Severe Sepsis Education

Why is there a Severe Sepsis Project?

• TJUH observed to expected mortality ratio in sepsis is high

– United Health Consortium expected mortality from sepsis 21%

– TJUH observed mortality from sepsis 34%

– Observed/expected ratio 1.59

– More patients died from sepsis than stroke and CHF combined

• Sepsis processes and outcomes will be monitored similarly to patients with chest pain, stroke, and community acquired pneumonia in regards to time sensitive treatment and therapy

• Implementation of a severe sepsis protocol reduces mortality*

*The Surviving Sepsis Campaign. Crit Care Med 2010(38):367.

Baseline Data at TJUH

• Gram negative pyelonephritis was the most common etiology (50%)

• Areas of needed improvement

– Early identification of severe sepsis

– Cultures before antibiotics

– Early, appropriate, adequate antibiotics

– Adequate fluid, vasopressor resuscitation

– Documentation of I/O’s

– Prompt triage to intensive care unit

Objectives

• To differentiate between SIRS, sepsis, severe sepsis, and septic shock

• To evaluate all patients for potential severe sepsis by clinical assessment and use of tools such as SIRS alerts and sepsis first line orders

• To implement severe sepsis protocol in an efficient and timely manner

• To promptly transition care to an intensive care unit

Sepsis: a growing concern

• 10th leading cause of death (200,000 deaths/year)

• 5-10 billion dollars/year of healthcare cost

The number of cases and case fatalities from sepsis is expected to increase due to:

– Aging of the population

– Increasing patients with multiple co-existing morbidities

– Increasing bacterial resistance and opportunistic infections

– Increasing use of invasive devices for monitoring and therapy

– Increasing use of immunosuppressive medications

SIRS/Sepsis: ACCP/SCCM Definitions

• Infection: inflammatory response to microorganisms, or invasion of normally sterile body tissues

• Systemic Inflammatory Response Syndrome (SIRS): systemic response to a variety of insults (burns, trauma, pancreatitis, infection)

• Sepsis is SIRS in the setting of suspected or proven infection

SIRS/Sepsis: Definitions

SIRS: presence of 2 or more of the following criteria

– Fever (core temperature > 38.3 C or 101.0 F) or hypothermia (core temperature < 36 C or 96.8 F)

– Heart rate > 90 beats/min

– Respiratory rate > 20 breaths/min or PaCO2 < 32 or need for mechanical ventilation for an acute respiratory process

– WBC > 12,000/mm3, < 4,000/mm3, or bands > 10%

Sepsis: patient meets the criteria for SIRS and has a suspected or confirmed infection.

Potential Clinical Clues for Suspected Infection

History/symptoms• Fever, chills, lethargy, or malaise• Productive cough• Headache• Sore throat• Diarrhea, abdominal pain• Dysuria, cloudy urine• Sick contacts• Recent surgery/instrumentation• Recent chemotherapy

Signs• Disorientation• Tachypnea• Tachycardia• Hypoxia• Hyper/hypo-thermia• Decreased urine output• Hypotension

Continuum from Sepsis to Septic Shock

• Sepsis

– 2 SIRS criteria plus suspected or documented infection

• Severe sepsis

– Sepsis plus at least one organ dysfunction (see next slide)

• Septic shock

– Sepsis plus persistent hypotension despite fluid resuscitation, or

– Perfusion abnormalities

Acute Organ Dysfunction in Severe SepsisAcute Organ Dysfunction in Severe Sepsis

TachycardiaHypotensionVasodilatation Contractility

Jaundice Enzymes Albumin PT

Altered ConsciousnessConfusionPsychosis

TachypneaPaO2 <70 mm HgSaO2 <90%PaO2/FiO2 300

OliguriaAnuria Creatinine

Platelets PT/APTT Protein C D-dimer

NeuropathyMyopathy

Increased Mortality Along a Continuum

Rangel-Frausto, et al. JAMA 1995;273:117-23.

