Sepsis is an important issue. Clinician s decision-making capability. Guideline recommendations
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1 Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 Clinicians decision-making capability Guideline recommendations Sepsis is an important issue 8.7% / y 28.7% 17.9% Severe Sepsis 751,000 cases/y Mortality 28.6% N Engl J Med 2003;348:
2 From Infection to Septic Shock Definition SIRS Sepsis Severe Sepsis sepsis-induced hypotension sepsis-induced hypoperfusion Septic shock Nguyen HB, et al. AnnEmergMed 2006;48:28-54 SIRS (Systematic Inflammatory Response Syndrome) Sepsis = SIRS + Presumed or confirmed infectious process BT > 38 or <36 HR > 90 bpm RR > 20 bpm or PaCO2 < 32 mmhg WBC > 12K, < 4K or > 10% bands Dear SIRS, I dont like you Dear SIRS, you are too sensitive Dear SIRS, you do not help us understand the pathophysiology of sepsis Dear SIRS, you do not reflect the severity of the disease Dear SIRS, you detract us from searching for the infection Dear SIRS, I am afraid we dont need you Diagnostic criteria for Sepsis General variables Inflammatory variables Hemodynamic variables Organ dysfunction variables Tissue perfusion variables Vincent JL. CCM 1997;25:372-74
3 Diagnostic criteria for Sepsis General variables Fever (core temperature > 38.3 C) Hypothermia (core temperature < 36 C) Heart rate > 90 bpm or >2 SD above the normal value Tachypnea Altered mental status Significant edema or positive fluid balance (>20 ml/kg over 24 hrs) Hyperglycemia (plasma glucose >140 mg/dl) in the absence of diabetes Diagnostic criteria for Sepsis Inflammatory variables Leukocytosis (WBC count > 12,000/L) Leukopenia (WBC count < 4000/L) Normal WBC count with > 10% immature forms Plasma C-reactive protein > 2 SD above the normal value Plasma procalcitonin > 2 SD above the normal value Diagnostic criteria for Sepsis Hemodynamic variables - Arterial hypotension SBP < 90 mm Hg, MAP < 70 mm Hg, or SBP decrease > 40 mm Hg in adults or < 2 SD below normal for age - Bundle thresholds 65 mmhg Diagnostic criteria for Sepsis Organ dysfunction variables Arterial hypoxemia (PaO2/FiO2 < 300) Acute oliguria (urine output < 0.5 ml/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase > 0.5 mg/dl Coagulation abnormalities (INR > 1.5 or aptt > 60 secs) Ileus (absent bowel sounds) Thrombocytopenia (platelet count < 100,000 /L) Hyperbilirubinemia (plasma total bilirubin > 4 mg/dl) Diagnostic criteria for Sepsis Tissue perfusion variables Hyperlactatemia ( > 1 mmol/l) Decreased capillary refill or mottling SIRS to Septic Shock Insult SIRS Sepsis Severe Sepsis Bone RC, et al. Chest 1992;101:1644 SIRS + presumed or confirmed infectious process Sepsis + 1 organ dysfunction Cardiovascular (Refractory low BP) Adrenal Hematologic Coagulation Renal Septic Shock Respiratory Hepatic CNS Unexplained metabolic acidosis 11
4 Severe Sepsis Sepsis induced tissue hypoperfusion or organ dysfunction Sepsis-induced hypotension Lactate > normal UL Urine output < 0.5 ml/kg/hr for > 2 hrs despite adequate fluid resuscitation Acute lung injury with PaO2/FiO2 < 250 for those w/o pneumonia as source Acute lung injury with PaO2/FiO2 < 200 for those w/ pneumonia as source Creatinine increase > 2.0 mg/dl Bilirubin > 2 mg/dl Platelet < 100K Coagulopathy (INR > 1.5) Sepsis-induced tissue hypoperfusion infection-induced hypotension, elevated lactate, or oliguria Septic shock sepsis-induced hypotension persisting despite adequate fluid resuscitation Crit Care Med 2013; 41: Epidemiology of Sepsis in US ( ) Organ dysfunction is a major outcome parameter Septic shock (n=1134) Severe Sepsis (n=827) Sepsis (n=1063) Infection no SIRS (n584) Total n=3608 N Engl J Med 2003; 348: Alberti et al. Am J Respir Crit Care Med. 2003;168:77-84 Methodology GRADE A B C D Decrease strength Factors Increase strength 1 or 2
5 Strong recommendation Standard of care Early Goal-Directed Therapy Rivers E. N Engl J Med 2001;345: EGDT 28 day mortality Early lactate clearance is associated with improved outcome % P = 0.01* % Standard Therapy n=133 EGDT n=130 Rivers E. N Engl J Med 2001;345: Nguyen HB, et al. CCM 2004;32:
6 Initial resuscitation Protocol with quantitative resuscitation Sepsis-induced tissue hypoperfusion Goals within first 6 hours 1. CVP 8-12 mmhg (MV mmhg) 2. MAP 65 mmhg 3. Urine output 0.5 ml/kg/hr 4. ScvO2 70 % or SvO2 65% (IC) Lactate normalization (2C) Fluid therapy Crystalloids: initial fluid of choice (1B) Hydroxyethyl starches: against (1B) Albumin: supplement of crystalloids (2C) Volume: minimun 30 ml/kg (1C) Challenge technique (UG) Responsiveness: dynamic or static (UG) Vasopressors NE is superior to dopamine Target: MAP 65 mmhg (1C) Norepinephrine: first choice (1B) Epinephrine: additional agent (2B) Vasopressin 0.03 U/min (UG) - to raise MAP or decrease NE dosage - not for single use - higher dose only for salvage therapy Vasopressors Dopamine (2C) - low risk of tachyarrhythmias - absolute or relative bradycardia Phenylephrine only for (1C) - NE associated with arrhythmias - High CO and Low BP - Salvage therapy Low-dose dopamine: not for renal protection (1A) Arterial catheter if available (UG) Inotropic therapy Dobutamine up to 20g/kg/min (1C) myocardial dysfunction - elevated cardiac filling pressure - low cardiac output ongoing hypoperfusion Not for supranormal cardiac index (1B)
7 Corticosteroids SSC performance improvement program US, Europe, South America Hydrocortisone - refractory septic shock (2C) mg/day (2C) - continous flow (2D) - no role for ACTH stimulation test (2B) - no vasopressor, no steroid (2D) - no shock, no steroid (1D) Crit Care Med 2010; 38: Low CVP and ScvO2 achievement BP & Lactate in Sepsis Low BP + Lac 4 Low BP Lac 4 Prevalence 16.6% 49.5% 5.4% Mortality 46.1% 36.7% 30% Crit Care Med 2010; 38: Crit Care Med 2010; 38: ScvO2 70% vs Lac clearance 10% Screening Earlier screening, earlier therapy implementation (1C) Hospital-based performance improvement (UG) - consistent education - protocol development & implementation - data collection - measurement of indicators - feedback to facilitate continuous improvement EMShockNet. JAMA 2010; 303;
8 SSC bundles (3 hrs) Lactate Lactate 36 mg/dl (4 mmol/l)30 ml/kg SSC bundles (6 hrs) MAP 65 mmhg Lactate 36 mg/dl (4 mmol/l) (CVP) * (ScvO2) * LactateLactate* (*): CVP 8 mmhg ScvO2 70% Normalization of lactate Data collection 3hr bundle 6hr bundle Diagnosis Cultures (1C) - Before antibiotics (no delay > 45 min) - At least 2 sets of B/C ( IC as potential source) - Volume of blood for culture 10 ml - Cultures of other sites - Rapid influenza test during pandemic periods 1,3 -D-glucan assay (2B), mannan and anti-mannan antibody assay(2c) for invasive candidiasis
9 Diagnosis The earlier the antibiotics, the better the survival Imaging - Seek for source of infection (UG) Biomarkers - No recommendation to distinguish between sepsis and inflammation 50% 7.6%/hr Kumar A, et al. CCM 2006;34: Main causative organisms 70% Septic patients : Blood culture (-) Antimicrobial therapy Goal of antimicrobial therapy (ideal but not standard) - for septic shock: < 1hr (1B) - for severe sepsis: < 1hr (1C) Broad spectrum with good penetration (1B) Reassess daily for potential deescalation (1B) Low biomarker to assist stop antibiotics (2C) Martin GS, et al. NEJM 2003;348: Annane D, et al. Lancet 2005;365:63-78 Antimicrobial therapy Combination therapy for neutropenic pt (2B) for difficult / resistant pathogens (2B) for resp. failure & septic shock by bacteremic P. aeruginosa, extended beta-lactam & AM or FQ (2B) for septic shock from bacteremic Streptococcus pneumonia, beta-lactam + macrolide (2B) no more than 3-5 days & de-escalation ASAP (2B) Antimicrobial therapy Duration for 7-10 days Longer course for - slow clinical response - undrainable foci of infection - bacteremia with S. aureus - special situations (fungal, viral, neutrpenic) (2C) Antiviral therapy for severe viral origin sepsis (2C) Not for SIRS with noninfectious cause (UG)
10 Source control Prevention Anatomical diagnosis & source control < first 12 hours; risk vs benefit (1C) Delayed intervention until adequate demarcation for necrotizing pancreatitis (2B) Intervention with least physiologic insult (UG) Remove suspicious IV devices ASAP (UG) Reducing VAP (ventilator-associated pneumonia) in health care setting (2B) selective oral decontamination (SOD) selective digestive decontamination (SDD) Reducing risk of VAP in ICU Oral chlohexidine gluconate (CHG) (2B)
11 High MAP: mmhg Low MAP: mmhg Heads of Sepsis hypotension, hypoperfusion, and organ dysfunction Criti Care Med. 2004;32(Suppl):S595-S597
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