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are more likely to fail extubation (1) and an increased work of breathing may also contribute to a failure to grow (2). The WOB can be assessed by measuring the diaphragm pressure time product (PTPdi), a correlate of respiratory muscle oxygen consumption. Prematurely born infants, however, may have poorly developed respiratory muscles. Objective: To determine if maturity at birth affected PTPdi. Methods: Results were analysed from 40 infants who had been entered into two studies: 20 with acute RDS and 20 being weaned from mechanical ventilation. PTPdi was assessed using a dual tipped catheter measuring gastric and oesophageal pressure; airow was assessed using a pneumotachograph and airway pressure from a side port on the pneumotachograph. Infants were ventilated using the SLE 5000 ventilator and the PTPdi results obtained when the infants were receiving time cycled, pressure limited ventilation. Results: The 40 infants had a median gestational age of 29 (24 to 38) weeks. PTPdi had a signicant correlation with gestational age at birth overall (r=0.644, p<0.001) and particularly in the infants with acute RDS (r=0.742, p<0.001). Conclusion: These results suggest that if comparison of PTPdi results is made between babies maturity at birth should be taken into account. References: 1 Szymankiewicz, M. et al. Pediatr Crit Care Med 2005; 6:44-49. 2 Guslits, B.G. et al. J Appl Physiol 1987; 62:1410-1415.

347. Respiratory disorders of the newborn

P4038 Prediction of respiratory outcome in fetuses with congenital diaphragmatic hernia who undergo fetoscopic endotracheal occlusion Michael Prendergast 1 , Jacque Jani 2 , Kypros Nicolaides 2 , Anne Greenough 1 . 1 Division of Asthma, Allergy and Lung Biology, Kings College London, London, United Kingdom; 2 Harris Birthright Centre for Fetal Medicine, Kings College Hospital, London, United Kingdom Background: Fetoscopic endotracheal occlusion with a balloon (FETO) has been developed to try and improve the outcome of fetuses with severe congenital diaphragmatic hernia (CDH). Both the lung area to head circumference ratio (LHR) and fetal lung volume (FLV) measurements have been used to predict the likely survival of possible candidates for FETO. Objective: To determine whether LHR or FLV results better predicted neonatal respiratory morbidity in fetuses with antenatally diagnosed CDH who underwent FETO. Methods: FLV was measured by three dimensional ultrasound using the virtual organ computer aided analysis technique (VOCAL) and results were expressed as the percentage of the observed to expected for gestational age (1). LHR was measured using two-dimensional ultrasound. Neonatal respiratory outcome was determined by the durations of oxygen and mechanical ventilation dependency. Results: FLV (but not LHR) results signicantly correlated with the durations of oxygen dependency (r=0.587, p-0.035) and mechanical ventilation dependency (r=0.618, p=0.024). Conclusion: These results suggest that assessment of fetal lung volumes using the VOCAL technique rather than LHR better predicts infant respiratory morbidity in fetuses with CDH who undergo FETO. Reference: 1. Peralta, C.F. et al. Ultrasound Obstet Gynecol 2006; 27:128-133. P4039 Neural respiratory drive assessed by measuring the diaphragm electromyography in infants weaning from mechanical ventialtion Katarzyna Swist-Szulik 1 , Zainab Kassim 1 , Charlie Reilly 2 , John Moxham 2 , Anne Greenough 1 , Gerrard Rafferty 1 . 1 Department Child Health, Kings College London School of Medicine, London, United Kingdom; 2 Allergy and Respiratory Science, Kings College London School of Medicine, London, United Kingdom Background: Neural respiratory drive (NRD) quantied by diaphragm electromyography (EMGdi) is a sensitive measure of the load on the respiratory muscles. Objectives: To test the hypothesis that measuring the NRD during weaning from mechanical ventilation would provide useful information on extubation outcome. Methods: A multipair oesophageal electrode was used to record the spontaneous EMGdi in 7 infants (median (range) gestational age 36 (33-38) wks) being weaned from mechanical ventilation. The oesophageal catheter consisted of 7 consecutive recording electrode coils. Each coil was 3 mm in length and the gap between adjacent coils was 5 mm. The electrode was positioned to cover the electrically active region of the diaphragm. The spontaneous breath by breath EMGdi was recorded during SIMV, CPAP (5cmH2O) and during a brief (5-7 breaths) inspiratory occlusion, during which the corresponding maximum inspiratory airway pressure was recorded. Results: Clear phasic activity of the EMGdi was obtained for all infants.There was no correlation between maximum EMGdi (mean (SD) 268.1 (152.8) uV and maximum airway pressure (mean (SD) 43.3 (25.7) cmH2O recorded during the occlusion (r = 0.181, p=0.697). Mean (SD) EMGdi was 96.6 (54.8) V on SIMV and 103.7 (57.5) V on CPAP, no signicant increase in EMGdi was observed (p=0.115). All patients were successfully extubated. Conclusion: Normalising EMGdi using a maximal inspiratory manoeuvre may not provide a reliable measure of relative neural respiratory drive during resting breathing in ventilated infants. Measuring the change in EMGdi between SIMVand CPAP may provide more reliable information on extubation outcome. P4040 Inuence of gestational age at birth on the diaphragm pressure time product Deena-Shefali Patel, Gerrard Rafferty, Silke Lee, Simon Hannam, Anne Greenough. Division of Asthma, Allergy and Lung Biology, Kings College London, London, United Kingdom Background: Infants with a high compared to a lower work of breathing (WOB)

