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Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study

Glenn Hernandez| Alejandro Bruhn| Cecilia Luengo| Tomas Regueira| Eduardo Kattan| Andrea Fuentealba| Jorge Florez| Ricardo Castro| Andres Aquevedo| Ronald Pairumani| Paul McNab| Can Ince
Original Article
Volume 39, Issue 8 / August , 2013

Pages 1435 - 1443

Abstract

Purpose

The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation.

Methods

We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m2 and hyperlactatemia. Primary outcome was sublingual perfused microvascular density.

Results

Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9–10.1) vs. 9.1 n/mm (7.9–9.9); p = 0.24] or microvascular flow index [2.1 (1.8–2.5) vs. 2.1 (1.9–2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO2 gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO2 gradient. The indocyanine green plasma disappearance rate [14.4 (9.5–25.6) vs. 18.8 %/min (11.7–24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1–3.1) vs. 2.5 %/s (1.2–3.4); p = 0.01] were worse with dobutamine compared to placebo.

Conclusions

Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.

Keywords

References

  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228
  2. Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J (2010) Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 182:752–761
    • View reference on PubMed
    • View reference on publisher's website
  3. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377
    • View reference on PubMed
    • View reference on publisher's website
  4. Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 330:1717–1722
    • View reference on PubMed
    • View reference on publisher's website
  5. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 collaborative group. N Engl J Med 333:1025–1032
    • View reference on PubMed
    • View reference on publisher's website
  6. Palizas F, Dubin A, Regueira T, Bruhn A, Knobel E, Lazzeri S, Baredes N, Hernandez G (2009) Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial. Crit Care 13:R44
    • View reference on PubMed
    • View reference on publisher's website
  7. De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL (2006) The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 34:403–408
    • View reference on PubMed
    • View reference on publisher's website
  8. Green RS, Djogovic D, Gray S, Howes D, Brindley PG, Stenstrom R, Patterson E, Easton D, Davidow JS (2008) Canadian association of emergency physicians sepsis guidelines: the optimal management of severe sepsis in canadian emergency departments. CJEM 10:443–459
    • View reference on PubMed
  9. Joly LM, Monchi M, Cariou A, Chiche JD, Bellenfant F, Brunet F, Dhainaut JF (1999) Effects of dobutamine on gastric mucosal perfusion and hepatic metabolism in patients with septic shock. Am J Respir Crit Care Med 160:1983–1986
    • View reference on PubMed
    • View reference on publisher's website
  10. Kern H, Schroder T, Kaulfuss M, Martin M, Kox WJ, Spies CD (2001) Enoximone in contrast to dobutamine improves hepatosplanchnic function in fluid-optimized septic shock patients. Crit Care Med 29:1519–1525
    • View reference on PubMed
    • View reference on publisher's website
  11. Lebuffe G, Levy B, Neviere R, Chagnon JL, Perrigault PF, Duranteau J, Edouard A, Teboul JL, Vallet B (2002) Dobutamine and gastric-to-arterial carbon dioxide gap in severe sepsis without shock. Intensive Care Med 28:265–271
  12. Levy B, Bollaert PE, Lucchelli JP, Sadoune LO, Nace L, Larcan A (1997) Dobutamine improves the adequacy of gastric mucosal perfusion in epinephrine-treated septic shock. Crit Care Med 25:1649–1654
    • View reference on PubMed
    • View reference on publisher's website
  13. Morelli A, De Castro S, Teboul JL, Singer M, Rocco M, Conti G, De Luca L, Di Angelantonio E, Orecchioni A, Pandian NG, Pietropaoli P (2005) Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med 31:638–644
  14. Morelli A, Donati A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Landoni G, Pelaia P, Pietropaoli P, Van Aken H, Teboul JL, Ince C, Westphal M (2010) Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care 14:R232
    • View reference on PubMed
    • View reference on publisher's website
  15. Enrico C, Kanoore Edul VS, Vazquez AR, Pein MC, Perez de la Hoz RA, Ince C, Dubin A (2012) Systemic and microcirculatory effects of dobutamine in patients with septic shock. J Crit Care 27:630–638
    • View reference on PubMed
    • View reference on publisher's website
  16. (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864–874
  17. Riker RR, Picard JT, Fraser GL (1999) Prospective evaluation of the sedation–agitation scale for adult critically ill patients. Crit Care Med 27:1325–1329
    • View reference on PubMed
    • View reference on publisher's website
  18. De Backer D, Hollenberg S, Boerma C, Goedhart P, Buchele G, Ospina-Tascon G, Dobbe I, Ince C (2007) How to evaluate the microcirculation: report of a round table conference. Crit Care 11:R101
    • View reference on PubMed
    • View reference on publisher's website
