Surviving sepsis

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Surviving sepsis

• Balraj APPADU M.D., FRCA, FFICM
• Consultant in Anaesthesia Intensive Care
  Medicine

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Agenda
Understand the scope of the sepsis epidemic
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Become familiar with the Surviving Sepsis
Campaign and the IHI defined sepsis bundles
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Recognize how time-critical therapies can save
lives in the emergency departments and ICUs
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What's the problem?

• Severe sepsis affects over 120,000 patients each
  year in the U.K. (increasing at a rate of 1.5
  per annum)
• Last year 78,000 of these patients admitted to
  ITU
• Mortality for these 30 80

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Comparable Global Epidemiology

• 95 cases per 100,000
• 2 week surveillance
• 206 French ICUs
• 95 cases per 100,000
• 3 month survey
• 23 Australian/New Zealand ICUs
• 51 cases per 100,000
• England, Wales and Northern Ireland.

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Severe Sepsis Comparison With Other Major
Diseases
Incidence of Severe Sepsis
Mortality of Severe Sepsis
Cases/100,000
Deaths/Year
AIDS
Colon
Breast
CHF
Severe Sepsis
Severe Sepsis
AIDS
Breast Cancer
AMI
Cancer
National Center for Health Statistics, 2001.
American Cancer Society, 2001. American Heart
Association. 2000. Angus DC et al. Crit Care
Med. 2001
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Sepsis Epidemiology Effect of the Aging
Population
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Economics of Sepsis

• Severe Sepsis
• 22,000 per case
• US annual cost 16.7 Billion
• Nosocomial Sepsis
• increased LOS - ICU 8 days, Hosp 24 days
• 40,890 per case

Angus CCM, 2001 Pittet JAMA, 1994
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Time Sensitive Interventions
Door to PCI Focus on the timely return of
blood flow to the affected areas of the heart.
AMI
Time is Brain The sooner that treatment
begins, the better are ones chances of
survival without disability.
Stroke
The Golden Hour Requires immediate response
and medical care on the scene. Patients
typically transferred to a qualified trauma
center for care.
Trauma
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Severe Sepsis vs. Current Care Priorities
Care Priorities U.S. Incidence of Deaths Mortality Rate
AMI (1) 900,000 225,000 25
Stroke (2) 700,000 163,500 23
Trauma (3) (Motor Vehicle) 2.9 million (injuries) 42,643 1.5
Severe Sepsis (4) 751,000 215,000 29
Source (1) Ryan TJ, et al. ACC/AHA Guidelines
for management of patients with AMI. JACC. 1996
28 1328-1428. (2) American Heart Association.
Heart Disease and Stroke Statistics 2005
Update. Available at www.americanheart.org. (3)
National Highway Traffic Safety Administration.
Traffic Safety Facts 2003 A Compilation of Motor
Vehicle Crash Data from the Fatality Analysis
Reporting System and the General Estimates
System. Available at http//www.nhtsa.dot.gov/.
(4) Angus DC et al. Crit Care Med 200129(7)
1303-1310.
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Surviving Sepsis Campaign

• Launched in Autumn 2002 as a collaborative effort
  of European Society of Intensive Care Medicine,
  the International Sepsis Forum, and the Society
  of Critical Care Medicine
• Goal reduce sepsis mortality by 25 in the next
  5 years
• Guidelines revealed at SCCM in Feb 2004, REVISED
  2008
• Critical Care Medicine March 2004 32(3)858-87.
• Website survivingsepsis . org

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What is sepsis?

• Sepsis, Septic Shock,
• SIRS (systemic inflammatory response syndrome),
• SSI (signs and symptoms of infection),
• Septicaemia, Bacteraemia,
• Toxic Shock Syndrome,
• Bloodstream infection etc, etc.

