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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
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
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
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
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
Sepsis incidence, 1999-2003
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 Severe Sepsis Septic shock Death in sepsis
Source: Nationwide Inpatient Sample
Sepsis incidence, 1999-2003e X1
03
20.7%21.7%
nciden
ce
1
In
16%
Sepsis Severe Sepsis Septic shock Death in sepsis
Source: Nationwide Inpatient Sample
Sepsis incidence, 1999-2003
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
Sepsis Severe Sepsis Septic shock Death in sepsis
Source: Nationwide Inpatient Sample
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
34
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
Daniels et al. Emerg Med J 2010
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
Daniels et al. Emerg Med J 2010
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
67
•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