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Vasopressors and inotropes in sepsis
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Vasopressors and inotropes in sepsis Presentation Transcript

  • 1.  
  • 2.  
  • 3. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study* Yasser Sakr, MB, BCh, MSc; Konrad Reinhart, MD, PhD; Jean-Louis Vincent, MD,PhD, FCCP; Charles L. Sprung, MD; Rui Moreno, MD, PhD; V. Marco Ranieri, MD; Daniel De Backer, MD, PhD; Didier Payen, MD Crit Care Med 2006
  • 4. Sakr et al. SOAP Crit Care Med 2006
  • 5. Shock due to any cause (N=1058) Sakr et al. (SOAP study) Crit Care Med 2006
  • 6. Septic shock (N=462) Sakr et al. (SOAPstudy) Crit Care Med 2006
  • 7. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial Djillali Annane, Philippe Vignon, Alain Renault, Pierre-Edouard Bollaert, Claire Charpentier, Claude Martin, Gilles Troché, Jean-Damien Ricard, Gérard Nitenberg, Laurent Papazian, Elie Azoulay, Eric Bellissant, for the CATS Study Group* Lancet 2007 ;370:676-84.
    • Methods
    • prospective, multicentre (19 ICU, France), randomised, double-blind
    • 330 patients with septic shock
    • Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169)
    • titrated to maintain mean blood pressure at 70 mm Hg or more.
    • Primary outcome was 28-day all-cause mortality.
    • Findings
    • 28 day mortality:
    • 64 ( 40 %) deaths in the epinephrine group vs. 58 ( 34 %) deaths in the norepinephrine+dobutamine group (p=0·31; relative risk 0·86, 95% CI 0·65–1·14).
    • no significant difference between the two groups in time to haemodynamic success (log-rank p=0·67), time to vasopressor withdrawal (log-rank p=0·09), and time course of SOFA score. Rates of serious adverse events were also similar.
    • Interpretation
    • There is no evidence for a diff erence in effi cacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.
  • 8.
    • Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
  • 9. Comparison of Dopamine and Norepinephrine in the Treatment of Shock Daniel De Backer, M.D., Ph.D., Patrick Biston, M.D., Jacques Devriendt, M.D., Christian Madl, M.D., Didier Chochrad, M.D., Cesar Aldecoa, M.D., Alexandre Brasseur, M.D., Pierre Defrance, M.D., Philippe Gottignies, M.D., and Jean-Louis Vincent, M.D., Ph.D. for the SOAP II Investigators N Engl J Med 2010; 362:779-789 1679 patients, 858 assigned to dopamine and 821 to norepinephrine Primary outcome: 28 days-mortality Secondary end points : number of days without need for organ support and the occurrence of adverse events. 28 days mortality : 52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10.
  • 10. CONCLUSIONS Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. arrhythmic events 207 events [24.1%] dopamine vs. 102 events [12.4%] norepinephrine, P<0.001) subgroup analysis dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock ( P = 0.03 ) but not among the 1044 patients with septic shock ( P = 0.19) or the 263 with hypovolemic shock ( P = 0.84 ) De Backer et al. N Engl J Med 2010; 362:779-789
  • 11.  
  • 12.
    • Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study*
    • Bruno Levy, MD, PhD; Pierre Perez, MD; Jessica Perny, MD; Carine Thivilier, MD; Alain Gerard, MD
    Crit Care Med 2011 Vol. 39, No. 3 designed to compare epinephrine and norepinephrine-dobutamine in dopamine-resistant cardiogenic shock. 30 patients, C.I.<2.2 L/min1/m2, MAP<60 mm Hg, resistant to combined dopamine(max 20/kg/min) dobutamine(max 10/kg/min) treatment signs of shock. NON ischemic randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain a MAP 65 - 70 mm Hg with a stable or increased cardiac index.
  • 13. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2 Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study *. Levy, Bruno; MD, PhD; Perez, Pierre; Perny, Jessica; Thivilier, Carine; Gerard, Alain Critical Care Medicine. 39(3):450-455, March 2011. DOI: 10.1097/CCM.0b013e3181ffe0eb Figure 2. Evolution of mean arterial pressure (MAP) (top), cardiac index (CI) (middle), and heart rate (HR) (bottom). Squares, epinephrine-treated patients; triangles, norepinephrine-dobutamine-treated patients. *p 0; +p 0 and p < .05 epinephrine vs. norepinephrine-dobutamine. In comparison to norepinephrine/dobutamine, the identical positive hemodynamic response induced by epinephrine was counterbalanced by a significantly higher rate-pressure product, which correlates with higher oxygen requirements of the heart.
