Request for clarification from Melody on disagreements with Mike Darwin (loose thread)

Request for clarification from Melody on disagreements with Mike Darwin (loose thread)

Joined: October 2nd, 2004, 8:27 pm

January 29th, 2009, 11:05 pm #1

Melody didn't get to a reply on this before the thread got locked, so I will repost it here. I think this deserves some answers, and hope that it was not just Darwin's turn to get Maximated
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You said: [You're not going to win any points with me, by making Mike Darwin's arguments. Not that I don't respect him in many ways, but he and I disagree on a LOT of issues related to cryonics, and I especially don't appreciate some of his opinions of medical professionals, in cryonics. Besides, I'm sure I could provide you with an equal number of arguments that our society IS engaging in significant medical research in areas that would be considered "risky," such as deep brain stimulation for Parkinson's Disease.]

This is a bit puzzling from what I've seen. What comments from Darwin on what issues and in what context, do you perceive that you disagree on "a LOT"?

Thanks,

FD

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Joined: April 30th, 2006, 1:38 am

January 30th, 2009, 4:09 pm #2

FD...I am strongly suspicious that you frequently, (and sometimes successfully!), attempt to provoke me. I probably should have written "I disagree strongly with Mike Darwin about a number of things, in cryonics." But, I could have, (and probably have in the past), written that he and I AGREE about a LOT of things, in cryonics. I don't know how to quantify what you are asking me to quantify.
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Joined: October 2nd, 2004, 8:27 pm

January 31st, 2009, 2:21 am #3

And now I guess it is my turn to get Maximated - I'm labelled a voyeur! Ya gotta love it.

But to the subject, I did not ask for anything to be quantified. Just tell us what comments/issues you disagree with Darwin on that constitute "a LOT" of them, as per your comment:

"...he and I disagree on a LOT of issues related to cryonics, and I especially don't appreciate some of his opinions of medical professionals, in cryonics.."

Is that so hard to do? You can go into detail as to why you disagree with them if you want, though I never really asked you to do that.

Is it unreasonable for me to ask? I don't think so, as I am having trouble determining very many areas at all where you disagree a lot with Darwin. Surely your readers should be able to understand exactly what you are talking about, no?

Am I provoking you in this? I fail to see how a simple request for clarifying something is a provocation.

Cheers,

FD
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Joined: April 30th, 2006, 1:38 am

January 31st, 2009, 3:55 pm #4

...can't you take a little teasing? I was just playfully provoking you, about provoking me. (I didn't realize it would work so well. ) I really just didn't have time to give a detailed answer to your inquiry, and I didn't feel like bringing up specific issues I might have with Mike Darwin, for several reasons. He didn't start the discussion, and there's no point in criticizing him, as he's not really currently involved with the cryonics organizations. Since he has so little current influence, what would the point be? There are a lot of other topics I would prefer to focus on, at the moment. (Like the activities at Alcor, I'm hearing about.) Besides, I think you know how to write to me, personally, if something I've written is keeping you awake at night.

FD: "Surely your readers should be able to understand exactly what you are talking about, no?"

"(My) readers"? I have my very own readers? If you knew me, you would understand how I would find such a comment somewhat comical. There are people who come here to read the forum, I'm just one of the people who write here. Since my comment seems to be so important to you, I'll either write some basic explanation on the forum, or send you an email, later. (And, "later," may mean a couple of days, so try to be patient.) Right now, I have a date to take my son to the skateboard shop, and then to the bridge to watch him do some "Ollies," whatever those are.

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Joined: October 2nd, 2004, 8:27 pm

January 31st, 2009, 5:00 pm #5

Oh now, I guess you could say I was playfully provoking you about playfully provoking me! If you thought that part was serious, you missed seeing my on it.

Readers? Sure you have readers. They reply to you, don't they? I even know of a few (and there are probably many more I don't know about) who don't even post to CF, but read your messages. You do indeed have a readership.

So I do appreciate your offer to write a "basic explanation on the forum" sometime soon, "couple of days" yeppers I can be patient with that!

