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  • 1.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Costantini, Mauro
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Echevarria, Camila
    Hosp Privado Comunidad Mar Del Plata, Dept Radiol, Buenos Aires, DF, Argentina..
    Pollioto, Sergio
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Abrego, Diego
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Doppler images of intra-pulmonary shunt within atelectasis in anesthetized children2016In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 8, article id 19Article in journal (Refereed)
    Abstract [en]

    Background: Doppler images of pulmonary vessels in pulmonary diseases associated with subpleural consolidations have been described. Color Doppler easily identifies such vessels within consolidations while spectral Doppler analysis allows the differentiation between pulmonary and bronchial arteries. Thus, Doppler helps in diagnosing the nature of consolidations. To our knowledge, Doppler analysis of pulmonary vessels within anesthesia-induced atelectasis has never been described before. The aim of this case series is to demonstrate the ability of lung ultrasound to detect the shunting of blood within atelectatic lung areas in anesthetized children.

    Findings: Three anesthetized and mechanically ventilated children were scanned in the supine position using a high-resolution linear probe of 6-12 MHz. Once subpleural consolidations were detected in the most dependent posterior lung regions, the probe was rotated such that its long axis followed the intercostal space. In this oblique position, color Doppler mapping was performed to detect blood flow within the consolidation. Thereafter, pulsed waved spectral Doppler was applied in the previously identified vessels during a short expiratory pause, which prevented interferences from respiratory motion. Different flow patterns were identified which corresponded to both, pulmonary and bronchial vessels. Finally, a lung recruitment maneuver was performed which leads to the complete resolution of the aforementioned consolidation thereby confirming the pathophysiological entity of anesthesia-induced atelectasis.

    Conclusions: Lung ultrasound is a non-invasive imaging tool that not only enables the diagnosis of anesthesia-induced atelectasis in pediatric patients but also analysis of shunting blood within this consolidation.

  • 2. Artigas, Antonio
    et al.
    Noël, Julie-Lyn
    Brochard, Laurent
    Busari, Jamiu O
    Dellweg, Dominic
    Ferrer, Miguel
    Geiseler, Jens
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nava, Stefano
    Navalesi, Paolo
    Orfanos, Stylianos
    Palange, Paolo
    Pelosi, Paolo
    Rohde, Gernot
    Schoenhofer, Bernd
    Vassilakopoulos, Theodoros
    Simonds, Anita K
    Defining a training framework for clinicians in respiratory critical care2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 3, p. 572-577Article in journal (Refereed)
  • 3.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Hosp Clin, Pulm Div Heart Inst InCor, Sao Paulo, Brazil..
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The "normal" ventilated airspaces suffer the most damaging effects of mechanical ventilation2017In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 43, no 7, p. 1057-1058Article in journal (Other academic)
  • 4.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergman, J. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy.
    Dussault, C.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    Amato, M. B. P.
    Univ Sao Paulo, Sch Med, Sao Paulo, Brazil..
    Montmerle-Borgdorff, S.
    Armed Forces Biomed Res Inst, Bretigny Sur Orge, France..
    First-Time Monitoring Of Simultaneous Effects Of Hypergravity On Heart And Lung By Electrical Impedance Tomography2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 5.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Santos, Arnoldo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lucchetta, L.
    Hosp San Matteo, Pavia, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Redistribution Of Regional Lung Perfusion During Mechanical Ventilation With An Open Lung Approach Impacts Pulmonary Vascular Mechanics2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A3751Article in journal (Other academic)
  • 6.
    Bellani, Giacomo
    et al.
    Univ Milano Bicocca, Sch Med & Surg, Monza, Italy.;San Gerardo Hosp, Dept Emergency & Intens Care, Monza, Italy..
    Laffey, John G.
    St Michaels Hosp, Dept Anesthesia & Crit Care Med, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;Univ Toronto, Dept Anesthesia, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Dept Physiol, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pham, Tai
    Grp Hosp Hop Univ Est Parisien, Hop Tenon, AP HP, Unite Reanimat Med Chirurgicale,Pole Thorax Voies, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, ECSTRA Team, UMR 1153,Inserm, Paris, France.;Univ Paris Est Creteil, UMR 915, INSERM, Creteil, France..
    Fan, Eddy
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Hlth Network, Dept Med, Toronto, ON, Canada.;Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.;Univ Toronto, Inst Hlth Policy Management & Evaluat, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Brochard, Laurent
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Esteban, Andres
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Hosp Univ Getafe, CIBER Enfermedades Respiratorias, Madrid, Spain..
    Gattinoni, Luciano
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    van Haren, Frank
    Canberra Hosp, Intens Care Unit, Canberra, ACT, Australia.;Australian Natl Univ, Canberra, ACT, Australia..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    McAuley, Daniel F.
    Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.;Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.;Royal Victoria Hosp, Reg Intens Care Unit, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland..
    Ranieri, Marco
    Policlin Umberto 1, SAPIENZA Univ ROMA, Dipartimento Anestesia & Rianimaz, Viale Policlin 155, I-00161 Rome, Italy..
    Rubenfeld, Gordon
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Sunnybrook Hlth Sci Ctr, Program Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada..
    Thompson, B. Taylor
    Harvard Univ, Sch Med, Div Pulm, Boston, MA USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Unit,Dept Med, Boston, MA USA..
    Wrigge, Hermann
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany..
    Slutsky, Arthur S.
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pesenti, Antonio
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries2016In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 315, no 8, p. 788-800Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of 29 144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95% CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95% CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5%(95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95% CI, 38.2-42.1), whereas 82.6%(95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95% CI, 31.4%-38.5%) for those with mild, 40.3%(95% CI, 37.4%-43.3%) for those with moderate, and 46.1%(95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS.

