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6/14/2011

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Sepsis – A Medical Emergency

State of the Science Symposium –Best Critical Care Practices 2011

Jim O’Brien, MD, [email protected]

Disclosures, 2004-May 2011

University grant monies: Davis/Bremer Medical Research Award ($50K, 3/05 – 2/07)

Non-industry grant monies: NHLBI K23 HL075076 ($520,992, 4/05 – 3/09); NIH Clinical Research Loan Repayment Program ($152,781, 10/03-6/05, 7/06-6/10 )

Industry grant monies: PI for aerosolized amikacin (Aerogen, $0, 8/05 – 6/06)

PI f lf t t (P $0 9/08 t)

I think sepsis is under‐appreciated.

I think sepsis is under‐funded.

PI for calfactant (Pneuma, $0, 9/08 – current)

Consultant/Speakers’ Bureau: Unrestricted educational grant from Lilly to present talk at SCCM (2005) Consultant to Medical Simulation Corporation ($4000, 2005-2006) Co-author on manuscript with Lilly employees Consultant to Keimar, Inc ($0) Board of Directors, Sepsis Alliance

Honoraria to Sepsis Alliance (Travel/accomodations may have been provided) Lecture on future perspectives on sepsis definitions (Brahms, 2009). Lecture on sepsis treatment (GE, 2011) Video on sepsis communication (GE, 2011) Webinar on sepsis (Siemens, 2011)

I think we over‐complicate sepsis care (MD effect)

I think that I have less to offer septic patients once they are in the ICU.

I think that it is inevitable that we will get our act together. Only question is how many of us will die first.

Goals today

Review the definition of sepsis

Review why ideal sepsis care continues to elude us Quality and Safety

Make the case for simplifying sepsis careMake the case for simplifying sepsis care (“Lean Sepsis”)

Antibiotics Fluids Medical emergency

At least one of you will save someone’s life as a result

24 hours

6 hours

Suspicion

Resuscitation

Initial ManagementrhAPC PACsVasopressors

antiTNF

4

Pre and post‐discharge

Hospitalization

24 hours

Maintenance

Recovery

Steroids

antiIL‐1

PAFase

tifacogin

ibuprofenGlucose control

24 hours

6 hours

Suspicion

Resuscitation

Initial Management

Pre and post‐discharge

Hospitalization

24 hours

Maintenance

Recovery

So what is sepsis anyway?

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So what is sepsis anyway?

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According to the Consensus definition, what is sepsis?

1. Blood poisoning2. Bacteremia3 Shock due to infection3. Shock due to infection4. Fever due to infection5. None of the above

Sepsis:Defining a Disease ContinuumSIRS = Systemic Inflammatory Response Syndrome

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

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SIRS with a presumed or confirmed

infectious process

Adapted from: Bone RC, et al. Chest 1992;101:1644, Opal SM, et al. Crit Care Med 2000;28:S81

According to the Consensus Conference definition, which of the following is NOT a SIRS criterion?

1. SBP<90 and/or MAP <702. Heart rate >903. Respiratory rate >20 or PaCO2<324. Temperature >38⁰C or <36⁰C5. WBC >12K or <4K or >10% bands

Sepsis:Defining a Disease ContinuumSIRS = Systemic Inflammatory Response Syndrome

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

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A clinical response arising from a nonspecific insult, including 2 of the following:• Temperature 38oC or 36oC• HR 90 beats/min

• Respirations 20/min

•WBC count 12,000/mm3 or4,000/mm3 or >10% immature neutrophils

Adapted from: Bone RC, et al. Chest 1992;101:1644Opal SM, et al. Crit Care Med 2000;28:S81

What do MDs think about sepsis?Poeze et al. Crit Care 2004; 8: R409-13

1058 in US and Europe surveyed by telephone by professional survey company

Based on everything you know, how do you define

•22% of intensivist gave Consensus definition (5% other MDs)•17% agreed on one definition6 diff t d fi iti

sepsis?•6 different definitions were mentioned by at least 10% of respondents



How do you communicate about sepsis?

•81% find it difficult to communicate with families about sepsis•85% describe sepsis as complication f d l i ditifrom underlying condition

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How do you communicate about sepsis? 10% say “SEPSIS”

What does the public know about sepsis?Harris Poll Funded by Sepsis Alliance

1004 in US surveyed by telephone by professional survey company from June 23-27, 2010

Have you heard the term “No” in 67%Have you heard the term sepsis?

No in 67%

Sepsis is a life‐threatening condition that arises when the body’s response to infection injures its own tissues

Talk the talk

15

the body s response to infection injures its own tissues and organs.

