Outline Defining Sepsis Suspected infection Sepsis Definitions - - PDF document

Shock and Sepsis 2014

Matthew Strehlow MD FAAEM FACEP Clinical Associate Professor of EM Co-Director Stanford Emergency Medicine International Stanford University School of Medicine

Disclosures

• Lensoo
• Online educational company focused on open

access education

Outline

• Sepsis Definitions
• Screening in the ED and prehospital
• ProCESS
• CVP and fluid responsiveness
• ScvO2 and Lactate
• Other therapies

Defining Sepsis

• Suspected infection
• And
• 2 of 4 SIRS (systemic inflammatory response syndrome)
• HR >90
• Temp <36 or >38
• RR >20 or PCO2 <32
• WBC <4 or >12, >10% bands

Re-defining Sepsis

• 2001 International Sepsis Definitions Conference
• “…the clinician goes to the bedside, identifies

myriad symptoms, and regardless of an evident infection, declares the patient to look septic.”

Re-defining Sepsis

• 2001 International

Sepsis Definitions Conference

• “…the clinician goes to

the bedside, identifies myriad symptoms, and regardless of an evident infection, declares the patient to look septic.”

Diagnostic criteria for sepsis

Infection, a documented or suspected, and some of the following: b General variables Fever (core temperature >38.3°C) Hypothermia (core temperature <36°C) Heart rate >90 min−1 or >2 sd above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 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

−1 ) Normal WBC count with >10% immature forms Plasma C-

reactive protein >2 sd above the normal value Plasma procalcitonin >2 sd above the normal valueHemodynamic variables Arterial hypotension b (SBP <90 mm Hg, MAP <70, or an SBP decrease >40 mm Hg in adults or <2 sd below normal for age) So2 >70% b Cardiac index >3.5 L·min−1 ·M−23 Organ dysfunction variables Arterial hypoxemia (Pao2 /Fio2 <300) Acute

• liguria (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 (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

mmol/L)Tissue perfusion variables Hyperlactatemia (>1 mmol/ L) Decreased capillary refill or mottling

Severe Sepsis and Shock

• Severe Sepsis:

Severe Sepsis: sepsis + organ dysfunction

• Septic Shock:

Septic Shock: sepsis + hypotension after fluid resuscitation (20-30 ml/kg)

Organ System Dysfunction Respiratory Hypoxia Hematologic Low Platelets Hepatic Cardiovascular Hypotension Neurologic Renal

ProCESS Trial and EGDT

• Multi-center (31 USA) RCT of ED severe sepsis and

septic shock

• Inclusion:
• Fluid refractory septic shock OR lactate ≥4
• Be enrolled within 2 hours of qualifying
• Exclusion:
• Terminal condition or DNR
• Active severe bleeding or coagulopathy
• Others
• 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

Outcomes Randomization

• Groups did not differ regarding baseline

characteristics or multiple severity of injury scores

EGDT- 21% Protocol - 18.2% Usual care - 18.9%

Secondary Outcomes

• No difference in other secondary outcomes

including

• No difference in 90 day mortality
• No difference in need for organ support
• Duration of ICU/hospital stay

Care Received

• IV fluiids
• 3.3 L in protocol*
• 2.8 L in EGDT*
• 2.3 L in usual care
• Vasopressors
• 52.2% in protocol
• 54.9% in EGDT
• 44.1% in usual care*

Care Received

• Dobutamine
• 1.1% in protocol
• 8.0% in EGDT*
• 0.9% in usual care
• Transfusions
• 8.3% in protocol
• 14.4% in EGDT
• 7.5% in usual care*

Limitations

• 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

• ICU not mandated for usual care and protocol based standard therapy

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 percentage of EGDT patients receiving ICU level care after leaving ED.

• Fluid requirement for enrollment was altered mid-study from 20-30mL/kg

to 1 L minimum

• Looks at patients detected early
• Limited power to evaluate specific subgroups

ProCESS Conclusions

• In patients that were identified rapidly and received
• ther care such as antibiotics early there was no

benefit to protocoled care or invasive care.