  • 7. Bellani, Giacomo
    et al.
    Laffey, John G
    Pham, Tài
    Madotto, Fabiana
    Fan, Eddy
    Brochard, Laurent
    Esteban, Andres
    Gattinoni, Luciano
    Bumbasirevic, Vesna
    Piquilloud, Lise
    van Haren, Frank
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    McAuley, Daniel F
    Bauer, Philippe R
    Arabi, Yaseen M
    Ranieri, Marco
    Antonelli, Massimo
    Rubenfeld, Gordon D
    Thompson, B Taylor
    Wrigge, Hermann
    Slutsky, Arthur S
    Pesenti, Antonio
    Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study.2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, no 1, p. 67-77Article in journal (Refereed)
    Abstract [en]

    Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.

    Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful.

    Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome.

    Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159–1.805]), but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mm Hg.

    Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg.

  • 8.
    Bergmann, Astrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Breitling, Christian
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kretzschmar, Moritz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kozian, Alf
    Hachenberg, Thomas
    Schilling, Thomas
    Data on the effects of remote ischemic preconditioning in the lungs after one-lung ventilation.2018In: Data in brief, ISSN 2352-3409, Vol. 21, p. 441-448Article in journal (Refereed)
    Abstract [en]

    This article contains data on experimental endpoints of a randomized controlled animal trial. Fourteen healthy piglets underwent mechanical ventilation including injurious one-lung ventilation (OLV), seven of them experienced four cycles of remote ischemic preconditioning (RIP) on one hind limb immediately before OLV, seven of them did not receive RIP and served as controls, in a randomized manner. The two major endpoints were (1) pulmonary damage assessed with the diffuse alveolar damage (DAD) score and (2) the inflammatory response assessed by cytokine concentrations in serum and in bronchoalveolar lavage fluids (BAL). The cytokine levels in the homogenized lung tissue samples are presented in the original article. Further interpretation and discussion of these data can be found in Bergmann et al. (in press).

  • 9.
    Bergmann, Astrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Schilling, Thomas
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ahlgren, Kerstin
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kretzschmar, Moritz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kozian, Alf
    Hachenberg, Thomas
    Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury.2018In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, article id S1569-9048(18)30231-3Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV.

    METHODS: Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score.

    RESULTS: Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP.

    CONCLUSIONS: OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.

  • 10.
    Bergquist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Jonasson, Sofia
    Hjoberg, Josephine
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hanrieder, Joerg
    Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma2014In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 14, p. 110-Article in journal (Refereed)
    Abstract [en]

    Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods: BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex T assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts. Results: Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex T analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation. Conclusion: Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.

  • 11.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L. V.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lucchetta, Luca
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Amato, Marcelo B. P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed)
    Abstract [en]

    Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

  • 12.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergman, Jakob S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo B. P.
    Avenel, Jacques
    Montmerle-Borgdorff, Stephanie
    First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity2015In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, no 2, p. 353-363Article in journal (Refereed)
    Abstract [en]

    Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+G(z)), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +G(z) accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5G(z). They performed this sequence three times, breathing AIR, 44.5 % O-2 or 100 % O-2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5G(z), compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (V-T) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O-2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional V-T measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O-2, EELV and V-T decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.

