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  • 1.
    Aakhus, Mark
    et al.
    Rutgers University.
    Ågerfalk, Pär
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Digital Innovation as Design of Digital Practice: Doctors as Designers in Healthcare2018In: Proceedings of the 51st Hawaii International Conference on System Sciences (HICSS), 2018, p. 4594-4601Conference paper (Refereed)
    Abstract [en]

    Medical professionals are increasingly assuming the role of maker and creator. At the same time, digital innovations, as part of evolving information infrastructures, are becoming increasingly prevalent in healthcare. In this paper, we adopt a Schönian approach to understand how a medical professional, who is not an IS designer by trade, engages in the design of digital practice - turning what may appear as a failed digital innovation effort into a successful design of digital practice. Our inquiry suggests three pragmatic principles that call for further investigation: (a) professionals can make a significant contribution to design work by inventing means for fact-based, reflective engagement with the situation; (b) the reorganization of work practice involves organizational design, information system design, and communication design; and (c) developing design as digital practice entails the development of fact-based design practice and must engage practical theories.

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  • 2.
    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: 2022-01-29Bibliographically 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: 2022-01-29Bibliographically 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.
    Show others...
    2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no 1, 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.

    Place, publisher, year, edition, pages
    Walter de Gruyter, 2017
    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: 2019-09-25Bibliographically 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
    Show others...
    (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.
    Show others...
    (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
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  • 3.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Linnman, Clas
    Harvard Med Sch, Boston Childrens Hosp, Dept Anesthesiol, Boston, MA USA.
    Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no 1, p. 418-424Article in journal (Refereed)
    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.

  • 4.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. PET Centre, Department of Medical Imaging, Uppsala University Hospital, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Linnman, Clas
    Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, United States.
    Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography2022In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 163, no 3, p. 489-495Article in journal (Refereed)
    Abstract [en]

    Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.

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  • 5.
    Abbasi, R.
    et al.
    Loyola Univ Chicago, Dept Phys, Chicago, IL 60660 USA.
    Beise, Jakob
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Botner, Olga
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Coleman, Alan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Glaser, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Glüsenkamp, Thorsten
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics. Friedrich Alexander Univ Erlangen Nurnberg, Erlangen Ctr Astroparticle Phys, D-91058 Erlangen, Germany..
    Hallgren, Allan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Heyer, Nils
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    O'Sullivan, Erin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Pérez de los Heros, Carlos
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Pontén, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Sharma, Aruna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Valtonen-Mattila, Nora
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zhelnin, P.
    Harvard Univ, Dept Phys, Cambridge, MA 02138 USA;Harvard Univ, Lab Particle Phys & Cosmol, Cambridge, MA 02138 USA.
    IceCat-1: The IceCube Event Catalog of Alert Tracks2023In: Astrophysical Journal Supplement Series, ISSN 0067-0049, E-ISSN 1538-4365, Vol. 269, no 1, article id 25Article in journal (Refereed)
    Abstract [en]

    We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT.

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  • 6.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ericson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Increased CSF Levels of Apolipoproteins and Complement Factors in Trigeminal Neuralgia Patients-In Depth Proteomic Analysis Using Mass Spectrometry2020In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 21, no 9-10, p. 1075-1084Article in journal (Refereed)
    Abstract [en]

    The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n = 17), scheduled to undergo microvascular decompression, and from controls (n = 20) was analyzed and compared with in depth mass spectrometry TMTbased quantitative proteomics. We identified 2552 unique proteins, of which 46 were significantly altered (26 increased, and 20 decreased, q-value < .05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein, such as Apolipoprotein A4, Apolipoprotein M, and Apolipoprotein A1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. Perspective: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and signif-icantly over-represented, implying an inflammatory component in the pathophysiology of the disease.

  • 7.
    Acosta, Cecilia M.
    et al.
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Lopez Vargas, Maria Paz
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Oropel, Facundo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Valente, Lisandro
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Ricci, Lila
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Natal, Marcela
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Autonoma Madrid, Hosp Univ Princesa, Inst Carlos III, CIBERES, Madrid, Spain; Univ Autonoma Madrid, Hosp Univ Princesa, Dept Crit Care, Madrid, Spain.
    Tusman, Gerardo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study2021In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 38, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND 

    Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified.

    OBJECTIVE 

    The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia.

    DESIGN 

    A randomised controlled study.

    SETTING 

    Single-institution study, community hospital, Mar del Plata. Argentina.

    PATIENTS 

    We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia.

    INTERVENTIONS 

    Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening.

    MAIN OUTCOME MEASURES 

    Lung aeration score and atelectasis assessed by LUS.

    RESULTS 

    Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ± 3.8 vs. 3.5 ± 3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ± 3.2 and 1.8 ± 2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ± 3.1) when compared with the CPAP group (0.5 ± 1.5; P < 0.01).

    CONCLUSION 

    The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour.

    TRIAL REGISTRY 

    Clinicaltrials.gov NCT03461770.

  • 8.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Poliotto, Sergio
    Hosp Privado Comun, Dept Pediat Surg, Mar Del Plata, Argentina..
    Abrego, Diego
    Hosp Privado Comun, Dept Pediat Surg, Mar Del Plata, Argentina..
    Bradley, Dolores
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    de Esteban, Santiago
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Mir, Francisco
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Ricci, Lila
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina..
    Natal, Marcela
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Solna Stockholm, Sweden.;Getinge Crit Care AB, Solna, Sweden..
    Hallbäck, Magnus
    Getinge Crit Care AB, Solna, Sweden..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory. CIBERES Network Biomed Res Ctr, Madrid, Spain.;Univ Autonoma Madrid, Hosp Univ La Princesa, Dept Crit Care, Madrid, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina.;Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, Argentina..
    Effect of an Individualized Lung Protective Ventilation on Lung Strain and Stress in Children Undergoing Laparoscopy: An Observational Cohort Study2024In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 140, no 3, p. 430-441Article in journal (Refereed)
    Abstract [en]

    Background: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children.

    Methods: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure.

    Results: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum.

    Conclusions: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits.

  • 9.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Costantini, Mauro
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Echevarria, Camila
    Hosp Privado Comunidad Mar Del Plata, Dept Radiol, Buenos Aires, DF, Argentina..
    Pollioto, Sergio
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Abrego, Diego
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Doppler images of intra-pulmonary shunt within atelectasis in anesthetized children2016In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 8, article id 19Article in journal (Refereed)
    Abstract [en]

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

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

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

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  • 10.
    Adamski, Jan
    et al.
    via media, S-75655 Uppsala, Sweden..
    Goraj, Radoslaw
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Onichimowski, Dariusz
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Gawlikowska, Ewa
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The differences between two selected intensive care units located in central and northern Europe: preliminary observation2015In: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 47, no 2, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to evaluate possible differences in the functioning of two selected intensive care units in Poland and Finland. The activity of the units was analysed over a period of one year. Methods: The following parameters were compared: demography of treated populations, site of admission, category of illness, severity of illness (APACHE-II scale), mean length of stay, demanded workload (TISS-28 scale), mortality (both ICU and hospital) and standardized mortality ratio (SMR). Results: The results of this study indicated that most of the patients in the Polish ICU, regardless of age, diagnosis and APACHE II score, presented significantly longer lengths of stay (14.65 +/- 13.6 vs 4.1 +/- 4.7 days, P = 0.0001), higher mean TISS-28 score (38.9 +/- 9.1 vs 31.2 +/- 6.1, P = 0.0001) and higher ICU and hospital mortality (41.5% vs 10.2% and 44.7% vs 21.8%, respectively, P = 0.0001). The values of SMR were 0.9 and 0.85 for the Finnish and Polish ICUs, respectively. Conclusion: The collected data indicate huge differences in the utilisation of critical care resources. Treatment in Polish ICU is concentrated on much more severely ill patients which might be sometimes accompanied by futility of care. In order to verify and correctly interpret the presented phenomena, further studies are needed.

