Sino-Fr Symposium - Oct 07C. Brun-Buisson Surviving Sepsis Barcelona declaration (ESICM congress, 2002) Surviving Sepsis Campaign Guidelines (CCM & ICM,

Sino-Fr Symposium - Oct 07 C. Brun-Buisson

“Surviving Sepsis”

• Barcelona declaration (ESICM congress, 2002)• Surviving Sepsis Campaign Guidelines (CCM & ICM, 2004) • SSC guidelines Version 2

Crit Care Med 2004; 32: 858-73.Intensive Care Med 2004 ; 30 : 536.


Potential conflicts of interestPotential conflicts of interest

« The challenges involved in producing first-rate guidelines and performance standards are only exacerbated by the intrusion of marketing strategies masquerading as evidence-based medicine. »

NEJ M 2006; 355: 1640-42.NEJ M 2006; 355: 1640-42.


240

83

Severe Sepsis: 34%

G.Martin et al, NEJM 2003; 348: 1546-54.

Population-adjusted Incidence of Sepsis, USA, 1979-2000

Severe Sepsis: 34%

France: Choc septique 9%

“Surviving Sepsis”?

1. Identification & initial 1. Identification & initial assessmentassessment

Recommandations SFAR – SRLF 2006


SIRS and Organ Dysfunction Criteria

SIRS: Conventional criteria• Fever / hypothermia• Tachypnea• Tachycardia• Leukocytosis / leukopenia

Others• Biomarkers:

Elevated PCT, ..

Organ dysfunctions- lactates > 4 mmol/l - SBP < 90 mm Hg - PaO2/FiO2 < 300 - Oliguria, creatinine > 176 mmol/L - INR > 1,5 / PT > 60 sec - thrombocytopenia < 100 000/mm3 - bilirubin > 34 µmol/l - Glasgow coma score ≤ 13

But < 50% of patients with SIRS have documented infection


Infection/Sepsis: Initial assessment

Biochemistry HematologyAnd coagulation

TachycardiaTachypnea

Fever orhypothermia

Skin perfusion

Neurologic status

Arterial pressure

Urine output

Lactate

Sev Sepsis?

Initial assessment (H0-H3)

Evaluation

of

sepsis



Algorithm for disposition of patients in ED Suspected

Severe Sepsis

Organ failure?Organ failure?

Monitoring HR, RR, AP, Urine Oxygen to SpO2>95% Biochemistry (lactate) & microbiology Cristalloids (500 ml/15 min) to mAP >65 Call referent intensivist

ICU Admission

Urine < 0,5 ml/kg/h ?

Urine < 0,5 ml/kg/h ?mAP < 65 ?mAP < 65 ?

YESYES YESYES

YESYES

Clinical Hypoperfusion

?

Clinical Hypoperfusion

?

mAP <65 ? mAP <65 ?

Lactate >4 ? Lactate >4 ?

Comorbidity ? Comorbidity ?

Etiology at risk ? Etiology at risk ?

YESIYESI

YESYES

YESYES

YESYES

YESYES

YESYES

Acute care areaMaintain non-invasive

monitoring + urine output

NoNo

NoNo

NoNo

NoNo NoNo

NoNo



Infection/Severe Sepsis: initial steps

Sev Sepsis ?

0 – 3 hrs

Source Control:Drainage?Surgery?

Re-assessment oforgan dysfunctions

Antibiotics

Blood cultures + site samples

Fluid Challenge

Imaging?


“Surviving Sepsis Campaign”

2. Recommendations and 2. Recommendations and Guideline Revision (2006-07)Guideline Revision (2006-07)

Sponsored exclusively by supporting societies


Impact on survival of early antibiotic administration

Kumar et al, Kumar et al, Crit Care Med 2006Crit Care Med 2006; 34: 1589-96; 34: 1589-96

Time (hrs)

Od

ds

Ra

tio o

f D

ea

th(9

5%

Co

nfid

en

ce I

nte

rval)

1

10

100



E. Rivers, 2001 - EGT


EGT – Mortality rates

46,549,2

56,9

30,533,3

44,3

20

25

30

35

40

45

50

55

60

Hospital 28 days 60 days

Control EGT

**

*

RR = 0.58 0.58 0.67 P = 0.01 0.01 0.03

E. Rivers et al, NEJM 2001


3,5

10,6

13,4

5,0

8,6

13,4

0

2

4

6

8

10

12

14

16

0-6 hours 6-72 hours 0-72 hours

Liters

ControlEGT

EGT - Volume of fluid infused

* P<0.01* P<0.01* P<0.01* P<0.01****

**

E. Rivers et al, NEJM 2001


Fluid Therapy

• We recommend fluid resuscitation with either natural/artificial colloids or crystalloids.

