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  • 1.
    Aarnio, Mikko
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An objective visualization and quantification of pain-generating processes in the periphery would alter pain diagnosis and represent an important paradigm shift in pain research. Positron emission tomography (PET) radioligand [11C]-D-deprenyl has shown an elevated uptake in painful inflammatory arthritis and whiplash-associated disorder. However, D-Deprenyl’s molecular binding target and uptake mechanism in inflammation and musculoskeletal injuries are still unknown. The present thesis aimed to gain insight into the mechanisms of D-deprenyl binding and uptake and to verify whether pain-associated sites and inflammation in acute musculoskeletal injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET-computed tomography (PET/CT).

    To identify the D-deprenyl binding target, a high-throughput analysis and competitive radioligand binding studies were performed. D-deprenyl inhibited monoamine oxidase A (MAO-A) activity by 55%, MAO-B activity by 99% and angiotensin-converting enzyme (ACE) by 70%, which identified these enzymes as higher-affinity targets. Furthermore, radioligand receptor binding assays pointed favorably towards the concept of MAO-B as the primary target. To investigate the biochemical characteristics of the binding site, we used radioligand binding assays to assess differences in the binding profile in inflamed human synovial membranes exhibiting varying levels of inflammation. D-deprenyl bound to a single, saturable population of membrane-bound protein in synovial membrane homogenates and the level of inflammation correlated with an increase in D-deprenyl binding affinity.

    To verify whether D-deprenyl can visualize pain-generating processes, patients with musculoskeletal injuries were investigated and followed-up with [11C]-D-deprenyl PET/CT. In the study of eight patients with ankle sprain, the molecular aspects of inflammation and tissue injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. The pain coexisted with increased [11C]-D-deprenyl uptake. In the study of 16 whiplash patients, an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self-rated disability.

    To further evaluate D-Deprenyl’s usefulness as a marker of inflammation, three PET tracers were compared in an animal PET/CT study. Preliminary findings showed that [11C]-D-deprenyl had an almost identical uptake pattern when compared with [11C]-L-deprenyl. The two deprenyl enantiomers showed no signs of specific binding or trapping and therefore may not be useful to study further in models of inflammatory pain, surgical pain, or both.

    This thesis demonstrates that D-deprenyl visualizes painful inflammation in musculoskeletal injuries and that the probable underlying mechanism of [11C]-D-deprenyl uptake is binding to MAO.

    List of papers
    1. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Open this publication in new window or tab >>High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
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    2016 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 152, p. 231-237Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-deprenyl is a useful positron emission tomography tracer for visualization of inflammatory processes. Studies with [C-11]-D-deprenyl showed robust uptake in peripheral painful sites of patients with rheumatoid arthritis or chronic whiplash injury. The mechanism of preferential D-deprenyl uptake is not yet known, but the existence of a specific binding site was proposed. Thus, in the present study, we sought to identify the binding site for D-deprenyl and verify the hypothesis about the possibility of monoamine oxidase enzymes as major targets for this molecule. Main methods: A high-throughput analysis of D-deprenyl activity towards 165 G-protein coupled receptors and 84 enzyme targets was performed. Additionally, binding studies were used to verify the competition of [H-3]D-deprenyl with ligands specific for targets identified in the high-throughput screen. Key findings: Our high-throughput investigation identified monoamine oxidase-B, monoamine oxidase-A and angiotensin converting enzyme as potential targets for D-deprenyl. Further competitive [3H] D-deprenyl binding studies with specific inhibitors identified monoamine oxidase-B as the major binding site. No evident high-affinity hits were identified among G-protein coupled receptors. Significance: Our study was the first to utilize a high-throughput screening approach to identify putative D-deprenyl targets. It verified 249 candidate proteins and confirmed the role of monoamine oxidase - B in D-deprenyl binding. Our results add knowledge about the possible mechanism of D-deprenyl binding, which might aid in explaining the increased uptake of this compound in peripheral inflammation. Monoamine oxidase-B will be further investigated in future studies utilizing human inflamed synovium.

    Keywords
    D-deprenyl High-throughput screening Binding site
    National Category
    Pharmaceutical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-291492 (URN)10.1016/j.lfs.2016.03.058 (DOI)000375728500028 ()27058977 (PubMedID)
    Funder
    Berzelii Centre EXSELENT, 2013-01495
    Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2018-04-09Bibliographically approved
    2. Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Open this publication in new window or tab >>Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
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    2018 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 194, p. 26-33Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for D-deprenyl in synovial membrane explants from arthritic patients.

    Main methods: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [H-3]D-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation.

    Key findings: The [H-3]D-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [H-3]D-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [H-3]D-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [H-3]D-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation.

    Significance: Our study was the first to show the biochemical characteristics of the [H-3]D-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.

    Keywords
    Arthritis, Binding target, Monoamine oxidase B, Synovium, d-Deprenyl
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Biochemistry; Medical Biochemistry
    Identifiers
    urn:nbn:se:uu:diva-347601 (URN)10.1016/j.lfs.2017.12.003 (DOI)000425052000004 ()29221756 (PubMedID)
    Funder
    Swedish Research Council, 9459
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-18Bibliographically approved
    3. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Open this publication in new window or tab >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
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    2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, p. 418-424Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

    Keywords
    Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
    Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-04-09Bibliographically approved
    4. Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Open this publication in new window or tab >>Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.

    Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.

    Keywords
    Whiplash; deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Molecular Medicine; Medical Cell Biology
    Identifiers
    urn:nbn:se:uu:diva-347602 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
    5. Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
    Open this publication in new window or tab >>Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.

    Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used.

    Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.

    Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.

    Keywords
    deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-347604 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
  • 2.
    Akca, Ozan
    et al.
    Univ Louisville, Dept Anesthesiol & Perioperat Med, Neurosci ICU, Louisville, KY 40292 USA..
    Ball, Lorenzo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Belda, F. Javier
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Biro, Peter
    Univ Hosp Zurich, Inst Anesthesiol, Zurich, Switzerland..
    Cortegiani, Andrea
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Eden, Arieh
    Lady Davis Carmel Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Haifa, Israel..
    Ferrando, Carlos
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gattinoni, Luciano
    Gottingen Univ, Dept Anesthesiol Emergency & Intens Care Med, Gottingen, Germany..
    Goldik, Zeev
    Gregoretti, Cesare
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anaesthesiol & Intens Care Med, Magdeburg, Germany..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hopf, Harriet W.
    Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA..
    Hunt, Thomas K.
    Univ Calif San Francisco, Div Gen Surg, San Francisco, CA 94143 USA..
    Pelosi, Paolo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Qadan, Motaz
    Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA..
    Sessler, Daniel I.
    Cleveland Clin, Inst Anesthesiol, Dept Outcomes Res, Cleveland, OH 44106 USA..
    Soro, Marina
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Sentürk, Mert
    Istanbul Univ, Istanbul Sch Med, Dept Anaesthesiol & Reanimat, Istanbul, Turkey..
    WHO Needs High FIO2?2017In: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, no 4, p. 181-192Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Akerlund, Emma
    et al.
    Inst för Experimentell och Klinisk medicin, Linköping.
    Huss, Fredrik R M
    Inst för Experimentell och Klinisk medicin, Linköping.
    Sjöberg, Folke
    Inst för Experimentell och Klinisk medicin, Linköping.
    Burns in Sweden: an analysis of 24,538 cases during the period 1987-2004.2007In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 33, no 1, p. 31-6Article in journal (Refereed)
    Abstract [en]

    Burn care is always progressing, but there is little epidemiological information giving a clear picture of the current number of treated burns in Sweden. This study was conducted to provide an update of patients admitted to hospital with burns in Sweden. Data were obtained for all patients who were admitted to hospitals with a primary or secondary diagnosis of burns (ICD-9/10 codes) from 1 January 1987 to 31 December 2004; 24,538 patients were found. Most of the patients were male (69%), giving a male:female ratio of 2.23:1. Children in the age-group 0-4 years old predominated, and accounted for 27% of the study material. The median length of stay was 3 days. Throughout the period 740 patients (3%) died of their burns. Significant reductions in mortality, incidence, and length of stay were seen during the study, which correlates well with other studies. However, most of the reductions were in the younger age-groups. Men accounted for the improved mortality, as female mortality did not change significantly. We think that the improvement in results among patients admitted to hospital after burns is a combination of preventive measures, improved treatment protocols, and an expanding strategy by which burned patients are treated as outpatients.

  • 4.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Platelet Inhibition and Bleeding in Coronary Artery Bypass Surgery2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A substantial number of patients undergoing cardiac surgery are on dual anti-platelet treatment with clopidogrel and aspirin. A disadvantage with this treatment is increased risk of bleeding. Bleeding is a complication of major concern associated with adverse outcome for the patient and increased hospital resource utilization. Great variability in individual response to clopidogrel has been reported. If in vitro measurements of platelet reactivity would correlate with clinical bleeding parameters, potential bleeders could be identified preoperatively.

    The aims of this thesis were: (1) to describe the degree of pre-operative platelet inhibition in patients scheduled for primary isolated coronary artery bypass graft surgery; (2) to prospectively investigate whether the pre-operative platelet inhibition correlated with intra- and postoperative bleeding and transfusion requirements; and (3) to test the ability of clinically relevant risk factors to predict re-exploration for bleeding. (4) In addition, a cost analysis was performed on patients re-explored for bleeding, to analyse the magnitude of added resource utilization and costs. Based on this, a cost model of prophylactic treatment with haemostatic drugs was calculated.

    Platelet function tests investigated were: (1) flow cytometry, (2) VASP, (3) VerifyNowSystem, (4) PlateletMapping (a modified TEG), and (5) PFA-100.

    Clinical risk factors for re-exploration and the influence of antiplatelet and antifibrinolytic therapy were evaluated in a retrospective analysis. Cost analysis at three cardiothoracic centres was performed in a case-control study.

    In conclusion, there was no clinically useful correlation between preoperative assessment of platelet inhibition and blood loss or transfusion requirements during coronary artery bypass surgery. Furthermore, there was only modest agreement between the methods evaluating ADP-receptor blockade.

