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  • 1.
    Akca, Ozan
    et al.
    Univ Louisville, Dept Anesthesiol & Perioperat Med, Neurosci ICU, Louisville, KY 40292 USA..
    Ball, Lorenzo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Belda, F. Javier
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Biro, Peter
    Univ Hosp Zurich, Inst Anesthesiol, Zurich, Switzerland..
    Cortegiani, Andrea
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Eden, Arieh
    Lady Davis Carmel Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Haifa, Israel..
    Ferrando, Carlos
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gattinoni, Luciano
    Gottingen Univ, Dept Anesthesiol Emergency & Intens Care Med, Gottingen, Germany..
    Goldik, Zeev
    Gregoretti, Cesare
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anaesthesiol & Intens Care Med, Magdeburg, Germany..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hopf, Harriet W.
    Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA..
    Hunt, Thomas K.
    Univ Calif San Francisco, Div Gen Surg, San Francisco, CA 94143 USA..
    Pelosi, Paolo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Qadan, Motaz
    Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA..
    Sessler, Daniel I.
    Cleveland Clin, Inst Anesthesiol, Dept Outcomes Res, Cleveland, OH 44106 USA..
    Soro, Marina
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Sentürk, Mert
    Istanbul Univ, Istanbul Sch Med, Dept Anaesthesiol & Reanimat, Istanbul, Turkey..
    WHO Needs High FIO2?2017In: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, no 4, p. 181-192Article in journal (Refereed)
    Abstract [en]

    World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations

  • 2. Antonelli, Massimo
    et al.
    Azoulay, Elie
    Bonten, Marc
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    De Backer, Daniel
    Lemaire, François
    Gerlach, Herwig
    Groeneveld, Johan
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Macrae, Duncan
    Mancebo, Jordi
    Maggiore, Salvatore M
    Mebazaa, Alexandre
    Metnitz, Philipp
    Pugin, Jerme
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine, 2007. II. Haemodynamics, pneumonia, infections and sepsis, invasive and non-invasive mechanical ventilation, acute respiratory distress syndrome2008In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 34, no 3, p. 405-422Article, review/survey (Refereed)
  • 3. Antonelli, Massimo
    et al.
    Azoulay, Elie
    Bonten, Marc
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    De Backer, Daniel
    Lemaire, François
    Gerlach, Herwig
    Groeneveld, Johan
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Macrae, Duncan
    Mancebo, Jordi
    Maggiore, Salvatore M
    Mebazaa, Alexandre
    Metnitz, Philipp
    Pugin, Jerôme
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine, 2007. I. Experimental studies. Clinical studies: brain injury and neurology, renal failure and endocrinology2008In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 34, no 2, p. 229-242Article, review/survey (Refereed)
  • 4. Antonelli, Massimo
    et al.
    Azoulay, Elie
    Bonten, Marc
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    De Backer, Daniel
    Lemaire, François
    Gerlach, Herwig
    Groeneveld, Johan
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Macrae, Duncan
    Mancebo, Jordi
    Maggiore, Salvatore
    Mebazaa, Alexandre
    Metnitz, Philipp
    Pugin, Jerôme
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine, 2007. III. Ethics and legislation, health services research, pharmacology and toxicology, nutrition and paediatrics2008In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 34, no 4, p. 598-609Article in journal (Refereed)
  • 5. Antonelli, Massimo
    et al.
    Bonten, Marc
    Cecconi, Maurizio
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J. R.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Maggiore, Salvatore M.
    Mancebo, Jordi
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-Francois
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2012: III. Noninvasive ventilation, monitoring and patient-ventilator interactions, acute respiratory distress syndrome, sedation, paediatrics and miscellanea2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 4, p. 543-557Article, review/survey (Refereed)
  • 6. Antonelli, Massimo
    et al.
    Bonten, Marc
    Cecconi, Maurizio
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J Randall
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Maggiore, Salvatore M
    Mancebo, Jordi
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-François
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 2, p. 232-246Article, review/survey (Refereed)
  • 7. Antonelli, Massimo
    et al.
    Bonten, Marc
    Cecconi, Maurizio
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J Randall
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Maggiore, Salvatore M
    Mancebo, Jordi
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-François
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2012. II: Pneumonia and infection, sepsis, coagulation, hemodynamics, cardiovascular and microcirculation, critical care organization, imaging, ethics and legal issues2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 3, p. 345-364Article in journal (Refereed)
  • 8. Antonelli, Massimo
    et al.
    Bonten, Marc
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J. Randall
    De Backer, Daniel
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Mancebo, Jordi
    Maggiore, Salvatore M.
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-Francois
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea2012In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, no 4, p. 542-556Article, review/survey (Refereed)
  • 9. Antonelli, Massimo
    et al.
    Bonten, Marc
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J Randall
    de Backer, Daniel
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Mancebo, Jordi
    Maggiore, Salvatore M
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-François
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2011: I. Nephrology, epidemiology, nutrition and therapeutics, neurology, ethical and legal issues, experimentals2012In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, no 2, p. 192-209Article, review/survey (Refereed)
  • 10. Appelberg, Jonas
    et al.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Pavlenko, Tatjana
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung aeration during sleep in patients with obstructive sleep apnoea2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies have indicated that patients with obstructive sleep apnoea (OSA) have altered ventilation and lung volumes awake and the results suggest that this may be a determinant of severity of desaturations during sleep. However, little is known about regional lung aeration during sleep in patients with OSA. METHODS: Twelve patients with OSA were included in the study. Computed tomography was used to study regional lung aeration during wakefulness and sleep. Lung aeration was calculated in ml gas/g lung tissue in four different regions of interest (ROI(1-4)), along the border of the lung from ventral to dorsal. RESULTS: Lung aeration in the dorsal (dependent) lung region (ROI(4)) was lower during sleep compared to wakefulness 0.78 +/- 0.19 versus 0.88 +/- 0.19 (mean +/- SD) ml gas/g lung tissue (P = 0.005). Associations were found between awake expiratory reserve volume and change in lung aeration from wakefulness to sleep in ROI(4) (r = -0.69; P = 0.012). In addition, the change in lung aeration in the dorsal region correlated to sleep time (r = 0.69; P = 0.014) but not to time in supine position. The difference in lung aeration between inspiration and expiration (i.e. ventilation), was larger in the ventral lung region when expressed as ml gas per g lung tissue. In two patients it was noted that, during on-going obstructive apnoea, lung aeration tended to be increased rather than decreased. CONCLUSIONS: Aeration in the dorsal lung region is reduced during sleep in patients with OSA. The decrease is related to lung volume awake and to sleep time.

