[HSF] Aprotonin

Wed Nov 21 22:21:05 EST 2007

Ani, 

I did overstate the "cost" associated with aprotinin which is more like $1000 or so.

Although some surgeons work diligently to avoid transfusion (as in the simplistic and misguided reinfusion of shed blood debate of the 1990's), I think there are several reasons to support my contention that surgeons fear the unknown more than the know, which is therefore more managable even if more common.

This analogy is certainly true for financial markets where risk is most greatly avoided even if desire for marginal improvement is ubiquitious. I doubt that surgeons think differently in type in their peculiar set of concerns.

As a thought experiment which drug would you use most often assuming only one could be used? Drug A that reduced blood loss by 500cc regardless of the total loss, or Drug B that limited total loss to say 1000cc (but some number more than the median in drug A)? 

In my personal experience the number of surgeons who reflexively give blood products at the first (and usely immediate) sight of "bleeding" is considerably higher than those that studiously avoid blood products until clearly necessary. Surely this use of blood product is not to "avoid" transfusion. 

The use of off pump surgery may corrrelate quite well, probably for a spectrum of reasons, with diligence in bloodless surgery. Off pump is incidentally well documented to have less transfusion at a level similar to aprotinin. The reasonably well known ratio of off to on pump surgeons is 1:4. This might well be a surrogate of similar behavior decisions by surgeons. Only a smaller portion work to do the "best" (least necessary transfusion or instrumentation) for everyone, while the most worry about rare but adverse risk.

Back to you. But you make me think harder and not just shoot from the hip.

tea

----- Original Message ----
From: Ani Anyanwu <anianyanwu at hotmail.com>
To: openheart-l at lists.hsforum.com
Sent: Sunday, November 18, 2007 8:55:15 AM
Subject: RE: [HSF] Aprotonin

"Surgeons however are not primarily interested paying $5000 for a drug that reduces the need for transfusion of a couple of units of blood worth $500. What they are really interested in is the "black swan" event of a patient dying from (near) exsanquination or near exhaustion of the surgeon from reexplorations in prevention of that death."

Tea I disagree with your statement above. It is not primarily cost or fear of exanguination that drives surgeons towards blood conservation. Surgeons are the least interested in cost and have minimal appreciation of health economics (as illustrated for example in your questioning the rationale for using a 2000 USD annuloplasty ring for prophylaxis when a suture could suffice). Also pharmacology does not prevent life threatening haemorrhage - if you look back at patients that have 'bled to death' would yu really think a vial of aprotinin, or any other agent, could have prevented that? Maybe a vial of prolene could but not aprotinin.

What drives blood conservation is primarily a belief that blood transfusion is a toxic drug so its use must be minimized to where the benefits outweigh the risks. It certainly must not be (as it often is in cardiac surgery) a convenience drug to compensate for a team's lack of interest or effort in minimizing blood loss during or after surgery. Remember that even in 2007 many patients die worldwide from direct complications (mainly ABO incompatability) of transfusion every year. In my career so far I have seen 4 patients transfused with the wrong patient's blood during cardiac surgery, the most recent few months ago in New York. These transfusion errors will continue to occur as long as we use blood, regardless of all the policies, protocols and education to prevent them. Then there is the issue of disease transmission. UK is still waiting to see if an epidemic of CJD will erupt in recipients of blood transfusion from the 1990s. Only last week we heard
 of four organ transplant recipients in USA who contracted *both* HIV and Hepatitis C from an organ transplant done earlier this year. And then of course there are all those other indirect consequences of transfusions.

While blood transfusion was one of the greatest medical discoveries of the 19th centuries and has saved millions of lives since, there are also a significant minority who have suffered death or major illness as a result of transfusion. As has been said before if blood transfusion had been discovered 150 years later we would still be struggling (likely without success) to get it through the FDA. Unlike agents like vioxx and aprotinin where while associations may be spurious or debatable, and direct causation of adverse events cannot be established, there are thousands and thousands dead, whose deaths were incontrovertibly caused by a blood transfusion.

It is a concern about the health of our patient, and not cost or fear of patient exanguinating, that should drive us to minimize blood transfusion. Havin said that Tea, I struggle to remember a single death in the last few years that I can directly attribute to post operative haemorrhage (i.e. patient bled to death) - surely this is rare in the present era?

Ani

> Date: Fri, 16 Nov 2007 21:48:12 -0800> From: tacuff at swbell.net> To: OpenHeart-L at lists.hsforum.com> CC: > Subject: [HSF] Aprotonin> > I just spent the last few days with Nassim Taleb's "Fooled by Randomness" there were several jewels and a lot to think about. I would like to put some form on the exuberant discussion that we have had on aprotonin. I won't say anything new, but as is my wont will try to provide some structure around the meaning of the discussion.> > Aprotonin reduces bleeding, but so do a lot of things like off pump approach to CAB, or careful technique, etc. Surgical coagulation is a complex process on top of a complex cascade confused by complex patients. However, because we lump everything together in a randomized study we are left with the simple finding that aprotonin causes less bleeding, nothing less and, particularly forgotten, nothing more. > > Surgeons however are not primarily interested paying $5000 for a drug that reduces the
 need for transfusion of a couple of units of blood worth $500. What they are really interested in is the "black swan" event of a patient dying from (near) exsanquination or near exhaustion of the surgeon from reexplorations in prevention of that death.> > Unfortunately we do not have any way to test for this rare and "random" occurrence. However, in testing for quantitative and manageable bleeding, we approximate a "chaotic" surrogate (like spilling ones tea by adding a large ice cube instead of a drop of water at a time) for the same and "find" other random "consequences" such as renal failure in the analysis.> > In toto, what has been shown is only that which we do not actually care much about. That is, $5000 dollars of drug can save $500 dollars of blood transfusion. Everything else is, or rationally should be, inferred from this small (relatively) objective point. Everything else statistically speaking is a "random walk" or alternative bet or
 outcome of our decision from whatever our thinking. Maybe some patients don't die of bleeding or maybe some do die of ATN or clotting. Who can tell?> > Why do we think what we do? Or why did you feel what you felt? That is the interesting question.> > "...mathematics is tool to meditate, not compute."> Nassim Taleb> > Meditate for a moment my friends. It is a behavior that will help your patients as much as, and perhaps more, than your computations.> > tea> _______________________________________________> OpenHeart-L mailing list> > Send postings to:> OpenHeart-L at lists.hsforum.com> > To UNSUBSCRIBE, to CHANGE email address, or to view archives:> http://mmp.cjp.com/mailman/listinfo/openheart-l> > All messages transmitted by the OpenHeart-L are subject to the policies and > disclaimers posted at:> http://www.hsforum.com/listdisclaim> -----------------------------------------
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