    Pre-operative treatment with the P2Y12-receptor inhibitor clopidogrel was an essential risk factor for re-exploration due to bleeding. Except for clopidogrel, no strong clinical factor to predict the risk of re-exploration was identified.

    The resource utilisation costs were 47% higher in patients requiring re-exploration due to bleeding than in those not requiring re-exploration. Prolonged stay in the ICU and recovery ward accounted for half of the added cost, a third was due to the costs of surgery, one fifth due to increased cost of transfusions, and <2% was due to haemostatic drug treatment.

     

     

    List of papers
    1. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
    Open this publication in new window or tab >>The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
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    2007 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, no 3, p. 353-359Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy. MATERIALS AND METHODS: The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients). RESULTS: With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel. CONCLUSION: A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.

    Keywords
    Clopidogrel, Flow cytometry, Thrombelastograph, Platelets, PFA-100
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-24441 (URN)10.1016/j.thromres.2006.10.009 (DOI)000247762600005 ()17137616 (PubMedID)
    Available from: 2007-02-15 Created: 2007-02-15 Last updated: 2017-12-07Bibliographically approved
    2. Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
    Open this publication in new window or tab >>Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
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    2009 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 5, p. 572-577Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: A substantial number of patients with coronary artery disease undergo cardiac surgery within five days of discontinuing anti-platelet treatment with aspirin and clopidogrel. The aims of this study were to describe the degree of platelet inhibition in patients with dual anti-platelet treatment scheduled for coronary artery bypass graft (CABG) surgery and to investigate whether the measured platelet inhibition correlated to intra- and postoperative risk for bleeding and transfusion requirements. MATERIAL AND METHODS: Sixty patients were included. Platelet inhibition was analysed with flow cytometry including phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP-assay) and two bed-side analyzers, VerifyNow-System and PlateletMapping, a modified thrombelastograph. All 60 patients were analysed with VerifyNow and PlateletMapping, and 48 were analysed with flow cytometry and VASP-assay. RESULTS: There was a correlation between the ADP-receptor inhibition as measured by VASP-assay and VerifyNowP2Y(12) (r = -0.29, p<0.05), and between VASP-assay and the expression of P-selectin (r = 0.29, p<0.05) as measured by flow cytometry when platelets were stimulated with 5 microM ADP. VerifyNowP2Y(12) was the only measurement of platelet inhibition correlated to total blood loss (Spearman r = 0.29, p=0.03) and red blood cell transfusion (Spearman r = 0.43, p<0.01) requirements, although this might be confounded by aprotinin treatment. CONCLUSION: We found a modest agreement between the methods for preoperative platelet inhibition, though not for PlateletMapping-MA(ADP). There was a correlation between preoperative platelet inhibition measured by VerifyNowP2Y(12) and surgical blood loss or transfusion requirements. However, for the individual patient, preoperative use of VerifyNowP2Y(12) as an instrument to decide bleeding and transfusion risk does not seem helpful.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-120242 (URN)10.1016/j.thromres.2009.06.024 (DOI)000271712800012 ()19631364 (PubMedID)
    Available from: 2010-03-10 Created: 2010-03-10 Last updated: 2017-12-12Bibliographically approved
    3.
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  • 5.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children2018In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, no 1, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Background

    Children often starve for longer than recommended by current preoperative fasting guidelines.

    Aims

    We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

    Methods

    Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

    Results

    Patients fasting according to the 6-4-2 fasting regimen (n=66) had a median fasting time for clear fluids of 4.0h and a 33.3% incidence of fasting more than 6h. After transitioning to the 6-4-0 fasting regimen (n=64), median duration of fasting for clear fluids decreased to 1.0h, and the incidence of fasting more than 6h decreased to 6.3%. In the second unit (n=73), median fasting time was 2.2h and the proportion of patients fasting more than 6h was 21.9%.

    Conclusion

    The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

  • 6.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Schmitz, Achim
    Univ Childrens Hosp Zürich, Dept Anesthesiol, Zürich, Switzerland.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Preoperative fasting guidelines in pediatric anesthesia: are we ready for a change?2018In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 31, no 3, p. 342-348Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review: Study after study shows that prolonged fasting before anesthesia is common in children. Pediatric anesthesiologists around the world are concerned that the current guidelines may be part of the problem. This review focuses on what can be done about it.

    Recent findings: We discuss new insights into the physiology of gastric emptying of different categories of food and drink. The evidence for negative effects of prolonged fasting occurring in spite of implementation of the current guidelines is examined. We also critically appraise the concept of a strict association between fasting time and the risk of aspiration and discuss recent studies in which children have been allowed clear fluids less than 2 h before anesthesia induction.

    Summary: Accumulating evidence indicates that changes of the current guidelines for preoperative fasting should be considered for children undergoing elective procedures.

    Video abstract: http://links.lww.com/COAN/A50

  • 7.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Zarén, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite2015In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, no 8, p. 770-777Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: International guidelines recommend 2 h of clear fluid fasting prior to general anesthesia. The pediatric anesthesia unit of Uppsala University Hospital has been implementing a more liberal fasting regime for more than a decade; thus, children scheduled for elective procedures are allowed to drink clear fluids until called to the operating suite.

    AIM: To determine the incidence of perioperative pulmonary aspiration in pediatric patients allowed unlimited intake of clear fluids prior to general anesthesia.

    METHOD: Elective pediatric procedures between January 2008 and December 2013 were examined retrospectively by reviewing anesthesia charts and discharge notes in the electronic medical record system. All notes from the care event and available chest x-rays were examined for cases showing vomiting, regurgitation, and/or aspiration. Pulmonary aspiration was defined as radiological findings consistent with aspiration and/or postoperative symptoms of respiratory distress after vomiting during anesthesia.

    RESULTS: Of the 10 015 pediatric anesthetics included, aspiration occurred in three (0.03% or 3 in 10 000) cases. No case required cancellation of the surgical procedure, intensive care or ventilation support, and no deaths attributable to aspiration were found. Pulmonary aspiration was suspected, but not confirmed by radiology or continuing symptoms, in an additional 14 cases.

    CONCLUSION: Shortened fasting times may improve the perioperative experience for parents and children with a low risk of aspiration.

  • 8. Arbeus, Mikael
    et al.
    Axelsson, Birger
    Friberg, Orjan
    Magnuson, Anders
    Bodin, Lennart
    Hultman, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Milrinone Increases Flow in Coronary Artery Bypass Grafts After Cardiopulmonary Bypass: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study2009In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 23, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    Objective: To compare the effects of a bolus of milrinone, 50 mu g/kg, versus placebo on flow in coronary artery bypass grafts after cardiopulmonary bypass (CPB). Design: A prospective, randomized, double-blind study. Setting: A university hospital. Participants: Forty-four patients with stable angina and left ventricular ejection fraction > 30% scheduled for elective coronary artery bypass graft (CABG) surgery were included. Intervention: Patients were randomized to receive 50 mu g/kg of milrinone (n = 22) or placebo (n = 22) after aortic declamping. Measurements and Main Results: The flow in coronary artery bypass grafts was measured with a transit time flow meter at 10 minutes and 30 minutes after termination of CPB. The hemodynamic evaluation included transesophageal echocardiography, mean arterial pressure (MAP), heart rate, and intracavitary measurement of left ventricular end-diastolic pressure (LVEDP). The flow in the saphenous vein grafts was significantly higher in the milrinone group when compared with the placebo group both at 10 and 30 minutes after termination of CPB (p < 0.001). At 10 minutes, the flow was 64.5 +/- 37.4 mL/min (mean +/- standard deviation) and 43.6 +/- 25.7 mL/min in nonsequential vein grafts for milrinone and placebo, respectively. Corresponding values at 30 minutes were 54.8 +/- 29.9 mL/min and 35.3 +/- 22.4 mL/min. The left internal thoracic artery (LITA) flow was higher in the milrinone group but did not reach statistical significance. The fractional area change was higher, and the MAP and calculated pressure gradient (MAP-LVEDP) were lower at 10 minutes in the milrinone group. Conclusion: Milrinone significantly increases the flow in anastomosed saphenous vein grafts after CPB, and has beneficial effects on left ventricular function.

  • 9.
    Athlin, Åsa Muntlin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Uppsala Hosp, Dept Emergency Care & Internal Med, Entrance 40, S-75185 Uppsala, Sweden.;Univ Adelaide, Sch Nursing, Adelaide, SA, Australia..
    Engström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Dept Hlth & Caring Sci, Gavle, Sweden.;Lishui Univ, Sch Med & Hlth, Dept Nursing, Lishui, Peoples R China..
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Uppsala Hosp, Qual Dept, Uppsala, Sweden..
    Baath, Carina
    Karlstad Univ, Fac Hlth Sci & Technol, Dept Hlth Sci, Karlstad, Sweden.;Cty Council Varmland, Karlstad, Sweden..
    Heel pressure ulcer, prevention and predictors during the care delivery chain - when and where to take action?: A descriptive and explorative study2016In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, article id 134Article in journal (Refereed)
    Abstract [en]

    Background: Hazardous healthcare settings, for example acute care, need to focus more on preventing adverse events and preventive actions across the care delivery chain (i.e pre-hospital and emergency care, and further at the hospital ward) should be more studied. Pressure ulcer prevalence is still at unreasonably high levels, causing increased healthcare costs and suffering for patients. Recent biomedical research reveals that the first signs of cell damage could arise within minutes. However, few studies have investigated optimal pressure ulcer prevention in the initial stage of the care process, e.g. in the ambulance care or at the emergency department. The aim of the study was to describe heel pressure ulcer prevalence and nursing actions in relation to pressure ulcer prevention during the care delivery chain, for older patients with neurological symptoms or reduced general condition. Another aim was to investigate early predictors for the development of heel pressure ulcer during the care delivery chain. Methods: Existing data collected from a multi-centre randomized controlled trial investigating the effect of using a heel prevention boot to reduce the incidence of heel pressure ulcer across the care delivery chain was used. Totally 183 patients participated. The settings for the study were five ambulance stations, two emergency departments and 16 wards at two hospitals in Sweden. Results: A total of 39 individual patients (21 %) developed heel pressure ulcer at different stages across the care delivery chain. Findings revealed that 47-64 % of the patients were assessed as being at risk for developing heel pressure ulcer. Preventive action was taken. However, all patients who developed pressure ulcer during the care delivery chain did not receive adequate pressure ulcer prevention actions during their hospital stay. Discussion and Conclusions: In the ambulance and at the emergency department, skin inspection seems to be appropriate for preventing pressure ulcer. However, carrying out risk assessment with a validated instrument is of significant importance at the ward level. This would also be an appropriate level of resource use. Context-specific actions for pressure ulcer prevention should be incorporated into the care of the patient from the very beginning of the care delivery chain.