P4041 The use of BiPAP in children with acute respiratory failure Sedat Oktem, Zeynep Seda Uyan, Erkan akir, Rabia Emel Senay, Reka Ersu, Bulent Karadag, Fazilet Karakoc, Elif Dagli. Department of Pediatric Pulmonology, Marmara University, Istanbul, Turkey Aim: Noninvasive ventilation (NIV) is extensively used in adults with acute respiratory failure (ARF) however data in children are limited. Our aim was to evaluate effectiveness of NIV in children with ARF. Method: We prospectively evaluated 19 patients who used BIPAP due to acute respiratory failure between 2005 and 2008 in our ward. Results: The mean age of the patients was 8.16.3 years (5 months-18 years; M/F=10/9). Two of the patients had malignity, 3 had immunodefciency, 3 had neuromusculer disease, 1 had diaphragm paralysis, 3 had persistant atelectasis and 7 had pneumonia. BIPAP was used due to hypoxic respiratory failure in 11 patients, hypercarbic respiratory failure in 1 patients and both hypoxic and hypercarbic respiratory failure in 7 patients. It was used for a mean duration of 67.845.5 hours in these patients. It was used via nasal mask in 13 patients and face mask in 6 patients. The need for respiratory support disappeared in 7 patients after the use of BIPAP, 9 patients were discharged with BIPAP but switch to mechanical ventilation was needed in 3 patients. Three of the patients who needed mechanical ventilation died. Conclusion: Improvement was seen in blood gas pH, pCO2, oxygen saturation, heart rate and respiratory rate of the patients after the use of BIPAP.
Respiratory parameters before and after NIV Before NIV pH pCO2 Oxygen saturation Heart rate Respiratory rate 7.370.08 47.417.1 867 13727 4811 After NIV 7.410.05 39.76.2 964 11519 3112 p 0.015 0.018 <0.001 0.001 <0.001

P4042 Assessment of BiPAP ventilation via tracheostomy tube supported for children with chronic respiratory failure Teh-Ming Wang, Jiann-Der Wang. Pediatrics, Taichung-Veterans General Hospital, Taichung, Taiwan Introduction: BiPAP ventilation via tracheostomy tube for the treatment of children with chronic respiratory failure has never been reported before. Therefore, we present our preliminary report here. Objectives: To evaluate the efcacy and complications of BiPAP ventilation via tracheostomy tube in pediatric patients with chronic respiratory insufciency or failure in a tertiary pediatric ICU. Material and Methods: Between Mar 2005 and Dec. 2007,6 of 9 patients underwent trachostomy owing to prolonged ventilator support (>4 wks) and couldnot be weaned from CMV in a short time enrolled to this study.They were shifted from CMV to ViPAP ventilator on Day 7-11 post tracheostomy. Clinical and laboratory variables immediately prior to ViPAP and 1- 4 hrs after institution, and 1- 4 hrs after add 3rd pole on BiPAP circuit were evaluated.The outcome was depended on whether patients could tolerate ViPAP support through tracheostomy and went home care. Results: All the patients were intolerated within few hours while ventilator mode were shifted from CMV to ViPAP initially and felt comfortable after added the 3rd pole on one way tube of the BiPAP except one case. No signicant complication occurred, such as air leak syndrome or compromised respiratory failure. All the patients could go home with ViPAP mode support but one patient. Conclusions: ViPAP ventilation via tracheosotomy tube is effective and safe method for respiratory assistance in pediatric patients with chronic respiratory

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insufciency or failure.It is the key factor to add the 3rd pole on the one way tube for pediatric patients with chronic respiratory insufciency or failure successfully supported by ViPAP. nonsuccess group (p=0.023). Oxygenation variables increased only in the success group. Among the NIV types, 58.6% of patients in the ventilator group, 55.7% in the two-pressure levels group, and 48.9% in the CPAP group progressed with success. Oxygenation and RR variables showed improvement only in the groups with two pressure levels. Conclusion: Newborns with hypoxemic ARF in the postoperative stage after thoracic surgery showed better oxygenation, RR, and HR during NIV application. In older newborns and those with higher baseline RR and HR values, NIV was not sufcient to reverse ARF. The two-pressure level modes showed better results.

