1. Severe Sepsis Education

2. 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.

3. 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

4. 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

5. 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

6. 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

7. SIRS/Sepsis: Definitions
SIRS: presence of 2 or more of the following criteria
Fever (core temperature > 38.3 C or 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.

8. 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

9. Continuum from Sepsis to Septic Shock
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

10. Acute Organ Dysfunction in Severe Sepsis
Tachycardia
Hypotension
Vasodilatation
 Contractility
Altered Consciousness
Confusion
Psychosis
Oliguria
Anuria
 Creatinine
Tachypnea
PaO2 <70 mm Hg
SaO2 <90%
PaO2/FiO2 300
 Platelets
 PT/APTT
 Protein C
 D-dimer
Jaundice
 Enzymes
 Albumin
 PT
Neuropathy
Myopathy

11. Increased Mortality Along a Continuum
Rangel-Frausto, et al. JAMA 1995;273:

12. 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

13. Early Antibiotics Improves Survival in Septic Shock

14. “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

15. 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

16. 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)

17. 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:

18. Second Step: First-line ED Order Sets

19. 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

20. 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

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

22. Sepsis Emergency Dept. Management(Meds)

23. 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

24. 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 hours by the antimicrobial stewardship program

25. History of multi-drug resistant gram negative infection/colonization within past 90 days
Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days
Beta Lactam Allergy NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES

26. for pip/tazo in suspected meningitis
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 NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES
Rationale for 4 hour infusion of Zosyn: piperacillin/tazobactam is a beta lactam antibiotic with time-dependent activity. A 4 hour infusion allows for prolonged exposure of antibiotic to suspected pathogens.

27. add metronidazole only if intra-abdominal infection suspected
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 NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES

28. Consider previous susceptibilities and/or ID consultation
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 NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES

29. History of multi-drug resistant gram negative infection/colonization within past 90 days
Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days
Beta Lactam Allergy NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES
Tigecycline being used for ESBL/KPC coverage in patients that have Hx of MDRGN infxn/colonization and/or broad spectrum abx in hospital or LTC for >72h w/in prev. 14d

30. History of multi-drug resistant gram negative infection/colonization within past 90 days
Prior broad spectrum IV antibiotics within a hospital or long term care facility for > 72 hrs within previous 14 days
Beta Lactam Allergy NO
YES
Aztreonam +
Vancomycin
Tobramycin
+ or -
Metronidazole
add metronidazole only if intra-abdominal infection suspected
Meropenem
Amikacin
Consider previous susceptibilities and/or ID consultation
Tigecycline
Pip/Tazo
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
Start antibiotics
within 1 hour
of recognizing suspected severe sepsis NO
YES

31. Antibiotic Compatibilities
Amik
Anid Az
Ceftri
Line
Mero
Met
Moxi
P/T
Tig
Tobra
Vanco
Amikacin (Amik) X C
Anidulafungin (Anid)
Aztreonam (Az)
Ceftriaxone (Ceftri)
Linezolid (Line)
Meropenem (Mero)
Metronidazole (Met)
Moxifloxacin (Moxi)
Piperacillin/tazobactam (P/T)
Tigecycline (Tig)
Tobramycin (Tobra)
Vancomycin (Vanco)
Compatible C
Incompatible or No Data Available Regarding Compatibilities X

32. Antibiotic Management Important Things to Remember
Check antibiotic compatibilities to see if antibiotics can be administered concurrently
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
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)
Check antibiotic compatibilities, as some antibiotics can be co-infused
If there are multiple lines available, DO NOT DELAY administration of other agents while infusing the first antibiotic

33. 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

34. 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

35. 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

36. 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
Vasopressin
100 units / 250mL NS
(0.4 units/mL)
0.04 units/min

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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***

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

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

45. Sepsis Inpatient Management Order Set (Choose the appropriate MEDS)
Choose Maintenance only
for those patients who HAVE received
one time dose of antibiotics
Choose Initial and Maintenance
for those patients who HAVE NOT received
any appropriate antibiotics thus far

46. 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)

47. 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

48. 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

49. 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