1. What is the relevance of central or mixed venous oxygen saturation ? K. Reinhart MD Dept. of Anaesthesiology and Intensive Care Medicine Friedrich-Schiller-University Jena, Germany ATS / ESICM / ERS / SCCM / SRLF 7th International Consensus Conference Paris, 2006

2. Tissue hypoxia, the final common pathway of the various clinical insults that are responsible for the development of multiple systems organ failiure. W. J. Sibbald

3. Shock is defined as inadequate tissue oxygenation

4. Which are the most appropriate cardio- respiratory variables to detect and to monitor the course of tissue hypoxia in the clinical setting ?

5. What can we learn from physiology ?

6. Conventional cardio- respiratory parameters are of limited value for the assessment of the adequacy of tissue oxygenation ! Conventional cardio- respiratory parameters are of limited value for the assessment of the adequacy of tissue oxygenation !

7. The cardio-respiratory system fullfills its physiological task by guaranteeing cellular oxygen supply and to remove the waste products of metabolism Pflüger 1872

8. It was fatal for the development of our understanding of circulation, that blood flow is relatively difficult to measure, whereas blood pressure is easily measured: This is the reason why the blood pressure meter has gained such a fascinating influence, although most organs do not need pressure, but blood flow. A. Jarisch, “Kreislauffragen“ 1928

9. The two main determinants of oxygen supply to the tissues are arterial oxygen content and cardiac output

11. DO 2 ml*m -2 *min -1 1003005007009001100 n= 1232 30 60 90 120 150 180 MAP mmHg Correlation Between Arterial Pressure And Oxygen Delivery

12. DO 2 ml*m -2 *min -1 1003005007009001100 n= 1236 30 60 90 120 150 180 HR b/min Correlation Between Heart Rate And Oxygen Delivery

13. Shepard AP et al. 1973 Am.J.Physiol. 225: 747 024681012 60 100 140 180 220 260 Control A-V  O 2 vol.% Control Cardiac Output ml/ min/ kg Control Oxygen Consumption ml/ min/ kg 12 10 8 6 4

14. Reinhart K et al. (1989) Am J Physiol 257: H238 Individual points of limb O 2 uptake vs. O 2 delivery over range of progressive ischemia O 2 Uptake (ml*kg -1 *min -1 ) O 2 Delivery (ml*kg -1 *min -1 ) 2 0 4 6 8 2520151050

15. Oxygen Debt: To Pay or Not to Pay?

16. SvO 2 (%) **p < 0.01 3.5 3.0 2.5 2.0 1.5 1.0 5060708090 ** n=9n=29 n=77 n=150 n=148 n=110 n=27 Lactate (mMol/l)

17. Cardic Index l/min/m 2 A-V Oxygen Content Difference Vols. % O 2 Uptake ml/min/m 2 4 6 8 10 12 24681012 300 500 700 900 1100 Donald K.W. et al. (1954) J.Clin.Invest. 33: 1146

18. Kenneth WD et al. (1954) J.Clin.Invest. 33: 1146 Cardic Index l/min/m 2 A-V Oxygen Content Difference Vols. % O 2 Uptake ml/min/m 2 0 2 4 6 8 246810121416 100 200 300 400 500

19. The arterio-venous oxygen content difference informs on the extent to which the compensatory mechanisms of the cardio- respiratory system are exhausted

20. 2540557085100 9.3 8.2 7.1 6.0 4.9 3.8 2.7 1.6 0.5 r= -0.864 y= 12.7 -0.12x n= 1191 S  O 2 % avDO 2 ml/dl Correlation of Arterio- Venous Oxygen Content Difference with Mixed Venous Oxygen Saturation

21. Rudolph, T., et al., 1989 ScvO 2 vs. avDO 2 30405060708090100 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 r= -0.707 n= 447 avDO 2 = 11.4 -0.1*ScvO 2 ScvO 2 % avDO 2 ml/dl

22. Correlation of Oxygen - Supply to - Demand Ratio with Mixed Venous Oxygen Saturation S  O 2 % DO 2 / VO 2 2570554085100 1.0 2.8 4.6 6.4 8.2 10.0 r= 0.906 y= -9.58 + 0.19*x n= 1149

23. 75% Factors that influence mixed and central venous SO 2  VO2  DO2  DO2  VO2 Stress Pain Hyperthermia Shivering  PaO2  Hb  Cardiac output  PaO2  Hb  Cardiac output Hypothermia Anesthesia _ +

25. What can we learn from clinical studies ?

26. November 8, 2001

27. Mortality 0.0090.58 (0.38-0.87)30.546.5In-hospital P-valueRR (95% C.I.)TreatmentControl 0.030.67 (0.46-0.96)44.356.9 60-day Mortality 0.010.58 (0.39 – 0.87)33.349.2 28-day Mortality

28. Resuscitation Endpoints

29. Global Tissue Hypoxia (Cryptic Shock) Despite Normalization of Vital Signs 39.8% of control vs. 5.1% of treatment group had global tissue hypoxia (  ScvO2 and  lactate) at 6 hours.

