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  • 1.
    Aarnio, Mikko
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Öppna denna publikation i ny flik eller fönster >>High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
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    2016 (Engelska)Ingår i: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 152, s. 231-237Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    D-deprenyl High-throughput screening Binding site
    Nationell ämneskategori
    Farmaceutiska vetenskaper Klinisk medicin
    Identifikatorer
    urn:nbn:se:uu:diva-291492 (URN)10.1016/j.lfs.2016.03.058 (DOI)000375728500028 ()27058977 (PubMedID)
    Forskningsfinansiär
    Berzelii Centre EXSELENT, 2013-01495
    Tillgänglig från: 2016-05-03 Skapad: 2016-05-03 Senast uppdaterad: 2022-01-29Bibliografiskt granskad
    2. Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Öppna denna publikation i ny flik eller fönster >>Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
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    2018 (Engelska)Ingår i: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 194, s. 26-33Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    Arthritis, Binding target, Monoamine oxidase B, Synovium, d-Deprenyl
    Nationell ämneskategori
    Farmaceutiska vetenskaper
    Forskningsämne
    Farmaceutisk biokemi; Medicinsk biokemi
    Identifikatorer
    urn:nbn:se:uu:diva-347601 (URN)10.1016/j.lfs.2017.12.003 (DOI)000425052000004 ()29221756 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 9459
    Tillgänglig från: 2018-04-04 Skapad: 2018-04-04 Senast uppdaterad: 2022-01-29Bibliografiskt granskad
    3. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Öppna denna publikation i ny flik eller fönster >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
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    2017 (Engelska)Ingår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, nr 1, s. 418-424Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    Walter de Gruyter, 2017
    Nyckelord
    Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
    Tillgänglig från: 2017-11-16 Skapad: 2017-11-16 Senast uppdaterad: 2019-09-25Bibliografiskt granskad
    4. Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Öppna denna publikation i ny flik eller fönster >>Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    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.

    Nyckelord
    Whiplash; deprenyl; inflammation; pain; PET; carbon-11
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Molekylär medicin; Medicinsk cellbiologi
    Identifikatorer
    urn:nbn:se:uu:diva-347602 (URN)
    Tillgänglig från: 2018-04-04 Skapad: 2018-04-04 Senast uppdaterad: 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.
    Öppna denna publikation i ny flik eller fönster >>Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    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.

    Nyckelord
    deprenyl; inflammation; pain; PET; carbon-11
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-347604 (URN)
    Tillgänglig från: 2018-04-04 Skapad: 2018-04-04 Senast uppdaterad: 2018-04-12
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  • 2.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. 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 study2021Ingår i: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 38, nr 1, s. 41-48Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Adamski, Jan
    et al.
    Satakunta Cent Hosp, Dept Intens Care Med, Sairaalantie 3,PL 317, FIN-28500 Pori, Finland..
    Weigl, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    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 study2020Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 64, nr 8, s. 1144-1153Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    Adamski, Jan
    et al.
    Univ Warmia & Mazury, Fac Med Sci, Dept Anaesthesiol & Intens Care, Ul Warszawska 30, PL-10082 Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    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 units2022Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 66, nr 4, s. 526-538Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Adielsson, Anna
    et al.
    Sahlgrens Univ Hosp, Dept Anaesthesiol & Intens Care Med, Gothenburg, Sweden..
    Danielsson, Christian
    Sahlgrens Univ Hosp, Dept Clin Pathol, Gothenburg, Sweden..
    Forkman, Pontus
    Mora Hosp, Dept Adult Psychiat, Mora, Sweden..
    Karlsson, Thomas
    Univ Gothenburg, Hlth Metr Sahlgrenska Acad, Gothenburg, Sweden..
    Pettersson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Herlitz, Johan
    Univ Coll Borås, Ctr Prehosp Res Western Sweden, Borås, Sweden..
    Lundin, Stefan
    Sahlgrens Univ Hosp, Dept Anaesthesiol & Intens Care Med, Gothenburg, Sweden..
    Outcome prediction for patients assessed by the medical emergency team: a retrospective cohort study2022Ingår i: BMC Emergency Medicine, ISSN 1471-227X, E-ISSN 1471-227X, Vol. 22, nr 1, artikel-id 200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Medical emergency teams (METs) have been implemented to reduce hospital mortality by the early recognition and treatment of potentially life-threatening conditions. The objective of this study was to establish a clinically useful association between clinical variables and mortality risk, among patients assessed by the MET, and further to design an easy-to-use risk score for the prediction of death within 30 days.

    Methods: Observational retrospective register study in a tertiary university hospital in Sweden, comprising 2,601 patients, assessed by the MET from 2010 to 2015. Patient registry data at the time of MET assessment was analysed from an epidemiological perspective, using univariable and multivariable analyses with death within 30 days as the outcome variable. Predictors of outcome were defined from age, gender, type of ward for admittance, previous medical history, acute medical condition, vital parameters and laboratory biomarkers. Identified factors independently associated with mortality were then used to develop a prognostic risk score for mortality.

    Results: The overall 30-day mortality was high (29.0%). We identified thirteen factors independently associated with 30-day mortality concerning; age, type of ward for admittance, vital parameters, laboratory biomarkers, previous medical history and acute medical condition. A MET risk score for mortality based on the impact of these individual thirteen factors in the model yielded a median (range) AUC of 0.780 (0.774-0.785) with good calibration. When corrected for optimism by internal validation, the score yielded a median (range) AUC of 0.768 (0.762-0.773).

    Conclusions: Among clinical variables available at the time of MET assessment, thirteen factors were found to be independently associated with 30-day mortality. By applying a simple risk scoring system based on these individual factors, patients at higher risk of dying within 30 days after the MET assessment may be identified and treated earlier in the process.

