Benoit Vallet Anesthesiology and Critical Care University Hospital of Lille France

1. 8th International Consensus Conference Hemodynamic Monitoring in Shock and Implications for Management How Does Hemorrhagic, Cardiogenic and Septic Shock Differ? Benoit Vallet Anesthesiology and Critical Care University Hospital of Lille France bvallet@chru-lille.fr

2. VO2: O2 consumed; 95% to synthesize ATP DO2: O2 delivered ERO2: O2 extracted VO2 = DO2. ERO2

3. VO2 = DO2. ERO2

4. VO2 = Q .CaO2. ERO2

5.  in intravascular volume: hypovolemic shock;  Q;  DO2  in cardiac output: cardiogenic shock;  Q;  DO2  in SaO2: hypoxemic shock;  CaO2;  DO2  in Hb: hemorrhagic shock; CaO2;  Q;  DO2 Abnormal tissue perfusion: distributive shock;  ERO2 Altered O2 utilization: cytopathic shock;  ERO2 Result in unmet O2 needs ( VO2)to sustain cell mitochondrial function, i.e. ATP synthesis (= dysoxia) VO2Q. Hb . SaO2. 1.39. ERO2

6. A-464 A-465 A-466 A-467 DYSOXIA A-468 A-469 DO2crit: 6.0 ± 0.5 Regional Ischemic Hypoxia: Low Q Vallet et al. J Appl Physiol 2000;89:1317-21 10 8 6 Limb O2 Uptake (ml.kg-1. min-1) 4 2 0 5 10 15 20 25 Limb O2 Delivery (ml.kg-1. min-1)

7. A-293 A-296 A-302 A-303 DYSOXIA A-304 A-305 DO2crit: 6.9 ± 0.6 Regional Hypoxic Hypoxia: Low CaO2 Vallet et al. J Appl Physiol 2000;89:1317-21 10 8 6 Limb O2 Uptake (ml.kg-1. min-1) 4 2 0 5 10 15 20 25 Limb O2 Delivery (ml.kg-1. min-1):

8. DO2crit 4 ml/kg.min ERO2crit VO2-to-DO2 Relationship and SvO2 in ICU PatientsRonco et al. JAMA 1993;270:1724-30 VO2 2.4 ml/kg.min DO2 ERO2 0.60 DO2

9. VO2-to-DO2 Relationship and SvO2 in ICU PatientsRonco et al. JAMA 1993;270:1724-30 VO2 4 ml/kg.min DO2 ERO2 0.60 : SvO2 = 0.40 DO2

10. Identifying Dysoxia at the Bedside SvO2

11. 4 situations responsible for a  in SvO2: SaO2  Q  Hb  VO2 not compensated by DO2  VO2 Hb . 1.39 . Q SvO2 SaO2 -

12. SvO2: a “gross estimation” of the VO2-to-DO2 relationship SvO2 as ERO2  ERO2 = VO2/DO2 (SaO2 - SvO2)/SaO2 When SaO2 = 1, ERO2 1- SvO2 When ERO2 is 60%, SvO2 is 40% VO2-to-DO2 Relationship and SvO2 in ICU Patients

13. Redistribution of blood flow among organs via  in sympathetic adrenergic tone and central vascular contraction [ Q in low ERO2 organs (skin, gut, kidney) and maintained Q in high ERO2 organs (heart, brain)] Capillary recruitment within organs responsible for peripheral vasodilation (opposite to central vasoconstriction) ERO2 via 2 Fundamental Adaptive Mechanisms

14. O2 Extraction: Role of Vasoconstrictor Tone Connolly et al. J Clin Invest 1997;99:228-38

15. Vascular Endothelium and Tissue PerfusionCurtis SE, Vallet B, Winn MJ, et al. J Appl Physiol 1995;79:1351-60  NO et PGI2  Hyperpolarization, microcirculatory embolization, endothelial edema…

16. Pathological Supply Dependence of O2 Uptake during Bacteremia Nelson et al. J Appl Physiol 1987;63:1487-92 CONTROL BACTEREMIC

17. When ERO2 and SVR , shock is associated with preserved vascular reactivity: Hemorrhagic shock Cardiogenic shock When ERO2 and SVR do not , shock is described as associated with non preserved vascular reactivity: Anaphylactic shock Septic shock As Q 

