Outline Defining Sepsis Suspected infection Sepsis Definitions - PDF document

Disclosures Shock and Sepsis 2014 • Lensoo Matthew Strehlow MD FAAEM FACEP Clinical Associate Professor of EM • Online educational company focused on open Co-Director Stanford Emergency Medicine International access education Stanford University School of Medicine Outline Defining Sepsis • Suspected infection • Sepsis Definitions • And • Screening in the ED and prehospital • 2 of 4 SIRS (systemic inflammatory response syndrome) • ProCESS • HR >90 • CVP and fluid responsiveness • Temp <36 or >38 • ScvO2 and Lactate • RR >20 or PCO2 <32 • Other therapies • WBC <4 or >12, >10% bands

Re-defining Sepsis Re-defining Sepsis Diagnostic criteria for sepsis • 2001 International Infection, a documented or suspected, and some of the following: b General variables Fever (core temperature >38.3°C) Hypothermia Sepsis Definitions (core temperature <36°C) Heart rate >90 min − 1 or >2 sd above the normal value for age Tachypnea Altered mental status Significant Conference edema or positive fluid balance (>20 mL/kg over 24 • 2001 International Sepsis Definitions Conference hrs) Hyperglycemia (plasma glucose >120 mg/dL or 7.7 mmol/L) in the absence of diabetesInflammatory variables Leukocytosis (WBC count >12,000 µL − 1 ) Leukopenia (WBC count <4000 µL • “…the clinician goes to − 1 ) Normal WBC count with >10% immature forms Plasma C- reactive protein >2 sd above the normal value Plasma • “…the clinician goes to the bedside, identifies procalcitonin >2 sd above the normal valueHemodynamic the bedside, identifies variables Arterial hypotension b (SBP <90 mm Hg, MAP <70, or an myriad symptoms, and regardless of an evident SBP decrease >40 mm Hg in adults or <2 sd below normal for myriad symptoms, and age) So 2 >70% b Cardiac index >3.5 L·min − 1 ·M − 23 Organ infection, declares the patient to look septic.” dysfunction variables Arterial hypoxemia (Pao 2 /Fio 2 <300) Acute regardless of an evident oliguria (urine output <0.5 mL·kg − 1 ·hr − 1 or 45 mmol/L for at least 2 hrs) Creatinine increase >0.5 mg/dL Coagulation abnormalities infection, declares the (INR >1.5 or aPTT >60 secs) Ileus (absent bowel sounds) Thrombocytopenia (platelet count <100,000 µL − 1 ) Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 patient to look septic.” mmol/L)Tissue perfusion variables Hyperlactatemia (>1 mmol/ L) Decreased capillary refill or mottling Severe Sepsis and Shock Organ System Dysfunction ProCESS Trial • Severe Sepsis: Severe Sepsis: sepsis Respiratory Hypoxia + organ dysfunction Hematologic Low Platelets and EGDT • Septic Shock: Septic Shock: sepsis + Hepatic hypotension after fluid resuscitation (20-30 Cardiovascular Hypotension ml/kg) Neurologic Renal

• Multi-center (31 USA) RCT of ED severe sepsis and • Exclusion: septic shock • Terminal condition or DNR • Inclusion: • Active severe bleeding or coagulopathy • Fluid refractory septic shock OR lactate ≥ 4 • Others • Be enrolled within 2 hours of qualifying • Randomized (1:1:1) to EGDT - Protocoled care - Standard • EGDT 439 pts • Protocoled care 446 pts • Usual care 456 pts

Usual Care • Care delivered without protocol • Care could not be delivered by primary site investigator • At Stanford it was not delivered by ProCESS trained physician • Data collected in same manner as other arms Randomization Outcomes • Groups did not differ regarding baseline characteristics or multiple severity of injury scores

EGDT- 21% Protocol - 18.2% Usual care - 18.9% Secondary Outcomes Care Received • IV fluiids • 3.3 L in protocol* • No difference in other secondary outcomes including • 2.8 L in EGDT* • 2.3 L in usual care • No difference in 90 day mortality • Vasopressors • No difference in need for organ support • 52.2% in protocol • Duration of ICU/hospital stay • 54.9% in EGDT • 44.1% in usual care*

Care Received Limitations • Dobutamine • Patients lower mortality than in original EGDT study. However, the most ill 1/3 of patients showed no difference in outcomes from less ill group • 1.1% in protocol • ICU not mandated for usual care and protocol based standard therapy • 8.0% in EGDT* groups (it was not for EGDT either but most centers cannot do CVP and ScvO2 outside of ED/ICU). This could bias in favor of a greater • 0.9% in usual care percentage of EGDT patients receiving ICU level care after leaving ED. • Transfusions • Fluid requirement for enrollment was altered mid-study from 20-30mL/kg to 1 L minimum • 8.3% in protocol • Looks at patients detected early • 14.4% in EGDT • Limited power to evaluate specific subgroups • 7.5% in usual care* ProCESS Conclusions ED and EMS • In patients that were identified rapidly and received Sepsis Screening other care such as antibiotics early there was no benefit to protocoled care or invasive care.

