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Sepsis – A MedicalSepsis A Medical EmergencyState of the Science Symposium –State of the Science Symposium –Best Critical Care Practices 2011

Jim O’Brien MD MScJim O Brien, MD, [email protected]

Disclosures, 2004-May 2011y 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:

I think sepsis is under‐appreciated.

I hi k i i d f d d Industry grant monies: PI for aerosolized amikacin (Aerogen, $0, 8/05 – 6/06) PI for calfactant (Pneuma, $0, 9/08 – current)

Consultant/Speakers’ Bureau:

I think sepsis is under‐funded.

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

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)

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

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).

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

Lecture on sepsis treatment (GE, 2011) Video on sepsis communication (GE, 2011) Webinar on sepsis (Siemens, 2011)

Goals today Review the definition of sepsis Review why ideal sepsis care continues to

elude us Quality and SafetyQuality and Safety Make the case for simplifying sepsis care

(“Lean Sepsis”)( Antibiotics Fluids Medical emergency Medical emergency

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

Suspicion

hResuscitation

6 hours

I iti l M thAPCVasopressors

24 hoursInitial ManagementrhAPC

Steroids

PACsantiTNF

tifacogin

Hospitalization

Maintenance antiIL‐1PAFase

ibuprofenGlucose control

Recovery

4

Pre and post‐discharge

Suspicion

hResuscitation

6 hours

I iti l M t24 hours

Initial Management

Hospitalization

Maintenance

RecoveryPre and post‐discharge

So what is sepsis anyway?

6

According to the Consensus definition what is sepsis?definition, what is sepsis?

1 Bl d i i1. Blood poisoning2. Bacteremia3. Shock due to infection4 Fever 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

SIRS with a presumed or confirmedor confirmed

infectious process

8Adapted 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 theConference definition, which of the following is NOT a SIRS criterion?

1. SBP<90 and/or MAP <702 Heart rate >902. Heart rate >903. Respiratory rate >20 or PaCO2<324. Temperature >38 C or <36 C5 WBC >12K or <4K or >10% bands5. WBC >12K or <4K or >10% bands

Sepsis:Defining a Disease ContinuumSIRS = Systemic Inflammatory Response Syndrome

SepsisSepsisSIRSSIRSInfection/Infection/TraumaTrauma Severe SepsisSevere Sepsis

A clinical response arising from a nonspecific insult, f fincluding 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

10

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•22% of intensivist gave Consensus definition (5% other MDs)Based on everything you

know, how do you define sepsis?

definition (5% other MDs)•17% agreed on one definition•6 different definitions were mentioned by at least 10% of respondents



How do you communicate•81% find it difficult to communicate with families about sepsisHow do you communicate

about sepsis?with families about sepsis•85% describe sepsis as complication from underlying condition



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

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

“No” in 67%sepsis?

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

and organs.and organs.

15

Sepsis incidence, 1999-2003

222%

e X1

03

44%

nciden

ce

73%

In

Sepsis Severe Sepsis Septic shock Death in sepsis

Source: Nationwide Inpatient Sample


In 2003In 2003,

1 in 35 of ALL hospital admissions involved sepsis

e X1

03

1 in 66 involved severe sepsis

1 in 233 involved septic shocknciden

ceIn



Sepsis incidence, 1999-2003e X1

03

20.7%21.7%

nciden

ce

1

In

16%




In 2003

22 In 2003,

1 in 35 of ALL hospital admissions involved sepsis

2%In 2003, 23.2% of all deaths during hospitalization involved sepsis

(up from 19.4% in 1999)

e X1

03

20.7%21.7%

1 in 66 involved severe sepsis

1 in 233 involved septic shock

44%1

In other words….1 in 4.3 deaths of hospitalized patients involves sepsis

nciden

ce

73%16%In



215,000 deaths a year in US

D th fDeaths from Breast cancerLung Cancer

+ Prostate Cancer228 Deaths every ~9 h

+ Prostate CancerTOTAL < Deaths

2974 Deaths Every ~5 days

3212 deaths

from Sepsis

every ~5.5 days

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

21

‐Roger Kint

Sepsis Recognition at OSUMCPatients admitted through ED Main Jan‐March 2009

(n = 4951)

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

h l dRandomly selected charts reviewed (n = 500, 53.1%)

That extrapolates to 768 unrecognized septic patients/year at OSU Main ED alone!

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

Recognized as septic in ED notes and/or H&P

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

( )(n = 35, 25.5%) (n = 102, 74.4%)

Dreher et al Manuscript in preparation……

Antibiotic Therapy & Blood CulturesAll Subjects: 56.2% 30.7% 77.4%

p = 0.004 p = 0.165 p = 0.001

All Subjects: 56.2% 30.7% 77.4%

All subjects Recognized Not recognized P valuej g g

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 2.6 2.1 2.8 0.043Administration (1.9 – 3.9) (1.7 – 3.7) (2.0 – 4.5)

Dreher et al Manuscript in preparation……

What can YOU do?

Say Sepsis Causes you to think yabout diagnosis Raises awarenessRaises awarenessMay improve care

Which of these is sepsis?

1. Confusion, cough, nausea2 F h t f b th h t2. Fever, shortness of breath, chest

pain3. Abdominal pain, lightheadedness,

diarrheaWe have to ACT when we are

uncertain.4. Rash, leg swelling, anorexia5 Tachycardia chills sweating

uncertain.

5. Tachycardia, chills, sweating

Stop RECOGNIZING Start SUSPECTING

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

Antibiotics - Minutes Matter

E h i d l f i t tb 7 6% l i l•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.

Shock to effective antibiotic time and mortality in septic shock*

80

90*Assuming 130,000 septic shock cases per year

shock

60

70

f patients

30

40

50

rcen

tage of

10

20

Per

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

%Mortality 26.7 36.1 36.6 46.8 62.3 83.1% f i

0

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

% of patients 26.8 9.0 7.8 12.8 18.8 24.9

Door to balloon time and mortality in STEMI*

20

25 *Assuming 400,000 STEMIs per year

15

20of patients

By getting door‐to‐balloon times of

10

ercentage o

<2h for ALL STEMI patients,we would save

5

Pe 4775 lives per year.(13 people a day)

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

% Mortality 4.9 5.2 6.5 6.7 6.9 5.5% f i

0

% of patients 8 23.5 21.1 21.6 17.3 8.5

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

Shock to effective antibiotic time and mortality in septic shock*

80

90*Assuming 130,000 septic shock cases per year

shock

60

70

f patients

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

30

40

50

rcen

tage of for ALL septic shock patients,

we would save 32 360 lives per year

10

20

Per 32,360 lives per year.

(89 people a day)(3 7 people an hour)

0‐2h >2‐3h >3‐4h >4‐6h >6‐12h >12h

%Mortality 26.7 36.1 36.6 46.8 62.3 83.1% f i

0(3.7 people an hour)

(3.5 times the effect of STEMI intervention)

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

% of patients 26.8 9.0 7.8 12.8 18.8 24.9

The first 12 hours matters even more

For first 12 hours, 1% mortality per 5 minute delayFor 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 SepsisSuspect Sepsis Common in hospitalized patientshospitalized patientsNo single symptom/signsymptom/sign Effective communcationcommuncation

Affecting the emergency response to sepsis: Antibiotics

ABX

•Education•Automatic triggers•Decision support

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

Sepsis onset ABX order administrationantibiotics for an infection in which you want the initial dose delayed?

ABX order time (Clinician Action)

ABX order to administration time (System Response)Maybe we should focus on time from order

Sepsis to ABX administration time (Performance measure)to administration?

33

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 itwith next scheduled delivery and administered when it arrives STAT – prints on different printer, different color paper, p p p p

prepped immediately, immediately delivered to unit

Order Priority Comparisons

Timeline

Pre‐intervention

Intervention Post intervention

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

•Educational•Sepsis Order Set•Data collection •Sepsis Order Set

•Antibiotics by Site •Antibiotics in Pyxis

platform

ATB By Site of Infection ICU

ATB By Site of Infection ICU-CAP

Order Priority

NOW ROUTINESTAT NOW ROUTINE

Median time to antibiotics (min) in septic shock

300

330

septic shock

210

240

270

150

180

60

90

120

0

30

4242

Patients receiving antibiotics within 2h of sepsis in septic shock

60%

65%

70%

of sepsis in septic shock

45%

50%

55%

60%

30%

35%

40%

10%

15%

20%

25%

-5%

0%

5%

10%

43

5%

Mean Times - STAT doses only

Septic Shock in OSUMC MICUs

Pre‐ During Post intervention Intervention Intervention

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

i l % % %Hospital mortality

26.8% 23.5% 22.2%

Adjusted relative 0 93 0 89Adjusted 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 Intervention8/24/08 – 12/31/08 1/1/09 – 5/2/11

Hospital LOS (mean) 13.4 10.8

Hospital days saved 1461 (19 4% decrease)(19.4% decrease)

ICU LOS (mean) 7.7 5.6

ICU days saved 1180 y(27.3% decrease)

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

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

47

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

B. Has an action plan A. Utilizes the

prefer a response that…

in place which activates particular structures and

expertise and commitment of the staff on duty to assess structures and

processes to provide default evidence-based actions for all

staff on duty to assess the situation and provide what they deem to be the based actions for all

such events.deem to be the appropriate care.

50

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

B. Has an action plan A. Utilizes the

Would you prefer a response that…

pin place which activates specific structures and

expertise and commitment of the staff on duty to assess structures and

processes to provide default evidence-based actions for all

staff on duty to assess the situation and provide what they deem to be the based actions for all

such events.deem to be the appropriate care.

51

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

A Utilizes the B Has an action plan

response that…

A. Utilizes the expertise and commitment of the

B. Has an action plan in place which activates specific

staff on duty to assess the situation and provide what they

structures and processes to provide default evidence-provide what they

deem to be the appropriate care.

default evidencebased actions for all such events.

52

The Surviving Sepsis Campaign Plan (Bundles)

24 hours6 hours

( )

SSC Intervention:1. Check lactate2. Blood cultures

1. Steroids per protocol2. Drotrecogin per protocol

•Educational materials•Web site•CD3. Antibiotics within 3h for ED, 1h for non-ED ICUadmits

3. Goldilocks glucose 4. Pplat<30

•CD•Protocols

•Advertising4. If shock, give fluids

(≥20ml/kg) ± pressors5 If shock continues

•Cards and posters•Data collection

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

53

Crit Care Med 2010;38:367‐74

SSC Results

Hospital mortality 37.0% 30.8% by 2 yearsNNT = 16.1

Crit Care Med 2010;38:367‐74

SSC Results – Initial Care (within 6h)

Crit Care Med 2010;38:367‐74

Systematically Raising Suspicion and Simplifying Interventionp y g

MEWS score every 4 hours WBC>14Trigger if >4

•New SIRS•Suspected infectionBedside RN Lab

Sepsis Team ( i l d)

•Suspected infection

(nursing‐led)

SBAR Communication to MD

“Sepsis Six”Daniels et al. Emerg Med J 2010

Sepsis Six

The Sepsis Six – to be delivered within 1 hour

3 I ti ti3 I ti ti 3 T t t3 T t t3 Investigations3 Investigations Blood cultures

3 Treatments3 Treatments High-flow oxygen

Measure lactate Measure urine output

IV antibiotics Fluid challengeg

…and Identify Severe Sepsis and Septic Shock

57

Daniels et al. Emerg Med J 2010

Results (within 1 hour)

Frequency Mortality when Mortality when Number needed achieved not achieved achieved 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% 8Lactate 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%Sepsis 6 Nurse 25.4% 82.6% 72.9% 25.5%

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

NNT 7.8

So, presuming 567 patients per year One could conclude a 24/7 program could save 73 lives a yearOne 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 yearsSebatSebat et al CHESTet al CHEST 2007; 35: 25682007; 35: 2568--25752575Sebat Sebat et al CHESTet al CHEST 2007; 35: 25682007; 35: 2568 25752575

HYPOTENSION (low BP)OR

l i h 3 f f ll iNormal BP with 3 of following: Mental status change, cool extremities, RR≥20, Low urine output, Elevated lactate, Fever

Fluid Bolus (over 10‐15 min)1000mL if ED43% of patients with septic shock250mL if ward(46% “hypovolemic”)

Reassess for Presence of Criteria

ACTIVATE TEAM

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 yearsSebatSebat et al Crit Care Medet al Crit Care Med 2007; 35: 25682007; 35: 2568--25752575Sebat Sebat et al Crit Care Med et al Crit Care Med 2007; 35: 25682007; 35: 2568 25752575

40.0%NNT = 4NNT = 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 yearsSebatSebat et al Crit Care Medet al Crit Care Med 2007; 35: 25682007; 35: 2568--25752575Sebat Sebat et al Crit Care Med et al Crit Care Med 2007; 35: 25682007; 35: 2568 25752575

e on

set

tes since

Among septic shock patients, mortality

Minu decreased from 50% to 10%

NNT = 2.5

Time to Antibiotics

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

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

Shock Team 50% 10% 40% 2.5 1.8 daysShock Team 50% 10% 40% 2.5 1.8 days

*assuming 500 patients per year

Speed Up, Simplify and Specialize?

That’s also between 8074 and 52,000Mortality ARR NNT Time to 1

life saved*Time to 1 life saved**Pre Post

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

current care.SSC 37.0% 30.8% 6.2% 16.1 11.8 days 65 min

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 minConsidering severe sepsis betweenShock Team 50% 10% 40% 2.5 1.8 days 6 min

*assuming 500 patients per year

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

we don’t provide this type of care.**assuming 130,000 patients per year

You can save livesSay Sepsis

S t S iSuspect SepsisSimplify Sepsisp y pTreat it like a

medical emergencyg yAntibioticsFluidsFluids

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

and organs.and organs.

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

66

treatments of infection within one hour of suspicion of sepsis.

“We choose to go to the 7/20/1969moon in this decade and do the other things, not because they are

b b h

/ /

easy, but because they are hard, because that goal will serve to organize and measureorganize and measure the best of our energies and skills, because the challenge is one we arechallenge is one we are willing to accept, one we are unwilling to postpone, and one p pwhich we intend to win."

•JFK 9/12/1962

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•JFK, 9/12/1962

“System awareness and systems design are important for healthdesign are important for health professionals, but are not enough. They are enabling

h i l It i thmechanisms only. It is the ethical dimension of individuals that is essential to a system’s ysuccess. Ultimately, the secret of quality is love…If you have love, you can then worklove, you can then work backward to monitor and improve the system.”

A di b di 1919 2000 Avedis Donabedian, 1919‐2000

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