  • 10. Backes, Yara
    et al.
    van der Sluijs, Koenraad F
    Mackie, David P
    Tacke, Frank
    Koch, Alexander
    Tenhunen, Jyrki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Schultz, Marcus J
    Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review2012In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, no 9, p. 1418-1428Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE:

    Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) positively correlate with the activation level of the immune system. We reviewed the usefulness of systemic levels of suPAR in the care of critically ill patients with sepsis, SIRS, and bacteremia, focusing on its diagnostic and prognostic value.

    METHODS:

    A PubMed search on suPAR was conducted, including manual cross-referencing. The list of papers was narrowed to original studies of critically ill patients. Ten papers on original studies of critically ill patients were identified that report on suPAR in sepsis, SIRS, or bacteremia.

    RESULTS:

    Systematic levels of suPAR have little diagnostic value in critically ill patients with sepsis, SIRS, or bacteremia. Systemic levels of suPAR, however, have superior prognostic power over other commonly used biological markers in these patients. Mortality prediction by other biological markers or severity-of-disease classification system scores improves when combining them with suPAR. Systemic levels of suPAR correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of suPAR remain elevated for prolonged periods after admission and only tend to decline after several weeks. Notably, the type of assay used to measure suPAR as well as the age of the patients and underlying disease affect systemic levels of suPAR.

    CONCLUSIONS:

    The diagnostic value of suPAR is low in patients with sepsis. Systemic levels of suPAR have prognostic value, and may add to prognostication of patients with sepsis or SIRS complementing severity-of-disease classification systems and other biological markers.

  • 11. Barr, Travis P.
    et al.
    Hrnjic, Alen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Khodorova, Alla
    Sprague, Jared M.
    Strichartz, Gary R.
    Sensitization of cutaneous neuronal purinergic receptors contributes to endothelin-1-induced mechanical hypersensitivity2014In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 155, no 6, p. 1091-1101Article in journal (Refereed)
    Abstract [en]

    Endothelin (ET-1), an endogenous peptide with a prominent role in cutaneous pain, causes mechanical hypersensitivity in the rat hind paw, partly through mechanisms involving local release of algogenic molecules in the skin. The present study investigated involvement of cutaneous ATP, which contributes to pain in numerous animal models. Pre-exposure of ND7/104 immortalized sensory neurons to ET-1 (30 nM) for 10 min increased the proportion of cells responding to ATP (2 mu M) with an increase in intracellular calcium, an effect prevented by the ETA receptor-selective antagonist BQ-123. ET-1 (3 nM) pre-exposure also increased the proportion of isolated mouse dorsal root ganglion neurons responding to ATP (0.2-0.4 mu M). Blocking ET-1-evoked increases in intracellular calcium with the IP3 receptor antagonist 2-APB did not inhibit sensitization to ATP, indicating a mechanism independent of ET-1-mediated intracellular calcium increases. ET-1-sensitized ATP calcium responses were largely abolished in the absence of extracellular calcium, implicating ionotropic P2X receptors. Experiments using quantitative polymerase chain reaction and receptor-selective ligands in ND7/104 showed that ET-1-induced sensitization most likely involves the P2X4 receptor subtype. ET-1-sensitized calcium responses to ATP were strongly inhibited by broad-spectrum (TNP-ATP) and P2X4-selective (5-BDBD) antagonists, but not antagonists for other P2X subtypes. TNP-ATP and 5-BDBD also significantly inhibited ET-1-induced mechanical sensitization in the rat hind paw, supporting a role for purinergic receptor sensitization in vivo. These data provide evidence that mechanical hypersensitivity caused by cutaneous ET-1 involves an increase in the neuronal sensitivity to ATP in the skin, possibly due to sensitization of P2X4 receptors.

  • 12.
    Bartha, Erzsebet
    et al.
    Karolinska Univ Hosp, Huddinge, Sweden..
    Helleberg, Johan
    Karolinska Univ Hosp, Huddinge, Sweden..
    Ahlstrand, Rebecca
    Orebro Univ Hosp, Orebro, Sweden..
    Bell, Max
    Karolinska Univ Hosp, Solna, Sweden..
    Bjorne, Hakan
    Karolinska Univ Hosp, Solna, Sweden..
    Brattstrom, Olof
    Karolinska Univ Hosp, Solna, Sweden..
    Nilsson, Lena
    Univ Hosp Linkoping, Linkoping, Sweden..
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Andreas
    Karolinska Univ Hosp, Solna, Sweden..
    Kalman, Sigridur
    Karolinska Univ Hosp, Huddinge, Sweden..
    Performance of prediction models of postoperative mortality in high-risk surgical patients in swedish university hospitals: Predictors, Risk factors and Outcome Following major Surgery study (PROFS study NCT02626546)2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1056-1057Article in journal (Other academic)
  • 13.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Liu, Xiaoli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nozari, Ala
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Miclescu, Adriana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation2003In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 37, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

  • 14.
    Baumgardner, James E.
    et al.
    Oscillogy LLC, Folsom, PA USA..
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ventilation/perfusion distributions revisited2016In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 29, no 1, p. 2-7Article, review/survey (Refereed)
    Abstract [en]

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

  • 15.
    Becriovic Agic, Mediha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Jönsson, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Genetic association of oxidative stress and fluid accumulation makes Balb/CJ mice more sensitive to decompensated heart failure2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 963-964Article in journal (Other academic)
  • 16. Bell, Max
    et al.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bellomo, Rinaldo
    Mårtensson, Johan
    Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury2015In: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 2015, article id 158658Article in journal (Refereed)
    Abstract [en]

    Purpose. To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels.

    Methods. We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression.

    Results. Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34-0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels.

    Conclusions. Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor.

  • 17.
    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.

  • 18. Bernal, William
    et al.
    Martin-Mateos, Rosa
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tallis, Caroline
    Woodsford, Kyne
    McPhail, Mark J
    Willars, Christopher
    Auzinger, Georg
    Sizer, Elizabeth
    Heneghan, Michael
    Cottam, Simon
    Heaton, Nigel
    Wendon, Julia
    Aerobic capacity at cardio-pulmonary exercise testing and survival with and without liver transplantation in patients with chronic liver disease2014In: Liver transplantation, ISSN 1527-6465, E-ISSN 1527-6473, Vol. 20, no 1, p. 54-62Article in journal (Refereed)
    Abstract [en]

    Background:

    Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined using cardiopulmonary exercise testing (CPET) may predict post liver transplant (LT) survival, but relation to non-transplant outcome is uncertain. In patients assessed for LT we examined the relation of CPET AC parameters to severity of liver disease, nutritional state and survival with and without LT.

    Patients and Methods:

    Patients assessed for elective first LT for who underwent CPET and anthropometric assessment at a single centre were studied. CPET-derived measures of AC evaluated were peak oxygen consumption (VO2 -peak) and Anaerobic Threshold (AT).

    Results:

    399 patients underwent CPET and 223 LT; 45% of patients had VO2 -peak <50% predicted and 31% AT<9ml/kg/min. VO2 -peak and AT correlated with MELD but more closely with serum sodium and albumin. Hand grip strength correlated strongly with VO2 -peak. Patients with impaired AC had prolonged post-LT hospitalisation and 1-year post-transplantation non-survivors had lower AT than survivors (p<0.05), significant on multivariate analysis. 176 patients did not undergo LT; 1-year mortality was 34.6%. AT (p<0.05) and VO2 -peak (p<0.001) were lower in non-survivors. On multivariate analysis, AT was independently associated with non-survival.

    Conclusions:

    Aerobic capacity is markedly impaired in many patients with CLD. In those not transplanted, impaired AT was predictive of mortality and in those undergoing LT related to post-operative hospitalisation and survival. AC should be evaluated as a modifiable factor to improve patient survival, whether or not LT is anticipated.

  • 19. Bjoernaa, Elin
    et al.
    Hammer, Niels Risoer
    Pontén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Valkonen, Heikki
    Current pediatric transfusion strategies in the Nordic countries2015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no S121, p. 12-12, article id O4-01Article in journal (Other academic)
  • 20.
    Bjurling-Sjöberg, Petronella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Clinical Pathway Implementation and Teamwork in Swedish Intensive Care: Challenges in Evidence-Based Practice and Interprofessional Collaboration2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Suboptimal quality of care is an evident issue in current healthcare services. Clinical pathways (CPs) have the potential to facilitate evidence-based practice and interprofessional teamwork, and thereby improve patient safety and quality of care.

    The overall aim of the thesis was to develop comprehensive empirical knowledge and understanding of CP implementation and teamwork in Swedish intensive care units (ICUs). Four studies were included (I-IV).

    Study I was a survey including all Swedish ICUs (N84) and a document analysis of CP examples (n12). In total, 17 (20%) ICUs used CPs and many had implementation plans. The quality, extent and content of the CPs (n56) varied greatly, with sometimes insufficient interprofessionalism, evidence base and renewal.

    Study II was a mixed method including ICUs using CPs. The implementation processes were retrospectively explored through questionnaire data (n15) and qualitative content analysis of interviews with key informants (n10). The CP implementation was revealed as a process directed at realizing the usefulness and creating new habits, which requires enthusiasm, support and time.