Cheers,

FD
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Joined: April 30th, 2006, 1:38 am

February 2nd, 2009, 6:36 pm #6

Melody didn't get to a reply on this before the thread got locked, so I will repost it here. I think this deserves some answers, and hope that it was not just Darwin's turn to get Maximated
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You said: [You're not going to win any points with me, by making Mike Darwin's arguments. Not that I don't respect him in many ways, but he and I disagree on a LOT of issues related to cryonics, and I especially don't appreciate some of his opinions of medical professionals, in cryonics. Besides, I'm sure I could provide you with an equal number of arguments that our society IS engaging in significant medical research in areas that would be considered "risky," such as deep brain stimulation for Parkinson's Disease.]

This is a bit puzzling from what I've seen. What comments from Darwin on what issues and in what context, do you perceive that you disagree on "a LOT"?

Thanks,

FD
I've been reluctant to answer FD's inquiries on this topic, mainly because I have no desire to engage in yet another "flame war," with yet another "cryonics expert." (I'm not sure any such thing exists!) Regardless, I made a remark, which FD wishes me to clarify, so I shall attempt to, though I know I'll ruffle a few feathers.

I believe my first introduction to Mike Darwin was when Charles Platt asked me to read a review of the SA facility, Mike had written. Being new to SA, I was under the impression they were operating on a semi-restrictive budget, and I was also under the impression that Charles Platt was some sort of well-intentioned person who really wanted my professional advice, (impressions that would both be shattered, within a matter of months). Mike's report seemed so hostile, I found his review truly offensive, from the first page, on. (In Mike's defense, many who haven't witnessed some of the bad behavior that goes on within cryonics organizations and who have read my posts on this forum, might feel the same thing about me. At this point in time, I can truly understand Mike's hostility.)

Even if I could look past what I perceived as Mike's hostility, I disagreed with a lot of Mike's advice and opinions, especially in regard to perfusion and perfusion equipment. (FD is going to want me to elaborate, but I truly can't remember many of the details, I just remember disagreeing with a lot of what I read. The technical details of the specifics I can remember would take me too long to explain, on this forum.)

Recently, Mike Darwin made some remarks in an online scientific discussion group, regarding errors made by medical professionals, in cryonics. I found his remarks to be more than a little offensive, and I responded that, surely, any "errors" made by medical professionals in cryonics paled in comparison to the many blunders made by laymen who don't know what the hell they are doing. Mike got all huffy and raised Cain about not having been informed that I had been added to the discussion group, (which led me to wonder if he would have not made his remarks about medical professionals, had he known one was going to read them.)

I don't have my response handy, (and I'm not inclined to duplicate it, in detail), but I believe I questioned Mike's perfusion expertise and his familiarity with current equipment. As I recall, he responded that he reads all the perfusion journals, that he has a collection of perfusion equipment, and that he was once eligible to sit for the perfusion board exams. I had stated I wasn't going to get into a "back-and-forth" with Mike, so I abstained, (at least, until now), from responding that I didn't quite think those things stacked up to my experience of actually passing the board exams and pumping approximately 1,500 human cases, with a large variety of equipment. I've never seen any record of Mike graduating from an accredited perfusion school, or pumping 100 clinical cases, in order to be eligible to sit for the boards. If he did so, why didn't he take the board exams? It doesn't make sense, to me, that someone who considers himself to be a "cryonics expert" wouldn't take the perfusion board exams, if they were eligible. Perfusion is the technology used to deliver both the washout and vitrification solutions, after all.

In my response, I also mentioned that, when I first started making suggestions, regarding changes to Suspended Animation's perfusion circuit, I had to debate with Mike on issues related to the perfusion circuit. Mike responded that he couldn't recall ever communicating with me. Actually he was correct...the communications were indirect. As I recall, I would suggest a change to Charles, he would relay it to Aschwin and/or Mathew, they would discuss it with Mike, and then I would be forwarded his response, (usually arguments against my suggested changes). At some point, I asked Charles if he had really brought me there to revise the perfusion circuit, or simply to engage in endless debate with people who might not understand perfusion as well as they thought they did. I said if he had hired me to approve of the existing circuit, he had wasted a lot of time and money. As I understood it, the circuit I was supposed to be modifying was nearly an exact replica of the circuit at Alcor that had been used by amateurs to pump gross amounts of air to quite a large percentage of patients, (by gross, I mean large boluses of air that can be seen with the naked eye).

