, continuous positive airway pressure, or proportional assist ventilation (PAV), require a continuous respiratory effort. Because of the frequent occurrence of periodic breathing and/or apnea, mechanical backup ventilation must be initiated during episodes of reduced or absent respiratory drive to maintain gas exchange. The common approach to this problem is a regular conventional mechanical ventilation, which is initiated and withdrawn in an "on/off" function. Objective: To develop and evaluate a mechanical backup ventilation mode that is adaptive to the rapidly changing breathing pattern of preterm infants. Design: Prospective randomized clinical crossover trial. Setting: Neonatal intensive care unit at the University of Munich, Germany. Patients: Preterm infants undergoing PAV. Interventions: The infants were ventilated with PAV using a newly developed adaptive backup support, with and without pulse-oximetryguided operation (SpO 2 -sensitive backup). Each infant was ventilated with both modes of backup support on 2 consecutive days, with the sequence randomized. Measurements and results: The analysis on 11 preterm infants showed a statistically significant and clinically relevant reduction of the incidence (33%) and duration of oxygen desaturations (52%) when SpO 2 -sensitive adaptive backup support was used. Conclusions: SpO 2 -sensitive adaptive backup proved safe and effective in reducing the incidence and duration of oxygen desaturation in this short-term trial. This technology is potentially applicable to other assisted modalities of ventilation, such as noninvasive nasal ventilation

Langzeitentwicklung von Kindern nach Extra Corporaler Membran Oxygenierung (ECMO).

Hintergrund Nach neonatalem Lungenversagen und insbesondere nach einer ECMO-Therapie können verschiedenste Langzeitmorbiditäten auftreten. Das Follow-up dieser schwer kranken Neugeborenen ist als Qualitätskriterium für ein ECMO-Zentrum unverzichtbar und sie besitzt einen hohen Stellenwert in der Beratung von Eltern. Da ECMO-Zentren ein großes Einzugsgebiet haben, ist eine feste Anbindung der Patienten an das Zentrum oft schwierig. Methode Nachsorgeuntersuchung und Entwicklungsscreening einer Kohorte (n=41) ehemaliger Neugeborener und Säuglinge mit schweren Lungenversagen auf Langzeitmorbiditäten durch eine Fragebogenerhebung sowie eine systematische, z.T. computergestützte Recherche mittels Arztbriefen und Telefonbefragung. Ergebnisse An 28 von 31 Familien überlebender Kinder konnten Fragebögen versendet werden. 23 Fragebögen wurden zurückgesandt, einer Rücklaufquote von 82% entsprechend. Vier Kinder hatten auffällige Fragebogenergebnisse, d. h. sie lagen unter der 90ten Perzentile der altersentsprechenden Werte und besaßen damit ein Risiko für eine Entwicklungsauffälligkeit. Davon waren 3 Kinder im Alter von 2 Jahren und waren im Rahmen ihres Lungenversagens konventionell behandelt worden. Ein Kind im Alter von 6 Jahren hatte eine ECMO-Therapie erhalten. Schlussfolgerung Die von uns erstmals an Kindern mit einem schweren neonatalen Lungenversagen eingesetzten Fragebögen können der Detektion einer Entwicklungsauffälligkeit dienen. In der klinischen Praxis sind sie als Entwicklun

Intrapulmonary instillation of perflurooctylbromide improves lung growth, alveolarization, and lung mechanics in a fetal rabbit model of diaphragmatic hernia.

