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From Theory to Evidence In the Management of Sepsis

Presented ByAlfonso Torress-Cook, Dr.P.H.

Director of Epidemiology/Patient SafetyPacific Hospital of Long Beach

Healthcare-associated infections are one of top 10 leading causes of death in the U.S.1 The US Centers for Disease Control and Prevention (CDC) estimates that 1.7 M patients experience a hospital-acquired infection each year.

Hospitals have invested considerable resources in methods to reduce hospital-acquired infections (HAI’s) – screening, hand washing, isolation, etc However, prevention measures often fail

The clinical and economic impact of an infection can be far greater if the patient becomes septic. Effective measures to prevent sepsis and to diagnose and manage these patients are critical to decrease mortality and reduce hospital costs.

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The Landscape of Healthcare-Associated (HCA) Infections Healthcare system is evolving to an increased use of

outpatient procedures and long-term care

Hospital or Acute care setting

Home careOutpatient facility

Long-term-care facility

Many long-term-care facilities now experience infection rates comparable to those in acute hospital settings Outbreaks are common

Raising the bar for Health care

Recent shift in health care with patient safety becoming a priority, and quality care delivered using evidence based practice and expectation.

IHI Collaborative 5 Million Lives Campaign CMS Measures (New changes October 2008) Joint Commission National Patient Safety Goals Media coverage of high profile

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Changing Vantage Points

Infection are not longer considered inevitable consequences of treating older, sicker or uninsured patients.

Now we hear terms like “zero tolerance". "pursuing perfection”, “irreducible minimum”, “lean”, and “six sigma”

The idea is to aim for perfection rather than match the bench marks set by (NHSN, APIC, SHEA)

PHLB adopted the Lean concept in 2009

“A pessimist see the difficulty in every opportunity; an optimist sees theopportunity in every difficulty.” Winston Churchill

A General Overview

Our hospital launched a program the second quarter of 2007, guided by the Institute for Healthcare Improvement (IHI), to improve the care and safety of our critical ill patients.

Our ICU implemented a Severe Sepsis and Septic Shock order set that includes all components of the Sepsis Resuscitation and Sepsis Management Bundles

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PACIFIC HOSPITAL OF LONG BEACHADULT SEVERE SEPSIS/SEPTIC SHOCK ORDERS SET

Goals1.Early identification and initial therapy for sever sepsis/septic shock patient.2.Increase central venous pressure (CVP) to 8-12 mm Hg with IV fluids prior to initiating a vasopressor if patient or ventilator may need CVP of 15 mm Hg.3.Maintain mean arterial pressure (MAP) greater than 65 mm Hg (or alternately SBP greater than 90 mm Hg) with vasopressor support if unable to achieve with fluid resuscitation.4.Maintain central venous O2 sat (ScvO2) at greater than or equal to 70% via venous blood gas. If PA catheter placed, keep mixed venous saturation (SmvO2) greater than or equal to 65%.5.Achieve/maintain adequate oxygen delivery to tissues with sepsis/resuscitation bundle (goals 1-4) within 6 hours and complete sepsis management bundle within 24 hours of initiating order set.

Admit to ICUDiagnosis: Severe Sepsis/Septic ShockAllergies ______________________________________Height ___________________Weight ___________________ Diet NPO___Diagnostic Tests Obtain and order STATo CBC, CMP, Mg, Phos Liver function test, PT, PTT, Type and screen, MI panel Lactic acido Blood cultures x 2 may be done same time from two different sites one from central venous access (if present);

one peripheralo Sputum /endotracheal asp. G/S and C&S.o Wound (if present) G/S and C/S specify location____________o MRSA rapid testingo UA, Urine C&S o ABGo Portable CXRo 12 lead EKGo Accucheck q 6 hrs (if indicated)Treatment and Interventions o IV, Normal Saline 1 liter bolus x 1 follow witho IV ________________ theno IV _______________ at ____ml/hro Other IV fluid_______0.9NS_______LR_____o Colloid ___________________________________o Insert Foley catheter and measure I/O Q1oo Consent and for central venous catheter to measure CVP (central venous pressure)o Measure CVP Q1oo If CVP is less than 8 mm Hg give 0.9NS__ @ 500 ml Q30 minutes until CVP is 8-12 mm Hg and notify house

