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Sepsis 3.0
Revised Sepsis Guidelines and the
Impact on Practice
Objectives
• Consider the impact of sepsis,
emphasizing the importance of early
recognition & treatment
• Review the current sepsis definitions
and discuss the proposed changes
• Examine key elements of the Surviving
Sepsis Guidelines
Cleveland Clinic—Fairview Hospital
Cleveland, Ohio
Disclosures
• I have no financial disclosures
• http://www.sepsisalliance.org/
Sepsis
• Sepein
– Greek, to rot
• Septikos
– Greek, characterized by putrefaction
• Septicus
– Latin, of or pertaining to putrefaction
http://www.montereybayaquarium.org/animal-guide/octopuses-and-kin/common-cuttlefish
What percentage of the
general public has even heard
of sepsis?
A. 19%
B. 31%
C. 43%
D. 55%
E. 67%
However, most people could not
place the correct context
Sepsis
• “Septicemia is a state of microbial
invasion from a portal of entry into the
bloodstream which causes signs of
illness.“
» Schottmueller, 1914
Sepsis
• Admissions for sepsis in 2000
621,000
• Admissions for sepsis in 2008
1,141,000
• Mortality rate of 28-50%
– http://www.cdc.gov/sepsis/basic/qa.html
Sepsis
• Contributed to 1 in every 2 to 3 hospital
deaths, and most of these patients were
admitted with sepsis
» JAMA July 2, 2014 Volume 312, Number 1, Page 90
• The most expensive hospital condition,
costing over $24 billion per year
» Statistical Brief #204, May, 2016
» Healthcare Cost and Utilization Project
Sepsis
• 40% of total ICU expenditure
– Davies, et al. 14th Annual Congress of the
European Society of Intensive Care
Medicine 2001
• The number of sepsis patients is
projected to increase by 1.5% per year
– Angus, et al. Crit Care Med 2001
Hospital Readmissions
• Patients who survived sepsis to be discharged
from the hospital
• More than 40% were readmitted within 90 days
• Half of these readmissions were deemed possibly
preventable
– JAMA March 10, 2015 Volume 313, Number 10
Hospital Readmissions
• Patients who survived sepsis to be discharged
from the hospital
– The majority of unplanned hospital readmissions after
sepsis are due to an infection and identified that many
rehospitalized survivors present through the ED with
recurrent sepsis
– Crit Care Med March 2016 • Volume 44 • Number 3
– Sepsis is a leading contributor to excess healthcare
costs due to hospital readmissions
– Crit Care Med October 2015 • Volume 43 • Number 10
Hospital Readmissions
• Index admission for heart failure
– Pneumonia & sepsis are frequent reasons for
readmission
• Index admission for acute myocardial infarction
– Pneumonia & sepsis
• Index admission for pneumonia
– Recurrent pneumonia, sepsis, C. diff infection
– JAMA January 23/30, 2013—Vol 309, No. 4
Mortality
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MI
All cancers combined
Sepsis
Stroke
COPD
Alzheimer’s
Motor vehicle crashes
Prescription drug overdose
Firearm deaths
~610,000 deaths/year
~600,000
~300,000
~140,000
~135,000
~85,000
~35,000
~35,000
~35,000
How many deaths could be prevented each year if
optimal care is provided to every septic patient?
A. 22,000
B. 37,000
C. 62,000
D. 77,000
E. 92,000
Crit Care Med 2007;35(5):1257
Definitions
• Systemic inflammatory response
syndrome (SIRS)
• Two or more of the following variables:
– Temperature greater than 38°C or less than 36°C
– Heart rate greater than 90 beats per minute
– Respiratory rate greater than 20 breaths per
minute or a PaCO2 level of less than 32 mm Hg
– Abnormal white blood cell count (>12,000/mL or
<4,000/mL or >10% bands)
Definitions
• Sepsis
– SIRS + infection
• Severe sepsis
ICD-10-CM A41.9
– SIRS + infection + new organ dysfunction
• Septic shock
ICD-10-CM R65.21
– Impaired perfusion despite adequate fluid
resuscitation
Organ Dysfunction
Increased thrombosis & decreased fibrinolysis
Microvascular thrombosis
Decreased microvascular flow
Ischemia
Organ Dysfunction
Capillary leak
Hypovolemia
Decreased cardiac output
Hypovolemic shock
Increased interstitial fluid
Edema
Acute lung injury
Decreased cardiac compliance
Organ Dysfunction
Increase in nitric oxide production
Vasodilation
Oxidative injury
Hypotension
Distributive shock
Direct cellular damage
Impaired mitochondrial function
Organ Dysfunction
• Damaged cell membranes
• Impaired cardiac output
– Hypovolemic
– Distributive
– Cardiogenic
• Blockage of microvascular flow
• Disordered oxygen metabolism
Organ Dysfunction
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Altered mental status
Acute kidney injury
Acute lung injury
Decreased cardiac output
Insulin resistance
Acid-base derangement
Thrombocytopenia
Ileus
Coagulopathy
Adrenal insufficiency
Sepsis can be diagnosed by:
A. Positive blood cultures
B. Elevated C-reactive protein
C. Elevated lactic acid
D. Elevated procalcitonin
E. All of the above
F. None of the above
Surviving Sepsis
• Surviving Sepsis Campaign (2002)
– Society of Critical Care Medicine
– European Society of Intensive Care Medicine
– International Sepsis Forum
• Surviving Sepsis Guidelines
– http://www.survivingsepsis.org/
Surviving Sepsis
• Routine screening of at-risk patients
• Obtain appropriate cultures & imaging
• The administration of effective intravenous
antimicrobials within the first hour of recognition
• Source Control
• Initial Resuscitation
Lactate
• “Measuring lactate levels
can risk stratify patients
with suspected sepsis, to
prompt aggressive early
treatment, and help
monitor the impact of
therapy”
– Chee C et al. Crit Care Med 2015
Lactate
• “The prognostic value of
lactate levels exceeds that of
blood pressure.”
