myths and misconceptions in the …administrative), but lacking vital data e.g. antibiotic...
TRANSCRIPT
SUR
VIVIN
G SEPS
IS C
OO
KBO
OK
SEPSIS M
ADE EASY
SEP
SI
S IS A P
IE
M E R V Y N S I N G E R B L O O M S B U R Y I N S T I T U T E O F I N T E N S I V E C A R E M E D I C I N E
U N I V E R S I T Y C O L L E G E L O N D O N , U K
MYTHS AND MISCONCEPTIONS IN THE MANAGEMENT OF SEPSIS
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
D I S C U S S I O N P O I N T S . .
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
I N D I V I D U A L S V E R S U S P O P U L A T I O N S
• Patients do NOT necessarily follow the rule book
• MUST tailor therapy to the individual
• Guidelines should NOT be used as rigid protocols/rules of stone
• Clinical expertise is VITAL
I N D I V I D U A L S V E R S U S P O P U L A T I O N S
• Patients do NOT necessarily follow the rule book
• MUST tailor therapy to the individual
• Guidelines should NOT be used as rigid protocols/rules of stone
• Clinical expertise is VITAL
.. not my words, but David Sackett’s
I N D I V I D U A L S V E R S U S P O P U L A T I O N S
Q U A L I T Y - O R L A C K - O F E V I D E N C E
• Overall evidence base for sepsis is - sadly - rather weak
• Only a few awarded ‘high’ quality (but generally ‘do nots’ rather than ‘do’s’)
Q U A L I T Y - O R L A C K - O F E V I D E N C E
• Need decent evidence to confirm need to change
• For example, Rivers showed EGDT was beneficial in 2001 .. but why?
D O G M A S H O U L D N ’ T R U L E …
• Need decent evidence to confirm need to change
• For example, Rivers showed EGDT was beneficial in 2001 .. but why?
D O G M A S H O U L D N ’ T R U L E …
• Need decent evidence to confirm need to change
• For example, Rivers showed EGDT was beneficial in 2001 .. but why?
D O G M A S H O U L D N ’ T R U L E …
• Need decent evidence to confirm need to change
• For example, Rivers showed EGDT was beneficial in 2001 .. but why?
D O G M A S H O U L D N ’ T R U L E …
• Need decent evidence to confirm need to change
• For example, Rivers showed EGDT was beneficial in 2001 .. but why?
D O G M A S H O U L D N ’ T R U L E …
• Identify patient early
• Treat promptly and appropriately
• .. but the specific Rivers’ protocol doesn’t seem to
offer any overall added benefit
T A K E - H O M E M E S S A G E
L O W E S T C O M M O N D E N O M I N A T O R ?
Standardised mortality ratiogood performing
hospitals
not-so-good performing hospitals
L O W E S T C O M M O N D E N O M I N A T O R ?
Standardised mortality ratiogood performing
hospitals
not-so-good performing hospitals
? rigid protocol application
L O W E S T C O M M O N D E N O M I N A T O R ?
Standardised mortality ratiogood performing
hospitals
not-so-good performing hospitals
? rigid protocol application
? rigid protocol application
L O W E S T C O M M O N D E N O M I N A T O R ?
Standardised mortality ratiogood performing
hospitals
not-so-good performing hospitals
? rigid protocol application
? rigid protocol application
Guidelines are often taken too literally by:
• clinical zealots
• institutions
• governments
B U T … .
Guidelines are often taken too literally by:
• clinical zealots
• institutions
• governments
.. with financial penalties or ‘name-and-shame’ for non-compliance
B U T … .
• Use guidelines/protocols as an aide memoire
• .. but not rules of stone
• Don’t be afraid to deviate .. but be able to justify why
T A K E - H O M E M E S S A G E
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
T H E I N T E R V E N T I O N . . O R T A R G E T E D E N D P O I N T . . M U S T B E R A T I O N A L F O R E V E R Y O N E
S O W H Y TA R G E T A P O P U L AT I O N ,
A N D N O T A N I N D I V I D U A L ! ! ! ! !
