Toward achieving reliable sepsis care

Toward achieving reliable sepsis care

Dr Ron Daniels FFICM FRCA FRCPEdChair, UK Sepsis Trust

CEO, Global Sepsis Alliance@SepsisUK

Breast cancer

Breast cancer

Bowel cancer Breast cancer

Bowel cancer Breast cancer

Annual UK sepsis deaths

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….

What is sepsis?

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

Severe Sepsis– Sepsis– Organ dysfunction

Septic shock– Sepsis– Hypotension despite fluid

resuscitation

Bone RC et al. Chest. 1992;101:1644-55.

ACCP/SCCM defs

Burns

Trauma

Other

Infection SIRS Virus

Fungi

Parasite

Pancreatitis

Bacteria

Sepsis

SEVERE

SEPSIS

Burns

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

Screening tool

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?

Tissue perfusion is not adequate for the tissues’ metabolic requirements

Septic Shock

Shock secondary to systemic

inflammatory response to a new

infection

Types of ShockCardiogenic Neurogenic

Hypovolaemic

Anaphylactic and…

What is shock?

Tissue perfusion is not adequate for the tissues’ metabolic requirements

For sepsis, shock is one of:

SBP < 90 mmHgMBP < 65 mmHg after IV fluidsDrop of < 40 mmHg

Lactate > 4 mmol/l

What is shock?

Severe Sepsis: Ensure Outreach and Senior Doctor attend NOW!

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 μmol/l

O2 Nec. to keep SpO2 > 90%

Platelets < 100 x 109/l

Creatinine > 177 μmol/l

UO < 0.5 ml/kg/hr

• 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

Merinoff definition

Why do we need to change??

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 2008

To be completed within 3?? hours:1) Measure lactate level2) Obtain blood cultures prior to administration of antibiotics3) Administer broad spectrum antibiotics4) 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*

SSC Bundle 2012

Severe Sepsis Acute coronary syndrome

No. cases per 100,000 per annum

337 200

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

Perspective

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 Hartmann’s or equivalent

5. Check lactate

6. Monitor hourly urine output consider catheterisation

within one hour..plus Critical Care support to complete EGDT

Aim to give 100% initially

In practice you can’t!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 1: Oxygen

Before starting antibiotics, at least one blood culture:

PercutaneouslyAND 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 – 532. 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

Step 2: Cultures

Alvarez-Lerma F, Alvarez B, Ruiz F et al for the ADANN Study Group. Crit Care 2006; 10: R 78

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 sourceGuided by local pathogensGive broad spectrum until defined

Step 3: Antibiotics

Early, appropriate antibiotics are the key to improved

outcomes

First hour antibiotics in 27%...

Kumar et al. CCM. 2006:34:1589-96.

time from hypotension onset (hrs)

0-0.50.5-1

1-2 2-3 3-4 4-5 5-6 6-9 9-1212-24

24-3636+

frac

tion

of to

tal p

atien

ts

0.0

0.2

0.4

0.6

0.8

1.0 survival fraction

cumulative antibiotic initiation

Effective Antimicrobial Therapy &Survival in Septic Shock

Funk and Kumar

Critical Care Clinics 2011 (in press)

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%

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%

Author n Setting Median time (mins)

Odds Ratio for death

GaieskiCrit Care Med 2010; 38:1045-53

261 ED, USA(Shock)

119 0.30(first hour vs all times)

DanielsEmerg Med J 2010; doi:10.1136

567 Whole hospital, UK

121 0.62(first hour vs all times)

KumarCrit Care Med 2006; 34(6):1589-1596

2154 ED, Canada(Shock)

360 0.59(first hour vs second hour)

AppelboamCritical Care 2010; 14(Suppl 1): 50

375 Whole hospital, UK

240 0.74(first 3 hours vs delayed)

LevyCrit Care Med 2010; 38 (2): 1-8

15022 Multi-centre 0.86(first 3 hours vs delayed)

Early abx are good.

0 10 20 30 40 50 60 70 80 90100

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Cumulative fraction of total survivors

Running average survival

Survival in septic shock based on antibiotic delay (n=4195)

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

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

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

64.4% septic shock patients developed early AKI

Median time shock to antibiotic = 5.5 h

Retrospective, 22 hospitals, n= 4532

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

64.4% septic shock patients developed early AKI

Median time shock to antibiotic = 5.5 h

OR for AKI1.14 (1.10-1.20) P < 0.001

per hour’s delay

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

CaO2 = Amount of O2 in arterial blood

Fluid therapy improves cardiac output by increasing venous return to the heart

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

DO2 = CaO2 x CO

Step 4: Fluids

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

CaO2 = ([Hb] x SaO2

DO2 = CaO2 x CO

Optimizing DO2

Judicious fluid challengesUp to 30ml/kg in divided boluses (min. 20ml/kg in shock)

Crystalloid (500ml boluses)Colloid (250-300ml boluses)

Reassess for effect after each challengeHR, BP, capillary refill, urine output, RR

In patients with cardiac diseaseUse smaller volumesMore frequent assessmentEarly CVC

Fluid resuscitation

High lactate identifies tissue hypoperfusion in patients at risk who are not hypotensive

‘Cryptic shock’

Gives an overview of current tissue oxygen delivery

The GoalLactate to improve

as resuscitation progresses

Step 5: Lactate

0

5

10

15

20

25

30

35

40

% i

n h

osp

ital

Mo

rtal

ity

Lactate threshold

Low (0 - 2.0)

Intermediate ( 2.1 - 3.9)

Severe (>4.0)

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

Risk stratification

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

Step 6: 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

However RBF is directly proportional to cardiac output

Renal blood flow

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

Sepsis

Screen!!

1c reco

mmendation 2013

Moore LJ, Jones SL, Kreiner LA, et al: Validation of a screening tool for the early identification of sepsis. J Trauma 2009; 66: 1539–1546

2 groups with 1 identical need

3. Respond and escalate appropriately

Sepsis Six delivery

39904 39965 40026 400870

10

20

30

40

50

60

70

Sepsis 6

Resusc

Both

Mortality

Compliance,GHH (%)

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 saved285 fewer bed days168 fewer CC bed days

Direct costs for survivors reduced by £0.25M

For UK, that’s 12,500 lives and £156 million. Every year.

ron@sepsistrust.org @SepsisUK

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