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Vasopressors in septic shock russie 2012
- 1.
- 2. Claude Martin Nord UniversityHospital Marseilles France (ICU and Trauma Center)
- 8. Septic Shock Absolutehypovolemia relative hypovolemia Distributive shock : area of VD/VC Cardiac dysfonction O2 extraction abnormalities
- 9. CCM , 2008, 36 , 296-327
- 10. CCM , 2008, 36 , 296-327
- 11. Initial Resuscitation MAP 65 mmHg CVP 8 - 12 mmHg UF 0.5 ml.kg-1.hr-1 ScvO2 70% SvO2 65% GRADE 1B
- 12. Treatment of Septic shock Hemodynamic source control managment Antibiotics Surgery Fluids Vaso-active drainage agents
- 13. Therapeutic Targets andTools Vessels : norepinephrine epinephrine dopamine Volemia : Fluid challenge Heart : dobutamine norepinephrine Rescue therapy : Vasopressin, terlipressin Microcirculation : Nitroglycerin ???
- 14. VASOPRESSORS Dopamine Epinephrenine Norepinephrine Vasopressin Terlipressin
- 15. Initial Resuscitation CCM , 2008 , 36 , 296-327 MAP 65 mmHg CVP 8 - 12 mmHg UF 0.5 ml.kg-1.hr-1 ScvO2 70% SvO2 65% Grade 1B
- 16. •Is venous return optimal ?????????
- 17. Fluid challenge Fluid challenge MAP (driving force) Venous return and ventricular preload SV
- 19. Fluid challenge Respiratory variation under MV Parameter threshold SAP 10 mmHg or 9% down 5 mmHg PP 12-13 % SVV 9-10% CVP < 5 mmHg French Consensus Conference 2005
- 20. Stroke Volume Variation SVmax SV min SV mean SV max + SV min SVV = 2
- 21. Pulse Pressure Variations ∆PP Michard et al. Am J Respir Crit Care Med PPmax 2000 PPmin
- 22. Fluid challenge Respiratory variation under MV Parameter threshold SAP 10 mmHg or 9% down 5 mmHg PP 12-13 % SVV 9-10% CVP < 5 mmHg French Consensus Conference 2005
- 23. Fluid Responsiveness inSpontaneously Breathing Patients PP No SVV !!! Teboul JL 8th Int. Consensus Conference ATS/SRLF/ERS/SCC/Esicm, Paris 27-28 April 2006
- 24. •Passive leg raising with > 12% increase in CO by PiCCO or oesophageal Döppler
- 25. Vasopressors Norepinephrine or Dopamine
- 26. 32 patients randomized: dopamine (Until 25 µg/kg/min) or norepi ( Until 5 µg/kg/min) Objective (n=11) success (n=5) failure : MAP > success (n=15)for failure (n=1) 80 mmHg 6h 10 to 25 µg/kg/min 25 µg/kg/min 1.5±1.2 µg/kg/min 5 µg/kg/min increase in urine output increase in urine output decrease in lactate decrease in lactate 10 (n=16) Norepi (n=16) Dopasuccess with Dopa + Norepi (25 µg/kg/min +1.7±1.8 µg/kg/min) Chest 1993, 103:1826-31
- 27. Dopamine or Norepinephrine? 93% 69% P < 0.001 31% 7% p < O.,001 Success Failure Success Failure Dopamine Norepinephrine C. Martin et al Chest 1993, 103, 1826
- 28. Dopamine or Norepinephrine? Hyperdynamic septic shock Dopamine Norepinephrine (2.5-25 mg (0.5-5.0 mg/kg/min) /kg/min) 16 patients 16 patients success : 5/16 (31%) p<0.001 success : 15/16 (93%) failure : 11/16 failure : 1/16 success : 0/1 success : 10/11 C. Martin et al Chest 1993, 103, 1826
- 29. Resistance to Dopamine 110patients MAP < 70 mmHg with 20 mg/kg/min 60% P < 0.001 40% Dopa S Dopa R Levy et al CCM 2005, 33.
- 30. Resistance to Dopamine Levy et al CCM 2005, 33
- 31. DOPAMINE vs NOREPINEPHRINE SOAPstudy 1058 pts in shock Mortality * * % 50 * 50 * P<0.05 40 43 45 42 36 37 30 20 10 0 ICU 30 Days Hospital Sakr et al Dopamine No dopamine CCM 2006
- 32. Dopamine for septic shock ??? Failure of Dopamine
- 35. Dopamine ou noradrénaline? N Engl J Med 2010 De Backer et al., N Engl J Med 2010
- 37.
