1. Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

2.  No financial conflict of interest  All works on this topic were supported by grants from the French ministry of health

3. Risks/Benefits Colloids Versus Risks/Benefits Crystalloids

4.  Inexpensive  Non-allergic  Depleted ECF  No transmission of infection  No effect on coagulation  Edema  Short half life  Chlorid acidosis  Prolonged plasma volume expansion  More rapid  Less edema  Decreased efficacy if capillary leaks  Allergic  Infection risk  Coagulopathy  Kidney problems  Cost CrystalloidsColloids Good Bad

6.  We recommend the protocolized, quantitative resuscitation of patients with sepsis- induced tissue hypoperfusion (defined as hypotension persisting after initial fluid challenge or lactate ≥ 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission.

7. During the first 6 hours of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as a part of a treatment protocol Grade 1C – CVP 8–12 mm Hg – MAP ≥ 65 mm Hg – Urine output ≥ 0.5 mL/kg/hour – Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively

8. Finfer et al, NEJM 2004 <0.001

9. Brunkhorst et al, NEJM 2008 Hours

10. Mybrugh et al, NEJM 2012

11. G. Martin, Crit Care Med 2002; 30: 2175 KA Powers, Crit Care Med 2003; 31: 2355

12. SSC 2012 Guidelines Initial Resuscitation We suggest, in patients with elevated lactate levels as a marker of tissue hypoperfusion, targeting resuscitation to normalize lactate as rapidly as possible Grade 2C

13. Arterial lactate * * * *

14. Bicarbonate *

16. Rochwerg et al, Ann Intern med 2014

25. Design VISEP N=537 6ES N=798 CHEST N=6651 CRISTAL N=2857 Setting 18 academic tertiary hospitals in Germany 26 university & non- university hospitals in Denmark, Norway, Finland, Iceland 32 hospitals in Australia and New Zeland 57 academic and non academic hospitals, in France, Belgium, Canada, Algeria, Tunisia,UK SubjectsSeptic shock All ControlRLRANS NS (86%), RL (18%) ExpHES HES (69%), Gelatins (35%) Primary outcome Composite: 28-day deaths + SOFA Composite: 90-day deaths + dialysis 90-day deaths 28-day deaths BlindingDouble blind Open

26. OUTCOMES VISEP N=537 6ES N=798 CHEST N=6651 CRISTAL N=2857 28-day deathsNO dif 90-day deathsNO dif Crys > Col P=0.04 NO dif Col > Crys P=0.03 RIFLE risk? Col> Crys 0.72 [0.52, 0.99] Col> Crys 0.94 [0.90, 0.98] ? RIFLE injury?NO Dif Col>Crys 0.91 [0.85, 0.97] ? RIFLE failure?NO Dif ? RRT Crys > Col 1.66 [1.22, 2.25] Crys > Col 1.35 [1.01, 1.80] NO Dif 1.21 [1.00, 1.45] NO Dif 0.88 [0.72, 1.08]

27. Penglin et al, 2013 Sino-french Crit Care Conference

29. Sepsis Initial Resuscitation First 24 hours Low risk of AKI Crystalloids RL>NS <3000 mL Starches <1000mL If more fluid needed Albumin Moderate to high risk of AKI Crystalloids RL If more fluid needed Albumin

30. 2nd Paris International Conference, June 7 & 8 2012