officer.o If CVP 8-12 mm Hg give 1L NS____LR____@150ml/houro If CVP greater than or equal to 13 - 18 mm Hg keep IV TKOo Notify the house officer if CVP less than 8 mg Hg or greater than 17 mm Hg.o If patient on ventilator, keep CVP at 12-15 mmHgVasopressorso Maintain MAP pressures greater than 65 mm Hg or SBP greater than 90 mm Hgo Vital signs Q15 minuteso Start vassopressor if (MAP greater than 65mmHg or SBP greater than 90 mmHg) if not achieved with fluids.o Norepinephrine/Levophed 4 mg/D5W 250 mL start at 2 mcg/min titrate to max of 20 mcg/min.o Dopamine (400 mg in D5W 250 ml) start at 5 mcg/Kg/min max of 20 mcg/Kg/mino If remains hypotensive despite use of the above pressors add Vasopressin 100 units in 250ml NS at 0.04

units/min.o Notify H.O. if MAP less than 65 mm Hg (or SBP less than 90 mm Hg) for use of additional pressor orders.o Notify H.O. if MAP greater than 160 mm Hg without pressors.Blood Transfusiono Consent for blood transfusion If Hct less than 24% and Hbg less than 8Gm/dl transfuse 2 units PRBC.o Premedicate prior to transfusion with o Tylenol (acetaminophen) 650 mg P.O or via G tube or Tylenol 650 mg PR, , ando Benadryl 25 mg IVP x 1O2 TherapyInsert arterial line – if indicated

Obtain daily lactate levels unless equal to or less than 2.5mmol/liter.

Check O2 Sat by pulse oximetry continuously.O2 by NC/face/mask/ bipap/ventilator to keep O2 sat greater than 92%HHN/Inline treatment with Albuterol/Atrovent unit dose Q 4o

Obtain central venous O2 saturation by sending venous blood gas from central line or obtain mixed venous blood gas For mechanically ventilated patients, contact pulmonologist to set VT 6ml per ideal body wt, and keep plateau pressure less than or equal to 30 cm H2O and add peep of 5 cm H2O unless contraindicatedMedicationso Tylenol 650 mg rectaly or G/tube every 6 hours PRN temperature greater than or equal to 100.4o F o Start insulin drip protocol for BS____DVT Prophylaxiso Heparin 5000 Units SQ every 8 hrso Fragmin 5000 IU SQ dailyo Sequential pneumatic compression boots continuouslyStress Ulcer Prophylaxiso Protonix 40 mg IVP daily oro Pepcid 20 mg IV q 12 hrsAntibiotic OrdersAntibiotics dosing shall be adjusted by pharmacy based on renal function (Clcr).Source: Unknown origin of infection, complicated UTI/pyelonephritis, abdominal/pelvic infections, and deep soft-tissue infections.Zosyn 4.5 gm IV every 8 hours PLUS Tobramycin 2 mg/kg IV x 1, then per pharmacy PLUSVancomycin 1 gm IV x 1 then per pharmacy (if MRSA is suspected)For patients with severe or unknown allergic reactions to PCNo Aztreonam 1 gm IV every * hours PLUS Tobramyxcin 2mg/Kg IV x 1 then per pharmacy PLUSo Vancomycin 1 gm IV x 1 then per pharmacy (if MRSA suspected) PLUSo Flagyl 500 mg IV every 6 hours (if anaerobes are suspected)Source: Complicated PNA o Zosyn 4.5 gm IV every 6 hours PLUS Tobramycin 2mg/kg IV x 1, then per pharmacy PLUSo Azithromycin 500 mg IV every 24 hours (if atypical pathogens are suspected)For patients with severe or unknown allergic reactions to PCNAztreonam 1 gm IV every 8 hours PLUS Levaquin 750 mg IV every 24 hours PLUS Tobramycin 2mg/kg IV x 1, then per pharmacy

