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  • 1.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Airway closure: nothing good during anesthesia2012In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 78, no 11, p. 1193-1195Article in journal (Other academic)
  • 2.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Esophageal pressure: benefit and limitations2012In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 78, no 8, p. 959-966Article in journal (Refereed)
    Abstract [en]

    The recording of esophageal pressure (Pes) in supine position as a Substitute for pleural pressure is difficult and fraught with potential errors. Pes is affected by the: 1) elastance and weight of the lung; 2) elastance and weight of the rib cage; 3) weight of the mediastinal organs; 4) elastance and weight of the diaphragm and abdomen; 5) elastance of the esophageal wall; and 6) elastance of the esophageal balloon (if filled with too much air). If the purpose is to measure lung compliance in the intensive care patient, reasonably useful information might be obtained by measuring airway pressure alone, considering chest wall compliance to be a weight that is forced away by the ventilation. Such weight requires a constant pressure for displacement. The transpulmonary pressure, whether calculated with Pes or by another measure of abdominal pressure, may guide in PEEP titration. It may also enable calculation of stresses applied to the lung and these may be more important in guiding an optimal ventilator setting than an optimum compliance or oxygenation of blood. Diaphragm function can be estimated by esophageal minus gastric pressure and with even more precision, when combined with diaphragm electromyography. (Minerva Anestesiol 2012;78:959-66)

  • 3.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Bellomo, R
    Hemodynamic management of septic shock2015In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, no 11, p. 1262-1272Article in journal (Refereed)
    Abstract [en]

    We present a review of the hemodynamic management of septic shock. Although substantial amount of evidence is present in this area, most key decisions on the management of these patients remain dependent on physiological reasoning and on pathophysiological principles rather than randomized controlled trials. During primary (early) resuscitation, restoration of adequate arterial pressure and cardiac output using fluids and vasopressor and/or inotropic drugs is guided by basic hemodynamic monitoring and physical examination in the emergency department. When more advanced level of monitoring is present in these patients, i.e. during secondary resuscitation (later phase in the emergency department and in the ICU), hemodynamic management can be guided by more advanced measurements of the macro--circulation. Our understanding of the microcirculation in septic shock is limited and reliable therapeutic modalities to optimize it do not yet exist. No specific hemodynamic treatment strategy, be it medications including fluids, monitoring devices or treatment algorithms has yet been proved to improve outcome. Moreover, there is virtually no data on the optimal management of the resolution phase of septic shock. Despite these gaps in knowledge, the data from observational studies and trials suggests that mortality in septic shock has been generally decreasing during the last decade.

  • 4.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mcnicol, L.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Parker, F.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Poustie, S.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Liu, G.
    Austin Hosp, Dept Anaesthesia, Melbourne, Vic 3084, Australia..
    Uchino, S.
    Jikei Univ, Dept Intens Care, Tokyo, Japan..
    Kattula, A.
    Alfred Hlth, Clin Practice Improvement, Melbourne, Vic, Australia..
    Bellomo, R.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Effect of perfusion pressure on the splanchnic circulation after CPB: a pilot study2015In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, no 7, p. 752-764Article in journal (Refereed)
    Abstract [en]

    Background. The impact of different blood pressure targets is unknown for post cardiac surgery patient in the intensive care unit. We, therefore, investigated the effects of a mean arterial pressure (MAP) target of 65 or 85 mmHg on splanchnic oxygenation, metabolic function, cytokine regulation and gastric tonometry after cardiopulmonary bypass. Methods. Sixteen patients were randomized to the HLH group (high-low-high) where MAP of 85-65-85 mmHg was targeted or the LHL group where MAP 65-85-65 mmHg was targeted with norepinephrine Results. MAP targets were achieved in all patients at all timepoints (64 +/- 3, 84 +/- 4; 65 +/- 5, LHL group; vs. 84 +/- 3; 66 +/- 2; 85 +/- 5 mmHg, HLH group). At corresponding timepoints, hepatic venous saturation was 41 +/- 15%; 58 +/- 24%; 56 +/- 21% in the LHL group vs. 50 +/- 19%; 43 +/- 20%; 41 +/- 18% in the HLH group (P<0.05). No changes were observed in cardiac output, global or trans-splanchnic lactate levels and cytokine levels or in gastric tonometry CO2. Conclusion. Achieving a MAP target of 85 mmHg by means of norepinephrine infusion after CPB appears safe for the splanchnic circulation.

