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  • 1. Antonsson, J B
    et al.
    Engström, L
    Rasmussen, I
    Wollert, S
    Haglund, U H
    Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.1995In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 23, no 11, p. 1872-81Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To establish the relationship between gut intramucosal pH and blood flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.

    DESIGN: Prospective, controlled study.

    SETTING: Experimental laboratory in a university teaching hospital.

    SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg.

    INTERVENTIONS: Animals were anesthetized, intubated, and mechanically ventilated. A flow probe was placed around the superior mesenteric artery for registration of blood flow. A tonometer was placed in the lumen of midileum for calculation of gut intramucosal pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric venous, and arterial blood. Five animals served as controls, ten animals had peritonitis induced by fecal instillation in the abdominal cavity, five were bled stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and five were bled rapidly and reinfused after 3 hrs.

    MEASUREMENTS AND MAIN RESULTS: Both peritonitis and hemorrhage caused decreases in gut blood flow and intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that of blood flow. In all experimental groups, oxygen delivery decreased over time; in both mild and severe peritonitis, this decrease was preceded by a decrease of intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66, but in intramucosal pH of < 7.12, a further decrease was accompanied only by minor changes in extraction ratio.

    CONCLUSIONS: Since a reduction in blood flow was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a decreasing intramucosal pH was associated with an increasing oxygen extraction ratio. In hemorrhage, this association had a sharp deflection point below which a further decrease in intramucosal pH occurred concomitantly with an unchanged gut oxygen extraction ratio. Increased extraction ratio was not sufficient, not even initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).

  • 2.
    Baker, Tim
    et al.
    Karolinska Univ Hosp, Dept Anaesthesia Intens Care & Surg Serv, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Div Anaesthesiol & Intens Care Med, Stockholm, Sweden.;Karolinska Inst, Dept Publ Hlth Sci, Global Hlth Hlth Syst & Policy, Stockholm, Sweden..
    Blixt, Jonas
    Karolinska Univ Hosp, Dept Anaesthesia Intens Care & Surg Serv, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Div Anaesthesiol & Intens Care Med, Stockholm, Sweden..
    Lugazia, Edwin
    Muhimbili Univ Hlth & Allied Sci, Dept Anaesthesia & Intens Care, Dar Es Salaam, Tanzania..
    Schell, Carl Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Sormland Cty Council, Nykoping Hosp, Dept Internal Med, Nykoping, Sweden..
    Mulungu, Moses
    Muhimbili Natl Hosp, Dept Anaesthesia & Intens Care, Dar Es Salaam, Tanzania..
    Milton, Anna
    Karolinska Univ Hosp, Dept Anaesthesia Intens Care & Surg Serv, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Div Anaesthesiol & Intens Care Med, Stockholm, Sweden..
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Eriksen, Jaran
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Lab Med, Div Clin Pharmacol, Stockholm, Sweden..
    Konrad, David
    Karolinska Univ Hosp, Dept Anaesthesia Intens Care & Surg Serv, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Div Anaesthesiol & Intens Care Med, Stockholm, Sweden..
    Single Deranged Physiologic Parameters Are Associated With Mortality in a Low-Income Country2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. 2171-2179Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. Design: Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. Setting: ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. Patients: All adults admitted to the ICU in a 15-month period. Measurements and Main Results: Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty-four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95-11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53-3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23-5.14]). Conclusion: Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed danger signs. Danger signs may be suitable for the basis of routines to identify and treat critically ill patients.

  • 3.
    Bassford, Christopher R.
    et al.
    Warwick Medical School, University of Warwick, Coventry, United Kingdom; University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
    Krucien, Nicolas
    Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
    Ryan, Mandy
    Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
    Griffiths, Frances E.
    Warwick Medical School, University of Warwick, Coventry, United Kingdom.
    Svantesson, Mia
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Center.
    Fritz, Zoe
    Warwick Medical School, University of Warwick, Coventry, United Kingdom; The Healthcare Improvement Studies (THIS) Institute, Cambridge University, Cambridge, United Kingdom.
    Perkins, Gavin D.
    Warwick Medical School, University of Warwick, Coventry, United Kingdom; University Hospitals Birmingham NHS Foundation Trust, Heartlands Hospital, Birmingham, United Kingdom.
    Quinton, Sarah
    University Hospitals Birmingham NHS Foundation Trust, Heartlands Hospital, Birmingham, United Kingdom.
    Slowther, Anne-Marie
    Warwick Medical School, University of Warwick, Coventry, United Kingdom.
    U.K. Intensivists' Preferences for Patient Admission to ICU: Evidence From a Choice Experiment2019In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 11, p. 1522-1530Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Deciding whether to admit a patient to the ICU requires considering several clinical and nonclinical factors. Studies have investigated factors associated with the decision but have not explored the relative importance of different factors, nor the interaction between factors on decision-making. We examined how ICU consultants prioritize specific factors when deciding whether to admit a patient to ICU.

    DESIGN: Informed by a literature review and data from observation and interviews with ICU clinicians, we designed a choice experiment. Senior intensive care doctors (consultants) were presented with pairs of patient profiles and asked to prioritize one of the patients in each task for admission to ICU. A multinomial logit and a latent class logit model was used for the data analyses.

    SETTING: Online survey across U.K. intensive care.

    SUBJECTS: Intensive care consultants working in NHS hospitals.

    MEASUREMENTS AND MAIN RESULTS: Of the factors investigated, patient's age had the largest impact at admission followed by the views of their family, and severity of their main comorbidity. Physiologic measures indicating severity of illness had less impact than the gestalt assessment by the ICU registrar. We identified four distinct decision-making patterns, defined by the relative importance given to different factors.