  • 11.
    Appelberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Pavlenko, Tatjana
    Bergman, Henrik
    Rothen, Hans Ulrich
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung aeration during sleep2007In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 131, no 1, p. 122-129Article in journal (Refereed)
    Abstract [en]

    Background: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. Methods: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. Results: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 ± 0.34 mL (± SD) of gas per gram of lung tissue during wakefulness to 1.04 ± 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 ± 0.77 to 3.73 ± 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R2 = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). Conclusions: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

  • 12.
    Batista Borges, João
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
    Amato, Marcelo B P
    Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (InCor), University of São Paulo, São Paulo, Brazil.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    The Increasing Call for Protective Ventilation During Anesthesia2017In: JAMA Surgery, ISSN 2168-6254, E-ISSN 2168-6262, Vol. 152, no 9, p. 893-894Article in journal (Other academic)
  • 13.
    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)
  • 14.
    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)
  • 15.
    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)
  • 16.
    Baumgardner, James E.
    et al.
    Oscillogy LLC, Folsom, PA USA..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ventilation/perfusion distributions revisited2016In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 29, no 1, p. 2-7Article, review/survey (Refereed)
    Abstract [en]

    Purpose of reviewA major cause of hypoxemia in anesthesia is ventilation-perfusion (V-A/Q) mismatch. With more advanced surgery and an aging population, monitoring of V-A/Q is of increasing importance.Recent findingsThe classic multiple inert gas elimination technique has been simplified with a new approach based on mass spectrometry. V-A/Q distributions can also be measured, at the bedside, by varying inspired oxygen concentration. MRI, 3-dimensional single photon emission computed tomography, positron emission tomography, and electrical impedance tomography enable imaging of perfusion and ventilation, and in some of the techniques also the distribution of inflammation. One-lung ventilation with thoracoscopy and capnothorax require careful monitoring of V-A/Q, made possible bedside by electrical impedance tomography. Carbon dioxide, but not air, for pneumoperitoneum enhances shift of perfusion to ventilated regions. Ventilatory support during cardiopulmonary resuscitation causes less V-A/Q mismatch when inspired oxygen concentrations are lower. Mechanisms of redistribution of lung blood flow by inhaled nitric oxide include endothelin-mediated vasoconstriction in collapsed lung regions.SummaryMethods are continuously developing to simplify measurement of V-A/Q and also to relate V-A/Q to inflammation. The recording of V-A/Q has helped to explain important aspects of gas exchange in thoracic anesthesiology and in intensive care medicine.