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  • 11.
    Adamski, Jan
    et al.
    Satakunta Dist Hosp, Dept Anaesthesia & Intens Care, Pori, Finland..
    Nowakowski, Piotr
    Czerniakowski Hosp, Dept Anaesthesiol & Intens Therapy, Warsaw, Poland..
    Gorynski, Pawel
    Ctr Monitoring Populat Hlth Status, Dept Hyg, Natl Inst Publ Hlth, Warsaw, Poland..
    Onichimowski, Dariusz
    Reg Specialist Hosp, Dept Anaesthesiol & Intens Therapy, Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Incidence of in-hospital cardiac arrest in Poland2016In: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 48, no 5, p. 288-293Article in journal (Refereed)
    Abstract [en]

    Background: In-hospital cardiac arrest with its poor prognosis is a challenging problem in hospitals. The aim of this study was to evaluate in Polish hospitals the frequency of in-hospital cardiac arrests with the subsequent mortality, with special emphasis on the type of unit at which the event occurred, and the patient's demographic data, such as age and sex.

    Methods: The study was a retrospective analysis of data for 2012 registered in the Polish General Hospital Morbidity Study. This research covered all Polish hospitals, excluding only government and psychiatric hospitals. The study inclusion criterion was the incidence of cardiac arrest in any hospital ward, recorded by the respective ICD-10 diagnosis code.

    Results: Of the 7,775,553 patients hospitalized, the diagnosis of cardiac arrest was reported in a total of 22,602 patients, which included 22,317 adults (98.7% of all patients) and 285 children (1.3%). Overall mortality after cardiac arrest among adults was 74.2%, and in children 46.7%. In both absolute numbers and as percentages of all documented cases, cardiac arrests occurred most often at the departments of intensive care, internal medicine, cardiology and emergency medicine. The accompanying mortality was lower than average at the departments of intensive care, cardiology, cardiology high dependency unit and emergency medicine. The median age of patients with cardiac arrest who died in the hospital was higher than the median age of those who survived (72 vs. 64; P < 0.05). Although cardiac arrests were reported more often among men than women (58.2% vs. 41.8%; P < 0.001), the hospital mortality was higher among women (79.2% vs. 71.6%; P < 0.001).

    Conclusion: The frequency of in-hospital cardiac arrests in Polish hospitals and the subsequent mortality is not substantially different from that observed in other countries. However, our study, based on ICD-10 diagnosis codes, gives only limited information about the patients and circumstances of this event. An in-depth analysis of the causes, prognoses, and outcome of in-hospital cardiac arrests could be facilitated by the creation of a national registry.

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  • 12.
    Adamski, Jan
    et al.
    Satakunta Cent Hosp, Dept Intens Care Med, Sairaalantie 3,PL 317, FIN-28500 Pori, Finland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lahtinen, Pasi
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Reinikainen, Matti
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland.;Univ Eastern Finland, Fac Hlth Sci, Sch Med, Inst Clin Med, Kuopio, Finland..
    Kaminski, Tadeusz
    Cent Hosp Middle Ostrobothnia, Dept Intens Care Med, Kokkola, Finland..
    Pietiläinen, Laura
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Musialowicz, Tadeusz
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Intensive care patient survival after limiting life-sustaining treatment-The FINNEOL* national cohort study2020In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 64, no 8, p. 1144-1153Article in journal (Refereed)
    Abstract [en]

    Background Few studies have examined survival in intensive care unit (ICU) patients after the restriction of life-sustaining treatment (LST). We aimed to analyse independent factors associated with hospital and 12-month survival rates in ICU patients after treatment restrictions. Methods This retrospective observational study examined all patients treated in adult ICUs from 1 January 2016 until 31 December 2016 included in the Finnish ICU Registry. Multivariable logistic regression analysis was performed to explain the effect on survival. Results Decisions to limit LST were made for 2444 patients (13.7%; 95% CI 13.2-14.2). ICU, hospital, and 12-month survival rates were 71% (95% CI 69-73), 49% (95% CI 47-51), and 24% (95% CI 22-26), respectively. In patients for whom life support was withheld, increased 12-month survival rates were associated with admission from the operating theatre (OR 1.9, 95% CI 1.1-3.4), good pre-hospital physical fitness (OR 4.7, 95% Cl 1.2-16.8) and being housed at home (OR 2.0, 95% Cl 1.4-2.8). Decreased survival rates were associated with admission from a hospital ward (OR 0.67, 95% Cl 0.5-0.9), higher comorbidity (OR 0.6, 95% Cl 0.4-0.9), cancer (OR 0.4, 95%CI 0.2-0.9), greater illness severity (SAPS II; OR 0.98, 95% Cl 0.98-0.99), and higher care intensity (TISS-76; OR 0.93, 95% Cl 0.92-0.95). Conclusion Survival among ICU patients with limited treatment was higher than expected. Advanced age was not associated with higher mortality, potentially because treatment restrictions may be set more easily for older patients.

  • 13.
    Adamski, Jan
    et al.
    Univ Warmia & Mazury, Fac Med Sci, Dept Anaesthesiol & Intens Care, Ul Warszawska 30, PL-10082 Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Musialowicz, Tadeusz
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Lahtinen, Pasi
    Cent Hosp South Ostrobothnia, Anaesthesiol & Intens Care Dept, Seinajoki, Finland..
    Reinikainen, Matti
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland.;Univ Eastern Finland, Fac Hlth Sci, Sch Med, Inst Clin Med, Kuopio, Finland..
    Predictors of treatment limitations in Finnish intensive care units2022In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 66, no 4, p. 526-538Article in journal (Refereed)
    Abstract [en]

    Background Few studies have examined the factors that predict the limitations of life-sustaining treatment (LST) to patients in intensive care units (ICUs). We aimed to identify variables associated with the decision of withholding of life support (WHLS) at admission, WHLS during ICU stay and the withdrawal of ongoing life support (WDLS). Methods This retrospective observational study comprised 17,772 adult ICU patients who were included in the nationwide Finnish ICU Registry in 2016. Factors associated with LST limitations were identified using hierarchical logistic regression. Results The decision of WHLS at admission was made for 822 (4.6%) patients, WHLS during ICU stay for 949 (5.3%) patients, and WDLS for 669 (3.8%) patients. Factors strongly predicting WHLS at admission included old age (adjusted odds ratio [OR] for patients aged 90 years or older in reference to those younger than 40 years was 95.6; 95% confidence interval [CI], 47.2-193.5), dependence on help for activities of daily living (OR, 3.55; 95% CI, 3.01-4.2), and metastatic cancer (OR, 4.34; 95% CI, 3.16-5.95). A high severity of illness predicted later decisions to limit LST. Diagnoses strongly associated with WHLS at admission were cardiac arrest, hepatic failure and chronic obstructive pulmonary disease. Later decisions were strongly associated with cardiac arrest, hepatic failure, non-traumatic intracranial hemorrhage, head trauma and stroke. Conclusion Early decisions to limit LST were typically associated with old age and chronic poor health whereas later decisions were related to the severity of illness. Limitations are common for certain diagnoses, particularly cardiac arrest and hepatic failure.

  • 14.
    Ahlström, Björn
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    The epidemiology of risk factors and short and long-term outcome in the Swedish intensive care cohort2021Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dissertation presented at Uppsala University to be publicly examined on Zoom: https://uu-se.zoom.us/j/7214327760, Tuesday, 11 May 2021 at 13:00 for the degree of Licentiate of Philosophy (Faculty of Medicine). The examination will be conducted in English and Swedish. Chairman of the Examining committee: Professor Karl Michaëlsson (Medical epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala) 

    Abstract Ahlström, B. 2021. The epidemiology of risk factors and short- and long-term out-come in the Swedish intensive care cohort. 76 pp.  

    Severe sepsis and septic shock, linked to persistent organ dysfunctions, have poor short- and long-term mortality outcomes. These conditions also adversely affect health-related quality of life. After intensive care with severe sepsis and septic shock, memory and other cognitive functions have shown deterioration. In addition, there are indications of an increased risk of dementia. Yet, whether severe sepsis and septic shock are independently linked to dementia or dementia development is linked to more general severe illness remains unclear. In the Swedish intensive care cohort we compared 16 115 one-year sepsis survivors without previous dementia to 194 219 patients (controls) admitted to intensive care for other reasons using a Cox proportional hazards model. The crude risk of dementia was increased in the severe sepsis and septic shock group. However, after adjustment for demographics, comorbidities and factors reflecting the severity of acute illness, severe sepsis and septic shock was found not to be a significant risk factor of incident dementia with a haz-ard ratio of 1.01 (95% confidence interval 0.91-1.11). Thus, we concluded that although the incidence of dementia is high after intensive care, severe sepsis or septic shock is not causative.  