OBJECTIVES: Fetal tracheal occlusion of hypoplastic rabbit lungs results in lung growth and alveolarization although the surfactant protein messenger RNA expression is decreased and the transforming growth factor-β pathway induced. The prenatal filling of healthy rabbit lungs with perfluorooctylbromide augments lung growth without suppression of surfactant protein synthesis. We hypothesizes that Intratracheal perfluorooctylbromide instillation improves lung growth, mechanics, and extracellular matrix synthesis in a fetal rabbit model of lung hypoplasia induced by diaphragmatic hernia. SETTING AND INTERVENTIONS: On day 23 of gestation, DH was induced by fetal surgery in healthy rabbit fetuses. Five days later, 0.8ml of perfluorooctylbromide (diaphragmatic hernia-perfluorooctylbromide) or saline (diaphragmatic hernia-saline) was randomly administered into the lungs of previously operated fetuses. After term delivery (day 31), lung mechanics, lung to body weight ratio, messenger RNA levels of target genes, assessment of lung histology, and morphological distribution of elastin and collagen were determined. Nonoperated fetuses served as controls. MEASUREMENTS AND MAIN RESULTS: Fetal instillation of perfluorooctylbromide in hypoplastic lungs resulted in an improvement of lung-to-body weight ratio (0.016 vs 0.013 g/g; p = 0.05), total lung capacity (23.4 vs 15.4 μL/g; p = 0.03), and compliance (2.4 vs 1.2 mL/cm H2O; p = 0.007) as compared to diaphragmatic hernia-saline. In accordance with the results from lung function analysis, elastin staining of pulmonary tissue revealed a physiological distribution of elastic fiber to the tips of the secondary crests in the diaphragmatic hernia-perfluorooctylbromide group. Likewise, messenger RNA expression was induced in genes associated with extracellular matrix remodeling (matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2). Surfactant protein expression was similar in the diaphragmatic hernia-perfluorooctylbromide and diaphragmatic hernia-saline groups. Distal airway size, mean linear intercept, as well as airspace and tissue fractions were similar in diaphragmatic hernia-perfluorooctylbromide, diaphragmatic hernia-saline, and control groups. CONCLUSIONS: Fetal perfluorooctylbromide treatment improves lung growth, lung mechanics, and extracellular matrix remodeling in hypoplastic lungs, most probably due to transient pulmonary stretch, preserved fetal breathing movements, and its physical characteristics. Perfluorooctylbromide instillation is a promising approach for prenatal therapy of lung hypoplasia

Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or mechanical ventilation in a murine model.

Background:Heterozygous ABCA3 (ATP-binding-cassette sub-family A member3) mutations are associated with neonatal respiratory complications. We investigated in an adult murine model whether Abca3 haploinsufficiency is a predisposing factor for lung injury induced by hyperoxia or mechanical ventilation.Methods:Abca3 haploinsufficient (Abca3+/-) and wild-type (WT) mice were prospectively randomized to 25 min of ventilation or 72 hours of hyperoxia or left unchallenged in air.Results:As compared to WT, unchallenged Abca3+/- mice had significantly decreased lung phosphatidylcholine (PC) and phosphatidylglycerol (PG) levels (p<0.02) and decreased lung compliance (p<0.05). When ventilated for 25 min, Abca3+/- mice demonstrated a significantly greater increase in bronchoalveolar lavage (BAL) interleukins (p<0.01) and lung wet to dry ratio (p<0.005). Hyperoxia resulted in increased compliance (p<0.05) and total lung capacity (TLC) (p=0.01) only in the Abca3+/- mice consistent with enlarged alveolar spaces. The ratio of PC to PG in BAL - relevant for surfactant dysfunction - was significantly elevated by oxygen exposure with the greatest increase in Abca3+/- mice.Conclusions:In a murine model, Abca3 haploinsufficiency results in an altered biochemical and lung mechanical phenotype as well as a greater lung injury induced by hyperoxia or mechanical ventilation. The inability to maintain a normal PC/PG ratio appears to play a key role

Improved Macro- and micronutrient supply for favorable growth and metabolomic profile with standardized parenteral nutrition solutions for very preterm infants.

Very preterm infants are at high risk for suboptimal nutrition in the first weeks of life leading to insufficient weight gain and complications arising from metabolic imbalances such as insufficient bone mineral accretion. We investigated the use of a novel set of standardized parenteral nutrition (PN; MUC PREPARE) solutions regarding improving nutritional intake, accelerating termination of parenteral feeding, and positively affecting growth in comparison to individually prescribed and compounded PN solutions. We studied the effect of MUC PREPARE on macro- and micronutrient intake, metabolism, and growth in 58 very preterm infants and compared results to a historic reference group of 58 very preterm infants matched for clinical characteristics. Infants receiving MUC PREPARE demonstrated improved macro- and micronutrient intake resulting in balanced electrolyte levels and stable metabolomic profiles. Subsequently, improved energy supply was associated with up to 1.5 weeks earlier termination of parenteral feeding, while simultaneously reaching up to 1.9 times higher weight gain at day 28 in extremely immature infants (<27 GA weeks) as well as overall improved growth at 2 years of age for all infants. The use of the new standardized PN solution MUC PREPARE improved nutritional supply and short- and long-term growth and reduced PN duration in very preterm infants and is considered a superior therapeutic strategy