18. CONTROL ENDOTOXIN Hyperemia + Hyperemia - Gut Mucosa Perfused Capillary Density during Endotoxemia Drazenovic et al. J Appl Physiol 1992;72:259-65 ERO2 > 65% ERO2 < 50%

19. Gut DO2 and VO2 in Hemorrhaged or Endotoxemic Dogs Curtis et al. Am J Physiol 1992;262:H778-86 Vallet et al. J Appl Physiol 1994;76:793-800 DO2 (ml/kg.min) VO2 (ml/kg.min) VO2 (ml/kg.min) DO2 (ml/kg.min)

20.  DO2 with  VO2 and  ScvO2?  Low cardiac output?

21. Yes  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

22. Quantitative shock  Q Yes  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

23. Quantitative shock  Q Yes  Elevated preload?  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

24. Cardiogenic or obstructive shock Yes Quantitative shock  Q Yes  Elevated preload?  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

25. Cardiogenic or obstructive shock Yes Quantitative shock  Q Yes  Elevated preload? No Hypovolemia  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

26. Cardiogenic or obstructive shock Yes Quantitative shock  Q Hypovolemia No Yes  Elevated preload? Hemorrhagic shock  Hb Yes  DO2 with  VO2 and  ScvO2 ?  Low cardiac output? Hemorrhage?

27. Cardiogenic or obstructive shock Yes Quantitative shock  Q Hypovolemia No Yes Hemorrhagic shock  Hb Yes Hemorrhage? Hypovolemic shock Fluid losses (gut, kidney, fever…) No  Elevated preload?  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

28. Quantitative shock  Q Yes Cardiogenic or obstructive shock Yes  Elevated preload? Hypovolemia No Hemorrhagic shock  Hb Yes  DO2 with  VO2 and  ScvO2 ?  Low cardiac output? Hemorrhage? Hypovolemic shock Fluid losses (gut, kidney, fever…) No No

29. Cardiogenic or obstructive shock Yes  Elevated preload? Quantitative shock  Q Hypovolemia No Yes Hemorrhagic shock  Hb Yes Hemorrhage Hypovolemic shock Fluid losses (gut, kidney, fever…) No No Acute respiratory failure?  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

30. Cardiogenic or obstructive shock Yes  Elevated preload? Quantitative shock  Q Hypovolemia No Yes Hemorrhagic shock  Hb Yes Hemorrhage Hypovolemic shock Fluid losses (gut, kidney, fever…) Hypoxemia  SaO2 No Yes No Acute respiratory failure?  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

31. Cardiogenic or obstructive shock Yes  Elevated preload? Quantitative shock  Q Hypovolemia No Yes Hemorrhagic shock  Hb Yes Hemorrhage Hypovolemic shock Fluid losses (gut, kidney, fever…) Hypoxemia  SaO2 No Yes No Acute respiratory failure? Infection  Septic shock Distributive shock  ERO2 No Cytopathic hypoxia Allergy  Anaphylactic shock  DO2 with  VO2 and  ScvO2 ?  Low cardiac output?

32. Cardiogenic or obstructive shock Yes  Elevated preload? Quantitative shock  Q Hypovolemia No Yes Hemorrhagic shock  Hb Yes  DO2 with  VO2 and  ScvO2?  Low cardiac output? Hemorrhage Hypovolemic shock Fluid losses (gut, kidney, fever…) Hypoxemia  SaO2 Yes No No Acute respiratory failure? Infection  Septic shock Distributive shock  ERO2 No Cytopathic hypoxia Allergy  Anaphylactic shock

33. Identifying Dysoxia at the Bedside Lactate Base excess DPCO2

34. ** VO2 (ml/kg.min) * * * * * 6 * 4 * 2 DO2crit Lactate (mM/l) * 6 * * 4 * ** * * 2 * ** DO2crit DO2crit P(v-a)CO2 (mmHg) * 20 * 15 ** * * * ** DO2(ml/kg.min) 5 10 20 30 VO2, Lactate and P(v-a)CO2 to DO2 Relationship during Hemorrhage Van der Linden et al. Anesth Analg 1995;80:269-75

35. Pathological Supply Dependence of O2 Uptake during Bacteremia Nelson et al. J Appl Physiol 1987;63:1487-92 CONTROL BACTEREMIC

