Mervyn Singer Bloomsbury Institute of Intensive Care Medicine

University College London, UK

The role of massage in sepsis

.. separating truth from fake news

“ S E P S I S I S A M A J O R K I L L E R ” …

P U T T I N G T H E N U M B E R S I N C O N T E X T . .

• 34 million antibiotic prescriptions by English GPs in 2015-6

• 1.3 million hospital patient episodes with a sepsis/infection code in England p.a.

• .. with 32,300 in-hospital deaths = 2.5% mortality rate

• .. only 12,000 of these deaths had an ICU admission

“Pneumonia is the old man’s friend” - Sir William Osler

Patients may be allowed to die from/with sepsis due to the severity of their

underlying comorbidity - terminal cancer, end-stage CHF/CKD/COPD,

severe stroke, severe dementia …

H O W M A N Y W A R R A N T E D L I F E - P R O L O N G I N G T H E R A P Y

± I C U A D M I S S I O N ? ? ?

D I D T H E Y D I E ‘ O F ’ O R ‘ W I T H ’ S E P S I S ?

0

200000

400000

600000

800000

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+

‘SUSPICION OF SEPSIS’ ADMISSIONS IN ENGLAND 2011-17N

Age

Mortality (%)

0

10

20

30

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+

‘SUSPICION OF SEPSIS’ MORTALITY 2011-17

Age

456

115

113

208

306

396

603

933

1812

3196

5165

8359

1470

8

2476

7

3527

0

5562

6

8254

4

9592

5

9803

9

77.5% OF DEATHS 8% OF DEATHS

Dementia? Stroke? Cancer? Other severe disability?

I S S E P S I S M O R TA L I T Y I N T H E U K

G O I N G U P O R D O W N ?

.. but decline in mortality is greater in non-septic admissions!

L O O K AT T H E D E N O M I N AT O R , N O T T H E % …

118,676

213,124300,270

781,725

??? under-reported

??? over-reported

R I S E I N S E P S I S I N U S ( 1 9 9 3 - 2 0 1 4 ) - A H R Q D ATA

C H A N G E I N D R G R E I M B U R S E M E N T

C H A N G E I N I C D D I S C H A R G E

C O D I N G

N H S E N G L A N D S E P S I S D A S H B O A R D

N H S E N G L A N D S E P S I S D A S H B O A R D

E M E R G E N C Y A D M I S S I O N S C O D E D A S S E P S I S O R B A C T E R I A L I N F E C T I O N

E M E R G E N C Y A D M I S S I O N S C O D E D A S S E P S I S

T O TA L E M E R G E N C Y A D M I S S I O N S

2791 patients 165 hospitals

509 patients 34 hospitals

n= 69 deaths

n= 84 deaths

1st iteration SSC guidelines

A N T I B I O T I C S -

“ E V E R Y H O U R O F D E L AY K I L L S ”

.. really??

• Studies claiming ‘every hour counts’ are all based on retrospective

analyses of databases collected for other reasons (usually

administrative), but lacking vital data e.g. antibiotic sensitivities

• .. and use complex adjustments to find a mortality difference

• .. and often incorporate very delayed treatment (>6h) into the analysis

• .. and often lack biological plausibility

• .. and cannot explain why there was a delay in treatment in some pts

I N T E R E S T I N G FA C T S - 1

time following hypotension (hours)

7.6% decrease in survival per hour of delay

n=558

n=2154

Survival

0

15

30

45

60

0-1 1-2 2-3 3-4 4-5 5-6 >6

EDWardICUREAL mortality (%)

Time to antibiotic (hr)

.. and why was there a delay if treatment was mandated???

Other = viral, fungal, anaerobic, mixed organisms

… and no data on antibiotic sensitivities, adequacy of dosing, source control, etc..

0.9 1.0 1.1 1.2 1.3 1.4

Odds ratio for in-hospital mortality

23.6% †22.6% †

2% of pts

82.5% of pts

15.5% of pts

D E S P I T E T H E O B V I O U S F L A W S , T H I S S T U D Y D R O V E T H E S U R V I V I N G S E P S I S C A M PA I G N T O P R O P O S E A 1 - H O U R B U N D L E

.. more later

P R O S P E C T I V E S T U D I E S S H O W N O D I F F E R E N C E I N M O R TA L I T Y F R O M A N T I B I O T I C S G I V E N F O R S E P S I S O V E R 1 S T 5 - 6 H O U R S

• Usually designed to specifically look at impact of antibiotics on outcomes

• None show an ‘each-hour-delay-kills’ signal

• Puskarich, CCM 2011 septic shock (ED)

• Hranjec, Lancet Infect Dis 2012 sepsis/septic shock (ICU)

