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�

Sepsis 2017Core Measures

Recognition and Management

Tom Ahrens PhD RN FAAN

� Research Scientist at Barnes-Jewish Hospital, St. Louis, MO

� No conflicts of interest to report

SEP-1

Core Measure

� Suspected infection

� 2 or more signs of SIRS

� Evidence of organ dysfunction

� Elevated lactate is one example

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�

Time Zero

When the patient meets criteria for severe

sepsis

CMS Core Measure

� Measure Description: This measure will focus on patients aged 18 years and older

who present with symptoms of severe sepsis or septic shock. These patients will be

eligible for the 3 hour (severe sepsis) and/or 6 hour (septic shock) early management

bundle.

� Numerator Statement: If:

measure lactate level

obtain blood cultures prior to antibiotics

administer broad spectrum antibiotics

administer 30 ml/kg crystalloid for hypotension or lactate >=4 mmol/L

What is sepsis?

� Sepsis is the body’s immune system response to an infection

� Bacteria, virus, protozoan

� Instead of a localized response to an infection (like a

pneumonia), sepsis is a systemic response that can be

catastrophic

� Highest cost to US hospitals (AHRQ)

� Leading cause of death in hospitals

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New Definitions

New Sepsis DefinitionqSOFA

� An alteration in mental status (not the GCS)

� A decrease in SBP of less than 100 mm Hg

� A respiratory rate > 22 bpm

�

Sequential Organ

Failure AssessmentSOFA Scores

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Method of Predicting Outcomes in

Critically Ill Patients

� An initial SOFA score of < 9 predicted a mortality of <

33%

� A SOFA > 11 predicted mortality of 95%

SOFA

Key Differences in New Definition

� Sepsis as infection and 2 or more SIRS is now just an infection

� Severe sepsis is now sepsis

� Septic shock is� Blood lactate > 2 mmol/L despite volume resuscitation

� Hypotension that persists after fluid resuscitation and requires vasopressors

� Sepsis definition now will carry a higher risk of death and increased ICU LOS

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Rationale for New Definition

� Based on review of 2 million patients in sepsis studies

� SIRS based on expert opinion

� SIRS should still be used when evaluating sepsis

Controversies with New

Definition

� Not a screening tool

� A better sepsis definition

� Concern is a delay in sepsis identification

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Benefits and Barriers

� Improved� Patient identification

� Coding and reimbursement

� SOI/ROM

� Reduced mortality

� Improved compliance with bundles

� Barriers� Multidisciplinary cooperation

� Funding

� Education

�

Can your staff

recognize sepsis?

Sepsis can be subtle until it is so obvious you can’t miss it

62 year old admitted to hospital

with hip infection

� On admission� T – 38.5

� RR – 24

� P – 104

� WBC – 19,000

� Where should he be admitted?

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�

36 hours post

admissionUrine output drops – What should be done?

�

48 hours post

admissionPulse oximeter drops and becomes difficult to read – what should

be done?

Modified from criteria published in: Balk RA. Crit Care Clin. 2000;16:337-352. Kleinpell RM. Crit Care Nurs Clin N Am 2003;15:27-34.

CardiovascularTachycardiaHypotension

Altered CVP and PAOP

Renal OliguriaAnuria

↑ Creatinine

Hematologic↓ platelets,

↑ PT/INR/ ↑ aPTT↓ protein C↑ D-dimer

Hepatic Jaundice

↑ Liver enzymes↓ Albumin

CNSAltered consciousness

Confusion

MetabolicMetabolic acidosis

↑ Lactate level↓ Lactate clearance

Respiratory Tachypnea

↓ PaO2

↓ PaO2/FiO2 ratio

Any Organ Can be Affected by Sepsis. If any organ shows signs of dysfunction related to the infection, sepsis is now called severe sepsis