    CONCLUSIONS: ICU consultants vary in the importance they give to different factors in deciding who to prioritize for ICU admission. Transparency regarding which factors have been considered in the decision-making process could reduce variability and potential inequity for patients.

  • 4. 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)
  • 5.
    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)
  • 6.
    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.

  • 7.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L. V.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lucchetta, Luca
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Amato, Marcelo B. P.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed)
    Abstract [en]

    Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

  • 8.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Costa, Eduardo L V
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury2014In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, p. e279-e287Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: A university animal research laboratory.

    SUBJECTS: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

    INTERVENTIONS: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: [F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

    CONCLUSIONS: The present findings suggest that normally and poorly aerated regions-corresponding to intermediate gravitational zones-are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

  • 9.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Senturk, Mert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Open Lung in Lateral Decubitus With Differential Selective Positive End-Expiratory Pressure in an Experimental Model of Early Acute Respiratory Distress Syndrome2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. e404-e411Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: After lung recruitment, lateral decubitus and differential lung ventilation may enable the titration and application of optimum-selective positive end-expiratory pressure values for the dependent and nondependent lungs. We aimed at compare the effects of optimum-selective positive end-expiratory pressure with optimum global positive end-expiratory pressure on regional collapse and aeration distribution in an experimental model of acute respiratory distress syndrome.

    DESIGN: Prospective laboratory investigation.

    SETTING: University animal research laboratory.

    SUBJECTS: Seven piglets.

    INTERVENTIONS: A one-hit injury acute respiratory distress syndrome model was established by repeated lung lavages. After replacing the tracheal tube by a double-lumen one, we initiated lateral decubitus and differential ventilation. After maximum-recruitment maneuver, decremental positive end-expiratory pressure titration was performed. The positive end-expiratory pressure corresponding to maximum dynamic compliance was defined globally (optimum global positive end-expiratory pressure) and for each individual lung (optimum-selective positive end-expiratory pressure). After new maximum-recruitment maneuver, two steps were performed in randomized order (15 min each): ventilation applying the optimum global positive end-expiratory pressure and the optimum-selective positive end-expiratory pressure. CT scans were acquired at end expiration and end inspiration.

    MEASUREMENTS AND MAIN RESULTS: Aeration homogeneity was evaluated as a nondependent/dependent ratio (percent of total gas content in upper lung/percent of total gas content in lower lung) and tidal recruitment as the difference in the percent mass of nonaerated tissue between expiration and inspiration. At the end of the 15-minute optimum-selective positive end-expiratory pressure, compared with the optimum global positive end-expiratory pressure, resulted in 1) decrease in the percent mass of collapse in the lower lung at expiratory CT (19% ± 15% vs 4% ± 5%; p = 0.03); 2) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-expiratory-CT and optimum-selective positive end-expiratory pressure-expiratory-CT (3.7 ± 1.2 vs 0.8 ± 0.5; p = 0.01); 3) decrease in the nondependent/dependent ratio between the optimum global positive end-expiratory pressure-inspiratory-CT and optimum-selective positive end-expiratory pressure-inspiratory-CT (2.8 ± 1.1 vs 0.6 ± 0.3; p = 0.01); and 4) less tidal recruitment (p = 0.049).

    CONCLUSIONS: After maximum lung recruitment, lateral decubitus and differential lung ventilation enabled the titration of optimum-selective positive end-expiratory pressure values for the dependent and the nondependent lungs, made possible the application of an optimized regional open lung approach, promoted better aeration distribution, and minimized lung tissue inhomogeneities.

  • 10.
    Broche, Ludovic
    et al.
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.;Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Tannoia, Angela
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Derosa, Savino
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Sindaco, Alessandra
    Univ Bari, Dept Emergency & Organ Transplant, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Degrugilliers, Loic
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Wexler, Anthony S.
    Univ Calif Davis, Dept Mech Engn, Davis, CA 95616 USA.;Univ Calif Davis, Environm Qual Lab, Davis, CA 95616 USA..
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France..
    Verbanck, Sylvia
    Univ Hosp UZ Brussel, Div Resp, Brussels, Belgium..
    Smith, Bradford J.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bates, Jason H. T.
    Univ Vermont, Dept Med, Burlington, VT USA. European Synchrotron Radiat Facil, Grenoble, France..
    Bayat, Sam
    Univ Picardie Jules Verne, INSERM, Dept Pediat Pulmonol, U1105, Amiens, France.;Amiens Univ Hosp, Amiens, France..
    Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 4, p. 687-694Article in journal (Refereed)
    Abstract [en]

    Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

  • 11.
    Broche, Ludovic
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pisa, Pauline
    Univ Picardie Jules Verne, Fac Med, Amiens, France.
    Porra, Liisa
    Univ Helsinki, Dept Phys, Helsinki, Finland;Univ Helsinki, Cent Hosp, Med Imaging Ctr, Helsinki, Finland.
    Degrugilliers, Loic
    Amiens Univ Hosp, Dept Pediat Intens Care, Amiens, France.
    Bravin, Alberto
    European Synchrotron Radiat Facil, Biomed Beamline ID17, Grenoble, France.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Batista Borges, João
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Bayat, Sam
    Univ Grenoble Alpes, Grenoble, France;INSERM, UA7, STROBE Lab, Grenoble, France;Grenoble Univ Hosp, Dept Pulmonol & Physiol, Grenoble, France.
    Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung2019In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 9, p. E774-E781Article in journal (Refereed)
    Abstract [en]

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

    Design: Laboratory animal investigation.

    Setting: European synchrotron radiation facility.

    Subjects: Six New-Zealand White rabbits.