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ACCP/SCCM Consensus Definitions

• Severe Sepsis
• Sepsis
• Organ dysfunction
• Septic shock
• Sepsis
• Hypotension despite fluid resuscitation

• Infection
• Inflammatory response to microorganisms, or
• Invasion of normally sterile tissues
• Systemic Inflammatory Response Syndrome (SIRS)
• Systemic response to a variety of processes
• Sepsis
• Infection plus
• ?2 SIRS criteria

Bone RC et al. Chest. 19921011644-55.
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What is SIRS?

• A systemic response to a nonspecific insult
• Infection, trauma, surgery, massive transfusion,
  etc
• Defined as ?2 of the following
• Temperature gt38.3 or lt36 0C
• Heart rate gt90 min-1
• Respiratory rate gt20 min-1
• White cells lt4 or gt12
• Acutely altered mental state
• Hyperglycaemia (BMgt7.7) in absence of DM

SEVERE SEPSIS
SIRS
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What counts as an infection?
Pneumonia 50 Urinary Tract infection Meningitis
Endocarditis Device related Central
line Cannula
Abdominal 25 Pain Diarrhoea Distension Urgen
t laparotomy Soft tissue/ musculoskeletal Cel
lulitis Septic arthritis Fasciitis Wound
infection
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what is Sepsis?

• SIRS due to an infection

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What is Severe Sepsis?

• Sepsis with organ dysfunction, hypoperfusion or
  hypotension
• CNS Acutely altered mental status
• CVS Syst lt 90 or mean lt 65 mmHg
• Resp SpO2 gt90 only with new/ more O2
• Renal Creatinine gt177 µmol/l
• or UO lt0.5 ml/kg/hr for 2 hrs
• Hepatic Bilirubin gt34 µmol/l
• Bone marrow Platelets lt100
• Hypoperfusion Lactate gt2 mmol/l
• Coagulopathy INRgt1.5 or aPTTgt60secs

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What is shock?

• Tissue perfusion is not adequate for the tissues
  metabolic requirements

Types of Shock Cardiogenic Neurogenic
Hypovolaemic Anaphylactic and
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What is shock?

• Tissue perfusion is not adequate for the tissues
  metabolic requirements

For sepsis, shock is one of SBP lt 90
mmHg MBP lt 65 mmHg after IV
fluids Drop of lt 40 mmHg Lactate gt
4 mmol/l
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The Sepsis Continuum

• A clinical response arising from a nonspecific
  insult, with ?2 of the following
• T gt38oC or lt36oC
• HR gt90 beats/min
• RR gt20/min
• WBC gt12,000/mm3 or lt4,000/mm3 or gt10 bands

• SIRS with a
• presumed
• or confirmed
• infectious
• process

Sepsis with organ failure
Refractory hypotension
SIRS systemic inflammatory response syndrome
Chest 19921011644.
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Severe Sepsis Screening Tool
Are any 2 of the following SIRS criteria present
and new to your patient? Obs Temperature
gt38.3 or lt36 0C Respiratory rate gt20
min-1 Heart rate gt90 bpm Acutely altered
mental state Bloods White cells lt4x109/l or
gt12x109/l Glucosegt7.7mmol/l (if patient is
not diabetic)
If yes, patient has SIRS
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• Is this likely to be due to an infection?
• For example
• Cough/ sputum/ chest pain Dysuria
• Abdo pain/ diarrhoea/ distension Headache
  with neck stiffness
• Line infection Cellulitis/wound
  infection/septic arthritis
• Endocarditis

If yes, patient has SEPSIS Start SEPSIS BUNDLE
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Check for SEVERE SEPSIS
BP Syst lt 90 / Mean lt 65 mmHg (after initial
fluid challenge) Lactate gt 4 mmol/l Urine
output lt 0.5 ml/kg/hr for 2 hrs INR gt 1.5
aPTT gt 60 s Bilirubin gt 34 µmol/l O2
Needed to keep SpO2 gt 90 Platelets lt 100 x
109/l Creatinine gt 177 µmol/l or UO lt 0.5
ml/kg/hr
Severe Sepsis Ensure Senior Doctor/ITU to
attend NOW!
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What is a Bundle?