    Studies III and IV were grounded theory studies in an action research project in an ICU. Study III explored everyday teamwork through focus group interviews with registered nurses, assistant nurses and anesthesiologists, as well as an individual interview with a physiotherapist (n38). Teamwork was revealed as an act of ‘balancing intertwined responsibilities.’ The type of teamwork fluctuated as the team processes were affected by circumstantial factors and involved individuals. Study IV prospectively explored the implementation process of a CP during a five-year period through repeated focus groups and individual interviews, questionnaires and logbooks/field notes, including the interprofessional project group, staff and managers (n71), and retrospective screening of health records (n136). ‘Struggling for a feasible tool’ was revealed as a central phenomenon. The implementation process included contextual and processual circumstances that enforced negotiations to achieve progress, which made the process tentative and prolonged and had consequences on the process output.

    In conclusion, CP implementation processes are affected by multiple interplaying factors. Although progress has been achieved in evidence-based practice and interprofessional collaboration there is still potential for substantial improvements, emphasizing a need for further facilitation.

    List of papers
    1. Prevalence and quality of clinical pathways in Swedish intensive care units: a national survey
    Open this publication in new window or tab >>Prevalence and quality of clinical pathways in Swedish intensive care units: a national survey
    Show others...
    2014 (English)In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 20, no 1, p. 48-57Article in journal (Refereed) Published
    Abstract [en]

    RATIONALE, AIMS AND OBJECTIVES

    To identify the prevalence of clinical pathways (CPs) in Swedish intensive care units (ICUs) and to explore the quality, content and evidence base of the documents.

    METHODS

    A descriptive and explorative survey of all Swedish ICUs (N84) and a review of submitted examples of CPs (n12) were conducted.

    RESULTS

    CPs were in use at 20% of the Swedish ICUs. There was a significant geographic variation but no relationship between the use of CPs and category of hospital, type of ICU, size of ICU or type of health record applied. In total, 56 CPs were reported within a range of scopes and extensions. The content of the ICUs' CPs, as well as the degree to which they were interprofessional, evidence based, and renewed varied.

    CONCLUSIONS

    Progress has been made in relation to CPs in recent years, but there is potential for further improvements. None of the ICUs had CPs that contained all key characteristics of a high-quality, interprofessional and evidence-based CP identified in the literature. Greater knowledge sharing and cooperation within the field would be beneficial, and further research is needed.

    Keywords
    clinical pathways, evidence-based practice, intensive care, organization, professional practice, standardized care plans
    National Category
    Medical and Health Sciences
    Research subject
    Anaesthesiology and Intensive Care; Health Care Research; Caring Sciences
    Identifiers
    urn:nbn:se:uu:diva-207939 (URN)10.1111/jep.12078 (DOI)000330802100008 ()24033437 (PubMedID)
    Projects
    Standardiserade vårdplaner inom svensk intensivvård
    Available from: 2013-09-22 Created: 2013-09-21 Last updated: 2018-01-29Bibliographically approved
    2. Factors affecting the implementation process of clinical pathways: A mixed method study within the context of Swedish intensive care
    Open this publication in new window or tab >>Factors affecting the implementation process of clinical pathways: A mixed method study within the context of Swedish intensive care
    Show others...
    2015 (English)In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 21, no 2, p. 255-261Article in journal (Refereed) Published
    Abstract [en]

    RATIONALE, AIMS AND OBJECTIVES: Clinical pathways (CPs) can improve quality of care on intensive care units (ICUs), but are infrequently utilized and of varying quality. Knowledge regarding factors that facilitate versus hinder successful implementation of CPs is insufficient and a better understanding of the activities and individuals involved is needed. The aim of this study was to explore the implementation process of CPs within the context of ICUs.

    METHODS: An exploratory design with a sequential mixed method was used. A CP survey, including all Swedish ICUs, was used to collect quantitative data from ICUs using CPs (n = 15) and interviews with key informants (n = 10) were used to collect qualitative data from the same ICUs. Descriptive statistics and qualitative content analysis were used, and the quantitative and qualitative findings were integrated.

    RESULTS: The CP implementation was conceptualized according to two interplaying themes: a process to realize the usefulness of CPs and create new habits; and a necessity of enthusiasm, support and time. Multiple factors affected the process and those factors were organized in six main categories and 14 subcategories.

    CONCLUSIONS: Bottom-up initiatives, interprofessional project groups and small ICUs seem to enhance successful implementation of CPs while inadequate electronic health record systems, insufficient support and time constrains can be barriers. Support regarding the whole implementation process from centralized units at the local hospitals, as well as cooperation between ICUs and national guidance, has the potential to raise the quality of CPs and benefit the progress of CP implementation.

    National Category
    Health Care Service and Management, Health Policy and Services and Health Economy
    Identifiers
    urn:nbn:se:uu:diva-244833 (URN)10.1111/jep.12301 (DOI)000351871200013 ()25678495 (PubMedID)
    Available from: 2015-02-21 Created: 2015-02-21 Last updated: 2018-01-29Bibliographically approved
    3. Balancing intertwined responsibilities: A grounded theory study of teamwork in everyday intensive care unit practice
    Open this publication in new window or tab >>Balancing intertwined responsibilities: A grounded theory study of teamwork in everyday intensive care unit practice
    Show others...
    2017 (English)In: Journal of Interprofessional Care, ISSN 1356-1820, E-ISSN 1469-9567, Vol. 31, no 2, p. 233-244Article in journal (Refereed) Published
    Abstract [en]

    This study aimed to describe and explain teamwork and factors that influence team processes in everyday practice in an intensive care unit (ICU) from a staff perspective. The setting was a Swedish ICU. Data were collected from 38 ICU staff in focus groups with registered nurses, assistant nurses, and anaesthetists, and in one individual interview with a physiotherapist. Constant comparative analysis according to grounded theory was conducted, and to identify the relations between the emerged categories, the paradigm model was applied. The core category to emerge from the data was balancing intertwined responsibilities. In addition, eleven categories that related to the core category emerged. These categories described and explained the phenomenon's contextual conditions, causal conditions, and intervening conditions, as well as the staff actions/interactions and the consequences that arose. The findings indicated that the type of teamwork fluctuated due to circumstantial factors. Based on the findings and on current literature, strategies that can optimise interprofessional teamwork are presented. The analysis generated a conceptual model, which aims to contribute to existing frameworks by adding new dimensions about perceptions of team processes within an ICU related to staff actions/interactions. This model may be utilised to enhance the understanding of existing contexts and processes when designing and implementing interventions to facilitate teamwork in the pursuit of improving healthcare quality and patient safety.

    Keywords
    Grounded theory, intensive care unit, interprofessional care, interviews, practice, roles, teamwork
    National Category
    Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-317286 (URN)10.1080/13561820.2016.1255184 (DOI)000395098400017 ()28140715 (PubMedID)
    Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2018-01-29Bibliographically approved
    4. Struggeling for a feasible tool- the process of implementing a clinical pathway in intensive care: A grounded theory study
    Open this publication in new window or tab >>Struggeling for a feasible tool- the process of implementing a clinical pathway in intensive care: A grounded theory study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-337410 (URN)
    Available from: 2017-12-26 Created: 2017-12-26 Last updated: 2018-01-29
  • 21.
    Bjurling-Sjöberg, Petronella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wadensten, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Pöder, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jansson, Inger
    Göteborgs universitet.
    Nordgren, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Centrum för klinisk forskning Sörmland.
    Struggeling for a feasible tool- the process of implementing a clinical pathway in intensive care: A grounded theory studyManuscript (preprint) (Other academic)
  • 22.
    Björnsson, Marcus A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Norberg, Åke
    Kalman, Sigridur
    Simonsson, Ulrika S H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A Recirculatory Model for Pharmacokinetics and the Effects on Bispectral Index After Intravenous Infusion of the Sedative and Anesthetic AZD3043 in Healthy Volunteers2015In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 121, no 4, p. 904-913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers.

    METHODS: Arterial and venous plasma concentrations of AZD3043 and BIS were measured in 2 clinical studies in 125 healthy volunteers, where AZD3043 was given as a 1-minute bolus (1-6 mg/kg), a 30-minute infusion (1-81 mg/kg/h), or 0.8 + 10, 1 + 15, 3 + 30, and 4 + 40 (mg/kg bolus + mg/kg/h infusion for 30 minutes). Population PK/pharmacodynamic analysis was performed with NONMEM.

    RESULTS: A recirculatory model, comprising a series of 5 compartments for the transit of drug between venous and arterial plasma, 2 peripheral distribution compartments, and 1 compartment for the nondistributive transit of drug from arterial to venous plasma, described the PK of AZD3043. Systemic clearance was high (2.2 L/min; 95% confidence interval, 2.12-2.25), and apparent volumes of distribution were low, leading to a short elimination half-life. The apparent volumes of distribution of the arterial and peripheral compartments increased with increasing administered dose, giving a total apparent volume of distribution of 15 L after the lowest dose and 37 L after the greatest dose. A sigmoid maximum effect (Emax) model with an EC50 of 15.6 µg/mL and a γ of 1.7 described the relationship between AZD3043 effect-site concentrations and BIS. The between-subject variability in EC50 was 37%. An effect compartment model, with a half-life of the equilibration rate constant ke0 of 1.1 min, described the delay in effect in relation to the arterial plasma concentrations.

    CONCLUSIONS: AZD3043 had a high clearance and a low apparent volume of distribution, leading to a short half-life. However, the apparent volume of distribution was dose dependent (P < 0.001), leading to an increased half-life with increasing dose. The distribution to the effect site was fast and together with the short plasma half-life led to a fast onset and offset of effects.

  • 23.
    Blomberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Influence of The Education and Training of Prehospital Medical Crews on Measures of Performance and Patient Outcomes2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Prehospital care has developed dramatically the last decades with the implementation of new devices and educational concepts. Clinical decisions and treatments have moved out from the hospitals to the prehospital setting. In Sweden this has been accompanied by an increase in the level of competence, i.e. by introducing nurses in the ambulances. With some exceptions the scientific support for these changes is poor.

