Piero Giuseppe Matassa

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants

Objective: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (<125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants.Methods: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation <125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h.Results: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37–56) breaths/min and 240 (160–353) ml/min per kg vs. 53 (28–67) breaths/min and 309 (223–434) ml/min per kg, respectively (p=0.0129 and p=0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p<0.0001). Percentage of time spent with spontaneous expiratory minute ventilation <125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves.Conclusion: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.

High total antioxidant activity and uric acid in tracheobronchial aspirate fluid of preterm infants during oxidative stress: an adaptive response to hyperoxia?

The effect of O2 exposure, expressed by mean daily fractional inspired oxygen concentration (FiO2), was evaluated during the first 6 d of life in the tracheobronchial aspirate fluid of 16 mechanically ventilated preterm infants in terms of both antioxidant response and oxidative damage, by measuring total antioxidant activity, uric acid concentrations and protein carbonyl content. Each day linear regression analysis was performed and a positive correlation was found between total antioxidant activity and FiO2 during the study period, especially on day 2 of life (r= 0.91, p < 0.0001), but uric acid correlated only in the first 3 d, especially on the 2nd day (r= 0.83, p < 0.0001). No correlation was found between carbonyl content and FiO2. The highest values of total antioxidant activity (416 and 790 μmol l−1) were found in 2 babies ventilated with highest FiO2: 1 and 0.80, respectively. Total antioxidant activity was not detectable or was very low in the babies not requiring O2 therapy. The highest value of uric acid (270 μmol l−1) was found in the baby ventilated with 100% oxygen. Uric acid concentrations obtained in these babies were much higher then those reported in the bronchoalveolar lavage fluid of adults.

Effect of Dexamethasone on Tracheobronchial Aspirate Fluid Cytology and Pulmonary Mechanics in Preterm Infants

The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight ≤1,250 g and gestational age ≤32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.

Genotypic analysis by 27A DNA fingerprinting of Candida albicans strains isolated during an outbreak in a neonatal intensive care unit.

We describe an outbreak of Candida albicans systemic infection involving five premature infants in a neonatal intensive care unit. Molecular and epidemiologic characterization of all C. albicans isolates was performed by DNA fingerprinting with the 27A probe. This genotypic analysis demonstrated that the isolates were identical, providing evidence for the circulation of a unique C. albicans strain.

Nasal Continuous Positive Airway Pressure With Heliox in Preterm Infants With Respiratory Distress Syndrome

OBJECTIVE: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP). METHODS: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed. RESULTS: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%). CONCLUSIONS: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.

Calcium signaling-related proteins are associated with broncho-pulmonary dysplasia progression.

UNLABELLED Broncho-pulmonary dysplasia (BPD) is a chronic pulmonary disorder that follows premature birth. It is preceded by respiratory distress syndrome (RDS), characterized by acute respiratory failure due to deficiency of surfactant at birth. Clinical characteristics of infants affected by BPD have widely changed in the last decades: they are extraordinarly immature, with impaired alveolar and vascular lung development. To build up new therapeutic strategies for BPD babies, it is necessary to understand the pathogenic mechanisms, which are complicated by environmental risk factors and genetic predisposition. Therefore, the aim of this study was to highlight protein changes in the broncho-alveolar lavage fluid (BALF), thus providing an appropriate picture on what is happening in the locus of injury. We analyzed BALF samples from preterm babies, born at different stages of lung development. We confirmed that gestational age is relevant for BPD progression, but we also detected few de-regulated proteins in the younger babies; we discovered less abundant calcium signaling-related proteins, consistent with BPD severity, comparing severe to mild BPD babies with matched gestational age. In conclusion, this study suggests a subset of proteins to be investigated to better treat BPD babies and facilitate the definition of potential drug targets for novel therapies. BIOLOGICAL SIGNIFICANCE Pulmonary biomarkers are needed to predict the clinical course of lung disease, status, progression and response to treatment. A key aspect in biomarker discovery is uncovering molecules that appear early during disease initiation, when the natural history of the disease can be modified. Using a proteomic-based approach we compared broncho-alveolar lavage fluid (BALF) protein profile from preterm neonates at different postmenstrual ages, to have a molecular description of broncho-pulmonary dysplasia (BPD) progression. BALF provided a snapshot of local molecular changes, which are relevant for early diagnosis, assessment and characterization of lung disorders. We showed that even if the studied patients had similar clinical phenotype (they all developed severe BPD and they were all cured in the same way in terms of mechanical ventilation, surfactant administration, antenatal steroid treatment and ibuprofen treatment for patent ductus arteriosus), however their BALF protein profiling displayed significant differences in a subset of proteins, which could be exploited to facilitate the development of novel effective therapies, distinct for age and severity of the disease.

