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IntroductionPersisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis.MethodsSystematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression.ResultsNinety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I2=95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I2=94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (−0.036; 95% CI −0.068 to –0.004; p=0.029), associations with fibrotic sequelae did not reach significance (−0.021; 95% CI −0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I2=92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I2=92.5%), neither were associated with follow-up time (p=0.207; p=0.864).DiscussionSequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity.PROSPERO registration numberCRD42020183139.

BACKGROUND: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement. RESEARCH QUESTION: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [Delta Prs]). STUDY DESIGN AND METHODS: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, Delta Prs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality. RESULTS: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.012.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher Delta Prs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: Delta Prs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality. INTERPRETATION: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.

Series describing the evolution of patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 and supported with extracorporeal membrane oxygenation (ECMO) during the first wave of the pandemic have reported mortalities ranging from 30 to 60% [1, 2]. More recent publications have demonstrated a trend towards a higher mortality in COVID-19 patients receiving support in later periods of the pandemic, even though the overall mortality of the disease seems lower [3, 4]. The reasons for this difference are not clear. Statistical analysis was carried out in the Statistics and Bioinformatics Unit (UEB) Vall d'Hebron Hospital Research Institute (VHIR). The following practitioners provided care for the study patients

Background Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease − 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI − 0.48 to − 0.14, p CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018). Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study. Trial registration: ACTRN12620000421932.

The Respiratory Intensive Care Assembly of the European Respiratory Society organised the first Respiratory Failure and Mechanical Ventilation Conference in Berlin in February 2020. The conference covered acute and chronic respiratory failure in both adults and children. During this 3-day conference, patient selection, diagnostic strategies and treatment options were discussed by international experts. Lectures delivered during the event have been summarised by Early Career Members of the Assembly and take-home messages highlighted.

Background: The impact of neutropenia in critically ill immunocompromised patients admitted in a context of acute respiratory failure (ARF) remains uncertain. The primary objective was to assess the prognostic impact of neutropenia on outcomes of these patients. Secondary objective was to assess etiology of ARF according to neutropenia. Methods: We performed a post hoc analysis of a prospective multicenter multinational study from 23 ICUs belonging to the Nine-I network. Between November 2015 and July 2016, all adult immunocompromised patients with ARF admitted to the ICU were included in the study. Adjusted analyses included: (1) a hierarchical model with center as random effect; (2) propensity score (PS) matched cohort; and (3) adjusted analysis in the matched cohort. Results: Overall, 1481 patients were included in this study of which 165 had neutropenia at ICU admission (11%). ARF etiologies distribution was significantly different between neutropenic and non-neutropenic patients, main etiologies being bacterial pneumonia (48% vs 27% in neutropenic and non-neutropenic patients, respectively). Initial oxygenation strategy was standard supplemental oxygen in 755 patients (51%), high-flow nasal oxygen in 165 (11%), non-invasive ventilation in 202 (14%) and invasive mechanical ventilation in 359 (24%). Before adjustment, hospital mortality was significantly higher in neutropenic patients (54% vs 42%; p = 0.006). After adjustment for confounder and center effect, neutropenia was no longer associated with outcome (OR 1.40, 95% CI 0.93–2.11). Similar results were observed after matching (52% vs 46%, respectively; p = 0.35) and after adjustment in the matched cohort (OR 1.04; 95% CI 0.63–1.72). Conclusion: Neutropenia at ICU admission is not associated with hospital mortality in this cohort of critically ill immunocompromised patients admitted for ARF. In neutropenic patients, main ARF etiologies are bacterial and fungal infections., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement. RESEARCH QUESTION: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [Delta Prs]). STUDY DESIGN AND METHODS: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, Delta Prs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality. RESULTS: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.012.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher Delta Prs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: Delta Prs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality. INTERPRETATION: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.