P4043 Analysis of ventilation and hemodynamic changes resulting from noninvasive bilevel pressure mechanical ventilation applied to newborn with acute pneumonia Konstantun Bertsun, Dmytro Dmytriiev, Kateruna Dmytriieva, Olexandr Katilov, Olexandr Mazulov. Vinnitsa National Medical University n.a N.I Pirogov, Vinnitsa, Ukraine Objective: To observe in practice how noninvasive bilevel positive pressure, applied at different levels, may interfere with systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), and peripheral oxygen saturation (SpO2), in newborn with acute pneumonia (AP). Methods: 82 AP newborns (mean age 12.4 days) were treated with noninvasive bilevel mechanical ventilation. Patients were consecutively treated with an expiratory positive airway pressure (EPAP) of 5 cmH2O, 10 cmH2O, 15 cmH2O, 10 cmH2O, and 5 cmH2O, maintaining a variation in pressure ( P) of 5 cmH2O between the inspiratory pressure (IPAP) and the expiratory pressure (EPAP). Ventilation and hemodynamic data were collected at these time points, as well as 5 minutes before the beginning of the protocol and 5 minutes after its completion. Results: A statistically signicant difference was observed in the respiratory rate between the moment just before the beginning of the protocol and 5 minutes after positive pressure mask placement (p=0.022), and in oxygen saturation, between the nal minute of EPAP at 5 cmH2O and after the removal of the mask (p=0.05). Conclusion: Noninvasive bilevel mechanical ventilation improves oxygenation and reduces respiratory work, thus being benecial for newborn with acute pneumonia.

P4046 Premorbid abnormal lung function, maturity at birth and risk for RSV lower respiratory tract infections Simon Drysdale 1 , Theresa Wilson 1 , Melvyn Smith 2 , Gerrard Rafferty 1 , Mark Zuckerman 2 , Anne Greenough 1 . 1 Division of Asthma, Allergy and Lung Biology, Kings College London, London, United Kingdom; 2 South London Specialist Virology Centre & Health Protection Agency London Regional Laboratory, Kings College Hospital, London, United Kingdom Background: Premorbid abnormal lung function may be a risk factor for symptomatic RSV lower respiratory tract infections (LRTI). In a pilot study, very prematurely born babies who subsequently developed an RSV LRTI, compared to those who did not, had higher resistance of the respiratory system at NICU discharge (1). Objective: To determine whether the relationship of premorbid abnormal lung function and subsequent RSV LRTI differed according to gestational age at birth. Methods: Lung function (FRC helium; FRC multiple breath washout; lung clearance index; compliance (Crs) and the resistance (Rrs) of the respiratory system) was measured at 36 weeks PMA. After NICU discharge, nasopharyngeal aspirates were obtained whenever in the community or hospital the infants had an LRTI and were examined for RSV A and B, rhinovirus, inuenza A and B, parainuenza 1, 2 and 3, human metapneumovirus and adenovirus. Results: 86 infants with a median gestational age of 34 (23-36) weeks were prospectively followed. Forty infants developed LRTIs; 12 were RSV positive. Overall and in the infants of 32-36 weeks gestational age, there were no signicant differences in the premorbird lung function between those who developed an RSV infection and those without any viral infection, whereas in those < 32 weeks GA at birth the RSV group tended to have higher premorbid Rrs and lower Crs. Conclusion: These results suggest maturity at birth may inuence the relationship of premorbid lung function and risk of RSV LRTI. Reference: 1. Broughton, S. et al. Arch Dis Child 2006; 91:26-30.