  19. Senn S (2002) Cross-over trials in clinical research. John Wiley and Sons, Chichester
  20. Jellema WT, Groeneveld AB, Wesseling KH, Thijs LG, Westerhof N, van Lieshout JJ (2006) Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock. Crit Care Med 34:2392–2398
    • View reference on PubMed
    • View reference on publisher's website
  21. De Backer D, Donadello K, Taccone FS, Ospina-Tascon G, Salgado D, Vincent JL (2011) Microcirculatory alterations: potential mechanisms and implications for therapy. Ann Intensive Care 1:27
    • View reference on PubMed
    • View reference on publisher's website
  22. Dubin A, Edul VS, Pozo MO, Murias G, Canullan CM, Martins EF, Ferrara G, Canales HS, Laporte M, Estenssoro E, Ince C (2008) Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med 36:535–542
    • View reference on PubMed
    • View reference on publisher's website
  23. Tugtekin IF, Radermacher P, Theisen M, Matejovic M, Stehr A, Ploner F, Matura K, Ince C, Georgieff M, Trager K (2001) Increased ileal-mucosal-arterial PCO2 gap is associated with impaired villus microcirculation in endotoxic pigs. Intensive Care Med 27:757–766
  24. Silverman HJ, Tuma P (1992) Gastric tonometry in patients with sepsis. Effects of dobutamine infusions and packed red blood cell transfusions. Chest 102:184–188
    • View reference on PubMed
    • View reference on publisher's website
  25. Woolsey CA, Coopersmith CM (2006) Vasoactive drugs and the gut: is there anything new? Curr Opin Crit Care 12:155–159
    • View reference on PubMed
    • View reference on publisher's website
  26. De Backer D, Zhang H, Manikis P, Vincent JL (1996) Regional effects of dobutamine in endotoxic shock. J Surg Res 65:93–100
    • View reference on PubMed
    • View reference on publisher's website
  27. Neviere R, Chagnon JL, Vallet B, Lebleu N, Marechal X, Mathieu D, Wattel F, Dupuis B (1997) Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of endotoxic shock. Crit Care Med 25:1371–1377
    • View reference on PubMed
    • View reference on publisher's website
  28. Secchi A, Ortanderl JM, Schmidt W, Walther A, Gebhard MM, Martin E, Schmidt H (2001) Effects of dobutamine and dopexamine on hepatic micro- and macro-circulation during experimental endotoxemia: an intravital microscopic study in the rat. Crit Care Med 29:597–600
    • View reference on publisher's website
  29. Sun Q, Tu Z, Lobo S, Dimopoulos G, Nagy N, Rogiers P, De Backer D, Vincent JL (2003) Optimal adrenergic support in septic shock due to peritonitis. Anesthesiology 98:888–896
    • View reference on PubMed
    • View reference on publisher's website
  30. Dubin A, Murias G, Sottile JP, Pozo MO, Baran M, Edul VS, Canales HS, Etcheverry G, Maskin B, Estenssoro E (2007) Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study. Intensive Care Med 33:485–494
  31. Heino A, Hartikainen J, Merasto ME, Koski EM, Tenhunen J, Alhava E, Takala J (2000) Effects of dobutamine on splanchnic tissue perfusion during partial superior mesenteric artery occlusion. Crit Care Med 28:3484–3490
    • View reference on PubMed
    • View reference on publisher's website
  32. Hiltebrand LB, Krejci V, Sigurdsson GH (2004) Effects of dopamine, dobutamine, and dopexamine on microcirculatory blood flow in the gastrointestinal tract during sepsis and anesthesia. Anesthesiology 100:1188–1197
    • View reference on PubMed
    • View reference on publisher's website
  33. Memis D, Inal MT, Sut N (2012) The effects of levosimendan versus dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock. J Crit Care 27(318):e311–e316
  34. Hernandez G, Bruhn A, Castro R, Regueira T (2012) The holistic view on perfusion monitoring in septic shock. Curr Opin Crit Care 18:280–286
    • View reference on PubMed
    • View reference on publisher's website
  35. Hernandez G, Pedreros C, Veas E, Bruhn A, Romero C, Rovegno M, Neira R, Bravo S, Castro R, Kattan E, Ince C (2012) Evolution of peripheral versus metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study. J Crit Care 27:283–288
    • View reference on PubMed
    • View reference on publisher's website
  36. Lima A, Jansen TC, van Bommel J, Ince C, Bakker J (2009) The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med 37:934–938
    • View reference on PubMed
    • View reference on publisher's website
  37. Patel MB, Kaplan IV, Patni RN, Levy D, Strom JA, Shirani J, LeJemtel TH (1999) Sustained improvement in flow-mediated vasodilation after short-term administration of dobutamine in patients with severe congestive heart failure. Circulation 99:60–64
    • View reference on PubMed
    • View reference on publisher's website
  38. Delehanty J, Liang CS, Odorisi ML (1999) Effects of dobutamine on ischemic vasodilation of the forearm in patients with severe congestive heart failure. J Card Fail 5:25–30
    • View reference on PubMed
    • View reference on publisher's website
  39. Qvisth V, Hagstrom-Toft E, Enoksson S, Bolinder J (2008) Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of -adrenoreceptor subtypes. J Clin Endocrinol Metab 93:240–246
    • View reference on PubMed
    • View reference on publisher's website

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