T A K E - H O M E M E S S A G E
• Titrate to the individual e.g. what BP suits them? MAP 55-60 or 75-80?
T A K E - H O M E M E S S A G E
• Titrate to the individual e.g. what BP suits them? MAP 55-60 or 75-80?
• Titrate to a goal
• if a patient needs fluid (if hypovolaemia -> hypoperfusion), give fluid
• if not hypovolaemic and hypoperfused, don’t give fluid
T A K E - H O M E M E S S A G E
• Titrate to the individual e.g. what BP suits them? MAP 55-60 or 75-80?
• Titrate to a goal
• if a patient needs fluid (if hypovolaemia -> hypoperfusion), give fluid
• if not hypovolaemic and hypoperfused, don’t give fluid
• Avoid excess - too much fluid, too much oxygen, too much catecholamine …
T A K E - H O M E M E S S A G E
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
I N T E R E S T I N G F A C T S - 1
• Multiple papers - including EVERY prospective study I’m aware of -
do NOT show a correlation between a short-term delay in
administering antibiotics and mortality
I N T E R E S T I N G F A C T S - 1
I N T E R E S T I N G F A C T S - 2
• 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
I N T E R E S T I N G F A C T S - 2
• 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
I N T E R E S T I N G F A C T S - 2
• 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
I N T E R E S T I N G F A C T S - 2
• 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
I N T E R E S T I N G F A C T S - 2
• 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
I N T E R E S T I N G F A C T S - 2
time following hypotension (hours)
Survival
time following hypotension (hours)
7.6% decrease in survival per hour of delay
Survival
time following hypotension (hours)
7.6% decrease in survival per hour of delay
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)
Survival
time following hypotension (hours)n=2154
Survival
time following hypotension (hours)n=2154
Survival
time following hypotension (hours)
n=558
n=2154
Survival
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
0
15
30
45
60
0-1 1-2 2-3 3-4 4-5 5-6 >6
EDWardICU
Mortality (%)
Time to antibiotic (hr)
• 1373 ICU patients between 2006-13 coded as septic/septic shock
• 1373 ICU patients between 2006-13 coded as septic/septic shock
• 1373 ICU patients between 2006-13 coded as septic/septic shock
• 1373 ICU patients between 2006-13 coded as septic/septic shock
… and no data on antibiotic sensitivities, adequacy of dosing, source control, etc..
.. yet 45% of patients (early and late treated) had ‘septic shock’!!
82.5% of pts
2% of pts
22.6% †
23.6% †
82.5% of pts
2% of pts
2% of pts
82.5% of pts
15.5% of pts
2% of pts
82.5% of pts
15.5% of pts
2% of pts
82.5% of pts
15.5% of pts
2% of pts
82.5% of pts
15.5% of pts
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
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
• Often 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)
• prospective observational study in 3 Dutch EDs
• hospitalized ED patients requiring iv antibiotics
• stratified by illness severity (low, intermediate, high)
• time to antibiotics <1 hour vs 1-3 hours v >3 hours
• 1168 patients enrolled - overall mortality 10%
• 85% received antibiotics within 3 hours, 95% within 6 hours
• No association between time to a/b and surviving days
outside hospital or mortality
• In low illness severity group, delayed (>3h) antibiotics
associated with more surviving days outside hospital (HR
1.46 (95%CI 1.05-202)
• 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
T A K E - H O M E M E S S A G E
T A K E - H O M E M E S S A G E
• Every second doesn’t count .. but
reasonable/rational to treat sepsis
and septic shock promptly
• Rather than simply throwing
antibiotics at the patient, apply
some thought, seek advice, and
think source control
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
• 6 month audit in University hospital medical-surgical ICU
• 6 month audit in University hospital medical-surgical ICU
• 113 bacteraemia episodes in 87 patients
• 6 month audit in University hospital medical-surgical ICU
• 113 bacteraemia episodes in 87 patients
• Short-course monotherapy (4-5 days) used in 65.7%
• 6 month audit in University hospital medical-surgical ICU
• 113 bacteraemia episodes in 87 patients
