Toward achieving reliable

sepsis care

Dr Ron Daniels FFICM FRCA FRCPEd

@SepsisUK Chair, UK Sepsis Trust
CEO, Global Sepsis Alliance
Breast cancer
Breast cancer
Breast cancer
Breast cancer
What is sepsis?
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.
ACCP/SCCM defs
Infection Severe Sepsis
Inflammatory response Sepsis
to microorganisms, or Organ dysfunction
Invasion of normally Septic shock
sterile tissues Sepsis
Systemic Inflammatory Hypotension despite fluid
Response Syndrome (SIRS) resuscitation
Systemic response to a
variety of processes
Sepsis
Infection plus
2 SIRS criteria
Bone RC et al. Chest. 1992;101:1644-55.
 Pancreatitis

Bacteria

Trauma
SEVERE
Virus Infection
SEPSIS
SIRS
Burns
Sepsis Burns
Fungi

Other
Parasite
Screening tool
Are any 2 of the following SIRS criteria present and new to your patient?

Obs: Temperature >38.3 or <36 0C Respiratory rate >20 min-1

Heart rate >90 bpm Acutely altered mental state

Bloods: White cells <4x109/l or >12x109/l Glucose>7.7mmol/l

(if patient is not diabetic)

If yes,
patient has SIRS
 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 SIX
What is shock?
What is shock?

Tissue perfusion is not adequate for the

tissues metabolic requirements

Types of Shock Septic Shock

Cardiogenic Shock secondary to
Neurogenic systemic
Hypovolaemic
Anaphylactic
inflammatory
and response to a new
infection
What is shock?

Tissue perfusion is not adequate for the

tissues metabolic requirements

For sepsis, shock is one of:

SBP < 90 mmHg
MBP < 65 mmHg after IV fluids
Drop of < 40 mmHg

Lactate > 4 mmol/l

BP Syst < 90 / Mean < 65
(after initial fluid challenge)

Lactate > 2 mmol/l

Urine output < 0.5 ml/kg/hr for 2 hrs

Clotting INR > 1.5 or aPTT > 60 s

Bilirubin > 34 mol/l

O2 Nec. to keep SpO2 > 90%

Platelets < 100 x 109/l

Creatinine > 177 mol/l

UO < 0.5 ml/kg/hr

Severe Sepsis: Ensure Outreach and Senior

Doctor attend NOW!
Merinoff definition
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

Why do we need to
change??
SSC Bundle 2008
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 (ScvO2) >70%
SSC Bundle 2012
To be completed within 3?? hours:
1) Measure lactate level
2) Obtain blood cultures prior to administration of antibiotics
3) Administer broad spectrum antibiotics
4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L

To be completed within 6 hours:

5) Apply vasopressors for hypotension that does not respond to initial fluid
resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg)
6) In the event of persistent arterial hypotension despite volume resuscitation
(septic shock) or initial lactate 4 mmol/L (36 mg/dL):
- Measure central venous pressure (CVP)*
- Measure central venous oxygen saturation (ScvO2)*
7) Remeasure lactate if initial lactate was elevated*
Perspective
Severe Sepsis Acute coronary
syndrome

No. cases per 100,000 per 337 200

annum

Sepsis Six (our data) 6 Clopidogrel 48

NNT basic care
First hour antibiotics 5 -blockade 42
Aspirin 26

EGDT (Rivers) 6 Thrombolysis 15

NNT invasive care
Resusc Bundle (SSC) 18 PCI over thrombolysis 33
Perspective
Available at sepsistrust.org
The Sepsis Six
The Sepsis Six

1. Give high-flow oxygen via non-rebreathe bag

2. Take blood cultures and consider source control
3. Give IV antibiotics according to local protocol
4. Start IV fluid resuscitation Hartmanns or equivalent
5. Check lactate
6. Monitor hourly urine output consider catheterisation

within one hour

..plus Critical Care support to complete EGDT
Step 1: Oxygen
Aim to give 100% initially
In practice you cant!
NRB with reservoir: 60-98%
Needs regular review
After initial resusc target SpO2 > 94%
Septic patients exempt from BTS guidelines
May still be appropriate in COPD!!
Monitor carefully
Step 2: Cultures
Before starting antibiotics, at least one blood culture:

Percutaneously
AND at least one from each vascular access device (if > 48 hrs)

Other cultures

urine, CSF, wounds, sputum, other fluids

Consider NOW diagnostic support such as imaging

1. Weinstein, MP Rev Infect Dis 1983; 5: 35 53

2. Blot F. J Clinical Microbiol 1999; 36; 105 -109
Step 2: Cultures
Reassess antimicrobial regimen daily to optimise
efficacy, prevent resistance, avoid toxicity & minimise
costs. (1C)