P4044 High frequency oscillatory ventilation for respiratory failure due to gastroschisis Konstantun Bertsun, Dmytro Dmytriiev, Kateruna Dmytriieva. Vinnitsa National Medical University n.a N.I Pirogov, Vinnitsa, Ukraine Objective: To describe the time course of high frequency oscillatory ventilation (HFOV) in gastroschisis. Methods: Design. Retrospective charts review. Setting. A tertiary paediatric intensive care unit. Patients and participants. Infants with respiratory failure due to gastroschisis. Intervention. HFOV. Measurements and results: Pattern of lung disease, ventilatory settings, blood gases, infants vital parameters, sedation and analgesia during the periods of conventional mechanical ventilation (CMV, 5 infants), after initiation of HFOV (HFOVi, 11 infants), in the middle of its course (HFOVm), at the end (HFOVe) and after extubation (Post-Extub) were compared. All infants showed a predominant overexpanded lung pattern. Mean airway pressure was raised from a mean (SD) 12.2 (2.0) during CMV to 17.8 (2.7) cmH2O during HFOVi (P < 0.05), then decreased to 11.2(1.3) at HFOVe (P < 0.05). Mean FiO2 was reduced from 0.64 (0.18) (CMV) to 0.60 (0.14) (HFOVi) then to 0.28 (0.06) (P < 0.05) at HFOVe and mean peak to peak pressure from 45.1 (12.4) cmH2O (HFOVi) to 21.1 (7.7) P < 0.05 (HFOVe) while mean (SD) PaCO2 showed a trend to decrease from 74 (22) (CMV) to 45 (8) mmHg (HFVOe) and mean infants respiratory rate a trend to increase from 21 (11) (HFOVi) to 33 (14) (HFOVe) breaths/min. With usual doses of sedatives and opiates, no infant was paralysed and all were extubated to CPAP or supplemental oxygen after a mean of 120 h. Conclusion: Gastroschisis induced respiratory failure with hypercapnia can be managed with HFOV using high mean airway pressure and large pressure swings while preserving spontaneous breathing.

P4047

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N W RA

P4045 Application of noninvasive ventilation in acute respiratory failure after thoracic surgery Dmytro Dmytriiev, Konstantin Bertsun. Anesthesiology, Vinnitsa National Medical University n.a N.I Pirogov, Vinnitsa, Ukraine Objective: To examine ventilatory response, oxygenation-related, and hemodynamics of newborns with acute respiratory failure (ARF) submitted to noninvasive mechanical ventilation (NIV) during the postoperative phase of thoracic surgery in order to identify predictive variables of success, and to compare the different types of NIV. Methods: 72 newborns with ARF were randomized to one of three modalities of NIV - continuous positive airway pressure (CPAP) and ventilation with two pressure levels (PEEP + SP and BiPAP). ventilation, oxygenation-related, and hemodynamics variables were analyzed at pre-application, and 3, 6, and 12 hours after the protocol began. Results: 31 newborns progressed to independence from ventilatory support and comprised the success group, and 26 required orotracheal intubation and were considered the nonsuccess group. Age, initial heart rate (HR), and respiratory rate (RR) showed elevated levels in the nonsuccess group (p=0.040, 0.027, and 0.004, respectively). A greater number of intraoperative complications were seen in the

P4048 Respiratory status in premature children with BPD follow up Soja Galbova, Milka Caparoska, Oliver Zarovski, Zorica Sarevska, Biljana Dimceva. Intensive Care Unit, Institute for Respiratory Diseases in Children-Kozle, Skopje, Fyrom Aim: Evaluation of the respiratory status in premature children with BPD. Material and methods: We analyzed the group of 15 premature infants with BPD. All of them were delivered before 32 week of gestation with main birth weight of 1100 gr. (900-1340), mean Apgar score 3, 3/3, 7, on mechanical ventilation during 21-70 days and oxygen support in 45-120 days. All children had radiological changes leading to BPD. Respiratory status was assesses on the base of clinical

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ndings, lung radiological changes, re-hospitalization needs and application of chronic medicament therapy. Results: After the initial hospitalization, 4 children (26, 6%) had no need of re-hospitalization with satisfactory regression of radiological ndings on the age of one year. They had no signicant co- morbidity and need of drugs therapy. Because of recidivate broncho-obstructive attacks, 7 children (46.7%) have received long-lasting anti-inammatory therapy (3 months-2 years); from them, 5 children (33.4%) have been more times re-hospitalized for more severe low respiratory infections; four of them were treated with conservative drug anti reux treatment for pathological GER and aspirations. In the rst 6 months of life, exitus letalis was registered in two children (13.3%) with more signicant CNS changes. Conclusion: Reports about following of respiratory status in premature children with BPD are in small number especially after discharging ICU in deliveries. There are no standard protocols. So, there are individual treatments depending on changes reversibility. High co-morbidity (GER, cerebral paralyze, mal development) enjoin need of complex following of this children leaded by good equipped team. Results: When inspired oxygen was reduced from 21% to 12%, there was 8% drop in oxygen saturation (99% to 91%) compared to 6% and 7% drop in Groups B and C respectively. When exposed to hypoxia, Group A had signicantly low RV basolateral strain (inversely related PAH). RV systolic velocity was lower in preterm children compared to term. Conclusions: We have demonstrated that children who were born prematurely and had CLD may be at risk of developing subclinical RV dysfunction and pulmonary arterial hypertension when exposed to hypoxia later on in life.