Some of Mike's suggestions might have made sense...IF we were dealing with REAL perfusionists, rather than metal fabricators and golf pros. However, to expect a layman to sit down with an industrial-grade occlusive pump and a small-volume, closed (bag) reservoir, and perfuse a human body without causing serious, and probably irreversible, damage is BEYOND naive, in my opinion, and to use advanced topics, (like air-fluid interfaces leading to micro-air embolization), to argue for such choices is misguided. The issue of micro-air embolization has yet to be resolved by the world's leading experts, in conventional medicine, so why is it even discussed in an arena where they've yet to eliminate the routine macro-air embolization of patients, and very few people are even capable of carrying on an informed discussion?

I often feel most of Mike's discussions are way over the heads of the people who are attempting to perform cryonics procedures, and therefore, serve little purpose. Based on his comments regarding medical professionals, I get this rather creepy feeling he thinks he could teach everyone in cryonics how to perform the necessary medical procedures, if they would just listen to him and follow his direction. (He may not feel that way, at all, that's just an impression I get from him. It may be that he's just frustrated, like me.) I, on the other hand, think the organizations should just oust everyone who doesn't have a clue what they are doing, and hire some professionals. There's this difference between "academics" and "clinicians," I've seen it, many times, at perfusion conferences. Though I know Mike has some clinical experience, he comes across as more of an "academic," to me, and that may be the fundamental difference between the two of us. Now, I know I've probably upset at least one close friend of mine, in cryonics, who considers Mike to be something of a demi-god, so I'll let it go, at that.
Last edited by melmax on February 2nd, 2009, 6:40 pm, edited 1 time in total.
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Joined: March 11th, 2007, 9:57 am

February 2nd, 2009, 6:49 pm #7

Oh now, I guess you could say I was playfully provoking you about playfully provoking me! If you thought that part was serious, you missed seeing my on it.

Readers? Sure you have readers. They reply to you, don't they? I even know of a few (and there are probably many more I don't know about) who don't even post to CF, but read your messages. You do indeed have a readership.

So I do appreciate your offer to write a "basic explanation on the forum" sometime soon, "couple of days" yeppers I can be patient with that!

Cheers,

FD
Finance Director writes: "But to the subject, I did not ask for anything to be quantified. Just tell us what comments/issues you disagree with Darwin on that constitute "a LOT" of them, as per your comment:

"...he and I disagree on a LOT of issues related to cryonics, and I especially don't appreciate some of his opinions of medical professionals, in cryonics.."

Is that so hard to do? You can go into detail as to why you disagree with them if you want, though I never really asked you to do that."

I, too, would be interested in seeing 'chapter and verse' on this, in particular, regarding the basis for these remarks:

"I especially don't appreciate some of his opinions of medical professionals, in cryonics."

As to my involvement in (and influence) upon contemporary cryonics, which Ms. Maxim comments upon, her remarks and conclusions are perhaps best answered by quoting Bastiat in a different (but relevant) context (indeed, relevant to events outside cryonics unfolding in the geopolitical economic realm, even as I write these words):

"There is only one difference between a bad economist and a good one: the bad economist confines himself to the visible effect; the good economist takes into account both the effect that can be seen and those effects that must be foreseen.

Yet this difference is tremendous; for it almost always happens that when the immediate consequence is favorable, the later consequences are disastrous, and vice versa. Whence it follows that the bad economist pursues a small present good that will be followed by a great evil to come, while the good economist pursues a great good to come, at the risk of a small present evil.

The same thing, of course, is true of health and morals. Often, the sweeter the first fruit of a habit, the more bitter are its later fruits: for example, debauchery, sloth, prodigality. When a man is impressed by the effect that is seen and has not yet learned to discern the effects that are not seen, he indulges in deplorable habits, not only through natural inclination, but deliberately.

This explains man's necessarily painful evolution. Ignorance surrounds him at his cradle; therefore, he regulates his acts according to their first consequences, the only ones that, in his infancy, he can see. It is only after a long time that he learns to take account of the others. Two very different masters teach him this lesson: experience and foresight. Experience teaches efficaciously but brutally. It instructs us in all the effects of an act by making us feel them, and we cannot fail to learn eventually, from having been burned ourselves, that fire burns. I should prefer, in so far as possible, to replace this rude teacher with one more gentle: foresight. For that reason I shall investigate the consequences of several economic phenomena, contrasting those that are seen with those that are not seen." -- Frédéric Bastiat

Mike Darwin
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Joined: April 30th, 2006, 1:38 am

February 3rd, 2009, 3:47 pm #8

...I'm glad we got that settled, without a ruckus!

