[HSF] Aprotonin

Mon Nov 19 11:43:05 EST 2007

Maybe so but there are ways round it. We said the same of aspirin 20 years ago - most surgeons I believe no longer discontinue aspiring before surgery. 
Reading through the cardiology literature, the increasing (consensus) advice is that the risks of withdrawing clopidogrel can be significant and include patient death so in general best to keep it going unless stents are not proximal or not drug-eluting.

I have also seen terrible bleeding in patients not on clopidogrel. No doubt patients sometimes do bleed as you say but nothing as bad as we have made it out to be.

Ani

> Date: Mon, 19 Nov 2007 14:35:28 +0530> From: prasannasimha at gmail.com> To: OpenHeart-L at lists.hsforum.com> Subject: Re: [HSF] Aprotonin> CC: > > I have seen terrible bleeding in patients on Clopdogrel. Not everyone bleeds> but when they do they flood.> Prasanna> > On Nov 19, 2007 9:59 AM, Donald Ross <donross at bigpond.com> wrote:> > > Ani,> > If they have a recent or eluting stent I don't stop it.> > I have not worried about it since I saw haw effective aprotonin is> > for the rare cases who clearly have a coagulopathy when the chest is> > opened.> > The trouble with clopidogrel, I believe, is it's unpredictability.> > Just occasionally it is a real problem and I lost a frail old dear> > from " clopidogrel bleeding".> > ( Probably just a convenient excuse but she really did bleed out!)> > Don> > On 19/11/2007, at 2:45 PM, Ani Anyanwu wrote:> >> > > Don> > >> > > Do you stop clopidogrel in non-emergency patients with coronary> > > stents?> > >> > > Must say we rarely stop clopidogrel before surgery now - indeed> > > tomorrow I have a scheduled reop sternotomy for an LVAD in patient> > > barely alive on IABP, inotropes etc with prior CABG, prior PCI and> > > ischemic heart disease and a stent in the left carotid artery. We> > > have not had the courage to stop the clopidogrel. Last week I did> > > another reop transplant in patient on clopidogrel and also did not> > > stop it before surgery.> > >> > > Ani> > >> > >> > >> > >> From: donross at bigpond.com> Subject: Re: [HSF] Aprotonin> Date:> > >> Mon, 19 Nov 2007 11:18:46 +1100> To: OpenHeart-> > >> L at lists.hsforum.com> CC: > > Ben,> What is the situation in Oz at> > >> present?> Our hospital, bless it's cockroaches, has withdrawn the> > >> drug from the > pharmacy more I suspect for financial than> > >> clinical reasons as > aprotonin has not been withdrawn by our> > >> FDA.> I rarely use it except for patients full of clopidogrel who> > >> have an > obvious coagulopathy. ( eyeball diagnosis ) but I will> > >> miss it and > now will require at least five clopidogrel free days> > >> prior to non > emergent CABG.> Don> > On 19/11/2007, at 9:43 AM,> > >> Ben Bidstrup wrote:> > > I suspect that is after the hospital> > >> management have bought the > > drug and then added its on-costs.> > >> This is what is charged out to > > the Insurer.> >> > I would be> > >> interested to see the actual cost the hospital pharmacy > > pays.> > >> In Australia it is around $500 depending on the deal he > >> > >> pharmacy has with the wholesaler.> >> > A bit of an historical> > >> overview.> >> > In the mid 80s a small group (Charles Wildevuur,> > >> Steve Westaby and > > Win van Overen) were looking at the> > >> possibility of reducing lung > > damage after OHS. Pump lung was> > >> still of concern. They surmised > > that complement activation was> > >> the cause (based on Kirklin's work). > > Westaby had worked with> > >> Kirklin. How did complement get activated? > > One pathway was via> > >> kallikrein. Enter aprotinin a broad based > > serine protease> > >> inhibitor that could inhibit kallikrein.> > High does regime> > >> developed and tested.> >> > Noted major reduction in bleeding.> > >> This was very topical at the > > time. Hep B was vey common and> > >> had resulted in deaths in a renal > > unit in the UK. HIV via> > >> transfusion> > was rearing its ugly head. Remember Arthur Ashe!>> > >> >> > USA and Germany amongst others paid for blood. UK had a> > >> 'free' > > system so less of an issue.> >> > But bleeding and> > >> transfusion after OHS was an issue. Bleeding in > > high risk> > >> cases was a bigger issue. So we pressed on.> >> > Now if we stop> > >> here and look at the impact of bleeding and > > transfusion on> > >> mortality, morbidity and cost esp in high risk > > cases, what> > >> might we find? I am talking not about 2007 but 1987. It > > was a> > >> major contributor to each of these domains.> >> > We have DDAVP> > >> studied, we have a few small studies with EACA, but > > Bayer bit> > >> the bullet and went down the pathway of looking at the > >> > >> regulatory requirements and did it. At what cost - significant.> > >> No, > > dose finding studies were not done. A regimen that worked> > >> was > > available. Reg bodies looked at that and were satisfied.>> > >> >> > It went through the hoops in the USA and was approved for use> > >> in > > CABG surgery. Not valves (that study did not achieve the> > >> needed > > reductions in transfusion).> > But we now know it gets> > >> used in almost all forms of cardiac > > surgery, esp high risk.>> > >> >> > As has been pointed out if we had a test or series of tests> > >> that > > could identify which patient was at high risk of bleeding> > >> over > > another, it would make life very easy for us all. It> > >> isn't there > > (yet).