High-throughput, "next-generation" sequencing methods are now being broadly applied across all fields of biomedical research, including respiratory disease, critical care, and sleep medicine. Although there are numerous review articles and best practice guidelines related to sequencing methods and data analysis, there are fewer resources summarizing issues related to study design and interpretation, especially as applied to common, complex, nonmalignant diseases. To address these gaps, a single-day workshop was held at the American Thoracic Society meeting in May 2017, led by the American Thoracic Society Section on Genetics and Genomics. The aim of this workshop was to review the design, analysis, interpretation, and functional follow-up of high-throughput sequencing studies in respiratory, critical care, and sleep medicine research. This workshop brought together experts in multiple fields, including genetic epidemiology, biobanking, bioinformatics, and research ethics, along with physician-scientists with expertise in a range of relevant diseases. The workshop focused on application of DNA and RNA sequencing research in common chronic diseases and did not cover sequencing studies in lung cancer, monogenic diseases (e.g., cystic fibrosis), or microbiome sequencing. Participants reviewed and discussed study design, data analysis and presentation, interpretation, functional follow-up, and reporting of results. This report summarizes the main conclusions of the workshop, specifically addressing the application of these methods in respiratory, critical care, and sleep medicine research. This workshop report may serve as a resource for our research community as well as for journal editors and reviewers of sequencing-based manuscript submissions in our research field.

The severe acute respiratory syndrome coronavirus 2 pandemic is to date affecting more than a million of patients and is challenging healthcare professionals around the world. Coronavirus disease 2019 may present with a wide range of clinical spectrum and severity, including severe interstitial pneumonia with high prevalence of hypoxic respiratory failure requiring intensive care admission. There has been increasing sharing experience regarding the patient's clinical features over the last weeks which has underlined the need for general guidance on treatment strategies. We summarise the evidence existing in the literature of oxygen and positive pressure treatments in patients at different stages of respiratory failure and over the course of the disease, including environment and ethical issues related to the ongoing coronavirus disease 2019 infection. Vranckx, P (corresponding author), Jessaziekenhuis Hasselt, Dept Cardiol & Intens Care, Stadsomvaart 11, B-3500 Hasselt, Belgium. pascal.vranckx@iccuhasselt.be

Objectives: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure.Design: Retrospective analysis of the Extracorporeal Life Support Organization's data registry.Setting: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992-2015.Patients: Adults (>= 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure.Interventions: None.Measurements and Main Results: We included 4,988 adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. Neurologic injury was defined as brain death, seizures, stroke, and intracranial hemorrhage occurring during extracorporeal membrane oxygenation support. We used multivariable logistic regression to explore patient and extracorporeal membrane oxygenation factors associated with neurologic injury. Median age of the study cohort was 46 (interquartile range, 32-58). Four hundred twenty-six neurologic complications were reported in 356 patients (7.1%), and included 181 intracranial hemorrhage (42.5%), 100 brain deaths (23.5%), 85 stroke (19.9%), and 60 seizure events (14.1%). In-hospital mortality was significantly higher for those with CNS complications (75.8% vs 37.8%; p Conclusions: Approximately 7% of adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure had neurologic injury. Intracranial hemorrhage was the most frequent type, and survival for patients with neurologic injury was poor. Future investigations should evaluate anticoagulation management as well as brain/extracorporeal membrane oxygenation interaction to reduce these life-threatening events.

The methods of nasal absorption (NA) and bronchial absorption (BA) use synthetic absorptive matrices (SAM) to absorb the mucosal lining fluid (MLF) of the human respiratory tract. NA is a non-invasive technique which absorbs fluid from the inferior turbinate, and causes minimal discomfort. NA has yielded reproducible results with the ability to frequently repeat sampling of the upper airway. By comparison, alternative methods of sampling the respiratory mucosa, such as nasopharyngeal aspiration (NPA) and conventional swabbing, are more invasive and may result in greater data variability. Other methods have limitations, for instance, biopsies and bronchial procedures are invasive, sputum contains many dead and dying cells and requires liquefaction, exhaled breath condensate (EBC) contains water and saliva, and lavage samples are dilute and variable. BA can be performed through the working channel of a bronchoscope in clinic. Sampling is well tolerated and can be conducted at multiple sites in the airway. BA results in MLF samples being less dilute than bronchoalveolar lavage (BAL) samples. This article demonstrates the techniques of NA and BA, as well as the laboratory processing of the resulting samples, which can be tailored to the desired downstream biomarker being measured. These absorption techniques are useful alternatives to the conventional sampling techniques used in clinical respiratory research.

Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research.The task force statement addresses general issues of experimental research (ethics, species, sex, age,ex vivoandin vitromodels, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension.The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality.

International audience; Objectives: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. Design: Post hoc analysis of a randomized clinical trial. Setting: Twenty-three ICUs. Patients: Patients with a respiratory rate greater than 25 breaths/min and a Pao(2)/Fio(2) ratio less than or equal to 300mm Hg. Intervention: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. Measurement and Main Results: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a Pao(2)/Fio(2) ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62-11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22-8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. Conclusions: In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A Pao(2)/Fio(2) below 200mm Hg and a high tidal volume greater than 9mL/kg were the two strong predictors of intubation under noninvasive ventilation.

