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Oxygen Transport Assessment

  • Arnaldo Dubin
  • Eliézer Silva
Chapter

Abstract

In critical conditions, oxygen transport (i.e., the product of cardiac output by arterial oxygen content) is the main determinant of tissue oxygenation. Its assessment, therefore, is a crucial task in the intensive care unit. Although the value of oxygen transport is easily determined in this setting, such measurement might be insufficient to characterize the global state of tissue oxygenation. Since oxygen demands are varied and changing, isolated values of oxygen transport might be misleading. Attempts to characterize the relationship between oxygen transport and consumption are also futile. The assessment of oxygen transport should not only include measurements of its actual value or some surrogate but also a comprehensive evaluation of tissue oxygenation. Thus, the main goal of the assessment of oxygen transport is to show its adequacy to satisfy metabolic oxygen needs. In the absence of a gold standard of tissue oxygenation, the approach should include clinical evaluation (blood pressure, mental status, diuresis, and peripheral perfusion), laboratory variables (arterial blood gases and lactate), and markers of microvascular perfusion. Despite a large body of evidence favoring the usefulness of tissue capnometry, this technique is not used anymore. In the last years, the direct visualization of sublingual microcirculation has been introduced for bedside evaluation. It provides relevant information, not available when monitoring systemic cardiovascular and oxygen transport. Nevertheless, its actual role in the assessment of oxygen transport in critically ill patients remains controversial.

Keywords

Oxygen transport Oxygen consumption Tissue oxygenation Microcirculation Hypoperfusion 

