Anne De Jaegere

Positive Pressure Ventilation with the Open Lung Concept Optimizes Gas Exchange and Reduces Ventilator-Induced Lung Injury in Newborn Piglets

Previous studies demonstrated that high-frequency oscillatory ventilation using the open lung concept (OLC) resulted in superior gas exchange and a reduction in ventilator-induced lung injury (VILI). We hypothesized that these beneficial effects could also be achieved by applying the OLC during positive pressure ventilation. After repeated whole-lung-lavage, newborn piglets were assigned to either OLC positive pressure ventilation (PPVOLC), OLC high-frequency oscillatory ventilation (HFOVOLC), or conventional positive pressure ventilation (PPVCON) and ventilated for 5 h. In both OLC groups, collapsed alveoli were actively recruited and thereafter stabilized using the lowest possible airway pressures. In the PPVCON group, ventilator settings were adjusted to prevent critical hypoxia. Airway pressure, blood gas analysis, pressure-volume curve, and alveolar protein infiltration was recorded. A lung injury score was used for histologic comparison. Mean airway pressures were comparable in the three ventilation groups over time (1.2-1.5 kPa). Arterial oxygenation increased to mean values above 60 kPa in both OLC groups compared with 10 kPa in the PPVCON group (p < 0.001). Maximal lung compliance was superior in both OLC groups (PPVOLC: 91 ± 23; HFOVOLC: 90 ± 31 mL/kPa/kg, p < 0.01) compared with the PPVCON group (39 ± 14 mL/kPa/kg). Alveolar protein infiltration was significantly reduced in the PPVOLC group (0.33 ± 0.10 mg/mL, p < 0.01) and the HFOVOLC group (0.40 ± 0.13 mg/mL, p < 0.01) compared with the PPVCON group (0.70 ± 0.15 mg/mL). Lung injury scores were significantly higher in the PPVCON group (33.5 ± 9.5, p < 0.01) compared with both OLC groups (PPVOLC: 10.5 ± 2.6; HFOVOLC: 11 ± 2.2). There were no differences between the two OLC groups. We conclude that, in surfactant-depleted newborn piglets, application of the OLC during PPV is feasible and results in superior gas exchange and a reduction in VILI compared with conventional PPV. These beneficial effects are comparable to HFOV.

Ventilation practices in the neonatal intensive care unit: a cross-sectional study

OBJECTIVE To assess current ventilation practices in newborn infants. STUDY DESIGN We conducted a 2-point cross-sectional study in 173 European neonatal intensive care units, including 535 infants (mean gestational age 28 weeks and birth weight 1024 g). Patient characteristics, ventilator settings, and measurements were collected bedside from endotracheally ventilated infants. RESULTS A total of 457 (85%) patients were conventionally ventilated. Time cycled pressure-limited ventilation was used in 59% of these patients, most often combined with synchronized intermittent mandatory ventilation (51%). Newer conventional ventilation modes like volume targeted and pressure support ventilation were used in, respectively, 9% and 7% of the patients. The mean tidal volume, measured in 84% of the conventionally ventilated patients, was 5.7 ± 2.3 ml/kg. The mean positive end-expiratory pressure was 4.5 ± 1.1 cmH(2)O and rarely exceeded 7 cmH(2)O. CONCLUSIONS Time cycled pressure-limited ventilation is the most commonly used mode in neonatal ventilation. Tidal volumes are usually targeted between 4 to 7 mL/kg and positive end-expiratory pressure between 4 to 6 cmH(2)O. Newer ventilation modes are only used in a minority of patients.

Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials

CONTEXT. Postnatal dexamethasone therapy reduces the incidence of bronchopulmonary dysplasia in preterm infants but may be associated with an increased risk for adverse neurodevelopmental outcome. OBJECTIVE. Our goal was to determine if the effects of dexamethasone on mortality and pulmonary and neurodevelopmental sequelae in preterm infants are modified by the cumulative dose given. METHODS. Randomized, controlled trials comparing dexamethasone with placebo in ventilated preterm infants >7 days old were identified by searching the electronic databases and the abstracts from the Pediatric Academic societies and by performing manual reference searches. Two reviewers independently assessed eligibility and quality of trials and extracted data on study design, patient characteristics, and relevant outcomes. Original trialists were asked to provide additional data. RESULTS. Sixteen trials including 1136 patients were analyzed by using meta-analysis and metaregression. Additional data were provided by 12 original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3-week) postnatal treatment onset were analyzed separately. Higher dexamethasone doses reduced the relative risk for the combined outcome, mortality or bronchopulmonary dysplasia, with the largest effect in trials that used a cumulative dose of >4 mg/kg. No effect was found of doses on the risk of neurodevelopmental sequelae in the delayed treatment studies, but in the moderately-early-treatment studies the risk of mortality or cerebral palsy decreased by 6.2%, and the risk of a Mental Developmental Index below −2 SDs decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose. CONCLUSIONS. Higher cumulative dexamethasone doses administered after the first week of life may decrease the risk for bronchopulmonary dysplasia without increasing the risk for neurodevelopmental sequelae in ventilated preterm infants. A large randomized trial is needed to confirm or refute these findings.