P4051 Can echocardiography be used to measure right ventricular dysfunction and pulmonary hypertension in newborn infants? Suchita Joshi 1 , Julie M. Edwards 2 , Dirk G. Wilson 3 , Joon K. Wong 3 , Alan G. Fraser 2 , Sailesh Kotecha 1 . 1 Child Health, Cardiff University, Cardiff, United Kingdom; 2 Cardiology, Cardiff University, Cardiff, United Kingdom; 3 Paediatric Cardiology, University Hospital of Wales, Cardiff, United Kingdom Background: Myocardial velocity imaging (MVI) is a useful non-invasive diagnostic tool for assessing pulmonary arterial hypertension (PAH) in adults. We have shown that this may be a useful diagnostic tool in preterm infants with respiratory distress syndrome (Joshi et al ERJ 2008 Suppl. 52:812s). However, reproducibility and thus clinical utility of off line analysis of MVI in newborn infants has not yet been established. Aims: To establish intra and inter-observer reproducibility for off-line analysis of RV myocardial velocities and strain in newborn infants. Methods: 3-beat myocardial velocity loops were acquired from newborn infants within 72 hours after birth, and processed using commercial software. Images from 16 infants, 8 term (>38 weeks) and 8 preterm (<34 weeks) were analysed twice by 4 different observers for inter-observer variability, and reanalysed by one observer after 6 months for intra-observer variability. Reproducibility is presented as pooled coefcients of variation (CV). Results:
CV % Intra-observer RV displacement (mm) RV s velocity (cm/s) RV e velocity (cm/s) RV a velocity (cm/s) RV isovolumic acceleration (m/s2 ) RV basal strain (%) RV apical strain (%) 12.8 17.7 15.0 18.5 43.6 19.0 23.9 Inter-observer 18.2 18.3 23.3 24.1 45 37.1 25.3

P4049 Screening surfactant protein genes in patients with hereditary pulmonary surfactant deciency UK experience Atul Gupta 1 , Lucy Jenkins 2 , Caroline Archer 2 , Gail Norbury 2 , Quen Mok 3 . 1 Paediatric Respiratory Medicine, Great Ormond Street Hospital for Sick Children NHS Trust, London WC1N 3JH, London, United Kingdom; 2 Regional Molecular Genetics, Great Ormond Street Hospital for Sick Children NHS Trust, London WC1N 3JH, London, United Kingdom; 3 Paediatric Intensive Care Unit, Great Ormond Street Hospital for Sick Children NHS Trust, London, London, United Kingdom Background: Pulmonary surfactant deciency is a rare chronic respiratory disorder that can be fatal. At least three genes are involved. Surfactant Pulmonary associated Protein B (SFTPB) and Surfactant Pulmonary associated Protein C (SFTPC) are secreted in the lung surfactant to increase pulmonary compliance. Adenosine Triphosphate-Binding Cassette subfamily A member 3 (ABCA3) transports these proteins across the cell membrane The rst UK diagnostic service was established in London and screening has now been offered for more than 5 years. Analyses of the genetic mutations are expensive & time consuming. We present genotypic and phenotypic data of the referred population. Results: 114 samples were received over 5 years, with referrals increasing by more than 500%. Of the 114, 67 were new referrals, 44 carrier testing, 1 perinatal & 2 prenatal testing Reasons for referral were Interstitial lung disease -18, Bronchopulmonary dysplasia (BPD)-15, Pulmonary hypertension-8, Unexplained respiratory failure-10, alveolar proteinosis-3, recurrent chest infection-2, no details - 11. All the patients referred with BPD, recurrent chest infections or pulmonary hypertension were negative on screening SFTPB mutations were identied in 5/56(9%), SFTPC mutation in 2/46(4%) and ABCA3 mutation in 5/46(11%). 5 patients with SFTPB deciency, 2 with ABCA3 and one with SFTPC deciency had unexplained respiratory failure/persisting high ventilatory requirements. 2 cases with ABCA3 deciency and 1 with SFTPC deciency had interstitial lung disease Conclusion: Surfactant mutation analysis is now well established in UK. Referrals need to be rationalised, for the service to be time and cost effective.

Conclusion: Intra-observer reproducibility for RV mocardial velocities and displacement are adequate; these parameters can be used in clinical research. Interobserver reproducibility is sub-optimal suggesting that caution is appropriate when using these measuremetns clinically. Reproducibility for myocardial acceleration, marker of contractile function and deformity indices were unsatisfactory.