    This thesis deals with such changes in three different subsets of prehospital care: Cardiopulmonary resuscitation (CPR), the stroke chain of survival and trauma care.

    We assessed the performance of ambulance crews during CPR, using a mechanical compression device, as compared to CPR using manual compressions. There was a strikingly poor quality of compressions using the mechanical device compared to CPR with manual compressions. The result calls for caution when implementing a chest compression device in clinical practice and reinforce the importance of randomised controlled trials to evaluate new interventions. Careful attention should be given to the assurance of correct application of the device. Further implementation without evaluation of the quality of mechanical compressions in a clinical setting is discouraged.

    Among patients with a prehospital suspicion of stroke we analysed the ambulance nurses’ ability to select the correct patient subset eligible for a CT scan as a preparation for potential thrombolysis. The results do not support an implementation of a bypass of the emergency department, using ambulance nurse competence to select patients eligible and suitable for a CT scan without a preceding assessment by a physician.

    The association between the Prehospital Trauma Life Support (PHTLS) course and the outcome in victims of trauma was analysed in two observational studies. A study covering one county gave some support for a protective effect from PHTLS, but the estimate had a low precision. A nationwide study, covering all of Sweden, could not confirm those results. Although there was a reduction in mortality over time coinciding with the implementation of PHTLS, it did not appear to be associated with the implementation of PHTLS. Thus, we could not detect any clear beneficial impact of the PHTLS course on the outcome of trauma patients.

    List of papers
    1. Poor chest compression quality with mechanical compressions in simulated cardiopulmonary resuscitation: A randomized, cross-over manikin study
    Open this publication in new window or tab >>Poor chest compression quality with mechanical compressions in simulated cardiopulmonary resuscitation: A randomized, cross-over manikin study
    Show others...
    2011 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 82, no 10, p. 1332-1337Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Mechanical chest compression devices are being implemented as an aid in cardiopulmonary resuscitation (CPR), despite lack of evidence of improved outcome. This manikin study evaluates the CPR-performance of ambulance crews, who had a mechanical chest compression device implemented in their routine clinical practice 8 months previously. The objectives were to evaluate time to first defibrillation, no-flow time, and estimate the quality of compressions. Methods: The performance of 21 ambulance crews (ambulance nurse and emergency medical technician) with the authorization to perform advanced life support was studied in an experimental, randomized cross-over study in a manikin setup. Each crew performed two identical CPR scenarios, with and without the aid of the mechanical compression device LUCAS. A computerized manikin was used for data sampling. Results: There were no substantial differences in time to first defibrillation or no-flow time until first defibrillation. However, the fraction of adequate compressions in relation to total compressions was remarkably low in LUCAS-CPR (58%) compared to manual CPR (88%) (95% confidence interval for the difference: 13-50%). Only 12 out of the 21 ambulance crews (57%) applied the mandatory stabilization strap on the LUCAS device. Conclusions: The use of a mechanical compression aid was not associated with substantial differences in time to first defibrillation or no-flow time in the early phase of CPR. However, constant but poor chest compressions due to failure in recognizing and correcting a malposition of the device may counteract a potential benefit of mechanical chest compressions. 

    Keywords
    Cardiopulmonary resuscitation (CPR), Defibrillation, Cardiac arrest, Chest compression, Out-of-hospital CPR, Cardiac-assist device
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-161559 (URN)10.1016/j.resuscitation.2011.06.002 (DOI)000296168700018 ()
    Available from: 2011-11-20 Created: 2011-11-15 Last updated: 2017-12-08Bibliographically approved
    2. Agreement between ambulance nurses and physicians in assessing stroke patients
    Open this publication in new window or tab >>Agreement between ambulance nurses and physicians in assessing stroke patients
    Show others...
    2013 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 129, no 1, p. 49-55Article in journal (Refereed) Published
    Abstract [en]

    Objectives: If an ambulance nurse could bypass the emergency department (ED) and bring suspected stroke patients directly to a CT scanner, time to thrombolysis could be shortened. This study evaluates the level of agreement between ambulance nurses and emergency physicians in assessing the need for a CT scan, and interventions and monitoring beforehand, in patients with suspected stroke and/or a lowered level of consciousness.

    Materials and Methods: From October 2008 to June 2009 we compared the ambulance nurses’ and ED physicians’ judgement of 200 patients with stroke symptoms . Both groups answered identical questions on patients’ need for a CT scan, and interventions and monitoring beforehand.  

    Results: There was a poor agreement between ambulance nurses and ED physicians in judging the need for a CT scan: κ = 0.22 (95% confidence interval (CI): 0.06–0.37). The nurses’ ability to select the same patients as the physician for a CT scan had a sensitivity of 84% (95% CI: 77–89) and a specificity of 37% (95% CI: 23–53). Agreement concerning the need for interventions and monitoring was also low: κ = 0.32 (95% CI: 0.18–0.47). In 18% of cases, the nurses considered interventions before a CT scan unnecessary when the physicians’ deemed them necessary.

    Conclusions: Additional tools to support ambulance nurses decisions appear to be required before suspected stroke patients can be taken directly to a CT scanner.

     

     

    Keywords
    acute stroke therapy; emergency; ischemic stroke; protocols; prehospital care; stroke teams; thrombolysis
    National Category
    Other Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-192626 (URN)10.1111/ane.12149 (DOI)000327608300008 ()23710712 (PubMedID)
    Available from: 2013-01-29 Created: 2013-01-23 Last updated: 2017-12-06Bibliographically approved
    3. Prehospital Trauma Life Support (PHTLS) training of ambulance caregivers and impact on survival of trauma victims
    Open this publication in new window or tab >>Prehospital Trauma Life Support (PHTLS) training of ambulance caregivers and impact on survival of trauma victims
    Show others...
    2012 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, no 10, p. 1259-1264Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    The Prehospital Trauma Life Support (PHTLS) course has been widely implemented and approximately half a million prehospital caregivers in over 50 countries have taken this course. Still, the effect on injury outcome remains to be established. The objective of this study was to investigate the association between PHTLS training of ambulance crew members and the mortality in trauma patients.

    METHODS:

    A population-based observational study of 2830 injured patients, who either died or were hospitalized for more than 24h, was performed during gradual implementation of PHTLS in Uppsala County in Sweden between 1998 and 2004. Prehospital patient records were linked to hospital-discharge records, cause-of-death records, and information on PHTLS training and the educational level of ambulance crews. The main outcome measure was death, on scene or in hospital.

    RESULTS:

    Adjusting for multiple potential confounders, PHTLS training appeared to be associated with a reduction in mortality, but the precision of this estimate was poor (odds ratio, 0.71; 95% confidence interval, 0.42-1.19). The mortality risk was 4.7% (36/763) without PHTLS training and 4.5% (94/2067) with PHTLS training. The predicted absolute risk reduction is estimated to correspond to 0.5 lives saved annually per 100,000 population with PHTLS fully implemented.

    CONCLUSIONS:

    PHTLS training of ambulance crew members may be associated with reduced mortality in trauma patients, but the precision in this estimate was low due to the overall low mortality. While there may be a relative risk reduction, the predicted absolute risk reduction in this population was low.

    National Category
    General Practice
    Identifiers
    urn:nbn:se:uu:diva-181577 (URN)10.1016/j.resuscitation.2012.02.018 (DOI)000309050600027 ()22366502 (PubMedID)
    Available from: 2012-09-26 Created: 2012-09-26 Last updated: 2018-08-24Bibliographically approved
    4. Impact of prehospital trauma life support (PHTLS) training of ambulance caregivers on the outcome of traffic injury victims – a nation-wide study.
    Open this publication in new window or tab >>Impact of prehospital trauma life support (PHTLS) training of ambulance caregivers on the outcome of traffic injury victims – a nation-wide study.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Prehospital trauma life support (PHTLS) is a widely implemented educational program for prehospital trauma care. Evidence for improved patient outcome is, however, limited. The primary aim of this nation-wide study was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    Methods: We extracted from the Swedish National Patient Registry and the Cause of Death Registry information on victims of motor vehicle traffic injuries in Sweden from 2001 to 2004 (n=28 041). During this time period, PHTLS training was implemented at a varying pace in different regions. We used a Bayesian approach with Markov chain Monte Carlo to estimate odds ratios (OR) for prehospital and 30-day mortality. We entered region and hospital into hierarchical models and controlled for the calendar year for each injury. We analyzed the time to death and time to return to work using Cox’s proportional hazards frailty models.

    Results: A total of 1395 individuals died before being admitted to hospital. After multivariable adjustment, the OR for prehospital mortality with PHTLS-trained prehospital staff was 1.11 (95% credibility interval, 0.88 to 1.38). For 30-day mortality (365 deaths), the adjusted OR was 0.80 (95% credibility interval, 0.53 to 1.17). There was no association between PHTLS training and time to death (hazard ratio 0.99; 95% confidence interval, 0.85 to 1.14) or time to return to work (hazard ratio 0.98, 95% confidence interval, 0.92 to 1.05).

    Conclusion: The implementation of PHTLS training did not appear to reduce mortality or disability after motor vehicle traffic injuries. 

    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-192628 (URN)
    Available from: 2013-01-29 Created: 2013-01-23 Last updated: 2018-08-24
  • 24.
    Blomberg, Hans
    et al.
    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.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Karlsten, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Poor chest compression quality with mechanical compressions in simulated cardiopulmonary resuscitation: A randomized, cross-over manikin study2011In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 82, no 10, p. 1332-1337Article in journal (Refereed)
    Abstract [en]

    Introduction: Mechanical chest compression devices are being implemented as an aid in cardiopulmonary resuscitation (CPR), despite lack of evidence of improved outcome. This manikin study evaluates the CPR-performance of ambulance crews, who had a mechanical chest compression device implemented in their routine clinical practice 8 months previously. The objectives were to evaluate time to first defibrillation, no-flow time, and estimate the quality of compressions. Methods: The performance of 21 ambulance crews (ambulance nurse and emergency medical technician) with the authorization to perform advanced life support was studied in an experimental, randomized cross-over study in a manikin setup. Each crew performed two identical CPR scenarios, with and without the aid of the mechanical compression device LUCAS. A computerized manikin was used for data sampling. Results: There were no substantial differences in time to first defibrillation or no-flow time until first defibrillation. However, the fraction of adequate compressions in relation to total compressions was remarkably low in LUCAS-CPR (58%) compared to manual CPR (88%) (95% confidence interval for the difference: 13-50%). Only 12 out of the 21 ambulance crews (57%) applied the mandatory stabilization strap on the LUCAS device. Conclusions: The use of a mechanical compression aid was not associated with substantial differences in time to first defibrillation or no-flow time in the early phase of CPR. However, constant but poor chest compressions due to failure in recognizing and correcting a malposition of the device may counteract a potential benefit of mechanical chest compressions. 