• Specifically selected care elements
• From evidence based guidelines
• Implemented together provide improved outcomes
  compared to individual elements alone

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6 Hour Resuscitation Bundle

• Early Identification
• Early Antibiotics and Cultures
• Early Goal Directed Therapy

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6 - hour Severe Sepsis/Septic Shock Bundle

• Early Detection
• Obtain serum lactate level.
• Early Blood Cx/Antibiotics
• within 3 hours of presentation.
• Early EGDT
• Hypotension (SBP lt 90, MAP lt 65) or lactate gt 4
  mmol/L
• initial fluid bolus 20-40 ml of crystalloid (or
  colloid equivalent) per kg of body weight.

• Vasopressors
• Hypotension not responding to fluid
• Titrate to MAP gt 65 mmHg.
• Septic shock or lactate gt 4 mmol/L
• CVP and ScvO2 measured.
• CVP maintained gt8 mmHg.
• MAP maintain gt 65 mmHg.
• ScvO2lt70with CVP gt 8 mmHg, MAP gt 65 mmHg
• PRBCs if hematocrit lt 30.
• Inotropes.

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Why does it matter?
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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 ß-blockade 42 Aspirin 26
NNT invasive care EGDT (Rivers) 6 Resusc Bundle (SSC) 18 Thrombolysis 15 PCI over thrombolysis 33
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The Sepsis Six

• Give high-flow oxygen via non-rebreath bag
• Take blood cultures and consider source control
• Give IV antibiotics according to local protocol
• Start IV fluid resuscitation Hartmanns or
  equivalent
• Check lactate
• Monitor hourly urine output consider
  catheterisation
• within one hour

..plus Critical Care support to complete EGDT
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Give Antibiotics

• Start therapy as soon as possible and certainly
  in the first hour...
• ...preferably after taking blood cultures!!
• Choice should include one or more with activity
  against likely pathogen
• Penetration of presumed source
• Guided by local pathogens
• Give broad spectrum till defined

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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)

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• 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

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Cumulative Initiation of Effective Antimicrobial
Therapy and Survival in Septic Shock
1.0
survival fraction
cumulative antibiotic initiation

0.8
0.6
fraction of total patients
0.4
0.2
0.0
12-24
24-36
0-0.5
0.5-1
9-12
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1-2
2-3
3-4
4-5
5-6
6-9
time from hypotension onset (hrs)
Kumar et al. CCM. 2006341589-96.
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Running average survival in septic shock based on
antibiotic delay (n4195)
Funk and Kumar Critical Care Clinics 2012(in
press)
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Running average survival in septic shock based on
antibiotic delay (n2154)
For each hours delay in administering
antibiotics in septic shock, mortality increases
by 7.6
Funk and Kumar Critical Care Clinics 2011 (in
press)
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Early antibiotics are good...
Author n Setting Median time (mins) Odds Ratio for death
Gaieski Crit Care Med 2010 381045-53 261 ED, USA (Shock) 119 0.30 (first hour vs all times)
Daniels Emerg Med J 2010 doi10.1136 567 Whole hospital, UK 121 0.62 (first hour vs all times)
Kumar Crit Care Med 2006 34(6)1589-1596 2154 ED, Canada (Shock) 360 0.59 (first hour vs second hour)
Appelboam Critical Care 2010 14(Suppl 1) 50 375 Whole hospital, UK 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)
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• Retrospective, 22 hospitals,
• n 4532
• 64.4 septic shock patients developed early AKI
• Median time shock to antibiotic 5.5 h
• OR for AKI 1.14 (1.10-1.20) P lt 0.001 per hours
  delay

Bagshaw SM et al Intensive Care
Med. 200935(5)871-81
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SSC Results Critical Care Medicine 2010 38(2)
1-8
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SSC Results Critical Care Medicine 2010 38(2)
1-8
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Appropriate antibiotics