P4050 Cardiovascular response to acute hypoxia in 8-12 year old children with chronic lung disease of prematurity Suchita Joshi 1 , Julie M. Edwards 2 , Dirk G. Wilson 3 , Mark Drayton 3 , Alan G. Fraser 2 , Sailesh Kotecha 1 . 1 Child Health, Cardiff University, Cardiff, United Kingdom; 2 Cardiology, Cardiff University, Cardiff, United Kingdom; 3 Paediatrics, University Hospital of Wales, Cardiff, United Kingdom Background: Pulmonary arterial hypertension (PAH) is a known complication of chronic lung disease of prematurity (CLD) in infants. It is not known whether the survivors of CLD are at risk of developing right ventricular (RV) dysfunction and PAH, especially in response to hypoxia later on in life in. Aims: To assess RV function and evidence of PAH in response to acute hypoxia in children who had CLD compared to healthy term and preterm controls, by using myocardial velocity imaging (MVI). Methods: We studied 32 children aged 8-12: 13 who had CLD (Group A), 13 were born prematurely but did not develop CLD (Group B) and 6 term born controls (Group C). All had echocardiography including MVI while breathing room air followed by inhalation of 15% oxygen for 20 minutes and 12% oxygen for another 20 minutes. After each period of hypoxia, echocardiography was repeated.
Goups RV systolic velocity, cm/s A B C A B C Mean (SD) 8.8 (2.2) 9.4 (1.5) 10.8 (2.3) -33.1 (8.5) -31.6 (8.4) -37.0 (8.7) 9.4 (2.3) 9.2 (1.6) 11.4 (1.5) -29.4 (7.5) -33.0 (8.7) -44.3 (8.3) p value B vs C 0.01 A vs C 0.001

P4052 Development of in-vitro models for aerosolized surfactant therapy to support customization of a novel nebulizer system based on eow technology Markus Tservistas, Carola Fuchs, Roman Egle, Ute Fleschhut, Sophie Ederer, Alexandra Nikolai, Karin Reul, Simone Maresch, Gerd Hochwimmer, Manfred Keller, Martin Knoch. Aerosol Research Institute, PARI Pharma GmbH, Munich, Germany Aerosolization of lung surfactant for treatment of premature newborns via a nebulizer would be benecial, since instillation via an intratracheal tube can be a harmful method. Development of a suitable nebulizer system requires adequate testing for such a specic use. In-vitro tests should be simple but close enough to mimic an in-vivo situation. In addition, tests should be fast, robust and economic to provide meaningful data. Usually, nebulizers are characterized by breath simulation applying age group specic breathing patterns. A more sophisticated characterization is possible by anatomical casts, such as the Sophia Anatomical Infant Nose Throat (SAINT) representing an upper airway model of a 9 months old baby or PrINT, representing a premature newborn cast. Ideally, tests are conducted with drug formulations. However, surrogates may also be considered in case of bioproducts which may be very expensive and of limited availability, such as Curosurf , a widely used lung surfactant derived from swine lungs. Hence, we developed both, an articial lung surfactant having a similar surface tension as Curosurf (26.6 mN/m vs. 25 mN/m) and corresponding analytical assays. When aerosolized by a novel nebulizer for premature newborns, both formulations had a MMAD between 2.4 and 2.8 m and a GSD around 1.5 based on data from NGI measurements. In conclusion, the physical properties of the articial lipid surfactant formulation are close to Curosurf allowing assessment of the delivered and respirable dose of a novel electronic nebulizer for newborns.

RV strain, %

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P4053 Effect of deadspace reduction by the kolobow tube on blood gases in small ventilated surfactant-depleted piglets Hans Proquitt, Charles Christoph Roehr, Gerd Schmalisch. Clinic of Neonatology, Charit Universitaetsmedzin Berlin, Berlin, Germany Background: In ventilated extremely low birth weight infants the apparatus dead space of the ow sensor (VDapp ) and the endotracheal tube (ET) impairs the gas exchange. The aim of the study was to quantify to which extent a deadspace reduced so called Kolobow tube (KB) without ow sensor improves the gas exchange compared with the conventional ventilation using the T-piece connector combined with ow sensor of the Babylog 8000 (BL). Methods: In a cross-over trial in 14 tracheotimized, surfactant-depleted, ventilated newborn piglets (< 12 hrs; 705-1200g) twice BL and KB was applied alternately for 15 minutes and blood gases were recorded. Stabilization after lavage was allowed for 1 hr, thereafter ventilator settings were kept constant. The inner diameter of the ET was 3.6mm and VDapp of BL and KB including the tube were 5.55mL and 1.3mL, respectively. Results: Despite the distinct reduction in VDapp by KB compared to BL the improvements in blood gases were statistically signicant only for body weights < 900g and with increasing weight the effect decreased.
Changes in blood gases in % (95%CI) by using a Kolobow tube < 900g (N=12) pCO2 PO2 SaO2 ph *p<0.05, **p<0.01. -8.4%** (-14.3% to 2.5%) 9.2%* (0.7% to 17.8%) 1.7% (-0.6% to 4.1%) 0.7%** (0.3% to 1.1%) >900g (N=16) -3.9% (-10.4% to 2.7%) 1.7% (-5.6% to 9.2%) 0.2% (-0.6% to 1.0%) 0.07% (-0.3% to 0.4%)