  • 25.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Jakob
    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.
    Impact of prehospital trauma life support (PHTLS) training of ambulance caregivers on the outcome of traffic injury victims – a nation-wide study.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Prehospital trauma life support (PHTLS) is a widely implemented educational program for prehospital trauma care. Evidence for improved patient outcome is, however, limited. The primary aim of this nation-wide study was to investigate the association between regional implementation of PHTLS training and mortality after traffic injuries.

    Methods: We extracted from the Swedish National Patient Registry and the Cause of Death Registry information on victims of motor vehicle traffic injuries in Sweden from 2001 to 2004 (n=28 041). During this time period, PHTLS training was implemented at a varying pace in different regions. We used a Bayesian approach with Markov chain Monte Carlo to estimate odds ratios (OR) for prehospital and 30-day mortality. We entered region and hospital into hierarchical models and controlled for the calendar year for each injury. We analyzed the time to death and time to return to work using Cox’s proportional hazards frailty models.

    Results: A total of 1395 individuals died before being admitted to hospital. After multivariable adjustment, the OR for prehospital mortality with PHTLS-trained prehospital staff was 1.11 (95% credibility interval, 0.88 to 1.38). For 30-day mortality (365 deaths), the adjusted OR was 0.80 (95% credibility interval, 0.53 to 1.17). There was no association between PHTLS training and time to death (hazard ratio 0.99; 95% confidence interval, 0.85 to 1.14) or time to return to work (hazard ratio 0.98, 95% confidence interval, 0.92 to 1.05).

    Conclusion: The implementation of PHTLS training did not appear to reduce mortality or disability after motor vehicle traffic injuries. 

  • 26.
    Body, Richard
    et al.
    Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Emergency Dept, Manchester, Lancs, England.;Univ Manchester, Cardiovasc Sci Res Grp, Oxford Rd, Manchester, Lancs, England..
    Mueller, Christian
    Univ Spital Basel, Dept Cardiol, Basel, Switzerland..
    Giannitsis, Evangelos
    Med Univ Klin Krehl Linik, Abt Innere Med Kardiol Angiol & Pneumol 3, Heidelberg, Germany..
    Christ, Michael
    Klinikum Nurnberg Nord, Klin Notfallmed & Internist Intens Med, Nurnberg, Germany..
    Ordonez-Llanos, Jorge
    Hosp Santa Creu & Sant Pau, IIB, Barcelona, Spain.;Univ Autonoma Barcelona, Barcelona, Spain..
    de Filippi, Christopher R.
    Univ Maryland, Div Cardiol, Baltimore, MD 21201 USA..
    Nowak, Richard
    Henry Ford West Bloomfield Hosp, West Bloomfield, MI USA..
    Panteghini, Mauro
    Azienda Osped Luigi Sacco, Lab Anal Chim Clin, Milan, Italy..
    Jernberg, Tomas
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Plebani, Mario
    Univ Padua, Lab Azienda Osped, Med Serv, Via Giustinianeo, Padua, Italy..
    Verschuren, Franck
    Catholic Univ Louvain, Clin Univ St Luc, Dept Acute Med, Brussels, Belgium..
    French, John K.
    Liverpool Hosp, Dept Cardiol, Liverpool, NSW, Australia..
    Christenson, Robert
    Univ Maryland, Sch Med, Baltimore, MD 21201 USA..
    Weiser, Silvia
    Roche Diagnost Germany, Penzberg, Germany..
    Bendig, Garnet
    Roche Diagnost Germany, Penzberg, Germany..
    Dilba, Peter
    Roche Diagnost Germany, Penzberg, Germany..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The Use of Very Low Concentrations of High-sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test2016In: Academic Emergency Medicine, ISSN 1069-6563, E-ISSN 1553-2712, Vol. 23, no 9, p. 1005-1013Article in journal (Refereed)
    Abstract [en]

    Background: Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. Objective: We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. Methods: TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. Results: We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). Conclusions: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

  • 27.
    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.

  • 28.
    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.

  • 29.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ribeiro Carvalho, Carlos Roberto
    The Quest for the Holy Grail: A Dead Lock2010In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 182, no 4, p. 579-580Article in journal (Refereed)
  • 30.
    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.

  • 31.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Sundell-Bergman, S.
    Swedish Univ Agr Sci, Dept Soil & Environm, Umea, Sweden.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice2018In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 120, no 3, p. 546-554Article in journal (Refereed)
    Abstract [en]

    Background: Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Methods: Male mice were exposed to a single dose of ketamine (7.5 mg kg(-1) body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (Cs-137). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Results: Animals co-exposed to IR and ketamine displayed significant (P <= 0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P <= 0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P <= 0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Conclusion: Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.

  • 32.
    Butler, Stephen H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Norwegian Univ Sci & Technol, Fac Med, Dept Circulat & Med Imaging, Trondheim, Norway..
    Landmark, Tormod
    St Olavs Univ Hosp, Natl Competence Ctr Complex Symptom Disorders, Trondheim, Norway..
    Glette, Mari
    Norwegian Univ Sci & Technol, Fac Med, Dept Circulat & Med Imaging, Trondheim, Norway..
    Borchgrevink, Petter
    Norwegian Univ Sci & Technol, Fac Med, Dept Circulat & Med Imaging, Trondheim, Norway.;St Olavs Univ Hosp, Natl Competence Ctr Complex Symptom Disorders, Trondheim, Norway..
    Woodhouse, Astrid
    St Olavs Univ Hosp, Natl Competence Ctr Complex Symptom Disorders, Trondheim, Norway.;Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, Trondheim, Norway..
    How widespread should pain be to be defined as widespread?: Reply2016In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 157, no 8, p. 1832-1833Article in journal (Refereed)
  • 33. Bäckryd, Emmanuel
    et al.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Berzelii Technology Center for Neurodiagnostics, Uppsala University, Uppsala, Sweden.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gerdle, Björn
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Berzelii Technology Center for Neurodiagnostics, Uppsala University, Uppsala, Sweden.
    High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls2017In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 12, p. 2487-2495Article in journal (Refereed)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called "gliotransmitters," a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain (n = 11 and n = 16, respectively) and healthy control subjects (n = 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain (eg, depression, anxiety, poor sleep, and tiredness) also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator.

  • 34.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Linköping, Sweden.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gerdle, Björn
    Linköping University, Linköping, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    High Levels of Cerebrospinal Fluid Chemokines Point to the Presence of Neuroinflammation in Peripheral Neuropathic Pain: A Cross-Sectional Study of Two Cohorts of Patients Compared to Healthy ControlsManuscript (preprint) (Other academic)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called “gliotransmitters”, a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile for neuropathic pain patients. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation.  

    CSF samples were collected from two cohorts of patients with neuropathic pain (n=11 and n=16, respectively) and healthy controls (n=11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek® Multiplex Inflammation I, Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares – discriminant analysis, were used for statistical analyses.

    CSF levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared to healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in fibromyalgia patients. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Since it has been suggested that prevalent co-morbidities to chronic pain (e.g., depression, anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation is a common mediator.

  • 35. Bäckström, D
    et al.
    Larsen, R
    Steinvall, I
    Fredrikson, M
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjöberg, F
    Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing.2018In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 44, no 4, p. 589-596Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage.

    METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression.

    RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r (2) = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r (2) = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r (2) = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r (2) = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r (2) = 0.84; p < 0.001) and poisoning (coefficient 0.13, r (2) = 0.69; p < 0.001).

    CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

  • 36. Cacciani*, Nicola
    et al.
    Salah*, Heba
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology. uppsala university.
    Li, Meishan
    Akkad, Hazem
    Ogilvie, Hannah
    Backeus, Anders
    Hedstrom, Yvette
    Larsson, Lars
    Does chaperone co-inducer BGP-15 mitigate the contractile dysfunction of the soleus muscle in a rat ICU model?Manuscript (preprint) (Other academic)
  • 37.
    Castegren, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Jonasson, Mikaela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Castegren, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Initial levels of organ failure, microbial findings and mortality in intensive care-treated primary, secondary and tertiary sepsis2015In: CRITICAL CARE AND RESUSCITATION, ISSN 1441-2772, Vol. 17, no 3, p. 174-181Article in journal (Refereed)
    Abstract [en]

    Objective: Analysis of whether patients with primary, secondary and tertiary sepsis, defined by the presence or absence of recent systemic inflammation-inducing events before the onset of sepsis, differ in clinical presentation, microbiological test results, treatment received and outcome. Design, setting and participants: A retrospective observational study in a single, general intensive care unit, of all patients treated for severe sepsis or septic shock from 2006 to 2011. Patients with haematological malignancies, with immunosuppressive diseases or being treated with immunosuppressive drugs were excluded. Interventions: None. Main outcome measures: Sequential Organ Failure Assessment score, incidence of organ failure, microbiological results of blood cultures and mortality. Results: We included 213 patients, who were classified as having primary (n = 121), secondary (n = 65) or tertiary sepsis (n = 27). The groups differed significantly in SOFA score, the incidence of kidney failure and coagulation failure at onset of sepsis in the ICU, as well as in blood culture findings. No differences in 7-day or 28-day mortality were seen, but the time of death occurred earlier among non-survivors in the primary sepsis group. Conclusions: Inflammatory insults before the onset of sepsis affect the clinical picture, blood microbial findings, and in non-survivors, the time of death. These results could, if validated in a prospective study, form a basis for a novel and simple strategy for stratifying patients in clinical studies for immunomodulation therapies in sepsis.