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Difference between Sepsis

States

Sepsis / ICD 995.91 Severe Sepsis/ ICD 995.92 Septic Shock/ ICD 785.52

Pulse ≥ than 90 beats per minute

Respiratory rate ≥ than 20 breaths

per minute

Temperature > 38.3 oC or < 36.0 oC

WBC < 4,000 or > 12,000; or bands

> 10%

Pulse ≥ than 90 beats per minute

Respiratory rate ≥ than 20 breaths

per minute

Temperature > 38.3 oC or < 36.0 oC

WBC < 4,000 or > 12,000; or bands

> 10%

Pulse ≥ than 90 beats per minute

Respiratory rate ≥ than 20 breaths

per minute

Temperature > 38.3 oC or < 36.0 oC

WBC < 4,000 or > 12,000; or bands

> 10%

Real or suspected infection: Real or suspected infection: Real or suspected infection:

Organ dysfunction: Organ Dysfunction

Hypotension

Key to Success in Sepsis

Management

� Prevent infections! Don’t let sepsis start

� Rapid Identification

� If sepsis is present, rapid treatment is needed

The Power of Our Immune System

““““Our arsenals for fighting off bacteria are so powerful, and involve so many different defense mechanisms, that we are more in danger from them than from the invaders.

““““We live in the midst of explosive devices; we are mined!””””Lewis Thomas - 1972Germs, New England Journal Of MedicineDR 32708 3000093662 1204.5 Copyright © 2004, Eli Lilly and Company. All rights reserved.

Xigris is a registered trademark of Eli Lilly and Company.

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Power of the Immune SystemVaccine Schedule – Too Much?

14 Vaccines now Recommended

� What causes immune response is number of proteins

that cause reaction - Epitopes

� 100 years ago only vaccine was against smallpox

� Large virus, 200 epitope inducing proteins

� Todays 14 vaccines have 160 epitope inducing

proteins

� Immune system has to respond, immediately at birth,

millions of bacteria

� Each of these bacteria have 2-6 thousand protein

which can induce epitopes

� Within days, a human baby has 100 trillion

bacteria in and on them (we have 10 trillion cells)

A Single Cold Virus Has More

Protein Inducing Epitopes than

All Vaccinations Combined

� Given the number of B cells in the

bloodstream, the average number of

epitopes contained in a vaccine, rapidity

with which a sufficient quantity of

antibodies could be made:

� Babies could respond to 100,000 vaccines

at one time.

Impact of Vaccines

Measles Example

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But few bacteria are dangerous

� Only a small amount of bacteria and viruses are dangerous

� Those are not likely to be on the floor

� But they can be on your hands or in the air

� Protecting yourself

�

Pathophysiology of

Sepsis

What do we need to know

5 second rule

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Immune ResponseImmune ResponseImmune ResponseImmune ResponseImmune ResponseImmune ResponseImmune ResponseImmune Response

Coagulation and Impaired Fibrinolysis

In

Severe Sepsis

Reprinted with permission from the National Initiative in Sepsis Education (NISE).

Endothelium

Neutrophil

Monocyte

IL-6IL-1TNF-α

IL-6

Inflammatory Responseto Infection

Thrombotic Responseto Infection

Fibrinolytic Responseto Infection

TAFI

PAI-1

Suppressedfibrinolysis

Factor VIIIaTissue Factor

COAGULATION CASCADE

Factor Va

THROMBIN

Fibrin

Fibrin clotTissue Factor

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“Except on few occasions, the patient appears to die from the body's response to infection rather than from it.”