36. Low Q vs low CaO2

37. Arterial Lactate during Ischemic or Hypoxic Hypoxia Nevière R, Chagnon JL, Teboul JL, Vallet B, Wattel F. Crit Care Med 2002;30:379-84

38. 6 30 5 20 4 mean ± SEM IH * p<0.05 vs HH HH 3 10 2 1 0 0 2 4 6 8 10 2 4 6 8 10 0 VO2-to-O2 Delivery Relationship and P(v-a)CO2 during Regional Ischemic or Hypoxic Hypoxia Vallet et al. J Appl Physiol 2000;89:1317-21 Limb O2 uptake (ml/kg.min) Limb PCO2 (mmHg) * * * * DO2 crit IH: 6.0 ± 0.5 DO2 crit HH: 6.9 ± 0.6 DO2 crit IH DO2 crit HH Limb O2 delivery (ml/kg.min) Limb O2 delivery (ml/kg.min)

39. Limb DpH 0.18 0.16 mean ± SEM 0.14 * * p<0.05 vs HH 0.12 IH * HH 0.10 * 0.08 0.06 0.04 0 2 4 6 8 10 Limb O2 delivery (ml/kg.min) DpH-to-O2 Delivery Relationship during Regional Ischemic or Hypoxic Hypoxia Vallet et al. J Appl Physiol 2000;89:1317-21 DO2 crit IH DO2 crit HH

40. Muscle vs gut

41. DYSOXIA DYSOXIA DYSOXIA DYSOXIA GMBF (perfusion units) P(r-a)CO2 (Torr) Hypoxemia Hypoxemia 60 30 40 20 10 20 0 0 0 10 20 30 0 10 20 30 DO2 (mL/kg.min) DO2 (mL/kg.min) Gut-to-Arterial CO2 Gap during Ischemic or Hypoxic Hypoxia Nevière R, Chagnon JL, Teboul JL, Vallet B, Wattel F. Crit Care Med 2002;30:379-84 GMBF (perfusion units) P(r-a)CO2 (Torr) Ischemia Ischemia 60 30 40 20 10 20 0 0 0 10 20 30 0 10 20 30 DO2 (mL/kg.min) DO2 (mL/kg.min)

42. DPCO2 helps in identifying low flow

43. SvO2vsDPCO2 and lactate:clinical studies

44. SvO2(%) 49+2 57+3 61+2 60+2 113+9 112+11 112+8 127+10 Cardiac Index, VO2, SvO2, and P(v-a)CO2 Relationships: Dobutamine Effects Teboul et al. Crit Care Med 1998;26:1007-10 VO2 (ml/min.m2)

45. Combination of P(v-a)CO2 with Arteriovenous O2 Content Mekontso-Dessap et al. Intensive Care Med 2002;28:272-77 ROC analysis (lactate >2mmol/L) DPCO2/C(a-v)O2: higher in Lac+ ( n=73): 2.0+0.9 vs. 1.1+0.6, p<0.0001); threshold value: 1.4

46. In septic shock, despite increased Q and SvO2 DPCO2 and lactate suggest  microcirculatory flow and perfusion heterogeneity

47. Excessive activation of cells (macrophages, neutrophils, and endothelial cells) and over-production of pro-inflammatory mediators (prostanoids, NO, kinins) and pyrogens lead to vasodilatation, vascular hyporeactivity (i.e. decreased responsiveness to catecholamines) and capillary leak with third space losses

48. Endotoxin-Induced Impaired Villus Microcirculation in Pigs Tugtekin et al. Intensive Care Med 2001;27:757-66 Baseline: DP(r-a)CO2 = 15 (8-17) mmHg

49. Endotoxin-Induced Impaired Villus Microcirculation in Pigs Tugtekin et al. Intensive Care Med 2001;27:757-66 12 hours of LPS infusion DP(r-a)CO2 = 18 (15-26) mmHg

50. Relationship between Gastric Mucosal Blood Flow and P(r-a)CO2 in Sepsis Nevière et al. Am J Respir Crit Care Med 1996;154:1684-8 45 40 35 30 25 Gastric intramucosal- arterial PCO2(mmHg) 20 15 10 5 0 0 100 200 300 400 500 Gastric mucosal blood flow (mvolts)