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  • 1. Berg, S
    et al.
    Delude, RL
    Linkoping Univ, S-58183 Linkoping, Sweden Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA Dept Pathol, Pittsburgh, PA USA Dept Crit Care Med, Pittsburgh, PA USA.
    Fink, MP
    Linkoping Univ, S-58183 Linkoping, Sweden Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA Dept Pathol, Pittsburgh, PA USA Dept Crit Care Med, Pittsburgh, PA USA.
    Pro-inflammatory cytokines increase ATP consumption rate in cultured rat enterocytes2001In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 29, no 12, p. 26-Conference paper (Other academic)
  • 2.
    Berg, Sören
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Fink, MP
    Linkoping Univ, S-58183 Linkoping, Sweden Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA.
    Delude, RL
    Linkoping Univ, S-58183 Linkoping, Sweden Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA.
    Cytokine exposure prior to hypoxia modulates HIF-1 nuclear binding in response to hypoxia in cultured rat (IEC-6) enterocytes2001In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 29, no 12, p. 77-Conference paper (Other academic)
  • 3.
    Berg, Sören
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Sappington, P.L.
    Department of Critical Care Medicine, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States.
    Guzik, L.J.
    Department of Critical Care Medicine, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States.
    Delude, R.L.
    Department of Critical Care Medicine, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States, Department of Pathology, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States.
    Fink, M.P.
    Department of Critical Care Medicine, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States, Department of Surgery, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh, PA, United States, 616 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, United States.
    Proinflammatory cytokines increase the rate of glycolysis and adenosine-5'-triphosphate turnover in cultured rat enterocytes2003In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 31, no 4, p. 1203-1212Article in journal (Refereed)
    Abstract [en]

    Objective: Measurements of steady-state adenosine-5'-triphosphate (ATP) levels in tissue samples from patients or experimental animals with sepsis or endotoxemia provide little information about the rate of ATP production and consumption in these conditions. Accordingly, we sought to use an in vitro "reductionist" model of sepsis to test the hypothesis that proinflammatory cytokines modulate ATP turnover rate. Design: In vitro "reductionist" model of sepsis. Setting: University laboratory. Subjects: Cultured rat enterocyte-like cells. Interventions: IEC-6 nontransformed rat enterocytes were studied under control conditions or following incubation for 24 or 48 hrs with cytomix, a mixture of tumor necrosis factor-a (10 ng/mL), interleukin-1ß (1 ng/mL), and interferon-? (1000 units/mL). To measure ATP turnover rate, ATP synthesis was acutely blocked by adding to the cells a mixture of 2-deoxyglucose (10 mM), potassium cyanide (8 mM), and antimycin A (1 µM). ATP content was measured at baseline (before metabolic inhibition) and 0.5, 1, 2, 5, and 10 mins later. Log-linear ATP decay curves were generated and the kinetics of ATP utilization thereby calculated. Measurements and Main Results: ATP consumption rate was higher in cytomix-stimulated compared with control cells (3.11 ± 1.39 vs. 1.25 ± 0.66 nmol/min, respectively, p < .01). Similarly, the half-time for ATP disappearance was shorter in cytomix-stimulated compared with control cells (2.63 ± 1.00 vs. 6.21 ± 3.49, p < .05). In contrast to these findings, the rate of ATP disappearance was similar in cytokine-naïve and immunostimulated IEC-6 cells when protein and nucleic acid synthesis were inhibited by adding 50 µg/mL cycloheximide and 5 µg/mL actinomycin D to cultures for 4 hrs. The rates of glucose consumption and lactate production were significantly greater in cytomix-stimulated compared with controls cells. Conclusions: Incubation of IEC-6 cells with cytomix significantly increased ATP turnover. Increased ATP turnover rate was supported by increases in the rate of anaerobic glycolysis. These findings support the view that proinflammatory mediators impose a metabolic demand on visceral cells. In sepsis, cells may be more susceptible to dysfunction on the basis of diminished oxygen delivery and/or mitochondrial dysfunction.

  • 4.
    Chen, Ke-Ling
    et al.
    Sichuan University, Peoples R China.
    Lv, Zhao-Ying
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Liu, Yong
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 8, p. E664-E677Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.

