Post on 16-Apr-2017
When to pull the Tx-trigger?
University ofCopenhagen
Anders Perner
University ofCopenhagen
COIsResearch funds from Fresenius Kabi, CSL Behring
Royal North Shore Hospital - Sydney
TRISS TRIAL
After fluid resuscitation, MAP is 75, HR 100 on 0.1mcg/kg/min of NA
Hb is 8.5 g/dl and ScvO2 50%
What would you do next?
Early sepsis case
Emerg Med J 2010;27:110-15
0
10
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90
100
US EM
ANZ ICU
ANZ EM
UK EM
UK ICU
US ICU
Transfuse until Hb > 10 g/dl
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20
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60
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US EM
ANZ ICU
ANZ EM
UK EM
UK ICU
US ICU
Transfuse until Hb > 10 g/dl
Transfuse until Hb > 10 g/dl
0
10
20
30
40
50
60
70
80
90
100
US EM
ANZ ICU
ANZ EM
UK EM
UK ICU
US ICU
Transfuse until Hb > 10 g/dl
0
10
20
30
40
50
60
70
80
90
100
US EM
ANZ ICU
ANZ EM
UK EM
UK ICU
US ICU
SSC
First 6 hours:Hematocrit above 30 percent if ScvO2 < 70%
EGDT protocol
More patients Tx‘ed in EGDT vs usual care groups in
ProCESS 14 vs 8%
ARISE 14 vs 7%
ProMise 9 vs 4%
More patients Tx‘ed in EGDT vs usual care groups in
ProCESS 14 vs 8%
ARISE 14 vs 7%
ProMise 9 vs 4%
Rivers 64 vs 19%
• Benefit vs. harm• Triggers• Blind spots• Expensive and limited resource
Blood Tx
Odds for Tx given in ICU• Sweden 5.0
• Denmark 4.0
• USA 3.8
• China 3.3
• Canada 1.0
• UK 0.9
• France 0.9
• NZ 0.5SAFE TRIPS 2007
Risks of transfusion Infectious
Non-infectious
Storage-lession
Immuno-modulation
Benefits vs harms
Risks of anemiaLow DO2
Ischemia
Organ dysfunction
Multiple organ dysfunction
TRISS TRIAL
32 Scandinavian ICUs TRISS TRIAL
1000 adult ICU patients with septic shock
1 unit leuko-reduced RBCs
at
Hb < 7 g/dl
1 unit leuko-reduced RBCs
at
Hb < 9 g/dl
Hb < 9 g/dl
TRISS TRIAL
HbTx-triggers
Chest pain
Hypotension
Tachycardia
Heart failure
Fatigue
SvO2 / ScvO2
Lactate
ECG-dynamics
SAP x heart rate
Severity
Cardiac output
ScreenedTRISS TRIAL
ExcludedTRISS TRIAL
AnalysedTRISS TRIAL
Median no. of units Tx’ed
Lower Threshold : 1 (IQR 0-3)
Higher Threshold : 4 (IQR 2-7)
(P <0.001)
TRISS TRIAL
Lowest median HbTRISS TRIAL
Many more red cellsvs.
Sustained severe anemia
TRISS TRIAL
Deaths within 90 daysTRISS TRIAL
Primary analysis supported by subgroup analyses
Age > 70 years
Chronic cardiovascular disease
Severely ill - SAPS II > 53
TRISS TRIAL
and…post-hoc subgroup analyses
Inclusion < 6 h of ICU admission
TRISS TRIAL
and…post-hoc subgroup analyses
Inclusion < 6 h of ICU admission
Lactate > 4 mM at randomisation
TRISS TRIAL
Lars B Holst et al. BMJ 2015;350:bmj.h1354
©2015 by British Medical Journal Publishing Group
RE-update
8000 patients randomised in lower risk of bias trials of Tx-triggers
RR 0.97 (0.79-1.19)
for mortality
Unpublished
3000 critically ill patients randomised in lower risk of bias trials of Tx-triggers
RR 0.92 (0.80-1.06)
for mortality
Holst et al. BMJ 2015
• No effect on mortality• Fewer patients Tx’ed and fewer Tx’s
7 g/dl as the new normal
• Myocardial infarction• Bleeding• Severe brain damage
Blind spots
200,000 MI patients can’t be wrong?
Or 20,000 trauma patients?
Perel et al. PLoS Med 2014
Or 20,000 trauma patients?
Perel et al. PLoS Med 2014
• Tx in MI - association with increased
mortality• Tx in trauma – association with
increased mortality in low risk patients• Severe brain damage – very little data
Blind Tx-spots
‘7 g/dl - the new normal’
?MI, bleeding, brain damage?
University ofCopenhagen