• Short-course monotherapy (4-5 days) used in 65.7%
• Low rates of bacteraemia breakthrough/relapse
• 6 month audit in University hospital medical-surgical ICU
• 113 bacteraemia episodes in 87 patients
• Short-course monotherapy (4-5 days) used in 65.7%
• Low rates of bacteraemia breakthrough/relapse
• Very low incidence of antimicrobial resistance or fungaemia
• 6 month audit in University hospital medical-surgical ICU
• 113 bacteraemia episodes in 87 patients
• Short-course monotherapy (4-5 days) used in 65.7%
• Low rates of bacteraemia breakthrough/relapse
• Very low incidence of antimicrobial resistance or fungaemia
• Less ICU-acquired MRSA, MDR Gram -tives, VRE and
fluconazole-resistant candidaemia c/f similar audit in 2000
fluconazole-resistant
fluconazole-resistant
methicillin-resistant
fluconazole-resistant
methicillin-resistant
VRE
MDR
fluconazole-resistant
methicillin-resistant
VRE
MDR
fluconazole-resistant
methicillin-resistant
VRE
no fluconazole-resistance
MDR
fluconazole-resistant
methicillin-resistant
VRE
no fluconazole-resistance
1 VRE
MDR
fluconazole-resistant
methicillin-resistant
VRE
no fluconazole-resistance
1 VRE
no MRSA
MDR
fluconazole-resistant
methicillin-resistant
VRE
no fluconazole-resistance
1 VRE
no MRSA
no MDR
4 vs 8 days
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
300,270
781,725
118,676
213,124300,270
781,725
118,676
213,124300,270
781,725
118,676
213,124300,270
781,725
??? under-reported
??? over-reported
• Guidelines should be slavishly followed
• One size fits all
• Every hour of antibiotic delay kills
• How long should a course of antibiotics last?
• Sepsis mortality is improving
• Why do people die of sepsis?
D I S C U S S I O N P O I N T S . .
M A I N T A I N I N G A S E N S E O F P R O P O R T I O N …
M A I N T A I N I N G A S E N S E O F P R O P O R T I O N …
▪ 34 million antibiotic prescriptions by English GPs in 2015-6
M A I N T A I N I N G A S E N S E O F P R O P O R T I O N …
▪ 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.
M A I N T A I N I N G A S E N S E O F P R O P O R T I O N …
▪ 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
M A I N T A I N I N G A S E N S E O F P R O P O R T I O N …
▪ 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
▪ BUT … only 11,000 cases of sepsis had an ICU admission
D O A L L S E P T I C P A T I E N T S W A R R A N T
L I F E - P R O L O N G I N G T R E A T M E N T ? ? ?
“Pneumonia is the old man’s friend” - Sir William Osler
Patients may be allowed to die from sepsis due to the severity
of their underlying comorbidity - terminal cancer, severe stroke,
end-stage chronic organ failure, severe dementia …
D O A L L S E P T I C P A T I E N T S W A R R A N T
L I F E - P R O L O N G I N G T R E A T M E N T ? ? ?
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’ HOSPITAL ADMISSIONS IN ENGLAND 2011-17N
Age
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’ HOSPITAL 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
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’ HOSPITAL 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
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’ HOSPITAL 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?Other severe disability?
Dementia?Stroke?Other severe disability?
C O N C L U S I O N
• Apply physiology to patient management
C O N C L U S I O N
• Apply physiology to patient management
• Personalization not rigid protocolization
C O N C L U S I O N
• Apply physiology to patient management
• Personalization not rigid protocolization
• Challenge dogma based on weak/contrived evidence
C O N C L U S I O N
• Apply physiology to patient management
• Personalization not rigid protocolization
• Challenge dogma based on weak/contrived evidence
• Sepsis only constitutes a small proportion of infection … but should be
identified and acted upon promptly .. but with some thought applied
C O N C L U S I O N
• Apply physiology to patient management
• Personalization not rigid protocolization
• Challenge dogma based on weak/contrived evidence
• Sepsis only constitutes a small proportion of infection … but should be
identified and acted upon promptly .. but with some thought applied
C O N C L U S I O N