Sepsis. ...striking a balance. Dr Ron Daniels.

Sepsis...striking a balance Dr Ron Daniels Fellow: NHS Improvement Faculty Chair: United Kingdom Sepsis Group, Sepsis Trust & UK SSC Sepsis as a Global Emergency Committee, Global Sepsis Alliance Midland Hotel Manchester, 15 th November 2011

Sepsis is under appreciated. Sepsis is under funded. We (us doctors) over complicate sepsis care. I have less to offer septic patients once they re in my ICU. It is inevitable that we will get our act together.

How to achieve the balance?

Media pressures Event reduction targets Over control Evangelism Informed patients Lack of availability Withhold antimicrobials Give antimicrobials

Lazy or no stewardship Naive patients Lazy clinicians Sepsis evangelism Sepsis/SSI etc targets Resultant public panic Withhold antimicrobials Give antimicrobials

Reduce injudicious use Promote rapid response when appropriate Withhold antimicrobials Give antimicrobials

What we need to do 1. Work out why ideal sepsis care continues to elude us 2. Move from recognizing sepsis to suspecting it 3. Make the case for simplifying sepsis care 4. Establish sepsis as a medical emergency And not forgetting

A U.K. Perspective

A U.K. Perspective North Stand

A U.K. Perspective Breast cancer

A U.K. Perspective

40 30 20 10 0 Lung 1 Colon 2 Breast 3 Sepsis 4 1,2,3 www.statistics.gov.uk, 4 Intensive Care National Audit Research Centre (2006)

Why do we need to simplify sepsis care?

Standards currently achieved for ~14% of UK patients 39% in my hospital How many in yours??? Source: UK SSC data

Comparison with ACS

Comparison with ACS 75% in 30 mins 80%

Perspective Severe Sepsis Acute coronary syndrome No. cases per 100,000 per annum 127 200 NNT basic care Sepsis Six (our data) 6 First hour antibiotics 5 Clopidogrel 48 β blockade 42 Aspirin 26 NNT invasive care EGDT (Rivers) 6 Resusc Bundle (SSC) 18 Thrombolysis 15 PCI over thrombolysis 33

Stroke 67,000 deaths per year FAST Campaign National Stroke Association Target: Specialist assessment in 60 min 40% mortality reduction Myocardial infarction/ ACS 89,000 deaths per year National Infarct Angioplasty Project Target: Call to needle 60 min Door to needle 20 min Sepsis 37,000 (+) deaths per year...

Are antibiotics the equivalent of PCI for sepsis?

SSC antibiotics Begin IV antibiotics as early as possible, and always within the first hour of recognising severe sepsis (1D) and septic shock. (1B) Broad spectrum: one or more agents active against likely bacterial/ fungal pathogens and with good penetration into presumed source. (1B) Reassess antimicrobial regimen daily to optimise efficacy, prevent resistance, avoid toxicity & minimise costs. (1C)

Cumulative Initiation of Effective Antimicrobial Therapy and Survival in Septic Shock 1.0 survival fraction cumulative antibiotic initiation fraction of total patients 0.8 0.6 0.4 0.2 0.0 time from hypotension onset (hrs) Kumar et al. CCM. 2006:34:1589 96.

Running average survival in septic shock based on antibiotic delay (n=2154) For each hour s delay in administering antibiotics in septic shock, mortality increases by 7.6% Funk and Kumar Critical Care Clinics 2011 (in press)

Begin IV antibiotics as early as possible, and always within the first hour of recognising severe sepsis (1D) and septic shock. (1B) Citation: Kumar A et al. Crit Care Med 2006: 34(6) Retrospective, 15 years, 14 sites n = 2,154 median 6 h, 50% administered in 6h Only 5% first 30 minutes survival 87% 12% first hour survival 84%

Early antibiotics are good... Author n Setting Median time (mins) Odds Ratio for death Gaieski Crit Care Med 2010; 38:1045 53 Daniels Emerg Med J 2010; doi:10.1136 Kumar Crit Care Med 2006; 34(6):1589-1596 Appelboam Critical Care 2010; 14(Suppl 1): 50 261 ED, USA (Shock) 567 Whole hospital, UK 2154 ED, Canada (Shock) 375 Whole hospital, UK 119 0.30 (first hour vs all times) 121 0.62 (first hour vs all times) 360 0.59 (first hour vs second hour) 240 0.74 (first 3 hours vs delayed) Levy Crit Care Med 2010; 38 (2): 1 8 15022 Multi centre 0.86 (first 3 hours vs delayed)

Running average survival in septic shock Running Average Survival in Septic Shock based Based on on antibiotic Antibiotic delay Delay (n=4195) (n=4195) 1.0 0.8 fraction 0.6 0.4 running average survival cumulative fraction of total survivors 0.2 Funk and Kumar Critical Care Clinics 2011 (in press) 0.0 0 20 40 60 80 100 AbRx Delay (hrs)

Will antibiotics prevent sepsis? Antimicrobials Infective insult SIRS CARS Organ dysfunction Time

Septic shock: the golden hour Shock threshold Acknowledgement to Anand Kumar

Septic shock: the golden hour Shock threshold Antimicrobials Acknowledgement to Anand Kumar

Adequacy of initial spectrum and timing of first delivery and achievement of MIC are collectively the key Reduce microbial and toxic load...so hit hard and hit fast... BUT...