Novikov Nikolay, Tumansky Valery, Fedotov Vasiliy. transformations of respiratory epitelium in fibrous stage of acute respiratory distress-syndrome = Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома. Journal of Health Sciences. 2014;4(14):117-120. ISSN 1429-9623 / 2300-665X. http://ojs.ukw.edu.pl/index.php/johs/article/view/2014%3B4%2814%29%3A117-120 http://journal.rsw.edu.pl/index.php/JHS/article/view/2014%3B4%2814%29%3A117-120 https://pbn.nauka.gov.pl/works/512256 DOI: 10.5281/zenodo.13322 http://dx.doi.org/10.5281/zenodo.13322 The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1107. (17.12.2013). © The Author (s) 2014; This article is published with open access at Licensee Open Journal Systems of Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. Conflict of interest: None declared. Received: 15.11.2014. Revised 05.12.2014. Accepted: 10.12.2014. transformations of respirAtory epitelium in fibrous stage of acute respiraTory distress-syndrome Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома Nikolay Yu Novikov Crimean State Medical University, Simferopol, Russian Federation Valery Alexeevich Tumansky Zaporozhye State Medical University, Ukraine Vasiliy Vladimirovich Fedotov Crimean State Medical University, Simferopol, Russian Federation Corr. Author Новиков Николай Юльевич докт. мед. наук, доцент ГУ «КГМУ имени С.И.Георгиевского», РФ, г.Симферополь Е-mail:tttravelll@yandex.ru Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома АННОТАЦИЯ Цель. Определение признаков эпителиально-мезенхимальной трансформации (ЭМТ) для установления ее роли в развитии фиброза легких у пациентов с острым респираторным дистресс-синдромом. Метод. Иммуногистохимическое окрашивание гистологических срезов. Результат. В большинстве альвеолоцитов обнаруживается экспрессия маркеров эпителиального иммунофенотипа. Признаки мезенхимальной дифференцировки определяются в единичных альвеолоцитах. Вывод. ЭМТ не играет существенной роли в формировании фиброза респираторного отдела при ОРДС. Ключевые слова: респираторный эпителий; легкие; дистресс-синдром. transformations of respirAtory epitelium in fibrous stage of acute respiraTory distress-syndrome ABSTRACT The epithelial-mesenchimal transition of respiratory epithelium in Acute Respiratory Distress Syndrome (ARDS) was goal of investigation. Postmortem immunohistochemical stain of respiratory part histological sections was methods. Result: epithelial immunofenotype of epithelial cells was determinate in more cases. Conclusion. The epitelial-mesenchimal transition does not play main role to lungs fibrosis in ARDS. Keywords: respiratory epitelium; lungs; distress-syndrome.

OBJECTIVE: Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to investigate whether SFTPD variations affect serum SP-D levels in infants and pulmonary outcome in premature infants.STUDY DESIGN: Serum SP-D levels were measured in 211 mature and 202 premature infants, and 7 SFTPD single-nucleotide polymorphisms (SNPs) were genotyped. SNP analysis and haplotype analysis were used to associate genetic variation to SP-D, respiratory distress (RD), oxygen requirement, and respiratory support.RESULTS: The 5'-upstream SFTPD SNP rs1923534 and the 3 structural SNPs rs721917, rs2243639, and rs3088308 were associated with the SP-D level. The same SNPs were associated with RD, a requirement for supplemental oxygen, and a requirement for respiratory support. Haplotype analyses identified 3 haplotypes that included the minor alleles of rs1923534, rs721917, and rs3088308 that exhibited highly significant associations with decreased SP-D levels and decreased ORs for RD, oxygen supplementation, and respiratory support.CONCLUSION: These findings extend and validate previous observations of SFTPD association with the risk of respiratory outcomes and suggest SFTPD as an essential factor affecting pulmonary adaptation in premature infants.