  • 13.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mechanical ventilation in itself can harm the lung and cause ventilator-induced lung injury (VILI), which can induce or aggravate acute respiratory distress syndrome (ARDS). Much debate remains over pivotal concepts regarding the pathophysiology of VILI, especially about the precise contribution, kinetics, and primary role of potential VILI mechanisms. Consequently, it remains largely unknown how best to design a well-timed and full-bodied mechanical ventilation strategy. Little is known also about small airways dysfunction in ARDS. Dynamic positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (18F-FDG) can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We studied the regional evolution of inflammation using dynamic PET/CT imaging of 18F-FDG in VILI and during different lung-protective mechanical ventilation strategies. By dynamic CT we investigated also the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction. Piglets were submitted to an experimental model of early ARDS combining repeated lung lavages and injurious mechanical ventilation. The animals were subsequently studied during sustained VILI, or submitted to distinct approaches of lung-protective mechanical ventilation: the one recommended by the ARDS Network (ARDSNet), or to one defined as open lung approach (OLA). The normally and poorly aerated regions - corresponding to intermediate gravitational zones - were the primary targets of the inflammatory process accompanying early VILI, which may be attributed to the small volume of the aerated lung that receives most of ventilation. The ARDSNet strategy did not attenuate global pulmonary inflammation during 27h and led to a concentration of inflammatory activity in the upper and poorly aerated lung regions. The OLA, in comparison with the ARDSNet approach, resulted in sustained and better gas exchange and lung mechanics. Moreover, the OLA strategy resulted in less global and regional inflammation. Dynamic CT data suggested that a significant amount of airway closure and related reabsorption atelectasis occurs in acute lung injury. Whether potential distal bronchioles injury (“bronchiolotrauma”) is a critical and decisive element in ventilator-associated lung injury is a matter for future studies.

    List of papers
    1. Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Open this publication in new window or tab >>Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
    Show others...
    2014 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

    National Category
    Medical and Health Sciences
    Research subject
    Clinical Physiology
    Identifiers
    urn:nbn:se:uu:diva-223348 (URN)10.1097/CCM.0000000000000161 (DOI)000332839700003 ()24448197 (PubMedID)
    Available from: 2014-04-17 Created: 2014-04-17 Last updated: 2017-12-05Bibliographically approved
    2. Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Open this publication in new window or tab >>Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-230045 (URN)
    Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2018-11-12Bibliographically approved
    3. Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    Open this publication in new window or tab >>Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-230046 (URN)
    Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2015-01-22Bibliographically approved
    4. Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
    Open this publication in new window or tab >>Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
    Show others...
    2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1464-1473Article in journal (Refereed) Published
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

    Keywords
    small airways dysfunction, absorption atelectasis, acute respiratory distress syndrome
    National Category
    Medical and Health Sciences Physiology
    Identifiers
    urn:nbn:se:uu:diva-213823 (URN)10.1152/japplphysiol.00763.2013 (DOI)000327398600007 ()
    Available from: 2014-01-05 Created: 2014-01-04 Last updated: 2018-01-11Bibliographically approved
  • 14.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L V
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury2014In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

  • 15.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eduardo, Costa LV
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Widström, Charles
    Maripuu, Enn
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Marcelo, Amato
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.Manuscript (preprint) (Other academic)
  • 16.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    The "normal" ventilated airspaces suffer the most damaging effects of mechanical ventilation.2017In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 43, no 7, p. 1057-1058Article in journal (Refereed)
  • 17.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Altering the mechanical scenario to decrease the driving pressure2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 342Article in journal (Refereed)
    Abstract [en]

    Ventilator settings resulting in decreased driving pressure (ΔP) are positively associated with survival. How to further foster the potential beneficial mediator effect of a reduced ΔP? One possibility is promoting the active modification of the lung's "mechanical scenario" by means of lung recruitment and positive end-expiratory pressure selection. By taking into account the individual distribution of the threshold-opening airway pressures to achieve maximal recruitment, a redistribution of the tidal volume from overdistended to newly recruited lung occurs. The resulting more homogeneous distribution of transpulmonary pressures may induce a relief of overdistension in the upper regions. The gain in lung compliance after a successful recruitment rescales the size of the functional lung, potentially allowing for a further reduction in ΔP.

  • 18.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Fac Med, Hosp Clin, Pulm Div,Heart Inst Incor, BR-05508 Sao Paulo, Brazil..
    Porra, L.
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Pellegrini, M.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Tannoia, A.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Derosa, S.
    Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, S.
    Univ Picardie Jules Verne, CHU Amiens, INSERM, UMR1105, Amiens, France.;Univ Picardie Jules Verne, CHU Amiens, Pediat Lung Funct Lab, Amiens, France..
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Bari, Dept Emergency & Organ Transplant, I-70121 Bari, Italy..
    Hedenstierna, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 7, p. 958-968Article in journal (Refereed)
    Abstract [en]

    BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.

  • 19.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Senturk, Mert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Open Lung in Lateral Decubitus With Differential Selective Positive End-Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. e404-e411Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: University animal research laboratory.

    SUBJECTS: Seven piglets.

    INTERVENTIONS: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum-recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% ± 15% vs 4% ± 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum-selective positive end-expiratory pressure-expiratory-CT (3.7 ± 1.2 vs 0.8 ± 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum-selective positive end-expiratory pressure-inspiratory-CT (2.8 ± 1.1 vs 0.6 ± 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049).

    CONCLUSIONS: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities.