Do we practice de-escalation?
As few as 23% of opportunities
Alvarez-Lerma F, Alvarez B, Ruiz F et al for the ADANN Study Group. Crit
Care 2006; 10: R 78
Step 3: 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 until defined
Early, appropriate antibiotics are
the key to improved outcomes
First hour antibiotics in 27%...
Effective Antimicrobial Therapy &
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 hours 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 abx are good.
Author n Setting Median time Odds Ratio for
(mins) death

Gaieski 261 ED, USA 119 0.30

Crit Care Med 2010; (first hour vs all times)
38:1045-53
(Shock)

Daniels 567 Whole hospital, 121 0.62

Emerg Med J 2010; (first hour vs all times)
doi:10.1136
UK

Kumar 2154 ED, Canada 360 0.59

Crit Care Med 2006; (first hour vs second hour)
34(6):1589-1596
(Shock)

Appelboam 375 Whole hospital, 240 0.74

Critical Care 2010; (first 3 hours vs delayed)
14(Suppl 1): 50
UK

Levy 15022 Multi-centre 0.86

Crit Care Med 2010; 38 (first 3 hours vs delayed)
(2): 1-8
Survival in septic shock based
on antibiotic delay (n=4195)
1
0.9
0.8
0.7
Cumulative fraction
0.6
of total survivors
0.5
0.4 Running average
0.3 survival

0.2
0.1
0
0 10 20 30 40 50 60 70 80 90 100 Funk and Kumar
Critical Care Clinics 2012
 Retrospective, 22 hospitals,
n= 4532

Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81

 Retrospective, 22 hospitals,
n= 4532

64.4% septic shock patients

developed early AKI

Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81

 64.4% septic shock patients developed early AKI
Retrospective, 22 hospitals,
n= 4532

Median time shock to antibiotic

= 5.5 h

Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81

 64.4% septic shock patients developed early AKI
Retrospective, 22 hospitals,
n= 4532
Median time shock to antibiotic = 5.5 h

OR for AKI
1.14 (1.10-1.20) P < 0.001
per
hours delay
Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81
Step 4: Fluids

Why?
To reduce organ dysfunction and
multi-organ failure

By optimising tissue oxygen delivery

By increasing organ perfusion

Step 4: Fluids
DO2 = Oxygen delivery to the tissue

DO2 = CaO2 x CO

CaO2 = Amount of O2 in arterial blood

CaO2 = ([Hb] x SaO2 x 1.34) + (PaO2 x 0.0225)

Fluid therapy improves cardiac output by increasing

venous return to the heart
Optimizing DO2
DO2 = Oxygen delivery to the tissue

DO2 = CaO2 x CO

CaO2 = Amount of O2 in arterial blood

CaO2 = ([Hb] x SaO2

Fluid therapy improves cardiac output by increasing

venous return to the heart
Fluid resuscitation
Judicious fluid challenges
Up to 30ml/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

In patients with cardiac disease

Use smaller volumes
More frequent assessment
Early CVC
Step 5: 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
Risk stratification

40
% in hospital Mortality

35
30 Low (0 - 2.0)
25
Intermediate ( 2.1 - 3.9)
20
15
Severe (>4.0)
10
5
0
Lactate threshold

Trzeciak, S et al , Acad Emerg Med; 13, 1150-1151. n-=1613

Step 6: Urine output

Accurate hourly urine output

monitoring
(for many, this will mean catheterisation)

The Goal
> 0.5 ml/kg/hr
> 40 ml/hour in the average adult
Renal blood flow
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

However RBF is directly

proportional to cardiac
output
2 groups with 2 sets of needs

1. Get patients with community-acquired

sepsis to hospital quickly
2 groups with 2 sets of needs

2. Recognise inpatient deterioration

reliably
Inpatient deterioration
Critical Care expenditure
Critical Care length of stay
Compared with ACS
Cost per episode
Moore LJ, Jones SL, Kreiner LA, et al: Validation of a screening tool
for the early identification of sepsis. J Trauma 2009; 66: 15391546
2 groups with 1 identical
need

3. Respond and escalate appropriately

Sepsis Six delivery
Compliance,GHH (%)
70

60

50

Sepsis 6
40
Resusc
Both
30
Mortality

20

10

0
Apr-09 Jun-09 Aug-09 Oct-09
Mortality

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)
What does doing sepsis
right look like?
For each year, for every 100k in the local population..

20 lives saved
285 fewer bed days
168 fewer CC bed days

Direct costs for survivors reduced by 0.25M

For UK, thats 12,500 lives and 156 million.

Every year.
ron@sepsistrust.org
@SepsisUK

www.sepsistrust.org
www.world-sepsis-day.org