0

10

20

30

40

50

60

No SIRS SIRS2 SIRS3 SIRS4 Sepsis SevereSepsis

SepticShockSeverity

Mo

rtal

ity

(%)

Severe Sepsis Criteria

Patient meets sepsis definition and has at least 1 sign of organ dysfunction*:

• SBP < 90 mmHg, MAP < 65 mmHg for at least one hour despite adequate fluid resuscitation (20 ml/kg saline) or use of vasopressors

• Lactate > 4 mmol/L• Urine output < 0.5 ml/kg/hr after adequate fluid resuscitation or rise in

creatinine > 0.5 mg/dL over baseline• PaO2/FiO2 ratio < 300 or requiring > 4 liters oxygen via nasal cannula to

maintain SpO2 > 90%• Platelets < 100,000/mm3, INR > 1.5, PTT > 60s

*Organ dysfunction must be new onset

Early Antibiotics Improves Survival in Septic Shock

“Golden Hours of Sepsis”

• Early recognition and intervention of patients with severe sepsis leads to improved outcomes

• Similar concept to:

– Acute coronary syndrome

– Stroke

– Trauma

Steps to Early Recognition and Management of Sepsis in ED

• First step: SIRS alert and identification

• Second step: First-line order sets

• Third step: Severe sepsis order set and rapid triage

First Step: SIRS Alert and Identification• SIRS alert will be triggered electronically in WellSoft when 2 or

more SIRS criteria are fulfilled (Clinical Decision Support column will turn pink)

Second Step: First-line ED Order Sets

• If there is a suspected or confirmed infection, sepsis first line (initial) orders are initiated in the emergency department:

Second Step: First-line ED Order Sets

Third Step: Severe Sepsis Initial Management Order Set in the ED and Rapid Triage

• Use Severe Sepsis ED initial management order set for patients who meet case definition

– Provides single doses broad spectrum IV antibiotics

– Other labs, vasopressors as needed

• Initiate rapid triage pathway

– Contact Pulmonary critical/care fellow and/or attending (or SICU attending for surgical patients) for admission

– Notify patient flow management center for ICU bed assignment

– Notify ICU charge nurse to help facilitate transfer

Severe Sepsis ED Initial Management Order Set

•Assess airway

•Insert/maintain 2 peripheral IV lines (18 gauge or larger) or place TLC for central IV access.

•Obtain baseline CBC with diff, Chem 7, lactate, Accucheck, VBG, blood cultures x 2, U/A with culture, PT/PTT, and CXR.

– Obtain further labs as indicated e.g. other cultures, cortisol level, LFTs, urine pregnancy.

•Begin broad spectrum IV antibiotics within 1 hour of RECOGNITION of severe sepsis* (see Figure)

•Administer 0.9% sodium chloride x 2 liter IV fluid bolus (or 20cc/kg)

•Place foley catheter to monitor urine output

*ED staff: Time from door to administration of antibiotics needs to be within 3 hours

Severe Sepsis Emergency Dept. Mgmt Orders (provides single doses of broad spectrum IV antibiotics)

Sepsis Emergency Dept. Management(Meds)

Severe Sepsis Order Set (continued)

•If MAP < 65 or SBP < 90 after initial bolus, place central venous line (preferably SC or IJ) and initiate vasopressors

•Continue IV fluids as per physician discretion

•Document vital signs (HR, BP including MAP, RR, O2 sat) and I&Os Q1hour x 2 sets, then frequency as per physician discretion

Antibiotic Management

•Begin intravenous antibiotics within 1 hour of recognizing severe sepsis

•Use broad spectrum agents active against likely bacterial/fungal pathogens and with good penetration into presumed source (see Figure on next slide)

•Reassess antimicrobial regimen daily to optimize efficacy, prevent resistance, and avoid toxicity

– All antibiotic regimens will be reviewed within 48-72 hours by the antimicrobial stewardship program

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if intra-

abdominal infection suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if intra-

abdominal infection suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if

intra-abdominal infection

suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if intra-

abdominal infection suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if intra-

abdominal infection suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID

consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

History of multi-drug resistant gram negative infection/colonization within past 90 days