  • 20.
    Brochard, Laurent
    et al.
    St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ten physiologic advances that improved treatment for ARDS2016In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 42, no 5, p. 814-816Article in journal (Other academic)
  • 21.
    Broche, L.
    et al.
    ESRF, Grenoble, France.;Univ Bari, Bari, Italy..
    Tannoia, A.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Derosa, S.
    Sindaco, A.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Porra, L.
    Univ Helsinki, Helsinki, Finland..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bravin, A.
    ESRF, Grenoble, France..
    Perchiazzi, G.
    Wexler, A. S.
    Univ Calif Davis, Davis, CA 95616 USA..
    Verbanck, S.
    UZ Brussel, Brussels, Belgium..
    Bates, J. H. T.
    Univ Vermont, Burlington, VT USA..
    Bayat, S.
    Univ Picardie Med Sch CHU Amiens, Amiens, France..
    Role Of Parenchymal Interdependence In The Short-Term Dynamics Of Recruitment/derecruitment In Injured Lung: A Modelling Study2015In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 191Article in journal (Other academic)
  • 22.
    Broche, Ludovic
    et al.
    Grenoble, France..
    Gaetano, Perchiazzi
    Univ Bari, Bari, Italy..
    Liisa, Porra
    Univ Helsinki, Helsinki, Finland..
    Angela, Tannoia
    Univ Bari, Bari, Italy..
    Mariangela, Pellegrini
    Univ Bari, Bari, Italy..
    Savino, Derosa
    Univ Bari, Bari, Italy..
    Alessandra, Sindaco
    Univ Bari, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Loic, Degrugilliers
    Univ Picardie Jules Verne, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Anthony, Wexler
    Univ Calif Davis, Davis, CA 95616 USA..
    Alberto, Bravin
    ESRF, Grenoble, France..
    Sylvia, Verbanck
    Univ Hosp UZ Brussel, Brussels, Belgium..
    Bradford, J. Smith
    Univ Vermont, Burlington, VT USA..
    Jason, H. T. Bates
    Univ Vermont, Burlington, VT USA..
    Sam, Bayat
    Univ Picardie Jules Verne, Amiens, France..
    Dynamic mechanical interactions between neighboring airspaces determine cyclic opening and closure in injured lung2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, p. 141-141Article in journal (Other academic)
  • 23.
    Broche, Ludovic
    et al.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.;Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Tannoia, Angela
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Derosa, Savino
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Sindaco, Alessandra
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Degrugilliers, Loic
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Wexler, Anthony S.
    Univ Calif Davis, Dept Mech Engn, Davis, CA 95616 USA.;Univ Calif Davis, Environm Qual Lab, Davis, CA 95616 USA..
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France..
    Verbanck, Sylvia
    Univ Hosp UZ Brussel, Div Resp, Brussels, Belgium..
    Smith, Bradford J.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bates, Jason H. T.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bayat, Sam
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 4, p. 687-694Article in journal (Refereed)
    Abstract [en]

    Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

  • 24.
    Dahl, Michael
    et al.
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Hayes, Chris
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Rasmussen, Bodil Steen
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Secher, Niels H.
    Univ Copenhagen, Dept Anesthesiol, Copenhagen Muscle Res Ctr, Rigshosp 2043, Blegdamsvej 9, DK-2100 Copenhagen, Denmark..
    Can a central blood volume deficit be detected by systolic pressure variation during spontaneous breathing?2016In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 16, article id 58Article in journal (Refereed)
    Abstract [en]

    Background: Whether during spontaneous breathing arterial pressure variations (APV) can detect a volume deficit is not established. We hypothesized that amplification of intra-thoracic pressure oscillations by breathing through resistors would enhance APV to allow identification of a reduced cardiac output (CO). This study tested that hypothesis in healthy volunteers exposed to central hypovolemia by head-up tilt. Methods: Thirteen healthy volunteers were exposed to central hypovolemia by 45 degrees head-up tilt while breathing through a facemask with 7.5 cmH(2)O inspiratory and/or expiratory resistors. A brachial arterial catheter was used to measure blood pressure and thus systolic pressure variation (SPV), pulse pressure variation and stroke volume variation. Pulse contour analysis determined stroke volume (SV) and CO and we evaluated whether APV could detect a 10 % decrease in CO. Results: During head-up tilt SV decreased form 91 (+/- 46) to 55 (+/- 24) mL (mean +/- SD) and CO from 5.8 (+/- 2.9) to 4.0 (+/- 1.8) L/min (p < 0.05), while heart rate increased (65 (+/- 11) to 75 (+/- 13) bpm; P < 0.05). Systolic pressure decreased from 127 (+/- 14) to 121 (+/- 13) mmHg during head-up tilt, while SPV tended to increase (from 21 (+/- 15)% to 30 (+/- 13) %). Yet during head-up tilt, a SPV >= 37 % predicted a decrease in CO >= 10 % with a sensitivity and specificity of 78 % and 100 %, respectively. Conclusion: In spontaneously breathing healthy volunteers combined inspiratory and expiratory resistors enhance SPV during head-up tilted induced central hypovolemia and allow identifying a 10 % reduction in CO. Applying inspiratory and expiratory resistors might detect a fluid deficit in spontaneously breathing patients.

