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  • 1.
    Ahlström, J. Zebialowicz
    et al.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Massaro, F.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Mikolka, P.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
    Feinstein, R.
    Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
    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. Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Basabe-Burgos, O.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Curstedt, T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
    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.
    Johansson, J.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Rising, A.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 245Article in journal (Refereed)
    Abstract [en]

    AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

  • 2. Artigas, Antonio
    et al.
    Noël, Julie-Lyn
    Brochard, Laurent
    Busari, Jamiu O
    Dellweg, Dominic
    Ferrer, Miguel
    Geiseler, Jens
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nava, Stefano
    Navalesi, Paolo
    Orfanos, Stylianos
    Palange, Paolo
    Pelosi, Paolo
    Rohde, Gernot
    Schoenhofer, Bernd
    Vassilakopoulos, Theodoros
    Simonds, Anita K
    Defining a training framework for clinicians in respiratory critical care2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 3, p. 572-577Article in journal (Refereed)
  • 3. Artigas, Antonio
    et al.
    Pelosi, Paolo
    Dellweg, Dominic
    Brochard, Laurent
    Ferrer, Miguel
    Geiseler, Jens
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nava, Stefano
    Navalesi, Paolo
    Noel, Julie-Lyn
    Orfanos, Stylianos
    Palange, Paolo
    Schoenhofer, Bernd
    Vassilakopoulos, Theodoros
    Simonds, Anita
    Respiratory critical care HERMES syllabus: defining competencies for respiratory doctors2012In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 39, no 6, p. 1294-1297Article in journal (Other academic)
  • 4.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Massaro, Fabrizia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Anthea Hosp, GVM Care & Res, Cardiac Anesthesia & Intens Care, Bari, Italy.
    Hansson, Hans Arne
    Univ Gothenburg, Inst Biomed, Gothenburg, Sweden.
    Feinstein, Ricardo
    Natl Vet Inst, Dept Pathol & Wildlife Dis, Uppsala, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967Article in journal (Refereed)
    Abstract [en]

    Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS.

    Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained.

    Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange.

    Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.

  • 5.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Harris, Holly
    Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, .
    Wolk, Alicja
    Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, .
    Rossary, Adrien
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Caldefie-Chézet, Florence
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Vasson, Marie-Paule
    Chaire d'Excellence Program, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, CRNH-Auvergne, INRA-UDA, Clermont-Ferrand, France;.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk: The Swedish Mammography Cohort2016In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 113, p. 28-32Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk.

    METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels.

    RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles.

    CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.

  • 6.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mattsson, Christer
    Eriksson, Örjan
    Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock2000In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 9, no 5, p. 1129-1137Article in journal (Refereed)
    Abstract [en]

    Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

  • 7.
    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)
  • 8.
    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)
  • 9.
    Bayat, S.
    et al.
    Grenoble Univ Hosp, Clin Physiol Sommeil & Exercice, Grenoble, France; Grenoble Univ Hosp, RSRM EA 7442, Grenoble, France; Univ Grenoble Alpes, Grenoble, France.
    Fardin, L.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Broche, L.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Lovric, G.
    Paul Scherrer Inst, Swiss Light Source, Villigen, Switzerland.
    Larsson, Anders 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.
    Bravin, A.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    High-Resolution Time-Resolved Phase-Contrast Synchrotron CT for Mapping Cardiac-Induced Lung Motion2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal (Other academic)
  • 10.
    Bellani, Giacomo
    et al.
    Univ Milano Bicocca, Sch Med & Surg, Monza, Italy.;San Gerardo Hosp, Dept Emergency & Intens Care, Monza, Italy..
    Laffey, John G.
    St Michaels Hosp, Dept Anesthesia & Crit Care Med, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;Univ Toronto, Dept Anesthesia, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Dept Physiol, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pham, Tai
    Grp Hosp Hop Univ Est Parisien, Hop Tenon, AP HP, Unite Reanimat Med Chirurgicale,Pole Thorax Voies, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, ECSTRA Team, UMR 1153,Inserm, Paris, France.;Univ Paris Est Creteil, UMR 915, INSERM, Creteil, France..
    Fan, Eddy
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Hlth Network, Dept Med, Toronto, ON, Canada.;Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.;Univ Toronto, Inst Hlth Policy Management & Evaluat, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Brochard, Laurent
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Esteban, Andres
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Hosp Univ Getafe, CIBER Enfermedades Respiratorias, Madrid, Spain..
    Gattinoni, Luciano
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    van Haren, Frank
    Canberra Hosp, Intens Care Unit, Canberra, ACT, Australia.;Australian Natl Univ, Canberra, ACT, Australia..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    McAuley, Daniel F.
    Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.;Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.;Royal Victoria Hosp, Reg Intens Care Unit, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland..
    Ranieri, Marco
    Policlin Umberto 1, SAPIENZA Univ ROMA, Dipartimento Anestesia & Rianimaz, Viale Policlin 155, I-00161 Rome, Italy..
    Rubenfeld, Gordon
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Sunnybrook Hlth Sci Ctr, Program Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada..
    Thompson, B. Taylor
    Harvard Univ, Sch Med, Div Pulm, Boston, MA USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Unit,Dept Med, Boston, MA USA..
    Wrigge, Hermann
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany..
    Slutsky, Arthur S.
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pesenti, Antonio
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries2016In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 315, no 8, p. 788-800Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

  • 12.
    Bergmann, Astrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Breitling, Christian
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kretzschmar, Moritz
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Kozian, Alf
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Hachenberg, Thomas
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Schilling, Thomas
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Data on the effects of remote ischemic preconditioning in the lungs after one-lung ventilation2018In: Data in Brief, E-ISSN 2352-3409, Vol. 21, p. 441-448Article in journal (Refereed)
    Abstract [en]

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

  • 13.
    Bergmann, Astrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Schilling, Thomas
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ahlgren, Kerstin M.
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kretzschmar, Moritz
    Kozian, Alf
    Hachenberg, Thomas
    Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury.2018In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 259, p. 111-118Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 14.
    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.

  • 15.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eduardo, Costa LV
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lucchetta, Luca
    Widström, Charles
    Maripuu, Enn
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Marcelo, Amato
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.Manuscript (preprint) (Other academic)
  • 16.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    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.

  • 17.
    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.

  • 18.
    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.

  • 19. Brink, M.
    et al.
    Hagberg, L.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gedeborg, Rolf
    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.
    Respiratory support during the influenza A (H1N1) pandemic flu in Sweden2012In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 56, no 8, p. 976-986Article in journal (Refereed)
    Abstract [en]

    Background Acute respiratory insufficiency characterised critically ill patients during the influenza A (H1N1) pandemic 20092010. Detailed understanding of disease progression and outcome in relation to different respiratory support strategies is important.

    Methods Data collected between August 2009 and February 2010 for a national intensive care unit influenza registry were combined with cases identified by the Swedish Institute for Infectious Disease Control.

    Results Clinical data was available for 95% (126/136) of the critically ill cases of influenza. Median age was 44 years, and major co-morbidities were present in 41%. Respiratory support strategies were studied among the 110 adult patients. Supplementary oxygen was sufficient in 15% (16), non-invasive ventilation (NIV) only was used in 20% (22), while transition from NIV to invasive ventilation (IV) was seen in 41% (45). IV was initiated directly in 24% (26). Patients initially treated with NIV had a higher arterial partial pressure of oxygen/fraction of oxygen in inspired gas ratio compared with those primarily treated with IV. Major baseline characteristics and 28-day mortality were similar, but 90-day mortality was higher in patients initially treated with NIV 17/67 (25%) as compared with patients primarily treated with IV 3/26 (12%), relative risk 1.2 (95% confidence interval 0.34.0).

