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SEPSIS: THE IMMUNE

SYSTEM’S RESPONSE TO INFECTION

Dee Ann Totten, RN, MSN, CNS, APRN, CCRN, CEN

Disclaimer

I do not represent any Special Interest Group, Pharmaceutical Company, or Equipment/Merchandise Sales Group, or have any promotional interest in presenting this lecture. I have not received any payment from anyone other than KCNPNM!!!

Sepsis FactsSepsis is the #1 killer in the United States.

About 600 deaths daily .

50% will die without appropriate treatment.

Early diagnosis & treatment is essential.

Relationship antibiotics & treatment:

Antibiotics in 30 minutes = 82% survival;

3-5 hours = 50% survival

Economics

Sepsis costs $24 billion dollars a year (2014)

Most expensive inpatient cost

5% of U.S. Health Care Budget

Enormous public health burden

(JAMA, Feb., 2017)

DefinitionAccording to the Joint Collaboration Society of Critical Care Medicine & European Society of Intensive Care Medicine:

SEPSIS:

A life-threatening organ dysfunction caused by dysregulatedhost response to infection.

SEPTIC SHOCK:

Sepsis complicated by either hypotension or hyperlactatemia.

Historical PerspectiveSepsis is the oldest, most elusive syndrome in medicine:

Hippocrates – Father of Medicine 460-377 BC

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HistoryGalen – Greatest Physician ancient Rome 130 AD

HistorySemmelweis – Pioneer Asepsis 1818-1865

HistoryPasteur – Germ Theory - 1822-1895

FLOProgressive Insurance – “Name Your Price Tool”

HistoryFlorence Nightingale – Founder of Nursing - 1820-1910

HistoryAdvent of Modern Antibiotics

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History

YOU!!!

____________ (Insert your name here!)

Surviving Sepsis Campaign (SSC)

Established 2002

Goal: To decrease mortality from severe sepsis &

septic shock worldwide.

Established guidelines/protocols for rapid diagnosis &

treatment.

SEPTEMBER IS SEPSIS MONTH!

2015

Centers for Medicare & Medicaid Services established

hospital requirement to report:

1. Sample size of sepsis patients

2. Whether or not meeting SSC guidelines

Initatives

June, 2017 - New England Journal of Medicine

World Health Organization (WHO) made Sepsis a

“global health priority”.

Adopted a resolution to improve sepsis by prevention, diagnosis, & management.

Who Gets Sepsis?80% Sepsis begins outside the hospital

Most sepsis arrives at the hospital’s “front door” (ED)

Ages over 65 & less than 12 months

Weakened immune systems

Chronic medical conditions

Drug –resistant bacteria

Who Gets Sepsis?Males > Females

Blacks > Whites

Hospitalized /Nosocomial

Healthy People

Non-Infectious Causes

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Ground Zero - Screening Suspected or Confirmed Infection:

None

Acute abdominal infection

Bloodstream catheter infection

Bone/joint infection

Endocarditis

Sepsis Front Porch“Ground Zer0”

University of Pittsburgh Medical Center

Dr. Elizabeth Tedestco, Director of Emergency Services conducted a study to evaluate the outcome of SSC protocols in reducing sepsis mortality (2016).

Participants 247: 161 confirmed infections

52% met sepsis protocol

Results were published in Journal of Emergency Nursing, May , 2017.

RESULTS: 28% reduction in mortality though the number of patients identified as infected or septic went up 21.5%!!!

Pediatrics & Sepsis

We’re fighting hard to improve outcomes in pediatric sepsis!!!

Sepsis #1 cause of death pediatrics worldwide.

In the US the CDC ranks sepsis as 7th cause of death

pediatric patient (2014). Mortality = 25%.

SSC Goal: Give broad –spectrum antibiotics within 3 hours of Admission.

Children’s ED WakeMedRaleigh, NC

Hassing & Stone conducted study at their Children’s ED (2016).

Instead of the SSC goal of ABX in 3 hours, they would strive for within 1 hour of arrival . This was termed the “golden hour”.

RESULTS: Reduction in mortality by 10%!!!