Sir William Osler – 1904

The Evolution of Modern Medicine

Hotchkiss, R. S. et al. N Engl J Med 2003;348:138-150

The Response to Pathogens, Involving "Cross-Talk" among Many Immune Cells, Including Macrophages, Dendritic Cells, and CD4 T Cells

Determining if your

Patient is In Danger

� Establishing urgency – use of Lactate� A measure of tissue hypoxia

� Normal 1-2 mmol

� > 4 mmol with metabolic acidosis suggests tissue hypoxia

� Lactate measurements need to be repeated to evaluate if therapy is effective and if the patient is improving

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Traditional Vital Signs Will Miss

Sepsis

Lactate N= 529

< 2 (N=219) 2-4 (N=177) > 4 (N = 104)

SBP > 90 158/219 (72%) 116/177 (65%) 64/104 (62%)

SBP < 90 61/219 (28%) 61/177 (34%) 40/104 (38%)

Sepsis will morph and

change during its course.

Begins like hypovolemia

Blood pressure 102/52 mm Hg

Pulse 108 beats/min

Stroke volume 44

Cardiac output 4.75

ScvO2 0.3738

Later Sepsis changes

from hypovolemia to

hyperdynamic

Blood pressure 100/56 mm Hg

Pulse 104 beats/min

Stroke volume 105

Cardiac output 10.9

SvO2 0.87

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Microvascular Blood Flow Is Impaired

in Severe Sepsis

Venous blood

Arterial bloodSO2 - .98

SO2

- .94

SO2

- .65

SO2

- .86

SO2

- .65

SO2

- .83

SO2

- .65

Sepsis often progresses when the

host cannot contain the primary

infection

� A problem most often related to� characteristics of the microorganism,

� such as a high burden of infection � the presence of super antigens and other

virulence factors, � resistance to phagocytosis � antibiotic resistance.

Cell dysoxia

� Epithelial cells have diminished oxygen consumption� due to a depletion of nicotinamide

adenine dinucleotide (NAD)

� Concept of cell stunning or hibernation

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Case Example – Is Action

Needed?

� 29 year old male with history of Crohn’s disease is admitted from ED with perirectal abscess.

� Lactate 5.9

� SpO2 - .94

� BP – 108/50

� HR – 81

� RR – 20

� T – 38.3

� UO – 1 ml/kg/hr (55 ml/hr)

�

How do We

Identify Sepsis

Now?

In absence of biomarkers, must rely on crude physical indicators

SIRS AND SEPSIS

Sepsis is defined as an infection

plus ≥≥≥≥2 SIRS criteria

• Temperature >38.3°°°°C or <36°°°°C

• HR >90 beats/min

• Respirations >20/min

• WBC count >12,000/mm3

or <4,000/mm3 or >10% immature neutrophils

SIRSSeveresepsis

MODSSeptic shock

SIRSSeveresepsis SepsisInfection

Other

Pancreatitis

Trauma

Burns

Sepsis

Levy MM, et al. Crit Care Med. 2003;31:1250-1256.

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Procalcitonin and Antibiotic

Therapy

Procalcitonin and Antibiotic

Therapy

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History of Treating Severe Sepsis

Clinical tx – fluids, vasopressors & antibiotics

AfelimomabAnti TNF F monoclonolantibody fragment

How Do We Treat Sepsis?

Sadly, little has changed in actual treatment of sepsis in decades. The key steps are:

1) Identify the infectious organism

Blood and site cultures

2) Remove the source of the infection if possible

3) Obtain lactate

4) Initiate Antibiotics

5) If severe sepsis is present, give fluids

6) If fluids do not restore hemodynamic stability, give vasopressors

7) If pressors do not improve hemodynamics, add steroids

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The New Surviving Sepsis

Campaign Bundles – April 2015

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New Volume and Tissue

Perfusion Elements

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Protocolized Care for Early Septic Shock (ProCESS) – 31 ED’s in US

Australasian Resuscitation in Sepsis Evaluation (ARISE) – 51 ED’s in Australia, New

The Protocolised Management in Sepsis (ProMISe) Trial Dr Salim Rezaie Clinical Assistant Professor of EM and IM at

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ProMise, ProCess and ARISE

Trials� Key points

� Fluid administration similar in both control and experimental

groups

� Vasopressor use similar in both groups

� Antibiotics administered similarly in both groups

� Lactates obtained in both groups

� Mortality rates (<20%) is not as common outside centers with well

designed sepsis recognition/management programs

� Problems– Antibiotics and fluids given in both control and

experimental groups within 3 hours.