  • 17. Bense, Laszlo
    et al.
    Eklund, Gunnar
    Jorulf, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Farkas, Arpad
    Balashazy, Imre
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Krebsz, Adam
    Gergely Madas, Balazs
    Eden Strindberg, Jerker
    Right main bronchus perforation detected by 3D-image2011In: BMJ case reports, ISSN 1757-790XArticle in journal (Refereed)
    Abstract [en]

    A male metal worker, who has never smoked, contracted debilitating dyspnoea in 2003 which then deteriorated until 2007. Spirometry and chest x-rays provided no diagnosis. A 3D-image of the airways was reconstructed from a high-resolution CT (HRCT) in 2007, showing peribronchial air on the right side, mostly along the presegmental airways. After digital subtraction of the image of the peribronchial air, a hole on the cranial side of the right main bronchus was detected. The perforation could be identified at the re-examination of HRCTs in 2007 and 2009, but not in 2010 when it had possibly healed. The occupational exposure of the patient to evaporating chemicals might have contributed to the perforation and hampered its healing. A 3D HRCT reconstruction should be considered to detect bronchial anomalies, including wall-perforation, when unexplained dyspnoea or other chest symptoms call for extended investigation.

  • 18.
    Bergquist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Hästbacka, Johanna
    Lindholm, Catharina
    Martijn, Cecile
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Rylander, Christian
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Fredén, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Glucocorticoid receptor expression and binding capacity in patients with burn injury2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 2, p. 213-221Article in journal (Refereed)
    Abstract [en]

    Background

    Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.

    Methods

    Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry.

    Results

    GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (< 0.05).

    Conclusions

    GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells.

  • 19.
    Bergquist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Jirholt, Pernilla
    Nurkkala, Merja
    Rylander, Christian
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lindholm, Catharina
    Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock2014In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 69, no 2, p. 113-122Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome.

    METHODS: Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied.

    RESULTS: Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration.

    CONCLUSION: The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.

  • 20.
    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.

  • 21.
    Bergquist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lindholm, Catharina
    Strinnholm, Morten
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Rylander, Christian
    Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock2015In: Intensive care medicine experimental, ISSN 2197-425X, Vol. 3, no 1, article id 23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may be explained by decreased expression or function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in patients during and after sepsis.

    METHODS: In this prospective, non-interventional clinical study, peripheral blood and clinical data were collected from 20 adult patients at five timepoints during sepsis and 5-13 months after recovery. GR expression and binding capacity were assessed by flow cytometry.

    RESULTS: GR expression was higher in T lymphocytes from patients with septic shock compared to healthy subjects (p = 0.01). While there was no difference in GR expression between GC-treated and non-treated patients, GR binding capacity was lower in GC-treated patients at admission compared to healthy subjects (p ≤ 0.03). After the acute inflammation inflammatory phase, GR binding capacity was still lower in neutrophils of GC-treated patients, compared to healthy subjects (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils was inversely correlated with noradrenaline dose and lactate (p ≤ 0.03).

    CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes during septic shock regardless of GC treatment, while GR binding capacity is decreased in neutrophils in GC-treated patients. As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.

  • 22.
    Bergquist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nurkkala, Merja
    Rylander, Christian
    Kristiansson, Erik
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lindholm, Catharina
    Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis2013In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 67, no 6, p. 574-583Article in journal (Refereed)
    Abstract [en]

    Introduction: Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated. Methods: Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed. Results: GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h). Conclusion: Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock. 