The long-term outcome of infants with severe respiratory distress syndrome can be improved by optimizing surfactant therapy and minimizing the risk for pulmonary barovolutrauma and oxygen toxicity. The authors hypothesized that this may be achieved with low frequency ventilation and extracorporeal CO2 removal (LFV-ECCO2R), in combination with intratracheal instillation of a large fluid volume with diluted surfactant. Lung lavaged rabbits were initially ventilated with continuous positive pressure ventilation. The rabbits were randomized to treatment with LFV-ECCO2R and surfactant (experimental group), or surfactant only (control group). In the experimental group, the rabbits were treated with a large volume (16 ml/kg) of diluted surfactant (6.25 mg/ml) at a dose of 100 mg/kg body weight. After surfactant therapy, the FiO(2) 100% was gradually decreased. During 4 hours, the extracorporeal bloodflow was adjusted to maintain the PaCO2 between 4.0-6.0 kPa. Thereafter, the rabbits were allowed to breathe spontaneously with 2.5 cm H2O continuous positive airway pressure ventilation (CPAP) and 40% oxygen. In the control group, the rabbits received the same surfactant therapy. During the study period, the rabbits remained ventilated with an inspiratory oxygen concentration (FiO(2)) of 100% for 4 hours. The ventilator flow was adjusted to maintain the PaCO2 between 4.0 and 6.0 kPa. Thereafter, positive-end expiratory pressure was decreased to 2.5 cm H2O and FiO(2) was gradually decreased to 40%. In the experimental group, FiO(2) was decreased to 40% in a stepwise fashion whereby the PaO2 could be maintained easily within the normal range. Extracorporeal flow rates during perfusion ranged from 20-35 ml/kg/min and were sufficient to keep the PaCO2 and pH within normal limits. After 4 hours, the rabbits could breathe spontaneously with CPAP and 40% oxygen, while normal blood gas values were maintained. All rabbits survived the experiment. In the control group, all rabbits experienced severe hypoxemia, despite FiO(2) of 100% oxygen and, during the course of weaning, all rabbits died because of hypoxia. In conclusion, the present study demonstrated that barovolutrauma due to mechanical ventilation, and oxygen toxicity due to high FiO(2), can be minimized in an animal model of acute respiratory failure by the combination of LFV-ECCO2R and surfactant therapy.

Refereed/Peer-reviewed

Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Methods: Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Results: Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Conclusions: Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468). © 2009 Kneyber et al.; licensee BioMed Central Ltd.

The long-term outcome of infants with severe respiratory distress syndrome can be improved by optimizing surfactant therapy and minimizing the risk for pulmonary barovolutrauma and oxygen toxicity. The authors hypothesized that this may be achieved with low frequency ventilation and extracorporeal CO2 removal (LFV-ECCO2R), in combination with intratracheal instillation of a large fluid volume with diluted surfactant. Lung lavaged rabbits were initially ventilated with continuous positive pressure ventilation. The rabbits were randomized to treatment with LFV-ECCO2R and surfactant (experimental group), or surfactant only (control group). In the experimental group, the rabbits were treated with a large volume (16 ml/kg) of diluted surfactant (6.25 mg/ml) at a dose of 100 mg/kg body weight. After surfactant therapy, the FiO(2) 100% was gradually decreased. During 4 hours, the extracorporeal bloodflow was adjusted to maintain the PaCO2 between 4.0-6.0 kPa. Thereafter, the rabbits were allowed to breathe spontaneously with 2.5 cm H2O continuous positive airway pressure ventilation (CPAP) and 40% oxygen. In the control group, the rabbits received the same surfactant therapy. During the study period, the rabbits remained ventilated with an inspiratory oxygen concentration (FiO(2)) of 100% for 4 hours. The ventilator flow was adjusted to maintain the PaCO2 between 4.0 and 6.0 kPa. Thereafter, positive-end expiratory pressure was decreased to 2.5 cm H2O and FiO(2) was gradually decreased to 40%. In the experimental group, FiO(2) was decreased to 40% in a stepwise fashion whereby the PaO2 could be maintained easily within the normal range. Extracorporeal flow rates during perfusion ranged from 20-35 ml/kg/min and were sufficient to keep the PaCO2 and pH within normal limits. After 4 hours, the rabbits could breathe spontaneously with CPAP and 40% oxygen, while normal blood gas values were maintained. All rabbits survived the experiment. In the control group, all rabbits experienced severe hypoxemia, despite FiO(2) of 100% oxygen and, during the course of weaning, all rabbits died because of hypoxia. In conclusion, the present study demonstrated that barovolutrauma due to mechanical ventilation, and oxygen toxicity due to high FiO(2), can be minimized in an animal model of acute respiratory failure by the combination of LFV-ECCO2R and surfactant therapy.