    Coronavirus disease 2019 (COVID-19) has put a tremendous strain on the healthcare system in general and intensive care, in particular, since its emergence in Wuhan, China, in late 2019. Risk factors of ICU admission and mortality from COVID-19 were reported early during the pandemic, but only as univariate variables. Under the hypothesis that there are several independent risk factors of critical COVID-19, we used statistical models to explore demographic characteristics and comorbidi-ties in the first 1 981 ICU-admitted patients with COVID-19 in Sweden. On the risk of ICU admission, we also included matched population controls in a 1:4 ratio. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission. Oral anticoagulants were associated with a protective effect. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors were independent risk factors of ICU mortality. Treatment with statins was protective. Our findings suggest that there are several independent risk factors of ICU admission and ICU mortality in COVID-19.

    Björn Ahlström, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, SE-75185 Uppsala, Sweden  

    and  Centre of clinical research, Region Dalarna, SE-79182 Falun, Sweden. 

    List of papers
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Open this publication in new window or tab >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed) Published
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Place, publisher, year, edition, pages
    BMC, 2020
    Keywords
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Available from: 2020-10-16 Created: 2020-10-16 Last updated: 2024-01-10Bibliographically approved
    2. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Open this publication in new window or tab >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Show others...
    2021 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed) Published
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Place, publisher, year, edition, pages
    John Wiley & SonsWiley, 2021
    Keywords
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2024-01-15Bibliographically approved
  • 15.
    Ahlström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The epidemiology of risk factors and short- and long-term outcome in the Swedish intensive care cohort2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The sepsis syndrome is present in ¼ to ⅓ of patients in intensive care units (ICUs) worldwide. The short-term prognosis is grim, with a 30-day mortality of 30–35%; however, the long- term outcomes are now being explored, as multi-professional follow-up after ICU care is increasingly being implemented. In 2020 the first and second waves of another severe infection, the Coronavirus disease 2019 (Covid-19) hit Sweden. The number of ICU beds were scaled up by several hundred percent while we simultaneously tried to understand the disease. Reports on risk factors for adverse outcomes in Covid-19 started to appear, but we needed to know more. Thus, we initiated this project aiming at assessing sepsis as an independent risk factor for later morbidity and mortality. Subsequently, with the onset of the pandemic, our focus shifted to identifying risk factors for adverse outcomes in Covid-19 and describing the functional recovery after severe Covid-19. We used the Swedish Intensive Care Registry and several governmental registries to this end.

    In Cox regression, we compared one-year ICU sepsis survivors without previous dementia with ICU patients without sepsis, finding no increased risk of dementia during follow- up. In a similar cohort, we assessed the impact of sepsis on long-term mortality and causes of death in a series of Cox and multinomial models. We found a surprisingly small overall association between sepsis and mortality and a persistently increased risk of infectious causes of death in sepsis patients. We compared the prevalence of several common comorbidities and medications as risk factors for ICU admission and mortality in ICU patients with Covid-19 with that of age- and sex-matched population controls and in patients discharged alive with those that were deceased at discharge. We found associations between several comorbidities and medications with these adverse outcomes. To better understand the meaning of these comorbidities as risk factors for short-term mortality, we compared them in logistic regression models on patients with Covid-19, sepsis and acute respiratory distress syndrome (ARDS). We found very similar impacts from the comorbidities; however, greater age was more associated with mortality in Covid-19 than in either sepsis or ARDS. Finally, we investigated the long-term functional recovery in ICU patients with Covid-19 compared to hospital-admitted patients with Covid-19 and population controls matched to the ICU group. The ICU patients had a markedly impeded recovery that was not explained by demographics or comorbidities in statistical models.

    List of papers
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Open this publication in new window or tab >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed) Published
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Place, publisher, year, edition, pages
    BMC, 2020
    Keywords
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Available from: 2020-10-16 Created: 2020-10-16 Last updated: 2024-01-10Bibliographically approved
    2. Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    Open this publication in new window or tab >>Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    (English)Manuscript (preprint) (Other academic)
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-519454 (URN)
    Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-10
    3. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Open this publication in new window or tab >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Show others...
    2021 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed) Published
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Place, publisher, year, edition, pages
    John Wiley & SonsWiley, 2021
    Keywords
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2024-01-15Bibliographically approved
    4. A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
    Open this publication in new window or tab >>A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
    Show others...
    2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 15703Article in journal (Refereed) Published
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

    Place, publisher, year, edition, pages
    Springer Nature, 2022
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-486398 (URN)10.1038/s41598-022-19539-0 (DOI)000857187000001 ()36127433 (PubMedID)
    Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2024-01-10Bibliographically approved
    5. One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Open this publication in new window or tab >>One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-519456 (URN)
    Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-10
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  • 16.
    Ahlström, Björn
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    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.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohortManuscript (preprint) (Other academic)
  • 17.
    Ahlström, Björn
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Frithiof, Robert
    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 Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    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.
    The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality2021In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Download full text (pdf)
    fulltext
  • 18.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Falun Cent Hosp, Ctr Clin Res Dalarna, Reg Dalarna, Nissers V6g 3, S-79182 Falun, Sweden..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    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.
    A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 15703Article in journal (Refereed)
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

    Download full text (pdf)
    FULLTEXT01
  • 19.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Ctr Clin Res Dalarna, Reg Dalarna, Nissers Vag 3, S-79182 Falun, Sweden..
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    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. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.;Uppsala Univ, CIRRUS, Dept Surg Sci, Hedenstierna Lab,Anesthesiol & Intens Care, Uppsala, Sweden..
    A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort2020In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed)
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Download full text (pdf)
    FULLTEXT01
  • 20.
    Ahlström, Björn
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohortManuscript (preprint) (Other academic)
  • 21.
    Ahlström, J. Zebialowicz
    et al.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Massaro, F.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Mikolka, P.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
    Feinstein, R.
    Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Basabe-Burgos, O.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Curstedt, T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Johansson, J.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Rising, A.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 245Article in journal (Refereed)
    Abstract [en]

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

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    FULLTEXT01
  • 22.
    Akerman, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Ctr Paediat Anaesthes & Intens Care Res, Uppsala, Sweden..
    Axelin, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Turku, Dept Nursing Sci, Turku, Finland..
    Traube, Chani
    Weill Cornell Med Ctr, Dept Pediat, New York, NY USA..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Ctr Paediat Anaesthes & Intens Care Res, Uppsala, Sweden..
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Adapting the Cornell assessment of pediatric delirium for Swedish context: translation, cultural validation and inter-rater reliability2024In: BMC Pediatrics, E-ISSN 1471-2431, Vol. 24, no 1, article id 413Article in journal (Refereed)
    Abstract [en]

    Background: Pediatric delirium causes prolonged hospital stays, increased costs, and distress for children and caregivers. Currently, there is no delirium screening tool available in Sweden that has been translated, culturally validated, and tested for reliability. This study aimed to translate, culturally adapt, and assess the suitability of the Cornell Assessment of Pediatric Delirium (CAPD) for implementation in Swedish healthcare settings.

    Methods: The CAPD was translated and culturally adapted to Swedish context following the ten-step process recommended by the International Society for Pharmacoeconomics and Outcomes Task Force for Translation and Cultural Adaptation. The Swedish CAPD was tested in the pediatric intensive care unit of Uppsala University Hospital, a tertiary hospital in Sweden. Inter-rater reliability was tested using intraclass correlation coefficient (ICC), with both Registered Nurses (RNs) and Assistant Nurses (ANs) conducting parallel measurements using the Swedish CAPD. A reliability score of ICC > 0.75 was considered indicative of good reliability.