    Conclusions Critical illness because of 2009 influenza A (H1N1) in Sweden was dominated by hypoxic respiratory failure. The majority of patients in need of respiratory support were initially treated with NIV. In spite of less severe initial hypoxemia, initiation of ventilatory support with NIV was not associated with improved outcome.

  • 20.
    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)
  • 21.
    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)
  • 22.
    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.

  • 23.
    Broche, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pisa, Pauline
    Univ Picardie Jules Verne, Fac Med, Amiens, France.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland;Univ Helsinki, Cent Hosp, Med Imaging Ctr, Helsinki, Finland.
    Degrugilliers, Loic
    Amiens Univ Hosp, Dept Pediat Intens Care, Amiens, France.
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Perchiazzi, Gaetano
    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.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, Sam
    Univ Grenoble Alpes, Grenoble, France;INSERM, UA7, STROBE Lab, Grenoble, France;Grenoble Univ Hosp, Dept Pulmonol & Physiol, Grenoble, France.
    Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung2019In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 9, p. E774-E781Article in journal (Refereed)
    Abstract [en]

    Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.

    Design: Laboratory animal investigation.

    Setting: European synchrotron radiation facility.

    Subjects: Six New-Zealand White rabbits.

    Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.

    Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).

    Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

  • 24. Chaireti, R.
    et al.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bremme, K.
    Lindahl, T.
    Higher thrombin generation during the luteal phase of a normal menstrual cycle does not depend on inflammatory activity2013In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 11, no S2, p. 871-871Article in journal (Other academic)
  • 25. Christensen, Steffen
    et al.
    Johansen, Martin B.
    Pedersen, Lars
    Jensen, Reinhold
    Larsen, Kim M.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tønnesen, Else
    Christiansen, Christian F.
    Sørensen, Henrik T.
    Three-year mortality among alcoholic patients after intensive care: a population-based cohort study2012In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 16, no 1, p. R5-Article in journal (Refereed)
    Abstract [en]

    Introduction: Alcoholic patients comprise a large proportion of patients in intensive care units (ICUs). However, data are limited on the impact of alcoholism on mortality after intensive care. Methods: We conducted a cohort study among 16,848 first-time ICU patients between 2001 and 2007 to examine 30-day and 3-year mortality among alcoholic patients. Alcoholic patients with and without complications of alcohol misuse (for example, alcoholic liver disease) were identified from previous hospital contacts for alcoholism-related conditions or redemption of a prescription for alcohol deterrents. Data on medication use, demographics, hospital diagnoses, and comorbidity were obtained from medical databases. We computed 30-day and 3-year mortality and mortality rate ratios (MRRs) by using Cox regression analysis, controlling for covariates. Results: In total, 1,229 (7.3%) ICU patients were current alcoholics. Among alcoholic patients without complications of alcoholism (n = 785, 4.7% of the cohort), 30-day mortality was 15.9% compared with 19.7% among nonalcoholic patients. Compared with nonalcoholic patients, the adjusted 30-day MRR was 1.04 (95% confidence interval (CI), 0.87 to 1.25). Three-year mortality was 36.2% compared with 40.9% among nonalcoholic patients, corresponding to an adjusted 3-year MRR of 1.16 (95% CI, 1.03 to 1.31). For alcoholic patients with complications (n = 444, 2.6% of the cohort), 30-day mortality was 33.6%, and 3-year mortality was 64.5%, corresponding to adjusted MRRs, with nonalcoholics as the comparator, of 1.64 (95% CI, 1.38 to 1.95) and 1.67 (95% CI, 1.48 to 1.90), respectively. Conclusions: Alcoholic ICU patients with chronic complications of alcoholism have substantially increased 30-day and 3-year mortality. In contrast, alcoholics without complications have no increased 30-day and only slightly increased 3-year mortality.

