1. Prof. Jean-Louis TEBOUL Medical ICU Bicetre hospital University Paris-South France Optimal blood pressure target in septic shock

2. 1- Why do we use a vasopressor in septic shock? 2- When to initiate a vasopressor in septic shock? 3- Which MAP target in septic shock? Questions

3. Hypotension Worsening of hypoperfusion Why do we use a vasopressor in septic shock? 1- Septic shock is characterized by a decreased vascular tone (inducible NO synthase activation, etc)

4. mean arterial pressure organ blood flow Autoregulation of organ blood flow

5. 2- Profound hypotension worsens organ hypoperfusion 1- Septic shock is characterized by a decreased vascular tone (inducible NO synthase activation, etc) …… and represents an independent risk of death Why do we use a vasopressor in septic shock?

6. 65 70 75 80 Area under MAP 65 mmHg Time under MAP 65 mmHg mmHg Best predictor of 30-day mortality Area under MAP 65 mmHg

7. 2- Profound hypotension worsens organ hypoperfusion 1- Septic shock is characterized by a decreased vascular tone (inducible NO synthase activation, etc) …… and represents an independent risk of death Why do we use a vasopressor in septic shock? 3- Correction of hypotension with a vasopressor allows improving organ perfusion

8. Creatinine clearance * 0-2 hrs 4-6 hrs 60 30 54 mmHg 72 mmHg while cardiac output did not change Urine flow (ml/h) * * baseline 4 hrs 8 hrs 54 mmHg 73 mmHg 72 mmHg Blood lactate (meq/l) * * baseline 4 hrs 8 hrs 54 mmHg 73 mmHg 72 mmHg Probable “arterial pressure” effect

9. 2- Profound hypotension worsens organ hypoperfusion 1- Septic shock is characterized by a decreased vascular tone (inducible NO synthase activation, etc) …… and represents an independent risk of death Why do we use a vasopressor in septic shock? 3- Correction of hypotension with a vasopressor allows improving organ perfusion and microcirculation

11. 95 90 85 80 75 70 65 60 55 StO 2 before NEwith NE % p < 0.05 StO 2 : 75 ± 9% 82 ± 4 * healthy volunteers

12. StO 2 (%) Time End point : 0.85 x baseline StO 2 Start point : 1.05 x minimal StO 2 Start point : 0.98 x baseline StO 2 Deflation of the pneumatic cuff Inflation of the pneumatic cuff Occlusion time AUC 40 50 60 70 80 90 Desaturation slope Vascular Occlusion Test Index of recruitment of microvessels Recovery slope

13. 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 StO 2 recovery slope before NE with NE (%/s) p < 0.05 Restoration of a “good” MAP with NE resulted in recruitment of microvessels and better tissue oxygenation

14. 1- Why do we use a vasopressor in septic shock? 2- When to initiate a vasopressor in septic shock? 3- Which MAP target in septic shock? Questions

16. 1- Why do we use a vasopressor in septic shock? 2- When to initiate a vasopressor in septic shock? 3- Which MAP target in septic shock? Questions

17. mean arterial pressure organ blood flow Autoregulation of organ blood flow ? 65 mmHg?

18. MAP: 65 mmHg MAP: 85 mmHg MAP: 75 mmHg tonometry PCO 2 gap red cell velocity capillary flow urine output 150 100 50 13 %

19. Mean Arterial Pressure (mmHg) organ blood flow Autoregulation of organ blood flow 657585

20. Crit Care Med 2000; 28:2729-2732 Crit Care Med 2005; 33:780 –786 increasing MAP above 65 mmHg results in little benefit

21. Vasopressors Vasopressor therapy initially to target a MAP of 65 mmHg (grade 1C)

22. Is it dangerous to target a MAP value up to “normal values” (around 85 mmHg) in septic shock?

23. Highly variable response among patients 20 pts with septic shock

24. 20 pts with septic shock Perfused capillary density improved in pts with an altered sublingual perfusion at baseline, and decreased in patients with preserved basal microvascular perfusion.

25. Probably higher target value if: History of chronic hypertension Vasopressors Vasopressor therapy initially to target a MAP of 65 mmHg (grade 1C)

26. MAP: 65 mmHg MAP: 85 mmHg MAP: 75 mmHg tonometry PCO 2 gap red cell velocity capillary flow urine output 150 100 50 13% 10 patients none with history of severe hypertension

27. Mean arterial pressure Organ Blood flow mmHg no prior hypertension with prior hypertension 65

28. Standard therapy 76 ± 24 EGDT 74 ± 27 Base Line 0 hr 6 hrs after the start of therapy 81 ± 18 95 ± 19 * MAP 2/3 patients had chronic hypertension

29. 80-85 mmHg 65-70 mmHg

30. Asfar et al. N Engl J Med 2014

34. Probably higher target value if: History of chronic hypertension Elevated CVP Vasopressors Vasopressor therapy initially to target a MAP of 65 mmHg (grade 1C)

35. Association between elevated CVP and AKI suggests a role of venous congestion in the development of AKI

36. Microvascular flow index CVP > 12  12

37. Probably higher target value if: History of chronic hypertension Elevated CVP Elevated abdominal pressure Vasopressors Vasopressor therapy initially to target a MAP of 65 mmHg (grade 1C)

38. Target blood pressure in circulatory shock We recommend individualizing the target blood pressure during shock resuscitation. Recommendation Level 1: QoE moderate (B) We recommend to initially target a MAP of ≥ 65 mmHg. Recommendation: Level 1; QoE low (C) We suggest a higher MAP in septic patients with a history of hypertension and in patients that improve with higher blood pressure. Recommendation: Level 2; QoE low (B)

39. 1- Why do we use a vasopressor in septic shock? 2- When to initiate a vasopressor in septic shock? 3- Which MAP target? Conclusion   at least 65 mmHg   probably higher if: History of chronic hypertension Elevated CVP Increased abdominal pressure Thank you 65-85 mmHg seems to be a safe range Individualized assessment is recommended