    Results: After translation of the CAPD into Swedish, 10 RNs participated in the cultural adaptation process. Issues related to word choice, education, and instructions were addressed. Wording improvements were made to ensure accurate interpretation. Supplementary training sessions were organized to strengthen users' proficiency with the Swedish CAPD. Additional instructions were provided to enhance clarity and usability. Inter-rater reliability testing resulted in an ICC of 0.857 (95% CI: 0.708-0.930), indicating good reliability.

    Conclusion: This study successfully translated and culturally adapted the CAPD to align with Swedish contextual parameters. The resulting Swedish CAPD demonstrated good inter-rater reliability, establishing its viability as a tool for measuring delirium among pediatric patients in Swedish pediatric intensive care units. Trail registration Not applicable.

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    FULLTEXT01
  • 23.
    Albert, Christian
    et al.
    Otto von Guericke Univ, Univ Clin Cardiol & Angiol, Med Fac, Magdeburg, Germany.;Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany..
    Zapf, Antonia
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Haase, Michael
    Otto von Guericke Univ, Fac Med, Magdeburg, Germany.;Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany..
    Rover, Christian
    Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany..
    Pickering, John W.
    Univ Otago Christchurch, Dept Med, Christchurch, New Zealand.;Christchurch Hosp, Emergency Dept, Christchurch, New Zealand..
    Albert, Annemarie
    Diaverum Renal Serv Germany, MVZ Neuen Garten 11, D-14469 Potsdam, Germany.;Klinikum Ernst von Bergmann, Dept Nephrol & Endocrinol, Potsdam, Germany..
    Bellomo, Rinaldo
    Austin Hosp, Dept Intens Care, Melbourne, Vic, Australia.;Univ Melbourne, Ctr Integrated Crit Care, Melbourne, Vic, Australia..
    Breidthardt, Tobias
    Univ Hosp Basel, Dept Internal Med, Basel, Switzerland.;Univ Hosp Basel, Dept Nephrol, Basel, Switzerland.;Univ Hosp Basel, Dept Cardiol, Basel, Switzerland..
    Camou, Fabrice
    CHU Bordeaux, Hop St Andre, Serv Reanimat Med, Bordeaux, France..
    Chen, Zhongquing
    Southern Med Univ, Nanfang Hosp, Dept Crit Care Med, Guangzhou, Guangdong, Peoples R China..
    Chocron, Sidney
    Univ Hosp Jean Minjoz, Dept Thorac & Cardiovasc Surg, Besancon, France..
    Cruz, Dinna
    Univ Calif San Diego, Div Nephrol Hypertens, San Diego, CA 92103 USA..
    de Geus, Hilde R. H.
    Erasmus MC, Dept Intens Care, Rotterdam, Netherlands..
    Devarajan, Prasad
    Univ Cincinnati, Div Nephrol & Hypertens, Cincinnati Childrens Hosp, Cincinnati, OH USA..
    Di Somma, Salvatore
    Univ Rome, Dept Med Surg Sci & Translat Med, Emergency Med, S Andrea Hosp, Rome, Italy..
    Doi, Kent
    Univ Tokyo, Dept Emergency & Crit Care Med, Tokyo, Japan..
    Endre, Zoltan H.
    Univ New South Wales, Prince Wales Hosp, Dept Nephrol, Sydney, NSW, Australia.;Univ New South Wales, Clin Sch, Dept Nephrol, Sydney, NSW, Australia..
    Garcia-Alvarez, Mercedes
    Hosp Santa Creu Sant & Pau, Dept Anesthesiol, Barcelona, Spain..
    Hjortrup, Peter B.
    Copenhagen Univ Hosp, Dept Intens Care, Copenhagen, Denmark..
    Hur, Mina
    Konkuk Univ, Dept Lab Med, Sch Med, Seoul, South Korea..
    Karaolanis, Georgios
    Natl & Kapodistrian Univ Athens, Med Sch, Laiko Gen Hosp, Vasc Unit,Dept Surg 1, Athens, Greece..
    Kavalci, Cemil
    Baskent Univ, Emergency Dept, Fac Med, Ankara, Turkey..
    Kim, Hanah
    Konkuk Univ, Dept Lab Med, Sch Med, Seoul, South Korea..
    Lentini, Paolo
    San Bassiano Hosp, Dept Nephrol & Dialysis, Bassano Del Grappa, Italy..
    Liebetrau, Christoph
    Kerckhoff Clin, Dept Cardiol, Bad Nauheim, Germany..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Martensson, Johan
    Karolinska Inst, Sect Anaesthesia & Intens Care Med, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Mueller, Christian
    Univ Hosp Basel, Dept Internal Med, Basel, Switzerland.;Univ Hosp Basel, Dept Nephrol, Basel, Switzerland.;Univ Hosp Basel, Dept Cardiol, Basel, Switzerland..
    Nanas, Serafim
    Natl & Kapodistrian Univ Athens, Evangelismos Gen Hosp, Crit Care Dept 1, Athens, Greece..
    Nickolas, Thomas L.
    Columbia Univ, Vagelos Coll Phys & Surg, New York, NY USA..
    Pipili, Chrysoula
    Natl & Kapodistrian Univ Athens, Evangelismos Gen Hosp, Crit Care Dept 1, Athens, Greece..
    Ronco, Claudio
    Univ Padua, Nephrol Dialysis & Transplantat, Padua, Italy.;San Bortolo Hosp, Int Renal Res Inst, Vicenza, Italy..
    Rosa-Diez, Guillermo J.
    Hosp Italiano Buenos Aires, Dept Nephrol Dialysis & Transplantat, Buenos Aires, DF, Argentina..
    Ralib, Azrina
    Int Islamic Univ Malaysia, Dept Anaesthesiol & Intens Care, Pahang, Malaysia..
    Soto, Karina
    Hosp Fernando Fonseca, Dept Nephrol, Amadora, Portugal.;Univ Lisbon, Ctr Estat & Aplicacoes, CEAUL, Lisbon, Portugal..
    Braun-Dullaeus, Ruediger C.
    Otto von Guericke Univ, Univ Clin Cardiol & Angiol, Med Fac, Magdeburg, Germany..
    Heinz, Judith
    Univ Med Ctr Gottingen, Dept Med Stat, Gottingen, Germany..
    Haase-Fielitz, Anja
    Univ Potsdam, Brandenburg Med Sch Theodor Fontane, Immanuel Diakonie Bernau, Heart Ctr Brandenburg,Dept Cardiol,Fac Hlth Sci, Potsdam, Germany..
    Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis2020In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 76, no 6, p. 826-+Article, review/survey (Refereed)
    Abstract [en]

    Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

    Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

    Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

    Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

    Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

    Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

    Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.

    Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

  • 24.
    Albertsson, Emilie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Solem, Evelina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Delaktighet inom anestesiologisk omvårdnad: En begreppsanalys2023Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    ABSTRACT

    Background: Participation is a concept that exists at different levels, in community organizations as well as health care. Being able to participate in one's care is a right by law in Sweden and a central part of person-centred care. Although participation is a well-established concept, there is no clear definition of the concept. Specialist nurses in anesthesia care have a responsibility in providing care that is person-centred and in creating a good relationship in the short meeting between the patient and specialist nurse where the patient is supported to participate.

    Purpose: To explore and propose definitions of the concept of participation in anesthesiology nursing.

    Method: A concept analysis was made based on Walker and Avant´s method. 

    Results: Information and communication contribute to participation, which is described as active participation where the patient participates by communicating and sharing their needs, obtains and receives information and takes part in joint decisions-making. Patients, relatives and staff all feel their own responsibility for participation, and participation arises through cooperation and good care relationships. Time, knowledge, the patient's will and condition in the form of level of consciousness, symptom or drug effects, structural factors in the organization and trust in the staff affect the conditions for participation. 

    Conclusion: In all care, the patient has the right to participate. The concept of participation in anesthesiological care can be compared to participation in other care settings, however, there are other types of restrictions in anesthesia care in enabling patient participation. The definition of participation includes good two-way communication, active participation and collaboration between patient and healthcare staff.

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  • 25.
    Ali, Mustafa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Uslu, Ahmed
    Baskent Univ, Ankara Hosp, Dept Anaesthesia & Intens Care, Ankara, Turkiye..
    Bodin, Lars
    Uppsala Univ Hosp, Uppsala, Sweden..
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Modiri, Ali-Reza
    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.
    Effects of caloric and nutrient content of oral fluids on gastric emptying in volunteers: a randomised crossover study2024In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 132, no 2, p. 260-266Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies demonstrated conflicting results regarding the determinants of gastric emptying for fluids. Our aim was to compare gastric emptying times of fluids with different caloric and nutrient content.