How do we know which septic patient is going to organ failure? We often don t know the source, let alone the bug... We don t adhere to guidelines, and the guidelines aren t much good We re not very good with our timing So...

SSC Results: Critical Care Medicine 2010; 38(2): 1 8

Should we have, for first dose, the Sepsis Antibiotic? Pip/ taz? Meropenem? Linezolid? Forget severe sepsis??

How to simplify sepsis care..where to start?

Sepsis Resuscitation Bundle (To be started immediately and completed within 6 hours) Serum lactate measured Blood cultures obtained prior to antibiotic administration From the time of presentation, broad spectrum antibiotics to be given within 1 hour Control infective source In the event of hypotension and/or lactate >4mmol/L (36mg/dl): Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent) Give vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) > 65 mm Hg. In the event of persistent arterial hypotension despite volume resuscitation (septic shock) and/or initial lactate >4 mmol/l (36 mg/dl): Achieve central venous pressure (CVP) of >8 mm Hg Achieve central venous oxygen saturation (ScvO 2 ) >70%

Sepsis as a CQUIN measure

Where to start? Unfortunately, only 30% will have severe sepsis in ED Median time to worst obs over 2.5 hours Range 71 284 minutes Nelson JL, Smith BL, Jared JD et al. Prospective trial of real time electronic surveillance to expedite early care of severe sepsis. Annals of Emergency Medicine 2011; 57: 500 4

Know your reliability Resuscitation bundle item Achieved Failed 2005 Data % % % Blood cultures taken 94 6 91 Antibiotics as per guidelines in <1hr 28 72 28 Lactate measured 48 52 59 Adequate fluid resuscitation 69 31 57

Know your processes Seen by first doctor Onset of Severe Sepsis Seen by Senior Doctor Discussed with Senior Doctor Arrive Critical Care Seen by Critical Care Specialist 12:00 13:00 14:00 15:00 16:00 17:00 18:00 19:00 20:00 21:00 Blood Culture taken Antibiotics given Radiology CVP line placed

Compliance at Good Hope Hospital (%) 70 60 50 40 30 Sepsis 6 Resusc Both 20 10 0 Apr-09 Jun-09 Aug-09 Oct-09

Compliance at Good Hope Hospital (%) 70 60 50 40 30 Sepsis 6 Resusc Both Mortality 20 10 0 Apr-09 Jun-09 Aug-09 Oct-09

Mortality by Sepsis Six Cohort size Mortality % RRR Total 567 34.7 Sepsis Six : Oxygen therapy Blood culture Antibiotic administration Fluid challenges Lactate and haemoglobin measurement Urine output monitoring. within one hour

Mortality by Sepsis Six Cohort size Mortality % RRR % (%) (NNT) Total 567 (100) 34.7 - Sepsis Six Sepsis Six 220 (38.8) 20.0 347 (61.2) 44.0 46.6 (4.16)

Mortality by antibiotics Cohort size Mortality % RRR % (NNT) Total 567 (100%) 34.7 - Delayed Antibiotics Antibiotics within 1 h 217 (38.4%) 45.4 350 (61.6%) 28.1 38.1 (5.77)

Mortality by fluid challenges Cohort size Mortality % RRR % (NNT) Total 567 (100%) 34.7 - No fluids in 1h 183 (32.3%) 44.8 Fluids in 1h 384 (67.7%) 30.0 33.0 (6.73)

For patients receiving the Sepsis Six 2.0 fewer Critical Care bed days 3.4 fewer hospital bed days Compared with other survivors Equates to c. 5,000 cost saving

The clincher

Achieving 80% reliability For each year, for every 500 beds.. 62 lives saved 883 fewer bed days 520 fewer CC bed days Direct costs for survivors reduced by 0.78M

Behind the scenes of UKSG

Response to National Outcomes Framework Consultation Response to NHS CE Innovation call Lobbying of NQB Lobbying of NCDs Successful engagement of Health Foundation QIPP NHS Institute Patient Safety Forum Media!

Summary Sepsis is a medical emergency and a big killer Awareness and recognition are the key Early antibiotics and fluids will save more lives than Critical Care Pre hospital recognition may improve the reliability of basic interventions We need to get the balance right, together

Sepsis should be afforded the same import as ACS and stroke Increasing public and media expectations and Department of Health attention will drive higher standards We will be the ones ultimately responsible for delivering those standards and for driving change Reliable delivery of early basic care depends on a seamless care process from home to specialist care: just like for ACS and stroke

Declaration of interests Within the last 24 months, I have received travel expenses and honoraria to deliver two U.K lectures from Astra Zeneca, manufacturers of the antibiotic Meropenem. I have also received consultancy fees from CareFusion, manufacturers of the antiseptic preparation ChloraPrep sepsisteam@gmail.com @sepsisuk www.uksepsis.org www.survivesepsis.org