PLUSVancomycin 1 gm IV x 1, then per pharmacy (if MRSA suspected)Source: Community-acquired PNAo Levaquin 750 mg IV every 24 hours PLUS Ceftriaxone 1 gm IV every 24 hoursFor patients with severe or unknown allergic reaction to PCN and/or Cephalosporinso Levaquin 750 mg Iv every 24 hours PLUS Aztreonam 1 gm IV every 8 hoursSource: Meningitiso Decadron 10mg IV every 6 hours for 2 days PLUS Vancomycin 1gm IV every 12 hours then per pharmacy

PLUS Rocephin 2 gm IV every 12 hours PLUS Ampicillin 2gm IV every 4 hourConsults: I.D. Consult_____________

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PHLB-Mortality Rate from Severe Sepsis/Septic Shock 2007 to 2011

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10

15

20

25

30

35

40

45

50

Per

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PHLB-Rate National Rate

Bundle Implementation

Re-evaluation ERParticipation

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The Burden of Severe Sepsis

ICU Post-Operative

E.R. MedicalSurgical

Units

U.S. Sepsis Statistics*Severe sepsis is reported in 2.26 cases per 100 hospital discharges and one in

five admissions to the ICU. 1

*Of the 750,000 + severe sepsis cases each year in the U.S., an estimated 215,000 (28.6%) patients die. 1

* Mortality associated with sever sepsis has been reported as high as 30 t0 50% 2

1. Angus, DC et al. Critical care Medicine. 2001; 29: 1303-13102. Shapiro NI, et al. Critical care medicine, 2006; 34: 1025-1032

Sepsis is Costly

Severe sepsis accounts for an estimated 40% of all ICU expenditures, totaling $16.& B in the U.S. alone. 1

The average length of stay and cost per case is 19.6 days and $22,100 respectively. 2

The cost of treating an ICU patient with sepsis is six times greater than that of treating a patient without sepsis. 3

1. Bone RC et al. Chest. 1992; 101: 1644-55 2. Angus, DC et al Critical care Medicine. 2001; 29: 1303-1310 3. Ed.brook, DL et al. Critical care medicine. 1999; 27: 1760-1767

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Sepsis: Leading cause of death in non-coronary ICUs

Opportunity Knocks

What if a series of interventions could markedly reduce the risk of Sepsis mortality ?

What if those interventions were already readily available in hospitals ?

What if all of those interventions were done all the time on each patient ?

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If Sepsis is an Infectious Disease , why aren’t we trying to prevent it?

Early Recognition is a Challenge

• 2% of all admissions – 20-25% of all mortality

• 60% from the ED, 40% from in-house pts.

No Diagnostic Test

•↑ Lactate means shock

• Mental status changes often only early sign

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PHLB-Mortality Rate from Severe Sepsis/Septic Shock 2007 to 2011

0

5

10

15

20

25

30

35

40

45

50

Per

cen

t D

istr

ibu

tion

PHLB-Rate National Rate

Bundle Implementation

Re-evaluation ERParticipation

Lean evaluation

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The Emergency Room

Implemented a “Sepsis Alert” screening tool in the Emergency Department.

Instituted ED chart review of patients admitted with a sepsis diagnosis to monitor compliance.