    Methods: Healthy adult volunteers underwent gastric ultrasound assessment for 4 h after consuming beverages with different caloric and nutrient content using a crossover design (oat drink with 3% fat [310 kcal], mango juice [310 kcal], oat drink with 0.5% fat [185 kcal], and blackcurrant juice [175 kcal]). Gastric emptying time, gastric content volume, and the area under the curve (AUC) of gastric content volume -time profiles were calculated.

    Results: Eight females and eight males completed the study protocol. The mean (SD) gastric emptying times were 89 (32) min for blackcurrant juice, 127 (54) min for oat drink with 0.5% fat, 135 (36) min for mango juice, and 152 (40) min for oat drink with 3% fat. Gastric emptying times were slower for oat drink with 3% fat (P=0.007) and mango juice (P=0.025) than for blackcurrant juice. At 1 h after ingestion, gastric content volume was greater for mango juice (P=0.021) and oat drink with 3% fat (P=0.003) than for blackcurrant juice. The AUC was greater for oat drink with 3% fat than mango juice (P=0.029), oat drink with 0.5% fat (P=0.004), and blackcurrant juice (P=0.002), and for mango juice than blackcurrant juice (P=0.019).

    Conclusions: Caloric and nutrient content significantly affected gastric emptying times. A high-calorie fruit juice (mango) exhibited delayed emptying times compared with a low-calorie fruit juice (blackcurrant).

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  • 26. Aliverti, A.
    et al.
    Kostic, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lo Mauro, Antonella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Andersson-Olerud, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Quaranta, M.
    Pedotti, A.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Effects of propofol anaesthesia on thoraco-abdominal volume variations during spontaneous breathing and mechanical ventilation2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 5, p. 588-596Article in journal (Refereed)
    Abstract [en]

    Background Anaesthesia based on inhalational agents has profound effects on chest wall configuration and breathing pattern. The effects of propofol are less well characterised. The aim of the current study was to evaluate the effects of propofol anaesthesia on chest wall motion during spontaneous breathing and positive pressure ventilation. Methods We studied 16 subjects undergoing elective surgery requiring general anaesthesia. Chest wall volumes were continuously monitored by opto-electronic plethysmography during quiet breathing (QB) in the conscious state, induction of anaesthesia, spontaneous breathing during anaesthesia (SB), pressure support ventilation (PSV) and pressure control ventilation (PCV) after muscle paralysis. Results The total chest wall volume decreased by 0.41 +/- 0.08 l immediately after induction by equal reductions in the rib cage and abdominal volumes. An increase in the rib cage volume was then seen, resulting in total chest wall volumes 0.26 +/- 0.09, 0.24 +/- 0.10, 0.22 +/- 0.10 l lower than baseline, during SB, PSV and PCV, respectively. During QB, rib cage volume displacement corresponded to 34.2 +/- 5.3% of the tidal volume. During SB, PSV and PCV, this increased to 42.2 +/- 4.9%, 48.2 +/- 3.6% and 46.3 +/- 3.2%, respectively, with a corresponding decrease in the abdominal contribution. Breathing was initiated by the rib cage muscles during SB. Conclusion Propofol anaesthesia decreases end-expiratory chest wall volume, with a more pronounced effect on the diaphragm than on the rib cage muscles, which initiate breathing after apnoea.

  • 27.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Granath, Fredrik
    Friberg, Orjan
    Ekbom, Anders
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risk factors for re-exploration due to bleeding after coronary artery bypass grafting2012In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 46, no 1, p. 39-44Article in journal (Refereed)
    Abstract [en]

    Objective. The study aimed to investigate relevant clinical risk factors for re-exploration due to bleeding after primary coronary artery bypass graft (CABG) surgery, and to evaluate the influence of antiplatelet and antifibrinolytic drugs. Design. Three retrospective analyses were performed on patients who underwent CABG: (1) Logistic regression was used to identify clinical risk factors for re-exploration (n = 3000). (2) A case-control study (n = 228) was used to obtain information on exposure of antithrombotic and hemostatic therapy. (3) Based on exposure to antiplatelet and antifibrinolytic therapy, and odds ratios (ORs) in multivariate logistic models, the proportion of re-explorations attributed to these drugs was calculated. Results. A receiver operating characteristic curve was created for clinical risk factors. The C-index was 0.64, indicating limited ability to predict re-exploration for bleeding. Clopidogrel was the only drug influencing the risk of re-exploration (OR 3.2, 95% CI 1.7-5.9). The harmful effect of clopidogrel was confirmed in multivariate model (OR 4.7, 95% CI 2.2-9.9), and aprotinin had a protective effect of the same magnitude (OR 0.2, 95% CI 0.1-0.6). Conclusions. Clopidogrel is an essential risk factor for re-exploration due to bleeding, and attributable to at least one-quarter of surveyed cases. Aside from pharmaceuticals, there are no strong clinical risk factors.

  • 28.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Granath, Fredrik
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Tydén, Hans
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery2009In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 5, p. 572-577Article in journal (Refereed)
    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.

  • 29.
    Alström, Ulrica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Levin, L-Å
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svedjeholm, R
    Friberg, Ö
    Cost analysis of re-exploration for bleeding after coronary artery bypass graft surgery2012In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 108, no 2, p. 216-222Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Re-exploration for bleeding after cardiac surgery is an indicator of substantial haemorrhage and is associated with increased hospital resource utilization. This study aimed to analyse the costs of re-exploration and estimate the costs of haemostatic prophylaxis.

    METHODS:

    A total of 4232 patients underwent isolated, first-time, coronary artery bypass graft (CABG) surgery during 2005-8. Each patient re-explored for bleeding (n=127) was matched with two controls not requiring re-exploration (n=254). Cost analysis was based on resource utilization from completion of CABG until discharge. A mean cost per patient for re-exploration was calculated. Based on this, the net cost of prophylactic treatment with haemostatic drugs for preventing re-exploration was calculated.

    RESULTS:

    Patients undergoing re-exploration had higher exposure to clopidogrel before operation, prolonged stays in the intensive care unit, and more blood transfusions than controls. The mean incremental cost for re-exploration was (sic)6290 [95% confidence interval (CI) (sic)3408-(sic)9173] per patient, of which 48% [(sic)3001 (95% CI (sic)249-(sic)2147)] was due to prolonged stay, 31% [(sic)1928 (95% CI (sic)1710-(sic)2147)] to the cost of surgery/anaesthesia, 20% [(sic)1261 (95% CI (sic)1145-(sic)1378)] to the increased number of blood transfusions, and <2% [(sic)100 (95% CI (sic)39-(sic)161)] to the cost of haemostatic drugs. A cost model, at an estimated 50% efficacy for recombinant activated clotting factor VIIa and a 50% expected risk for re-exploration without prophylaxis, demonstrated that to be cost neutral, prophylaxis of four patients needed to result in one avoided re-exploration.

    CONCLUSIONS:

    The resource utilization costs were substantially higher in patients requiring re-exploration for bleeding. From a strict cost-effectiveness perspective, clinical interventions to prevent haemorrhage might be underutilized.

  • 30.
    Anderberg, Sara B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no 3, p. 575-590Article, review/survey (Refereed)
    Abstract [en]

    Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

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  • 31.
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Reduced Preoperative Fasting in Children2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Preoperative fasting is recommended in order to reduce the risk of perioperative pulmonary aspiration. However, preoperative fasting may have negative effects on patient wellbeing and homeostasis. In this thesis, more lenient regimens for preoperative fasting in elective paediatric patients were assessed, with the aim to further improve preoperative fasting regimens.

    Paper I investigated if paediatric patients allowed to drink clear fluids until called to surgery, had an increased risk of pulmonary aspiration. The incidence of perioperative pulmonary aspiration in children allowed free clear fluids until called to surgery was 3 in 10 000, as compared to 1-10 in 10 000 in previous studies where longer fasting intervals were studied. Hence, no increase of incidence for pulmonary aspiration was found.

