sepsis where are the goal posts now?. what is the new evidence? rcts: trilogy of egdt trials...
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SEPSISWhere are the
goal posts now?
What is the new evidence?
• RCTs: Trilogy of EGDT trials (2014-2015)
• RCT: SEPSIS-PAM (2014)• RCT: ALBIOS (2014)• Observational data: fluids and vasopressors (2014)• Observational data: peripheral norad (2015)
A new PROCESS
ARISE strikes Back
PROMISE of the Jedi
A new PROCESS
ARISE strikes Back
PROMISE of the Jedi
PROCESS
ARISE
PROMISE
RIVERS EGDT
Detroit 1997-2000Control (133 patients)
Mortality 46.5%
EGDT SUPERIOR (30.5%)
31 Academic centres in USA – 2008-2013Control (456 patients)
Mortality 19%
51 centres (95% pts from ANZ) – 2008-2014Control (798 patients)
Mortality 16%
56 centres in the UK – 2011-2014Control (630 patients)
Mortality 25%
PROCESS
ARISE
PROMISE
RIVERS EGDT
Detroit 1997-2000Control (133 patients)
Mortality 46.5%
EGDT SUPERIOR (30.5%)
31 Academic centres in USA – 2008-2013Control (456 patients)
Mortality 19%
51 centres (95% pts from ANZ) – 2008-2014Control (798 patients)
Mortality 16%
56 centres in the UK – 2011-2014Control (630 patients)
Mortality 25%
EGDT NO BENEFIT
PROCESS
ARISE
PROMISE
RIVERS EGDT
Detroit 1997-2000Control (133 patients)
Mortality 46.5%
EGDT SUPERIOR (30.5%)
31 Academic centres in USA – 2008-2013Control (456 patients)
Mortality 19%
51 centres (95% pts from ANZ) – 2008-2014Control (798 patients)
Mortality 16%
56 centres in the UK – 2011-2014Control (630 patients)
Mortality 25%
EGDT NO BENEFIT
EGDT NO BENEFIT
PROCESS
ARISE
PROMISE
RIVERS EGDT
Detroit 1997-2000Control (133 patients)
Mortality 46.5%
EGDT SUPERIOR (30.5%)
31 Academic centres in USA – 2008-2013Control (456 patients)
Mortality 19%
51 centres (95% pts from ANZ) – 2008-2014Control (798 patients)
Mortality 16%
56 centres in the UK – 2011-2014Control (630 patients)
Mortality 25%
EGDT NO BENEFIT
EGDT NO BENEFIT
EGDT NO BENEFIT
EGDT studies – early activities
RIVERS ProMISE ProCESS ARISE
Time to randomisation
<1 hour 2 hrs 30 mins 3 hours 2 hrs 45 mins
Fluid before randomisation
UNK (0-1) 2.0 litres 2.1 litres 2.5 litres
Initial ScvO2 (EGDT arm)
49% 70% 71% 72%
Lactate at randomisation(EGDT arm)
7.7 mmol/l 5.1 mmol/l 4.9 mmol/l 4.4 mmol/l
Antibiotics(EGDT arm)
86% by 6hrs 100% before randomisation
76% before randomisation,
98% by 6 hrs
100% before randomisation
Control mortality
46.5% 24.5% 18.9% 15.7%
Take home from EGDT studies:
1. Don’t put in a CVL to measure ScvO22. Aggressive early fluid is probably a good thing3. Mortality of ED septic shock in ANZ: <20%
PROCESS
ARISE
PROMISE
Early Therapy for Septic Shock
• Early fluids • Early antibiotics
• MAP>65• Lactate clearance Fluids, vasopressors• Urine output
• Source control, organ support.
The many questions
• How much fluid?• What filling target?• What type of fluid?• What BP target?• When to start norad?• How much norad?• What’s after norad?• Is there a role for inotropes?• What transfusion target?
The many questions
• How much fluid?• What filling target?• What type of fluid?• What BP target?• When to start norad?• How much norad?• What’s after norad?• Is there a role for inotropes?• What transfusion target?
What type of fluid? Saline Balanced crystalloid – Hartmann’s Colloids – starch, gels, albumin
Retrospective analysis (USA )Database : 53,500 ICU patients with vasopressor dependent septic shock
3,365 patients - balanced crystalloid in 1st 2 days
Propensity-matched analysis
Hospital mortality
Balanced = 19.6% Isotonic = 22.8%
RR 0.86 (0.78-0.94) p = 0.001
Should we use Hartmann’s as crystalloid for septic shock resuscitation?
Should we use Hartmann’s as crystalloid for septic shock resuscitation?
Sometimes maybe
The ALBIOS trial
The ALBIOS trial1818 Italian ICU patients with severe sepsis in last 24 hours
SALINEALBUMIN300ml 20% Albumin initially
Further albumin for 30g/l
The ALBIOS trial1818 Italian ICU patients with severe sepsis in last 24 hours
SALINEALBUMIN300ml 20% Albumin initially
Further albumin for 30g/l
The ALBIOS trial1818 Italian ICU patients with severe sepsis in last 24 hours
SALINEALBUMIN300ml 20% Albumin initially
Further albumin for 30g/l
The ALBIOS trial1818 Italian ICU patients with severe sepsis in last 24 hours
NO significant difference
28d mortality:Albumin 31.8%Saline 32%
90d mortality:Albumin 41.1%Saline 43.6%
Albumin you have chosen?