  • 26. Christensen, Steffen
    et al.
    Johansen, Martin Berg
    Tonnesen, Else
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pedersen, Lars
    Lemeshow, Stanley
    Sorensen, Henrik Toft
    Preadmission beta-blocker use and 30-day mortality among patients in intensive care: a cohort study2011In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 15, no 2, p. R87-Article in journal (Refereed)
    Abstract [en]

    Introduction: Beta-blockers have cardioprotective, metabolic and immunomodulating effects that may be beneficial to patients in intensive care. We examined the association between preadmission beta-blocker use and 30-day mortality following intensive care. Methods: We identified 8,087 patients over age 45 admitted to one of three multidisciplinary intensive care units (ICUs) between 1999 and 2005. Data on the use of beta-blockers and medications, diagnosis, comorbidities, surgery, markers of socioeconomic status, laboratory tests upon ICU admission, and complete follow-up for mortality were obtained from medical databases. We computed probability of death within 30 days following ICU admission for beta-blocker users and non-users, and the odds ratio (OR) of death as a measure of relative risk using conditional logistic regression and also did a propensity score-matched analysis. Results: Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score-matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)]. The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients. The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardioselective beta-blockers. Conclusions: Preadmission beta-blocker use is associated with reduced mortality following ICU admission.

  • 27.
    Crockett, D. C.
    et al.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    Cronin, J. N.
    Kings Coll London, Ctr Human & Appl Physiol Sci, London, England.
    Bommakanti, N.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England;Columbia Univ, Vagelos Coll Phys & Surg, New York, NY USA.
    Chen, R.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    Hahn, C. E. W.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    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.
    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. D.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England.
    Formenti, F.
    Univ Oxford, Nuffield Div Anaesthet, Oxford, England;Kings Coll London, Ctr Human & Appl Physiol Sci, London, England;Univ Nebraska, Dept Biomech, Omaha, NE 68182 USA.
    Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model2019In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 122, no 2, p. 277-285Article in journal (Refereed)
    Abstract [en]

    Background: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. Methods: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O-2 (FiO(2)) of 0.7 and a tidal volume of 10 ml kg(-1) Protocolised changes in pressure-and volume-controlled modes, inspiratory: expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. Results: During tidal ventilation, the expiratory lung collapse increased when I: E <1 [mean (standard deviation) lung collapse = .7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [ 2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). Conclusions: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

  • 28.
    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.

  • 29.
    Engström, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bruno, E.
    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, Anaesthesiology and Intensive Care.
    Jonsson, H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sannervik, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Physiological changes associated with routine nursing procedures in critically ill are common: an observational pilot study2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 1, p. 62-72Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nursing procedures that are routinely performed in the intensive care unit (ICU) are assumed to have minimal side effects. However, these procedures may sometimes cause physiological changes that negatively affect the patient. We hypothesized that physiological changes associated with routine nursing procedures in the ICU are common.

    METHODS: A clinical observational study of 16 critically ill patients in a nine-bed mixed university hospital ICU. All nursing procedures were observed, and physiological data were collected and subsequently analyzed. Minor physiological changes were defined as minimal changes in respiratory or circulatory variables, and major physiological changes were marked as hyper/hypotension, bradycardia/tachycardia, bradypnea/tachypnea, ventilatory distress, and peripheral blood oxygen desaturation.

    RESULTS: In the 16 patients, 668 procedures generated 158 major and 692 minor physiological changes during 187 observational hours. The most common procedure was patient position change, which also generated the majority of the physiological changes. The most common major physiological changes were blood oxygen desaturation, ventilatory distress, and hypotension, and the most common minor changes were arterial pressure alteration, coughing, and increase in respiratory rate.

    CONCLUSION: In this pilot study, we examined physiological changes in connection with all regular routine nursing procedures in the ICU. We found that physiological changes were common and sometimes severe.

  • 30.
    Engström, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bruno, Erik
    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, Anaesthesiology and Intensive Care.
    Jonsson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sannervik, Jerker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Non-reported adverse events during routine nursing procedures in critically ill patients are common: an observational studyArticle in journal (Other academic)
  • 31.
    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.)