ED and EMS Sepsis Screening

Adults with Suspected Infection in the ED

Admitted = 84%

Shapiro et al. Ann Emerg Med. 2006;48:583-590.

Mortality of Patients with Suspected Infection in ED

Gille-Johnson P, et al. Scan J of Infect Dis. 2013

Mortality of Prehospital Severe Sepsis Patients

Guerra et al. JEM 2013

1 Millionth Vital Sign?

• Shock Index = HR/SBP
• ≥ 0.8 concerning

Berger et al. WestJEM 2013

Summary: Sepsis Screening in the ED

• Increasing sepsis awareness in the hospital improves
• utcomes
• SIRS alone is not a useful tool to screen for sepsis in the ED
• 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

Sepsis Management

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 CURVE

Goal IVF: ⬆cardiac output CO = HR x SV ∆ CO ∝ ∆ SV

Stroke Volume Preload

CONTRACTILITY EFFECTS CARDIAC OUTPUT

Stroke Volume Preload

Normal Ventricular Contractility Impaired Ventricular Contractility

CONTRACTILITY EFFECTS CARDIAC OUTPUT

Preload Stroke Volume Preload

Normal Ventricular Contractility Impaired Ventricular Contractility = small ⬆ in SV = large ⬆ in SV

FLUID RESPONSIVE

IVF bolus incr IVF bolus increases CO >10-15% eases CO >10-15%

Marik P, P, Crit Care e Med ed 2013 “No data to support the widespread practice

• f using CVP to guide fluid therapy”

AUC 0.56 57% of patients were fluid responders

Boyd, Crit Care e Med ed 2011 Positive fluid balance at 12 hrs and 4 days was associated with ⬆ mortality (Quartile 1 vs 4 HR 0.57, CI 0.41-0.80) Average fluid balance at 12 hours was +4.2L (day 4 +11L) CVP <8 mmHg at 12 hrs associated with lower mortality

Static measurement to determine need for fluid Dynamic measurement to determine need for fluid Measure cardiac output Measure cardiac output Give a fluid challenge

Give a fluid challenge Give 500mL Fluid Bolus Passive Leg Raise Test

Feet at 45° 45° semi-upright

• 200-300 mL fluid bolus
• Lasts 30-90 seconds

Pulse Pressure Differential Stroke Volume Variability IVC Caval Index Pleth Variability Index Left Ventricular End Diastolic Area End-Expiratory Occlusion Test Doppler Monitoring

Cardiac Output

Lakhal, Ann Fren ench Anes est Rea eanima mation 2012 112 intubated ICU pts in shock received PLR ≥17% increase in SBP, then fluid responsive (+LR=26) Not helpful if increase <17% If CVP increase ≥2 mmHg then, ≥9% SBP predictive of fluid responsiveness (+LR 5.7, -LR 0.07)

ETCO2 AS AN ESTIMATE FOR CARDIAC OUTPUT

• ≥5% increase in ETCO2 with PLR in sedated,

mechanically ventilated patients predicts fluid responsiveness

• +LR= 4.5-15
• -LR= 0.1-0.3

Monnet, Intensive Care Med 2013 Garcia, Ann Intensive Care 2012

Fluids for Undifferentiated Shock

*If volume overload at any point then stop IVF and start vasopressors Undifferentiated Shock* 30 mL/kg NS or LR

YES

Observe Fluid Challenge Shock Improved?

Fluid Challenge (IVF/PLR)

Patient- MV/sedated Measure- ETCO2 Patient- CVP Available Measure- CVP & SBP Patient- No MV/CVP Measure- SBP ∆ ≥5% ∆ <5% ∆ <2 CVP & <17% SBP ∆ ≥2 CVP & <9% SBP ∆ ≥2 CVP & ≥9% SBP ∆ ≥17% SBP ∆ <17% SBP ∆ ≥17% SBP

• Fluid Responsive
• Indeterminate
• Not Fluid Responsive

IV FLUIDS IN SEPSIS

• Initial 30 mL/kg NS/LR bolus over 1 hour
• Single CVP poor predictor of need for fluids
• Over administration of fluids is harmful
• Fluid challenges (PLR) and assessment of cardiac
• utput changes are the future