  • 23.
    Bluth, T.
    et al.
    Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, Pulmonary Engn Grp, Dresden, Germany..
    Teichmann, R.
    Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, Pulmonary Engn Grp, Dresden, Germany..
    Kiss, T.
    Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, Pulmonary Engn Grp, Dresden, Germany..
    Bobek, I.
    Semmelweis Egyet, Aneszteziol & Intenz Terapias Klin, Budapest, Hungary..
    Canet, J.
    Hosp Badalona Germans Trias & Pujol, Dept Anesthesiol, Badalona, Spain..
    Cinnella, G.
    Univ Foggia, Dept Anesthesiol & Intens Care Med, Foggia, Italy..
    De Baerdemaeker, L.
    Univ Ghent, Dept Anesthesiol, Ghent, Belgium..
    Gregoretti, C.
    Policlin P Giaccone, Dept Biopathol & Med Biotechnol, Palermo, Italy..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hemmes, S. N.
    Univ Amsterdam, Acad Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, LEICA, Amsterdam, Netherlands..
    Hiesmayr, M.
    Med Univ Vienna, Div Cardiac Surg, Vienna, Austria.;Med Univ Vienna, Div Thorac Dis, Vienna, Austria.;Med Univ Vienna, Div Vasc Surg, Vienna, Austria.;Med Univ Vienna, Dept Anesthesia Intens Care & Pain Med, Vienna, Austria..
    Hollmann, M. W.
    Univ Amsterdam, Acad Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, LEICA, Amsterdam, Netherlands..
    Jaber, S.
    St Eloi Univ Hosp, Dept Crit Care Med & Anesthesiol SAR B, Montpellier, France..
    Laffey, J. G.
    St Michaels Hosp, Dept Anesthesia, Crit Care Med Program, Toronto, ON, Canada.;Univ Toronto, Dept Anesthesia, Toronto, ON, Canada.;Univ Toronto, Dept Physiol, Toronto, ON, Canada.;Univ Toronto, Interdepartmental Div Crit Care Med, Toronto, ON, Canada..
    Licker, M. J.
    Univ Hosp Geneva, Dept Anesthesiol Pharmacol & Intens Care, Geneva, Switzerland..
    Markstaller, K.
    Med Univ Vienna, Dept Anesthesia Intens Care & Pain Med, Vienna, Austria..
    Matot, I.
    Tel Aviv Univ, Sackler Sch Med, Tel Aviv Med Ctr, Dept Anesthesia & Crit Care, Tel Aviv, Israel..
    Mueller, G.
    Tech Univ Dresden, Ctr Evidence Based Healthcare, Univ Hosp, Dresden, Germany.;Tech Univ Dresden, Med Fac Carl Gustav Carus, Dresden, Germany..
    Mills, G. H.
    Sheffield Teaching Hosp, OSCCA, Sheffield, S Yorkshire, England.;Univ Sheffield, Sheffield, S Yorkshire, England..
    Mulier, J. P.
    AZ Sint Jan Brugge Oostende AV, Dept Anesthesiol, Brugge, Belgium..
    Putensen, C.
    Univ Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany..
    Rossaint, R.
    Univ Aachen, Dept Anesthesiol, Aachen, Germany..
    Schmitt, J.
    Tech Univ Dresden, Ctr Evidence Based Healthcare, Univ Hosp, Dresden, Germany.;Tech Univ Dresden, Med Fac Carl Gustav Carus, Dresden, Germany..
    Senturk, M.
    Istanbul Univ, Istanbul Fac Med, Dept Anesthesiol & Intens Care Med, Istanbul, Turkey..
    Serpa Neto, A.
    Fac Med ABC, Hosp Israelita Albert Einstein, Dept Crit Care Med, Sao Paulo, Brazil.;Fac Med ABC, Program Postgrad Res & Innovat, Sao Paulo, Brazil..
    Severgnini, P.
    Univ Insubria, Dept Biotechnol & Sci Life, ASST Sette Laghi, Osped Cricolo & Fdn Macchi, Varese, Italy..
    Sprung, J.
    Mayo Clin, Dept Anesthesiol, Rochester, MN USA..
    Melo, M. F. Vidal
    Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA..
    Wrigge, H.
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Leipzig, Germany..
    Schultz, M. J.
    Univ Amsterdam, Acad Med Ctr, Dept Anesthesiol, Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, LEICA, Amsterdam, Netherlands..
    Pelosi, P.
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    de Abreu, M. Gama
    Univ Hosp Carl Gustav Carus, Dept Anesthesiol & Intens Care Med, Pulmonary Engn Grp, Dresden, Germany..
    Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial2017In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 18, article id 202Article in journal (Refereed)
    Abstract [en]

    Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients.

    Methods/design: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index >= 35 kg/m(2) scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH(2)O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH(2)O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint.

    Discussion: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs.

  • 24.
    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.

  • 25.
    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.