References

  1. 1.
    Weissman C, Kemper M, Damask MC, Askanazi J, Hyman AI, Kinney JM. Effect of routine intensive care interactions on metabolic rate. Chest. 1984;86:815–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Kanoore Edul VS, Ince C, Dubin A. What is microcirculatory shock? Curr Opin Crit Care. 2015;21:245–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Saugel B, Cecconi M, Wagner JY, Reuter DA. Noninvasive continuous cardiac output monitoring in perioperative and intensive care medicine. Br J Anaesth. 2015;114:562–75.CrossRefPubMedGoogle Scholar
  4. 4.
    Frasca D, Dahyot-Fizelier C, Catherine K, Levrat Q, Debaene B, Mimoz O. Accuracy of a continuous noninvasive hemoglobin monitor in intensive care unit patients. Crit Care Med. 2011;39:2277–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Hiscock R, Kumar D, Simmons SW. Systematic review and meta-analysis of method comparison studies of Masimo pulse co-oximeters (Radical-7™ or Pronto-7™) and HemoCue® absorption spectrometers (B-Hemoglobin or 201+) with laboratory haemoglobin estimation. Anaesth Intensive Care. 2015;43:341–50.PubMedGoogle Scholar
  6. 6.
    Walley KR. Use of central venous oxygen saturation to guide therapy. Am J Respir Crit Care Med. 2011;184:514–20.CrossRefPubMedGoogle Scholar
  7. 7.
    ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRefGoogle Scholar
  8. 8.
    ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506.CrossRefGoogle Scholar
  9. 9.
    Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM, ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301–11.CrossRefPubMedGoogle Scholar
  10. 10.
    Pope JV, Jones AE, Gaieski DF, Arnold RC, Trzeciak S, Shapiro NI, Emergency Medicine Shock Research Network (EMShockNet) Investigators. Multicenter study of central venous oxygen saturation ScvO2 as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40–46.e1.CrossRefPubMedGoogle Scholar
  11. 11.
    Gutierrez G, Comignani P, Huespe L, Hurtado FJ, Dubin A, Jha V, Arzani Y, Lazzeri S, Sosa L, Riva J, Kohn W, Suarez D, Lacuesta G, Olmos D, Mizdraji C, Ojeda A. Central venous to mixed venous blood oxygen and lactate gradients are associated with outcome in critically ill patients. Intensive Care Med. 2008;34:1662–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Schlichtig R, Cowden WL, Chaitman BR. Tolerance of unusually low mixed venous oxygen saturation. Adaptations in the chronic low cardiac output syndrome. Am J Med. 1986;80:813–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Dubin A, Estenssoro E. Mechanisms of tissue hypercarbia in sepsis. Front Biosci. 2008;13:1340–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Vallée F, Vallet B, Mathe O, Parraguette J, Mari A, Silva S, Samii K, Fourcade O, Genestal M. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med. 2008;34:2218–25.CrossRefPubMedGoogle Scholar
  15. 15.
    Dubin A, Edul VS, Pozo MO, Murias G, Canullán CM, Martins EF, Ferrara G, Canales H, Laporte M, Estenssoro E, Ince C. Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med. 2008;36:535–42.CrossRefPubMedGoogle Scholar
  16. 16.
    Dubin A, Murias G, Estenssoro E, Canales H, Sottile P, Badie J, Barán M, Rossi S, Laporte M, Pálizas F, Giampieri J, Mediavilla D, Vacca E, Botta D. End-tidal CO2 pressure determinants during hemorrhagic shock. Intensive Care Med. 2000;26:1619–23.CrossRefPubMedGoogle Scholar
  17. 17.
    Ferrara G, Kanoore Edul VS, Martins E, Canales HS, Canullán C, Murias G, Pozo MO, Estenssoro E, Ince C, Dubin A. Intestinal and sublingual microcirculation are more severely compromised in hemodilution than in hemorrhage. J Appl Physiol (1985). 2016;120:1132–40.CrossRefGoogle Scholar
  18. 18.
    Almac E, Bezemer R, Hilarius-Stokman PM, Goedhart P, de Korte D, Verhoeven AJ, Ince C. Red blood cell storage increases hypoxia-induced nitric oxide bioavailability and methemoglobin formation in vitro and in vivo. Transfusion. 2014;54:3178–85.CrossRefPubMedGoogle Scholar
  19. 19.
    Schumacker PT, Cain SM. The concept of a critical oxygen delivery. Intensive Care Med. 1987;13:223–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Cain SM. Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. J Appl Physiol Respir Environ Exerc Physiol. 1977;42:228–34.PubMedGoogle Scholar
  21. 21.
    Dubin A, Estenssoro E, Murias G, Canales H, Sottile P, Badie J, Barán M, Pálizas F, Laporte M, Rivas Díaz M. Effects of hemorrhage on gastrointestinal oxygenation. Intensive Care Med. 2001;27:1931–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Danek SJ, Lynch JP, Weg JG, Dantzker DR. The dependence of oxygen uptake on oxygen delivery in the adult respiratory distress syndrome. Am Rev Respir Dis. 1980;122:387–95.PubMedGoogle Scholar
  23. 23.
    Bihari D, Smithies M, Gimson A, Tinker J. The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med. 1987;317:397–403.CrossRefPubMedGoogle Scholar
  24. 24.
    Dantzker DR, Foresman B, Gutierrez G. Oxygen supply and utilization relationships. A reevaluation. Am Rev Respir Dis. 1991;143:675–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Phang PT, Cunningham KF, Ronco JJ, Wiggs BR, Russell JA. Mathematical coupling explains dependence of oxygen consumption on oxygen delivery in ARDS. Am J Respir Crit Care Med. 1994;150:318–23.CrossRefPubMedGoogle Scholar
  26. 26.