Peds “Takes Guts”Signs & symptoms of illness/sepsis may be vague:

1. Poor feeding or not wanting to feed

2. Irritability

3. Inconsolability

4. Typically not hypotensive till too late

5. Prematurity risk

6. Auscultate to confirm VS.

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Suspected Infection & 2 or more SIRS? (10%)

HR > 90

RR > 20

Temp > 101 F or < 96.8 F (38.3 C or 36.0 C)

WBC > 12,000 or < 4,000

Bands > 10%

Altered Mental Status (AMS)

Severe Sepsis (40%)

Mental Status Changes; Decreased LOC

SBP < 90 or MAP < 65

O2 saturation < 90%

Lactic Acid > 2 mmol/L

SEPSIS AWARENESSUL HOSPITAL TIME CLOCK:

UL Employee Name Badge

ALERT

Sepsis – Main ED

Severe Sepsis – Room 9

MAIN ED ALERTWithin 15 minutes:

Sepsis Alert Broadcast

Measure Lactate POC (Repeat in 2 hours if up)

Labs: CBC, CMP, Lactic with Reflex if > 2 mmol/L

Blood Culture #1 on hold

Initiate Cardiac, SpO2, NIBP monitoring

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(continued)Start IV

Notify Attending Lactate POC result

Systemic Inflammatory Response Syndrome

SIRS = Identified by 2 or more: - fever or low temp

- tachycardia

- tachypnea

- change in blood

leukocytes

SIRS

Sepsis = SIRS + Infection

Sepsis is response to infection.

Severe Sepsis = SIRS + Infection + Organ Dysfunction,

Hypoperfusion, or Hypotension.

SOFAOrgan dysfunction is represented by the SOFA Score.

Stands for Sepsis Organ Failure Score

Score of 2 or more points is associated with a

increase in hospital mortality by > 10%.

• Out of hospital bedside SOFA Score: RR > 22, AMS,

SBP 100 or less.

Within 1st Hour:Blood culture #2 (Phlebotomy)

IVF 30 ml/kg if lactate > 4 or hypotension (crystalloids)

Start Antibiotics (Broad Spectrum)

Identify source of infection

(PCXR, UA POC & Culture, Sputum Culture)

If Septic Shock, assess fluid status

Repeat Lactate, reassess volume, vasopressors use (MAP < 65 after IVF’s or initial Lactate > 4mmol/L.

Additional SIRSGlucose (serum) > 140 or < 200 dl (if no DM)

Greater risk poor outcome:

B/P < 100 systolic

AMS

Decreased UO

Decreased platelet count

Decreased Hemoglobin

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Screening Tools Screening Tools

Screening Tools Signs & SymptomsS = Shivering, fever, very cold

E = External pain/discomfort

P = Pale, discolored skin

S = Sleepy, difficult to arouse, confused

I = “ I feel like I might die!”

S = SOA (shortness of air)

Infection

FEVER IS THE FIRST SIGN OF A BACTERIAL INFECTION!

“OH, RATS”

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Culprit MicroorganismsGram + Microorganisms: Staphlococcus

(purple) Streptococcus

Culprit MicroorganismsGram – Microorganisms: E-Coli

(red) Pseudomonas

Klebsiella

Enterobacter

Culprit MicroorganismsCombination m/o both + & -

Fungus

Parasites

Host1. Innate Immunity: “Alarmers”

2. Protease-Activated Receptors (PARS)

* PAR 1 in particular is implicated in sepsis.

3. Mechanism of Organ Failure:

- Low B/P

- Low RBC’s

- Microvascular thrombosis

- Inflammation

- Mitochondial dysfunction

- “Alarms” released

1. Endocarditis

Etiology: The Source Etiology: The Source2. Urinary Tract Infection (UTI)

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Etiology: The Source3. Pneumonia/Emphyema

Etiology: The Source4. Wound Infection

Etiology: The Source5. Acute Abdominal Infection

Etiology: The Source6. Meningitis

Etiology: The Source7. Implantable Device Infection

Etiology: The Source8. Bone/Joint Infection

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Etiology: The Source9. Skin & Soft Tissue Infection

Etiology: The Source10. Bloodstream Catheter Infection

Etiology: The Source11. “Found Down”

Etiology: The Source12. Non-infectious

Complications

*Blood flow to vital organs, brain, lungs, heart, &

kidneys becomes impaired.

* Blood clots form in organs & arms, legs, fingers,

toes …which leads to organ failure & tissue death.

Lab Tests*WBC

*Lactate

*Blood Cultures X 2

UA & Culture

CRP

PT/PTT/D-Dimer

Procalcitonin (PCT)

CMP

Cultures : Sputum/Abdominal/Wound

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Studies“Usefulness of Procalcitonin for the Diagnosis of

Sepsis in the ICU”

Balci, Swagurtekein, et al (August, 2017)

RESULTS: PCT was best predictor of Sepsis in the ICU.

Comparative study of PCT & CRP in early dx.

Better than WBC & temperature.

DiagnosticsPCXR

Abdominal US

Abdominal CT or MRI

ABG

EKG/Cardiac Enzymes

InvasiveThoracentesis

Paracentesis

Swan-Ganz Catheters

Evaluation for Surgery

Confirmatory Tests

Endotoxin

Procalcitonin

Septicyte (genetic component)

“Bundles” (2)SSC organized sepsis protocol into 2 “Bundles”.