I was going to leave it at that, but I'm compelled to add a little more...

Mike Darwin quoting Bastiat: "There is only one difference between a bad economist and a good one: the bad economist confines himself to the visible effect; the good economist takes into account both the effect that can be seen and those effects that must be foreseen."

Yeah...

If only the people funding cryonics had foreseen that relying on arrogant self-taught amateurs would result in their perfusion equipment and medical procedures remaining decades behind the quality of care provided in conventional medicine...

If only the people funding cryonics had foreseen that spending millions for laymen to perform medical procedures would result in a large percentage of cryonics patients being subjected to inappropriate pressurization and air-embolization of their vascular systems, (not to mention their BRAINS)...

If only most of the self-proclaimed "experts" in cryonics had foreseen that their bumbling attempts to perform medical procedures they aren't qualified to perform, would lead to the general population perceiving their activities as idiotic and "cultish"...

If only Charles Platt had foreseen that activities like paying himself $50 an hour, (for many hours over the course of at least a year), to design a rinky-dink imitation of an existing $385 medical device was a foolish waste of time and money, and would make him look like a crook...

If only Charles Platt had foreseen how foolish it was to send three people with no medical or cryonics experience, whatsoever, to perform medical procedures on a cryonics patient...

If only Charles and Aschwin had foreseen that their CI-81 case report would be interpreted as a glaring description of gross incompetence and critical errors, by medical professionals...

If only Dr. Steven B. Harris had foreseen that the gossip he posted on this forum, regarding a fellow medical professional he didn't know, nor work with, could be proven to be lies...

If only CI-81's family had foreseen that three people with no medical experience, whatsoever, were going to be sent to perform advanced medical procedures on their loved one, they might not have elected for SA's services.

If only Catherine Baldwin had foreseen that some cryonicists are smart enough to realize sending the grossly overpaid and underqualified staff members of SA to EMT-Basic school was largely an empty gesture and a really poor management decision...

If only Alcor had foreseen the ramifications of cryopreserving a patient who was neither officially signed up, nor funded, with their organization...

If only Alcor had foreseen that Ted Williams' heirs would disagree on what his last wishes were...

If only the person who allegedly injected a drug that expedited the "legal death" of an Alcor patient had foreseen that a discussion regarding that incident might someday be taped and made public...

If only the person who allegedly injected a drug that expedited the "legal death" of the same Alcor patient had foreseen that he might someday be accused of murder...

I could go on with this, all day, but let's face it...none of these things require a crystal ball, just plain common sense would suffice, for most.
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Joined: July 1st, 2007, 8:16 am

February 3rd, 2009, 5:15 pm #9

Melody: “If only the person who allegedly injected a drug that expedited the "legal death" of the same Alcor patient had foreseen that he might someday be accused of murder...
I could go on with this, all day, but let's face it...none of these things require a crystal ball, just plain common sense would suffice, for most.”

Despite the spending of countless millions of Dollars by the cryo organizations during the past 30 years, there is very little progress, if any, in the way they operate. Crystal ball will not help. Plain common sense is no match for the incompetence and special interest activities that prevail in this unregulated industry. What is needed is accountability and strict oversight by the cemetery boards, or much more preferably, central oversight by the FDA, which has the necessary experiences and expertise for it. Unless that happens, the next 30 years will be a mirror image of the previous 30 years. Which is to say, one disaster will follow another. Larry Johnson is a much reviled person, but I doubt that his claims are only his fantasies. I hope that he succeeds in one thing, namely that the cryonics industry finally gets some watchdog. It is badly needed. So far the whole world, with very few exceptions, is laughing at the industry. The sad part is that for the most part justifiably.

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Mike Darwin
Mike Darwin

February 4th, 2009, 1:02 am #10

I've been reluctant to answer FD's inquiries on this topic, mainly because I have no desire to engage in yet another "flame war," with yet another "cryonics expert." (I'm not sure any such thing exists!) Regardless, I made a remark, which FD wishes me to clarify, so I shall attempt to, though I know I'll ruffle a few feathers.