    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 6.
    Ahlström, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    The epidemiology of risk factors and short and long-term outcome in the Swedish intensive care cohort2021Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    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. 

    Delarbeten
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Öppna denna publikation i ny flik eller fönster >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (Engelska)Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikel-id 548Artikel i tidskrift (Refereegranskat) 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).

    Ort, förlag, år, upplaga, sidor
    BMC, 2020
    Nyckelord
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Tillgänglig från: 2020-10-16 Skapad: 2020-10-16 Senast uppdaterad: 2024-01-10Bibliografiskt granskad
    2. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Öppna denna publikation i ny flik eller fönster >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Visa övriga...
    2021 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 4, s. 525-533Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    John Wiley & SonsWiley, 2021
    Nyckelord
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Tillgänglig från: 2021-04-14 Skapad: 2021-04-14 Senast uppdaterad: 2024-01-15Bibliografiskt granskad
  • 7.
    Ahlström, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The epidemiology of risk factors and short- and long-term outcome in the Swedish intensive care cohort2024Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Öppna denna publikation i ny flik eller fönster >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (Engelska)Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikel-id 548Artikel i tidskrift (Refereegranskat) 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).

    Ort, förlag, år, upplaga, sidor
    BMC, 2020
    Nyckelord
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Tillgänglig från: 2020-10-16 Skapad: 2020-10-16 Senast uppdaterad: 2024-01-10Bibliografiskt granskad
    2. Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    Öppna denna publikation i ny flik eller fönster >>Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-519454 (URN)
    Tillgänglig från: 2024-01-08 Skapad: 2024-01-08 Senast uppdaterad: 2024-01-10
    3. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Öppna denna publikation i ny flik eller fönster >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Visa övriga...
    2021 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 4, s. 525-533Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    John Wiley & SonsWiley, 2021
    Nyckelord
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Tillgänglig från: 2021-04-14 Skapad: 2021-04-14 Senast uppdaterad: 2024-01-15Bibliografiskt granskad
    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
    Öppna denna publikation i ny flik eller fönster >>A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
    Visa övriga...
    2022 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, artikel-id 15703Artikel i tidskrift (Refereegranskat) 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.

    Ort, förlag, år, upplaga, sidor
    Springer Nature, 2022
    Nationell ämneskategori
    Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-486398 (URN)10.1038/s41598-022-19539-0 (DOI)000857187000001 ()36127433 (PubMedID)
    Tillgänglig från: 2022-10-10 Skapad: 2022-10-10 Senast uppdaterad: 2024-01-10Bibliografiskt granskad
    5. One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Öppna denna publikation i ny flik eller fönster >>One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-519456 (URN)
    Tillgänglig från: 2024-01-08 Skapad: 2024-01-08 Senast uppdaterad: 2024-01-10
    Ladda ner fulltext (pdf)
    UUThesis_B-Ahlström-2024
    Ladda ner (jpg)
    presentationsbild
  • 8.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohortManuskript (preprint) (Övrigt vetenskapligt)
  • 9.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality2021Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 4, s. 525-533Artikel i tidskrift (Refereegranskat)
    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.

    Ladda ner fulltext (pdf)
    fulltext
  • 10.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Ctr Clin Res Dalarna, Reg Dalarna, Nissers Vag 3, S-79182 Falun, Sweden..
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. 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 cohort2020Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikel-id 548Artikel i tidskrift (Refereegranskat)
    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).

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  • 11.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohortManuskript (preprint) (Övrigt vetenskapligt)
  • 12.
    Akca, Ozan
    et al.
    Univ Louisville, Dept Anesthesiol & Perioperat Med, Neurosci ICU, Louisville, KY 40292 USA..
    Ball, Lorenzo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Belda, F. Javier
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Biro, Peter
    Univ Hosp Zurich, Inst Anesthesiol, Zurich, Switzerland..
    Cortegiani, Andrea
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Eden, Arieh
    Lady Davis Carmel Med Ctr, Dept Anesthesiol Crit Care & Pain Med, Haifa, Israel..
    Ferrando, Carlos
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Gattinoni, Luciano
    Gottingen Univ, Dept Anesthesiol Emergency & Intens Care Med, Gottingen, Germany..
    Goldik, Zeev
    Gregoretti, Cesare
    Univ Palermo, Policlin Paolo Giaccone, Sect Anesthesia Analgesia Intens Care & Emergency, Dept Biopathol & Med Biotechnol DIBIMED, Palermo, Italy..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anaesthesiol & Intens Care Med, Magdeburg, Germany..
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Hopf, Harriet W.
    Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA..
    Hunt, Thomas K.
    Univ Calif San Francisco, Div Gen Surg, San Francisco, CA 94143 USA..
    Pelosi, Paolo
    Univ Genoa, IRCCS AOU San Martino IST, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Qadan, Motaz
    Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA..
    Sessler, Daniel I.
    Cleveland Clin, Inst Anesthesiol, Dept Outcomes Res, Cleveland, OH 44106 USA..
    Soro, Marina
    Univ Valencia, Hosp Clin Univ, Dept Anesthesiol & Crit Care, Valencia, Spain..
    Sentürk, Mert
    Istanbul Univ, Istanbul Sch Med, Dept Anaesthesiol & Reanimat, Istanbul, Turkey..
    WHO Needs High FIO2?2017Ingår i: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, nr 4, s. 181-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 13.
    Akerlund, Emma
    et al.
    Inst för Experimentell och Klinisk medicin, Linköping.
    Huss, Fredrik R M
    Inst för Experimentell och Klinisk medicin, Linköping.
    Sjöberg, Folke
    Inst för Experimentell och Klinisk medicin, Linköping.
    Burns in Sweden: an analysis of 24,538 cases during the period 1987-2004.2007Ingår i: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 33, nr 1, s. 31-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 14.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    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-analysis2020Ingår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 76, nr 6, s. 826-+Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 15.
    Alström, Ulrica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Platelet Inhibition and Bleeding in Coronary Artery Bypass Surgery2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