  • 26.
    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.

  • 27.
    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)
  • 28.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    The Rediscovery of Galligas REPLY2011In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 52, no 6, p. 1004-1004Article in journal (Refereed)
  • 29.
    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.

  • 30.
    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.

  • 31.
    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.

  • 32.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Costa, Eduardo L. V.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Comment on Borges et al. "Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse" Reply2012In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 12, p. 2128-2128Article in journal (Refereed)
  • 33.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    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.
    Bohm, Stephan H
    Tusman, Gerardo
    Melo, Alexandre
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Park, Marcelo
    Costa, Eduardo L V
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Regional Lung Perfusion estimated by Electrical Impedance Tomography in a piglet model of lung collapse2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 1, p. 225-236Article in journal (Refereed)
    Abstract [en]

    The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology which provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT) based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6 %, with a standard deviation of 2.9 %. This method outperformed the estimates of lung perfusion based on impedance-pulsatility. In conclusion, we describe a novel method based on Electrical Impedance Tomography for estimating regional lung perfusion at the bedside. In both, healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this paper has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

  • 34.
    Brander, Lukas
    et al.
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;Cantonal Hosp Lucerne, Dept Intens Care Med, CH-6000 Luzern, Switzerland..
    Moerer, Onnen
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;Univ Gottingen, Dept Anaesthesiol Emergency & Crit Care Med, Gottingen, Germany..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Beck, Jennifer
    Univ Toronto, Dept Pediat, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.;Ryerson Univ, Inst Biomed Engn & Sci Technol, Toronto, ON, Canada.;St Michaels Hosp, Toronto, ON, Canada..
    Takala, Jukka
    Univ Hosp Bern, Inselspital, Dept Intens Care Med, Bern, Switzerland.;Univ Bern, CH-3012 Bern, Switzerland..
    Slutsky, Arthur S.
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada..
    Sinderby, Christer
    Univ Toronto, Dept Crit Care Med, Interdept Div Crit Care Med, St Michaels Hosp, Toronto, ON, Canada.;St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.;Ryerson Univ, Inst Biomed Engn & Sci Technol, Toronto, ON, Canada.;St Michaels Hosp, Toronto, ON, Canada..
    Neural control of ventilation prevents both over-distension and de-recruitment of experimentally injured lungs2017In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 237, p. 57-67Article in journal (Refereed)
    Abstract [en]

    Background: Endogenous pulmonary reflexes may protect the lungs during mechanical ventilation. We aimed to assess integration of continuous neurally adjusted ventilatory assist (cNAVA), delivering assist in proportion to diaphragm's electrical activity during inspiration and expiration, and Hering-Breuer inflation and deflation reflexes on lung recruitment, distension, and aeration before and after acute lung injury (ALI).

    Methods: In 7 anesthetised rabbits with bilateral pneumothoraces, we identified adequate cNAVA level (cNAVA(AL)) at the plateau in peak ventilator pressure during titration procedures before (healthy lungs with endotracheal tube, [HLETT]) and after ALI (endotracheal tube [ALI(ETT)] and during non-invasive ventilation [ALI(NIV)]). Following titration, cNAVA(AL) was maintained for 5 min. In 2 rabbits, procedures were repeated after vagotomy (ALI(ETT+VAG)). In 3 rabbits delivery of assist was temporarily modulated to provide assist on inspiration only. Computed tomography was performed before intubation, before ALI, during cNAVA titration, and after maintenance at cNAVA(AL).

    Results: During ALI(ETT) and ALI(NIV), normally aerated lung-regions doubled and poorly aerated lung-regions decreased to less than a third (p < 0.05) compared to HLETT; no over-distension was observed. Tidal volumes were <5 ml/kg throughout. Removing assist during expiration resulted in lung de-recruitment during ALI(ETT) but not during ALI(NIV). During ALI(ETT+VAG) the expiratory portion of EAdi disappeared, resulting in cyclic lung collapse and recruitment.

    Conclusions: When using cNAVA in ALI, vagally mediated reflexes regulated lung recruitment preventing both lung over-distension and atelectasis. During non-invasive cNAVA the upper airway muscles play a role in preventing atelectasis. Future studies should be performed to compare these findings with conventional lung-protective approaches.

  • 35.
    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)
  • 36.
    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)
  • 37.
    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)
  • 38.
    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.