30. S V O 2 Monitoring in Cardiac Surgery Polonen et al have studied a cohort 403 of cardiac surgical patients –The control group received standard care whilst in the protocol group, SvO 2 was maintained above 70% and lactate below 2mmol/l with fluid and inotropes –The study was undertaken in the immediate 8 hour post-operative period Polonen Anesth. Analg 2000

31. Goal oriented hemodynamic therapy in cardiac surgical patients n = 411 Goals: SvO 2 > 70% and lactate  2mmol/l from admission to the ICU and 8 hrs thereafter 6 p<0,005 7 hospital stay (days) 1,1% p<0,001 6,1% morbidity at hospital discharge n.s. ICU stay goal oriented control (Polonen et al., Anesthesia and Analgesia 2000)

32. * * % morbidity Polonen Anesth. Analg 2000 S V O 2 Monitoring in Cardiac Surgery

33. Failure of Vital Signs 31 of 36 medical shock patients: –Resuscitated to normal MAP and CVP –Have global tissue hypoxia (Scv0 2 2 mmol/L). Rady, AJEM, 1994

34. S CV O 2 Can Predict Occult Shock in CHF Patients enrolled in decompensated CHF with EF<30% No difference in vital signs or clinical category of HF between groups. Ander Am J Card 98

35. ScvO 2 is superior to CVP to reflect reduced central blood volume (Madsen et al., Scand J Clin Lab Invest 1993) before blood loss after blood loss CVP mm Hg 3 * (6 – 1) 1 (5 – -3) ScvO 2 % 75 ** (69 – 78) 60 (49 – 67)

36. S CV O 2 Monitoring in Trauma 26 consecutive patients with injury suggestive of blood loss. HR, BP, Urine output, CVP and S CV O 2 measured. Blood loss estimated. S CV O 2 most sensitive indicator blood loss S CV O 2 <65% associated with increased injury, blood loss and transfusion requirements. Scalea J Trauma 1990

37. ScvO 2 discriminates between patients with clinically indistinguishable, mildly decompensated or stable CHF Control group n = 17 High lactate n = 5 Low lactacte n = 22 ScvO 2 60 ± 6%32 ± 12%***51 ± 13% Treatment resulted in a drop in lactate by 3.65 ± 3.65 nmol/l and an increase in ScvO 2 by 32 ± 13%. (Ander et al. Am. J. Cardiol. 1988)

38. Continuous central venous ScvO 2 monitoring can reliably indicate ROSC during CPR (n = 100) Patients with ROSC had higher initial mean and maximal ScvO 2. No ROSC in patients without ScvO 2 > 30% A ScvO 2 > 75% was 100% predictive of ROSC. (Rivers et al., Ann Emerg. Med. 1992)

39. Complications in patients with high vs. low ScvO 2 after major surgery

40. Evolution of ScvO 2, base excess, and lactate in 65 patients with septic shock Parks M et al. CLINICS 2006;61(1):47

41. Does it matter wether we measure central venous or mixed venous oxygen saturation ?

43. Lee J et al. (1972) Anaesthesiology 36: 472 % Ssvc O 2 % S  O 2 100 80 60 40 20 0 406080100 r= 0.73 r= 0.88 Shock Normal

44. Reinhart K et al, Chest, 1989; 95:1216-1221 SvO 2 closely correlates with ScvO 2 Zeit (min) % Sat 80 60 40 20 0 3006090120150180210240 Normoxie Blutung Volumentherapie (HAES) Blutung Hypoxie Normoxie Hyperoxie Gemischt-venösZentral-venös

45. t (min) % 2030405060100 SvO 2 50 60 70 80 90 100 40 ScvO 2

46. Zeit (min) % 0102030 40 50 60 70 80 90 100 ScvO 2 SvO 2

47. All Determinations Scheinmann MM et al. 1969 Circulation 40: 165  M.V. O 2 - % Saturation  R.A. O 2 and  C.V. O 2 - %Saturation R.A. O 2 (r= 0.95) C.V. O 2 (r= 0.90)

48.  SvO 2 % Sat  ScvO 2 % Sat 80 60 40 20 0 -20 -40 -60 -80 -60-40-20020406080 r= 0.9761 p< 0.001 n= 131 Reinhart K et al, Chest, 1989; 95:1216-1221