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

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

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

     

     

    Delarbeten
    1. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
    Öppna denna publikation i ny flik eller fönster >>The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment
    Visa övriga...
    2007 (Engelska)Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 120, nr 3, s. 353-359Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

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

    Nyckelord
    Clopidogrel, Flow cytometry, Thrombelastograph, Platelets, PFA-100
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-24441 (URN)10.1016/j.thromres.2006.10.009 (DOI)000247762600005 ()17137616 (PubMedID)
    Tillgänglig från: 2007-02-15 Skapad: 2007-02-15 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
    Öppna denna publikation i ny flik eller fönster >>Platelet inhibition assessed with VerifyNow, flow cytometry and PlateletMapping in patients undergoing heart surgery
    Visa övriga...
    2009 (Engelska)Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, nr 5, s. 572-577Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

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

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-120242 (URN)10.1016/j.thromres.2009.06.024 (DOI)000271712800012 ()19631364 (PubMedID)
    Tillgänglig från: 2010-03-10 Skapad: 2010-03-10 Senast uppdaterad: 2022-01-28Bibliografiskt granskad
    3.
    Posten kunde inte hittas. Det kan bero på att posten inte längre är tillgänglig eller att du har råkat ange ett felaktigt id i adressfältet.
    4.
    Posten kunde inte hittas. Det kan bero på att posten inte längre är tillgänglig eller att du har råkat ange ett felaktigt id i adressfältet.
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    FULLTEXT01
  • 16.
    Andersson, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Reduced Preoperative Fasting in Children2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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.

    Delarbeten
    1. Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    Öppna denna publikation i ny flik eller fönster >>Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite
    2015 (Engelska)Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, nr 8, s. 770-777Artikel i tidskrift (Refereegranskat) 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.

    Nationell ämneskategori
    Pediatrik Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-256491 (URN)10.1111/pan.12667 (DOI)000357730600003 ()25940831 (PubMedID)
    Tillgänglig från: 2015-06-24 Skapad: 2015-06-24 Senast uppdaterad: 2019-10-06Bibliografiskt granskad
    2. Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    Öppna denna publikation i ny flik eller fönster >>Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
    2018 (Engelska)Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, nr 1, s. 46-52Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    anesthesia, children, fasting, fluids, preoperative
    Nationell ämneskategori
    Anestesi och intensivvård Pediatrik
    Identifikatorer
    urn:nbn:se:uu:diva-343890 (URN)10.1111/pan.13282 (DOI)000417604600008 ()29168341 (PubMedID)
    Tillgänglig från: 2018-03-05 Skapad: 2018-03-05 Senast uppdaterad: 2019-10-06Bibliografiskt granskad
    3. Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study
    Öppna denna publikation i ny flik eller fönster >>Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study
    2019 (Engelska)Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 29, nr 12, s. 1173-1178Artikel i tidskrift (Refereegranskat) 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.

    Nyckelord
    general anesthesia, paediatric, preoperative fasting, ultrasound
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-394230 (URN)10.1111/pan.13755 (DOI)000493655400001 ()31608517 (PubMedID)
    Tillgänglig från: 2019-10-05 Skapad: 2019-10-05 Senast uppdaterad: 2020-04-21Bibliografiskt granskad
    4. Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    Öppna denna publikation i ny flik eller fönster >>Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational study
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    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.

    Nyckelord
    General Anesthesia, child < Age, Dehydration, Fasting, Hypoglycaemia, Ketosis
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård; Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-394231 (URN)
    Tillgänglig från: 2019-10-05 Skapad: 2019-10-05 Senast uppdaterad: 2019-10-06
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  • 17.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Elias, Eerola
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Preoperative weight loss, hypoglycaemia and ketosis in elective paediatric patients, preliminary results from a prospective observational studyManuskript (preprint) (Övrigt vetenskapligt)
    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.

  • 18.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gastric content assessed with gastric ultrasound in paediatric patients prescribed a light breakfast prior to general anaesthesia: A prospective observational study2019Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 29, nr 12, s. 1173-1178Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children2018Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, nr 1, s. 46-52Artikel i tidskrift (Refereegranskat)
    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.

  • 20.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Schmitz, Achim
    Univ Childrens Hosp Zürich, Dept Anesthesiol, Zürich, Switzerland.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Preoperative fasting guidelines in pediatric anesthesia: are we ready for a change?2018Ingår i: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 31, nr 3, s. 342-348Artikel, forskningsöversikt (Refereegranskat)
    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

  • 21.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Zarén, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Low incidence of pulmonary aspiration in children allowed intake of clear fluids until called to the operating suite2015Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 25, nr 8, s. 770-777Artikel i tidskrift (Refereegranskat)
    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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  • 22.
    Andersson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). School of Medical Sciences, Örebro University, Örebro, Sweden.
    Nordgren, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Cheng, Ivy
    Nilsson, Ulrica
    Kurland, Lisa
    Long emergency department length of stay: A concept analysis2020Ingår i: International Emergency Nursing, ISSN 1755-599X, E-ISSN 1878-013X, Vol. 53, artikel-id 100930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Emergency Department (ED) Length of stay (LOS) has been associated with poor patient outcomes, which has led to the implementation of time targets designed to keep EDLOS below a specific limit. The cut-offs defining long EDLOS varies across settings and seem to be arbitrarily chosen. This study aimed to clarify the meaning of long EDLOS.