Aim: In a pneumonia model we studied how PEEP and RMs affect lung mechanics and hypothesized that loss of lung volume would be deleterious. Methods: Groups of 2 week old rats received saline or lipopolysaccharide (LPS) via trachea. The next day rats were ventilated for 4 h with a VT of 8 ml/kg at PEEP of 4 (PEEP4), PEEP of 8 (PEEP8), or PEEP of 4 cmH2 O with RMs applied every h (PEEP4RM). PV curves were constructed and airway resistance (Raw ) and the coefcient of tissue elastance (H) were obtained from respiratory input impedance measurements using the low-frequency forced oscillation technique. Cytokines were measured in bronchoalveolar lavage (BAL). Results: PEEP4RM resulted in minor changes in Raw and H. PEEP4 resulted in a linear rise of Raw and H by 30 and 100%, respectively. Raw and H initially rose after allocation to PEEP8, but were stable thereafter. Quasi-static lung compliance improved the most with PEEP8. Compared to PEEP4 and PEEP4RM, PEEP 8 also reduced BAL neutrophils by 40% in both saline and LPS exposed animals. The inammatory prole induced by LPS was not affected by the ventilation strategy. RMs produced short-lived reversal of the increases of Raw and H. Conclusion: High PEEP provided stable lung mechanics and reduced numbers of alveolar neutrophils. This infant rat study shows that in keeping lungs open high PEEP is benecial and preferable over RM-induced transient improvements of lung mechanics.

P4056 Inhaled no decreased endothelial nitric oxide synthase expression in normal newborn rat lungs Thong Hua-Huy 1 , Sy Duong-Quy 1 , Xiao-Kui Tang 1 , Hoa Pham 2 , Julien Pansiot 2 , Paul Olivier 2 , Olivier Baud 2 , Jean-Christophe Mercier 3 , Anh-Tuan Dinh-Xuan 1 . 1 Service de Physiologie-Explorations Fonctionnelles, Hpital Cochin, Paris, France; 2 INSERM Avenir R05230HS, Hpital Robert Debr, Paris, France; 3 Service des Urgences Pdiatriques, Hpital Robert Debr, Paris, France Rationale: Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill preterm newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (NOS-3) activity and expression in vascular endothelial cell cultures or adult rat models. However, the effects of iNO on NOS-3 expression in newborn rat lungs have not yet been described. Objective: We assessed the effects of inhaled NO on NOS-3 expression in newborn rat lungs. Methods: Rat pups, postnatal days (P) 0 to P7, and their dams were placed in a chamber containing NO at 5ppm (iNO-5ppm) or 20ppm (iNO-20ppm) (< 1ppm NO2 ). NO and NO2 levels were continuously monitored using iNOvent (DatexOhmeda, Madison, USA). Control litters were kept in room air condition. Rat pups were sacriced at P7 and P14. Pulmonary NOS-3 protein expressions were evaluated by immunohistochemistry (IHC) and Western Blot (WB). The amounts of NOS-3 mRNA were quantied by qRT-PCR. Results: At P7, NOS-3 expressions in total lung lysates (WB), in bronchial and arterial sections (IHC) were signicantly decreased in iNO-20ppm versus control groups but did not signicantly differ between animals inhaling NO (5ppm) and control group. At P14, NOS-3 expression was comparable in all three groups of animals. Results of qRT-PCR conrmed the signicant difference of NOS-3 mRNA at P7 between iNO-20ppm and control groups. Conclusion: Inhalation of NO at 20ppm early after birth decreased lung bronchial and arterial NOS-3 expression at transcriptional level or mRNA stability, that might explain the rebound phenomenon observed in some patients treated with inhaled NO.

Conclusion: In very small lungs the use of KB improved the gase exchange signicantly, however, the improvement was moderate and does not justify the loss of ow measurements.