Application of the Open-Lung Concept during Positive-Pressure Ventilation Reduces Pulmonary Inflammation in Newborn Piglets

It has been shown that application of the open-lung concept (OLC) during high-frequency oscillatory ventilation (HFOV) attenuates pulmonary inflammation. We hypothesized that this attenuation could also be achieved by applying the OLC during positive-pressure ventilation (PPV). After repeated whole-lung lavage, newborn piglets were assigned to one of three ventilation groups: (1) PPVOLC; (2) HFOVOLC, or (3) conventional PPV (PPVCON). After a ventilation period of 5 h, analysis of bronchoalveolar lavage fluid showed a reduced influx of polymorphonuclear neutrophils, interleukin 8, and thrombin activity in both OLC groups as compared with the PPVCON group. There were no differences in tumor necrosis factor alpha levels. We conclude that application of the OLC during PPV reduces pulmonary inflammation as compared with conventional PPV and that the magnitude of this reduction is comparable to that of HFOV.

Effects of higher versus lower dexamethasone doses on pulmonary and neurodevelopmental sequelae in preterm infants at risk for chronic lung disease: a meta-analysis.

OBJECTIVES. Systemic postnatal dexamethasone treatment reduces the risk of chronic lung disease in preterm infants but also may be associated with increased risk of neurodevelopmental impairment. Because it is not known whether these effects are modulated by the cumulative dexamethasone dose, we systematically reviewed the available randomized evidence on the effects of lower versus higher cumulative dexamethasone doses, in terms of death, pulmonary morbidity, and neurodevelopmental outcomes, in preterm infants. METHODS. Randomized, controlled trials comparing higher- versus lower-dosage dexamethasone regimens in ventilated preterm infants were identified by searching the main electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research (from 1990 onward). Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted. RESULTS. Six studies that enrolled a total of 209 participants were included; 2 studies contrasted cumulative dexamethasone doses in the higher ranges (>2.7 mg/kg in the higher-dosage regimen) and 4 in the lower ranges (≤2.7 mg/kg in the higher-dosage regimen). Meta-analysis revealed no effect of dexamethasone dose on rates of death and neurodevelopmental sequelae in these 2 subgroups. Subgroup analysis of the studies contrasting dexamethasone doses in the higher ranges showed that the higher dose of dexamethasone was more effective in reducing the occurrence of chronic lung disease than was the lower dose. Interpretation of these data was hampered by the small samples of randomly assigned children, heterogeneity of study populations and designs, use of late rescue glucocorticoids, and lack of long-term neurodevelopmental data in some studies. CONCLUSIONS. Recommendations for optimal dexamethasone doses for preterm infants at risk for chronic lung disease cannot be based on current evidence. A well-designed, large, randomized, controlled trial is urgently needed to establish the optimal dexamethasone dosage regimen.

Open lung ventilation improves gas exchange and attenuates secondary lung injury in a piglet model of meconium aspiration