• Kaasch, Infection 2013 S aureus bacteraemia (Ward/ICU)

• Bloos, Crit Care 2014 sepsis/septic shock (ICU)

• De Groot, Crit Care 2015 ED sepsis/septic shock (ED)

• Fitzpatrick, Clin Microbiol Infect 2016 Gm -tive bacteraemia (Ward)

• Alan, Lancet Respir Dis 2018 sepsis (pre-hospital ED)

• 2672 patients randomised to receive pre-hospital antibiotics (ceftriaxone 2g)

from paramedics on suspicion of sepsis OR start antibiotics in ED

• Mean 96 minute difference in time to administration of antibiotics

2672 patients Intervention group: TTA 26 min (IQR 19–34) pre-arrival at ED Usual care group: TTA 70 min (IQR 36–128) post-arrival at ED

Guidelines are taken too literally by:

• clinical zealots

• institutions

• government bodies

• lawyers

.. with financial penalties, litigation or ‘name-and-shame’ for non-compliance

R U L E S O F S T O N E

We were given a six hour bundle and a 24 hour bundle ...

.. and were told this was the one true way

T H E S U R V I V I N G S E P S I S C A M PA I G N A N D T H E I N S T I T U T E F O R H E A LT H C A R E I M P R O V E M E N T D E L I V E R E D B U N D L E S T O U S F R O M O N H I G H . .

• four beers make the evening more pleasant

• a bottle of wine makes the evening more pleasant

• four cognacs make the evening more pleasant

• four beers plus a bottle of wine plus four cognacs should

guarantee a very pleasant evening

Study abandoned due to unanticipated side effects

T H E S C I E N C E B E H I N D A B U N D L E

• four beers make the evening more pleasant

• a bottle of wine makes the evening more pleasant

• four cognacs make the evening more pleasant

• four beers plus a bottle of wine plus four cognacs should

guarantee a very pleasant evening

Study abandoned due to unanticipated side effects

• four beers make the evening more pleasant

• a bottle of wine makes the evening more pleasant

• four cognacs make the evening more pleasant

• four beers plus a bottle of wine plus four cognacs should

guarantee a very pleasant evening

Study abandoned due to unanticipated side effects

T H E S C I E N C E B E H I N D A B U N D L ET H E S C I E N C E B E H I N D A B U N D L E

• The SSC 24 hour bundle abandoned following ‘negative’ RCTs

on steroids, activated Protein C, and tight glycaemic control

• SSC then abandoned the 6-hour EGDT bundle following a

‘trilogy’ of negative RCTs (ProCESS, ARiSE and ProMISe)

B E L I E F C O N Q U E R S A L L …

. . U N T I L E V I D E N C E P R O V E S O T H E R W I S E

12 Sept 2018

• Need to be first proven to work for everyone .. and not cause harm to any

Q U A L I T Y I M P R O V E M E N T M A N D AT E S

• One size doesn’t fit all

• A loose structure is important (a shirt generally needs two arms) ..

• .. but needs to fit the occasion

N H S S E P S I S C Q U I N

N H S C Q U I N D ATA

sepsis = life-threatening organ dysfunction due

to a dysregulated host response to infection

S E P S I S - 3 D E F I N I T I O N

S E P S I S - 3

sepsis = life-threatening organ dysfunction due

to a dysregulated host response to infection

I N F E C T I O N

D E F I N I T I O N

C L I N I C A L C R I T E R I A

= ≥1 0 % R I S K O F D Y I N G

S O FA S C O R E

circulatory, cellular and metabolic abnormalities

associated with greater risk of mortality than

sepsis aloneI N F E C T I O N

V E R YD E F I N I T I O N

C L I N I C A L C R I T E R I A

≥2 mmol/l

= 4 0 - 5 0 % R I S K O F D Y I N G

S E P T I C S H O C K

BRAZILUK

809 patients, 49 ICUs - hospital mortality: sepsis 27.6% septic shock 51%

JAPAN 1195 patients, 42 ICUs - hospital mortality: septic shock 41.9%

C O D I N G

• Sepsis-3 definitions and clinical criteria for sepsis and septic shock

have been incorporated into ICD-11

• First time a coding change has been based on validated data!

S U M M A R Y

• Current practice is largely driven by dogma, propaganda, institutional pressures

and Twitter … rather than hard fact

• Challenge the dogma where facts are lacking e.g. antibiotics

• One size doesn’t fit all .. personalisation not rigid protocolization

• Apply physiology - and thought - to individual patient management

• Don’t delay unnecesarily roportionate response

• Sepsis-3 is - hopefully - a step forward toward standardisation