• “Many studies have
confirmed the association
between initial serum
lactate level and mortality
independently of clinical
signs of organ dysfunction”
– Cecconi M, et al. Intensive Care
Med 2014;40:1795
• “In this multicenter, openlabel randomized controlled
study, lactate monitoring
during the first 8 hours of
ICU admission, aimed at
reducing lactate levels by at
least 20% per 2 hours,
significantly reduced ICU
length of stay and also ICU
and hospital mortality”
– Jansen TC, et al. Am J Respir
Crit Care Med 2010;182:752
Initial Resuscitation
• “We recommend the protocolized,
quantitative resuscitation of patients with
sepsis-induced tissue hypoperfusion”
– Surviving Sepsis Guidelines
Initial Resuscitation
• “We suggest targeting resuscitation to
normalize lactate in patients with elevated
lactate levels as a marker of tissue
hypoperfusion”
– Surviving Sepsis Guidelines
Surviving Sepsis
• TIME SENSITIVE!
– Identify patients early in their course
– Administer antibiotics promptly
– Fluid resuscitation—fast & furious
The minimum volume of the initial fluid
resuscitation for the septic patient is:
A. 250 ml
B. 500 ml
C. 1000 ml
D. 10 ml/kg
E. 30 ml/kg
Surviving Sepsis
3-hour bundle
• Measure lactate level
• Draw blood cultures
• Administer broad
spectrum antibiotics
• Administer 30 ml/kg
crystalloid fluid bolus
6-hour bundle
• If persistent
hypotension after
initial fluid
resuscitation, then:
– Add vasopressors
– Measure CVP, SvO2
– Remeasure lactate
Surviving Sepsis
• Compliance with the Surviving Sepsis
Campaign bundles is associated with
improved mortality
– Levy MM, et al. Crit Care Med 2015;43:3
– Levy MM et al. Intensive Care Med 2010;36:222
National Inpatient Quality Measures
• Within 3 hours of identification of severe sepsis:
– Initial lactate level measurement
– Broad spectrum or other antibiotics administered
– Blood cultures drawn prior to antibiotics
• Within 6 hours:
– Repeat lactate measurement if initially elevated
National Inpatient Quality Measures
• Within 3 hours of identification of septic shock:
– Initial lactate level measurement
– Broad spectrum or other antibiotics administered
– Blood cultures drawn prior to antibiotics
• Within 6 hours:
– Repeat lactate measurement if initially elevated
– Resuscitation with 30 ml/kg crystalloid fluids
– Vasopressors if hypotension persists after fluid
administration
National Inpatient Quality Measures
Reassessment to include
OR • Any 2 of the following:
• A focused exam
including:
– Central venous
– Vital signs, AND
– Cardiopulmonary
exam, AND
– Capillary refill
evaluation, AND
– Peripheral pulse
evaluation, AND
– Skin examination
pressure measurement
– Central venous oxygen
measurement
– Bedside Cardiovascular
Ultrasound
– Passive Leg Raise or
Fluid Challenge
Challenges
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Can
Can
Can
Can
we screen patients effectively?
we measure the lactate quickly?
fluids be administered rapidly?
the patient be frequently re-assessed?
Challenges
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Can
Can
Can
Can
we screen patients effectively?
we measure the lactate quickly?
fluids be administered rapidly?
the patient be frequently re-assessed?