  • 25.
    Derosa, Savino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tannoia, Angela
    Pellegrini, Mariangela
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Perchiazzi, Gaetano
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1464-1473Article in journal (Refereed)
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

  • 26.
    El-Dash, S. A.
    et al.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil.
    Costa, E. L. V.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil.;Hosp Sirio Libanes, Res & Educ Inst, Sao Paulo, Brazil..
    Tucci, M. R.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Ranzani, O. T.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Caramez, M. P.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Carvalho, C. R. R.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    Amato, M. B. P.
    Univ Sao Paulo, Hosp Clin, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil..
    There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 6, p. 767-779Article in journal (Refereed)
    Abstract [en]

    Background: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs.

    Methods: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH(2)O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2O every 4 min, and a semi-complete scan performed at the end of each PEEP step.

    Results: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (beta = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP.

    Conclusions: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions.

  • 27.
    Fardin, L.
    et al.
    European Synchrotron Radiat Facil, Grenoble, France..
    Broche, Ludovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Coll, J. -L
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, S.
    Grenoble Univ Hosp, Grenoble, France..
    Bravin, A.
    European Synchrotron Radiat Facil, Grenoble, France..
    Enhancing Lung Tumor Visibility Using In-Vivo Analyzer-Based X-Ray Phase Contrast Imaging In Mouse: A Feasibility Study2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A6514Article in journal (Other academic)
  • 28.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Romero, Carolina
    Consorci Hosp Gen Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar De Plata, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Canet, Jaume
    Hosp Badalona Germans Trias & Pujol, Anesthesiol & Crit Care, Badalona, Spain..
    Dosda, Rosa
    Hosp Clin Univ Valencia, Dept Radiol, Valencia, Spain..
    Valls, Paola
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Villena, Abigail
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Serralta, Ferran
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Jurado, Ana
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Carrizo, Juan
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Navarro, Jose
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Parrilla, Cristina
    Hosp Clin Univ Valencia, Dept Radiol, Valencia, Spain..
    Romero, Jose E.
    Univ Politecn Valencia, ITACA Inst, Grp IBIME, Valencia, Spain..
    Pozo, Natividad
    INCLIVA Clin Res Inst, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Villar, Jesus
    Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.;Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain..
    Belda, Francisco Javier
    Hosp Clin Univ Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    The accuracy of postoperative, non-invasive Air-Test to diagnose atelectasis in healthy patients after surgery: a prospective, diagnostic pilot study2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 5, article id e015560Article in journal (Refereed)
    Abstract [en]

    Objective To assess the diagnostic accuracy of peripheral capillary oxygen saturation (SpO(2)) while breathing room air for 5 min (the 'Air-Test') in detecting postoperative atelectasis. Design Prospective cohort study. Diagnostic accuracy was assessed by measuring the agreement between the index test and the reference standard CT scan images. Setting Postanaesthetic care unit in a tertiary hospital in Spain. Participants Three hundred and fifty patients from 12 January to 7 February 2015; 170 patients scheduled for surgery under general anaesthesia who were admitted into the postsurgical unit were included. Intervention The Air-Test was performed in conscious extubated patients after a 30 min stabilisation period during which they received supplemental oxygen therapy via a venturi mask. The Air-Test was defined as positive when SpO(2) was >= 96% and negative when SpO(2) was >= 97%. Arterial blood gases were measured in all patients at the end of the Air-Test. In the subsequent 25 min, the presence of atelectasis was evaluated by performing a CT scan in 59 randomly selected patients. Main outcome measures The primary study outcome was assessment of the accuracy of the Air-Test for detecting postoperative atelectasis compared with the reference standard. The secondary outcome was the incidence of positive Air-Test results. Results The Air-Test diagnosed postoperative atelectasis with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.82 to 0.98) with a sensitivity of 82.6% and a specificity of 87.8%. The presence of atelectasis was confirmed by CT scans in all patients (30/30) with positive and in 5 patients (17%) with negative Air-Test results. Based on the Air-Test, postoperative atelectasis was present in 36% of the patients (62 out of 170). Conclusion The Air-Test may represent an accurate, simple, inexpensive and non-invasive method for diagnosing postoperative atelectasis.