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

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

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

  • 12.
    Brynildsen, Jon
    et al.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway.
    Petaja, Liisa
    Univ Helsinki, Div Anaesthesiol Intens Care & Pain Med, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Myhre, Peder L.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway.
    Lyngbakken, Magnus N.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway.
    Nygard, Stale
    Oslo Univ Hosp, Bioinformat Core Facil, Inst Med Informat, Oslo, Norway;Univ Oslo, Oslo, Norway.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Christensen, Geir
    Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway;Oslo Univ Hosp, Expt Med Res Inst, Oslo, Norway.
    Ottesen, Anett H.
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway;Oslo Univ Hosp, Expt Med Res Inst, Oslo, Norway.
    Pettila, Ville
    Univ Helsinki, Div Anaesthesiol Intens Care & Pain Med, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Omland, Torbjorn
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway.
    Rosjo, Helge
    Akershus Univ Hosp, Div Med, Sykehusveien 25, N-1478 Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway.
    Circulating Secretoneurin Concentrations After Cardiac Surgery: Data From the FINNish Acute Kidney Injury Heart Study2019In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 47, no 5, p. E412-E419Article in journal (Refereed)
    Abstract [en]

    Objectives:

    Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known.

    Design:

    Prospective, observational, single-center sub-study of a multicenter study.

    Setting:

    Prospective observational study of survival in patients undergoing cardiac surgery.

    Patients:

    A total of 619 patients undergoing cardiac surgery.

    Interventions:

    Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery.

    Measurements and Main Results:

    We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow- up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1-3, 147-206 pmol/L] vs 160 pmol/L [131-193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129-217 pmol/L] vs 143 pmol/L [111-173 pmol/L]; p < 0.001). Secretoneurin concentrations decreased from preoperative to postoperative measurements in survivors, whereas we observed no significant decrease in secretoneurin concentrations among nonsurvivors. Secretoneurin concentrations were weakly correlated with established risk indices. Patients with the highest postoperative secretoneurin concentrations had worse outcome compared with patients with lower secretoneurin concentrations (p < 0.001 by the log-rank test) and postoperative secretoneurin concentrations were associated with time to death in multivariate Cox regression analysis: hazard ratio ln secretoneurin 2.96 (95% CI, 1.46-5.99; p = 0.003). Adding postoperative secretoneurin concentrations to European System for Cardiac Operative Risk Evaluation II improved patient risk stratification, as assessed by the integrated discrimination index: 0.023 (95% CI, 0.0043-0.041; p = 0.016).

    Conclusions:

    Circulating postoperative secretoneurin concentrations provide incremental prognostic information to established risk indices in patients undergoing cardiac surgery.

  • 13.
    Carlsson, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock: a model of endotoxin elimination2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 3, p. 1031-e4Article in journal (Refereed)
    Abstract [en]

    Objective:

    To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.

    Design:

    Prospective parallel-grouped placebo-controlled randomized interventional experimental study.

    Setting:

    University research unit.

    Subjects:

    Healthy pigs.

    Interventions:

    The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.

    Measurements and Main Results:

    During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.

    Conclusions:

    Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.

  • 14.
    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.

  • 15. Chew, M S
    et al.
    Brandberg, J
    Bjarum, S
    Baek-Jensen, K
    Sloth, E
    Ask, P
    Hasenkam, J M
    Janerot-Sjöberg, B
    Hälsouniversitetet, Linköping University.
    Pediatric cardiac output measurement using surface integration of velocity vectors: an in vivo validation study.2000In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, no 11, p. 3664-71Article 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.

  • 16.
    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.

  • 17.
    Claesson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Lehtipalo, Stefan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Bergstrand, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Anestesiologi och intensivvård.
    Negative mesenteric effects of lung recruitment maneuvers in oleic acid lung injury are transient and short lasting.2007In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 1, p. 230-238Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test the hypothesis that repeated recruitment maneuvers (RMs) have sustained negative effects on mesenteric circulation, metabolism, and oxygenation 60 mins after RMs in pigs with oleic acid lung injury. Further, we aimed to test the hypothesis that an infusion of prostacyclin (PC) at 33 ng.kg.min would attenuate such possible negative mesenteric effects. DESIGN: Randomized, experimental, controlled study. SETTING: University hospital animal laboratory. SUBJECTS: A total of 31 anesthetized, fluid-resuscitated pigs with oleic acid lung injury. INTERVENTIONS: Animals were randomized to one of the following four groups: a control group (n = 7) that received no intervention, recruitment group (n = 8) that underwent the RM sequence, a prostacyclin group (n = 8) that received an infusion of PC, and a recruitment-prostacyclin group (n = 8) that received an infusion of PC and concomitant RM sequence. MEASUREMENTS AND MAIN RESULTS: We measured systemic and mesenteric hemodynamic variables, jejunal mucosal perfusion, mesenteric lactate flux, jejunal tissue oxygen tension, and mesenteric oxygen delivery, uptake, and extraction ratio. Five minutes after RMs, mesenteric oxygen extraction ratio and mesenteric lactate flux were more prominently increased in the recruitment group, giving evidence of worsened mesenteric conditions after RMs. These signs of worsened conditions were further supported by more decreased jejunal tissue oxygen tension and portal vein oxygen saturation in the recruitment group. PC preserved mesenteric oxygenation, as indicated by less of a decrease in portal vein oxygen saturation at the time corresponding to 5 mins after RM and less of a decrease in mesenteric oxygen delivery at the time corresponding to 15 mins after RM. PC preserved mesenteric oxygenation as indicated by less of a decrease in portal vein oxygen saturation at 5 mins after RM and an attenuated increase in mesenteric oxygen extraction ratio at 5 mins after RM. There was a trend toward worsened jejunal mucosal perfusion, although not significant. CONCLUSIONS: In an oleic acid lung injury model, three repeated RMs did not improve systemic oxygenation or lung mechanics. Negative effects on mesenteric oxygenation and metabolism were transient and short lasting. The intestinal effects of PC during RMs were minor and opposing, showing preserved oxygenation but a trend toward worsened mucosal perfusion.