  • 5.
    Chew, Michelle
    et al.
    Departments of Anaesthesia and Intensive Care, Institute of Experimental Clinical Research, Skejby Sygehus, Aarhus University Hospital, Denmark.
    Brandberg, Joakim
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Bjarum, Steinar
    Department of Biomerical Engineering, Trondheim University, Norway.
    Baek-Jensen, Katrine
    Institute of Experimental Clinical Research, Skejby Sygehus, Aarhus University Hospital, Denmark.
    Sloth, Erik
    Departments of Anaesthesia and Intensive Care, Skejby Sygehus, Aarhus University Hospital, Denmark.
    Ask, Per
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Hasenkam, J. Michael
    Department of Cardiothoracic Surgery, Skejby Sygehus, Aarhus University Hospital, Denmark.
    Janerot Sjöberg, Birgitta
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Pediatric cardiac output measurement using surface integration of velocity vectors: an in vivo validation study2000In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, no 11, p. 3664-3671Article in journal (Refereed)
    Abstract [en]

    Objective: To test the accuracy and reproducibility of systemic cardiac output (CO) measurements using surface integration of velocity vectors (SIVV) in a pediatric animal model with hemodynamic instability and to compare SIVV with traditional pulsed-wave Doppler measurements.

    Design: Prospective, comparative study.

    Setting: Animal research laboratory at a university medical center.

    Subjects: Eight piglets weighing 10-15 kg.

    Interventions: Hemodynamic instability was induced by using inhalation of isoflurane and infusions of colloid and dobutamine.

    Measurements: SIVV CO was measured at the left ventricular outflow tract, the aortic valve, and ascending aorta. Transit time CO was used as the reference standard.

    Results: There was good agreement between SIVV and transit time CO. At high frame rates, the mean difference ± 2 sd between the two methods was 0.01 ± 0.27 L/min for measurements at the left ventricular outflow tract, 0.08 ± 0.26 L/min for the ascending aorta, and 0.06 ± 0.25 L/min for the aortic valve. At low frame rates, measurements were 0.06 ± 0.25, 0.19 ± 0.32, and 0.14 ± 0.30 L/min for the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. There were no differences between the three sites at high frame rates. Agreement between pulsed-wave Doppler and transit time CO was poorer, with a mean difference ± 2 sd of 0.09 ± 0.93 L/min. Repeated SIVV measurements taken at a period of relative hemodynamic stability differed by a mean difference ±2 sd of 0.01 ± 0.22 L/min, with a coefficient of variation = 7.6%. Intraobserver coefficients of variation were 5.7%, 4.9%, and 4.1% at the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. Interobserver variability was also small, with a coefficient of variation = 8.5%.

    Conclusions: SIVV is an accurate and reproducible flow measurement technique. It is a considerable improvement over currently used methods and is applicable to pediatric critical care.

  • 6. Cucchiara, BL
    et al.
    Kasner, SE
    Wolk, DA
    Lyden, PD
    Knappertz, VA
    Ashwood, T
    Odergren, T
    Nordlund, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Work and Rehabilitation .
    Early impairment in consciousness predicts mortality after hemispheric ischemic stroke2004In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 32, no 1, p. 241-245Article in journal (Refereed)
    Abstract [en]

    Objective: Early predictors of poor outcome after acute ischemic stroke may be useful in selecting patients for potentially beneficial but high-risk interventions. Design. Cohort study of patients given placebo in a randomized clinical trial. Setting. Multicenter trial at 139 U.S. and 14 Canadian hospitals. Patients. A cohort of 564 placebo-treated patients with major anterior circulation ischemic stroke enrolled in the Clomethiazole in Acute Stroke Study-Ischemic Stroke (CLASS-I) trial. Patients did not have significant impairment in consciousness at baseline and were enrolled within 12 hrs of symptom onset. Interventions: Prospective data collection of a number of clinical variables including use of a 6-point level of consciousness scale (1 = awake, 6 = no reaction to pain) to measure patients' level of consciousness at enrollment and 12 additional times during the first 24 hrs after enrollment. The ability of level of consciousness score and additional clinical data to predict 30-day mortality was assessed. Measurements and Main Results., At 1 month, 114 of 564 patients (20%) had died. In univariate analysis, factors significantly associated with mortality included older age, white race, higher National Institutes of Health Stroke Scale score, higher serum glucose, atrial fibrillation, and any impairment in level of consciousness (p < .05). After controlling for these factors, increasing level of consciousness score at 3 hrs after enrollment and at all but one subsequent time point was significantly associated with increased mortality (odds ratio, 1.8 per point, 95% confidence interval, 1.2-2.6, p = .003 at 3-hr time point). Maximum level of consciousness score during the initial 24 hrs of monitoring also predicted mortality (odds ratio, 1.9 per point, 95% confidence interval, 1.4-2.5, p < .001). Conclusion: The development of a decreased level of consciousness within the initial hours after stroke onset, as evaluated by a simple six-point scale, is a powerful independent predictor of mortality after major anterior circulation ischemic stroke.