    METHODS: A concept analysis using the Walker and Avant approach was conducted. It included a literature search aiming to identify all uses of the concept, resulting in a set of defining attributes and a way of measuring the concept empirically.

    RESULTS: Long EDLOS was primarily used as proxy for other phenomena, e.g. boarding or crowding. The definitions had cut-offs ranging between 4 and 48 h. The attributes defining long EDLOS was waiting, a crowded ED environment and an inefficient organization.

    DISCUSSION: Time targets are probably more suitable when directed towards and tailored for specific sub-groups of the ED population.

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  • 23.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    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 Physiology2021Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 56, nr 3, s. 352-359Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 24.
    Arakelian, Erebouni
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Nyholm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Enblad: Neurokirurgi.
    Öster, Caisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    How Anesthesiologists and Nurse Anesthetists Assess and Handle Patients' Perioperative Worries Without a Validated Instrument2019Ingår i: Journal of Perianesthesia Nursing, ISSN 1089-9472, E-ISSN 1532-8473, Vol. 34, nr 4, s. 810-819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To study how nurse anesthetists and anesthesiologists assess and handle patients' perioperative anxiety without using a validated instrument.

    DESIGN: Qualitative study.

    METHODS: Individual in-depth face-to-face interviews were conducted with nurse anesthetists (n = 9) and anesthesiologists (n = 5) from a university hospital in Sweden. Data were analyzed with thematic analysis according to Braun and Clark.

    FINDINGS: Two themes were identified: (1) I ask about anxiety, look for visual signs, and observe communication and (2) I handle patients' anxieties individually. In addition to subthemes describing assessment and handling of adults, it appeared that parents played an important role in children's perioperative anxiety.

    CONCLUSIONS: When not using a validated instrument, assessing perioperative anxiety is commonly based on the anesthesiologist's and nurse anesthetist's experience, knowledge, views, and attitudes. The evaluator's capability of using different strategies in the assessment and handling of perioperative anxiety is important.

  • 25. Arbeus, Mikael
    et al.
    Axelsson, Birger
    Friberg, Orjan
    Magnuson, Anders
    Bodin, Lennart
    Hultman, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Milrinone Increases Flow in Coronary Artery Bypass Grafts After Cardiopulmonary Bypass: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study2009Ingår i: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 23, nr 1, s. 48-53Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Aronsson Dannewitz, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Medicinsk epidemiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Medicinsk epidemiologi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Optimized diagnosis-based comorbidity measures for all-cause mortality prediction in a national population-based ICU population2022Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 26, artikel-id 306Artikel i tidskrift (Refereegranskat)
    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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  • 27.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Franzén, Stephanie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bülow Anderberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kristensen, Bjarne
    Thermo Fisher Scientific, DK-84 3450 Alleröd, Denmark..
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19: A Swedish Cohort Study2023Ingår i: Biomedicines, E-ISSN 2227-9059, Vol. 11, nr 1, artikel-id 164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included-102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2-0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.

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  • 28.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Ruge, Thoralph
    Department of Clinical Sciences, Lund University, Malmö, Sweden, Lund, 221 00, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Bülow Anderberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Plasma endostatin correlates with hypoxia and mortality in COVID-19-associated acute respiratory failure2021Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 15, nr 16, s. 1509-1517Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease.

    Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection.

    Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival.

    Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml.

    Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.

  • 29.
    Athlin, Åsa Muntlin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Univ Uppsala Hosp, Dept Emergency Care & Internal Med, Entrance 40, S-75185 Uppsala, Sweden.;Univ Adelaide, Sch Nursing, Adelaide, SA, Australia..
    Engström, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. Univ Gavle, Fac Hlth & Occupat Studies, Dept Hlth & Caring Sci, Gavle, Sweden.;Lishui Univ, Sch Med & Hlth, Dept Nursing, Lishui, Peoples R China..
    Gunningberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. Univ Uppsala Hosp, Qual Dept, Uppsala, Sweden..
    Baath, Carina
    Karlstad Univ, Fac Hlth Sci & Technol, Dept Hlth Sci, Karlstad, Sweden.;Cty Council Varmland, Karlstad, Sweden..
    Heel pressure ulcer, prevention and predictors during the care delivery chain - when and where to take action?: A descriptive and explorative study2016Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 24, artikel-id 134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 30. Aydin, N.
    et al.
    Yilmaz, O.
    Deveci, M.
    Lv, Z.
    Heuristics Based Optimization for Multidepot Drone Location and Routing Problem to Detect Post-Earthquake Damages2022Ingår i: IEEE transactions on intelligent transportation systems (Print), ISSN 1524-9050, E-ISSN 1558-0016, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this research is to detect the post-disaster damage by drones as soon as possible so that decision makers can assign search and rescue teams effectively and efficiently. The main differences of this research from the others, which use drones in literature, are as: First, the regions are divided into grids and different importance values are assigned according to the number of buildings that are likely to be damaged and are vital for the response stage, such as hospitals, schools, and fire stations. Second, these importance levels are updated based on the day and time, which helps ordering the grids in a more realistic manner. Third, the depots are selected among the pre-determined candidate locations in accordance with the purpose of objective function. Fourth, detection times at grids are considered as uncertain. Fifth, two versions of Ant Colony Optimization (ACO) are developed as alternatives to exact solution tools. Last, sensitivity analyzes are performed by reducing the number of sorties, reducing the number of drones, and comparing day and night importance values for each instance. According to the results, only for very small-scale instances, exact solution tool was able to reach the optimal while both versions of ACO reached to similar results within a very less CPU times. Additionally, these ACO algorithms also found good results for the larger scaled problems. Then the performance of these ACO algorithms and the exact solution method are compared based on the CPU time and solution quality. IEEE

  • 31.
    Bachmann, M. Consuelo
    et al.
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morais, Caio
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Bugedo, Guillermo
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Morales, Arturo
    Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Resp, Santiago, Chile.
    Batista Borges, João
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Costa, Eduardo
    Univ Sao Paulo, Inst Coracao Incor, Hosp Clin, Div Pneumol,Fac Med, Sao Paulo, Brazil.
    Retamal, Jaime
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile;Acute Resp & Crit Illness Ctr ARCI, Santiago, Chile.
    Electrical impedance tomography in acute respiratory distress syndrome2018Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, artikel-id 263Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.