Positional effects on lung mechanics of ventilated preterm infants with acute and chronic lung disease

The role of prone position in preterm infants has not been completely clarified. We investigated prone versus supine posture‐related changes in respiratory system resistance (Rrs) and reactance (Xrs) measured by the Forced Oscillation Technique (FOT) in mechanically ventilated preterm newborns.

EXPIRATORY MINUTE SPONTANEOUS VENTILATION IS A PREDICTOR OF WEANING FROM MECHANICAL VENTILATION IN PRETERM INFANTS

EXPIRATORY MINUTE SPONTANEOUS VENTILATION IS A PREDICTOR OF WEANING FROM MECHANICAL VENTILATION IN PRETERM INFANTS

A new FOT set-up for the assessment of respiratory system mechanics in mechanically ventilated infants

The assessment of respiratory system mechanics in mechanically ventilated newborns would help in tailoring the ventilatory settings. The Forced Oscillations Technique (FOT) is a non-invasive method for the measurement of the mechanical properties of the respiratory system. The aim of the present work was to develop a measurement set-up suitable to apply FOT in mechanically ventilated newborns. Forced oscillations were generated by a servo-controlled linear motor connected to the inspiratory line of the ventilator. Pressure and flow were measured at the inlet of the tracheal tube and used to compute impedance. The set-up was tested on a mechanical analog of the infants respiratory system showing good agreement with a traditional FOT set-up. The performance of the system was not influenced by the positive pressures generated by the ventilator. Finally, the system was well tolerated by 5 preterm babies and the measurements allowed to track changes in respiratory mechanics associated to changes in the pressure delivered by the ventilator.

398 Serum Levels of IL-6, IL-8 and IL-10 in Premature Newborns Treated with two Ventilatory Strategies: HFOV and sIMV.

Background/aim: Severity of pulmonary dysfunction and later development of chronic lung disease in preterm neonates depends on several factors, including oxygen administration and ventilatory strategies. Aim of this report is the comparison of the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) on serum cytokine levels (IL-6, IL-8, IL-10) during the first week of life.Methods: Forty preterm neonates with RDS and gestational age (GA) < 30 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 minutes from birth: Group HFOV: N: 20; mean GA: 27.1±1.4 wks; mean birth weight (BW): 882 ±157 g. Group sIMV: N: 20; mean GA: 27.4 ± 1.2 wks; mean BW: 936 ± 285 g. At 1, 3 and 5 days, the babies were monitored by means of ventilator indices and three pro-inflammatory cytokines in sera.Results: No clinical or biochemical differences were observed at baseline. The neonates assigned to HFOV benefited from early and sustained improvement in gas exchange (significantly lower FiO2 and significantly higher a/A ratio) with earlier extubation, and showed a significant reduction (p<0.05) of serum IL-6, IL-8 and IL-10 over time, as compared to the neonates assigned to sIMV treatment. In addition, at days 3 and 5, the IL-6 levels were significantly lower in the HFOV group as compared to sIMV patients [median (range) values: 7 (1–47) pg/ml vs 20 (4–144) pg/ml respectively at day 3, and 6 (2–44) pg/ml vs 14 (5–145) pg/ml at day 5, p<0.05].Conclusions: The results of this randomized clinical trial support the hypothesis that early use of HFOV, combined with optimum volume strategy, has a beneficial effect, reducing serum levels of pro-inflammatory cytokines and consequently the acute phase leading to lung injury.