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1:1 Blood Resuscitation, Round 3.1

McSwain, Norman E Jr. nmcswai at tulane.edu
Thu Feb 21 03:19:03 GMT 2008

You will remember that Carl Jelenco discovered the same physiologic outcome with burn resuscitation in the early 1980"s.
He found less ET time (or none at all) and patients were eating the entire time even with >50% burns. No puffy patients. Did not reduce infection so it never caught on.
Typed by the thumbs of
Norman on his BlackBerry 

Norman McSwain, MD
Tulane Univ Surgery
504 988-5111

----- Original Message -----
From: trauma-list-bounces at trauma.org <trauma-list-bounces at trauma.org>
To: Trauma &amp; Critical Care mailing list <trauma-list at trauma.org>
Sent: Wed Feb 20 21:04:22 2008
Subject: RE: 1:1 Blood Resuscitation, Round 3.1

Karim's points are spot on. May actually be a combination of permissive hypotension, preventing hypothermia, and limiting crystalloid until bleeding is stopped that really works. The blood transfusion ratios may be a distant 2nd priority.
Whatever the reason, since implementing an aggressive combination of these steps with 1:1 or 1:2, we have not had significant ARDS following major hemorrhagic injury. APRV and other modes of advanced ventilatory support have become distant memories. 
Soooo, anecdotal "1:1 mania" easy to catch. No question that appropriate trials needed.
Mike Sise
San Diego


From: Karim Brohi [mailto:karim at trauma.org]
Sent: Wed 2/20/2008 4:30 PM
To: 'Trauma &amp; Critical Care mailing list'
Subject: RE: 1:1 Blood Resuscitation, Round 3.

That is exactly what I was driving at when I threw in the "BUT" - the fact
is that we know it is better then what we have been doing, and so to subject
someone to the other treatment arm would be unethical.  Simple, really.
Take care,

We should be getting better at this by now shouldn't we?  Recurrently
blindly accepting the next magic bullet that falls in our laps that will
stop all trauma patients dying ever - only for it to lapse when the real
evidence finally does emerge.  This year it's high-dose plasma.  Last year
it was whole blood (thankfully fading quietly with embarrassment).  The year
before, Factor VIIa.  Before that crystalloid resuscitation, pelvic ex-fix,
mast suits etc etc.  Why do we insist on extreme levels of evidence for some
interventions and essentially none for others?

Yes there is undoubtedly a signal from database reviews that patients who
receive 1:1 may do better.  But let me highlight a few points.

1. Most people are basic their stance on the military data published by
Borgman/Holcomb (J Trauma 2007).  They describe three groups, those who
received plasma:PRBC ratios of  (0:12-1:5), (1:3-1:2.3) and (1:1.7-1:1.2) -
interquartile ranges.  Note almost nobody received 1:1.  Most of the signal
in this paper, and in all the other studies, is in patients who everyone
would consider, was UNDER-TREATED, at ratios below 1:3.  So for a patient
who required a 12 unit transfusion, most people would think that anyone who
got only 0-3 units of plasma was sub-optimally managed. 

2. If you look at the available datasets and compare 1:3, 1:2 and 1:1 the
differences become much smaller.  In some cases they disappear or even
reverse (see Jeff Kashuk's paper from Denver at last year's AAST).  They
also disappear as less red cells are required.  So the vast majority of the
signal is in the UNDER-TREATED group.

3. No paper has shown that lower ratios actually lead to less blood products
being transfused overall.  If this is true then where is the plasma effect
coming from??  What exactly is it treating?  Further most studies look at 24
hour blood use.  Gonzalez (J Trauma 2007) has shown that many patients who
receive less plasma during the ED/OR phase end up getting more plasma in ICU
- often down to near 1:1 levels - based on the results of coagulation tests
rather than empiric therapy.  SO what does a 1:1 ratio at 24-hours mean?  Do
you have to give the plasma concurrently with each unit of red cells from
unit 1, or if you simply 'catch up' and appropriately correct clotting by 24
hours is that OK?  Is 6-hours important as some studies are looking at?  Or
is it the time to bleeding control?  Restoration of normovolaemia?

4. Geeraedts (Resuscitation 2007) has elegantly shown how patients who are
bleeding faster get less plasma - as the team and blood bank struggle to
keep up.  There is no measure of 'bleeding faster' in any of these studies -
nor even a useful surrogate.  So it is likely that patients who got lower
ratios were actually losing more blood a lot quicker and were more likely to
die.  The lower ratio of plasma achieved may actually be a marker of more
severe bleeding rather than a cause of excess mortality.  <<-- THIS IS

5. What we are talking about is moving from standard therapy of 1:3 to 1:1.
That is a three-fold increase in plasma dose. For 12 units of red cells not
4 units but 12 units of plasma.  That is a massive increase based on a
suggestion of effect from retrospective studies. (and for a product that has
*never* been subjected to a controlled trial in trauma).

6. Plasma is potentially the highest risk of all blood products.  If you've
moved to male-only donor plasma you've reduced the risk of TRALI but there
are still issues around sepsis, ARDS etc.  Also 3-times the dose = 3 times
the risk of errors.

7. The donor pool is shrinking and is projected to shrink even faster over
the next few years.  There is a significant implication for the donor pool
if 1:1 is widely adopted for massive transfusion.

8. I suggest you try to model a mass casualty event in your institution with
your blood bank, and see if they can provide you with 1:1.  Hospitals who
have been providing 1:1 for years (eg. Rigshospitalet in Copenhagen -
arguably the most advanced transfusion/coagulation management of trauma
patients in the world) have been through this exercise and admit that 1:1 is
simply not feasible in those situations.

My reading of the data is that there is clear evidence that UNDER-TREATMENT
(<1:4 ratio) is associated with poor outcomes.  I think the data is far far
from clear for ratios of 1:3, 1:2 and 1:1 and subject to significant
conounding factors, bias and difficulties with endpoints.  Remember again
that moving from 1:4 to 1:3 is a dose increase of 8%; 1:2 to 1:1 is a 100%
increase in plasma dose - these are exponential dose increases.  If a robust
randomised control trial of good size was conducted and concluded that there
was no additional benefit of giving 1:1 over 1:3 - would you still give 1:1?

Personally I think this is crying out for a prospective RCT - and quickly
before the hype makes equipoise and therefore recruitment difficult, much as
it has done for Factor VIIa.  Perhaps this will all go away when we get
useful functional near-patient coagulation tests.  Or perhaps we just have
to wait for the next magic bullet.

Needless to say, I do not think "we KNOW it works".


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