  • 38. Chen, Lin
    et al.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Guo, Jiangfeng
    Muresanu, Dafin
    Huang, Hongyun
    Skaper, Stephen
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Conference Report Annual advances in neurorestoratology: a summary of IANR VI and 10th GCNN conference, Bucharest, Romania, April 4-7, 20132013In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 12, no 5, p. 547-549Article in journal (Refereed)
  • 39.
    Chen, Luni
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Inhaled Nitric Oxide Therapy: Non-response and Rebound Response2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertension. However, around 30-40% of the patients are non-responders to this therapy, and a life-threatening rebound response may occur during attempts to withdraw INO. This thesis investigated the link between vasoconstrictors and non- and rebound responses in piglets subjected to acute lung injury by exposure to endotoxin or oleic acid (OA). We found that INO had strong effect in mainly ET-1 related, endotoxin-induced pulmonary hypertension, and there was a rebound response after INO withdrawal. Thus, the weaker the response to INO, the greater the rebound. Neither response nor rebound was seen in oleic acid-induced, mainly prostaglandin related pulmonary hypertension. INO decreased expression of the ET-A receptor, and this might be another signal transduction pathway whereby INO relieves pulmonary vasoconstriction besides increasing c-GMP. Thus INO might have better effect in pulmonary vasoconstriction that is mainly mediated by ET-1 than when other vasoconstrictors are involved in the vascular reaction. Increased production and/or release of vasoconstrictor peptide endothelin-1 (ET-1) during INO, and release of prostaglandin TXA2 and PGF after INO withdrawal, were more important causes of the rebound, than a decreasing endogenous NO production during INO. The latter mechanism has been proposed in previous studies. An increase in prostaglandins after INO withdrawal is possibly secondary to the increase in ET-1 during INO. Combination of INO with the COX inhibitor diclofenac blocked the rebound reaction. These findings may open the way for new therapeutic modalities.

  • 40.
    Chew, Michelle S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mangelus, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spetz, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lyckner, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Surgery was successful - but how did it go for the patient?: Experiences from and hopes for the Swedish Perioperative Register2015In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 32, no 7, p. 453-454Article in journal (Other academic)
  • 41. Christensson, Eva
    et al.
    Franklin, Karl A
    Sahlin, Carin
    Palm, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Ulfberg, Jan
    Eriksson, Lars I
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Hagel, Eva
    Jonsson Fagerlund, Malin
    Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?2018In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 127, no 3, p. 736-743Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA.

    METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m, Age >50 years, Neck circumference >40 cm, and male Gender.

    RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64-0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI, 0.92-0.98) to exclude an AHI >15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87-0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively.

    CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of <2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for screening for sleep apnea (ie, before surgery).

  • 42.
    Colldén, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Birgisdottir, Birgitta
    Akad Sjukhuset, Uppsala, Sweden..
    Case of subdural hematoma after labor epidural: implications for follow-up of post dural puncture head ache2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 985-985Article in journal (Other academic)
  • 43. Corpeno Kalamgi, Rebeca
    et al.
    Salah, Heba
    Gastaldello, Stefano
    Martinez-Redondo, Vicente
    Ruas, Jorge L
    Fury, Wen
    Bai, Yu
    Gromada, Jesper
    Sartori, Roberta
    Guttridge, Denis C
    Sandri, Marco
    Larsson, Lars
    Mechano-signalling pathways in an experimental intensive critical illness myopathy model.2016In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 594, no 15, p. 4371-88Article in journal (Refereed)
    Abstract [en]

    KEY POINTS: Using an experimental rat intensive care unit (ICU) model, not limited by early mortality, we have previously shown that passive mechanical loading attenuates the loss of muscle mass and force-generation capacity associated with the ICU intervention. Mitochondrial dynamics have recently been shown to play a more important role in muscle atrophy than previously recognized. In this study we demonstrate that mitochondrial dynamics, as well as mitophagy, is affected by mechanosensing at the transcriptional level, and muscle changes induced by unloading are counteracted by passive mechanical loading. The recently discovered ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that similarly is prevented by passive mechanical loading.

    ABSTRACT: The complete loss of mechanical stimuli of skeletal muscles, i.e. loss of external strain related to weight bearing and internal strain related to activation of contractile proteins, in mechanically ventilated, deeply sedated and/or pharmacologically paralysed intensive care unit (ICU) patients is an important factor triggering the critical illness myopathy (CIM). Using a unique experimental ICU rat model, mimicking basic ICU conditions, we have recently shown that mechanical silencing is a dominant factor triggering the preferential loss of myosin, muscle atrophy and decreased specific force in fast- and slow-twitch muscles and muscle fibres. The aim of this study is to gain improved understanding of the gene signature and molecular pathways regulating the process of mechanical activation of skeletal muscle that are affected by the ICU condition. We have focused on pathways controlling myofibrillar protein synthesis and degradation, mitochondrial homeostasis and apoptosis. We demonstrate that genes regulating mitochondrial dynamics, as well as mitophagy are induced by mechanical silencing and that these effects are counteracted by passive mechanical loading. In addition, the recently identified ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that is reversed by passive mechanical loading. Thus, mechano-cell signalling events are identified which may play an important role for the improved clinical outcomes reported in response to the early mobilization and physical therapy in immobilized ICU patients.

  • 44.
    Covaciu, Lucian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Intranasal Cooling for Cerebral Hypothermia Treatment2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The controlled lowering of core body temperature to 32°C to 34°C is defined as therapeutic hypothermia (TH). Therapeutic hypothermia has been shown to improve neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest. Brain temperature is important for cerebral protection therefore methods for primarily cooling the brain have also been explored.

    This thesis focuses on the likelihood that intranasal cooling can induce, maintain and control cerebral hypothermia. The method uses bilaterally introduced intranasal balloons circulated with cold saline.

    Selective brain cooling induced with this method was effectively accomplished in pigs with normal circulation while no major disturbances in systemic circulation or physiological variables were recorded. The temperature gradients between brain and body could be maintained for at least six hours.

    Intranasal balloon catheters were used for therapeutic hypothermia initiation and maintenance during and after successful resuscitation in pigs. Temperature reduction was also obtained by combined intranasal cooling and intravenous ice-cold fluids with possible additional benefits in terms of physiologic stability after cardiac arrest. Rewarming was possible via the intranasal balloons.

    In these studies brain temperature was recorded invasively by temperature probes inserted in the brain. The fast changes in pig’s brain temperature could also be tracked by a non-invasive method. High-spatial resolution magnetic resonance spectroscopic imaging (MRSI) without internal reference showed a good association with direct invasive temperature monitoring. In addition the mapping of temperature changes during brain cooling was also possible.

    In awake and unsedated volunteers subjected to intranasal cooling brain temperature changes were followed by two MR techniques. Brain cooling was shown by the previously calibrated high-spatial resolution MRSI and by the phase-mapping method. Intranasal cooling reduced body temperature slightly. The volunteers remained alert during cooling, the physiological parameters stable, and no shivering was reported.

    List of papers
    1. Intranasal selective brain cooling in pigs
    Open this publication in new window or tab >>Intranasal selective brain cooling in pigs
    Show others...
    2008 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 78, no 1, p. 83-88Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Special clinical situations where general hypothermia cannot be recommended but can be a useful treatment demand a new approach, selective brain cooling. The purpose of this study was to selectively cool the brain with cold saline circulating in balloon catheters introduced into the nasal cavity in pigs. MATERIAL AND METHODS: Twelve anaesthetised pigs were subjected to selective cerebral cooling for a period of 6 h. Cerebral temperature was lowered by means of bilaterally introduced nasal balloon catheters perfused with saline cooled by a heat exchanger to 8-10 degrees C. Brain temperature was measured in both cerebral hemispheres. Body temperature was measured in rectum, oesophagus and the right atrium. The pigs were normoventilated and haemodynamic variables were measured continuously. Acid-base and electrolyte status was measured hourly. RESULTS: Cerebral hypothermia was induced rapidly and within the first 20 min of cooling cerebral temperature was lowered from 38.1+/-0.6 degrees C by a mean of 2.8+/-0.6 to 35.3+/-0.6 degrees C. Cooling was maintained for 6 h and the final brain temperature was 34.7+/-0.9 degrees C. Concomitantly, the body temperature, as reflected by oesophageal temperature was decreased from 38.3+/-0.5 to 36.6+/-0.9 degrees C. No circulatory or metabolic disturbances were noted. CONCLUSIONS: Inducing selective brain hypothermia with cold saline via nasal balloon catheters can effectively be accomplished in pigs, with no major disturbances in systemic circulation or physiological variables. The temperature gradients between brain and body can be maintained for at least 6 h.