  • 32.
    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.
    Ström, Jennie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bergström, Monica Frick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lung complications are common in intensive care treated patients with pelvis fractures: a retrospective cohort study2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 52Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of severe respiratory complications in patients with pelvis fractures needing intensive care have not previously been studied. Therefore, the aims of this registry study were to 1) determine the number of ICU patients with pelvis fractures who had severe respiratory complications 2) whether the surgical intervention in these patients is associated with the pulmonary condition and 3) whether there is an association between lung complications and mortality. We hypothesized that acute hypoxic failure (AHF) and acute respiratory distress syndrome (ARDS) 1) are common in ICU treated patients with pelvis fractures, 2) are not related to the reconstructive surgery, or to 3) to mortality. Methods: All patients in the database cohort (n = 112), scheduled for surgical stabilization of pelvis ring and/or acetabulum fractures, admitted to the general ICU at Uppsala University Hospital between 2007 and 2014 for intensive care were included. Results: The incidence of AHF/ARDS was 67 % (75/112 patients), i.e., the percentage of patients that at any period during the ICU stay fulfilled the AHF/ARDS criteria. The incidence of AHF was 44 % and incidence of ARDS was 23 %. The patients with AHF/ARDS had more lung contusions and pneumonia than the patients without AHF/ARDS. Overall, there were no significant changes in oxygenation variables associated with surgery. However, 23 patients with pre-operative normal lung status developed AHF/ARDS in relation to the surgical procedure, whereas 12 patients with AHF/ARDS normalized their lung condition. The patients who developed AHF/ARDS had a higher incidence of lung contusion (P = 0.04) and the surgical stabilization was performed earlier (5 versus 10 days) in these patients (P = 0.03). Conclusions: We found that the incidence of respiratory failure in ICU treated patients with pelvis fractures was high, that the procedure around surgical stabilization seems to be associated with a worsening in the respiratory function in patients with lung contusion, and that mortality was low and was probably not related to the respiratory condition.

  • 33.
    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.
    Ström, Jennie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frick Bergström, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lung complications in intensive care treated patients with pelvis fractures - common but probably not fatal: a retrospective cohort studyArticle in journal (Other academic)
  • 34.
    Eriksson, Mats B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Saldeen, Tom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Mattsson, C
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of melagatran, an inhibitor of thrombin, on fibrin deposits,haemodynamics, and platelet count in endotoxaemic pigs.2000In: Acta Anaesthesiol. Scand., Vol. 44, p. 24-Article in journal (Refereed)
  • 35.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nelson, D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Increased platelet microvesicle formation is associated with mortality ina porcine model of endotoxemia1998In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 42, no 5, p. 551-557Article in journal (Refereed)
    Abstract [en]

    Background:

    Gram-negative sepsis in humans and endotoxemia in pigs induce the formation of platelet microvesicles. These microvesicles are active in homeostasis and may thus contribute to the outcome in patients with activated coagulation and fibrinolysis. We decided to prospectively evaluate the effects of endotoxemia on microvesicle formation and some common physiologic variables against survival in a porcine model.

    Methods:

    Nineteen included pigs were anesthetized, monitored and subjected to an infusion of E. coli endotoxin. Microvesicle formation was determined by flow cytometry.

    Results:

    The formation of microvesicles was significantly increased in the 6 pigs that died during endotoxin exposure. This increased formation became significant from the 3rd hour of endotoxemia. Microvesicle formation did not increase in surviving endotoxemic pigs. Cardiac index, mean arterial blood pressure, base excess and systemic vascular resistance index were distinctly reduced in the animals that died as compared to those surviving the endotoxemic period.

    Conclusion:

    The increased formation of platelet microvesicles seems to be associated with poor prognosis in porcine endotoxemia. Since microvesicles are active in coagulation, they may contribute to the derangement of the coagulation system caused by endotoxemia. Different degrees of microvesicle formation may reflect inter-individual responses to a given challenge.