    De Backer D, Moraine JJ, Berre J, Kahn RJ, Vincent JL. Effects of dobutamine on oxygen consumption in septic patients. Direct versus indirect determinations. Am J Respir Crit Care Med. 1994;150:95–100.CrossRefPubMedGoogle Scholar
  27. 27.
    Nelson DP, Samsel RW, Wood LD, Schumacker PT. Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol (1985). 1988;64:2410–9.CrossRefGoogle Scholar
  28. 28.
    Wasserman K, Whipp BJ, Koyl SN, Beaver WL. Anaerobic threshold and respiratory gas exchange during exercise. J Appl Physiol. 1973;35:236–43.CrossRefPubMedGoogle Scholar
  29. 29.
    Cohen IL, Sheikh FM, Perkins RJ, Feustel PJ, Foster ED. Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine. Crit Care Med. 1995;23:545–52.CrossRefPubMedGoogle Scholar
  30. 30.
    Mekontso-Dessap A, Castelain V, Anguel N, Bahloul M, Schauvliege F, Richard C, Teboul JL. Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect anaerobic metabolism in patients. Intensive Care Med. 2002;28:272–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Perner A, Gordon AC, De Backer D, Dimopoulos G, Russell JA, Lipman J, Jensen JU, Myburgh J, Singer M, Bellomo R, Walsh T. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016;42:1958–69.CrossRefPubMedGoogle Scholar
  32. 32.
    Ferrara G, Edul VSK, Canales HS, Martins E, Canullán C, Murias G, Pozo MO, Caminos Eguillor JF, Buscetti MG, Ince C, Dubin A. Systemic and microcirculatory effects of blood transfusion in experimental hemorrhagic shock. Intensive Care Med Exp. 2017;5:24.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Dubin A, Ferrara G, Kanoore Edul VS, Martins E, Canales HS, Canullán C, Murias G, Pozo MO, Estenssoro E. Venoarterial PCO2-to-arteriovenous oxygen content difference ratio is a poor surrogate for anaerobic metabolism in hemodilution: an experimental study. Ann Intensive Care. 2017;7:65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Nevière R, Mathieu D, Chagnon JL, Lebleu N, Wattel F. The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med. 1996;154:1684–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Joly HR, Weil MH. Temperature of the great toe as an indication of the severity of shock. Circulation. 1969;39:131–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Kaplan LJ, McPartland K, Santora TA, Trooskin SZ. Start with a subjective assessment of skin temperature to identify hypoperfusion in intensive care unit patients. J Trauma. 2001;50:620–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Ait-Oufella H, Bige N, Boelle PY, Pichereau C, Alves M, Bertinchamp R, Baudel JL, Galbois A, Maury E, Guidet B. Capillary refill time exploration during septic shock. Intensive Care Med. 2014;40:958–64.CrossRefPubMedGoogle Scholar
  38. 38.
    Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009;37:934–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Meakins J, Long CN. Oxygen consumption, oxygen debt and lactic acid in circulatory failure. J Clin Invest. 1927;4:273–93.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Weil MH, Afifi AH. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation. 1970;41:989–1001.CrossRefPubMedGoogle Scholar
  41. 41.
    Mecher C, Rackow EC, Astiz ME, Weil MH. Unaccounted for anion in metabolic acidosis during severe sepsis in humans. Crit Care Med. 1991;19:705–11.CrossRefPubMedGoogle Scholar
  42. 42.
    Masevicius FD, Rubatto Birri PN, Risso Vazquez A, Zechner FE, Motta MF, Valenzuela Espinoza ED, Welsh S, Guerra Arias EF, Furche MA, Berdaguer FD, Dubin A. Relationship of at admission lactate, unmeasured anions, and chloride to the outcome of critically ill patients. Crit Care Med. 2017;45:e1233.CrossRefPubMedGoogle Scholar
  43. 43.
    Tuhay G, Pein MC, Masevicius FD, Kutscherauer DO, Dubin A. Severe hyperlactatemia with normal base excess: a quantitative analysis using conventional and Stewart approaches. Crit Care. 2008;12:R66.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nichol AD, Egi M, Pettila V, Bellomo R, French C, Hart G, Davies A, Stachowski E, Reade MC, Bailey M, Cooper DJ. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-Centre study. Crit Care. 2010;14:R25.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32:1637–42.CrossRefPubMedGoogle Scholar
  46. 46.
    Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet. 2005;365:871–5.CrossRefPubMedGoogle Scholar
  47. 47.
    Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J, LACTATE Study Group. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752–61.CrossRefPubMedGoogle Scholar
  48. 48.
    Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med. 2006;32:516–23.CrossRefPubMedGoogle Scholar
  49. 49.
    Vallet B, Teboul JL, Cain S, Curtis S. Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol (1985). 2000;89:1317–21.CrossRefGoogle Scholar
  50. 50.
    Dubin A, Murias G, Estenssoro E, Canales H, Badie J, Pozo M, Sottile JP, Barán M, Pálizas F, Laporte M. Intramucosal-arterial PCO2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia. Crit Care. 2002;6:514–20.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Dubin A, Estenssoro E, Murias G, Pozo MO, Sottile JP, Barán M, Piacentini E, Canales HS, Etcheverry G. Intramucosal-arterial PCO2 gradient does not reflect intestinal dysoxia in anemic hypoxia. J Trauma. 2004;57:1211–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Gutierrez G. A mathematical model of tissue-blood carbon dioxide exchange during hypoxia. Am J Respir Crit Care Med. 2004;169:525–33.CrossRefPubMedGoogle Scholar