P4054 High tidal volume ventilation is not deleterious in infant rats exposed to severe hemorrhage Vincenzo Cannizzaro 1,2 , Luke Berry 1 , Philip Nicholls 3 , Zoltan Hantos 1,4 , Peter Sly 1 . 1 Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, WA, Australia; 2 Intensive Care Medicine and Neonatology, University Childrens Hospital, Zurich, Switzerland; 3 School of Veterinary Biology and Biomedical Sciences, Murdoch University, Murdoch, WA, Australia; 4 Department of Medical Informatics and Engineering, University of Szeged, Szeged, Hungary High VT ventilation with low PEEP is deleterious in adult rats. We aimed to determine a) whether high VT ventilation (21 ml/kg) with low PEEP (1 cmH2 O) was deleterious when compared to low VT ventilation (7ml/kg) with high PEEP (5 cmH2 O) in infant rats and b) whether high VT augmented lung injury after induction of severe hemorrhage. Two week old healthy rats were allocated to low VT or high VT and ventilated for 4 h. Additional rats were subjected to volume-controlled hemorrhage (30% of blood volume) and delayed saline resuscitation, followed by low VT or high VT ventilation for 4 h. Non-ventilated control groups with and without hemorrhage were also included. Airway resistance and the coefcient of tissue elastance (H) were derived from respiratory input impedance measurements using the low-frequency forced oscillation technique. IL-6, MIP-2 and TNFa were determined in bronchoalveolar lavage (BAL) and serum. Compared to low VT in both healthy and hemorrhage-exposed animals high VT resulted in reduced H (by 15%), better quasistatic lung compliance (by 25%), and better oxygenation (99.4 vs. 96.2%) after 4 h. IL-6 in BAL was higher in ventilated animals when compared to non-ventilated controls, but not different between ventilated groups. No signicant differences were found for all other inammatory mediators, total protein concentration in BAL, and histology. High VT ventilation with low PEEP improves lung mechanics without causing additional damage to healthy and hemorrhage-exposed infant rats. This study highlights the tolerance towards high VT ventilation in infant rats and underscores the need for age-specic animal models in the eld of ventilator-associated lung injury.

P4057 Urine levels of plasticizers in children on long-term mechanical ventilation via PVC tracheostomy tubes Gunilla Bjorling 1 , Michael Laub 2 , Claes Frostell 3 , Ragnhild E. Aune 4 , Sigbritt Karlsson 5 , Bo A.G. Jnsson 6 . 1 Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital; Sophiahemmet University College, Stockholm, Sweden; 2 Respiratory Centre East, Copenhagen University Hospital, Copenhagen, Denmark; 3 Karolinska Insitutet, Karolinska University Hospital, Stockholm, Sweden; 4 Royal Institute of Technology, Material Sciences, Stockholm, Sweden; 5 Royal Institute of Technology, Fibre and Polymer Technology, Stockholm, Sweden; 6 Lund University Hospital, Environmental Medical Chemistry, Lund, Sweden Background: In spite of proven toxicity Polyvinyl Chloride (PVC) is commonly used in medical devices. The added plasticizer Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and an endocrine modulator in humans. Especially children are at risk. A PVC tube contains >30% of DEHP. In-vivo studies have shown that DEHP migrates from the tube material (Bjorling et al. 2007 Laryngoscope;117:1552-9). Children, on long-term mechanical ventilation via tracheostomy have an increased risk for exposure. Aim: The aim was to measure the content of the metabolites from DEHP in urine in children who was treated with long-term ventilation via tracheostomy tubes made of PVC. Methods: Nine children aged 5-15 years on long-term home mechanical ventilation via tracheostomy were included in the study. One urine sample from each patient was collected. Analyses were performed

P4055 High PEEP produced more stable respiratory mechanics than recruitment maneuvers in an infant rat pneumonia model Vincenzo Cannizzaro 1,2 , Philip Nicholls 3 , Luke Berry 1 , Zoltan Hantos 4 , Peter Sly 1 . 1 Division of Clinical Sciences, Telethon Institute for Child Health Research, Perth, WA, Australia; 2 Intensive Care Medicine and Neonatology, University Childrens Hospital, Zurich, Switzerland; 3 School of Veterinary Biology and Biomedical Sciences, Murdoch University, Murdoch, WA, Australia; 4 Department of Medical Informatics and Engeneering, University of Szeged, Szeged, Hungary Background: High PEEP and recruitment maneuvers (RMs) are effective in keeping lungs open during mechanical ventilation.

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Thematic Poster Session

Hall A-33 - 12:50-14:40

T UESDAY, S EPTEMBER 15 TH 2009

using liquid chromatography tandem mass spectrometry as previously described (Jonsson et al. Epidemiology 2005;16:487-93) but with some modication. Results: The median concentrations of Mono(2-ethylhexyl) phthalate (MEHP), Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and Mono(2-ethyl-5oxohexyl) phthalate (MEOHP) in the nine children were 41 (range 16-170) ng/ml, 28 (range 7-86) ng/ml, and 30 (range 4-84) ng/ml, respectively. The obtained levels are higher than the average levels reported from Swedish and US population studies. Conclusions: Children, on long-term mechanical ventilation via PVC tracheostomy tubes, have an increased level of metabolites of DEHP compared to subjects from reference populations in Sweden and the US. Further long-term clinical studies are needed to conrm the results.

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