Gave feedback to ED staff and physicians ED staff and physician were educated to the

Sepsis Resuscitation Bundle Intensivists assisted the ED as needed

Initiated sepsis resuscitation (lactates, blood cultures, antibiotics, fluid resuscitation)

PACIFIC HOSPITAL OF LONG BEACH

ED Algorithm

CVP

MAP

Goal Achieved

Less than65mmHg

Less Than 8 mmHg 1000 mL crystalloid

8-12 mmHg

Norepinepherine

Greater than65 mmHg

Central VenousABG

Sats greater than70%

Sats lessThan 70%

Hct

Greater than 30 Less than 30

Dobutamine PRBCs

Initiate Broad Spectrum Antibiotic

Disclaimer: This is a clinical template and clinicians should use judgment for individualpatient encounter.

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Sepsis Bundle: Antibiotic Selection Clinical Pathway

Suspected Source of Infection

Suggested Antibiotics

Unknown Vancomycin per clinical pharmacy consult PLUS EITHER

Piperacillin/tazobactam 4.5 grams IV q6h

Intrabdominal Source Ampicillin/sulbactam 3 grams IV q6h OR

Piperacillin/tazobactam 3.375 grams IV q6h

OR Metronidazole 500 mg IV q8h PLUS Ciprofloxacin 400 mg IV every 12

hours Note: If risk factors for nosocomial or pseudomonas infection exist consider adding:

Tobramycin—dosing per clinical pharmacy consult

Urinary Tract Ciprofloxacin 400 mg IV q12h OR

Piperacillin/tazobactam 3.375 grams IV q6h

OR Ampicillin 2 grams IV q6h PLUS gentamicin per clinical pharmacy

consult.

Skin/Soft Tissue: Staphylococcus aureus (MRSA)

Vancomycin per clinical pharmacy consult OR

Linezolid 600 mg IV q12h OR

Daptomycin 4 mg/kg q24h OR

Oxacillin 2 grams IV q4h if MRSA not suspected or ruled out Skin/Soft Tissue: Clostridium perfringens (“Gas gangrene”), Group A Streptococcus

Penicillin G 6 million units IV q4h PLUS

Clindamycin 900 mg IV q8h

Aggressive surgical debridement recommended. Skin/Soft Tissue: Polymicrobial Necrotizing fasciitis

Meropenem 500 mg IV q6h

Aggressive surgical debridement recommended.

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GRAM POSITIVES

ureus - 94 - - - - - - - - - - 35 - - 97 100 385 erococcus faecalis - 35 - - - - - - - - 44 92 - - - - 90 98

erococcus faecium - - - - - - - - - - - - - - - - 10 20

p. pneumonia - - - - - - - - - - 100 - - - - 85 100 13

RAM NEGATIVES

netobacter baumanii - 23 35 - - - - - 23 -- 9 - - - - - - 66

oli 98 77 71 99 99 71 73 73 100 71 40 25 - - 83 50 - 456

erobacter cloacae 100 100 99 - - 85 90 96 100 90 78 - - - 88 85 - 27

bsiella pneumoniae 85 78 70 60 95 71 71 71 88 71 0 - - - 77 77 - 104

domonas aeruginosa 91 67 80 - - - 75 - 73 - 52 - - - 70 - - 122

teus mirabilis 100 68 80 64 100 98 98 75 - 65 25 63 - - 98 50 - 188

videncia stuartii 100 - - - 100 70 70 81 - 97 13 - - - 72 56 - 32

DE TO EMPIRIC ADULT ANTIBIOTIC THERAPY

AGNOSIS RECOMMENDED FORMULARY ANTIBIOTIC REGIMENS (DOSAGE IS BASED ON CICr ≥50 ml/mim)

SPIRATORY pical Pneumonia: oplasma, Legionella, Chlamydia pneumoniae;respiratory viruses

1. Azithromycin 500mg IV q24h 2. Levofloxacin 750 mg IV q24h 3. Doxycycline 100 mg PO BID (out-patient)

mmunity Acquired Pneumonia: p. pneumonia; H. influenza; M. Catarrhalis + Atypical microorganisms coplasma, Legionella, Chlamydia,)