OR

Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days

Beta Lactam Allergy Beta Lactam Allergy

NO YES

Aztreonam

+

Vancomycin

+

Tobramycin

+ or -

Metronidazole

add metronidazole only if intra-

abdominal infection suspected

Meropenem

+

Vancomycin

+

Amikacin

Consider previous susceptibilities

and/or ID consultation

Aztreonam

+

Vancomycin

+

Amikacin

+

Tigecycline

Consider previous susceptibilities and/or ID consultation

Pip/Tazo

+

Vancomycin

+

Tobramycin

SUBSTITUTE

Ceftriaxone

for pip/tazo in suspected meningitis

If suspected intra-abdominal catastrophe (i.e. perforation) suspected, add anidulafungin

If community acquired or health-care associated pneumonia is suspected, add moxifloxacin

YES NOStart antibiotics

within 1 hour

of recognizing suspected severe

sepsis

Start antibiotics

within 1 hour

of recognizing suspected severe

sepsis

NO YES

Antibiotic Compatibilities

  Amik Anid Az Ceftri Line Mero Met Moxi P/T Tig Tobra Vanco

Amikacin (Amik) X C C X C X C X C C X X

Anidulafungin (Anid) C X X X C C C X C X C C

Aztreonam (Az) C X X X C X X X C C C C

Ceftriaxone (Ceftri) X X X X X X X X X X X X

Linezolid (Line) C C C X X X C X C C C C

Meropenem (Mero) X C X X X X X X X X X X

Metronidazole (Met) C C X X C X X X C X X X

Moxifloxacin (Moxi) X X X X X X X X X X X X

Piperacillin/tazobactam (P/T) C C C X C X C X X C X C

Tigecycline (Tig) C X C X C X X X C X C C

Tobramycin (Tobra) X C C X C X X X X C X X

Vancomycin (Vanco) X C C X C X X X C C X X

C Compatible

X Incompatible or No Data Available Regarding Compatibilities

Antibiotic ManagementImportant Things to Remember

1. Check antibiotic compatibilities to see if antibiotics can be administered concurrently

2. If antibiotics can not be administered together due to incompatibility (e.g. piperacillin/tazobactam and tobramycin), use second peripheral IV line (or different lumens of TLC) to avoid delay

3. If only one IV line available, give gram negative agent first (piperacillin/tazobactam, aztreonam, or meropenem) unless specified (e.g. suspect gram positive line infection)

Hemodynamic Management

•Administer 0.9% Sodium chloride x 2 L IV bolus (or 20 ml/kg IV bolus) for volume resuscitation

• If MAP < 65 or SBP < 90 after initial bolus, place central venous line (ideally SC or IJ) and initiate vasopressors

•Continue IV fluids as per physician discretion

Vasopressor Management

• If MAP < 65 or SBP < 90 after initial volume resuscitation, initiate norepinephrine at 0.1 mcg/kg/min. (preferred) or dopamine

• If patient has persistent or increasing vasopressor requirements, initiate vasopressin infusion at 0.04 units/min.

•All patients on vasopressors require vital signs with every titration and every 1 hour once blood pressure goal is achieved

– IV site should be checked frequently

Vasopressors in Severe Sepsis

• Administer norepinephrine or dopamine via central line– Peripheral administration of norepinephrine or dopamine permitted for no

longer than 60 minutes via at least a 20 gauge catheter until central line placed

Drug Standard Concentration

Dosing

Norepinephrine 16 mg / 250 mL NS

(64 mcg/mL)

Initiate at 0.1 mcg/kg/min

Titrate by 0.1 mcg/kg/min Q5min to achieve MAP > 65 mmHg

Maximum infusion rate: 2 mcg/kg/min

Dopamine 800 mg / 250 mL D5W

(3.2 mg/mL)

Initiate at 10 mcg/kg/min

Titrate by 5 mcg/kg/min Q10min to achieve MAP > 65 mmHg

Maximum infusion rate: 20 mcg/kg/min

Vasopressors in Severe Sepsis

• If patient has persistent or increasing vasopressor requirements, initiate vasopressin continuous infusion– Emergent peripheral administration of vasopressin permitted for no longer

than 60 minutes via at least a 20 gauge catheter until central line placed

Drug Standard Concentration Dosing

Vasopressin100 units / 250mL NS

(0.4 units/mL)0.04 units/min

Importance of Documentation

• Documentation in a manner that is accurate and accessible to all disciplines is imperative:

– Necessary for the ongoing treatment of the patient

– Necessary to monitor quality of care metrics

• Blood cultures before antibiotics

• Early, appropriate, adequate antibiotics

• Initial fluid resuscitation

• Use of vasopressors for hypotension despite initial fluids

Documentation: Antibiotics

• Name of antibiotics

• Dosage of antibiotics

• Time started

• Route of administration

• Note: 2 blood cultures, U/A, and urine culture should be obtained before administration of antibiotics

Documentation: Fluid Resuscitation

• All fluid boluses must be ordered in Jeff Chart

• Nursing must sign out each bolus and record in a timely matter

• Document response to fluids (Vital signs, urine output)

• Accurate documentation of inputs and outputs

• Document initiation and titration of vasopressor

Rapid Triage Pathway

• Patients identified as having SEVERE SEPSIS will have the rapid triage pathway initiated:

– Call MICU Pulmonary/Critical Care fellow and/or attending (or SICU attending for surgical patients) for admission

– Notify patient flow management center for bed assignment. Patient will be prioritized to MICU (or SICU for surgical patients).

– Notify ICU charge nurse to help facilitate transfer

****Process of transfer should not delay therapy ****

• Antibiotics MUST be initiated in ED

• Provide vasopressors, additional IV fluids, perform imaging, etc. as needed prior to transfer

Hand-off Communication

• Physician to physician communication

– ED physician must sign out patient to ICU resident OR nurse practitioner

• Nurse to nurse communication - ED nurse report

– Time severe sepsis identified and pathway initiated

– Labs, cultures sent

– Times each antibiotic started

– Fluids received (IV fluid type and amount); urine output

– Venous access available (central access/large bore peripherals)

– Pending diagnostic studies (i.e. CXR, ABGs, labs, CT scans)

– Next steps for therapy

ICU Nurse Report

• Highlight on report sheet “severe sepsis protocol”

• Important documentation for severe sepsis patient

– Time severe sepsis was identified

– Total amount of fluids given for resuscitation and when

– Time and type of pressor (if started)

– Confirm 2 blood cultures, U/A, and urine culture sent

– Times each antibiotic was started

– ***If delay in antibiotics, document why and notify the physician immediately***

ICU Initial Care

**Sepsis Inpatient Management order set must be entered into JeffChart

• Assure room properly prepared for admission

• Possible arterial line set up (cables)

• Have line cart available

• Communicate with pharmacy regarding any need for back up IV drips (i.e. vasopressors, fluids)

• Charge Nurse enters patient name in database with primary diagnosis of severe sepsis

• Notify respiratory if ventilator is needed

Use Severe Sepsis Inpatient Management Order (following ED order set with one time antibiotic doses )

Sepsis Inpatient Management Order Set (Choose the appropriate MEDS)

Choose Initial and Maintenance

for those patients who HAVE NOT received

any appropriate antibiotics thus far

Choose Maintenance only

for those patients who HAVE received

one time dose of antibiotics

Other Sepsis Management Steps

• Control the source of infection

• Use the ARDS protocol if there is a concern for acute lung injury

• Consider use of cortisol replacement

• Use goal directed resuscitation (lactate clearance, CVP, ScVO2 acceptable)

Continued Sepsis Management

• Promptly de-escalate/ alter antibiotics based on culture results and other clinical data

• Stop antimicrobial therapy if cause is found to be noninfectious

• Remove catheters (central lines, foley) as soon as no longer required

• Duration of antibiotic therapy typically limited to 7-10 days, longer if response is slow or there are undrainable foci of infection or immunologic deficiencies

Summary

• Promptly identify Severe Sepsis using clinical judgment and ED assessment tools such as the WellSoft SIRS alert and first-line order set

• Use severe sepsis order set to expedite treatment

• Efficient management also requires:

– Rapid triage to ICU

– Accurate documentation

– Effective communication during transition of care

Severe Sepsis Protocol Key Elements

• Collect blood cultures before antibiotics

• Start appropriate IV antibiotics within 1 hour

• Administer rapid, adequate fluid resuscitation

• Start vasopressor if MAP <65 after initial IV fluid bolus