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Early Management of Severe Sepsis ( the role of biomarkers )

Early Management of Severe Sepsis ( the role of biomarkers ). Frans JV Pangalila Intensivist. Do You Know – What has been reported by Global Sepsis Alliance ?. every few seconds someone dies of sepsis across the globe and 20 000 000 - 30 000 000 people are affected every year.

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Early Management of Severe Sepsis ( the role of biomarkers )

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  1. Early Management of Severe Sepsis( the role of biomarkers ) Frans JV Pangalila Intensivist

  2. Do You Know – What has been reported by Global Sepsis Alliance ? • every few seconds someone dies of sepsis • across the globe and 20 000 000 - 30 000 000 • people are affected every year

  3. Sepsis is one of the most common but least recognized disease !!

  4. Reducing Mortality in Severe Sepsis Severe Sepsis Bundle Sepsis resuscitation bundle Sepsis management bundle

  5. Sepsis Resuscitation Bundle : Rationale Infectious insult-Sepsis Coagulation activity Inflammatory mediators Hypovolemia Vasodilatation Myocardial depression Cytopathic tissue hypoxia and microcirculation impairment Cardiac output is not adequate to bring O2 delivery to meet O2 demand Cardiovascular insufficiency • Lactate • Scvo2 (mixed vein) • Inflammatory markers • - eosinophil, netrofil, CRP • procalcitonin Global Tissue Hypoxia Markers of the High Risk paients Organ dysfunction

  6. “ Sepsis Resuscitation Bundle “( 3 → 7 Indicators ) If No Hypotension Indicators 1 → 3 : within 6 hours Hypotension or Lactate > 4 mmol Indicators : 4 → 7 1. measure lactate :if lactate > 4 mmol 2. obtain blood culture 3. administration broad spectrum antibiotic within : - 3 hours in ED - 1 hours in ICU 4. delivery of an initial of a 20 ml/kg of crystalloid (or colloid equivalent) 5. Hypotension (+)→ vasopresor (+) maintain MAP > 65 mmhg → if persistent hypotension + lactate > 4mmol Indicators 6 , 7 6. insertion CVC : achieves CVP > 8 mmHg 7. and achieves mixed vein > 70 %

  7. Lactate Metabolism Anaerob Aerobic 02 (+)

  8. 28-Days in Hospital Mortality risk stratified by Blood pressure and Lactate level Vernon Ch et al.Critical Care Clinic(26) 2010

  9. Mixed Vein Oxygen Saturation (Svo2) Mixed Vein (Sv02) ( 65 – 75% ) • ( < 65% ) • DO2 ↓ : • - PaO2 ↓ • - Hb↓ • - CO ↓ • VO2 • - stress/pain • - hyperthermia • - WOB ↑ • ( > 75%) • good responds to • resuscitation • cytopathic hypoxia

  10. J Inflammation 2010

  11. Assess adequacy of Hemodynamic Support by Keeping Monitor for Scvo2 and Lactate level alow capillary extraction binhibition of pyruvate dehydrogenase, low O2 utilization cmitocondrial cytopathy, low O2 utilization Vincent et al ICM 2006

  12. Situation Today ...death from the hospital superbugs could double over the next five years, experts have warned !!!.....18 june 2004, BBC News Wensel et al 2008 ↑ microorganism resistant / superbugs

  13. Situation Today High Mortality Reaching 75% !! - How to Treat ? CID 2009

  14. The Impact of MDR Pathogens • Infection with MDR is associated with negative • health outcome • increase of morbidity and mortality • length of ICU and Hospital stay • healthcare cost • Few antibiotic choice remains • highlights the need to optimize existing classes of • antimicrobials through adequate – appropriate use • and infection prevention

  15. Factors that influence the acquisition of a MDR infection Driven by Two main factors : antibiotic misused or overused by physician - lack of confidence to diagnose infection - poor understanding of antibiotic pk/pd parameter poor understanding of sensitivity patterns of the local community Population of patients not infected with MDR Subpopulation of patients infected with MDR colonization Infection Another factors : severity of ilness Immune system age and comorbid conditions nurse patient ratio hand washing and barrier precautions health care workers compliance

  16. “ Get it Right the First Time “ Axiom : its really important for the physician to appreciate - what they entertained for the first time !!....severe sepsis ?....high risk of MDR ? (CHEST 2003)

  17. Should be given : Antibiotic ?? If we given overused antibiotic ? misused antibiotic ? Congestive Heart Failure Std III - alveolar edema Chest Trauma

  18. So , the Clinician need a Biomarker just to help to maked an Early Good Diagnosis A Good Biomarker Would be improve clinical diagnosis of infections-sepsis early increase upon infection increase despite the presence of immunosuppresive medication guidence of antibiotic therapy prognostic marker and better corelation with outcome

  19. A large number of investigations on biomarkers We focus on : Neutrophil C-Reactive Protein (CRP) Procalcitonin

  20. CCR 2010 • Conclusions : • absolute lymphopenia is a • predictor bacteremia • NLCR even higher predicting • bacteremia ROC Curve of five markers infection markers for differentiating bacteremia from non bacteremia

  21. Conclusion : maximum daily CRP variation > 4.1 mgdl from previous day plus an absolute concentration > 8.7 mgdl associated with an 88% risk for acute infection

  22. Note : A. Fast Response : CRP ratio day 4 < 0.4 B. Slow Response C. non Response : CRP ratio day 4 > 0.8 D. Biphasic Response day 4 decreased < 0.8 after that increased > 0.8

  23. Procalcitonin : “HORMOKINES”in Sepsis • During aBacterial Infection there is induction of CT-m RNA by LPS alone or in • combination with IL-1beta/TNF alpha in all parenchymal tissues, and a general • release of PCT, into the bloodstream • During a Viral Infection IFN-gamma is being released, IFN-gamma inhibits IL- • 1beta and by doing so inhibits the release of PCT

  24. The Role of PCT : differentiate SIRS vs Sepsis

  25. Ann Surg 2007 Infected pancreatitis with MODS Infected pancreatitis without MODS SAP

  26. Typical Course of PCT SerumLevelAccording to PatientResponse to Antibiotic Christ-Crain. Yearbook of Intensive Care and Emergency Medicine2005

  27. The Big Question:when to stop the antibiotic therapy ?? “ the expert said 8 days “ “ patient is stable “ “ patient is transferred to the ward “ “ patient developed a rash “ “ renal function is deteriorating “ “ cultures came back negative “

  28. Stopping Rules guided by PCT

  29. Wow....p < 0.001, its really SAVE the patients, pockets and planets - Christ-Crain . Am J Respir CCM 2006

  30. Priorities in the Early Management of Sepsis -Severe Sepsis Cytokine leak MOF MODS Bacterial Invasion • Localised response • vasodilatation • netrofil transmigration • hibernation Systemic Pro-inflammatory state Macrocirculatory satge (0-6 hrs) Microcirculatory stage (6-24 hrs) Mitochondrial stage ( > 24 hrs) Antibiotic Therapy Goal Directed Haemodynamic Support Natural Inhibitors of Haemcoagulation Elimination of trigger factors maximizing tissue perfusion minimizing iatrogenic injury of physiologic support Legend : maximum effectivity of intervention effectivity decreased

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