  • 7.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Kramer, Andrew A.
    Prescient Healthcare Consulting, Charlottesville, VA.
    Nolin, Thomas
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    The Swedish Intensive Care Registry, Karlstad, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Academic Research Center, Linköping University, Linköping, Sweden.
    Walther, Sten M
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Comparing Time-Fixed Mortality Prediction Models and Their Effect on ICU Performance Metrics Using the Simplified Acute Physiology Score 3.2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 11Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference.

    DESIGN: Retrospective cohort study of ICU admissions from 2010 to 2014.

    SETTING: Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry.

    PATIENTS: The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729).

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping (< 1.00, not significant, > 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs.

    CONCLUSIONS: The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

  • 8.
    Engerström, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nolin, Thomas
    Central Hospital Kristianstad, Sweden.
    Mårdh, Caroline
    Landstinget Värmland, Sweden.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Karlström, Göran
    Landstinget Varmland, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Walther, Sten
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model*2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 12, p. 2006-2013Article in journal (Refereed)
    Abstract [en]

    Objectives: The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 models performance. Design: Retrospective analysis of prospectively collected data. Setting: Sixty-three ICUs in the Swedish Intensive Care Registry. Patients: Patients admitted during 2011-2014 (n = 107,310). Interventions: None. Measurements and Main Results: Model performance was analyzed using the area under the receiver operating curve, scaled Briers score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. Conclusions: There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

  • 9.
    Johansson, Mats
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Wiklund, Andreas
    Department of Anaesthesia and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
    Flatebø, Torun
    Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Norway..
    Nicolaysen, Anne
    Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Norway.
    Nicolaysen, Gunnar
    Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Norway..
    Walther, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Positive end-expiratory pressure affects regional redistribution of ventilation differently in prone and supine sheep2004In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 32, no 10, p. 2039-2044Article in journal (Refereed)
    Abstract [en]

    Objective: To examine interactions between positive end-expiratory pressure (PEEP) and posture on regional distribution of ventilation and to compare measurements of regional ventilation with two aerosols: a wet fluorescent microsphere aerosol (FMS, median mass aerodynamic diameter 1.1 μm) and a dry 99mTc-labeled carbon particle aerosol (Technegas, TG, median mass aerodynamic diameter ≈0.1 μm). Design: Experimental study. Setting. Academic laboratory. Subjects: Anesthetized and mechanically ventilated sheep (n = 16). Interventions: Four conditions were studied: prone or supine posture with of without 10 cm H2O PEEP. Measurements and Main results: Comparisons of FMS and TG were made in five animals. The median correlation coefficient of the two ventilation tracers was .95 (range, .91-.96). The mean ventilation per unit weight of dry lung for horizontal planes was almost identical whether measured with TG or FMS. The distribution of ventilation was assessed by analyzing deposition of aerosol in about 1,000 lung regions per animal. Distribution of ventilation down the vertical axis was linear in prone (the slope indicated a dorsal-to-ventral three-fold difference in ventilation) but unimodal in supine animals with the mode in the center of the lung. Redistribution of ventilation with 10 PEEP differed between posture, shifting the mode in supine toward dependent lung regions while eliminating the dorsal-to-ventral gradient in prone. The regional heterogeneity in ventilation was greater in supine sheep at both levels of PEEP, and this was due mostly to greater isogravitational heterogeneity in supine than in prone position. Conclusions: The wet fluorescent microsphere aerosol was as reliable as Technegas for high-resolution measurements of regional ventilation. The markedly different effects of 10 PEEP in supine and prone sheep may have important implications for gas exchange both in noninjured and injured lungs.

  • 10.
    Linder, Adam
    et al.
    Lund University, Sweden.
    Arnold, Ryan
    Christiana Care Health Syst, DE USA; Christiana Care Health Syst, DE USA.
    Boyd, John H.
    University of British Columbia, Canada.
    Zindovic, Marko
    Lund University, Sweden.
    Zindovic, Igor
    Lund University, Sweden.
    Lange, Anna
    Örebro University Hospital, Sweden.
    Paulsson, Magnus
    Lund University, Sweden.
    Nyberg, Patrik
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Linköping University.
    Russell, James A.
    University of British Columbia, Canada.
    Pritchard, David
    Axis Shield Diagnost, Scotland.
    Christensson, Bertil
    Lund University, Sweden.
    Akesson, Per
    Lund University, Sweden.
    Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 11, p. 2378-2386Article in journal (Refereed)
    Abstract [en]

    Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (greater than 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