    Keywords
    Brain ischaemia, Brain injury, Cardiac arrest, Cerebral blood flow, Hypothermia, Selective brain cooling, Temperature
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-100190 (URN)10.1016/j.resuscitation.2007.07.002 (DOI)000253204500016 ()17709167 (PubMedID)
    Available from: 2009-03-26 Created: 2009-03-26 Last updated: 2017-12-13Bibliographically approved
    2. Intranasal cooling with or without intravenous cold fluids during and after cardiac arrest in pigs
    Open this publication in new window or tab >>Intranasal cooling with or without intravenous cold fluids during and after cardiac arrest in pigs
    2010 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 54, no 4, p. 494-501Article in journal (Refereed) Published
    Abstract [en]

    Background: Intranasal balloon catheters circulated with cold saline have previously been used for the induction and maintenance of selective brain cooling in pigs with normal circulation. In the present study, we investigated the feasibility of therapeutic hypothermia initiation, maintenance and rewarming using such intranasal balloon catheters with or without addition of intravenous ice-cold fluids during and after cardiac arrest treatment in pigs. Material and methods: Cardiac arrest was induced in 20 anaesthetised pigs. Following 8 min of cardiac arrest and 1 min of cardiopulmonary resuscitation (CPR), cooling was initiated after randomisation with either intranasal cooling (N) or combined with intravenous ice-cold fluids (N+S). Hypothermia was maintained for 180 min, followed by 180 min of rewarming. Brain and oesophageal temperatures, haemodynamic variables and intracranial pressure (ICP) were recorded. Results: Brain temperatures reductions after cooling did not differ (3.8 +/- 0.7 degrees C in the N group and 4.3 +/- 1.5 degrees C in the N+S group; P=0.47). The corresponding body temperature reductions were 3.6 +/- 1.2 degrees C and 4.6 +/- 1.5 degrees C (P=0.1). The resuscitation outcome was similar in both groups. Mixed venous oxygen saturation was lower in the N group after cooling and rewarming (P=0.024 and 0.002, respectively) as compared with the N+S group. ICP was higher after rewarming in the N group (25.2 +/- 2.9 mmHg; P=0.01) than in the N+S group (15.7 +/- 3.3 mmHg). Conclusions: Intranasal balloon catheters can be used for therapeutic hypothermia initiation, maintenance and rewarming during CPR and after successful resuscitation in pigs.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-113241 (URN)10.1111/j.1399-6576.2009.02157.x (DOI)000274932800017 ()19912127 (PubMedID)
    Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2017-12-12Bibliographically approved
    3. Noninvasive monitoring of brain temperature during mild hypothermia
    Open this publication in new window or tab >>Noninvasive monitoring of brain temperature during mild hypothermia
    Show others...
    2009 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 27, no 7, p. 923-932Article in journal (Refereed) Published
    Abstract [en]

    The main purpose of this study was to verify the feasibility of brain temperature mapping with high-spatial- and reduced-spectral-resolution magnetic resonance spectroscopic imaging (MRSI). A secondary goal was to determine the temperature coefficient of water chemical shift in the brain with and without internal spectral reference. The accuracy of the proposed MRSI method was verified using a water and vegetable oil phantom. Selective decrease of the brain temperature of pigs was induced by intranasal cooling. Temperature reductions between 2 degrees C and 4 degrees C were achieved within 20 min. The relative changes in temperature during the cooling process were monitored using MRSI. The reference temperature was measured with MR-compatible fiber-optic probes. Single-voxel (1)H MRS was used for measurement of absolute brain temperature at baseline and at the end of cooling. The temperature coefficient of the water chemical shift of brain tissue measured by MRSI without internal reference was -0.0192+/-0.0019 ppm/degrees C. The temperature coefficients of the water chemical shift relative to N-acetylaspartate, choline-containing compounds and creatine were -0.0096+/-0.0009, -0.0083+/-0.0007 and -0.0091+/-0.0011 ppm/degrees C, respectively. The results of this study indicate that MRSI with high spatial and reduced spectral resolutions is a reliable tool for monitoring long-term temperature changes in the brain.

    Keywords
    Selective brain cooling, Hypothermia, Temperature mapping, Spectroscopy, Spectroscopic imaging
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-113253 (URN)10.1016/j.mri.2009.01.011 (DOI)000269613000005 ()19282122 (PubMedID)
    Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2017-12-12Bibliographically approved
    4. Brain temperature in healthy volunteers subjected to intranasal cooling
    Open this publication in new window or tab >>Brain temperature in healthy volunteers subjected to intranasal cooling
    Show others...
    2011 (English)In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Other academic) Published
    Abstract [en]

    Purpose:

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.

    Methods:

    Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.

    Results:

    Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   

    Conclusion:

    Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.

    Keywords
    Therapeutic hypothermia, Brain temperature, Magnetic resonance spectroscopy, selective brain cooling, trigeminal reflex
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-134228 (URN)10.1007/s00134-011-2264-7 (DOI)21647717 (PubMedID)
    Available from: 2010-11-23 Created: 2010-11-23 Last updated: 2017-12-12Bibliographically approved
  • 45.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, M
    Lunderquist, A
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Refereed)
    Abstract [en]

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.

  • 46.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, Mats
    Division of thoracic sciences, Department of clinical sciences, Lund University.
    Lunderquist, Anders
    Department of radiology, Lund University.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in healthy volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Other academic)
    Abstract [en]

    Purpose:

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.

    Methods:

    Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.

    Results:

    Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   

    Conclusion:

    Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.

  • 47.
    Dahl, Michael
    et al.
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Hayes, Chris
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Rasmussen, Bodil Steen
    Aalborg Univ Hosp, Dept Anesthesiol & Intens Care Med, Hobrovej 18-21, DK-9000 Aalborg, Denmark..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Secher, Niels H.
    Univ Copenhagen, Dept Anesthesiol, Copenhagen Muscle Res Ctr, Rigshosp 2043, Blegdamsvej 9, DK-2100 Copenhagen, Denmark..
    Can a central blood volume deficit be detected by systolic pressure variation during spontaneous breathing?2016In: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 16, article id 58Article in journal (Refereed)
    Abstract [en]

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

  • 48. Dankiewicz, Josef
    et al.
    Schmidbauer, Simon
    Nielsen, Niklas
    Kern, Karl B.
    Mooney, Michael R.
    Stammet, Pascal
    Riker, Richard R.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Seder, David
    Smid, Ondrej
    Sunde, Kjetil
    Soreide, Eldar
    Unger, Barbara T.
    Friberg, Hans
    Safety, Feasibility, and Outcomes of Induced Hypothermia Therapy Following In-Hospital Cardiac Arrest-Evaluation of a Large Prospective Registry2014In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 12, p. 2537-2545Article in journal (Refereed)
    Abstract [en]

    Objectives: Despite a lack of randomized trials, practice guidelines recommend that mild induced hypothermia be considered for comatose survivors of in-hospital cardiac arrest. This study describes the safety, feasibility, and outcomes of mild induced hypothermia treatment following in-hospital cardiac arrest. Design: Prospective, observational, registry-based study. Setting: Forty-six critical care facilities in eight countries in Europe and the United States reporting in the Hypothermia Network Registry and the International Cardiac Arrest Registry. Patients: A total of 663 patients with in-hospital cardiac arrest and treated with mild induced hypothermia were included between January 2004 and February 2012. Interventions: None. Measurements and Main Results: A cerebral performance category of 1 or 2 was considered a good outcome. At hospital discharge 41% of patients had a good outcome. At median 6-month follow-up, 34% had a good outcome. Among in-hospital deaths, 52% were of cardiac causes and 44% of cerebral cause. A higher initial body temperature was associated with reduced odds of a good outcome (odds ratio, 0.79; 95% CI, 0.68-0.92). Adverse events were common; bleeding requiring transfusion (odds ratio, 0.56; 95% CI, 0.31-1.00) and sepsis (odds ratio, 0.52; 95% CI, 0.30-0.91) were associated with reduced odds for a good outcome. Conclusions: In this registry study of an in-hospital cardiac arrest population treated with mild induced hypothermia, we found a 41% good outcome at hospital discharge and 34% at follow-up. Infectious complications occurred in 43% of cases, and 11% of patients required a transfusion for bleeding. The majority of deaths were of cardiac origin.

  • 49. De Waele, Jan J
    et al.
    Kaplan, Mark
    Sugrue, Michael
    Sibaja, Pablo
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    How to deal with an open abdomen?2015In: Anaesthesiology intensive therapy, ISSN 1731-2515, Vol. 47, no 4, p. 372-378Article, review/survey (Refereed)
    Abstract [en]

    Appropriate open abdomen treatment is one of the key elements in the management of patients who require decompressive laparotomy or in whom the abdomen is left open prophylactically. Apart from fluid control and protection from external injury, fluid evacuation and facilitation of early closure are now the goals of open abdomen treatment. Abdominal negative pressure therapy has emerged as the most appropriate method to reach these goals. Especially when combined with strategies that allow progressive approximation of the fascial edges, high closure rates can be obtained. Intra-abdominal pressure measurement can be used to guide the surgical strategy and continued attention to intra-abdominal hypertension is necessary. This paper reviews recent advances as well as identifying the remaining challenges in patients requiring open abdomen treatment. The new classification system of the open abdomen is an important tool to use when comparing the efficacy of different strategies, as well as different systems of temporary abdominal closure.

  • 50.
    Drevhammar, Thomas
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Ostersund Hosp, Dept Anaesthesiol, S-83183 Ostersund, Sweden..
    Nilsson, Kjell
    Ventinvent AB, Ostersund, Sweden..
    Zetterstrom, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jonsson, Baldvin
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Seven Ventilators Challenged With Leaks During Neonatal Nasal CPAP: An Experimental Pilot Study2015In: Respiratory care, ISSN 0020-1324, E-ISSN 1943-3654, Vol. 60, no 7, p. 1000-1006Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nasal CPAP is the most common respiratory support for neonates. Several factors are considered important for effective treatment, including leaks at the patient interface and the delivery of pressure-stable CPAP. Investigations of pressure stability during leaks should include both the change in the mean delivered CPAP and the pressure variation during each breath. The aim of this study was to examine the response of ventilators delivering nasal CPAP when challenged with leaks at the patient interface. METHODS: Seven ventilators providing nasal CPAP at 4 cmH(2)O were challenged with leaks during simulated neonatal breathing. Leak was applied for 15 consecutive breaths at a constant level (1-4 L/min). RESULTS: The 2 aspects of pressure stability were evaluated by measuring the mean delivered CPAP and the amplitude of pressure swings before, during, and after leaks. The ability to maintain the delivered CPAP and the amplitude of pressure swings varied greatly among the 7 ventilators before, during, and after leaks. Four of the ventilators tested have built-in leak compensation. CONCLUSIONS: There was no simple relationship between maintaining delivered CPAP during leaks and providing CPAP with low pressure swing amplitude. Maintaining the delivered CPAP and providing this without pressure swings are 2 separate aspects of pressure stability, and investigations concerning the clinical importance of pressure stability should address both aspects. This study also shows that compensation for leaks does not necessarily provide pressure-stable CPAP.

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