ObjectivePrevious studies failed to show clear benefits of high-frequency ventilation compared with conventional positive pressure ventilation (PPVCON) in experimental meconium aspiration syndrome. However, none of these studies applied an open lung ventilation strategy (OLC), which aims to reduce intrapulmonary shunt due to alveolar collapse. We hypothesized that, if combined with an open lung strategy, both high-frequency oscillatory ventilation (HFOVOLC) and positive pressure ventilation (PPVOLC) would improve gas exchange and attenuate ventilator-induced lung injury in experimental meconium aspiration syndrome. DesignProspective, randomized animal study. SettingResearch laboratory of a large university. SubjectsForty-two newborn piglets. InterventionsThirty minutes after intratracheal meconium instillation, 36 newborn piglets were assigned to one of three ventilation groups—PPVOLC, HFOVOLC, or PPVCON—and ventilated for 5 hrs. In both OLC groups, collapsed alveoli were actively recruited and thereafter stabilized using the lowest possible airway pressures. During PPVCON, ventilator settings were adjusted to prevent critical hypoxia (Pao2 <60 torr [8 kPa]). Six animals served as saline controls. Measurements and Main ResultsCompared with the PPVCON group, arterial oxygenation and lung mechanics were superior in both OLC groups and the saline controls. Analysis of the bronchoalveolar lavage fluid obtained after 5 hrs of ventilation showed increased myeloperoxidase activity in the PPVCON group compared with both OLC groups and saline controls. Alveolar protein influx was not different between the groups. Histologic analysis revealed a higher lung injury score in the PPVCON group compared with the PPVOLC and the HFOVOLC groups. ConclusionsApplication of the OLC during PPV and HFOV is feasible in experimental meconium aspiration syndrome and results in superior oxygenation and less ventilator-induced lung injury compared with PPVCON.

Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation

Aim:  To predict early nasal continuous positive airway pressure failure within the first 2 h after birth in preterm infants.

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

BackgroundRandomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.Methods/DesignThe SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.DiscussionThis trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.Trial registration numberNetherlands Trial Register (NTR): NTR2768

Surfactant Replacement Therapy in Preterm Infants: A European Survey

Background: Exogenous surfactant is an undisputed treatment for neonatal respiratory distress syndrome but its efficacy is highly dependent on the treatment strategy. International guidelines have published recommendations on the optimal surfactant replacement strategy. Objective: To determine how evidence-based guidelines on surfactant replacement therapy are implemented in daily clinical practice. Methods: Data on surfactant replacement therapy, including preparation, dosing and timing, were collected in 173 European neonatal intensive care units (NICUs) by questionnaire and in a cohort of preterm infants mechanically ventilated on two separate predefined dates in these units. Results: All NICUs used animal-derived surfactant in the treatment of respiratory distress syndrome, with Poractant being most widely used (86%). The most frequently used first dose was 100 mg/kg (58%) and 200 mg/kg (39%) and all NICUs allowed for repeat dosing. 39% of the NICUs claimed to use prophylactic treatment (<15 min of life). Data on surfactant treatment were collected in 338 infants, with a median gestational age of 27 weeks and a birth weight of 860 g. All infants were treated with animal-derived surfactant. The median first dose was 168 mg/kg in the Poractant group compared with 100 mg/kg in the Beractant and Bovactant groups. Prophylactic treatment was used in 23% of the infants and 28% of the infants received surfactant >2 h after birth. 43% of the infants received multiple doses. Conclusions: With the exception of surfactant timing, guidelines on surfactant replacement therapy seem to be implemented in daily clinical practice in European NICUs.

Incidence of hypo- and hyper-capnia in a cross-sectional European cohort of ventilated newborn infants

Objective To determine the incidence of hypo- and hyper-capnia in a European cohort of ventilated newborn infants. Design and setting Two-point cross-sectional prospective study in 173 European neonatal intensive care units. Patients and methods Patient characteristics, ventilator settings and measurements, and blood gas analyses were collected for endotracheally ventilated newborn infants on two separate dates. Results A total of 1569 blood gas analyses were performed in 508 included patients with a mean±SD Pco2 of 48±12 mm Hg or 6.4±1.6 kPa (range 17–104 mm Hg or 2.3–13.9 kPa). Hypocapnia (Pco2<30 mm Hg or 4 kPa) and hypercapnia (Pco2>52 mm Hg or 7 kPa) was present in, respectively, 69 (4%) and 492 (31%) of the blood gases. Hypocapnia was most common in the first 3 days of life (7.3%) and hypercapnia after the first week of life (42.6%). Pco2 was significantly higher in preterm infants (49 mm Hg or 6.5 kPa) than term infants (43 mm Hg or 5.7 kPa) and significantly lower during pressure-limited ventilation (47 mm Hg or 6.3±1.6 kPa) compared with volume-targeted ventilation (51 mm Hg or 6.8±1.7 kPa) and high-frequency ventilation (50 mm Hg or 6.7±1.7 kPa). Conclusions This study shows that hypocapnia is a relatively uncommon finding during neonatal ventilation. The higher incidence of hypercapnia may suggest that permissive hypercapnia has found its way into daily clinical practice.