  • 14. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2 Figure 3. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study *. Levy, Bruno; MD, PhD; Perez, Pierre; Perny, Jessica; Thivilier, Carine; Gerard, Alain Critical Care Medicine. 39(3):450-455, March 2011. DOI: 10.1097/CCM.0b013e3181ffe0eb Figure 3. Evolution of lactate (top), PCO2 gap (middle), and diuresis (bottom). Squares, epinephrine-treated patients; triangles, norepinephrine-dobutamine-treated patients. +p 0 and *p < .05 epinephrine vs. norepinephrine-dobutamine.
  • 15.
    • New-onset arrhythmias were observed in three patients in the epinephrine group but in none in the norepinephrine/dobutamine group.
    • Combination NOREP/DOBU  potential benefit to selectively titrate vasoactive and inotropic hemodynamic effects.
    • This could translate into a better adherence to favorable hemodynamic corridors with an optimized balance between blood pressure and blood flow.
    • Interestingly, no globally refractory patients or patients with an increase in blood pressure but a decrease in cardiac index resulting from increased systemic vascular resistance were observed in this study.
    • In clinical practice, these patients form a group with ultimately bad prognoses and are usually seen as candidates for alternative therapeutic approaches such as the on-top addition of the calcium sensitizer levosimendan or the implantation of left ventricular assist devices.
  • 16. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2 Table 1. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study *. Levy, Bruno; MD, PhD; Perez, Pierre; Perny, Jessica; Thivilier, Carine; Gerard, Alain Critical Care Medicine. 39(3):450-455, March 2011. DOI: 10.1097/CCM.0b013e3181ffe0eb Table 1. Characteristics of the study groups (mean +/- sd)
  • 17. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2 Table 2. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study *. Levy, Bruno; MD, PhD; Perez, Pierre; Perny, Jessica; Thivilier, Carine; Gerard, Alain Critical Care Medicine. 39(3):450-455, March 2011. DOI: 10.1097/CCM.0b013e3181ffe0eb Table 2. Hemodynamic parameters
  • 18. © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. 2 Table 3. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study *. Levy, Bruno; MD, PhD; Perez, Pierre; Perny, Jessica; Thivilier, Carine; Gerard, Alain Critical Care Medicine. 39(3):450-455, March 2011. DOI: 10.1097/CCM.0b013e3181ffe0eb Table 3. Metabolic, splanchnic, and renal parameters
  • 19. Guidelines Dellinger et al. [3] Severe sepsis; septic shock 1st line vasopressors norepinephrine or dopamine; 2nd line (when 1st line ineffective) low dose AVP (0.03 U/min); stress dose steroids (200–300 mg/day) when unresponsive to fluids and vasopressors Adrenergic agonists Annane et al. [4] 330 Vasodilatory shock; septic shock No evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock Myburgh et al. [5] 280 Vasodilatory shock No difference in the achievement of an MAP goal between epinephrine and norepinephrine; potential drug-related side effects with epinephrine De Backer et al. [6] 1,679 Vasodilatory shock No significant difference in the rate of death between dopamine or norepinephrine; the use of dopamine was associated with a greater number of adverse events Vasopressin Russell et al. [9] 778 Vasodilatory shock; septic shock Overall no difference in mortality rates as compared with norepinephrine; in less severe septic shock (norepinephrine requirement C5 lg/min and B15 lg/min = 0.08–0.25 lg kg-1 min-1), the mortality rate was lower in the AVP group than in the norepinephrine group at 28 days (26.5 vs. 35.7%) Torgersen et al. [10] 50 Advanced vasodilatory shock AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock (C0.6 lg kg-1 min-1) more effectively than AVP at 0.033 IU/min Corticosteroids Bauer et al. [11] 42 Septic shock Although corticosteroids did not improve the time to withdrawal of vasopressin-containing vasopressor therapy, they significantly increased the proportion of patients alive without vasopressors at day 7 Russell et al. [12] 779 Septic shock Combination of low-dose AVP and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids Torgersen et al. [10] 50 Advanced vasodilatory shock AVP plasma levels increased in both (low and high dose AVP) groups (both P0.001), but were higher in the 0.067 IU/min group (P0.001) and in patients on concomitant hydrocortisone
  • 20.