  • 29. Ferrando, Carlos
    et al.
    Soro, Marina
    Canet, Jaume
    Carmen Unzueta, Ma
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Librero, Julian
    Peiro, Salvador
    Llombart, Alicia
    Delgado, Carlos
    Leon, Irene
    Rovira, Lucas
    Ramasco, Fernando
    Granell, Manuel
    Aldecoa, Cesar
    Diaz, Oscar
    Balust, Jaume
    Garutti, Ignacio
    de la Matta, Manuel
    Pensado, Alberto
    Gonzalez, Rafael
    Eugenia Duran, Ma
    Gallego, Lucia
    Garcia del Valle, Santiago
    Redondo, Francisco J.
    Diaz, Pedro
    Pestana, David
    Rodriguez, Aurelio
    Aguirre, Javier
    Garcia, Jose M.
    Garcia, Javier
    Espinosa, Elena
    Charco, Pedro
    Navarro, Jose
    Rodriguez, Clara
    Tusman, Gerardo
    Javier Belda, Francisco
    Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial2015In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 16, article id 193Article in journal (Refereed)
    Abstract [en]

    Background: Postoperative pulmonary and non-pulmonary complications are common problems that increase morbidity and mortality in surgical patients, even though the incidence has decreased with the increased use of protective lung ventilation strategies. Previous trials have focused on standard strategies in the intraoperative or postoperative period, but without personalizing these strategies to suit the needs of each individual patient and without considering both these periods as a global perioperative lung-protective approach. The trial presented here aims at comparing postoperative complications when using an individualized ventilatory management strategy in the intraoperative and immediate postoperative periods with those when using a standard protective ventilation strategy in patients scheduled for major abdominal surgery. Methods: This is a comparative, prospective, multicenter, randomized, and controlled, four-arm trial that will include 1012 patients with an intermediate or high risk for postoperative pulmonary complications. The patients will be divided into four groups: (1) individualized perioperative group: intra-and postoperative individualized strategy; (2) intraoperative individualized strategy + postoperative continuous positive airway pressure (CPAP); (3) intraoperative standard ventilation + postoperative CPAP; (4) intra-and postoperative standard strategy (conventional strategy). The primary outcome is a composite analysis of postoperative complications. Discussion: The Individualized Perioperative Open-lung Ventilatory Strategy (iPROVE) is the first multicenter, randomized, and controlled trial to investigate whether an individualized perioperative approach prevents postoperative pulmonary complications.

  • 30.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Unzueta, Carmen
    Hosp Santa Creu & Sant Pau, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Canet, Jaume
    Hosp Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Librero, Julian
    Navarrabiomed Fdn Miguel Servet, Red Invest Serv Salud Enfermedades Cron REDISSEC, Pamplona, Spain..
    Peiro, Salvador
    Ctr Super Invest Salud Publ CSISP FISABIO, Red Invest Serv Salud Enfermedades Cron REDISSEC, Valencia, Spain..
    Pozo, Natividad
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Delgado, Carlos
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Ibanez, Maite
    Hosp Villajoyosa, Dept Anesthesiol, Villajoyosa, Spain..
    Aldecoa, Cesar
    Hosp Villajoyosa, Dept Anesthesiol & Crit Care, Villajoyosa, Spain..
    Garutti, Ignacio
    Hosp Gen Gregorio Maranon, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Pestana, David
    Hosp Ramon & Cajal, Anesthesiol & Crit Care, Madrid, Spain..
    Rodriguez, Aurelio
    Hosp Dr Negrin, Anesthesiol & Crit Care, Gran Canaria, Spain..
    Garcia del Valle, Santiago
    Hosp Fdn Alcorcon, Anesthesiol & Crit Care, Alcorcon, Spain..
    Diaz-Cambronero, Oscar
    Hosp La Fe, Anesthesiol & Crit Care, Valencia, Spain..
    Balust, Jaume
    Hosp Clin Barcelona, Anesthesiol & Crit Care, Barcelona, Spain..
    Javier Redondo, Francisco
    Hosp Gen, Anesthesiol & Crit Care, Ciudad Real, Spain..
    De La Matta, Manuel
    Hosp Virgen del Rocio, Anesthesiol & Crit Care, Seville, Spain..
    Gallego, Lucia
    Hosp Miguel Servet, Anesthesiol & Crit Care, Zaragoza, Spain..
    Granell, Manuel
    Hosp Gen Valencia, Anesthesiol & Crit Care, Valencia, Spain..
    Martinez, Pascual
    Hosp Albacete, Anesthesiol & Crit Care, Albacete, Spain..
    Perez, Ana
    Hosp Elche, Anesthesiol & Crit Care, Elche, Spain..
    Leal, Sonsoles
    Hosp Povisa, Anesthesiol & Crit Care, Vigo, Spain..
    Alday, Kike
    Hosp La Princesa, Anesthesiol & Crit Care, Madrid, Spain..
    Garcia, Pablo
    Hosp 12 Octubre, Anesthesiol & Crit Care, Madrid, Spain..
    Monedero, Pablo
    Clin Univ Navarra, Anesthesiol & Crit Care, Pamplona, Spain..
    Gonzalez, Rafael
    Hosp Univ Leon, Anesthesiol & Crit Care, Leon, Spain..
    Mazzinari, Guido
    Hosp Manises, Anesthesiol & Crit Care, Manises, Spain..
    Aguilar, Gerardo
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Villar, Jesus
    Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.;Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Gran Canaria, Spain.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada..
    Javier Belda, Francisco
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Rationale and study design for an individualised perioperative open-lung ventilatory strategy with a high versus conventional inspiratory oxygen fraction (iPROVE-O2) and its effects on surgical site infection: study protocol for a randomised controlled trial2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 7, article id e016765Article in journal (Refereed)
    Abstract [en]