  • 18.
    Claesson Lingehall, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Smulter, Nina
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Cardiothoracic Surgery Division, Heart Center.
    Lindahl, Elisabeth
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Gustavsson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Olofsson, Birgitta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Preoperative Cognitive Performance and Postoperative Delirium Are independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery: A Longitudinal Cohort Study2017In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 8, p. 1295-1303Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery.

    Design: Longitudinal cohort study.

    Setting: Cardiothoracic Division, Umeå University Hospital, Sweden.

    Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009.

    Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively.

    Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p < 0.001; odds ratio, 0.68; 95% CI, 0.54–0.84) and the occurrence of postoperative delirium (p = 0.002; odds ratio, 7.57; 95% CI, 2.15–26.65) were associated with dementia occurrence.

    Conclusions: Our findings suggest that older patients with reduced preoperative cognitive functions or who develop postoperative delirium are at risk of developing dementia within 5 years after cardiac surgery. Cognitive functions should be screened for preoperatively, those who develop postoperative delirium should be followed up to enable early detection of dementia symptoms, and management should be implemented.

  • 19. 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.

  • 20.
    Da, Jiping
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Chen, Luni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nitric oxied up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis2007In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 1, p. 26-32Article in journal (Refereed)
    Abstract [en]

    Objectives: Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: A total of 45 anesthetized and mechanically ventilated pigs. Interventions: Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Measurements and Main Results: Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-κB and tumor necrosis factor-a. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. Conclusion: We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

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

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

  • 22. Derde, Sarah
    et al.
    Hermans, Greet
    Derese, Inge
    Güiza, Fabian
    Hedström, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Wouters, Pieter J
    Bruyninckx, Frans
    Dʼhoore, André
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Van den Berghe, Greet
    Vanhorebeek, Ilse
    Muscle atrophy and preferential loss of myosin in prolonged critically ill patients2012In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 40, no 1, p. 79-89Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and denervation, and the myosin/actin ratio in limb and abdominal wall skeletal muscle, of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness.

    DESIGN:

    Secondary analysis of two large, prospective, single-center randomized clinical studies.

    SETTING:

    University hospital surgical and medical intensive care unit.

    PATIENTS:

    Critically ill patients and matched controls.

    INTERVENTIONS:

    Intensive care unit patients had been randomized to blood glucose control to 80-110 mg/dL with insulin infusion or conventional glucose management, where insulin was only administered when glucose levels rose above 215 mg/dL.

    MEASUREMENTS AND MAIN RESULTS:

    As compared with controls, rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size, decreased mRNA levels for myofibrillar proteins, increased proteolytic enzyme activities, and a lower myosin/actin ratio, virtually irrespective of insulin therapy. Increased forkhead box protein O1 action may have played a role. Most alterations were more severe in patients treated with corticosteroids. Duration of corticosteroid treatment, independent of duration of intensive care unit stay or other risk factors, was a dominant risk factor for a low myosin/actin ratio. The immature acetylcholine receptor subunit γ mRNA expression was elevated in vastus lateralis, independent of the myosin/actin ratio.

    CONCLUSIONS:

    Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis. This affected myosin to a greater extent than actin, resulting in a decreased myosin/actin ratio. Muscle atrophy was not ameliorated by intensive insulin therapy, but possibly aggravated by corticosteroids.

  • 23. Derde, Sarah
    et al.
    Vanhorebeek, Ilse
    Ververs, Eric-Jan
    Vanhees, Ine
    Darras, Veerle M
    Van Herck, Erik
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Van den Berghe, Greet
    Increasing intravenous glucose load in the presence of normoglycemia: Effect on outcome and metabolism in critically ill rabbits2010In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 2, p. 602-611Article in journal (Refereed)
    Abstract [en]

    Objectives: Endocrine disturbances and a feeding-resistant wasting syndrome, characterized by a negative protein balance, promote delayed recovery and poor outcome of critical illness. Parenteral nutrition alone cannot counteract the hypercatabolic state, possibly in part as a result of aggravation of the hyperglycemic response to illness. In critically ill rabbits, we investigated the impact of varying amounts of intravenous glucose while maintaining normoglycemia on mortality, organ damage, and markers of catabolism/anabolism. Design: Prospective, randomized laboratory investigation. Setting: University animal and molecular laboratory. Subjects: Three-month-old male rabbits. Interventions: Critically ill rabbits were randomized into a fasting group, a standard parenteral nutrition group, and two groups receiving either intermediate or high additional physiological amounts of intravenous glucose while maintained normoglycemic with insulin. These groups were compared with a hyperglycemic group and healthy rabbits. Protein and lipid load was equal for all fed groups. Measurements and Main Results: Varying intravenous glucose load did not affect mortality or organ damage provided hyperglycemia was prevented. Fasted critically ill rabbits lost weight, which was attenuated by increasing intravenous glucose load. As compared with healthy rabbits, mRNA expression and/or activity of several ubiquitin-proteasome pathway components, cathepsin-L and calpain-1, was elevated in skeletal muscle of fasted critically ill rabbits. Intravenous feeding was able to counteract this response. Excessive glucose load and/or hyperglycemia, however, reduced the protective effect of feeding. Genes investigated in the diaphragm and myocardium revealed roughly a similar response. Except in the normoglycemic group with intermediate glucose load, circulating thyroid hormone and insulin-like growth factor-1 levels decreased, most pronounced in hyperglycemic rabbits. Conclusions: Increasing intravenous glucose infusion within the physiological range, while maintaining normoglycemia, was safe for organ function and survival of critically ill rabbits. Concomitantly, it reduced the catabolic responses as compared with fasting. Whether this has a beneficial effect on muscle function and mass remains to be investigated.