> >> > So in 2007 what are the risks of> > >> transfusion? Especially say 20 > > donor exposures. What are the> > >> risks of rVIIa?> >> > The BART study is an independent study> > >> comparing 3 regimens in > > patients considered at high risk of> > >> bleeding. In the USA as has > > also been noted in this forum, not> > >> all of those included patients > > would be given aprotinin (or> > >> any other agent for that matter). It > > is somewhat interesting> > >> to note that many centres will now use an > > antifibrinolytic as> > >> part of their blood conservation programme (or > > is it sleeping> > >> at night or patient safety). There is a general > >> > >> acknowledgement that something extra is needed. So is that a > >> > >> convenience drug or a bit like heparin (maybe not a good choice)> > >> or > > prophylactic antibiotics? Or is it now accepted that we> > >> should be > > doing something to stop exposure to what is a living> > >> transplant .> >> > I like many others want to see the science in> > >> the BART study > > analysis. I would predict and am prepared to> > >> say I am wrong if it > > should prove so, that there will be a> > >> risk analysis that will > > reduce the hazard ratio or risk ratio> > >> of aprotinin exposure to a > > low figure (say 1.5). Now this> > >> would indicate that there is a > > confounder that has not been> > >> accounted for even with the > > randomisation.> >> > If the ratio> > >> crosses 1, then it will not be significant (but also > > could be> > >> a type II error as the study stopped recruiting in that arm).> >>> > >> > But we must wait for the BART people to do their analyses.> >> >> > >> Is aprotinin dangerous?> >> > If it had caused all these problems> > >> that Mangano and others have > > described with such passion and> > >> venom, we would have seen it by > > now. A RCT would not be> > >> needed.> >> > Unfortunately the STS database does not collect> > >> information on the > > use of aprotinin or any other agent.> > But> > >> we know high risk cases have a higher risk of renal impairment, >> > >> > sepsis, stroke and death. We are looking for incremental > >> > >> improvements viz aortic cannulae with a trap, (show me the> > >> evidence > > for that!), pexelizumab (complement inhibitor - not> > >> so good), > > cariporide (where did that go?> >> > Many have got> > >> to the initial RCT stage but fallen at the first > > hurdle.> > >> Aprotinin has been to the finish line many times. But in > > Grand> > >> Nationals and 3 day events not 1000m straight dashes.> >> >> > >> Written with the passion of someone who was there at the beginning> > >> > > and who has been supported by Bayer in many ways and who has >> > >> > supported them by doing the work.> >> > I would also state that> > >> in my personal dealings with Bayer, they > > have not in any way> > >> suppressed adverse findings, nor sought to > > suggest ways of> > >> expressing outcomes that were not supported by the > > data.> >>> > >> >> >> >> $5000 for a dose of aprotinin??? No wonder Bayer do`nt>> > >> >> seem to care too much about the outcome, they`ve been> >>> > >> fleecing you all in the USA.> >>> >> In S Africa, the cost is> > >> about $400, the same price as> >> 3 units of blood!> >>> >> Dave> > >> Harris> >>> >>> >> --- Ani Anyanwu <anianyanwu at hotmail.com>> > >> wrote:> >>> >>> "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>> >>>> > >> -----------------------------------------> >>>> >>> > >> _________________________________________________________________>> > >> >>> The next generation of MSN Hotmail has arrived -> >>> Windows> > >> Live Hotmail> >>>> >> http:// > >>> > >> www.newhotmail.co.uk_______________________________________________>> > >> >>> 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>> > >> >>> -----------------------------------------> >>>> >>> >>> >> Dr.> > >> David G. Harris, FCS, MMED,> >> Cardiothoracic Surgeon Suite > >>> > >> 207 Kuils River Private > >> Hospital, PO Box 1200, Kuils River,> > >> 7579, Cape Town, South > >> Africa. Tel +27-21-9006411 Fax > >>> > >> +27-21-9006412 Mobile +27-83-3309587> >>> > >> _______________________________________________> >> 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> >>> > >> -----------------------------------------> >> >> > -- > > Ben> > >> Bidstrup FRACS FRCSEd FEBCTS> > Consultant Cardiothoracic Surgeon>> > >> > _______________________________________________> > 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> >> > >> -----------------------------------------> >> > >> _______________________________________________> 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>> > >> -----------------------------------------> > > _________________________________________________________________> > > The next generation of MSN Hotmail has arrived - Windows Live Hotmail> > > http://> > > www.newhotmail.co.uk_______________________________________________> > > 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> > > -----------------------------------------> >> > _______________________________________________> > 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> > -----------------------------------------> >> > > > -- > Prasanna Simha M> _______________________________________________> 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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