    Paper II investigated actual fasting times for clear fluids when applying two-hour fasting for clear fluids, and zero-hour fasting for clear fluids. When applying two-hour fasting, children were fasted median four hours for clear fluids. After transitioning to zero-hour fasting, median fasting time decreased to one hour, and the incidence of children fasting for more than six hours decreased from 35 % to 6 %. Abandoning the time limit for clear fluids significantly reduced the proportion of patients fasting for extended periods.

    Paper III assessed gastric content volume after a light breakfast in children scheduled for elective general anaesthesia. Patients were examined with gastric ultrasound four hours after a light breakfast. Of the 20 patients included in the study, 15 had an empty stomach, 4 had clear fluids < 0.5 ml kg-1 and one had solid content in the stomach. A light breakfast preoperatively might be safe, but amount and caloric restriction is needed to avoid the risk of perioperative pulmonary aspiration.

    Paper IV investigated preoperative weight loss, glucose level and ketone bodies in paediatric patients presenting for elective surgery. The outcomes were tested for correlation to preoperative fasting times. Of the 43 children enrolled in the study, three had weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time, and the respective outcomes. Even with a lenient fasting regimen, there is risk of mild preoperative dehydration, hypoglycaemia and ketogenesis.

    In conclusion, the results obtained in the present thesis supports the shift to more lenient preoperative fasting regimens for clear fluids in elective paediatric patients.

    List of papers
    1. Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    Open this publication in new window or tab >>Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    2015 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, no 8, p. 770-777Article in journal (Refereed) Published
    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.

    National Category
    Pediatrics Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-256491 (URN)10.1111/pan.12667 (DOI)000357730600003 ()25940831 (PubMedID)
    Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2019-10-06Bibliographically approved
    2. Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    Open this publication in new window or tab >>Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    2018 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, no 1, p. 46-52Article in journal (Refereed) Published
    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.

    Keywords
    anesthesia, children, fasting, fluids, preoperative
    National Category
    Anesthesiology and Intensive Care Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-343890 (URN)10.1111/pan.13282 (DOI)000417604600008 ()29168341 (PubMedID)
    Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-10-06Bibliographically approved
    3. Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study
    Open this publication in new window or tab >>Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study
    2019 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 29, no 12, p. 1173-1178Article in journal (Refereed) Published
    Abstract [en]

    Background

    A light breakfast has been found to empty from the stomach within 4 hours in healthy volunteers.

    Aim

    The aim of this study was to investigate whether a light breakfast of yoghurt or gruel empties from the stomach within 4 hours, in children scheduled for general anaesthesia.

    Method

    In this observational cohort study, children aged 1‐6 years scheduled for elective general anaesthesia were prescribed free intake of yoghurt or gruel 4 hours prior to induction. They were subsequently examined with gastric ultrasound within 4 hours of ingestion. In case of gastric contents, the gastric antral area was measured, and gastric content volume (GCV) was calculated.

    Results

    Twenty children were included in the study and the ingested amount of gruel or yoghurt ranged 2.5‐25 mL kg−1. In 15 cases, the stomach was empty with juxtaposed walls and no further measurements were made. In four cases, there was fluid present in the stomach, but the calculated gastric contents were <0.5 mL kg−1. One patient had solids in the stomach, and GCV in this patient was calculated to 2.1 mL kg−1. The patient with solids present had ingested 25 mL kg−1 of gruel 4 hours prior to assessment. The planned procedure was therefore delayed 1 hour. There were no cases of pulmonary aspiration or vomiting.

    Conclusion

    A light breakfast 4 hours prior to induction may be considered, but there is need for further studies on safe limits for the volume ingested.

    Keywords
    general anesthesia, paediatric, preoperative fasting, ultrasound
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-394230 (URN)10.1111/pan.13755 (DOI)000493655400001 ()31608517 (PubMedID)
    Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2020-04-21Bibliographically approved
    4. Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    Open this publication in new window or tab >>Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background

    New paediatric fasting guidelines allow free clear fluids up until one hour prior to surgery. At the paediatric anaesthesia department of Uppsala University Hospital, children are fasted six hours for solids, four hours for breast milk and are allowed free clear fluids up until called to theatre. Preoperative fasting is necessary to avoid perioperative pulmonary aspiration. However, extended fasting times have detrimental effects for fluid homeostasis and may cause hypoglycaemia and ketone bodies.

    Aim

    The aim of the current study was to investigate if preoperative weight loss, glucose level and ketone bodies were related to preoperative fasting times.

    Methods

    Paediatric patients aged 0-72 months were included in this prospective, observational study. All children included were instructed to fast from midnight for solids, four hours for breast milk or semi-solids and from when they are called to theatre for clear fluids. Fasting times were registered, and patient weight was measured in the evening prior to surgery, and before induction. Blood glucose and ketone body levels were measured before induction. Multiple regression was used to determine how fasting time affected the outcomes weight change, blood glucose level and ketone bodies, respectively.

    Results

    43 patients were enrolled. Three children had a weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time and the respective outcomes.

    Conclusion

    Even with a lenient preoperative fasting regimen, mild dehydration or hypoglycaemia may occur. This methodology may be used in further studies of the effects of preoperative fasting in settings where dehydration may be more significant.

    Keywords
    General Anesthesia, child < Age, Dehydration, Fasting, Hypoglycaemia, Ketosis
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care; Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-394231 (URN)
    Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2019-10-06
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  • 32.
    Andersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Elias, Eerola
    Frykholm, Peter
    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.
    Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    New paediatric fasting guidelines allow free clear fluids up until one hour prior to surgery. At the paediatric anaesthesia department of Uppsala University Hospital, children are fasted six hours for solids, four hours for breast milk and are allowed free clear fluids up until called to theatre. Preoperative fasting is necessary to avoid perioperative pulmonary aspiration. However, extended fasting times have detrimental effects for fluid homeostasis and may cause hypoglycaemia and ketone bodies.

    Aim

    The aim of the current study was to investigate if preoperative weight loss, glucose level and ketone bodies were related to preoperative fasting times.

    Methods

    Paediatric patients aged 0-72 months were included in this prospective, observational study. All children included were instructed to fast from midnight for solids, four hours for breast milk or semi-solids and from when they are called to theatre for clear fluids. Fasting times were registered, and patient weight was measured in the evening prior to surgery, and before induction. Blood glucose and ketone body levels were measured before induction. Multiple regression was used to determine how fasting time affected the outcomes weight change, blood glucose level and ketone bodies, respectively.

    Results

    43 patients were enrolled. Three children had a weight loss of more than 5 %, five children presented with blood glucose level < 3.3 mmol l-1, and 11 children presented with ketone bodies > 0.6 mmol l-1. There was no correlation between fasting time and the respective outcomes.

    Conclusion

    Even with a lenient preoperative fasting regimen, mild dehydration or hypoglycaemia may occur. This methodology may be used in further studies of the effects of preoperative fasting in settings where dehydration may be more significant.

  • 33.
    Andersson, Hanna
    et al.
    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.
    Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study2019In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 29, no 12, p. 1173-1178Article in journal (Refereed)
    Abstract [en]

    Background

    A light breakfast has been found to empty from the stomach within 4 hours in healthy volunteers.

    Aim

    The aim of this study was to investigate whether a light breakfast of yoghurt or gruel empties from the stomach within 4 hours, in children scheduled for general anaesthesia.

    Method

    In this observational cohort study, children aged 1‐6 years scheduled for elective general anaesthesia were prescribed free intake of yoghurt or gruel 4 hours prior to induction. They were subsequently examined with gastric ultrasound within 4 hours of ingestion. In case of gastric contents, the gastric antral area was measured, and gastric content volume (GCV) was calculated.

    Results

    Twenty children were included in the study and the ingested amount of gruel or yoghurt ranged 2.5‐25 mL kg−1. In 15 cases, the stomach was empty with juxtaposed walls and no further measurements were made. In four cases, there was fluid present in the stomach, but the calculated gastric contents were <0.5 mL kg−1. One patient had solids in the stomach, and GCV in this patient was calculated to 2.1 mL kg−1. The patient with solids present had ingested 25 mL kg−1 of gruel 4 hours prior to assessment. The planned procedure was therefore delayed 1 hour. There were no cases of pulmonary aspiration or vomiting.