  • 24.
    Elf, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care2002In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 30, no 9, p. 2129-2134Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate today's refined neurosurgical intensive care of patients with traumatic brain injury after implementation of an organized secondary insult program focused on the importance of avoiding secondary brain damage together with a standardized treatment protocol system.

    DESIGN: Clinical observational patient study.

    PATIENTS: A total of 154 patients 16-79 yrs of age with acute head trauma and pathologic computed tomographic findings treated between 1996 and 1997.

    SETTING: Neurointensive care unit.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Good recovery was obtained in 44% of the patients, moderate disability in 35%, severe disability in 16%, and no patient remained in a vegetative state. Six percent of the patients died, but only two of these patients (1.3%) died as direct result of their head injury. When the results for patients with Glasgow Coma Scale motor scores of >or=4 were compared with the periods 1980-1981 (preneurosurgical intensive care) and 1987-1988 (basic neurosurgical intensive care), mortality had decreased from 40% in the first period to 27% in the second period and to 2.8% in the present series. Favorable outcome in the same group of patients had increased steadily from 40% in the first period, to 68% in the second period, and finally, to 84% in the present series.

    CONCLUSIONS: The main observation in this hospital series of traumatic brain injury patients was a low rate of death directly caused by head injury and a high rate of favorable outcome. The comparison of patients with Glasgow Coma Scale motor scores of >or=4 with the previously reported results from the same unit indicate that substantial improvement in outcome has been achieved.

  • 25.
    Enblad, Per
    et al.
    Uppsala universitet, Neurokirurgi.
    Skoglund, Karin
    Mälardalen University, School of Health, Care and Social Welfare. Uppsala universitet, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Neurokirurgi.
    Wake-up test and stress hormone levels in patients with brain injury: A focus on mechanisms involved: Reply2012In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 40, no 6, p. 2002-2003Article in journal (Refereed)
  • 26.
    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.

  • 27.
    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.

  • 28.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Silander, H C
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation2000In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, no 5, p. 1423-1430Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.

    DESIGN:

    Randomized controlled study.

    SETTING:

    University hospital research laboratory.

    SUBJECTS:

    A total of 20 male anesthetized piglets.

    INTERVENTIONS:

    Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.

    MEASUREMENTS AND MAIN RESULTS:

    Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.

    CONCLUSIONS:

    Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.

  • 29.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    The impact of clinically undiagnosed injuries on survival estimates2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 2, p. 449-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:: Missed injury diagnoses may cause potentially preventable deaths. To estimate the effect of clinically undiagnosed injuries on injury-specific survival estimates and the accuracy of an injury severity score. To also estimate the potentially preventable mortality attributable to these injuries. DESIGN, SETTING, AND PATIENTS:: In a nation-wide, population-based study, data were collected from all hospital admissions for injuries in Sweden between 1998 and 2004. We studied 8627 deaths in hospital among 598,137 incident hospital admissions. MEASUREMENTS AND MAIN RESULTS:: New specific-injury categories were added in 7.4% (95% confidence interval [CI] 6.8-8.0) of all deaths with an autopsy rate of 24.2%. It was estimated that this proportion would have increased to 25.1% (95% CI 23.0-27.2), if all deaths had been autopsied. The most pronounced effect of clinically undiagnosed injuries was found for internal organ injury in the abdomen or pelvis, where they reduced the estimated survival from 0.83 to 0.69 (95% CI for the difference: 0.09-0.20). Autopsy diagnoses also revealed substantial bias of survival estimates for vascular injuries in the thorax and crush injuries to the head. The performance of the International Classification of Diseases Injury Severity Score improved when autopsy diagnoses were added to hospital discharge diagnoses. The maximum proportion of injury deaths attributable to missed injuries was estimated to be 6.5%. CONCLUSIONS:: Maintaining a high autopsy rate and merging accurate hospital discharge data and autopsy data are effective ways to improve the accuracy of survival estimates and mortality prediction models, and to estimate mortality attributable to diagnostic failures.

  • 30.
    Halmin, Marit
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Chiesa, Flaminia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Vasan, Senthil K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Wikman, Agneta
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Norda, Rut
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Rostgaard, Klaus
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Pedersen, Ole Birger Vesterager
    Naestved Hosp, Dept Clin Immunol, Naestved, Denmark..
    Erikstrup, Christian
    Aarhus Univ Hosp, Dept Clin Immunol, DK-8000 Aarhus, Denmark..
    Nielsen, Kaspar Rene
    Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark..
    Titlestad, Kjell
    Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense, Denmark..
    Ullum, Henrik
    Copenhagen Univ Hosp, Dept Clin Immunol, Copenhagen, Denmark..
    Hjalgrim, Henrik
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Edgren, Gustaf
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden..
    Epidemiology of Massive Transfusion: A Binational Study From Sweden and Denmark2016In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 44, no 3, p. 468-477Article in journal (Refereed)
    Abstract [en]

    Objective: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. Design: Descriptive cohort study. Setting: Nationwide study with data from Sweden and Denmark. Patients: The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. Measurements and Main Results: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. Conclusions: This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.