    Introduction Surgical site infection (SSI) is a serious postoperative complication that increases morbidity and healthcare costs. SSIs tend to increase as the partial pressure of tissue oxygen decreases: previous trials have focused on trying to reduce them by comparing high versus conventional inspiratory oxygen fractions (FIO 2) in the perioperative period but did not use a protocolised ventilatory strategy. The open-lung ventilatory approach restores functional lung volume and improves gas exchange, and therefore it may increase the partial pressure of tissue oxygen for a given FIO 2. The trial presented here aims to compare the efficacy of high versus conventional FIO 2 in reducing the overall incidence of SSIs in patients by implementing a protocolised and individualised global approach to perioperative open-lung ventilation. Methods and analysis This is a comparative, prospective, multicentre, randomised and controlled two-arm trial that will include 756 patients scheduled for abdominal surgery. The patients will be randomised into two groups: (1) a high FIO 2 group (80% oxygen; FIO 2 of 0.80) and (2) a conventional FIO 2 group (30% oxygen; FIO 2 of 0.30). Each group will be assessed intra-and postoperatively. The primary outcome is the appearance of postoperative SSI complications. Secondary outcomes are the appearance of systemic and pulmonary complications. Ethics and dissemination The iPROVE-O2 trial has been approved by the Ethics Review Board at the reference centre (the Hospital Clinico Universitario in Valencia). Informed consent will be obtained from all patients before their participation. If the approach using high FIO 2 during individualised open-lung ventilation decreases SSIs, use of this method will become standard practice for patients scheduled for future abdominal surgery. Publication of the results is anticipated in early 2019.

  • 31.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Soro, Marina
    Unzueta, Carmen
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Canet, Jaume
    Hosp Univ Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Librero, Julian
    REDISSEC, Navarrabiomed Fdn Miguel Servet, Pamplona, Spain..
    Pozo, Natividad
    Hosp Clin Univ Valencia, INCLIVA Clin Res Inst, Valencia, Spain..
    Peiro, Salvador
    REDISSEC, CSISP FISABIO, Valencia, Spain..
    Llombart, Alicia
    Hosp Univ Politecn Fe, IISLAFE Clin Res Inst, Valencia, Spain..
    Leon, Irene
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain..
    India, Inmaculada
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Aldecoa, Cesar
    Hosp Univ Rio Hortega, Dept Anesthesiol & Crit Care, Valladolid, Spain..
    Diaz-Cambronero, Oscar
    Hosp Univ Politecn Fe, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Pestana, David
    Hosp Univ Ramon & Cajal, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Redondo, Francisco J.
    Hosp Gen Univ Ciudad Real, Dept Anesthesiol & Crit Care, Ciudad Real, Spain..
    Garutti, Ignacio
    Hosp Gen Univ Gregorio Maranon, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Balust, Jaume
    Hosp Clin & Prov Univ, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia, Jose I.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Hosp Univ Politecn Fe, Dept Anesthesiol & Crit Care, Valencia, Spain.;Hosp Fdn Alcorcon, Dept Anesthesiol & Crit Care, Alcorcon, Spain.;Hosp Univ Puerta Hierro, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Ibanez, Maite
    Hosp Marina Baixa Vila Joiosa, Dept Anesthesiol, Alicante, Spain..
    Granell, Manuel
    Hosp Gen Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Rodriguez, Aurelio
    Hosp Univ Doctor Negrin, Dept Anesthesiol, Las Palmas Gran Canaria, Spain..
    Gallego, Lucia
    Hosp Univ Miguel Servet, Dept Anesthesiol & Crit Care, Zaragoza, Spain..
    de la Matta, Manuel
    Hosp Univ Virgen Rocio, Dept Anesthesiol & Crit Care, Seville, Spain..
    Gonzalez, Rafael
    Hosp Univ Leon, Dept Anesthesiol, Leon, Spain..
    Brunelli, Andrea
    Hosp Univ Germans Tries & Pujol, Dept Anesthesiol & Crit Care, Badalona, Spain..
    Garcia, Javier
    Rovira, Lucas
    Hosp Manises, Dept Anesthesiol, Valencia, Spain..
    Barrios, Francisco
    Hosp Principe Asturias Madrid, Dept Anesthesiol & Crit Care, Madrid, Spain..
    Torres, Vicente
    Hosp Son Espases, Dept Anesthesiol & Crit Care, Palma de Mallorca, Spain..
    Hernandez, Samuel
    Hosp NS Candelaria, Dept Anesthesiol, Santa Cruz de Tenerife, Spain..
    Gracia, Estefania
    Gine, Marta
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia, Maria
    Hosp Univ Rio Hortega, Dept Anesthesiol & Crit Care, Valladolid, Spain..
    Garcia, Nuria
    Miguel, Lisset
    Sanchez, Sergio
    Pineiro, Patricia
    Pujol, Roger
    Hosp Clin & Prov Univ, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Garcia-del-Valle, Santiago
    Hosp Fdn Alcorcon, Dept Anesthesiol & Crit Care, Alcorcon, Spain..
    Valdivia, Jose
    Hosp Marina Baixa Vila Joiosa, Dept Anesthesiol, Alicante, Spain..
    Hernandez, Maria J.
    Hosp Gen Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Padron, Oto
    Hosp Univ Doctor Negrin, Dept Anesthesiol, Las Palmas Gran Canaria, Spain..
    Colas, Ana
    Hosp Univ Miguel Servet, Dept Anesthesiol & Crit Care, Zaragoza, Spain..
    Puig, Jaume
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain..
    Azparren, Gonzalo
    Hosp Univ Sant Pau, Dept Anesthesiol & Crit Care, Barcelona, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Villar, Jesus
    Hosp Univ Doctor Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain..
    Belda, Javier
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia 46010, Spain.;Univ Valencia, Dept Surg, Valencia, Spain..
    Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial2018In: The Lancet Respiratory Medicine, ISSN 2213-2600, E-ISSN 2213-2619, Vol. 6, no 3, p. 193-203Article in journal (Refereed)
    Abstract [en]