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  • 32. Backes, Yara
    et al.
    van der Sluijs, Koenraad F
    Mackie, David P
    Tacke, Frank
    Koch, Alexander
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Schultz, Marcus J
    Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review2012Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 38, nr 9, s. 1418-1428Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    PURPOSE:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

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  • 33.
    Balintescu, Anca
    et al.
    Section of Anaesthesia and Intensive Care, Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden..
    Palmgren, Ida
    Section of Anaesthesia and Intensive Care, Hudiksvall Hospital, Hudiksvall, Sweden..
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Oldner, Anders
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Cronhjort, Maria
    Section of Anaesthesia and Intensive Care, Department of Clinical Science and Education Södersjukhuset, Karolinska Institute, Stockholm, Sweden..
    Lind, Marcus
    Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden..
    Wernerman, Jan
    Division of Anaesthesia and Intensive Care, Department of Clinical Science Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden..
    Mårtensson, Johan
    n of Anaesthesia and Intensive Care, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden..
    Prevalence and impact of chronic dysglycemia in intensive care unit patients-A retrospective cohort study.2021Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 1, s. 82-91Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to Swedish intensive care units (ICUs) is unknown. We aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centered outcomes in critically ill patients.

    METHODS: In this retrospective observational cohort study, we obtained glycated hemoglobin A1c (HbA1c) in patients admitted to four tertiary ICUs in Sweden between March and August 2016. Based on previous diabetes history and HbA1c we determined the prevalence of chronic dysglycemia. We used multivariable regression analyses to study the association of chronic dysglycemia with the time-weighted average blood glucose concentration, glycemic lability index (GLI), and development of hypoglycemia (co-primary outcomes), and with ICU length of stay, mechanical ventilation duration, renal replacement therapy (RRT) use, vasopressor use, ICU-acquired infections, and mortality (exploratory clinical outcomes).

    RESULTS: Of 943 patients, 312 (33%) had chronic dysglycemia. Of these 312 patients, 84 (27%) had prediabetes, 43 (14%) had undiagnosed diabetes and 185 (59%) had known diabetes. Chronic dysglycemia was independently associated with higher time-weighted average blood glucose concentration (P < .001), higher GLI (P < .001), and hypoglycemia (P < .001). Chronic dysglycemia was independently associated with RRT use (adjusted odds ratio 1.97, 95% CI 1.24-3.13, P = .004) but not with other exploratory clinical outcomes.

    CONCLUSIONS: In four tertiary Swedish ICUs, measurement of HbA1c showed that one-third of patients had chronic dysglycemia. Chronic dysglycemia was associated with marked derangements in glycemic control, and a greater need for renal replacement therapy.

  • 34.
    Ball, Lorenzo
    et al.
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS San Martino IST, Genoa, Italy.
    Pelosi, Paolo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS San Martino IST, Genoa, Italy.
    de Abreu, Marcelo Gama
    Tech Univ Dresden, Dept Anesthesiol & Intens Care Therapy, Dresden, Germany.
    Rocco, Patricia R. M.
    Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Lab Pulm Invest, Rio De Janeiro, Brazil.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Injurious Ventilation and Post-Operative Residual Curarization: A Dangerous Combination Reply2017Ingår i: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION, ISSN 2149-0937, Vol. 45, nr 1, s. 61-62Artikel i tidskrift (Övrigt vetenskapligt)
  • 35.
    Bandert, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Department of Anaesthesiology and Intensive Care, Gävle Hospital, Lasarettvägen 1, 80324, Gävle, Sweden.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Smekal, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    In an endotoxaemic model, antibiotic clearance can be affected by different central venous catheter positions, during renal replacement therapy2023Ingår i: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, nr 1, artikel-id 32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In intensive care, different central venous catheters (CVC) are often used for infusion of drugs. If a patient is treated with continuous renal replacement therapy (CRRT) a second catheter, a central venous dialysis catheter (CVDC), is needed. Placing the catheters close together might pose a risk that a drug infused in a CVC could be directly aspirated into a CRRT machine and cleared from the blood without giving the effect intended. The purpose of this study was to elucidate if drug clearance is affected by different catheter placement, during CRRT. In this endotoxaemic animal model, an infusion of antibiotics was administered in a CVC placed in the external jugular vein (EJV). Antibiotic clearance was compared, whether CRRT was through a CVDC placed in the same EJV, or in a femoral vein (FV). To reach a target mean arterial pressure (MAP), noradrenaline was infused through the CVC and the dose was compared between the CDVDs.

    RESULTS: The main finding in this study was that clearance of antibiotics was higher when both catheter tips were in the EJV, close together, compared to in different vessels, during CRRT. The clearance of gentamicin was 21.0 ± 7.3 vs 15.5 ± 4.2 mL/min (p 0.006) and vancomycin 19.3 ± 4.9 vs 15.8 ± 7.1 mL/min (p 0.021). The noradrenaline dose to maintain a target MAP also showed greater variance with both catheters in the EJV, compared to when catheters were placed in different vessels.

