Trigger performance of five pediatric home ventilators and one ICU ventilator depending on circuit type and system leak in a physical model of the lung.

BACKGROUND: The population of children with chronic respiratory failure requiring long-term mechanical ventilation in the home has grown worldwide. The optimal choice from an increasing number of home ventilators commercialized for children is often challenging for the attending physicians. The aim of the present study was to compare the trigger performance of five pediatric bilevel home ventilators and one intensive care unit ventilator depending on circuit type and system leak. METHODS: The trigger performances of the ventilators were compared in combination with all compatible circuits using a physical model of the lung with increasing system leak. The flow generator simulated the patient's breathing effort with flow rates of 2.7-6.4 L/min at a frequency of 30 breaths/min. All ventilators were set to deliver 16 cmH2 O inspiratory pressure support and 4 cmH2 O positive end-expiratory pressure. RESULTS: Trigger thresholds varied from 1.5 to 8 L/min, the pressure rise time to 90% of the maximum from 140 to 385 ms and the trigger work from 0.5 to 6.6 mbar · s. All devices had very short trigger delays below 40 ms. The leak compensation depended on the circuit type. The internal diameter of the circuit had no relevant impact on the trigger performance or the leak compensation. CONCLUSION: We observed considerable differences in the triggering performance of the evaluated home ventilators depending on leak size and type of circuit. Therefore, an optimal combination of device and circuit should consider the patient's age and condition and the probability of system leak.

Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia.

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas. The family history was positive for von Willebrand disease type 2B (VWD 2B). Diagnosis of VWD 2B was identified analyzing von Willebrand factor (VWF) parameters (VWF:antigen, VWF:activity, VWF multimer analyses) and performing light transmission aggregometry (with half concentration of ristocetin). In addition, the diagnosis was confirmed by molecular genetic analysis: identification of a disease-causing missense mutation (Val1316Met) in the VWF gene associated with a severe course of VWD 2B, which had been previously reported. Treatment with a VWF-containing plasma concentrate was initiated. Because the combination of prematurity and very low platelet count is often associated with intracranial bleeding, at the beginning platelet concentrates were transfused. Fortunately, the patient did not develop serious bleeding episodes. Interestingly, the patient had a mutation in the VWF gene, which had been described to be associated with aggravation of thrombocytopenia especially in stressful situations. Therefore, we replaced venous blood withdrawals by capillary blood samplings when possible and, consequently, we observed an increase of the platelet count after this change in management. At the age of 2 months, the patient was discharged after stabilization of the platelet count without any bleeding signs and without a need of long-term medication.

Ultrashort inspiratory times homogenize ventilation distribution in an inhomogeneous two-compartment model of the neonatal lung.

BACKGROUND: Inhomogeneous lung ventilation and pulmonary air leaks are common adverse effects of mechanical ventilation in preterm infants suffering from respiratory distress syndrome. We hypothesized that shortening of inspiratory times can improve the homogeneity of lung aeration. We assumed that ultrashort inspiratory times lead to a full build-up of pressure in regions with low compliance while maintaining incomplete filling of regions with high compliance. METHODS: We connected a two-compartment model of the lung with different compliances of the two compartments to a neonatal ventilator. Pressures and flow rates were measured separately for each compartment at inspiratory times ranging from 0.1 to 0.8 s and various combinations of tidal volumes. RESULTS: An inspiratory time of 0.8 s resulted in near total pressure equalization between the airway pressure and the two compartments, as 97% of the maximum applied peak pressure was reached in the low compliance compartment and 95% in the high compliance compartment. The distribution of the tidal volume was proportional to the compartment compliance. Ultrashort inspiratory times lowered the peak pressure and tidal volume in the high compliance compartment but maintained higher pressure and volume in the low compliance compartment. An inspiratory time of 0.2 s resulted in a peak pressure of 80% of peak airway pressure in the low compliance compartment and in 61% of peak airway pressure in the high compliance compartment (p < .001). CONCLUSION: Ventilation with ultrashort inspiratory times may improve homogeneity of air distribution in inhomogeneous lungs of ventilated preterm or term infants.

Non-invasive high-frequency oscillatory ventilation in preterm infants: a randomised controlled cross-over trial.

OBJECTIVE: Non-invasive high-frequency oscillatory ventilation (nHFOV) has recently been described as a novel mode of respiratory support for premature infants. This study was designed to determine whether nHFOV decreases CO2 partial pressure (pCO2) in premature infants more effectively than non-invasive continuous positive airway pressure (nCPAP). DESIGN: Non-blinded prospective randomised controlled cross-over study. SETTING: University Medical Center tertiary neonatal intensive care unit. PATIENTS: 26 premature infants of 27±2 weeks of gestational age after extubation or non-invasive surfactant treatment. INTERVENTIONS: Infants were treated with 4 hours of nHFOV and 4 hours of nCPAP in a cross-over design. The sequence of the ventilation mode was randomly allocated. MAIN OUTCOME MEASURES: The primary outcome measure was pCO2 of arterial or arterialised blood 4 hours after commencing the respective mode of respiratory support. Secondary outcome criteria included events of apnoea and bradycardia, respiratory rate, heart rate, pain and/or discomfort, mean airway pressure, fraction of inspired oxygen and failure of non-invasive respiratory support. RESULTS: pCO2 after 4 hours of nHFOV was similar compared with 4 hours of nCPAP (p=0.33). pCO2 was 54.8 (14.6) vs 52.7 (9.3) mm Hg mean (SD) for the nHFOV-nCPAP period (n=13) and 49.0 (8.1) vs 47.7 (9.5) mm Hg for the nCPAP-nHFOV period (n=13). There was no difference in any of the secondary outcome measures. nHFOV was terminated prematurely in five cases for predefined failure criteria (p=0.051). CONCLUSIONS: We could not demonstrate an increased carbon dioxide clearance applying nHFOV compared with nCPAP in this cohort of preterm infants. TRIAL REGISTRATION NUMBER: DRKS00007171, results.

PTBP1 is required for glucose-stimulated cap-independent translation of insulin granule proteins and Coxsackieviruses in beta cells.

Glucose and GLP-1 stimulate not only insulin secretion, but also the post-transcriptional induction of insulin granule biogenesis. This process involves the nucleocytoplasmic translocation of the RNA binding protein PTBP1. Binding of PTBP1 to the 3'-UTRs of mRNAs for insulin and other cargoes of beta cell granules increases their stability. Here we show that glucose enhances also the binding of PTBP1 to the 5'-UTRs of these transcripts, which display IRES activity, and their translation exclusively in a cap-independent fashion. Accordingly, glucose-induced biosynthesis of granule cargoes was unaffected by pharmacological, genetic or Coxsackievirus-mediated inhibition of cap-dependent translation. Infection with Coxsackieviruses, which also depend on PTBP1 for their own cap-independent translation, reduced instead granule stores and insulin release. These findings provide insight into the mechanism for glucose-induction of insulin granule production and on how Coxsackieviruses, which have been implicated in the pathogenesis of type 1 diabetes, can foster beta cell failure.