  • 11.
    Naredi, S.
    et al.
    Dept. Anaesthesia and Intensive Care.
    Koskinen, L.-O.
    Department of Neurosurgery, Umeå University Hospital, Sweden.
    Grande, P.-O.
    Grände, P.-O., Dept. Anaesthesia and Intensive Care.
    Nordstrom, C.-H.
    Nordström, C.-H., Department of Neurosurgery, Lund University Hospital, Sweden.
    Nellgard, B.
    Nellgård, B., Dept. Anaesthesia and Intensive Care.
    Rydenhag, B.
    Department of Neurosurgery, Shalgrens University Hospital, Gothenbourg, Sweden.
    Vegfors, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Anaesthesiology and Intensive Care VHN.
    Treatment of Traumatic Head Injury - U.S./European Guidelines or the Lund Concept [1]2003In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 31, no 11, p. 2713-2714Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 12.
    Olofsson, Pia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Berg, Sören
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Casimir Ahn, Henrik
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Brudin, Lars
    Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Wikström, Thore
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Kenth J M
    Department of Surgery, Västervik, Sweden.
    Gastrointestinal microcirculation and cardiopulmonary function during experimentally increased intra-abdominal pressure2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 1, p. 230-239Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to assess gastric, intestinal, and renal cortex microcirculation parallel with central hemodynamics and respiratory function during stepwise increase of intra-abdominal pressure (IAP).

    Design: Prospective, controlled animal study.

    Setting: Research laboratory, University Hospital.

    Subjects: Twenty-six anesthetized and mechanically ventilated pigs.

    Interventions: Following baseline registrations, CO2 peritoneum was inflated (n = 20) and IAP increased stepwise by 10 mm Hg at 10 mins intervals up to 50 mm Hg and subsequently exsufflated. Control animals (n = 6) were not insufflated with CO2.

    Measurements and Main Results: The microcirculation of gastric mucosa, small bowel mucosa, small bowel seromuscular layer, colon mucosa, colon seromuscular layer, and renal cortex were selectively studied at all pressure levels and after exsufflation using a four-channel laser Doppler flowmeter (Periflex 5000, Perimed). Central hemodynamic and respiratory function data were registered at each level and after exsufflation. Cardiac output decreased significantly at IAP levels above 10 mm Hg. The microcirculation of gastric mucosa, renal cortex and the seromuscular layer of small bowel and colon was significantly reduced with each increase of IAP. The microcirculation of the small bowel mucosa and colon mucosa was significantly less affected compared with the serosa (p < 0.01).

    Conclusions: Our animal model of low and high IAP by intraperitoneal CO2-insufflation worked well for studies of microcirculation, hemodynamics, and pulmonary function. During stepwise increases of pressure there were marked effects on global hemodynamics, respiratory function, and microcirculation. The results indicate that intestinal mucosal flow, especially small bowel mucosal flow, although reduced, seems better preserved in response to intra-abdominal hypertension caused by CO2-insufflation than other intra-abdominal microvascular beds.

  • 13.
    Orwelius, Lotti
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Nordlund, Anders
    Linköping University, Department of Medical and Health Sciences, Work and Rehabilitation. Linköping University, Faculty of Health Sciences.
    Edéll-Gustafsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Simonsson, Eva
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jonkoping, Sweden.
    Nordlund, Peter
    Department of Anaesthesia and Intensive Care, Ryhov Hospital, Jonkoping, Sweden.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Role of preexisting disease in patients' perceptions of health-related quality of life after intensive care.2005In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 33, no 7, p. 1557-1564Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To find out how patients perceive their health-related quality of life after they have been treated in an intensive care unit and whether preexisting disease influenced their perception.

    DESIGN:: Follow-up, quantitative, dual-site study.

    SETTING: Combined medical and surgical intensive care units of one university and one general hospital in Sweden.

    PATIENTS: Among the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the intensive care unit, and age >18 yrs). The effect of preexisting disease was assessed by use of a large reference group, a random sample (n = 10,000) of the main intake area of the hospitals.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: During 2000-2002, data were collected from the intensive care unit register and from a questionnaire mailed to the patients 6 months after their discharge from hospital. Subjects in the reference group were sent postal questionnaires during 1999. Of the patients in the intensive care unit group, 74% had preexisting diseases compared with 51% in the reference group. Six months after discharge, health-related quality of life was significantly lower among patients than in the reference group. When comparisons were restricted to the previously healthy people in both groups, the observed differences were about halved, and when we compared the patients in the intensive care unit who had preexisting diseases with subjects in the reference group who had similar diseases, we found little difference in perceived health-related quality of life. In some dimensions of health-related quality of life, we found no differences between patients in the intensive care unit and the subjects in the reference population.