� Hawthorne Effect Likely

� Contamination of practice

Take away Points

� If Patients are

� identified early,

� Receive antibiotics EARLY

� receive IVF EARLY

� Then ScvO2 and CVP monitoring does not seem to add a

benefit

� BUT EGDT with ScvO2 not really tested since resuscitation

had already occurred

Hemodynamics of Sepsis

� Concept of early resuscitation� Establishing urgency – use of

Lactate

� Normal 1-2 mmol

� > 4 mmol with metabolic acidosis suggests tissue hypoxia

� Fluids with a goal� The role of mixed venous

oxyhemoglobin (ScvO2)

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�CVP and PAOP should never be used in isolation� Inconsistent in revealing information about volume and flow

�Flow and pressure do not always correlate� Marik et al. Based on the results of our systematic review, we

believe that CVP should no longer be routinely measured in the ICU, operating room, or emergency department.

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Marik P, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness?A Systematic Review ofthe Literature and the Tale of Seven Mares. Chest 2008;134;172-178

� Is BP is measured because it can be measured

� If BP increases, does blood flow increase?� think of use of levophed

� Blalock 1943, says:

“It is well known by those interested in this “It is well known by those interested in this “It is well known by those interested in this “It is well known by those interested in this subject that the blood volume and cardiac subject that the blood volume and cardiac subject that the blood volume and cardiac subject that the blood volume and cardiac output are usually diminished in traumatic output are usually diminished in traumatic output are usually diminished in traumatic output are usually diminished in traumatic shock before the arterial blood pressure shock before the arterial blood pressure shock before the arterial blood pressure shock before the arterial blood pressure declines significantly”declines significantly”declines significantly”declines significantly”

Blalock A, (1943) Surgery 14: 487-508

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BP Measurement - Useful or

Misleading?

BP Measurement - Useful or

Misleading?

Uses Ease of use Accuracy Professional Reimbursement

Doppler -USCOM

Anywhere Good Good -

Doppler (EDM) OR, ICU Excellent Excellent $$$

ECON OR, ICU Good Fair -

Bioimpedance Anywhere Good Fair $

Pulse contour(FloTrac, LiddCo, PICCO)

OR, ICU Difficult Fair -

NICO OR, ICU Difficult Fair -

PAC OR, ICU Difficult Good $$

Bioreactance OR, ICU Good Good $ 63

Methods of Measuring SVMethods of Measuring SVMethods of Measuring SVMethods of Measuring SV

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Non Invasive CO/SV

Measurement

Non invasive CO/SV measurement

Diagnostics

� Cultures as clinically appropriate before antimicrobial therapy

if no significant delay (> 45 mins) in the start of antimicrobial(s)

(grade 1C). At least 2 sets of blood cultures (both aerobic and

anaerobic bottles) be obtained before antimicrobial therapy

with at least 1 drawn percutaneously and 1 drawn through

each vascular access device, unless the device was recently

(<48 hrs) inserted (grade 1C).

� Imaging studies performed promptly to confirm a potential

source of infection (UG).

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Antibiotics

� Administration of effective intravenous antimicrobials within the first hour of

recognition of septic shock (grade 1B) and severe sepsis without septic shock

(grade 1C) as the goal of therapy.

� Broad spectrum antibiotics should be initiated

� Initial empiric anti-infective therapy of one or more drugs that have activity

against all likely pathogens and that penetrate in adequate concentrations into

tissues presumed to be the source of sepsis (grade 1B).

� Antimicrobial regimen should be reassessed daily for potential deescalation

(grade 1B).

� Use of low procalcitonin levels or similar biomarkers to assist the clinician in the

discontinuation of empiric antibiotics in patients who initially appeared septic, but

have no subsequent evidence of infection (grade 2C).