• Who’s going to do all of this?
Definitions
• Sepsis
– SIRS + infection
• Severe sepsis
– SIRS + infection + new
organ dysfunction
• Septic shock
– Impaired perfusion
despite adequate fluid
resuscitation
• Many patients with severe
sepsis do not have SIRS
• Many patients with severe
sepsis do not initially have
any obvious organ
dysfunction
• Infection + new organ
dysfunction can occur in the
absence of severe sepsis
The Third International Consensus
Definitions for Sepsis and Septic Shock
(Sepsis-3)
• Definitions of sepsis, severe sepsis, and septic
shock revisited
• Fair sensitivity & poor specificity of SIRS
• Recognition of inflammation as a normal
response to infection
– JAMA February 23, 2016 Volume 315, Number 8
Key Concepts
• Difficult to distinguish between “normal”
and “dysregulated” inflammatory response
• Organ dysfunction may not be obvious
• Sepsis might not be the cause of organ
dysfunction
Key Concepts
• No “gold standard” diagnostic test for sepsis
• Change in approach to screening patients for
sepsis
– New infectionlook for organ dysfunction
– New or worsening organ dysfunctionlook for
infection
Proposed Definitions
• Sepsis is defined as life-threatening organ
dysfunction caused by a dysregulated host
response to infection
– Organ dysfunction can be identified as an acute
change in total SOFA score ≥2 points consequent
to the infection
• JAMA 2016;315(8):801-810
Proposed Definitions
• Septic shock is defined as a subset of sepsis
in which underlying circulatory and cellular
metabolism abnormalities are profound
enough to substantially increase mortality
– Hypotension requiring vasopressor therapy to
maintain mean BP 65mmHg or greater and having
a serum lactate level greater than 2 mmol/L after
adequate fluid resuscitation
• JAMA 2016;315(8):775-787
Logistic Organ Dysfunction System
LODS
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Heart rate
Systolic blood pressure
pO2/fiO2
Glasgow Coma Score
Serum creatinine
Serum urea
Bilirubin
White blood cell count
Prothrombin time
Platelets
– JAMA 1996;276(10):802-810
http://statpages.info/lods.html
Sequential Organ Failure Assessment
SOFA
Crit Care Med 1998; 26:1793-1800
qSOFA
• 0-3 points
• 1 point each for:
– Respiratory rate ≥ 22
– Glasgow Coma Score ≤ 13
– Systolic blood pressure ≤100
• JAMA February 23, 2016 Volume 315, Number 8
qSOFA
• The presence of 2 or more qSOFA points
associated with a greater risk of death or
prolonged intensive care unit stay
• Prompt to identify infected patients outside
the ICU who are likely to be septic
– JAMA February 23, 2016 Volume 315, Number 8
Which are risks factors for sepsis?
A. Age > 65 years
B. Age < 1 year
C. Immunocompromised
D. Recent surgery
E. Chronic disease
F. Wounds
G. Previous sepsis
H. Invasive devices
All are risk
factors
Keys to Surviving Sepsis
• Prevention
• Prevention
• Prevention
Prevention
• Central venous catheter maintenance bundle
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Hand hygiene
Scrub the hub
Aseptic access technique
Daily review of line necessity
Appropriate dressing changes
https://www.jointcommission.org/assets/1/6/CLABSI_Toolkit_Tool_3-22_CVC_Maintenance_Bundles.pdf
Prevention
• Minimize the need to access a vascular
catheter
– Minimize blood draws
– Batch blood draws
– Convert medications from parenteral to
enteral as soon as practical
Prevention (maybe)
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Antimicrobial catheter
Antithrombogenic catheter
Antimicrobial patch
Antimicrobial dressing
Sutureless securement device
Disinfecting port protector
Antimicrobial lock
Daily chlorhexidine bath
Keys to Surviving Sepsis
• Early recognition
– New organ dysfunction—look for infection
– New infection—look for organ dysfunction
– Check the lactate
• Antibiotics immediately
– Blood cultures prior to antibiotics
• Brisk fluid resuscitation
– 30 ml/kg
Sample Sepsis Screening Tool
Sample Sepsis Screening Tool
Sepsis Screening
• Look for trends
– Leukocytosis & fever
– Heart rate increasing
– Blood sugars increasing
– Platelets decreasing
• Monitor for signs of new organ dysfunction
– qSOFA
Keys to Surviving Sepsis
• It is even better to act quickly and err than
to hesitate until the time of action is past
– Carl von Clausewitz
Keys to Surviving Sepsis
• Remember—this is a time-sensitive
problem, just like
– MI
– Stroke
– Trauma
Thank You!