sepsis where are the goal posts now?. what is the new evidence? rcts: trilogy of egdt trials...

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

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


Mortality 46.5%



Mortality 19%


Mortality 16%


Mortality 25%

EGDT NO BENEFIT

PROCESS

ARISE

PROMISE

RIVERS EGDT


Mortality 46.5%



Mortality 19%


Mortality 16%


Mortality 25%

EGDT NO BENEFIT

EGDT NO BENEFIT

PROCESS

ARISE

PROMISE

RIVERS EGDT


Mortality 46.5%



Mortality 19%


Mortality 16%


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?

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

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


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)



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

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!!!!!!

sepsis where are the goal posts now?. what is the new evidence? rcts: trilogy of egdt trials...

Documents

academic centres

egdt superior

patients mortality

new processarise

trilogy of egdt trials

new evidence

randomisation3 litres

observational data