    Conclusion

    A light breakfast 4 hours prior to induction may be considered, but there is need for further studies on safe limits for the volume ingested.

  • 34.
    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.

  • 35.
    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

  • 36.
    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.

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  • 37.
    Andersson, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nilsson, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Patientdelaktighet vid extubation: Don’t put the patient in the corner - En observationsstudie2023Independent thesis Advanced level (degree of Master (One Year)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    ABSTRACT.

    Background: Specialist nurses consider extubation more difficult and complext than intubation. Extubation requires a lot of focus on the patient's physical needs, which can prove it difficult for specialist nurses to fulfill the patient's psychosocial needs. Research shows that patients have unpleasant memories of being intubated and being extubated.

    Aim: The aim was to investigate how patient participation was fulfilled during extubation in a intensive care unit.

    Method: The design was a focused ethnographic observational study with a deductive approach. The sample was patients who underwent elective surgery and received postoperative care in the thoracic intensive care unit in a university hospital. Ten patients were observed as they were extubated by the intensive care personnel. A semi-structured interview was then conducted about the patient's experience of being extubated and whether they felt involved.

    Main result: To increase the patience participation, the staff were informative and supportive, present and respected the patient's dignity and privacy. Staff did this through physical touch, calling the patient by name, and performing extubation separately. The results cannot ensure that it is possible to establish a care relationship during extubation as a care relationship was only established on two out of ten occasions. The majority of patients had no memory of being extubated. 

    Conclusion: Patient participation during extubation can be achieved through information, staff presence and support. It’s possible to achieve patientparticipant without establishing a caring relationship. The majority of participants did not have memories of extubation, however, patient participation should still be achieved. 

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  • 38.
    Aneman, Anders
    et al.
    Liverpool Hosp, South Western Sydney Local Hlth Dist, Intens Care Unit, Sydney, NSW, Australia.;Univ New South Wales, South Western Sydney Clin Sch, Sydney, NSW, Australia.;Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia..
    Wilander, Petter
    Hallands Hosp, Dept Anaesthesiol & Intens Care Med, Halmstad, Sweden.;Linköping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Drug Res, Linköping, Sweden..
    Zoerner, Frank
    Liverpool Hosp, South Western Sydney Local Hlth Dist, Intens Care Unit, Sydney, NSW, Australia..
    Lipcsey, Miklós
    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.
    Chew, Michelle S.
    Linköping Univ, Fac Hlth Sci, Biomed & Clin Sci, Dept Anaesthesia & Intens Care, Linköping, Sweden..
    Vasopressor Responsiveness Beyond Arterial Pressure: A Conceptual Systematic Review Using Venous Return Physiology2021In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 56, no 3, p. 352-359Article, review/survey (Refereed)
    Abstract [en]

    We performed a systematic review to investigate the effects of vasopressor-induced hemodynamic changes in adults with shock. We applied a physiological approach using the interacting domains of intravascular volume, heart pump performance, and vascular resistance to structure the interpretation of responses to vasopressors. We hypothesized that incorporating changes in determinants of cardiac output and vascular resistance better reflect the vasopressor responsiveness beyond mean arterial pressure alone. We identified 28 studies including 678 subjects in Pubmed, EMBASE, and CENTRAL databases. All studies demonstrated significant increases in mean arterial pressure (MAP) and systemic vascular resistance during vasopressor infusion. The calculated mean systemic filling pressure analogue increased (16 +/- 3.3 mmHg to 18 +/- 3.4 mmHg; P = 0.02) by vasopressors with variable effects on central venous pressure and the pump efficiency of the heart leading to heterogenous changes in cardiac output. Changes in the pressure gradient for venous return and cardiac output, scaled by the change in MAP, were positively correlated (r (2) = 0.88, P < 0.001). Changes in the mean systemic filling pressure analogue and heart pump efficiency were negatively correlated (r (2) = 0.57, P < 0.001) while no correlation was found between changes in MAP and heart pump efficiency. We conclude that hemodynamic changes induced by vasopressor therapy are inadequately represented by the change in MAP alone despite its common use as a clinical endpoint. The more comprehensive analysis applied in this review illustrates how vasopressor administration may be optimized.

  • 39. Antonen, Jaakko
    et al.
    Leppanen, Ilona
    Tenhunen, Jyrki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Arvola, Pertti
    Makela, Satu
    Vaheri, Antti
    Mustonen, Jukka
    A severe case of Puumala hantavirus infection successfully treated with bradykinin receptor antagonist icatibant2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 6, p. 494-496Article in journal (Refereed)
    Abstract [en]

    A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.

  • 40.
    Antoni, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lindström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Elgland, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Translational PET Imaging.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sigfridsson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    In Vivo Visualization and Quantification of Neutrophil Elastase in Lungs of COVID-19 Patients: A First-in-Humans PET Study with 11C-NES2023In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 64, no 1, p. 145-148Article in journal (Refereed)
    Abstract [en]

    COVID-19 can cause life-threatening lung-inflammation that is suggested to be mediated by neutrophils, whose effector mechanisms in COVID-19 is inexplicit. The aim of the present work is to evaluate a novel PET tracer for neutrophil elastase in COVID-19 patients and healthy controls.

    METHODS: In this open-label, First-In-Man study, four patients with hypoxia due to COVID-19 and two healthy controls were investigated with positron emission tomography (PET) using the new selective and specific neutrophil elastase PET-tracer [11C]GW457427 and [15O]water for the visualization and quantification of NE and perfusion in the lungs, respectively.

    RESULTS: [11C]GW457427 accumulated selectively in lung areas with ground-glass opacities on computed tomography characteristic of COVID-19 suggesting high levels on NE in these areas. In the same areas perfusion was severely reduced in comparison to healthy lung tissue as measured with [15O]water.

    CONCLUSION: The data suggests that NE may be responsible for the severe lung inflammation in COVID-19 patients and that inhibition of NE could potentially reduce the acute inflammatory process and improve the condition.

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  • 41.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Gunningberg, Lena
    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, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Norlén, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Factors influencing early postoperative recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy2011In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 37, no 10, p. 897-903Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can prolong survival in selected patients with peritoneal carcinomatosis (PC). However, there is little data on patients' recovery process after this complex treatment. This study aimed to describe the in-hospital postoperative recovery and factors related to the recovery of patients who undergo CRS and HIPEC.

    METHOD:

    A retrospective audit of the electronic health record (EHR) was undertaken for 76 PC patients (42 women, 34 men) treated primarily with CRS and HIPEC between 2005 and 2006 in Sweden.

    RESULTS:

    Oral intake, regaining bowel functions and mobilisation usually occurred between 7 and 11 days postoperatively. Patients experienced nausea for up to 13 days postoperatively. Forty-two patients were satisfied with their pain management, which usually took the form of epidural anaesthesia and which continued for about one week post-surgery. Sleep disturbance was observed in 51 patients and psychological problems in 49 patients during the first three postoperative weeks. Tumour burden, stoma formation, use of CPAP, primary diagnosis, and the length of stay in the ICU were factors related to an early recovery process.

    CONCLUSION:

    Drinking, eating, regaining bowel functions and mobilisation were re-established within 11 days of CRS and HIPEC. Tumour burden, stoma formation, use of CPAP, primary diagnosis and the length of stay in the ICU all had an impact on postoperative recovery, and should be discussed with the patients preoperatively and taken into consideration in designing an individualised patient care plan, in order to attain a more efficient recovery.