    CONCLUSION: The results in this study indicate that close placement of central venous catheter tips could lead to unreliable drug concentration, due to direct aspiration, during CRRT.

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  • 36. Barr, Travis P.
    et al.
    Hrnjic, Alen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Khodorova, Alla
    Sprague, Jared M.
    Strichartz, Gary R.
    Sensitization of cutaneous neuronal purinergic receptors contributes to endothelin-1-induced mechanical hypersensitivity2014Ingår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 155, nr 6, s. 1091-1101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 37.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Massaro, Fabrizia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Anthea Hosp, GVM Care & Res, Cardiac Anesthesia & Intens Care, Bari, Italy.
    Hansson, Hans Arne
    Univ Gothenburg, Inst Biomed, Gothenburg, Sweden.
    Feinstein, Ricardo
    Natl Vet Inst, Dept Pathol & Wildlife Dis, Uppsala, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Does the antisecretory peptide AF-16 reduce lung oedema in experimental ARDS?2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 4, s. 246-253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

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  • 38.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    van der Heijden, Jaap
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Blokhin, Ivan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Massaro, Fabrizia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Cardiac Anesthesia and Intensive Care, Anthea Hospital, GVM Care & Research, Bari, Italy.
    Hansson, Hans Arne
    Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
    Feinstein, Ricardo
    Department of Pathology and Wildlife Diseases, National Veterinary Institute, Uppsala, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The antisecretory peptide AF-16 may modulate tissue edema but not inflammation in experimental peritonitis induced sepsis2020Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 15, nr 8, artikel-id e0232302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.

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  • 39.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    van der Heijden, Jaap
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Dogné, Sophie
    Molecular Physiology Research Unit (URPhyM), Namur Research Institute for Life Sci-ences (NARILIS), University of Namur (Unamur), Belgium.
    Flamion, Bruno
    Molecular Physiology Research Unit (URPhyM), Namur Research Institute for Life Sci-ences (NARILIS), University of Namur (Unamur), Belgium.
    Weigl, Wojciech
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    High molecular weight hyaluronan: a potential adjuvant to fluid resuscitation in abdominal sepsis?2023Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 59, nr 5, s. 763-770Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypo-perfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis.

    In a prospective, parallel-grouped, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy) (n=8) or 0.9% saline (n=8). After the onset of hemodynamic instability the animals received an initial bolus of 0.1 % hyaluronan 1 mg/kg/10 min or placebo (0.9% saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation <13%) and/or attenuate the inflammatory reaction.

    Total volumes of intravenous fluids infused were 17.5 ± 11 ml/kg/h vs. 19.0 ± 7 ml/kg/h in intervention and control groups, respectively (p = 0.442). Plasma IL-6 increased to 2450 (1420 – 6890) pg/ml and 3690 (1410 – 11960) pg/ml (18 hours of resuscitation) in the intervention and control groups (NS). The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis-sepsis alone (mean peak elution fraction (18 hours of resuscitation) control group: 17.9 ± 0.6 vs. intervention group: 16.8 ± 0.9 (p = 0.031).

    In conclusion, hyaluronan did not reduce the volume needed for fluid resuscitation or decrease the inflammatory reaction, even though it counterbalanced the peritonitis induced shift towards increased proportion of fragmented hyaluronan.

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  • 40.
    Barrueta Tenhunen, Annelie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    van der Heijden, Jaap
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Maccarana, Marco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Perchiazzi, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Fluid restrictive resuscitation with high molecular weight hyaluronan infusion in early peritonitis sepsis2023Ingår i: Intensive Care Medicine Experimental, E-ISSN 2197-425X, Vol. 11, nr 1, artikel-id 63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.

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  • 41.
    Bartek, Jiri, Jr.
    et al.
    Copenhagen Univ Hosp, Dept Neurosurg, Rigshosp, Copenhagen, Denmark;Karolinska Univ Hosp, Dept Neurosurg, Karolinskavagen, Stockholm, Sweden.
    Laugesen, Christian
    Copenhagen Univ Hosp, Dept Neurosurg, Rigshosp, Copenhagen, Denmark.
    Mirza, Sadia
    Karolinska Univ Hosp, Dept Neurosurg, Karolinskavagen, Stockholm, Sweden.
    Forsse, Axel
    Odense Univ Hosp, Dept Neurosurg, Odense, Denmark.
    Petersen, Michael Anders
    Odense Univ Hosp, Dept Neurosurg, Odense, Denmark.
    Corell, Alba
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden.
    Dyhrfort, Philip Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala Univ Hosp, Dept Neurosurg, Uppsala, Sweden.
    Redebrandt, Henrietta Nittby
    Lund Univ Hosp, Dept Neurosurg, Lund, Sweden.
    Reen, Linus
    Lund Univ Hosp, Dept Neurosurg, Lund, Sweden.
    Zolfaghari, Shaian
    Lund Univ Hosp, Dept Neurosurg, Lund, Sweden.
    Tobieson, Lovisa
    Linkoping Univ Hosp, Dept Neurosurg, Linkoping, Sweden.
    Carlsvard, Bjoern
    Linkoping Univ Hosp, Dept Neurosurg, Linkoping, Sweden.
    Bergholt, Bo
    Arhus Univ Hosp, Dept Neurosurg, Aarhus, Denmark.
    Bashir, Asma
    Arhus Univ Hosp, Dept Neurosurg, Aarhus, Denmark.
    Soerensen, Preben
    Alborg Univ Hosp, Dept Neurosurg, Aalborg, Denmark.
    Bilgin, Arzu
    Alborg Univ Hosp, Dept Neurosurg, Aalborg, Denmark.
    Johansson, Conny
    Umea Univ Hosp, Dept Neurosurg, Umea, Sweden.
    Lindvall, Peter
    Umea Univ Hosp, Dept Neurosurg, Umea, Sweden.
    Förander, Petter
    Uppsala Univ Hosp, Dept Neurosurg, Uppsala, Sweden.
    Bellander, Bo-Michael
    Karolinska Univ Hosp, Dept Neurosurg, Karolinskavagen, Stockholm, Sweden.
    Springborg, Jacob B.
    Copenhagen Univ Hosp, Dept Neurosurg, Rigshosp, Copenhagen, Denmark.
    Jakola, Asgeir S.
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden;Sahlgrens Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study: Study Protocol for a Multinational Population-Based Consecutive Cohort2019Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 84, nr 3, s. 799-803Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    Traumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved.