  • 39.
    Chen, Luni
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Liu, Peng
    Gao, He
    Sun, Bing
    Chao, Desheng
    Wang, Fei
    Zhu, Yuanjue
    Hedenstierna, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wang, Chen G
    Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome:: A Rescue Trial in Beijing2004In: Clinical Infectious Diseases, Vol. 39, p. 1531-1535Article in journal (Refereed)
  • 40.
    Da, Jiping
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Chen, Luni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nitric oxied up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis2007In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 1, p. 26-32Article in journal (Refereed)
    Abstract [en]

    Objectives: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: A total of 45 anesthetized and mechanically ventilated pigs. Interventions: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Measurements and Main Results: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-κB and tumor necrosis factor-a. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. Conclusion: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

  • 41.
    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.

  • 42.
    Edmark, Lennart
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Auner, U
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Post-operative atelectasis: a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 6, p. 681-688Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen concentration during recovery would reduce post-operative atelectasis.

    METHODS: Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FI O2 ) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2 O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6-8 cmH2 O in both groups. Before removal of the LMA, FI O2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post-operatively.

    RESULTS: In one patient in the group given an FI O2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0-16.9 cm(2) (median and range), and 6.8, 0-27.5 cm(2) in the groups given FI O2 0.3 or FI O2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post-hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively).

    CONCLUSION: Inducing anaesthesia with CPAP/PEEP and FI O2 1.0 and deliberately reducing FI O2 during recovery before removal of the LMA did not reduce post-operative atelectasis compared with FI O2 1.0 before removal of the LMA.

  • 43.
    Edmark, Lennart
    et al.
    Departments of Anaesthesiology and Intensive Care, Central Hospital, Västerås, Sweden.
    Auner, Udo
    Enlund, Mats
    Departments of Anaesthesiology and Intensive Care, Central Hospital, Västerås, Sweden.
    Östberg, Erland
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 1, p. 75-81Article in journal (Refereed)
    Abstract [en]

    Background:

    Atelectasis is a common consequence of pre-oxygenation with 100% oxygen during induction of anaesthesia. Lowering the oxygen level during pre-oxygenation reduces atelectasis. Whether this effect is maintained during anaesthesia is unknown.

    Methods:

    During and after pre-oxygenation and induction of anaesthesia with 60%, 80% or 100% oxygen concentration, followed by anaesthesia with mechanical ventilation with 40% oxygen in nitrogen and positive end-expiratory pressure of 3 cmH2O, we used repeated computed tomography (CT) to investigate the early (0–14 min) vs. the later time course (14–45 min) of atelectasis formation.

    Results:

    In the early time course, atelectasis was studied awake, 4, 7 and 14 min after start of pre-oxygenation with 60%, 80% or 100% oxygen concentration. The differences in the area of atelectasis formation between awake and 7 min and between 7 and 14 min were significant, irrespective of oxygen concentration (P<0.05). During the late time course, studied after pre-oxygenation with 80% oxygen, the differences in the area of atelectasis formation between awake and 14 min, between 14 and 21 min, between 21 and 28 min and finally between 21 and 45 min were all significant (P<0.05).

    Conclusion:

    Formation of atelectasis after pre-oxygenation and induction of anaesthesia is oxygen and time dependent. The benefit of using 80% oxygen during induction of anaesthesia in order to reduce atelectasis diminished gradually with time.

  • 44.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Hallén, Jan
    Lassinantti-Olowsson, Lena
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    A ventilation strategy during general anaesthesia to reduce postoperative atelectasis2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 242-250Article in journal (Refereed)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy, without recruitment manoeuvres, using a combination of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and a reduced end-expiratory oxygen fraction (FETO2) before ending mask ventilation with CPAP after extubation would reduce the area of postoperative atelectasis.

    Methods:

    Thirty patients were randomized into three groups. During induction and emergence, inspiratory oxygen fractions (FIO2) were 1.0 in the control group and 1.0 or 0.8 in the intervention groups. No CPAP/PEEP was used in the control group, whereas CPAP/PEEP of 6 cmH2O was used in the intervention groups. After extubation, FIO2 was set to 0.30 in the intervention groups and CPAP was applied, aiming at FETO2 < 0.30. Atelectasis was studied by computed tomography 25 min postoperatively.