I believe my first introduction to Mike Darwin was when Charles Platt asked me to read a review of the SA facility, Mike had written. Being new to SA, I was under the impression they were operating on a semi-restrictive budget, and I was also under the impression that Charles Platt was some sort of well-intentioned person who really wanted my professional advice, (impressions that would both be shattered, within a matter of months). Mike's report seemed so hostile, I found his review truly offensive, from the first page, on. (In Mike's defense, many who haven't witnessed some of the bad behavior that goes on within cryonics organizations and who have read my posts on this forum, might feel the same thing about me. At this point in time, I can truly understand Mike's hostility.)

Even if I could look past what I perceived as Mike's hostility, I disagreed with a lot of Mike's advice and opinions, especially in regard to perfusion and perfusion equipment. (FD is going to want me to elaborate, but I truly can't remember many of the details, I just remember disagreeing with a lot of what I read. The technical details of the specifics I can remember would take me too long to explain, on this forum.)

Recently, Mike Darwin made some remarks in an online scientific discussion group, regarding errors made by medical professionals, in cryonics. I found his remarks to be more than a little offensive, and I responded that, surely, any "errors" made by medical professionals in cryonics paled in comparison to the many blunders made by laymen who don't know what the hell they are doing. Mike got all huffy and raised Cain about not having been informed that I had been added to the discussion group, (which led me to wonder if he would have not made his remarks about medical professionals, had he known one was going to read them.)

I don't have my response handy, (and I'm not inclined to duplicate it, in detail), but I believe I questioned Mike's perfusion expertise and his familiarity with current equipment. As I recall, he responded that he reads all the perfusion journals, that he has a collection of perfusion equipment, and that he was once eligible to sit for the perfusion board exams. I had stated I wasn't going to get into a "back-and-forth" with Mike, so I abstained, (at least, until now), from responding that I didn't quite think those things stacked up to my experience of actually passing the board exams and pumping approximately 1,500 human cases, with a large variety of equipment. I've never seen any record of Mike graduating from an accredited perfusion school, or pumping 100 clinical cases, in order to be eligible to sit for the boards. If he did so, why didn't he take the board exams? It doesn't make sense, to me, that someone who considers himself to be a "cryonics expert" wouldn't take the perfusion board exams, if they were eligible. Perfusion is the technology used to deliver both the washout and vitrification solutions, after all.

In my response, I also mentioned that, when I first started making suggestions, regarding changes to Suspended Animation's perfusion circuit, I had to debate with Mike on issues related to the perfusion circuit. Mike responded that he couldn't recall ever communicating with me. Actually he was correct...the communications were indirect. As I recall, I would suggest a change to Charles, he would relay it to Aschwin and/or Mathew, they would discuss it with Mike, and then I would be forwarded his response, (usually arguments against my suggested changes). At some point, I asked Charles if he had really brought me there to revise the perfusion circuit, or simply to engage in endless debate with people who might not understand perfusion as well as they thought they did. I said if he had hired me to approve of the existing circuit, he had wasted a lot of time and money. As I understood it, the circuit I was supposed to be modifying was nearly an exact replica of the circuit at Alcor that had been used by amateurs to pump gross amounts of air to quite a large percentage of patients, (by gross, I mean large boluses of air that can be seen with the naked eye).

Some of Mike's suggestions might have made sense...IF we were dealing with REAL perfusionists, rather than metal fabricators and golf pros. However, to expect a layman to sit down with an industrial-grade occlusive pump and a small-volume, closed (bag) reservoir, and perfuse a human body without causing serious, and probably irreversible, damage is BEYOND naive, in my opinion, and to use advanced topics, (like air-fluid interfaces leading to micro-air embolization), to argue for such choices is misguided. The issue of micro-air embolization has yet to be resolved by the world's leading experts, in conventional medicine, so why is it even discussed in an arena where they've yet to eliminate the routine macro-air embolization of patients, and very few people are even capable of carrying on an informed discussion?

I often feel most of Mike's discussions are way over the heads of the people who are attempting to perform cryonics procedures, and therefore, serve little purpose. Based on his comments regarding medical professionals, I get this rather creepy feeling he thinks he could teach everyone in cryonics how to perform the necessary medical procedures, if they would just listen to him and follow his direction. (He may not feel that way, at all, that's just an impression I get from him. It may be that he's just frustrated, like me.) I, on the other hand, think the organizations should just oust everyone who doesn't have a clue what they are doing, and hire some professionals. There's this difference between "academics" and "clinicians," I've seen it, many times, at perfusion conferences. Though I know Mike has some clinical experience, he comes across as more of an "academic," to me, and that may be the fundamental difference between the two of us. Now, I know I've probably upset at least one close friend of mine, in cryonics, who considers Mike to be something of a demi-god, so I'll let it go, at that.
To the best of my knowledge, reproduced below is all of the communication(s)I have had with Melody Maxim, including those on the CI list-serve. Some of these communications were indirect, and not responded to by her. Where she has responded I have included her responses.