Journal Critical Care Medicine – August – 2013

Bundle 1: Initial management within 6 hours of pt.

presentation.

Includes: CPR, IVF’s, Vasopressors, O2 therapy,

Mechanical Ventilation, Probable dx.,

Cultures, ABX, Source Control.

“Bundles”Bundle 2: Management ICU after 6 hours.

Includes:

- Organ Support

- Avoiding Complications

- De-escalating Care (if possible)

- Decreasing Antibiotics

- Immunotherapy Treatment

- Discontinuing Vasopressors

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Antibiotic Rules*Make sure you know patient’s medication

allergies!!!

Give 1 antibiotic at a time!

More than 1 IV line!

Best Antibiotics SepsisCarbapenems:

Meropenum (Merrem)

Imipenem (Pimaxin)

AntibioticsCephalosporins

Cefepime (Maxipime) 4th Generation

Ceftriaxone (Rocephin) 3rd Generation

AntibioticsPenicillins

Piperacillin-Tazobactum (Zosyn)

AntibioticsQuinolones

Levofloxacin (Levaquin) 3rd Generation

AntibioticsOther

Tigecycline (Tygacil)

Metronidazole (Flagyl)

Aztreonam (Azactam)

Vancomycin (Vancocin)

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Antimicrobial TherapyHandout

Depends on adequate coverage resident flora

presumed to be the source of sepsis process &

potential antimicrobial resistance patterns.

(“Bacterial Sepsis” – Emergency Medical Journal )

August, 2017

Studies“Fluid Resuscitation in Sepsis”

Annals of Internal Medicine – September 2015

RESULTS: 14 Studies Canada 2014, 18, 916 pts.

Compared crystalloids, colloids, starches.

* RESULTS: Best IVF replacement sepsis are

crystalloids!

EGDT

Early Goal-Directed Therapy

ICD 10 Code: Sepsis

Minimal 2 codes for severe sepsis:

1. Underlying systemic infection

2. Followed by code for

Severe Sepsis – R 65.2

3. If organ dysfunction other than septic shock

is present, the codes for the specific organ

dysfunction are added.

Post-Sepsis SyndromeAffects 50% of sepsis survivors! (increased risk if in ICU)

Physical and/or psychological long-term effects:

- Insomnia

-Nightmares

-Disability Muscles & Joint Pains

-PTSD

-Hair Loss

-Damage kidneys, lungs, liver

- Other: Amputations, Anxiety, Neurosensory loss, Chronic Pain/Fatigue.

Post-Sepsis Mortality

Mortality : SIRS = 6-7%

Mortality: Septic Shock = 50% (if source of infection was abdominal = 72%)

PROGNOSIS: POOR!!!

* Only 30% alive 1 year after hospital admission.

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Public EducationSepsis Alliance Group (non-profit)

Goal: Save lives & reduce suffering by raising awareness of sepsis as medical emergency.

2016 Survey found 55% of adults had never heard of sepsis, even though it was the 11th leading cause of death in 2014 according to the Center for Disease Control & Prevention.

Sepsis Alliance Newsletter

Question/Answer Format:

What is Sepsis?

Causes?

Population at Risk?

Signs & Symptoms?

Infection

Treatment

Long-term effects?

Prevention

Emergency

Events

Prevention: What About Us?

Wash Your Hands!!!

Clean your equipment!!!

Limit Antibiotic Therapy

Great History & Physical Exam Skills

Listen “to your gut”

Prevention1. Get vaccinated (flu/pneumonia)

2. Prevent infections: Clean wounds

Good handwashing

3. Know the signs & symptoms of sepsis.

4. Smoking Cessation

5. Urge parents unvaccinated kids to limit exposure

seek immediate care fever if < 28 days old.

CASE STUDY #1“New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction”

Julie Jacob, MA (JAMA – February, 2016)

Queens, NY

Male, age 12. Cut arm playing basketball @ school.

Next day, fever & leg pain. Pediatrician – ABX.

Day 2: ED – Diagnosis: “Upset stomach”. Discharged.

Died 3 days later from sepsis – Mortality!

* Parents funded Foundation to increase public awareness of sepsis!

Case Study #2“Management of Septic Shock”

Berger, Rivera, Levy MD’s (NEJM - June, 2017)

65 year old F with 3 day history of dysuria

PMH: HTN on Amlodipine 10 mg PO daily

ED: Chief complaint : “Dizziness”

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Case Study #2VS:

Ht: 65 inches; Wt. 70 kg (154#)

Temp 38.6 (101.4) Lungs: CTA

HR = 125 Warm extremities

B/P: = 85/55 Suprapubic tenderness

RR = 28

O2 Sat = 94% on RA

Case Study #2Labs:

Creatinine = 1.8 Hemoglobin = 9.0

BUN = 76 UA = 3+ leukocytes;

Lactate = 5.0 > 100,000 bacteria

Anion Gap = 25

WBC = 20,000

Case Study #2Started IV & ABX. F/C inserted. – Diagnosis = Probable

UTI

After 2100 ml NS IVF, CVP was 8.0. B/P 80/50 (MAP =60).