• Citation Ibrahim et al. Chest 2000118146155
• BSI, n 492
• 59.1 HAI
• 29.9 inadequate
• 8.3 fungal
• VREs
• Pseudomonas
• Coag-neg Staph
• MONARCS trial OR 0.65 for death with adequate
  cover (n2634)

MacArthur RD et al. Clin Infect Dis 2004
38284-288
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Fluids

• Why?
• To reduce organ dysfunction and
• multi-organ failure
• By optimising tissue oxygen delivery
• By increasing organ perfusion

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Optimising oxygen delivery

• DO2 Oxygen delivery to the tissue
• CaO2 Amount of O2 in arterial blood
• Fluid therapy improves cardiac output by
  increasing venous return to the heart

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How to fluid resuscitate

• Judicious fluid challenges
• Up to 60ml/kg in divided boluses (min. 20ml/kg
  in shock)
• Crystalloid (500ml boluses)
• Colloid (250-300ml boluses)
• Reassess for effect after each challenge
• HR, BP, capillary refill, urine output, RR

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Lactate

• High lactate identifies tissue hypoperfusion in
  patients at risk who are not hypotensive
• Cryptic shock
• Gives an overview of current tissue oxygen
  delivery
• The Goal
• Lactate to improve
• as resuscitation
• progresses

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Risk stratification by lactate
Trzeciak, S et al , Acad Emerg Med 13,
1150-1151. n-1613
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Urine Output

• Accurate hourly urine output monitoring
• (for many, this will mean catheterisation)
• The Goal
• gt 0.5 ml/kg/hr
• gt 40 ml/hour in the average adult

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Urine Output

• Urine output is a direct measure of GFR
• GFR Glomerular Filtration Rate
• GFR is directly proportional to CO
• Kidneys receive 1/5 cardiac output (1 L/min)
• CO falls UO falls
• Therefore urine output in the early stages is a
  useful assessment of cardiac output

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Renal Blood Flow Urine Output
In health, kidneys autoregulate, so UO is
independent of BP over a wide range In sepsis,
this is lost and UO will fall as BP falls
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Early Goal Directed Therapy
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EGDT Call for specialist support
CVP line
lt 8mmHg
Crystalloid Colloid
gt8 mmHg
MAP
lt 65 or lt90 mmHg
Vasoactive Drugs
gt65 gt90mmHg
ScvO2
lt 70
Transfuse red cells until Hb gt 10 g/dl
YES
ScvO2 gt70
gt70
NO
Goals Achieved
Inotropic agents
Rivers et al 2001, NEJM 345, 1368-1377
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The Importance of Early Goal-Directed Therapy
for Sepsis Induced Hypoperfusion
Adapted from Table 3, page 1374, with permission
from Rivers E, Nguyen B, Havstad S, et al. Early
goal-directed therapy in the treatment of severe
sepsis and septic shock. N Engl J Med 2001
3451368-1377
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Mortality by Sepsis Six
Cohort size () Mortality RRR (NNT)
Total 567 (100) 34.7 -
Sepsis Six? 347 (61.2) 44.0
Sepsis Six? 220 (38.8) 20.0 46.6 (4.16)
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Mortality by antibiotics
Cohort size Mortality RRR (NNT)
Total 567 (100) 34.7 -
Delayed Antibiotics 217 (38.4) 45.4
Antibiotics within 1 h 350 (61.6) 28.1 38.1 (5.77)
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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)
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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

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The clincher
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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

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Summary

• Improve recognition/diagnosis
• Alter attitude treat sepsis like MI
• Early aggressive treatment
• Use EGDT
• Collaborate with ITU early

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• Sepsis is a life-threatening condition that
  arises when the body's response to an infection
  injures its own tissues and organs.
• Sepsis leads to shock, multiple organ failure and
  death especially if not recognized early and
  treated promptly.
• Sepsis remains the primary cause of death from
  infection despite advances in modern medicine,
  including vaccines, antibiotics and acute care.
• Millions of people die of sepsis every year
  worldwide

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Comments and Questions