    Results:

    The median area of atelectasis was 5.2 cm(2) (range 1.6-12.2 cm(2)) and 8.5 cm(2) (3-23.1 cm(2)) in the groups given FIO2 1.0 with or without CPAP/PEEP, respectively. After correction for body mass index the difference between medians (2.9 cm(2)) was statistically significant (confidence interval 0.2-7.6 cm(2), p = 0.04). In the group given FIO2 0.8, in which seven patients were ex- or current smokers, the median area of atelectasis was 8.2 cm(2) (1.8-14.7 cm(2)).

    Conclusion:

    Compared with conventional ventilation, after correction for obesity, this ventilation strategy reduced the area of postoperative atelectasis in one of the intervention groups but not in the other group, which included a higher proportion of smokers.

  • 45.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. 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.
    Atelectasis after anaesthesia: a randomised trial of positive airway pressure and low oxygen2013Article in journal (Other academic)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen fraction (FETO2) before extubation would reduce postoperative atelectasis.

    Methods:

    Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fractions (FIO2) were 1.0, and depending on weight, CPAP 6–8 cm H2O was applied in both groups via face mask. During maintenance of anaesthesia, a laryngeal mask airway was used, and depending on weight, PEEP was 6–8 cm H2O in both groups. Before extubation, FIO2 was set to 0.3 in the intervention groups and 1.0 in the control group. Atelectasis was studied by computed tomography approximately 13 min postoperatively.

    Results:

    The area of atelectasis was 5.5, 0–16.9 cm2 (median and range), and 6.8, 0–27.5 cm2 in the groups given FIO2 0.3 or FIO2 1.0 before extubation, a difference that was not statistically significant.

    Conclusion:

    Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 before extubation did not reduce postoperative atelectasis compared with FIO2 1.0 before extubation.

  • 46.
    Edmark, Lennart
    et al.
    Vastmanland Hosp Vasteras, Dept Anesthesia & Intens Care, Vasteras, Sweden..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Pro-con debate on preoxygenation: Cons: We shall moderate the inspired oxygen concentration or avoid the fall in the resting lung volume when inducing anesthesia2016In: Trends in Anaesthesia and Critical Care, ISSN 2210-8440, E-ISSN 2210-8467, Vol. 10, p. 42-44Article in journal (Other academic)
  • 47.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kostova-Aherdan, Kamelia
    Enlund, Mats
    Department of Anesthesiology and Intensive Care, Central Hospital, Västerås, Sweden.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Optimal Oxygen Concentration during Induction of General Anesthesia2003In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 98, no 1, p. 28-33Article in journal (Other academic)
    Abstract [en]

    BACKGROUND:

    The use of 100% oxygen during induction of anesthesia may produce atelectasis. The authors investigated how different oxygen concentrations affect the formation of atelectasis and the fall in arterial oxygen saturation during apnea.

    METHODS:

    Thirty-six healthy, nonsmoking women were randomized to breathe 100, 80, or 60% oxygen for 5 min during the induction of general anesthesia. Ventilation was then withheld until the oxygen saturation, assessed by pulse oximetry, decreased to 90%. Atelectasis formation was studied with computed tomography.

    RESULTS:

    Atelectasis in a transverse scan near the diaphragm after induction of anesthesia and apnea was 9.8 +/- 5.2 cm2 (5.6 +/- 3.4% of the total lung area; mean +/- SD), 1.3 +/- 1.2 cm2 (0.6 +/- 0.7%), and 0.3 +/- 0.3 cm2 (0.2 +/- 0.2%) in the groups breathing 100, 80, and 60% oxygen, respectively (P < 0.01). The corresponding times to reach 90% oxygen saturation were 411 +/- 84, 303 +/- 59, and 213 +/- 69 s, respectively (P < 0.01).

    CONCLUSION:

    During routine induction of general anesthesia, 80% oxygen for oxygenation caused minimal atelectasis, but the time margin before unacceptable desaturation occurred was significantly shortened compared with 100% oxygen.

  • 48.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Östberg, Erland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Scheer, H
    Wallquist, W
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Zetterström, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Preserved oxygenation in obese patients receiving protective ventilation during laparoscopic surgery: a randomized controlled study2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 1, p. 26-35Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Venous admixture from atelectasis and airway closure impedes oxygenation during general anaesthesia. We tested the hypothesis that continuous positive airway pressure (CPAP) during pre-oxygenation and reduced fraction of inspiratory oxygen (FIO2 ) during emergence from anaesthesia can improve oxygenation in patients with obesity undergoing laparoscopic surgery.