  • 36.
    Fardin, L.
    et al.
    European Synchrotron Radiat Facil, Grenoble, France..
    Broche, Ludovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Coll, J. -L
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, S.
    Grenoble Univ Hosp, Grenoble, France..
    Bravin, A.
    European Synchrotron Radiat Facil, Grenoble, France..
    Enhancing Lung Tumor Visibility Using In-Vivo Analyzer-Based X-Ray Phase Contrast Imaging In Mouse: A Feasibility Study2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, article id A6514Article in journal (Other academic)
  • 37.
    Fardin, Luca
    et al.
    European Synchrotron Radiat Facil, Grenoble, France.
    Broche, Ludovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lovric, Goran
    Swiss Light Source Paul Scherrer Inst, Lausanne, Switzerland;Ecole Polytech Fed Lausanne, CIBM, Lausanne, Switzerland.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bravin, Alberto
    European Synchrotron Radiat Facil, Grenoble, France.
    Bayat, Sam
    European Synchrotron Radiat Facil, Grenoble, France.
    Mapping cardiac-induced lung motion using high-resolution time-resolved phase-contrast synchrotron computed tomography2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 38.
    Feldreich, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, p. 109-116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 39.
    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)
  • 40. Formenti, Federico
    et al.
    Bommakanti, Nikhil
    Chen, Rongsheng
    Cronin, John N
    McPeak, Hanne
    Holopherne-Doran, Delphine
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hahn, Clive E W
    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, Andrew D
    Respiratory oscillations in alveolar oxygen tension measured in arterial blood.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7499Article in journal (Refereed)
    Abstract [en]

    Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.

  • 41. Goscinski, Gunilla
    et al.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tano, Eva
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock2004In: Critical care, ISSN 1364-8535, Vol. 8, no 1, p. 35-41Article in journal (Refereed)
  • 42. Guérin, C
    et al.
    Beuret, P
    Constantin, J M
    Bellani, G
    Garcia-Olivares, P
    Roca, O
    Meertens, J H
    Maia, P Azevedo
    Becher, T
    Peterson, J
    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.
    Gurjar, M
    Hajjej, Z
    Kovari, F
    Assiri, A H
    Mainas, E
    Hasan, M S
    Morocho-Tutillo, D R
    Baboi, L
    Chrétien, J M
    François, G
    Ayzac, L
    Chen, L
    Brochard, L
    Mercat, A
    A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study2018In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 1, p. 22-37Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

    AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

    METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).

    RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

    CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

  • 43.
    Hedenstierna, Göran
    et al.
    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.
    Influence of abdominal pressure on respiratory and abdominal organ function2012In: Current Opinion in Critical Care, ISSN 1070-5295, E-ISSN 1531-7072, Vol. 18, no 1, p. 80-85Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review:

    Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been realized as severe complications in the intensive care patient. Laparoscopic surgery in older and more obese patients increases the risk of IAH and ACS.

    Recent findings:

    The incidence of IAH may be larger than thought of being approximately one-third of mechanically ventilated intensive care patients. In shock/trauma, three-fourths of all patients may suffer from IAH. Kidney and liver may dysfunction and the gut barrier may be impeded, permitting spread of inflammation to other organs. IAH and ACS have an impact on respiratory mechanics and may impede ventilation and require higher ventilation pressures than under normal conditions. Prone position and alternating (asynchronous) ventilation may moderate the IAH. In addition, surgical decompression should be considered.

    Summary:

    In view of the frequent occurrence of IAH in intensive care, the need of better understanding of the mechanisms behind IAH is a prerequisite for better treatment. Respiratory mechanics are affected but may also indicate routes of ventilatory treatment to lower IAH.