• Which vasopressor would select?
• A. Epinephrine
• B. Norepinephrine
• C. Dopamine
• D. Vasopressin
• Which vasopressor would select?
• A. Epinephrine
• B. Norepinephrine
• C. Dopamine
• D. Vasopressin

Vasopressors Vasopressors

• Norepinephrine is now sole 1st line medication
• Epinephrine is second line (swap for NE or add to

NE)

Tissue Hypoperfusion

• Central venous oxygen saturation (ScvO2)
• Lactate (venous or arterial)

Tissue

ScvO2

SaO2 ScvO2 95% 75% Tissue SaO2 ScvO2 Tissue

Sepsis

ScvO2

95% 75% Tissue SaO2 ScvO2

ScvO2

Tissue 95% 55%

Sepsis

ScvO2 Monitoring

• Continuous reading via PreSep

catheter

• Send serial central VBGs every

1/2 to 1 hour

Lactate Clearance, An Alternative to ScvO2

• Check initial lactate (Time 0 hours)
• Optimize CVP and MAP
• Recheck lactate (Time ≥2 hours)
• If, <10% clearance use transfusion and

dobutamine

• Recheck, lactate every 0.5 to 1 hour

Jones A. et al. JAMA 2010;303:739-46 Jansen et al. Am J Resp Crit Care

• Med. 2010

Tissue SaO2 ScvO2 Tissue

Sepsis

ScvO2

95% 55%

Tissue SaO2 ScvO2 Tissue

Sepsis

ScvO2

95% 90% Shunt Tissue SaO2 ScvO2 Tis sue

Sepsis

ScvO2

95% 90%

Mortality Grouped by ScvO2

(≥90%) (<70%) (70-89%)

Pope et al. Annals of EM 2010

Markers of Possible “Occult” Hypoperfusion

• ScvO2 <70% or

ScvO2 <70% or ≥90% 90%

• Lactate >4 mmol/dL

Lactate >4 mmol/dL

• Urine output <0.5ml/kg
• Cool extremities
• Delayed capillary refill >4 sec
• AMS

270 270

ScvO2 <70% or <10%⬇ lactate >3

270 Hgb <7

Transfuse Dobutamine

Hgb >10 Hgb 7-10

Signs of ischemia?

270 270 No Yes

Summary: Occult Hypoperfusion

• ScvO2 and lactate guided therapy are options for

patients with signs of persistent hypoperfusion after fluid resuscitation and vasopressors

• Lactate guided therapy is alternative
• Target 10-20% reduction over 2 hours
• Consider NTG for persistent lactate >3 (or other

markers of hypoperfusion) and normal/elevated ScvO2

Other Goals of Resuscitation Source Control

• Indwelling lines should be

removed after alternative access has been established if it is a likely source of infection

Steroids

• Consider only for patients that

have sustained hypotension despite adequate fluids and vasopressors

• No ACTH stim test

Glucose Control

• Target <180 mg/dL
• Consider insulin gtt if 2

consecutive values >180 mg/ dL

• Caution with capillary blood

glucose as they may be inaccurate

Acute Lung Injury

• Prevention
• Keep plateau pressures ≤30 cm H2O
• Utilize Positive end-expiratory pressure (PEEP) to

avoid alveolar collapse

• If ARDS with PaO2/FiO2 <150 mmHg, target
• tidal volumes 6mL/kg
• conservative fluid strategy

Plateau pressure measures actual pressure alveoli are exposed to

Plateau Pressure

Antimicrobial Therapy

0-2 hour broad spectrum ABX in ED Reassess in ICU Daily Recheck

Hours Hours

Summary

• ED screening for SIRS and sepsis is not evidence

based

• Central lines and CVP guided resuscitation remains

standard of care but US or PLR are simple early guides

• ScvO2 is preferred over lactate guided

resuscitation but lactate guided resuscitation is a reasonable alternative