Vasopressors in septic shock - PDF Free Download

Vasopressors in septic shock Prof. Jean-Louis TEBOUL Medical ICU Bicetre hospital University Paris-South France

Questions 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? 5- What to do in case of refractory hypotension?

Why do we use vasopressors in septic shock? Septic shock is characterized by a decreased vascular tone (inducible NO synthase activation, etc) Hypotension Hypoperfusion worsening

Autoregulation of organ blood flow organ blood flow mean arterial pressure

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

48 hrs 65 mmhg

mmhg 80 75 70 65 Area under MAP 65 mmhg Time under MAP 65 mmhg Area under MAP 65 mmhg Best predictor of 30-day mortality

during the first 24 hours

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

Autoregulation of renal blood flow renal blood flow 54 72 mean arterial pressure

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

NIRS technology

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

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

Questions 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? 5- What to do in case of refractory hypotension?

Vasopressors Norepinephrine as the first choice vasopressor (grade 1B)

Questions 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? 5- What to do in case of refractory hypotension?

140 140 120 SAP 120 100 80 MAP DAP 100 80 60 60 vasodilatation 40 20 reflects the vascular tone 40 20 low DAP Consider vasopressors When to start vasopressors? when MAP is < 65 mmhg despite adequate fluid resuscitation or when MAP is < 65 mmhg and DAP is low even if the patient has not been yet fully fluid resuscitated

Questions 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? 5- What to do in case of refractory hypotension?

Autoregulation of organ blood flow organ blood flow? 65 mmhg? mean arterial pressure

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

Autoregulation of organ blood flow organ blood flow 65 75 85 Mean Arterial Pressure (mmhg)

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

Crit Care Med 2000; 28:2729-2732 Crit Care Med 2005; 33:780 786 MAP target value: 65 mmhg

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

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

Organ Blood flow no prior hypertension with prior hypertension 65 mmhg Mean arterial pressure

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

80-85 mmhg 65-70 mmhg

Asfar et al. N Engl J Med 2014

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

Vasopressors Vasopressor therapy initially to target a MAP of 65 mmhg (grade 1C) Probably higher target value if: History of chronic hypertension Elevated CVP Elevated abdominal pressure Initial renal impairment

Pts without AKI at H 72 Pts with AKI at H 6 (n =101) Pts with AKI at H 72 Hourly MAP (mmhg) from H 1 to H 24

Pts without AKI at H 72 Pts without AKI at H 6 (n =116) Pts with AKI at H 72 Hourly MAP (mmhg) from H 1 to H 24

Is it dangerous to target a MAP value up to normal values (around 85 mmhg) in septic shock?

6 pts with septic shock Perfused Vessel Density No worsening but improvement of microcirculation for MAP target up to 85 mmhg with NE Microvascular Flow Index

Highly variable response among patients 20 pts with septic shock

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.

Questions 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? 5- What to do in case of refractory hypotension?

Vasopressors Vasopressor therapy initially to target a MAP of 65 mmhg (grade 1C) Norepinephrine (NE) as the first choice vasopressor (grade 1B) Epinephrine (added to and substituted for NE) when an additional agent is needed to maintain adequate blood pressure (grade 2B) Vasopressin (0.03 units/min can be added to NE) with intent of either raising MAP or decreasing NE dosage)

Conclusion 1- Why do we use vasopressors in septic shock? 2- Which first-line agent? 3- When to start? 4- Which therapeutic target? at least 65 mmhg probably higher value if: History of chronic hypertension Elevated CVP Elevated abdominal pressure Initial renal impairment 65-85 mmhg seems to be a safe range Thank you