  • 42.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hellman, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Svartengren, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Experiences of the Initial Phase Implementation of the STAMINA-Model in Perioperative Context Addressing Environmental Issues Systematically: A Qualitative Study2020In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 17, no 9, article id 3037Article in journal (Refereed)
    Abstract [en]

    (1) Background: Challenges in perioperative settings put demands on staff working with systematic work environment management. A support model, STAMINA (Structured and Time-effective Approach through Methods for an Inclusive and Active working life), was implemented in a hospital in Sweden, to help staff address environmental issues systematically. The aim was to describe the experiences of the initial phase of implementation of the adapted STAMINA model in perioperative context. (2) Methods: Qualitative individual interviews were held with 14 managers and employees (three men and 11 women). Data were analysed by systematic text condensation. (3) Results: Five themes were identified: Limited knowledge of the model and the implementation process; scepticism, lack of confidence in the model and a passive attitude; the model offered increased participation; the culture in the organization-to understand one's role as employees and managers; and endurance and feedback are key factors for success in the implementation process. (4) Conclusions: Scepticism turned to positive attitude by recognising that the STAMINA model offered increased participation. In order to have successful implementation, the organisational culture must be taken into consideration by giving the employees increased responsibilities and timely feedbacks. Role description, goal definition, feedback, and sticking to one model are key factors for success.

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  • 43.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Paulsson, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Molin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. The Institute for Organizational and Leadership Development (IPF).
    Svartengren, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    How Human Resources Index, Relational Justice, and Perceived Productivity Change after Reorganization at a Hospital in Sweden That Uses a Structured Support Model for Systematic Work Environment Management2021In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 18, no 21, article id 11611Article in journal (Refereed)
    Abstract [en]

    To facilitate systematic work environment management, which should be a natural part of business development, a structured support model was developed. The Stamina model has previously been used in Swedish municipalities, showing positive results. The aim was to study how the Human Resources Index (HRI), relational justice, short-term recovery and perceived productivity changed in a recently reorganised perioperative setting in a hospital in Sweden that uses a structured support model for systematic work environment management. A longitudinal design that took measurements at four time points was used in a sample of 500 employees in a perioperative hospital department. The results for the overall sample indicated a positive trend in the HRI (Mt1 = 48.5, SDt1 = 22.5; Mt3 = 56.7, SDt1 = 21.2; p < 0.001). Perceived health-related production loss (Mdt1 = 2, IQR = 3; Mdt3 = 0, IQR = 3; p < 0.001) and perceived work environment-related production loss (Mdt1 = 2, IQR = 3; Mdt3 = 0, IQR = 4; p < 0.001) showed major improvements. Short-term recovery showed a minor improvement (Mt1 = 2.61, SDt1 = 1.33; Mt3 = 2.65, SDt3 = 1.22; p = 0.872). In conclusion, the implementation of the Stamina model, of which the HRI constitutes an important part, seems to be a helpful tool to follow-up on work environment processes, and minimise production losses due to health and work environment-related issues.

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  • 44.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rudolfsson, Gudrun
    Nord Univ, Fac Nursing & Hlth Sci, N-8049 Bodo, Norway.;Univ West, Div Nursing, Dept Hlth Sci, SE-46186 Trollhättan, Sweden..
    Managerial challenges faced by Swedish nurse managers in perioperative settings: a qualitative study2021In: BMC Nursing, E-ISSN 1472-6955, Vol. 20, article id 117Article in journal (Refereed)
    Abstract [en]

    Background: Nurse managers need to create cultures that are worthy, not only of the commitment of everyone who comes to work but also of the trust of everyone who comes to be served. The aim of our study was to describe the challenges faced by Swedish nurse managers in a perioperative setting.

    Methods: A qualitative study was conducted. The participants were chosen by convenience sampling, and individual in-depth interviews were conducted. Data were analysed by Systematic Text Condensation. The COREQ checklist was consulted throughout the study to optimise the quality.

    Results: Nineteen nurse managers (all women) participated. Six themes were identified: "striving to treat employees with consideration and solicitude"; "the obligation to take care of each employee's individual needs"; "convincing others was an uphill battle", "finding solutions when things seem impossible"; "staff recruitment, allocation, and management"; "working with constantly changing planning".

    Conclusions: The nurse managers faced challenges because of the overwhelming amount of work tasks, with almost no time for reflection. Having carefully chosen tasks and a realistic time schedule for each work task, plus time to find one's own path to inner peace, are essential for nurse managers. Organisations that provide these prerequisites show that they care about their nurse managers. The results of this study indicate the need for time to reflect, as well as support from superior managers and from the human resources department.

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  • 45.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Torkzad, Michael R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergman, Antonina
    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.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: a retrospective study2012In: World Journal of Surgical Oncology, E-ISSN 1477-7819, Vol. 10, p. 258-Article in journal (Refereed)
    Abstract [en]

    Background: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. Methods: Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Results: Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1-2) in nine patients. Conclusions: Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.

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  • 46. 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.

  • 47.
    Arnell, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Koskinen, Lars-Owe D.
    Malm, Jan
    Eklund, Anders
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices2009In: Journal of neurosurgery. Pediatrics, ISSN 1933-0707, Vol. 3, no 3, p. 166-72Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs). METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined. RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure. CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 48.
    Arnell, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Olsen, L.
    Wester, T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Hydrocephalus2008In: Pediatric surgery: Diagnosis and management, Berlin: Springer Verlag , 2008, p. 418-426Chapter in book (Other (popular science, discussion, etc.))
  • 49.
    Aronsson Dannewitz, Anna
    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, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology.
    Lipcsey, Miklós
    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.
    Optimized diagnosis-based comorbidity measures for all-cause mortality prediction in a national population-based ICU population2022In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 26, article id 306Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to optimize prediction of long-term all-cause mortality of intensive care unit (ICU) patients, using quantitative register-based comorbidity information assessed from hospital discharge diagnoses prior to intensive care treatment.

    Material and methods: Adult ICU admissions during 2006 to 2012 in the Swedish intensive care register were followed for at least 4 years. The performance of quantitative comorbidity measures based on the 5-year history of number of hospital admissions, length of stay, and time since latest admission in 36 comorbidity categories was compared in time-to-event analyses with the Charlson comorbidity index (CCI) and the Simplified Acute Physiology Score (SAPS3).

    Results: During a 7-year period, there were 230,056 ICU admissions and 62,225 deaths among 188,965 unique individuals. The time interval from the most recent hospital stays and total length of stay within each comorbidity category optimized mortality prediction and provided clear separation of risk categories also within strata of age and CCI, with hazard ratios (HRs) comparing lowest to highest quartile ranging from 1.17 (95% CI: 0.52-2.64) to 6.41 (95% CI: 5.19-7.92). Risk separation was also observed within SAPS deciles with HR ranging from 1.07 (95% CI: 0.83-1.38) to 3.58 (95% CI: 2.12-6.03).

    Conclusion: Baseline comorbidity measures that included the time interval from the most recent hospital stay in 36 different comorbidity categories substantially improved long-term mortality prediction after ICU admission compared to the Charlson index and the SAPS score. Trial registration ClinicalTrials.gov ID NCT04109001, date of registration 2019-09-26 retrospectively.

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  • 50.
    Arthursson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kjellberg, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tovedal, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cerebral oxygenation and autoregulation during rewarming on cardiopulmonary bypass2023In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 38, no 3, p. 523-529Article in journal (Refereed)
    Abstract [en]

    Background Rewarming on cardiopulmonary bypass (CPB) is associated with increased metabolic demands; however, it remains unclear whether cerebral autoregulation is affected during this phase. This RCT aims to describe the effects of 20% supranormal, compared to normal CPB flow, on monitoring signs of inadequate perfusion, oxygenation, and disturbed cerebral autoregulation, during the rewarming phase of CPB. Method Thirty two patients scheduled for coronary artery bypass grafting were allocated to a Control group (n = 16) receiving a CPB pump flow corresponding to preoperatively measured cardiac output, and an Intervention group (n = 16) receiving the corresponding CPB pump flow increased by 20% during rewarming. Cerebral Oximetry Index (COx) was calculated with the aid of Near Infrared Spectroscopy. Results Twenty five patients were included in the data. Results show a median COx value of 0.0 (IQR -0.33-0.5) (Control) and 0.0 (IQR -0.15-0.25) (Intervention), respectively; p = .85 with individual variations within groups. The median cerebral perfusion pressure (CPP) was 55 (52-58) (Control) and 61 (54-66) mmHg (Intervention); p = .08. No significant difference in rSO2 values was observed between the groups (58.5% (50-61) versus 64% (58-68); p = .06). Conclusion The present study showed no difference between increased and normal CPB pump flow with respect to cerebral autoregulation during rewarming. Large variations in cerebral autoregulation were seen at individual level.

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