UO was 20 ml for the 3 hours she was in the ED.

CVP line placed & Levophed started at 4 mcg/min.

Moved to ICU

Case Study #2ICU: Diagnosis = Septic Shock

HR = 100

MAP = 65-70

CXR: Acute lung injury & good central line placement.

SvO2 < 70; transfused 1 unit packed RBC’s (HCT 30%)

Case Study #2ICU: Diagnosis = Septic Shock

EGDT Protocol Followed:

Continued on Vasopressors Hemodynamics

Intubated/Mechanical Ventilation SvO2 & CVP

Early resuscitation Early CVP line

ABX/IVF’s RBC’s – Hgb 10.0

*SURVIVAL: EGDT improves outcomes in patients sepsis &

septic shock ! (&7% vs. 23%)

Case Study #336 year old , white, F . Ht. = 62 inches. Wt. = 105#.

PMH: Appendecomy age 22. Mild Anemia.

Diagnosed with Crohn’s Disease age 32.

Numerous episodes N/V/D. Multi trips to ED with SBO.

Taking 64 meds a day to control inflammation.

PCP/GI MD/Surgical Consultations

Mao Clinic 3 day evaluation – PE, Labs, Colonoscopy, Consult

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Case Study #3Decides on OR, Small Bowel Resection in 1 week.

Presents day of OR to Pre-Op: N/V/D. Severe RLQ pain.

Fever 104 F. Abdominal distention. Hyperactive high-pitched BS. Guarding & rebound tenderness. Frail, pale, cool & clammy. Thready pulse @ 124/min. B/P 70/palpable. AMS. RR = 26. O2 sat = 95%. Rates pain as 10/10 “twisting pain that takes my breath away”. Vomitus – stool-colored brown & intractable. Family members at bedside.

Case Study #3Labs:

CBC = 22, 000 with 15% bands (left shift)

H & H = 9.0 & 40.

CMP = K+ 1.8

UO = < 20 ml/hr. Normal UA other than elevated BUN

No lactate or PCT (not available @ this time.

Case Study #3CXR = No active pulmonary disease

EKG = Sinus Tachycardia @ 124/min.

CT Abdomin & Pelvis: Free air; Bowel Perforation.

Management: T & C for 2 units PRBC’s

IV/IVF’s F/C to BSD urometer

Morphine/Phenergan Non-invasive monitoring

IV/IVF’s N/G Tube to LWS

ABX: Cephalosporin (Keflex) ; Cimetadine prophylaxis; IV K+ runs

Case Study #3Stabilized & OR 2 hours later: Small Bowel & Colon

Resection; Perforation

Recovery uneventful other than hypoxia RR 2nd to MS.

Hospitalized x 7 days. IVF’s & ABX. Discharged.

Home: 2 weeks later to ED intractable N/V.

TO ED: K+ 1.6. IV, Phenergan, IVF’s, K+ runs, Discharged.

SURVIVED!!! Alive & well; con’t battling Crohn’s.

Case Study #3

SEPSIS CAN HAPPEN TO ANYONE!!! EVEN YOU!!!

“Gloom & Doom”Sepsis…damages critical tissue

Sepsis…leads to failure of vital organs

Sepsis…causes death

The number of deaths from sepsis has increased in the last 20 years because the number of cases of sepsis have increased.

Mortality > 80% 30 years ago; now close to 20-30%.

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What’s In The Future?Failure last 30 years to develop effective strategies in

correcting underlying features of sepsis.

1. Glucocorticoids associated with most benefits.

2. Antibiotics

3. Better pre & clinical research trials.

4. Genetics

Future…5. More targeted drug development.

6. Activated Protein C

7. Interleukins/Interferons

8. Continue protocol revision & evaluation.

9. Education – public & medical personnel

10. *PREVENTION!!!

Studies

“Activated Protein C for Management of Sepsis”

NEJM December, 2009

RESULTS: Benefits controversial.

- Increased bleeding risks

+ Inhibited procoagulation state in sepsis

Future Is Bright!!!

VIDEO

“I’m Bringing Sepsy Back”

Kern Medical Center

Bakersfield, California

CONCLUSIONS = Screening patient for sepsis

E= Early intervention (Antibiotics; IVF’s)

P= Phlebotomy (Labs)

S= Source Identification

I = Interventions (Vasopressors; Hemodynamics)

S= Support Post-Sepsis

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Finally…

Reflections:

REMEMBER WHY?

The End!

Questions???

Thank-You!!!