“Surviving Sepsis”

1. Crit Care Med 2004; 32: 858-73. Intensive Care Med 2004 ; 30 : 536. “Surviving Sepsis” • Barcelona declaration (ESICM congress, 2002) • Surviving Sepsis Campaign Guidelines (CCM & ICM, 2004) • SSC guidelines Version 2 C. Brun-Buisson

2. Potential 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. » C. Brun-Buisson

3. 240 83 Population-adjusted Incidence of Sepsis, USA, 1979-2000 Severe Sepsis: 34% France: Choc septique 9% Severe Sepsis: 34% G.Martin et al, NEJM 2003; 348: 1546-54. C. Brun-Buisson

4. Recommandations SFAR – SRLF 2006 “Surviving Sepsis”? 1. Identification & initial assessment

5. SIRS: Conventional criteria Fever / hypothermia Tachypnea Tachycardia Leukocytosis / leukopenia Others Biomarkers: Elevated PCT, .. SIRS and Organ Dysfunction Criteria • 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 C. Brun-Buisson

6. Tachycardia Tachypnea Arterial pressure Urine output Fever or hypothermia Skin perfusion Lactate Neurologic status Sev Sepsis? Hematology And coagulation Biochemistry Initial assessment (H0-H3) Infection/Sepsis: Initial assessment Evaluation of sepsis Recommandations SFAR – SRLF 2006 C. Brun-Buisson

7. Clinical Hypoperfusion ? Acute care area Maintain non-invasive monitoring + urine output mAP <65 ? No No YESI Lactate >4 ? mAP < 65 ? Urine < 0,5 ml/kg/h ? YES No YES YES Comorbidity ? YES No Etiology at risk ? YES No YES YES Suspected Severe Sepsis Algorithm for disposition of patients in ED • Monitoring HR, RR, AP, Urine • Oxygen to SpO2>95% • Biochemistry (lactate) & microbiology • Cristalloids (500 ml/15 min) to mAP >65 • Call referent intensivist Organ failure? No YES ICU Admission Recommandations SFAR – SRLF 2006 C. Brun-Buisson

8. Re-assessment of organ dysfunctions Antibiotics Blood cultures + site samples Fluid Challenge Source Control: Drainage? Surgery? Imaging? Infection/Severe Sepsis: initial steps Sev Sepsis ? 0 – 3 hrs Recommandations SFAR – SRLF 2006 C. Brun-Buisson

9. “Surviving Sepsis Campaign” 2. Recommendations and Guideline Revision (2006-07) Sponsored exclusively by supporting societies

10. Impact on survival of early antibiotic administration Kumar et al, Crit Care Med 2006; 34: 1589-96 C. Brun-Buisson

11. C. Brun-Buisson

12. E. Rivers, 2001 - EGT C. Brun-Buisson

13. * * * EGT – Mortality rates RR = 0.58 0.58 0.67 P = 0.01 0.01 0.03 E. Rivers et al, NEJM 2001 C. Brun-Buisson

14. EGT - Volume of fluid infused * P<0.01 * * E. Rivers et al, NEJM 2001 C. Brun-Buisson

15. 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 C. Brun-Buisson

16. C. Brun-Buisson

17. Potential 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. Conclusion Les 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. C. Brun-Buisson

18. 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). C. Brun-Buisson

19. SSC: Objectives for the first 6 hours • Mesure arterial lactate level • Obtain blood cultures before administering antibiotics • Prescribe within 3 (1) hrs broad-spectrum empiric antibiotic therapy • If hypotension (PAS < 90 mmHg or mAP < 70mmHg) or hyperlactatemia (lactate > 4 mmol/l) : • Start fluid loading with cristalloïds (or equivalent colloïd) 20-40 ml /kg estimated ideal body weight. • Administer vasopressors to maintain mAP ≥ 65 mmHg, if persisting hypotension despite adequate fluid loading. C. Brun-Buisson

20. SSC: Objectives for the first 6 hours • 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) Recommandations SFAR – SRLF 2006 C. Brun-Buisson

21. Responders Low-dose Steroids: 28 d survival Non-Responders HR = 0.67 p=0.023 D. Annane & al, JAMA 2002;288: 862-871. C. Brun-Buisson

22. 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 therapy 2C • We recommend corticosteroids notbe administered for the treatment of sepsis in the absence of shock. 1D C. Brun-Buisson

23. 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)

24. C. Brun-Buisson

25. Recombinant HumanActivated Protein C (rhAPC) • Suggest usein patients withclinical 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 ) C. Brun-Buisson

26. Surviving Sepsis 3. Experience with implementation of the guidelines

27. 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. C. Brun-Buisson

28. Aware Accept Target Doable Recall Agree Done Valid Research Many “Leaks” from research to practice 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 C. Brun-Buisson