Sepsis incidence, 1999-2003

22%

44%ence X103

Sepsis Severe Sepsis Septic shock Death in sepsis

%73%

Source: Nationwide Inpatient Sample

Incid


In 2003,

1 in 35 of ALL hospital admissions involved sepsis

1 in 66 involved severe sepsis

ence X103

Sepsis Severe Sepsis Septic shock Death in sepsis

1 in 233 involved septic shock

Incid



20 7%

ence X103

Sepsis Severe Sepsis Septic shock

20.7%21.7%

Death in sepsis

Incid

16%


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20 7%

In 2003,

1 in 35 of ALL hospital admissions involved sepsis

1 in 66 involved severe sepsis

22%

44%

In 2003, 23.2% of all deaths during hospitalization involved sepsis

(up from 19.4% in 1999)

In other words….ence X103

Sepsis Severe Sepsis Septic shock

20.7%21.7%

Death in sepsis

1 in 233 involved septic shock

%73%

16%

1 in 4.3 deaths of hospitalized patients involves sepsis

Incid


215,000 deaths a year in US

Deaths from Breast cancerLung Cancer

228 Deaths every ~9 h

2974 Deaths Every ~5 days

3212 deaths every ~5.5 days

Lung Cancer+ Prostate Cancer

TOTAL < Deaths from Sepsis

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The greatest trick the Devil ever pulled was convincing the world he didn’t exist.

‐Roger Kint

Patients admitted through ED Main Jan‐March 2009 (n = 4951)

Randomly selected charts reviewed

Received ATBs within 24 hrs of admission (n = 941, 19.0%)

Sepsis Recognition at OSUMC

That extrapolates to 768 unrecognized septic / l !

Patients with sepsis upon ED presentation (n = 137, 27.4%)

Recognized as septic in ED notes and/or H&P (n = 35, 25.5%)

Not recognized as septic in ED notes and/or H&P

(n = 102, 74.4%)

(n = 500, 53.1%)

Dreher et al Manuscript in preparation……

patients/year at OSU Main ED alone!

Antibiotic Therapy & Blood Cultures

p = 0.004 p = 0.165 p = 0.001

All Subjects: 56.2% 30.7% 77.4%

All subjects Recognized Not recognized P value

Hours to Order 1.9 (1.1 – 3.0)

1.3 (1.0 – 2.0)

2.1(1.3 – 3.5)

0.012

Hours to Administration

2.6 (1.9 – 3.9)

2.1 (1.7 – 3.7)

2.8 (2.0 – 4.5)

0.043

Dreher et al Manuscript in preparation……

What can YOU do?

Say Sepsis Causes you to think about diagnosisg Raises awarenessMay improve care

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Which of these is sepsis?

1. Confusion, cough, nausea2. Fever, shortness of breath, chest

pain3. Abdominal pain, lightheadedness, We have to ACT when we are p , g ,

diarrhea4. Rash, leg swelling, anorexia5. Tachycardia, chills, sweating

uncertain.

Stop RECOGNIZING Start SUSPECTING

Levy et al, Crit Care Med 2003; 31: 1250‐6

Antibiotics - Minutes Matter

•Every hour in delay of appropriate atbx = 7.6% lower survival

•Median time to appropriate atbx = 6h

Kumar et al. Crit Care Med 2006; 34: 1589‐96.

40

50

60

70

80

90

age of patients

*Assuming 130,000 septic shock cases per year

Shock to effective antibiotic time and mortality in septic shock*

Adapted from Kumar et al. Crit Care Med 2006; 34: 1589‐96.

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

%Mortality 26.7 36.1 36.6 46.8 62.3 83.1

% of patients 26.8 9.0 7.8 12.8 18.8 24.9

0

10

20

30

40

Percenta

15

20

25

tage of patients

*Assuming 400,000 STEMIs per year

Door to balloon time and mortality in STEMI*

By getting door‐to‐balloon times of <2h for ALL STEMI patients,

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

% Mortality 4.9 5.2 6.5 6.7 6.9 5.5

% of patients 8 23.5 21.1 21.6 17.3 8.5

0

5

10

Percent

Adapted from Cannon et al. JAMA 2000; 283: 2941‐7.

we would save 4775 lives per year.(13 people a day)

40

50

60

70

80

90

age of patients

*Assuming 130,000 septic shock cases per year

Shock to effective antibiotic time and mortality in septic shock*

By getting shock‐to‐antibiotic times of <2h for ALL septic shock patients,

we would save

Adapted from Kumar et al. Crit Care Med 2006; 34: 1589‐96.

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

%Mortality 26.7 36.1 36.6 46.8 62.3 83.1

% of patients 26.8 9.0 7.8 12.8 18.8 24.9

0

10

20

30

40

Percenta we would save

32,360 lives per year.(89 people a day)

(3.7 people an hour)(3.5 times the effect of STEMI intervention)

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The first 12 hours matters even more

For first 12 hours, 1% mortality per 5 minute delay

Funk and Kumar, Crit Care Clinics 2011; 53‐76.

What can YOU do?

Say Sepsis Suspect Sepsis Common in Common in hospitalized patientsNo single symptom/sign Effective communcation

Affecting the emergency response to sepsis: Antibiotics

Sepsis onset ABX orderABX

administration

•Education•Automatic triggers•Decision support

•Processes•StructuresIs there any situation in which you are giving

antibiotics for an infection in which you

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ABX order time (Clinician Action)

ABX order to administration time (System Response)

Sepsis to ABX administration time (Performance measure)

want the initial dose delayed?

Maybe we should focus on time from order to administration?

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Not all orders are created equal

ROUTINE – will be scheduled for next usual scheduled administration time. QD = 9am

NOW– will be prepared in usual queue then delivered with next scheduled delivery and administered when it arrives

STAT – prints on different printer, different color paper, prepped immediately, immediately delivered to unit

Order Priority Comparisons

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Timeline

Pre‐intervention

Intervention Post intervention

8/24/08 1/1/09 3/31/09 6/7/10

•Educational•Sepsis Order Set

•Antibiotics by Site •Antibiotics in Pyxis

•Data collection platform

ATB By Site of Infection ICU

ATB By Site of Infection ICU-CAP

Order Priority

STAT NOW ROUTINE

180

210

240

270

300

330

Median time to antibiotics (min) in septic shock

4242

0

30

60

90

120

150

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35%

40%

45%

50%

55%

60%

65%

70%

Patients receiving antibiotics within 2h of sepsis in septic shock

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-5%

0%

5%

10%

15%

20%

25%

30%

35%

Mean Times - STAT doses only

Septic Shock in OSUMC MICUs

Pre‐intervention

During Intervention

Post Intervention

8/24/08 – 12/31/08 1/1/09 – 3/31/09 4/1/09 – 5/2/11

Hospital mortality

26.8% 23.5% 22.2%mortality

Adjusted relative risk of dying

0.93 0.89

Lives saved 1.3 13.1

That’s a life saved for every 39 patients treated.

Patients with sepsis onset within 24h of ICU admissionSOFA shock score of >0

Septic Shock in OSUMC MICUs

Pre‐intervention Since Intervention

8/24/08 – 12/31/08 1/1/09 – 5/2/11

Hospital LOS (mean) 13.4 10.8

H i l d d 1461Hospital days saved 1461 (19.4% decrease)

ICU LOS (mean) 7.7 5.6

ICU days saved 1180 (27.3% decrease)

Patients with sepsis onset within 24h of ICU admissionSOFA shock score of >0

But 20% are still dying.It must be more complex than this

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It must be more complex than this.

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B. Has an action plan in place which activates particular structures and processes to provide d f lt id

A. Utilizes the expertise and commitment of the staff on duty to assess the situation and

id h t th

The person you care about the most has chest pressure and the ECG shown below. Would you prefer a response that…

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default evidence-based actions for all such events.

provide what they deem to be the appropriate care.

B. Has an action plan in place which activates specific structures and processes to provide


The person you care about the most is on a plane which is failing after flying through a flock of birds. Would you prefer a response that…

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p pdefault evidence-based actions for all such events.

provide what they deem to be the appropriate care.


B. Has an action plan in place which activates specific structures and processes to provide

The person you care about the most is febrile, confused and lightheaded. Would you prefer a response that…

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the situation and provide what they deem to be the appropriate care.

processes to provide default evidence-based actions for all such events.

24 hours1. Check lactate

2. Blood cultures

3. Antibiotics within 3h for ED 1h for non-ED ICU

6 hours1. Steroids per protocol

2. Drotrecogin per protocol

3. Goldilocks glucose

4 P l t 30

The Surviving Sepsis Campaign Plan (Bundles)

SSC Intervention:•Educational materials

•Web site•CD•Protocols

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ED, 1h for non ED ICUadmits

4. If shock, give fluids (≥20ml/kg) ± pressors

5. If shock continues, CVP>8 and CVO2>70%

4. Pplat<30•Advertising•Cards and posters

•Data collection

Crit Care Med 2010;38:367‐74

SSC Results

Hospital mortality 37.0% 30.8% by 2 years

Crit Care Med 2010;38:367‐74

Hospital mortality 37.0% 30.8% by 2 yearsNNT = 16.1

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SSC Results – Initial Care (within 6h)

Crit Care Med 2010;38:367‐74

Systematically Raising Suspicion and Simplifying Intervention

MEWS score every 4 hoursTrigger if >4

•New SIRS•Suspected infectionBedside RN

WBC>14

Lab

Daniels et al. Emerg Med J 2010

Sepsis Team (nursing‐led)

SBAR Communication to MD

“Sepsis Six”

3 Investigations3 Investigations Blood cultures

Measure lactate

3 Treatments3 Treatments

High-flow oxygen

IV antibiotics

The Sepsis Six – to be delivered within 1 hour

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Measure urine output Fluid challenge

…and Identify Severe Sepsis and Septic Shock


Results (within 1 hour)

Frequency achieved

Mortality when not achieved

Mortality when achieved

Number needed to treat

High flow oxygen 74.3% 43.1% 31.8% 9

Antibiotics 61.6% 45.4% 28.1% 6

Fluids 67.7% 44.8% 30.0% 7

Blood cultures 63.0% 49.1% 26.3% 4

Lactate 69.1% 43.4% 30.9% 8

Urine output 68.8% 42.9% 31.0% 8

All “Sepsis 6” 38.6% 44.1% 20.0% 4


Do you want a Sepsis 6 Nurse?

N=567 % patients Sepsis 6 Achieved (1h)

Resuscitation Bundle Achieved (SSC – 6h)

Mortality

Sepsis 6 Nurse 25.4% 82.6% 72.9% 25.5%

No Sepsis 6 Nurse 74.6% 23.9% 23.4% 38.4%p

NNT 7.8


So, presuming 567 patients per year One could conclude a 24/7 program could save 73 lives a year – that’s one person saved ever 5 days AT THAT HOSPITAL

Effect of a rapid response system for patients in shock on time to Effect of a rapid response system for patients in shock on time to treatment and mortality during 5 yearstreatment and mortality during 5 yearsSebat Sebat et al CHESTet al CHEST 2007; 35: 25682007; 35: 2568--25752575

HYPOTENSION (low BP)OR

Normal BP with 3 of following: Mental status change, cool extremities, RR≥20, Low urine output, Elevated lactate, Fever

Fluid Bolus (over 10‐15 min)Fluid Bolus (over 10‐15 min)1000mL if ED250mL if ward

Reassess for Presence of Criteria

ACTIVATE TEAM

43% of patients with septic shock(46% “hypovolemic”)

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Effect of a rapid response system for patients in shock on time to Effect of a rapid response system for patients in shock on time to treatment and mortality during 5 yearstreatment and mortality during 5 yearsSebat Sebat et al Crit Care Med et al Crit Care Med 2007; 35: 25682007; 35: 2568--25752575

40.0%

11 8%

NNT = 4

11.8%

Effect of a rapid response system for patients in shock on time to Effect of a rapid response system for patients in shock on time to treatment and mortality during 5 yearstreatment and mortality during 5 yearsSebat Sebat et al Crit Care Med et al Crit Care Med 2007; 35: 25682007; 35: 2568--25752575

since onset

Time to Antibiotics

Minutes s

Among septic shock patients, mortality decreased from 50% to 10%

NNT = 2.5

Speed Up, Simplify and Specialize?

Mortality ARR NNT Time to 1 life saved*Pre Post

SSC 37.0% 30.8% 6.2% 16.1 11.8 days

S i 6 RN 38 4% 25 5% 12 9% 7 8 5 dSepsis 6 RN 38.4% 25.5% 12.9% 7.8 5 days

Shock Team 50% 10% 40% 2.5 1.8 days

*assuming 500 patients per year

Speed Up, Simplify and Specialize?

Mortality ARR NNT Time to 1 life saved*

Time to 1 life saved**Pre Post

SSC 37.0% 30.8% 6.2% 16.1 11.8 days 65 min

S i 6 RN 38 4% 25 5% 12 9% 7 8 5 d 31 i

That’s also between 8074 and 52,000 deaths from septic shock caused by our

current care.

Sepsis 6 RN 38.4% 25.5% 12.9% 7.8 5 days 31 min

Shock Team 50% 10% 40% 2.5 1.8 days 6 min

*assuming 500 patients per year

**assuming 130,000 patients per year

Considering severe sepsis, between 28,057 and 132,859 people die because

we don’t provide this type of care.

You can save livesSay SepsisSuspect SepsisSimplify SepsisTreat it like aTreat it like a

medical emergencyAntibioticsFluids

Sepsis is a life‐threatening condition that arises when the body’s response to infection injures its own tissues

Talk the talk

66

the body s response to infection injures its own tissues and organs.

Walk the walk Recognize sepsis as a medical emergency requiring the administration of fluids, antibiotics and other appropriate treatments of infection within one hour of suspicion of

sepsis.

6/14/2011

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“We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies

7/20/1969

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and skills, because the challenge is one we are willing to accept, one we are unwilling to postpone, and one which we intend to win."

•JFK, 9/12/1962

“System awareness and systems design are important for health professionals, but are not enough. They are enabling mechanisms only. It is the ethical dimension of individuals that is essential to a system’s success. Ultimately, the secret f lit i l If hof quality is love…If you have

love, you can then work backward to monitor and improve the system.” Avedis Donabedian, 1919‐2000

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