  • 44.
    Hedenstierna, Göran
    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, Hedenstierna laboratory. Univ Hosp, Med Sci, Uppsala, Sweden.
    Lundin, S.
    Univ Hosp, Anesthesia & Intens Care, Gothenburg, Sweden.
    Pesenti, A.
    Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy.
    Chiumello, D.
    Università degli Studi di Milano, Anesthesia and Intensive Care, Milan, Italy.
    Larsson, Anders 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.
    Stenqvist, O.
    Sahlgrens Univ Hosp, Anaesthesiol & Intens Care, Gothenburg, Sweden.
    Chest Wall Elastance During Passive Mechanical Ventilation: An Alternative Hypothesis2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal (Other academic)
  • 45.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Meyhoff, Christian S
    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.
    Who Can Make Sense of the WHO Guidelines to Prevent Surgical Site Infection?2017In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 126, no 5, p. 771-773Article in journal (Refereed)
  • 46.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Björklund-Bodegard, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 145-153Article in journal (Refereed)
    Abstract [en]

    Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.

  • 47.
    Holzgraefe, Bernhard
    et al.
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Andersson, Christin
    Karolinska Univ Hosp, Dept Psychol, Huddinge, Sweden; Karolinska Univ Hosp, Dept Clin Neurosci, Stockholm, Sweden.
    Kalzén, Håkan
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    von Bahr, Viktor
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Mosskin, Mikael
    Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Palmér, Kenneth
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    Frenckner, Björn
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    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.
    Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure2017In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, no 2, p. 98-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied.

    OBJECTIVES: We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided.

    DESIGN: Long-term follow-up study after ECMO.

    SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013.

    PATIENTS: Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation.

    INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.

    MAIN OUTCOME MEASURES: Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days.

    RESULTS: Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean +/- SD peripherally measured arterial saturation during the observation period was 79 +/- 10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia.

    CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.

  • 48.
    Holzgraefe, Bernhard
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Arvika Community Hosp, Cty Council Varmland, Dept Anaesthesia Surg Serv & Intens Care Med, Arvika, Sweden..
    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.
    von Kobyletzki, Laura
    Lund Univ, Skane Univ Hosp, Dept Dermatol, Malmo, Sweden.;Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden..
    Do we have scientific evidence about the effect of hypoxaemia on cognitive outcome in adult patients with severe acute respiratory failure?2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 68-70Article in journal (Refereed)
  • 49.
    Höstman, Staffan
    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.
    Borges, João Batista
    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.
    Ahlgren, Kerstin M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Joakim
    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. 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.
    THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

    METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

    RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

    CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

  • 50.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Engström, Joakim
    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.
    Intensive buffering can keep pH above 7.2 for over 4 h during apnea: an experimental porcine study2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 1, p. 63-70Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Ventilation with low tidal volumes reduces mortality in acute respiratory distress syndrome. A further reduction of tidal volumes might be beneficial, and it is known that apneic oxygenation (no tidal volumes) with arteriovenous CO(2) removal can keep acid-base balance and oxygenation normal for at least 7 h in an acute lung injury model. We hypothesized that adequate buffering might be another approach and tested whether tris-hydroxymethyl aminomethane (THAM) alone could keep pH at a physiological level during apneic oxygenation for 4 h.

    METHODS:

    Six pigs were anesthetized, muscle relaxed, and normoventilated. The lungs were recruited, and apneic oxygenation as well as administration of THAM, 20 mmol/kg/h, was initiated. The experiment ended after 270 min, except one that was studied for 6 h.

    RESULTS:

    Two animals died before the end of the experiment. Arterial pH and arterial carbon dioxide tension (PaCO(2) ) changed from 7.5 (7.5, 7.5) to 7.3 (7.2, 7.3) kPa, P < 0.001 at 270 min, and from 4.5 (4.3, 4.7) to 25 (22, 28) kPa, P < 0.001, respectively. Base excess increased from 5 (3, 6) to 54 (51, 57) mM, P < 0.001. Cardiac output and arterial pressure were well maintained. The pig, which was studied for 6 h, had pH 7.27 and PaCO(2) 27 kPa at that time.

    CONCLUSION:

    With intensive buffering using THAM, pH can be kept in a physiologically acceptable range for 4 h during apnea.

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