    OBJECTIVE

    To evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables.

    METHODS

    This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190.

    EXPECTED OUTCOMES

    We expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified.

    DISCUSSION

    An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.

  • 42.
    Bartha, Erzsebet
    et al.
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Huddinge, Sweden..
    Ahlstrand, Rebecca
    Örebro Univ, Fac Med & Hlth, Dept Anaesthesiol, Örebro, Sweden..
    Bell, Max
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Solna, Sweden..
    Björne, Håkan
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Huddinge, Sweden..
    Brattström, Olof
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Solna, Sweden..
    Helleberg, Johan
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Huddinge, Sweden..
    Nilsson, Lena
    Linköping Univ, Dept Anesthesiol & Intens Care, Dept Biomed & Clin Sci, Linköping, Sweden..
    Semenas, Egidijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kalman, Sigridur
    Karolinska Univ Hosp, Dept Perioperat Med & Intens Care, Huddinge, Sweden..
    ASA classification and surgical severity grading used to identify a high-risk population, a multicenter prospective cohort study in Swedish tertiary hospitals2021Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 9, s. 1168-1177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Identification of surgical populations at high risk for negative outcomes is needed for clinical and research purposes. We hypothesized that combining two classification systems, ASA (American Society of Anesthesiology physical status) and surgical severity, we could identify a high-risk population before surgery. We aimed to describe postoperative outcomes in a population selected by these two classifications system.

    Methods: Data were collected in a Swedish multicentre, time-interrupted prospective, consecutive cohort study. Eligibility criteria were age >= 18 years, ASA >= 3, elective or emergent, major to Xmajor/complex (Specialist Procedure Codes used in United Kingdom), gastrointestinal, urogenital or orthopaedic procedures. Postoperative morbidity was identified by the Postoperative Morbidity Survey on postoperative days 3 +/- 1, 7 +/- 1, 10 + 5 and graded for severity by the Clavien-Dindo system. Mortality was assessed at 30, 180 and 360 days.

    Results: Postoperative morbidity was 78/48/47 per cent on postoperative days 3/7/10. Majority of morbidities (67.5 per cent) were graded as >1 by Clavien-Dindo. Any type of postoperative morbidity graded >1 was associated with increased risk for death up to one year. The mortality was 5.7 per cent (61/1063) at 30 days, 13.3 per cent (142/1063) at 6 months and 19.1 per cent (160/1063) at 12 months.

    Conclusion: Severity classification as major to Xmajor/complex and ASA >= 3 could be used to identify a high-risk surgical population concerning postoperative morbidity and mortality before surgery. Combining the two systems future electronic data extraction is possible of a high-risk population in tertiary hospitals.

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  • 43.
    Bartha, Erzsebet
    et al.
    Karolinska Univ Hosp, Huddinge, Sweden..
    Helleberg, Johan
    Karolinska Univ Hosp, Huddinge, Sweden..
    Ahlstrand, Rebecca
    Orebro Univ Hosp, Orebro, Sweden..
    Bell, Max
    Karolinska Univ Hosp, Solna, Sweden..
    Bjorne, Hakan
    Karolinska Univ Hosp, Solna, Sweden..
    Brattstrom, Olof
    Karolinska Univ Hosp, Solna, Sweden..
    Nilsson, Lena
    Univ Hosp Linkoping, Linkoping, Sweden..
    Semenas, Egidijus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Andreas
    Karolinska Univ Hosp, Solna, Sweden..
    Kalman, Sigridur
    Karolinska Univ Hosp, Huddinge, Sweden..
    Performance of prediction models of postoperative mortality in high-risk surgical patients in swedish university hospitals: Predictors, Risk factors and Outcome Following major Surgery study (PROFS study NCT02626546)2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 1056-1057Artikel i tidskrift (Övrigt vetenskapligt)
  • 44.
    Basu, Samar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Liu, Xiaoli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nozari, Ala
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation2003Ingår i: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 37, nr 3, s. 251-256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 45.
    Baumgardner, James E.
    et al.
    Oscillogy LLC, Folsom, PA USA..
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Ventilation/perfusion distributions revisited2016Ingår i: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 29, nr 1, s. 2-7Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

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

  • 46.
    Baumgardner, James E.
    et al.
    Univ Pittsburgh, Med Ctr, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15213 USA.;Oscill LLC, Pittsburgh, PA USA..
    Kretzschmar, Moritz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Kozian, Alf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Schilling, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Otto von Guericke Univ, Dept Anesthesiol & Intens Care Med, Magdeburg, Germany..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics2021Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 135, nr 6, s. 1042-1054Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (V-A/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane.