A wise decision you have made…
The Force
What MAP target?
SEPSISPAM
SEPSISPAM776 septic shock patients in French ICUs
MAP 65-70 MAP 80-85
SEPSISPAM776 septic shock patients in French ICUs
MAP 65-70 MAP 80-85
SEPSISPAM776 septic shock patients in French ICUs
SEPSISPAM776 septic shock patients in French ICUs
MAP 65-70 MAP 80-85
MAP 65 is a good start…
What’s the
target??
When should we start norad?
Retrospective study 213 surgical ICU patients with septic shock
Examined outcomes related to time of norad commencement
Less hypotensionLess noradLess fluid in 24h
Crit Care Med 2014;42:2158-2168
Crit Care Med 2014;42:2158-2168
2849 ICU patients with septic shock (Canada, USA, Saudi Arabia)
Documented fluid given TEV 0-1TEV 1-6TEV 6-24
And classified time of norad commencement
Crit Care Med 2014;42:2158-2168 (2) (3.7)
Crit Care Med 2014;42:2158-2168
Noncompliant odds ratio for mortality (referent compliant)
ED process of care (POC) Compliant (n, %)
unadjusted adjusted SAPS II
Lactate measured a 197 (91.2) 1.56 (0.56-4.34) 1.97 (0.63-6.23)
Time to appropriate AB < 2hrsb
151 (39.1) 0.74 (0.44-1.24) 1.54 (0.83-2.89)
Fluid >2 litres in 1st 6 hours 237 (59.4) 1.09 (0.66-1.80) 2.01 (1.11-3.67)
Fluid >3 litres in 1st 6 hours 139 (34.8) 1.16 (0.69-1.98) 2.47 (1.29-4.72)
Fluid >4 litres in 1st 6 hours 88 (22.1) 1.37 (0.73-2.58) 3.52 (1.59-7.78)
NA in ED for hypotension admitted to ICU c
81 (72.3) 2.33 (0.78-6.94) 3.58 (1.07-12.00)
Albumin given in ED 132 (33.1) 0.80 (0.48-1.33) 1.49 (0.81-2.74)
Septic shock in the RBWH ED399 cases of septic shock admitted over 162 weeks
Denominators: a216 (hypotension), b386, c112, otherwise = 399.
Noncompliant odds ratio for mortality (referent compliant)
ED process of care (POC) Compliant (n, %)
unadjusted adjusted SAPS II
Lactate measured a 197 (91.2) 1.56 (0.56-4.34) 1.97 (0.63-6.23)
Time to appropriate AB < 2hrsb
151 (39.1) 0.74 (0.44-1.24) 1.54 (0.83-2.89)
Fluid >2 litres in 1st 6 hours 237 (59.4) 1.09 (0.66-1.80) 2.01 (1.11-3.67)
Fluid >3 litres in 1st 6 hours 139 (34.8) 1.16 (0.69-1.98) 2.47 (1.29-4.72)
Fluid >4 litres in 1st 6 hours 88 (22.1) 1.37 (0.73-2.58) 3.52 (1.59-7.78)
NA in ED for hypotension admitted to ICU c
81 (72.3) 2.33 (0.78-6.94) 3.58 (1.07-12.00)
Albumin given in ED 132 (33.1) 0.80 (0.48-1.33) 1.49 (0.81-2.74)
Septic shock in the RBWH ED399 cases of septic shock admitted over 162 weeks
Denominators: a216 (hypotension), b386, c112, otherwise = 399.
Noncompliant odds ratio for mortality (referent compliant)
ED process of care (POC) Compliant (n, %)
unadjusted adjusted SAPS II
Lactate measured a 197 (91.2) 1.56 (0.56-4.34) 1.97 (0.63-6.23)
Time to appropriate AB < 2hrsb
151 (39.1) 0.74 (0.44-1.24) 1.54 (0.83-2.89)
Fluid >2 litres in 1st 6 hours 237 (59.4) 1.09 (0.66-1.80) 2.01 (1.11-3.67)
Fluid >3 litres in 1st 6 hours 139 (34.8) 1.16 (0.69-1.98) 2.47 (1.29-4.72)
Fluid >4 litres in 1st 6 hours 88 (22.1) 1.37 (0.73-2.58) 3.52 (1.59-7.78)
NA in ED for hypotension admitted to ICU c
81 (72.3) 2.33 (0.78-6.94) 3.58 (1.07-12.00)
Albumin given in ED 132 (33.1) 0.80 (0.48-1.33) 1.49 (0.81-2.74)
Septic shock in the RBWH ED399 cases of septic shock admitted over 162 weeks
Denominators: a216 (hypotension), b386, c112, otherwise = 399.
START THE NORAD EARLY!(Rebel Scum)
PERIPHERAL NORADRENALINE
PERIPHERAL NORADRENALINE
http://emcrit.org/podcasts/peripheral-vasopressors-extravasation/
Podcast 107 – Peripheral Vasopressor Infusions and Extravasation
PERIPHERAL NORADRENALINE
Sept 16, 2013
The force is strong with you
That’s my timely
peripheral norad
Summary
• Early fluid – cystalloid or albumin ALBIOS• MAP 65-70 SEPSISPAM
• Early norad – peripherally is OK to start convert to CVL if required • Don’t use CVL to measure ScvO2 ProCESS / ARISE / ProMISE
TWO!
FREAKIN!
BLOOD!
CULTURES!!!!!!
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