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Resuscitating Sepsis – How I do it after CRISTAL? Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

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

Resuscitating Sepsis – How I do it after CRISTAL?

Djillali AnnaneUniversité de Versailles SQY

Université de Paris SaclayHôpital Raymond Poincaré - APHP

Page 2: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Disclosures No financial conflict of interest All works on this topic were

supported by grants from the French ministry of health

Page 3: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Risks/Benefits Colloids Versus

Risks/Benefits Crystalloids

Page 4: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Theoretical Consideration

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

Crystalloids Colloids

Goo

dB

ad

Page 5: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Colloids versus Crystalloids to achieve Resuscitation

Goals

Page 6: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

SSC 2012 Guidelines Initial Resuscitation

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.

Page 7: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

SSC 2012 Guidelines Initial Resuscitation

• 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

Page 8: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Resuscitation Goals

7

9

11

13

Cen

tral

Ven

ous

Pre

ssur

e m

mH

g

Basal Day1 Day2 Day3 Day4

AlbuminSaline

Finfer et al, NEJM 2004

<0.001<0.001<0.001 <0.001

Page 9: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Resuscitation Goals

Brunkhorst et al, NEJM 2008

Hours

Page 10: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Resuscitation Goals

Mybrugh et al, NEJM 2012

Page 11: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Resuscitation Goals

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

Page 12: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

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

Page 13: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

0

2

4

6

8ColloidCrystalloid

Time

Art

eria

l lac

tate

s (m

mol

/L)

Arterial lactate

*

*

**

Page 14: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

15

20

25

30ColloidCrystalloid

Time

Art

eria

l Bic

arbo

nate

(mm

ol/L

)Bicarbonate

*

Page 15: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

METAANALYSIS OF STARCH VS OTHER FLUIDS

Page 16: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Mortality

Rochwerg et al, Ann Intern med 2014

Page 17: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Mortality

Rochwerg et al, Ann Intern med 2014

Page 18: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Mortality

Rochwerg et al, Ann Intern med 2014

Page 19: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

RENAL ADVERSE EVENTS

Page 20: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

RIFLE: risk or worse

Page 21: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

RIFLE: injury or worse

Page 22: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

RIFLE: failure

Page 23: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Use of RRT

Page 24: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

CHEST

Page 25: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

In PracticeDesign VISEP

N=5376ES

N=798CHEST

N=6651CRISTALN=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

Subjects

Septic shock Septic shock All All

Control RL RA NS NS (86%), RL (18%)

Exp HES HES HES HES (69%), Gelatins (35%)

Primary outcome

Composite: 28-day

deaths + SOFA

Composite: 90-day deaths

+ dialysis

90-day deaths 28-day deaths

Blinding Double blind Double blind Double

blind Open

Page 26: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

In PracticeOUTCOMES VISEP

N=5376ES

N=798CHEST

N=6651CRISTALN=2857

28-day deaths NO dif NO dif NO dif NO dif

90-day deaths NO dif Crys > Col

P=0.04NO dif Col > Crys

P=0.03

RIFLE risk ?Col> Crys 0.72 [0.52,

0.99]

Col> Crys0.94 [0.90,

0.98]?

RIFLE injury ? NO DifCol>Crys0.91 [0.85,

0.97]?

RIFLE failure ? NO Dif NO Dif ?

RRTCrys > Col1.66 [1.22,

2.25]

Crys > Col1.35 [1.01,

1.80]

NO Dif1.21 [1.00,

1.45]

NO Dif0.88 [0.72,

1.08]

Page 27: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Role of Fluid Balance

Penglin et al, 2013 Sino-french Crit Care Conference

Page 28: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Role of Fluid Balance

Penglin et al, 2013 Sino-french Crit Care Conference

Page 29: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

In Practice

Sepsis Initial ResuscitationFirst 24 hours

Low risk of AKI

Crystalloids RL>NS

<3000 mL

Starches <1000mL

If more fluid neededAlbumin

Moderate to high risk of AKI

Crystalloids RL

If more fluid neededAlbumin

Page 30: Djillali Annane Université de Versailles SQY Université de Paris Saclay Hôpital Raymond Poincaré - APHP

Thank you

2nd Paris International Conference, June 7 & 8 2012