  • 5.
    Martensson, J.
    et al.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Karolinska Inst, Sect Anesthesia & Intens Care Med, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Glassford, N. J.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Monash Univ, Sch Prevent Med & Publ Hlth, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic 3004, Australia..
    Jones, S.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Eastwood, G. M.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Deakin Univ, Sch Nursing & Midwifery, Melbourne, Vic 3004, Australia..
    Young, H.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Peck, L.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia..
    Ostland, V.
    Intrins LifeSci LLC, La Jolla, CA USA..
    Westerman, M.
    Intrins LifeSci LLC, La Jolla, CA USA..
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bellomo, R.
    Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.;Monash Univ, Sch Prevent Med & Publ Hlth, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic 3004, Australia..
    Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients2015In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 81, no 11, p. 1192-1200Article in journal (Refereed)
    Abstract [en]

    Background. Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher urinary hepcidin levels are associated with absence of AKI. We aimed to investigate the value of combining both biomarkers to estimate the severity and progression of AKI in intensive care unit (ICU) patients. Methods. Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in patients with the systemic inflammatory response syndrome and early kidney dysfunction (oliguria for >= 2 hours and/or a 25 mu mol/L creatinine rise from baseline). Diagnostic and prognostic characteristics were assessed by logistic regression and receiver operating characteristics (ROC) analysis. Results. Of 102 patients, 26 had mild AKI and 28 patients had severe AKI on admission. Sepsis (21%), cardiac surgery (17%) and liver failure (9%) were primary admission diagnoses. NGAL increased (P=0.03) whereas hepcidin decreased (P=0.01) with increasing AKI severity. The value of NGAL/hepcidin ratio to detect severe AKI was higher than when NGAL and hepcidin were used individually and persisted after adjusting for potential confounders (adjusted OR 2.40, 95% CI 1.20-4.78). The ROC areas for predicting worsening AKI were 0.50, 0.52 and 0.48 for NGAL, 1/hepcidin and the NGAL/hepcidin ratio. Conclusion. The NGAL/hepcidin ratio is more strongly associated with severe AKI than the single biomarkers alone. NGAL and hepcidin, alone or combined as a ratio, were unable to predict progressive AKI in this selected ICU cohort.

  • 6.
    Pelosi, Paolo
    et al.
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS AOU San Martino IST, Genoa, Italy.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ball, Lorenzo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS AOU San Martino IST, Genoa, Italy.
    Edmark, Lennart
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden.
    Bignami, Elena
    IRCCS, San Raffaele Sci Inst, Dept Anesthesia & Intens Care, Via Olgettina 60, I-20132 Milan, Italy.
    The real role of the PEEP in operating room: pros & cons2018In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 84, no 2, p. 229-235Article in journal (Refereed)
  • 7.
    Schilling, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kretzschmar, Moritz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hachenberg, T.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kozian, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The immune response to one-lung-ventilation is not affected by repeated alveolar recruitment manoeuvres in pigs2013In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 79, no 6, p. 590-603Article in journal (Refereed)
    Abstract [en]

    Background. Acute lung injury after thoracic surgery relates to alveolar inflammation induced by one-lung ventilation (OLV) and surgical manipulation. However, alveolar recruitment manoeuvres (ARM), conventional ventilation, and airway manipulation may increase alveolar trauma. This study evaluates pulmonary immune effects of these co-factors in a porcine model. Methods. Twenty-two piglets (27.3 kg) were randomised to spontaneous breathing (N.=4), two-lung ventilation (TLV, N.=6), OLV with propofol (6 mg/kg/h, N.=6) or desflurane anesthesia (1MAC, N.=6). Mechanical ventilation settings were constant throughout the experiment: V-T=10 mL/kg, F1O2=0.4, PEEP=5 cmH(2)O. OLV was performed by left-sided bronchial blockade. Thoracic surgery was simulated for 60 min. ARM (airway pressure of 40 mbar for 10 s) was applied before and after each airway manipulation. Cytokines and mRNA-expression were assessed by immunoassays and semi-quantitative RT-PCR in alveolar lavage fluids, serum and tissue samples prior to and after OLV (TLV in controls). Results. Repetitive ARM and TLV induced no significant proinflammatory effects. OLV enhanced cytokine release but less with desflurane inhalation than propofol infusion (median (IQR) [pg/mL], dependent lung): Interleukin-8: TLV 44 (17) to 68 (35), propofol 82 (17) to 494 (231), desflurane 89 (30) to 282 (44). Likewise, serum cytokines were different: tumour necrosis factor-a: TLV 37 (13) to 62 (7), propofol 55 (39) to 94 (60), desflurane 43 (33) to 41 (25). Expression of interleukin-8-mRNA increased after OLV, but mRNA expression was not modulated by anesthetics. Conclusion. ARM, standard TLV and repetitive BAL do not additionally contribute to lung injury resulting from OLV for thoracic surgery in healthy porcine lungs. OLV induces expression of interleukin-8-mRNA in alveolar cells, which is not modulated by different anesthetic drugs.