• There is no evidence-based support for one type of fluid over another. 1B

Supportive Care: Glucose Control

• Recommend glucose control with intravenous insulin after initial stabilization 1B

• Suggested glucose target: Normal and < 150 mg/dL 2C



Potential conflicts of interestPotential conflicts of interest

Pour un moratoire sur l’utilisation des hydroxyéthylamidons

L. Brochard1, F. Schortgen1, C. Brun-Buisson1, D. Dreyfuss2, J.-J. Rouby3, J. Chastre4, D. Robert5, G. Hilbert6, D. Payen7, E. L’Her8, C. Richard9, M. Gainnier10, J. Pugin11, J.-C. M. Richard12.

ConclusionLes données dont nous disposons actuellement suggèrent fortement que la balance entre les bénéfices attendus et les risques observés avec l’administration des hydroxyéthylamidons est défavorable. Dans ces conditions, il ne parait pas justifié de continuer à utiliser ces produits pour le remplissage vasculaire en réanimation, alors que des alternatives moins toxiques (et moins coûteuses) sont disponibles. Il ne s’agit pas à notre sens d’une querelle d’experts, et nous suggérons à titre protecteur qu’un moratoire soit mis en place sur l’utilisation des hydroxyéthylamidons dans le remplissage vasculaire chez les patients de réanimation, dans l’attente de nouveaux essais démontrant de manière convaincante leur avantage et leur innocuité.


Vasopressors

• We recommend either norepinephrine or dopamine as the first choice vasopressor agent to correct hypotension in septic shock (administered through a central catheter as soon as one is available) (1C)

• We suggest that epinephrine, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock (2C).


SSC: Objectives for the first 6 hours

1. Mesure arterial lactate level2. Obtain blood cultures before administering

antibiotics3. Prescribe within 3 (1) hrs broad-spectrum

empiric antibiotic therapy 4. If hypotension (PAS < 90 mmHg or mAP <

70mmHg) or hyperlactatemia (lactate > 4 mmol/l) : 1. Start fluid loading with cristalloïds (or equivalent

colloïd) 20-40 ml /kg estimated ideal body weight.2. Administer vasopressors to maintain mAP ≥ 65

mmHg, if persisting hypotension despite adequate fluid loading.


SSC: Objectives for the first 6 hours

5. If persisting hypotension or hyperlactatemia (> 4 mmol/l) despite initial fluid loading, measure PVC and ScvO2 (or SvO2), and:

Maintain CVP at 8 - 12 mmHg. Consider inotropic therapy and/or RBC

transfusion if hematocrit is ≤ 30 % when ScvO2 is < 70 %, or SvO2 < 65 % and CVP ≥ 8 mmHg. (2B)



Low-dose Steroids: 28 d survival

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

0 4 8 12 16 20 24 28Jours post-inclusion

Prob

abilit

é de

sur

vie

Placebo Stéroides

HR = 0.67

p=0.023

D. Annane & al, JAMA 2002D. Annane & al, JAMA 2002;288: 862-871.;288: 862-871.

Non-Responders

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

0 4 8 12 16 20 24 28J ours post- inclusion

Prob

abilité

de

surv

ie

Placebo Stéroides

Responders


Low-dose Steroids

• We suggest intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy2C

• We recommend corticosteroids not be administered for the treatment of sepsis in the absence of shock.1D

Low-dose Steroids

• ACTH stimulation test (250-g) not

recommended (2B) Variability in assay Variability in response on same day Free versus protein bound measurement

• Fludrocortisone optional (2C)• Dexamethasone only if

hydrocortisone not available (2B)



Recombinant HumanActivated Protein C (rhAPC)

• Suggest use in patients with clinical assessment of high risk of death due to sepsis induced organ dysfunction, typically with APACHE II ≥25 or multiple organ failure (2B) And no absolute contraindications Weighing the risk/benefit of relative

contraindications

• We recommend that adult patients with severe sepsis and low risk of death, most of whom will have APACHE II <20 or one organ failure, do not receive rhAPC (1A )

Surviving Sepsis

3. Experience with implementation of the

guidelines


Probability of survival of patients with septic shock managed before or after (open circles) the

implementation of standardized hospital order set

Micek S. Crit Care Med 2006; 34: 2707.


Many “Leaks” from research to practice

Aware Accept Target Doable Recall Agree Done

ValidResearch

If 80% achieved at each stage then0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 = 0.21

Sino-Fr Symposium - Oct 07C. Brun-Buisson Surviving Sepsis Barcelona declaration (ESICM congress, 2002) Surviving Sepsis Campaign Guidelines (CCM & ICM,

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