Adults with Suspected Mortality of Patients with Infection in the ED Suspected Infection in ED Gille-Johnson P, et al. Scan J of Infect Dis. Admitted = 84% Shapiro et al. Ann Emerg Med. 2006;48:583-590. 2013 Mortality of Prehospital 1 Millionth Vital Sign? Severe Sepsis Patients • Shock Index = HR/SBP • ≥ 0.8 concerning Berger et al. WestJEM 2013 Guerra et al. JEM 2013

Summary: Sepsis Screening in the ED • Increasing sepsis awareness in the hospital improves outcomes • SIRS alone is not a useful tool to screen for sepsis in the ED Sepsis Management • Increasing and protocoling use of lactates and shock index may improve sepsis identification in the ED • Early detection of severe sepsis and septic shock may improve outcomes • Further study is needed on ED and prehospital sepsis screening CASE • 80 yo F with AMS and hypotension • 30 mL/kg IV NS given • Repeat VS • HR 60 • BP 85/45 • RR 16 • SaO2 95% NC

FRANK-STARLING CONTRACTILITY EFFECTS CURVE CARDIAC OUTPUT Normal Ventricular Contractility Stroke Stroke Impaired Ventricular Goal IVF: ⬆ cardiac output Volume Volume Contractility CO = HR x SV ∆ CO ∝ ∆ SV Preload Preload CONTRACTILITY EFFECTS FLUID RESPONSIVE CARDIAC OUTPUT Normal Ventricular Contractility = large ⬆ in SV Stroke Impaired Ventricular Volume IVF bolus increases CO >10-15% IVF bolus incr eases CO >10-15% Contractility = small ⬆ in SV Preload Preload

Marik P, P, Crit Care e Med ed 2013 Boyd, Crit Care e Med ed 2011 Positive fluid balance at 12 hrs and 4 days was associated “No data to support the widespread practice with ⬆ mortality (Quartile 1 vs 4 HR 0.57, CI 0.41-0.80) of using CVP to guide fluid therapy” Average fluid balance at 12 hours was +4.2L (day 4 +11L) AUC 0.56 CVP <8 mmHg at 12 hrs associated with lower mortality 57% of patients were fluid responders Measure cardiac output Static measurement to determine need for fluid Give a fluid challenge Dynamic measurement to determine need for fluid Measure cardiac output

45° semi-upright Feet at 45° Give a fluid challenge Give 500mL Passive Leg Fluid Bolus Raise Test • 200-300 mL fluid bolus • Lasts 30-90 seconds Output Cardiac Stroke Volume Variability Pulse Pressure Left Ventricular End Differential Diastolic Area Lakhal, Ann Fren ench Anes est Rea eanima mation 2012 Pleth Variability Index 112 intubated ICU pts in shock received PLR IVC ≥ 17% increase in SBP, then fluid responsive (+LR=26) Doppler Monitoring Caval Index Not helpful if increase <17% End-Expiratory Occlusion If CVP increase ≥ 2 mmHg then, ≥ 9% SBP predictive of Test fluid responsiveness (+LR 5.7, -LR 0.07)

ETCO2 AS AN ESTIMATE Fluids for Undifferentiated Shock FOR CARDIAC OUTPUT Undifferentiated Shock* • ≥ 5% increase in ETCO2 with PLR in sedated, 30 mL/kg NS or LR mechanically ventilated patients predicts fluid responsiveness Shock Improved? Observe YES • +LR= 4.5-15 • -LR= 0.1-0.3 Fluid Challenge *If volume overload at any point then stop IVF and start Monnet, Intensive Care Med 2013 vasopressors Garcia, Ann Intensive Care 2012 Fluid Challenge (IVF/PLR) IV FLUIDS IN SEPSIS Patient- Patient- Patient- CVP Available No MV/CVP MV/sedated Measure- Measure- Measure- ETCO2 CVP & SBP SBP • Initial 30 mL/kg NS/LR bolus over 1 hour ∆ ≥ 2 CVP & ≥ 9% ∆ ≥ 17% SBP ∆ ≥ 5% SBP • Single CVP poor predictor of need for fluids ∆ ≥ 17% SBP • Over administration of fluids is harmful ∆ <17% SBP ∆ <2 CVP & <17% SBP • Fluid challenges (PLR) and assessment of cardiac • output changes are the future ∆ ≥ 2 CVP & <9% Fluid Responsive ∆ <5% • SBP Indeterminate • Not Fluid Responsive

• Which vasopressor would select? • Which vasopressor would select? A. Epinephrine A. Epinephrine B. Norepinephrine B. Norepinephrine C. Dopamine C. Dopamine D. Vasopressin D. Vasopressin Vasopressors Vasopressors • Norepinephrine is now sole 1st line medication • Epinephrine is second line (swap for NE or add to NE)

Tissue Hypoperfusion ScvO2 SaO2 95% Tissue • Central venous oxygen saturation (ScvO2) ScvO2 • Lactate (venous or arterial) 75% ScvO2 Sepsis ScvO2 Sepsis SaO2 SaO2 95% 95% Tissue Tissue Tissue Tissue ScvO2 ScvO2 75% 55%