Medical Floor: 1. Ceftriaxone 1gm IV q24h + Azithromycin 500 mg IV q24h 2. Levofloxacin 750mg IV q24h Intensive Care Unit (ICU): 1. Ceftriaxone 1 gm IV q24h + Azithromycin 500 mg IV q24h 2. Ceftriaxone 1 gm IV q24h + Levofloxacin 750mg IV q24h 3. PCN allergy: Aztreonam 1 gm q8h + Levofloxacin 750mg Iv q24h

iration Pneumonia: erobes, Klebsiella, Strep. pneumonia

1. Levofloxacin 750 mg Iv q24h + Clindamycin 600 mg IV q8h 2. Piperacillin/tazobactam 4.5 gm IV q6h

lthcare -associated Pneumonia / Hospital acquired pneumonia / tilator-associated pneumonia

erobacter sp, Serratia sp, Pseudomonas aeruginosa, S. aureus

1. Piperacillin/tazobactam 4.5 gm IV q6h + tobramycin 2. Cefepime 2 gm IV q8h + tobramycin 3. Add vancomycin if there is a risk of MRSA for empiric coverage

onic Bronchitis, Acute Exacerbations (Treat as outpatient)p pneumoniae, H. influenza, M.catarrhalis

1. Azithromycin 500mg PO x 1, then 250 mg PO daily x 4 days 2. Doxycycline 100mg PO BID 3. Levofloxacin 500mg PO daily Above regimens may be administered intravenously at the same dose and frequency

INE omplicated UTI: ve plus Klebsiella, Pseudomonas aeruginosa, S. aureus and MRSA

1. Nitrofurantoin macrocrystals 100 mg orally four times a day x 7 day 2. Trimethoprim/sulfamethoxazole 160/800 mg (DS) orally BID x 3-7

days, prescribe if E.coli resistance is 20% or less. 3. Levofloxacin 250 mg orally daily x 3-7 days; prescribe if E.coli

resistance is more than 20%. mplicated UTI or Pyelonephritis; above plus Klebsiella, Pseudomonas uginosa, S. aureus, MRSA

1. Cefepime2 gm IV q8h 2. Levofloxacin 500 mg IV q24h 3. Piperacillin/tazobactam 4.5 gm IV q8h. May add vancomycin if there

is a risk of MRSA

OOD teremia Gram (-) and (+), Anaerobes 1. Piperacillin/tazobactam 3.375 gm IV q6h +/- tobramycin

2. Cefepime2 gm IV q8h +/- tobramycin. May add vancomycin if there is a risk of MRSA.

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Antibiotic Utilization

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What does it take to improve?

Ideas

Execution

Will

Your commitment

Change Packages & Ideas from 

Peers

Testing, implementing and spreading at the hospital – PDSA 

cycles

Role of Leadership

Committed: Staff cannot improve withoutsupportive leadership.

Set the standard: “This is how we will practice”

Resources: Make time to work on testing

Share data: to motivate staff for change

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Me and What Army?

Form… a team (include adiverse staff)

Identify… a project champion

Identify… a process owner

Making your case to your CEO-COO-CFO-CNO

The Advisory Board Company .15096 S.090607

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Potential impact of EGDT-Your Hospital

Hospital’s Total discharges per year

Hospital Specific data

Estimated Numbers of Severe Sepsis Patients(based on 2.26% Incidence )

=Total Hospital Discharges per year x 2.26%

Estimated Severe SepsisPatients Treated(based on 51.2% compliance rate)

=Estimated Number of Severe Sepsis Patients x

51.2%

Potential Lives Saved(15.4% EGDT mortality based on 46% relative reduction in mortality rate of 28.6% )

=(Number of treated Severe Sepsis patients x 28.6% -Number of Treated Severe

patients x 15.4% EGDT mortality rate)

Potential Cost Reduction(based on 27% reduction)

=Number of Treated Severe Sepsis patients x 5,882

Nguyen, HB et al. Critical care Medicine. 2007; 35: 1105-1112Angus, DC et al. Critical care Medicine. 2001; 29: 1303-1310

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