    CONCLUSIONS: Preexisting diseases significantly affect the extent of the decline of health-related quality of life after critical care, and this effect may have been underestimated in the past. As most patients who are admitted to an intensive care unit have at least one preexisting disease, it is important to account for these effects when examining outcome.

  • 14.
    Wahlter, Sten
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Domino, K
    Robb, G
    Hlastala, M
    Positive end-expiratory pressure redistributes perfusion to dependent lung regions in supine but not in prone lambs.1999In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 27, p. 37-45Article in journal (Refereed)
  • 15.
    Wang, Jianpu
    et al.
    Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Oldner, A.
    Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Winskog, C.
    Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Edston, Erik
    Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Walther, Sten
    Östergötlands Läns Landsting, Center for Disaster Medicine and Traumatology, Centre for Teaching and Research in Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas2006In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, no 6, p. 1731-1737Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test the hypothesis that the endothelin system is involved in chlorine gas-induced lung injury.

    DESIGN: Experimental study.

    SETTING: Academic research laboratory.

    SUBJECTS: Twenty-four domestic juvenile pigs.

    INTERVENTIONS: Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million in air) for 20 mins and then randomly allocated to four groups (n = 6 in each group). The tezosentan pretreatment group received the dual endothelin receptor antagonist tezosentan 20 mins before and hyperoxic gas (Fio2 0.6) after chlorine gas exposure. The tezosentan postinjury treatment group received hyperoxic gas after chlorine gas exposure and tezosentan 60 mins later. Animals in the oxygen group received hyperoxic gas after chlorine gas exposure. Pigs in the fourth group (air) were ventilated with room air (Fio2 0.21) throughout the experiment.

    MEASUREMENTS AND MAIN RESULTS: Hemodynamics, gas exchange, lung mechanics, and plasma endothelin-1 were evaluated for 6 hrs. Chlorine gas exposure induced an increase in circulating endothelin-1 by 90% (p < .05). The acute chlorine gas-induced rise in pulmonary vascular resistance was partly blocked by tezosentan pretreatment (p < .001). Tezosentan postinjury treatment also decreased pulmonary vascular resistance to levels significantly lower than in the air and oxygen groups (p < .001). Recovery of peak airway pressure was better in the tezosentan-treated groups than in the air group. There were significant linear relationships between circulating endothelin-1 and pulmonary vascular resistance (r = .47, p < .001) and endothelin-1 and peak airway pressure (r = .41, p < .001). These relationships were modified by tezosentan.

    CONCLUSIONS: Tezosentan modified chlorine gas-induced pulmonary dysfunction, indicating that the endothelin system is involved in this mode of acute lung injury.

  • 16.
    Zdolsek, Hans Joachim
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Lisander, Björn
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Jones, Wayne A.
    National Laboratory of Forensic Chemistry, Linköping, Sweden.
    The effect of hypermetabolism induced by burn trauma on the ethanol-oxidizing capacity of the liver1999In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 27, no 12, p. 2622-2625Article in journal (Refereed)
    Abstract [en]

    Objective: To study the rate of elimination of ethanol after a major burn trauma.

    Design: Prospective, controlled study.

    Setting: National burns unit in a Swedish university hospital.

    Patients and Subjects: Eight consecutive patients suffering from 18%-72% total burned surface area and nine healthy male control subjects.

    Interventions: The patients received ethanol, 0.35-0.60 g/kg body weight intravenously, during 1 hr. This was repeated daily during the first week postburn. The control subjects received the same amount of ethanol once.

    Measurements and Main Results: Blood samples were drawn at 20- to 30-min intervals during 5 hrs after the start of the infusion. Serum ethanol was determined by headspace gas chromatography. The rate of elimination of ethanol was calculated from the concentration time profile. In the control subjects, the median elimination rate was 0.074 g/kg/hr (range, 0.059-0.083 g/kg/hr). In the patients, it was already 0.138 g/kg/hr (range, 0.111-0.201 g/kg/hr) on the first day; this increased even further over the following 6 days, reaching 0.183 g/kg/hr (range, 0.150-0.218 g/kg/hr) on the seventh day.

    Conclusions: Ethanol elimination is augmented postburn. A more effective reoxidation of reduced nicotinamide adenine dinucleotide seems the most likely explanation for the increased rate of ethanol elimination in these hypermetabolic trauma patients. This finding suggests that the oxidative capacity of the liver may be assessed by studying the rate of ethanol elimination in burn victims.

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