    Background The effects of individualised perioperative lung-protective ventilation (based on the open-lung approach [OLA]) on postoperative complications is unknown. We aimed to investigate the effects of intraoperative and postoperative ventilatory management in patients scheduled for abdominal surgery, compared with standard protective ventilation. Methods We did this prospective, multicentre, randomised controlled trial in 21 teaching hospitals in Spain. We enrolled patients who were aged 18 years or older, were scheduled to have abdominal surgery with an expected time of longer than 2 h, had intermediate-to-high-risk of developing postoperative pulmonary complications, and who had a body-mass index less than 35 kg/m(2). Patients were randomly assigned (1: 1: 1: 1) online to receive one of four lung-protective ventilation strategies using low tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after a lung recruitment manoeuvre] plus individualised postoperative continuous positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative ventilation plus postoperative CPAP), or STD-O-2 (standard intraoperative ventilation plus standard postoperative oxygen therapy). Patients were masked to treatment allocation. Investigators were not masked in the operating and postoperative rooms; after 24 h, data were given to a second investigator who was masked to allocations. The primary outcome was a composite of pulmonary and systemic complications during the first 7 postoperative days. We did the primary analysis using the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02158923. Findings Between Jan 2, 2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available for 967 patients, whom we included in the final analysis. Risk of pulmonary and systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of 241, relative risk 0.89 [95% CI 0.74-1.07; p=0.25]), OLA-CPAP (111 [47%] of 238, 0.91 [0.76-1.09; p=0.35]), or STD-CPAP groups (118 [48%] of 244, 0.95 [0.80-1.14; p=0.65]) when compared with patients in the STD-O-2 group (125 [51%] of 244). Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard perioperative ventilation groups because of hypoxaemia, and no patients from either of the OLA groups required rescue manoeuvres. Interpretation In patients who have major abdominal surgery, the different perioperative open lung approaches tested in this study did not reduce the risk of postoperative complications when compared with standard lung-protective mechanical ventilation.

  • 32. Ferrando, Carlos
    et al.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gutierrez, Andrea
    Tusman, Gerardo
    Carbonell, Jose
    Garcia, Marisa
    Piqueras, Laura
    Compan, Desamparados
    Flores, Susanie
    Soro, Marina
    Llombart, Alicia
    Javier Belda, Francisco
    Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, article id 9Article in journal (Refereed)
    Abstract [en]

    Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

  • 33.
    Ferrando, Carlos
    et al.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, GIBER Enfermedades Resp, Madrid, Spain.
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Buenos Aires, Argentina..
    Leon, Irene
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Romero, Esther
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gracia, Estefania
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Mugarra, Ana
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Arocas, Blanca
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Pozo, Natividad
    Hosp Clin Univ, INCLIVA Clin Res Inst, Valencia, Spain..
    Soro, Marina
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Belda, Francisco J.
    Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177399Article in journal (Refereed)
    Abstract [en]

    Background: Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia.

    Methods: Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml.kg(-1)) and standard PEEP of 5 cmH(2)O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography.

    Results: OL-PEEP was found at 8 +/- 2 cmH(2)O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035).

    Conclusions: Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery.