Jim O Brien, MD, MSc James.OBrien@osumc.edu Sepsis A Medical Emergency State of the Science Symposium Best Critical Care Practices 2011 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 I think sepsis Loan Repayment is under appreciated. Program ($152,781, 10/03-6/05, 7/06-6/10 ) Industry grant monies: I think sepsis is under funded. PI for aerosolized amikacin (Aerogen, $0, 8/05 6/06) PI for calfactant t (Pneuma, $0, 9/08 current) I think we over complicate sepsis care (MD effect) I think that I have less to offer septic patients once they are in the Consultant/Speakers Bureau: Unrestricted educational grant from Lilly to present talk at SCCM (2005) Consultant to Medical Simulation Corporation ($4000, 2005-2006) ICU. Co-author on manuscript with Lilly employees Consultant to Keimar, Inc ($0) Board of Directors, Sepsis Alliance Honoraria to question Sepsis Alliance is how (Travel/accomodations many of us will may die have first. 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 that it is inevitable that we will get our act together. Only 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 care ( Lean Sepsis ) Antibiotics Fluids Medical emergency At least one of you will save someone s life as a result Suspicion Resuscitation 6 hours Vasopressors rhapc Initial PACs Management 24 hours antitnf Steroids tifacogin Glucose Maintenance antiil 1 ibuprofen control PAFase Hospitalization Recovery Pre and post discharge 4 Suspicion 6 hours Resuscitation 24 hours Hospitalization Initial Management Maintenance So what is sepsis anyway? Pre and post discharge Recovery 6 1
According to the Consensus definition, what is sepsis? 1. Blood poisoning 2. Bacteremia 3. Shock due to infection 4. Fever due to infection 5. None of the above Infection/ Trauma Sepsis: Defining a Disease Continuum SIRS = Systemic Inflammatory Response Syndrome SIRS Sepsis SIRS with a presumed or confirmed infectious process Severe Sepsis 8 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 <70 2. Heart rate >90 3. Respiratory rate >20 or PaCO2<32 4. Temperature >38⁰C or <36⁰C 5. WBC >12K or <4K or >10% bands Infection/ Trauma Sepsis: Defining a Disease Continuum SIRS = Systemic Inflammatory Response Syndrome SIRS Sepsis Severe Sepsis A clinical response arising from a nonspecific insult, including 2 of the following: Temperature 38 o C or 36 o C HR 90 beats/min Respirations 20/min WBC count 12,000/mm 3 or 4,000/mm 3 or >10% immature neutrophils 10 Adapted from: Bone RC, et al. Chest 1992;101:1644 Opal 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 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 sepsis? 22% of intensivist gave Consensus definition (5% other MDs) 17% agreed on one definition 66 different dfiiti 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 from underlying condition 2
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 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 How do you communicate about sepsis? 10% say SEPSIS Have you heard the term No in 67% sepsis? Sepsis incidence, 1999-2003 Talk the talk Sepsis is a life threatening condition that arises when the body s response to infection injures its own tissues and organs. ence X10 3 Incid 22% 44% 73% Sepsis Severe Sepsis Septic shock Death in sepsis Source: Nationwide Inpatient Sample 15 Sepsis incidence, 1999-2003 Sepsis incidence, 1999-2003 In 2003, ence X10 3 Incid 1 in 35 of ALL hospital admissions involved sepsis 1 in 66 involved severe sepsis 1 in 233 involved septic shock ence X10 3 Incid 21.7% 16% 20.7% Sepsis Severe Sepsis Septic shock Death in sepsis Sepsis Severe Sepsis Septic shock Death in sepsis Source: Nationwide Inpatient Sample Source: Nationwide Inpatient Sample 3
Sepsis incidence, 1999-2003 215,000 deaths a year in US ence X10 3 Incid 21.7% In 2003, In 2003, 23.2% of all deaths during hospitalization involved sepsis 1 in 35 of ALL hospital admissions involved sepsis (up from 19.4% in 1999) 22% 44% 1 in 66 involved severe sepsis In other words. 1 in 4.3 deaths of hospitalized patients 20.7% involves sepsis 1 in 233 involved septic shock % 16% 73% Sepsis Severe Sepsis Septic shock Source: Nationwide Inpatient Sample Death in sepsis Deaths from Breast cancer Lung Cancer + Prostate Cancer TOTAL < Deaths from Sepsis 228 Deaths every ~9 h 3212 deaths every ~5.5 days 2974 Deaths Every ~5 days Sepsis Recognition at OSUMC Patients admitted through ED Main Jan March 2009 (n = 4951) Received ATBs within 24 hrs of admission (n = 941, 19.0%) That extrapolates Randomly selected to 768 charts unrecognized reviewed septic patients/year (n = at 500, OSU 53.1%) Main ED alone! 21 The greatest trick the Devil ever pulled was convincing the world he didn t exist. Roger Kint 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%) Dreher et al Manuscript in preparation Antibiotic Therapy & Blood Cultures All Subjects: 56.2% 30.7% 77.4% p = 0.004 p = 0.165 p = 0.001 Hours to Order 1.9 (1.1 3.0) Hours to Administration All subjects Recognized Not recognized P value 2.6 (1.9 3.9) 1.3 (1.0 2.0) 2.1 (1.7 3.7) 2.1 (1.3 3.5) 2.8 (2.0 4.5) Dreher et al Manuscript in preparation 0.012 0.043 What can YOU do? Say Sepsis Causes you to think about diagnosis Raises awareness May improve care 4
Which of these is sepsis? Stop RECOGNIZING Start SUSPECTING 1. Confusion, cough, nausea 2. Fever, shortness of breath, chest pain 3. Abdominal We have pain, to ACT lightheadedness, when we are diarrhea uncertain. 4. Rash, leg swelling, anorexia 5. Tachycardia, chills, sweating 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. Shock to effective antibiotic time and mortality in septic shock* age of patients Percenta 90 80 70 60 50 40 30 20 10 0 *Assuming 130,000 septic shock cases per year 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 Adapted from Kumar et al. Crit Care Med 2006; 34: 1589 96. Door to balloon time and mortality in STEMI* tage of patients Percent 25 20 *Assuming 400,000 STEMIs per year 15 By getting door to balloon times of <2h for ALL STEMI patients, 10 we would save 5 4775 lives per year. (13 people a day) 0 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 Adapted from Cannon et al. JAMA 2000; 283: 2941 7. Shock to effective antibiotic time and mortality in septic shock* age of patients 90 80 70 *Assuming 130,000 septic shock cases per year By getting shock to antibiotic times of <2h 60 50 for ALL septic shock patients, 40 we would save 30 32,360 lives per year. 20 (89 people a day) 10 (3.7 people an hour) 0 0 2h >2 3h >3 4h >4 6h >6 12h >12h (3.5 times the effect of STEMI intervention) Percenta %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 Adapted from Kumar et al. Crit Care Med 2006; 34: 1589 96. 5
The first 12 hours matters even more What can YOU do? For first 12 hours, 1% mortality per 5 minute delay Funk and Kumar, Crit Care Clinics 2011; 53 76. Say Sepsis Suspect Sepsis Common in hospitalized patients No single symptom/sign Effective communcation Affecting the emergency response to sepsis: Antibiotics Education Automatic triggers Decision support Sepsis onset ABX order Processes Structures Is there any situation in which you are giving antibiotics for an infection in which you want the initial dose delayed? ABX order time (Clinician Action) ABX order to administration time (System Response) Sepsis to ABX administration time (Performance measure) ABX administration Maybe we should focus on time from order to administration? 33 34 Not all orders are created equal Order Priority Comparisons 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 6
Timeline ATB By Site of Infection ICU Preintervention Intervention Post intervention 8/24/08 1/1/09 3/31/09 6/7/10 Data collection platform Educational Sepsis Order Set Antibiotics by Site Antibiotics in Pyxis ATB By Site of Infection ICU-CAP Order Priority 330 Median time to antibiotics (min) in septic shock 300 270 240 210 180 150 120 90 60 30 STAT NOW ROUTINE 0 42 7
70% 65% Patients receiving antibiotics within 2h of sepsis in septic shock Mean Times - STAT doses only 60% 55% 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% -5% 43 Septic Shock in OSUMC MICUs Septic Shock in OSUMC MICUs Hospital mortality Preintervention During Intervention Post Intervention 8/24/08 12/31/08 1/1/09 3/31/09 4/1/09 5/2/11 26.8% 23.5% 22.2% Adjusted relative 0.93 0.89 risk of dying Lives saved 1.3 13.1 That s a life saved for every 39 patients treated. Patients with sepsis onset within 24h of ICU admission SOFA shock score of >0 Pre intervention Since Intervention 8/24/08 12/31/08 1/1/09 5/2/11 Hospital LOS (mean) 13.4 10.8 Hospital ldays 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 admission SOFA shock score of >0 But 20% are still dying. It must be more complex than this. 47 8
The person you care about the most has chest pressure and the ECG shown below. Would you prefer a response that A. Utilizes the expertise and commitment of the staff on duty to assess the situation and provide what they deem to be the appropriate care. B. Has an action plan in place which activates particular structures and processes to provide default evidencebased actions for all such events. 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 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 expertise and in place which commitment of the activates specific staff on duty to assess structures and the situation and provide what they deem to be the appropriate care. processes to provide default evidencebased actions for all such events. A. Utilizes the expertise and commitment of the staff on duty to assess the situation and provide what they deem to be the appropriate care. B. Has an action plan in place which activates specific structures and processes to provide default evidencebased actions for all such events. 51 52 The Surviving Sepsis Campaign Plan (Bundles) 6 hours Educational 1. Check lactate materials 2. Web Blood site cultures 3. CD Antibiotics within 3h for Protocols ED, 1h for non-ed ICU Advertising admits 4. Cards If shock, and give posters fluids Data ( 20ml/kg) collection ± pressors 5. If shock continues, CVP>8 and CVO2>70% SSC Intervention: 24 hours 1. Steroids per protocol 2. Drotrecogin per protocol 3. Goldilocks glucose 4. Pplat<30 SSC Results Hospital mortality 37.0% 30.8% by 2 years NNT = 16.1 53 Crit Care Med 2010;38:367 74 Crit Care Med 2010;38:367 74 9
SSC Results Initial Care (within 6h) Systematically Raising Suspicion and Simplifying Intervention Bedside RN MEWS score every 4 hours Trigger if >4 New SIRS Suspected infection SBAR Communication to MD WBC>14 Sepsis Team (nursing led) Lab Sepsis Six Crit Care Med 2010;38:367 74 Daniels et al. Emerg Med J 2010 The Sepsis Six to be delivered within 1 hour 3 Investigations Blood cultures Measure lactate Measure urine output 3 Treatments High-flow oxygen IV antibiotics 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 57 Daniels et al. Emerg Med J 2010 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% 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 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 treatment and mortality during 5 years Sebat et al CHEST 2007; 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) 1000mL if ED 250mL if ward 43% of patients with septic shock (46% hypovolemic ) Reassess for Presence of Criteria Daniels et al. Emerg Med J 2010 ACTIVATE TEAM 10
Effect of a rapid response system for patients in shock on time to treatment and mortality during 5 years Sebat et al Crit Care Med 2007; 35: 2568-25752575 Effect of a rapid response system for patients in shock on time to treatment and mortality during 5 years Sebat et al Crit Care Med 2007; 35: 2568-25752575 40.0% NNT = 4 11.8% since onset Minutes s Among septic shock patients, mortality decreased from 50% to 10% NNT = 2.5 Time to Antibiotics Speed Up, Simplify and Specialize? Speed Up, Simplify and Specialize? Mortality ARR NNT Time to 1 Pre Post life saved* SSC 37.0% 30.8% 6.2% 16.1 11.8 days Sepsis 6 RN 38.4% 25.5% 5% 12.9% 78 7.8 5 days Shock Team 50% 10% 40% 2.5 1.8 days *assuming 500 patients per year That s also between 8074 and 52,000 deaths from septic shock caused by our Mortality ARR NNT Time to 1 Time to 1 current care. Pre Post life saved* life saved** SSC 37.0% 30.8% 6.2% 16.1 11.8 days 65 min Sepsis 6 RN 38.4% 25.5% 5% 12.9% 78 7.8 5 days 31 min Shock Team 50% 10% 40% 2.5 1.8 days Considering severe sepsis, between 6 min 28,057 and 132,859 people die because we don t *assuming provide 500 this patients type of per care. year **assuming 130,000 patients per year You can save lives Say Sepsis Suspect Sepsis Simplify Sepsis Treat it like a medical emergency Antibiotics Fluids Talk the talk Sepsis is a life threatening condition that arises when 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. 66 11
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 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 7/20/1969 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 of quality is love If you have love, you can then work backward to monitor and improve the system. Avedis Donabedian, 1919 2000 67 12