- 38. Dopamine or Norepinephrine? Hyperdynamic septic shock Dopamine Norepinephrine (2.5-25 mg) /kg/min (0.5-5.0 16 patients mg/kg/min) success : 5/16 (31%) p<0.001 16 patients failure : 11/16 success : 15/16 -93%) success : 0/1 failure : 1/16 success : 10/11 C. Martin et al Chest 1993, 103, 1826
- 39. % Survival Septic Shock : 100 Norepinephrine 90 80 70 60 Norepinephrine 50 40 p < 0.0001 30 20 Martin C et al Crit Care Med 10 Other vasopressors 2000 , 28 , 2758 . 0 0 5 10 15 20 25 30 35 40 45 50 Days
- 44. Adrénaline ou noradrénaline? Noradrénaline Adrénaline
- 45. Adrénaline ou noradrénaline? Catécholamine utilisée en première ligne Noradrénaline Dopamine Adrénaline 158 (57%) 102 (37%) 22 (8%)
- 50. •Dopamine or Norepinephrinein Human Hyperdynamic Sepsis ? 700 * 200 * 190 650 * DO2 180 VO2 600 170 160 * 550 H0 150 H0 H6 H6 140 500 130 450 120 110 400 NE Dopa 100 * NE Dopa 7,3 7,25 * pHi 7,2 H0 7,15 H6 7,1 Marik JAMA 1994 , 272 , 1354 7,05 NE Dopa
- 52. Effects of Norepinephrine on Renal Function 200 250 180 160 200 140 120 150 100 Before NE Before NE 100 During NE 80 During NE 60 50 40 20 0 Urine Serum Creat 0 flow creat clear Urine flow Serum creatinine creat clearance Martin et al Desjars et al 1990 1989
- 53. Vasopressors Epinephrine is an alternative
- 54. CATS Study (Epinephrine/ norepi-dobu) Epinephrine Norepi-dobu n = 161 (n = 169) Hospital survival Hospital survival 47.8% 51.5% Power 90% p = 0.51 D. Annane et al Lancet 2007
- 56. Metaraminol ? Norepinephrinetreated patients switched to metaraminol (NE : 0.3 + 0.28 µg/kg/min, Meta : 2.5 + 1.7 µg/kg/min) = MAP = CI (70/71) (3.7/3.6) = SvO2 (72/72) Natalini et al ICM 2005, 31, 634-637
- 59. In caseof failure ???
- 60. a1-AR AC AC a b g a Gs protein b g P P P Receptor arrestin resensitization clathrin Receptor endosome Receptor internalization Receptor degradation dephosphorylation
- 61.
- 62. Vasopressors Vasopressin : no recommendation Avoid high-dose 2B
- 64. Norepinephrine > 15mcg/min
- 65.
- 69. Terlipressin? 15 patients with catecholamine - resistant septic shock: NE ( 2.2 mcg/kg/min ) dopamine ( 25 mcg/kg/min ) Terlipressin 1 or 2 bolus of 1 mg MAP CI l/min/m2 mmHg 5.3+/-1.2 84+/- 6 4.7+/-1.3 55+/- 5 P< 0.01 NE + dopa TER NE + dopa TER 1147+/-134 SVRI dyn.sec 654+/-108 .cm-5.m-2 NE + dopa TER Leone,, Martin Shock 2004,22,3146319
- 70. 15 patientswith catecholamine - resistant Terlipressin ? septic shock: NE ( 2.2 mcg/kg/min ) dopamine ( 25 mcg/kg/min ) Terlipressin 1 or 2 bolus of 1 mg UF ml/h 76+/-21 Cr Cl ml/min 47+/-36 15+/-12 21+/-15 baseline TER baseline TER Leone,, Martin Shock 2004,22,3146319
- 71. Survival ?
- 72.
- 73.
- 74. 150 Renal Blood Flow Renal Autoregulation (% baseline) in Disease Control 3 weeks 100 1 week 50 0 20 40 60 80 100 Renal Artery Pressure (mmH g)
- 75. 150 Renal Blood Flow Renal Autoregulation (% baseline) in Disease Control 3 weeks 100 1 week 50 0 20 40 60 80 100 Renal Artery Pressure (mmH g)
- 76. 150 Renal Blood Flow Renal Autoregulation (% baseline) in Disease Control 3 weeks 100 1 week 50 0 20 40 60 80 100 Renal Artery Pressure (mmH g)
- 77. 150 Renal Blood Flow Renal Autoregulation (% baseline) in Disease Control 3 weeks 100 1 week 50 0 20 40 60 80 100 Renal Artery Pressure (mmH g)
- 78. 65 85
- 79. Lactate Increasing MAP ? 65 DO2 85 VO2 A Bourgoin et al CCM 2005,33,780-786
- 80. UF Increasing MAP ? 65 Creatinine 85 Cr Cl A Bourgoin et al CCM 2005,33,780-786
- 83. Conclusions : Prefere norepinephrine Dopamine??????? Epinephrine 2 nd line Vasopressin and terlipressin : rescue therapy Have a protocol
- 84.