    Methods: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung V-A/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different V-A/Q conditions: normal, low, and high.

    Results: The mathematical model predicts that the global V-A/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three V-A/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure P-art/P-mv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant.

    Conclusions: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The V-A/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower V-A/Q ratios.

  • 47.
    Becriovic Agic, Mediha
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Jönsson, Sofia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Genetic association of oxidative stress and fluid accumulation makes Balb/CJ mice more sensitive to decompensated heart failure2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 963-964Artikel i tidskrift (Övrigt vetenskapligt)
  • 48. Bell, Max
    et al.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bellomo, Rinaldo
    Mårtensson, Johan
    Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury2015Ingår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 2015, artikel-id 158658Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

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  • 49.
    Bellani, Giacomo
    et al.
    Univ Milano Bicocca, Sch Med & Surg, Monza, Italy.;San Gerardo Hosp, Dept Emergency & Intens Care, Monza, Italy..
    Laffey, John G.
    St Michaels Hosp, Dept Anesthesia & Crit Care Med, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.;Univ Toronto, Dept Anesthesia, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Dept Physiol, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pham, Tai
    Grp Hosp Hop Univ Est Parisien, Hop Tenon, AP HP, Unite Reanimat Med Chirurgicale,Pole Thorax Voies, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, ECSTRA Team, UMR 1153,Inserm, Paris, France.;Univ Paris Est Creteil, UMR 915, INSERM, Creteil, France..
    Fan, Eddy
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Hlth Network, Dept Med, Toronto, ON, Canada.;Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.;Univ Toronto, Inst Hlth Policy Management & Evaluat, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Brochard, Laurent
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Esteban, Andres
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Hosp Univ Getafe, CIBER Enfermedades Respiratorias, Madrid, Spain..
    Gattinoni, Luciano
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    van Haren, Frank
    Canberra Hosp, Intens Care Unit, Canberra, ACT, Australia.;Australian Natl Univ, Canberra, ACT, Australia..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    McAuley, Daniel F.
    Queens Univ Belfast, Ctr Med Expt, Belfast, Antrim, North Ireland.;Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland.;Royal Victoria Hosp, Reg Intens Care Unit, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland..
    Ranieri, Marco
    Policlin Umberto 1, SAPIENZA Univ ROMA, Dipartimento Anestesia & Rianimaz, Viale Policlin 155, I-00161 Rome, Italy..
    Rubenfeld, Gordon
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Sunnybrook Hlth Sci Ctr, Program Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada..
    Thompson, B. Taylor
    Harvard Univ, Sch Med, Div Pulm, Boston, MA USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Unit,Dept Med, Boston, MA USA..
    Wrigge, Hermann
    Univ Leipzig, Dept Anesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany..
    Slutsky, Arthur S.
    Univ Toronto, Interdept Div Crit Care Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.;Univ Toronto, St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, 30 Bond St, Toronto, ON M5B 1W8, Canada..
    Pesenti, Antonio
    Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, Ist Ricovero & Cura Carattere Sci, Milan, Italy..
    Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries2016Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 315, nr 8, s. 788-800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 50.
    Berglund, Ellinor
    et al.
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Olsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Hälsovetenskap och e-hälsa.
    Jonsson, Martin
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Svensson, Leif
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Hollenberg, Jacob
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Claesson, Andreas
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Nordberg, Per
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Lundgren, Peter
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Borås, Prehospen Ctr Prehosp Res, Borås, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Reg Vastra Gotaland, Gothenburg, Sweden..
    Hogstedt, Asa
    Univ Borås, Fac Caring Sci Work Life & Social Welf, Borås, Sweden..
    Ringh, Mattias
    Karolinska Inst, Ctr Resuscitat Sci, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11884 Stockholm, Sweden..
    Wellbeing, emotional response and stress among lay responders dispatched to suspected out-of-hospital cardiac arrests2022Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 170, s. 352-360Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Systems for smartphone dispatch of lay responders to perform cardio-pulmonary resuscitation (CPR) and bring automated external defibrillators to out-of-hospital cardiac arrests (OHCAs) are advocated by recent international guidelines and emerging worldwide.

    Objectives: This study aimed to investigate the emotional responses, posttraumatic stress reactions and levels of wellbeing among smartphonealerted lay responders dispatched to suspected OHCAs.

    Methods: Lay responders were stratified by level of exposure: unexposed (Exp-0), tried to reach (Exp-1), and reached the suspected OHCA (Exp2). Participants rated their emotional responses online, at 90 minutes and at 4-6 weeks after an incident. Level of emotional response was measured in two dimensions of core affect: "alertness" - from deactivation to activation, and "pleasantness" - from unpleasant to pleasant. At 4-6 weeks, WHO wellbeing index and level of posttraumatic stress (PTSD) were also rated.

    Results: Altogether, 915 (28%) unexposed and 1471 (64%) exposed responders completed the survey. Alertness was elevated in the exposed groups: Exp-0: 6.7 vs. Exp-1: 7.3 and Exp-2: 7.5, (p < 0.001) and pleasantness was highest in the unexposed group: 6.5, vs. Exp-1: 6.3, and Exp-2: 6.1, (p < 0.001). Mean scores for PTSD at follow-up was below clinical cut-off, Exp-0: 9.9, Exp-1: 8.9 and Exp-2: 8.8 (p = 0.065). Wellbeing index showed no differences, Exp-0: 78.0, Exp-1: 78.5 and Exp-2: 79.9 (p = 0.596).

    Conclusion: Smartphone dispatched lay responders rated the experience as high-energy and mainly positive. No harm to the lay responders was seen. The exposed groups had low posttraumatic stress scores and high-level general wellbeing at follow-up.

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