  • 31.
    Hillered, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Nonischemic energy metabolic crisis in acute brain injury2008In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 36, no 10, p. 2952-2953Article in journal (Refereed)
  • 32. Hostman, Staffan
    et al.
    Borges, Joao
    Engstrom, Joakim
    Suarez-Sipmann, Fernando
    Hedenstierna, Goran
    Larsson, Anders
    Is tham a useful adjunct to normalize ph during lung protective ventilation with permissive hypercapnia?2012In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 40, no 12, p. U63-U63Article in journal (Other academic)
  • 33.
    Howells, Tim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Smielewski, Peter
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Donnelly, Joseph
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Czosnyka, Marek
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England.;Warsaw Univ Technol, Inst Elect Syst, Warsaw, Poland..
    Hutchinson, Peter J. A.
    Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Neurosurg Unit,Div Anaesthesia, Cambridge, England..
    Menon, David K.
    Univ Cambridge, Addenbrookes Hosp, Div Anaesthesia, Cambridge, England..
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Aries, Marcel J. H.
    Maastricht Univ, Med Ctr, Dept Crit Care, Maastricht, Netherlands..
    Optimal Cerebral Perfusion Pressure in Centers With Different Treatment Protocols2018In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, no 3, p. e235-e241Article in journal (Refereed)
    Abstract [en]

    Objectives: The three centers in this study have different policies regarding cerebral perfusion pressure targets and use of vasopressors in traumatic brain injury patients. The aim was to determine if the different policies affected the estimation of cerebral perfusion pressure which optimizes the strength of cerebral autoregulation, termed "optimal cerebral perfusion pressure." Design: Retrospective analysis of prospectively collected data. Setting: Three neurocritical care units at university hospitals in Cambridge, United Kingdom, Groningen, the Netherlands, and Uppsala, Sweden. Patients: A total of 104 traumatic brain injury patients were included: 35 each from Cambridge and Groningen, and 34 from Uppsala. Interventions: None. Measurements and Main Results: In Groningen, the cerebral perfusion pressure target was greater than or equal to 50 and less than 70mm Hg, in Uppsala greater than or equal to 60, and in Cambridge greater than or equal to 60 or preferably greater than or equal to 70. Despite protocol differences, median cerebral perfusion pressure for each center was above 70mm Hg. Optimal cerebral perfusion pressure was calculated as previously published and implemented in the Intensive Care Monitoring+ software by the Cambridge group, now replicated in the Odin software in Uppsala. Periods with cerebral perfusion pressure above and below optimal cerebral perfusion pressure were analyzed, as were absolute difference between cerebral perfusion pressure and optimal cerebral perfusion pressure and percentage of monitoring time with a valid optimal cerebral perfusion pressure. Uppsala had the highest cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Uppsala patients were older than the other centers, and age is positively correlated with cerebral perfusion pressure/optimal cerebral perfusion pressure difference. Optimal cerebral perfusion pressure was significantly lower in Groningen than in Cambridge. There were no significant differences in percentage of monitoring time with valid optimal cerebral perfusion pressure. Summary optimal cerebral perfusion pressure curves were generated for the combined patient data for each center. These summary curves could be generated for Groningen and Cambridge, but not Uppsala. The older age of the Uppsala patient cohort may explain the absence of a summary curve. Conclusions: Differences in optimal cerebral perfusion pressure calculation were found between centers due to demographics (age) and treatment (cerebral perfusion pressure targets). These factors should be considered in the design of trials to determine the efficacy of autoregulation-guided treatment.

  • 34.
    Iyer, Kartik K.
    et al.
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia.;Univ Queensland, Fac Med & Biomed Sci, Sch Med, Brisbane, Qld 4072, Australia..
    Roberts, James A.
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia..
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wikstrom, Sverre
    Karlstad Cent Hosp, Dept Pediat, Karlstad, Sweden..
    Pupp, Ingrid Hansen
    Lund Univ, Inst Clin Sci, Dept Pediat, Lund, Sweden..
    Ley, David
    Lund Univ, Inst Clin Sci, Dept Pediat, Lund, Sweden..
    Breakspear, Michael
    QIMR Berghofer Med Res Inst, Syst Neurosci Grp, Brisbane, Qld, Australia.;Metro North Mental Hlth Serv, Brisbane, Qld, Australia..
    Vanhatalo, Sampsa
    Univ Helsinki, Cent Hosp, HUS Med Imaging Ctr, Dept Childrens Clin Neurophysiol, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Univ Cent Hosp, Childrens Hosp, Dept Pediat, Helsinki, Finland..
    Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography2015In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 10, p. 2219-2227Article in journal (Refereed)
    Abstract [en]

    Objectives: Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. Design: Cross-sectional study. Setting: Level III neonatal ICU. Patients: Twenty-five extremely preterm infants (22-28 wk gestational age). Measurements and Main Results: We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0-24 hr) and day 3 (48-72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1-2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3-4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. Conclusions: Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates.

  • 35.
    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.

  • 36.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Experimental animal models of muscle wasting in intensive care unit patients2007In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 35, no 9, p. S484-S487Article in journal (Refereed)
    Abstract [en]

    The muscle wasting and loss of muscle function associated with critical illness and intensive care have significant negative consequences for weaning from the respirator, duration of hospital stay, and quality of life for long periods after hospital discharge. There is, accordingly, a significant demand for focused research aiming at improving our understanding of the mechanisms underlying the impaired neuromuscular function in intensive care unit (ICU) patients. However, the study of generalized muscle weakness in critically ill ICU patients is further complicated by the coexistence of multiple independent factors, such as different primary diseases, large variability in pharmacologic treatment, collection of muscle samples several weeks after admission to the ICU, and exposure to causative agents. This has led to the design of specific animal models mimicking ICU conditions. These models have often been used to study the mechanisms underlying the paralysis and muscle wasting associated with acute quadriplegic myopathy in ICU patients. This short review aims at presenting existing and recently introduced experimental animal models mimicking the conditions in the ICU (i.e., models designed to determine the mechanisms underlying the muscle wasting associated with ICU treatment).