49. Changes in SvO 2 and ScvO 2 in general anesthesia during neurosurgery Conclusion: Despite some large differences between absolute values, in patients with varying hemodynamic situations, the trend in ScvO 2 may be used as a surrogate variable for the trend in SvO 2. Dueck MH et al. Anesthesiology 2005; 103:249

50. Changes in mixed venous oxygen saturation are well matched by changes in central venous oxygen saturation !

51. Differences between SvO 2 and ScvO 2 in different patient groups  SO 2 n = number of measurements high risk surgical n = 18 7,25 %220 313 septic shock n = 11 7,90 %148 534 severe head injury n = 3 10,7 %26 281 Reinhart K et al., unpublished

52. SvO 2 - ShO 2 [%] SvO 2 [%] Differences between mixed venous and hepato-venous O 2 saturation in patients with septic shock -10 0 10 20 30 40 606264666870727476788082 Normalbereich

53. Percentage of splanchnic O 2 consumption from total body O 2 consumption in septic shock patients 60% (n=34)

54. In patients with severe sepsis or septic shock a goal of 70% for central venous oxygen saturation corresponds to a mixed venous oxygen saturation between 60 and 65% !!!

55. Does it matter wether we measure central venous oxygen saturation continuously or discontinuously ?

56. Lee J et al. (1972) Anaesthesiology 36: 472 % Ssvc O 2 % S  O 2 100 80 60 40 20 0 406080100 r= 0.73 r= 0.88 Shock Normal

57. Does it matter wether we measure central venous oxygen saturation continuously or discontinuously and is continuous measurement costeffective ?

58. Blood gas analyses in patients with severe sepsis and septic shock Central venous blood gas analysis Total amount all patients; all days 16,936 Average amount during ICU stay (range) 76.9 (1-393) Average amount per patient and day 1 3.5 1 : average ICU length of stay 21.5 days All patients with severe sepsis or septic shock between April 2004 and May 2005 (n=221) Average costs per patient (Euro) approx. 300,00

59. Cost assessment for central venous blood gas analysis Costs of a single analysis: 2.12 € Blood gas analysis: 1.80 € Closing cones: 0.02 € 2 x 5cc syringes:0.05 € Heparinized tube:0.25 € 163,24 €/patient (estimating an average of 77 analyses/patient) 6 min from begin of withdrawal until analysis is available Average time needed for measurements per patient 7.7 h/patient Cost for nurse per day approx. 135 €

60. Blood gas analyses in patients with severe sepsis and septic shock Arterial blood gas analysis Central venous blood gas analysis Total amount all patients; all days 42,52016,936 Average amount during ICU stay (range) 192.4 (5-1108)76.9 (1-393) Average amount per patient and day 1 8.93.5 1 : average ICU length of stay 21.5 days All patients with severe sepsis or septic shock between April 2004 and May 2005 (n=221)

61. Limitations of mixed and central venous oxygen saturation for the assessment of tissue oxygenation

62. pHi rCO 2 Hepatic venous blood flow (splanchnic blood flow) ICG-clearance MEGX-test Hepatic venous O 2 -saturation

65. Transcutaneous liver near infrared spectroscopy (TOI) in 20 children during surgical hemorrhage TOI Liver provided a better trend monitor of central venous oxygen saturation than gastric intramucosal pH. Because of its limited sensitivity and specificity to indicate deterioration of SvO 2, liver tissue oxygenation measured by transcutaneous NIRS does not provide additional practical information for clinical management. Weiss M et al. Pediatric Anesthesia 2004; 14: 989

66. Correlation between central venous oxygen saturation and near-infrared spectroscopic cerebral oxygenation (cTOI) in 43 critically ill children Nagdyman N. et al. Intensive Care Med (2004) 30:468

67. Inadequate tissue oxygenation may exist on the regional and organ level despite normal central and mixed venous oxygen saturation

68. Summary ScvO 2 and SvO 2 are superior to conventional hemodynamic monitoring parameters in the assessment of the adequacy of global tissue oxygenation Continuous monitoring of ScvO 2 and SvO 2 in the framework of hemodynamic goals and treatment algorithms have resulted im improved patient outcome ScvO 2 closely parallels SvO 2 saturation In patients with shock ScvO 2 is 7 – 10% (mean) higher than SvO 2 These differences between ScvO 2 and SvO 2 saturation result from changes in the regional blood flow and oxygen supply/demand ratio Normal or high ScvO 2 and SvO 2 do not rule out tissue hypoxia on the organ or regional level

70. Patient Enrollment