early management of severe sepsis ( the role of biomarkers )
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Early Management of Severe Sepsis( the role of biomarkers )
Frans JV PangalilaIntensivist
• every few seconds someone dies of sepsis across the globe and 20 000 000 - 30 000 000 people are affected every year
Do You Know – What has been reported by Global Sepsis Alliance ?
Sepsis is one of the most common but least recognized disease !!
Reducing Mortality in Severe Sepsis
Severe Sepsis Bundle Sepsis resuscitation bundle Sepsis management bundle
Sepsis Resuscitation Bundle : Rationale
Infectious insult-Sepsis
Inflammatory mediators
Hypovolemia
Vasodilatation
Myocardial depression
Cytopathic tissue hypoxia and
microcirculation impairment
Coagulation activity
Cardiovascular insufficiency
Global Tissue Hypoxia
Markers of the High Risk paients
Organ dysfunction
Cardiac output is not adequate to bring O2 delivery to meet O2 demand
• Lactate• Scvo2 (mixed vein)• Inflammatory markers - eosinophil, netrofil, CRP procalcitonin
“ Sepsis Resuscitation Bundle “( 3 → 7 Indicators )
1. measure lactate : if lactate > 4 mmol
2. obtain blood culture3. administration broad spectrum antibiotic within :
- 3 hours in ED- 1 hours in ICU
Hypotension or Lactate > 4 mmol
Indicators : 4 → 7
No Hypotension Indicators 1 → 3 : within 6
hours4. 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 , 76. insertion CVC : achieves CVP > 8 mmHg7. and achieves mixed vein > 70 %
If
Aerobic02 (+)
Anaerob
Lactate Metabolism
28-Days in Hospital Mortality risk stratified by Blood pressure and Lactate level
Vernon Ch et al.Critical Care Clinic(26) 2010
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
J Inflammation 2010
ScvO2 Lactate Interpretation
↑ ↓ good response to resuscitation
↑ ↑ Shunt a Sepsis b or Cytopathic c
↓ ↓ well compensated low CO or low SaO2
↓ ↑ poor response to resuscitationa low capillary extraction
b inhibition of pyruvate dehydrogenase, low O2 utilizationc mitocondrial cytopathy, low O2 utilization
Assess adequacy of Hemodynamic Support by Keeping Monitor for Scvo2 and Lactate level
Vincent et al ICM 2006
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
High Mortality Reaching 75% !!- How to Treat ? CID 2009
Situation Today
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
Population of patients not infected with
MDR
Subpopulation of patients infected
with MDRInfectioncolonization
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
Factors that influence the acquisition of a MDR infection
Another factors : severity of ilness Immune system age and comorbid conditions nurse patient ratio hand washing and barrier precautions health care workers compliance
(CHEST 2003)
“ 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 ?
Should be given : Antibiotic ??
Congestive Heart Failure Std III - alveolar edema Chest Trauma
If we given
overused antibiotic ? misused antibiotic ?
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
A large number of investigations on biomarkers
We focus on :
Neutrophil C-Reactive Protein
(CRP) Procalcitonin
ROC Curve of five markers infection markers for differentiating bacteremia from non bacteremia
CCR 2010
Conclusions :• absolute lymphopenia is a predictor bacteremia• NLCR even higher predicting bacteremia
Conclusion : maximum daily CRP variation > 4.1 mgdl from previous day plus anabsolute concentration > 8.7 mgdl associated with an 88% risk for acute infection
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
Procalcitonin : “HORMOKINES” in Sepsis
-During a Bacterial 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
The Role of PCT : differentiate SIRS vs Sepsis
Infected pancreatitis with MODS
Infected pancreatitis without MODS
SAP
Ann Surg 2007
Typical Course of PCT Serum Level According to Patient Response to Antibiotic
Christ-Crain. Yearbook of Intensive Care and Emergency Medicine 2005
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 “
Stopping Rules guided by PCT
- Christ-Crain . Am J Respir CCM 2006
Wow....p < 0.001, its really SAVE the patients, pockets
and planets
Priorities in the Early Management of Sepsis -Severe Sepsis
BacterialInvasion
Localised response• vasodilatation
• netrofil transmigration• hibernation
Systemic Pro-inflammatory state
Macrocirculatory satge (0-6 hrs)
Microcirculatorystage (6-24 hrs)
Mitochondrial stage ( > 24 hrs)
Cytokine leak
MOFMODS
Antibiotic Therapy
Goal Directed Haemodynamic Support
Natural Inhibitors of Haemcoagulation
Legend : maximum effectivity of intervention effectivity decreased
Elimination of trigger factors
maximizing tissue perfusion
minimizing iatrogenic injury of physiologic support
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