  53. 53.
    Hamilton-Davies C, Mythen MG, Salmon JB, Jacobson D, Shukla A, Webb AR. Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry. Intensive Care Med. 1997;23:276–81.CrossRefPubMedGoogle Scholar
  54. 54.
    Fiddian-Green RG. Associations between intramucosal acidosis in the gut and organ failure. Crit Care Med. 1993;21(2 Suppl):S103–7.CrossRefPubMedGoogle Scholar
  55. 55.
    Hurtado FJ, Berón M, Olivera W, Garrido R, Silva J, Caragna E, Rivara D. Gastric intramucosal pH and intraluminal PCO2 during weaning from mechanical ventilation. Crit Care Med. 2001;29:70–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Silva E, De Backer D, Creteur J, Vincent JL. Effects of fluid challenge on gastric mucosal PCO2 in septic patients. Intensive Care Med. 2004;30:423–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Doglio GR, Pusajo JF, Egurrola MA, Bonfigli GC, Parra C, Vetere L, Hernandez MS, Fernandez S, Palizas F, Gutierrez G. Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med. 1991;19:1037–40.CrossRefPubMedGoogle Scholar
  58. 58.
    Levy B, Gawalkiewicz P, Vallet B, Briancon S, Nace L, Bollaert PE. Gastric capnometry with air-automated tonometry predicts outcome in critically ill patients. Crit Care Med. 2003;31:474–80.CrossRefPubMedGoogle Scholar
  59. 59.
    Gutierrez G, Palizas F, Doglio G, Wainsztein N, Gallesio A, Pacin J, Dubin A, Schiavi E, Jorge M, Pusajo J, et al. Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet. 1992;339:195–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Vallée F, Mateo J, Dubreuil G, Poussant T, Tachon G, Ouanounou I, Payen D. Cutaneous ear lobe PCO2 at 37°C to evaluate microperfusion in patients with septic shock. Chest. 2010;138:1062–70.CrossRefPubMedGoogle Scholar
  61. 61.
    De Backer D, Orbegozo Cortes D, Donadello K, Vincent JL. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence. 2014;5:73–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Lam C, Tyml K, Martin C, Sibbald W. Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest. 1994;94:2077–83.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R. Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis. Am J Physiol Heart Circ Physiol. 2002;282:H156–64.CrossRefPubMedGoogle Scholar
  64. 64.
    Ince C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med. 1999;27:1369–77.CrossRefPubMedGoogle Scholar
  65. 65.
    De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166:98–104.CrossRefPubMedGoogle Scholar
  66. 66.
    Edul VS, Enrico C, Laviolle B, Vazquez AR, Ince C, Dubin A. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock. Crit Care Med. 2012;40:1443–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004;32:1825–31.CrossRefPubMedGoogle Scholar
  68. 68.
    De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med. 2013;41:791–9.CrossRefPubMedGoogle Scholar
  69. 69.
    Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, Arnold RC, Colilla S, Zanotti S, Hollenberg SM, Microcirculatory Alterations in Resuscitation and Shock Investigators. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007;49:88–98.CrossRefPubMedGoogle Scholar
  70. 70.
    Kanoore Edul VS, Ince C, Risso Vazquez A, Rubatto PN, Valenzuela Espinoza ED, Welsh S, Enrico C, Dubin A. Similar microcirculatory alterations in patients with normodynamic and hyperdynamic septic shock. Ann Am Thorac Soc. 2016;13:240–7.CrossRefGoogle Scholar
  71. 71.
    Hernandez G, Boerma EC, Dubin A, Bruhn A, Koopmans M, Edul VK, Ruiz C, Castro R, Pozo MO, Pedreros C, Veas E, Fuentealba A, Kattan E, Rovegno M, Ince C. Severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients. J Crit Care. 2013;28:538.e9–14.CrossRefGoogle Scholar
  72. 72.
    Pranskunas A, Koopmans M, Koetsier PM, Pilvinis V, Boerma EC. Microcirculatory blood flow as a tool to select ICU patients eligible for fluid therapy. Intensive Care Med. 2013;39:612–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Dubin A, Pozo MO, Casabella CA, Pálizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Pálizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13:R92.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Enrico C, Kanoore Edul VS, Vazquez AR, Pein MC, Pérez de la Hoz RA, Ince C, Dubin A. Systemic and microcirculatory effects of dobutamine in patients with septic shock. J Crit Care. 2012;27:630–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Boerma EC, van der Voort PH, Spronk PE, Ince C. Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis. Crit Care Med. 2007;35:1055–60.CrossRefPubMedGoogle Scholar
  76. 76.
    Kanoore Edul VS, Ince C, Navarro N, Previgliano L, Risso-Vazquez A, Rubatto PN, Dubin A. Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis. Ann Intensive Care. 2014;4:39.CrossRefGoogle Scholar
  77. 77.
    Lipcsey M, Woinarski NCZ, Bellomo R. Near infrared spectroscopy (NIRS) of the thenar eminence in anesthesia and intensive care. Ann Intensive Care. 2012;2:11.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Arnaldo Dubin
    • 1
    • 2
    • 3
  • Eliézer Silva
    • 4
  1. 1.La PlataArgentina
  2. 2.Cátedra de Farmacología Aplicada, Facultad de Ciencias MédicasUniversidad Nacional de La PlataBuenos AiresArgentina
  3. 3.Servicio de Terapia IntensivaSanatorio Otamendi y MiroliBuenos AiresArgentina
  4. 4.Medical School Hospital of the Albert EinsteinSao PauloBrazil

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