    METHODS: In the intervention group (n = 20, median BMI 41.9), a CPAP of 10 cmH2 O was used during pre-oxygenation and induction of anaesthesia, but no CPAP was used in the control group (n = 20, median BMI 38.1). During anaesthesia, all patients were ventilated in volume-controlled mode with an FIO2 of 0.4 and a positive end-expiratory pressure (PEEP) of 10 cmH2 O. During emergence, before extubation, the control group was given an FIO2 of 1.0 and the intervention group was divided into two subgroups, which were given an FIO2 of 1.0 or 0.31. Oxygenation was assessed perioperatively by the estimated venous admixture (EVA).

    RESULTS: The median EVA before pre-oxygenation was about 8% in both groups. During anaesthesia after intubation, the median EVA was 8.2% in the intervention vs. 13.2% in the control group (P = 0.048). After CO2 pneumoperitoneum, the median EVA was 8.4% in the intervention vs. 9.9% in the control group (P > 0.05). One hour post-operatively, oxygenation had deteriorated in patients given an FIO2 of 1.0 during emergence but not in patients given an FIO2 of 0.31.

    CONCLUSIONS: A CPAP of 10 cmH2 O during pre-oxygenation and induction, followed by PEEP after intubation, seemed to preserve oxygenation during anaesthesia. Post-operative oxygenation depended on the FIO2 used during emergence.

  • 49.
    Engström, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Reinius, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fröjd, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Jonsson, Hans
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Maintenance of Airway Pressure During Filter Exchange Due to Auto-Triggering2014In: Respiratory care, ISSN 0020-1324, E-ISSN 1943-3654, Vol. 59, no 8, p. 1210-1217Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Daily routine ventilator-filter exchange interrupts the integrity of the ventilator circuit. We hypothesized that this might reduce positive airway pressure in mechanically ventilated ICU patients, inducing alveolar collapse and causing impaired oxygenation and compliance of the respiratory system. METHODS: We studied 40 consecutive ICU subjects (P-aO2/F-IO2 ratio <= 300 mm Hg), mechanically ventilated with pressure-regulated volume control or pressure support and PEEP >= 5 cm H2O. Before the filter exchange, (baseline) tidal volume, breathing frequency,end-inspiratory plateau pressure, and PEEP were recorded. Compliance of the respiratory system was calculated; F-IO2, blood pressure, and pulse rate were registered; and P-aO2, P-aCO2, pH, and base excess were measured. Measurements were repeated 15 and 60 min after the filter exchange. In addition, a bench test was performed with a precision test lung with similar compliance and resistance as in the clinical study. RESULTS: The exchange of the filter took 3.5 +/- 1.2 s (mean +/- SD). There was no significant change in P-aO2 (89 +/- 16 mm Hg at baseline vs 86 +/- 16 mm Hg at 15 min and 88 +/- 18 mm Hg at 60 min, P = .24) or in compliance of the respiratory system (41 +/- 11 mL/cm H2O at baseline vs 40 +/- 12 mL/cm H2O at 15 min and 40 +/- 12 mL/cm H2O at 60 min, P = .32). The bench study showed that auto-triggering by the ventilator when disconnecting from the expiratory circuit kept the tracheal pressure above PEEP for at least 3 s with pressure controlled ventilation. CONCLUSIONS: This study showed that a short disconnection of the expiratory ventilator circuit from the ventilator during filter exchange was not associated with any significant deterioration in lung function 15 and 60 min later. This result may be explained by auto-triggering of the ventilator with high inspiratory flows during the filter exchange, maintaining airway pressure. (ISRCTN.org registration ISRCTN76631800.)

  • 50.
    Formenti, F.
    et al.
    Kings Coll London, London, England.;Univ Oxford, Oxford, England..
    Bommakanti, N.
    Univ Oxford, Oxford, England..
    Chen, R.
    Univ Oxford, Oxford, England..
    Cronin, J.
    Kings Coll London, London, England..
    McPeak, H.
    Univ Oxford, Oxford, England..
    Holopherne-Doran, D.
    Univ Bristol, Bristol, Avon, England..
    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.
    Hahn, C.
    Univ Oxford, Oxford, England..
    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.
    Farmery, A.
    Univ Oxford, Oxford, England..
    Alveolar oxygen respiratory oscillations measured in arterial blood2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 221, no SI, p. 20-20Article in journal (Other academic)
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