  • 37.
    Lattuada, Marco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Abdominal lymph flow in an endotoxin sepsis model: Influence of spontaneous breathing and mechanical ventilation2006In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, no 11, p. 2792-2798Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Lymph flow from the abdomen was investigated in a sepsis model. We also compared the effect on thoracic duct lymph flow of mechanical ventilation with different levels of positive end-expiratory pressure (PEEP) and spontaneous breathing with continuous positive airway pressure (CPAP). DESIGN: Experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Thirty-two pigs. INTERVENTIONS: Animals were anesthetized. In study 1 (n = 18), an ultrasonic flow probe was put around the intact thoracic duct just caudal to the diaphragm, and animals were randomized to receive mechanical ventilation with a PEEP of 5 cm H2O or 15 cm H2O or breathed spontaneously in CPAP with a PEEP of 5 cm H2O. In study 2 (n = 6), the thoracic duct was cannulated and the cannula externalized through the abdominal wall for lymph collection; animals were then ventilated as in study 1. In all animals, endotoxin was infused at 15 μg/kg/hr for 2.5 hrs and then continued at 5 μg/kg/hr. In study 3, healthy (n = 4) and endotoxin-exposed (n = 4) pigs had intra-abdominal pressure increased to 27 cm H2O for 2 hrs by pneumoperitoneum. Lymph flow was measured as in study 1. MEASUREMENTS AND MAIN RESULTS: Lymph flow (mean ± se) was 2.5 ± 0.4 mL/min at baseline and increased to 3.9 ± 0.8 mL/min after 90 mins and 6.3 ± 1.6 mL/min after 150 mins (p < .005) of endotoxin exposure. PEEP 15 cm H2O decreased lymph flow in pigs with intact thoracic duct (flow probe recording) and in pigs with cannulated lymph duct when drained against the central venous pressure. However, when drained against atmospheric pressure, PEEP increased flow. Spontaneous breathing increased flow both in intact and in cannulated animals. CONCLUSIONS: Endotoxin increases lymph flow from the abdomen. Mechanical ventilation with high PEEP impedes lymph drainage and could increase lymph production. Spontaneous breathing increases flow and improves drainage of abdominal edema.

  • 38.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Molnar, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cerebral effects of hyperglycemia in experimental cardiac arrest2010In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 8, p. 1726-1732Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effects of cardiac arrest on cerebral perfusion and oxidative stress during hyperglycemia and normoglycemia. Design: Experimental animal model. Setting: University laboratory. Subjects: Triple-breed pigs (weight, 22-27 kg). Interventions: Thirty-three pigs were randomized and clamped at blood glucose levels of 8.5-10 mM (high) or 4-5.5 mM (normal) and thereafter subjected to alternating current-induced 12-min cardiac arrest followed by 8 mins of cardiopulmonary resuscitation and direct-current shock to restore spontaneous circulation. Measurements and Main Results: Hemodynamics, regional near-infrared light spectroscopy, regional venous HbO(2), and biochemical markers (Protein S100 beta, troponin I, F-2-isoprostanes reflecting oxidative stress and inflammation) were monitored and/or sampled throughout an observation period of 4 hrs. No significant differences were seen in hemodynamics or biochemical profile. The cerebral oxygenation by means of regional near-infrared light spectroscopy was higher in the hyperglycemic (H) than in the normal (N) group after restoration of spontaneous circulation (p < .05). However, tendencies toward increased protein S100 beta and 15-keto-dihydro-prostaglandin F-2 alpha were observed in the H group but were not statistically significant. Conclusions: The responses to 12-min cardiac arrest and cardiopulmonary resuscitation share large similarities during hyperglycemia and normoglycemia. The higher cerebral tissue oxygenation observed in the hyperglycemia needs to be confirmed and the phenomenon needs to be addressed in future studies.

  • 39.
    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.

  • 40.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Carlsson, Markus
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Algotsson, Lars
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 10, p. 2782-2790Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.

    DESIGN:

    Prospective, randomized, placebo-controlled experimental study.

    SETTING:

    University research unit.

    SUBJECTS:

    Twenty-four healthy pigs.

    INTERVENTIONS:

    The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.

    MEASUREMENTS AND MAIN RESULTS:

    The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.

    CONCLUSIONS:

    The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.

  • 41.
    Miclescu, Adriana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest2006In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, no 11, p. 2806-2813Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the production and actions of nitric oxide, may counteract excessive vasodilatation induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest and cardiopulmonary resuscitation were investigated. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University animal research laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins of cardiopulmonary resuscitation) was employed to assess the addition or no addition of MB to a hypertonic saline-dextran solution. These two groups (MB and hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only group) of 21 animals were each compared with a group receiving isotonic saline (n = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in baseline values, 4-hr survival in the MB group was increased (p = .02) in comparison with the isotonic saline group. Hemodynamic variables were somewhat improved at 15 mins after restoration of spontaneous circulation in the MB group compared with the other two groups. The jugular bulb levels of 8-isoprostane-prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of peroxidation and inflammation) were significantly decreased in the MB group compared with the isotonic saline group. Significant differences were recorded between the three groups in levels of protein S-100beta (indicator of neurologic injury), with lower levels in the MB group compared with the isotonic saline and hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine kinase isoenzyme arterial concentrations (indicators of myocardial damage) were also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an experimental porcine model of cardiac arrest and reduced oxidative, inflammatory, myocardial, and neurologic injury.