  • 8. Schumann, S.
    et al.
    Goebel, U.
    Haberstroh, J.
    Vimlati, Laszlo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Schneider, M.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Guttmann, J.
    Determination of respiratory system mechanics during inspiration and expiration by FLow-controlled EXpiration (FLEX): a pilot study in anesthetized pigs2014In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 80, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Background. Differences between inspiratory and expiratory lung mechanics result in the hysteresis of the pressure volume-loop. While hysteresis area is a global parameter describing the difference between inspiration and expiration in mechanics under quasi-static conditions, a detailed analysis of this difference under the dynamic conditions of mechanical ventilation is feasible once inspiratory and expiratory compliance (C-in/C-ex) are determined separately. This requires uncoupling of expiratory flow rate and volume (V). Methods. Five piglets were mechanically ventilated at positive end-expiratory pressure (PEEP) levels ranging from 0 to 15 cmH(2)O. Expiratory flow rate was linearized by a computer-controlled resistor (flow-controlled expiration). The volume-dependent C-in(V) and C-ex(V) profiles were calculated from the tracheal pressure volume-loops. Results. The intratidal curve-progression of C-ex(V) was altogether higher with a steeper slope compared to C-in(V). With increasing positive end-expiratory pressure (PEEP) dynamic hysteresis area decreased and C-ex(V) tended to run more parallel to C-in(V), Conclusion. The relation between inspiratory and expiratory compliance profiles is associated with the hysteresis area and behaves PEEP dependent. Analysing the C-in-C-ex-relation might therefore potentially offer a new approach to titrate PEEP and tidal volume.

  • 9.
    Strang, Christof M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ebmeyer, U.
    Maripuu, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Hachenberg, T.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Improved ventilation-perfusion matching by abdominal insufflation (pneumoperitoneum) with CO2 but not with air2013In: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 79, no 6, p. 617-625Article in journal (Refereed)
    Abstract [en]

    Background. Pneumoperitoneum (PP) by CO2-insufflation causes atelectasis however with maintained or even improved oxygenation. We studied the effect of abdominal insufflation by carbon dioxide (CO2) and air on gas exchange during PP. Methods. Twenty-seven anesthetized pigs were studied during PP with insufflations to 12 mmHg by either 1/CO2, 2/ air or 3/CO2 during intravenous nitroprusside infusion (SNP) (N.=9 in each group). In 3 pigs in each group, gamma camera technique (SPECT) was used to study ventilation and perfusion distributions, in another 6 pigs an inert-gas technique (MIGET) was used for assessing ventilation-perfusion matching (V-A/Q). Measurements were made during anesthesia before and after 60 minutes of PP. Results. CO2-PP caused a shift of blood flow away from dependent, non-ventilated (atelectatic) to ventilated regions. Air-PP caused smaller, and SNP-PP even less shift of lung blood flow. Shunt decreased luring CO2-PP (6+/-1% compared to baseline 9+/-2%, P<0.05), did not change during Air-PP (10+/-2%) and increased during SNP-PP (16+/-2%, P<0.05). PaO2 increased from baseline 35+/-2 to 41+/-3 kPa during CO2-PP and decreased to 32+/-3 kPa during Air-PP and to 27+/-3 kPa during SNP-PP (P<0.05 for all three comparisons). PaCO2 increased during CO2- and SNP-PP. Conclusion. CO2-PP enhanced the shift of blood flow towards better ventilated areas of the lung compared to Air-PP and SNP blunted the effects seen with CO2-PP. SNP may thus have blunted and CO2 potentiated vasoconstriction, by hypoxic pulmonary vasoconstriction or another mechanism.

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