Fluid Therapy of Severe Sepsis

Crystalloids such as normal saline as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B).

� Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients (grade 1C).

�Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C).

�Fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG).

Loss of perfusion is a common feature of sepsis. This patient has altered perfusion of his hand

Vasopressors in Severe Sepsis(only after adequate fluid has been given)

� Vasopressor therapy initially to target a mean arterial pressure

(MAP) of 65 mm Hg (grade 1C).

� Norepinephrine as the first choice vasopressor (grade 1B).

� Epinephrine when an additional agent is needed to maintain

adequate blood pressure (grade 2B).

� Vasopressin 0.03 units/minute can be added to

norepinephrine (NE) with intent of either raising MAP or

decreasing NE dosage (UG).

� Dopamine only in patients with low risk of tachyarrhythmias

and absolute or relative bradycardia) (grade 2C).

� Phenylephrine is not recommended in the treatment of septic

shock except in circumstances where (a) norepinephrine is

associated with serious arrhythmias,

� All patients requiring vasopressors have an arterial catheter placed

as soon as practical if resources are available (UG).

Vasopressors are powerful agents. Side effects include loss of perfusion to periphery

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Corticosteroids in Severe Sepsis

� Intravenous hydrocortisone only if adequate fluid resuscitation and vasopressor

therapy are unable to restore hemodynamic stability

� suggest intravenous hydrocortisone alone at a dose of 200 mg per day (grade 2C).

� In treated patients hydrocortisone tapered when vasopressors are no longer

required (grade 2D).

� When hydrocortisone is given, use continuous flow (grade 2D).

Setting Goals

� Discuss goals of care and prognosis with

patients and families (grade 1B).

� Sepsis has a high mortality rate.

Families should understand and

recognize that determining what the

patient’s wishes are may help dictate

the aggressiveness of therapy

� Incorporate goals of care into treatment and

end-of-life care planning, utilizing palliative

care principles where appropriate (grade

1B).

� Address goals of care as early as feasible, but

no later than within 72 hours of ICU

admission (grade 2C).

Summary

� Prevent Infections

� Early treatment

� Identify agent

� Remove source

� Antibiotics

� Fluids

� Pressors

� Steroids

� Set goals for end of life

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�

Case Study 1

Case Study

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• 63 year old male in MICU with CAP, pneumothorax

• Progressing well but on day 4 • Develops spontaneous pneumothorax• RLL infiltrate

• Temp increases to 39.1• P – 122• BP – 82/52 (following EGDT)

• WBC 16,500

• Is SOB, requires intubation, 50% FIO2, AMV• 12/14, Vt – 500 ccs, PEEP +10

• Day 4 • SpO2 - .92, PaO2 64 (P/F ratio > 100), pH 7.28,

PaCO2 32, HCO3 - 17

• Sepsis is suspected with treatment rapidly started

• Has received EGDT• 4 L NS

• Lactate 6.2

• Platelets – 110,000

Chest x-ray Day 3 AM

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Day 3 PM

What to do?

� What is happening?

� Any therapies missing?

� Family communication issues?

Case Study 2

• 33-year-old, 150 kg female with failed gastric bypass

• Bowel was nicked during surgery• 4 days post-op develops

wound infection• 8 liters of fluids over past 48 hours• On cefotaxime and gentamicin• Norepinephrine at

10 µg/min• Hydrocortisone 200 mg IV daily• PEEP 12 cm H2O, FiO2 90%• Sedated (RASS – -2)• Lactate 5.9

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Summary

� Recognize sepsis early

� All infections should be examined for signs of SIRS

� IF sepsis is present

� Obtain blood or site cultures

� Obtain lactate

� Initiate antibiotics

� If organ failure is present, or increased lactate – give 30 ml/kg of

fluids

� If these measures are done in a timely basis, sepsis mortality can

be reduced 50%