  • 42.
    Miclescu, Adriana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Martijn, Cécile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions2010In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 11, p. 2199-2206Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the effects of cardiac arrest and the reperfusion syndrome on blood-brain barrier permeability and evaluate whether methylene blue counteracts blood-brain barrier disruption in a pig model of controlled cardiopulmonary resuscitation. Design: Randomized, prospective, laboratory animal study. Setting: University-affiliated research laboratory. Subjects: Forty-five piglets. Interventions: Forty-five anesthetized piglets were subjected to cardiac arrest alone or 12-min cardiac arrest followed by 8 mins cardiopulmonary resuscitation. The first group (n = 16) was used to evaluate blood-brain barrier disruptions after untreated cerebral ischemia after 0, 15, or 30 mins after untreated cardiac arrest. The other two groups received either an infusion of saline (n = 10) or infusion of saline with methylene blue (n = 12) 1 min after the start of cardiopulmonary resuscitation and continued 50 mins after return of spontaneous circulation. In these groups, brains were removed for immunohistological analyses at 30, 60, and 180 mins after return of spontaneous circulation. Measurements and Main Results: An increase of injured neurons and albumin immunoreactivity was demonstrated with in-creasing duration of ischemia/reperfusion. Less blood-brain barrier disruption was observed in subjects receiving methylene blue as demonstrated by decreased albumin leakage (p<.01), water content (p<.05), and neuronal injury (p<.01). Methylene blue treatment reduced cerebral tissue nitrite/nitrate content (p<.05) and the number of inducible and neuronal nitric oxide synthase-activated cortical cells during administration (p<.01). Meanwhile, the number of cortical endothelial nitric oxide synthase-activated cells increased over time (p<.001). Conclusion: Cerebral tissue water content, blood-brain barrier permeability and neurologic injury were increased early in reperfusion after cardiac arrest. Methylene blue exerted neuroprotective effects against the brain damage associated with the ischemia/reperfusion injury and ameliorated the blood-brain barrier disruption by decreasing nitric oxide metabolites. (Crit Care Med 2010; 38: 2199-2206)

  • 43. Moa, Gunnar
    et al.
    Nilsson, Kjell
    Zetterström, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jonsson, Lars O
    A new device för administration of nasal CPAP in the newborn1988In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 16, p. 1238-1242Article in journal (Refereed)
  • 44.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, M. B.
    Wikström, B. G.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berggren-Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia2003In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 31, no 6, p. 1780-1785Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics.

    DESIGN: Prospective, randomized, placebo-controlled trial with parallel groups.

    SETTING: Animal research laboratory at the University Hospital of Uppsala, Sweden.

    SUBJECTS: Thirteen piglets aged 12-14 wks receiving general anesthesia.

    INTERVENTIONS: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin.

    MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed.

    CONCLUSION: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

  • 45.
    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]

  • 46. Nielsen, Niklas
    et al.
    Sunde, Kjetil
    Hovdenes, Jan
    Riker, Richard R.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Stammet, Pascal
    Nilsson, Fredrik
    Friberg, Hans
    Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia2011In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To investigate the association between adverse events recorded during critical care and mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia.

    Design:

    Prospective, observational, registry-based study.

    Setting:

    Twenty-two hospitals in Europe and the United States.

    Patients:

    Between October 2004 and October 2008, 765 patients were included. Interventions: None.

    Measurements and Main Results:

    Arrhythmias (7%-14%), pneumonia (48%), metabolic and electrolyte disorders (5%-37%), and seizures (24%) were common adverse events in the critical care period in cardiac arrest patients treated with therapeutic hypothermia, whereas sepsis (4%) and bleeding (6%) were less frequent. Sustained hyperglycemia (blood glucose >8 mmol/L for >4 hrs; odds ratio 2.3, 95% confidence interval 1.6-3.6, p < .001) and seizures treated with anticonvulsants (odds ratio 4.8, 95% confidence interval 2.9-8.1, p < .001) were associated with increased mortality in a multivariate model. An increased frequency of bleeding and sepsis occurred after invasive procedures (coronary angiography, intravascular devices for cooling, intra-aortic balloon pump), but bleeding and sepsis were not associated with increased mortality (odds ratio 1.0, 95% confidence interval 0.46-2.2, p = .91, and odds ratio 0.30, 95% confidence interval 0.12-0.79, p = .01, respectively).

    Conclusions:

    Adverse events were common after out-of-hospital cardiac arrest. Sustained hyperglycemia and seizures treated with anticonvulsants were associated with increased mortality. Bleeding and infection were more common after invasive procedures, but these adverse events were not associated with increased mortality in our study.

  • 47.
    Nilsson, Manja C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hambraeus-Jonon, Kristina
    Lattuada, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Luni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Li, Ren
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alving, Kjell
    Wiklund, Peter
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fredén, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Distant effects of nitric oxide inhalation in endotoxemic pigs2010In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 38, no 1, p. 242-248Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO. DESIGN: Prospective, randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Twenty-two pairs of domestic pigs. INTERVENTIONS: Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group). MEASUREMENTS AND MAIN RESULTS: NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004). CONCLUSIONS: As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.

  • 48. Nunnally, Mark E.
    et al.
    Jaeschke, Roman
    Bellingan, Geoffrey J.
    Lacroix, Jacques
    Mourvillier, Bruno
    Rodriguez-Vega, Gloria M.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Vassilakopoulos, Theodoros
    Weinert, Craig
    Zanotti-Cavazzoni, Sergio
    Buchman, Timothy G.
    Targeted temperature management in critical care: A report and recommendations from five professional societies2011In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, no 5, p. 1113-1125Article in journal (Refereed)
    Abstract [en]

    Objective: Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations.

    Data Sources: Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies.

    Study Selection: Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis.

    Conclusions and Recommendations: 1) The jury opines that the term "targeted temperature management" replace "therapeutic hypothermia."

    2) The jury opines that descriptors (e. g., "mild") be replaced with explicit targeted temperature management profiles.

    3) The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome.

    4) The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32 degrees C-34 degrees C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence).

    5) The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33 degrees C-35.5 degrees C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

  • 49.
    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.

  • 50.
    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.

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