The first item is a communication from me to Suspended Animation, Inc. (SA), and my comments are delineated by *** before and at the end *** of my comments (beginning after the 'homily' that opens the piece). I suppose my most important question regarding this piece is, 'how could Ms. Maxim have read the extensive criticisms of the then (and current) technical and administrative state of cryonics and subsequently be so shocked and surprised at the ghastly situation she found there?' The section entitled 'Some Painful and Arduous Background'makes the situation with regard to flawed technical competence and the excreable level of care cryonics patients were (and are) receiving abundantly clear. *Many of the specifics cited in that section are ones Ms. Maxim was to complain about here on CF Forum 3 years after she began working for SA and (presumably)read my remarks.*

It is also interesting to note that one of her major points on the CI Forum is about failure of anyone in cryonics to understand the concept back pressure in the (arterial) line between flow restricting cannula(ae) and a pressure gauge (because of the flow restriction and flow resistance imposed by the cannula, pressure must be measured pressure distal to the cannula, or elsewhere in the patient's arterial system in order to obtain an accurate reading). That very point was made by me at length in my comments to Suspended Animation (SA) many years ago.
I've included all of my communications with Ms. Maxim (direct or indirect) below including materials sent to SA years ago. As far as I can tell, about the only disagreement I have with Ms. Maxim is that it is desirable, or even possible, to simply insert medical professionals into cryonics and expect they will fix everything. That has never happened. It took Jerry Leaf years to become competent at cryonics as medicine; ditto the few other physicians, perfusionists, RNs and LPNs who have functioned responsibly and competently in cryonics in the past. Some learn faster than others, and some don't learn at all, but, the point is (and it is valid), that no one can enter any complex discipline, in or out of medicine, without a learning curve. Cryonics is no exception.

I can't imagine this is controversial, or even open to much debate. Indeed, Ms. Maxim herself did not instantly discover the problems with cryonics (this took many months, even given the extensive criticism and cautions from me and at least one other person) and she was herself unsuccessful in changing things in no small measure because she did not learn the requisite technical, as well the social/political/ethical facts about cryonics (which arguably could have empowered her to make real changes. This an oft repeated pattern: a complete failure of dissatisfied individuals banding together and working collegially and in a coordinated way to fix the system.

The material below contains a great deal of technical jargon and deals with a number of technical issues related to in-field perfusion and blood washout of human cryopatients. Having said that, I would go on to say that any reader who takes the time to slog through this material should be able to understand the issues under discussion. Where there is no no understanding or where lay-level explanations are desired, please feel free to ask and I will do my best to explain the issues and further explain my reasoning in taking the positions that I did. I believe that reasoning behind technical decisions such as roller pumps versus centrifugal pumps, open reservoirs versus closed reservoirs can answer some of the most troubling questions raised on the forum. Feel free to ask.

Mike Darwin
--------------------------

This is the report from me that Ms. Maxim characterizes as follows:

Mike's report seemed so hostile, I found his review truly offensive, from the first page, on. (In Mike's defense, many who haven't witnessed some of the bad behavior that goes on within cryonics organizations and who have read my posts on this forum, might feel the same thing about me. At this point in time, I can truly understand Mike's hostility.)

Even if I could look past what I perceived as Mike's hostility, I disagreed with a lot of Mike's advice and opinions, especially in regard to perfusion and perfusion equipment. (FD is going to want me to elaborate, but I truly can't remember many of the details, I just remember disagreeing with a lot of what I read. The technical details of the specifics I can remember would take me too long to explain, on this forum.)

Judge for yourselves:

[Note: My agreement with SA was that none of the consulting done was confidential, and at that time SA had a policy of complete transparency with regard to technical and scientific issues.]

_Input From Mike Darwin 08 June, 2006_

My comments below will be in red where embedded in the text below.

Some Painful and Arduous Background

Before I get into the text I want to provide some commentary and background on the major paradigm shift suggested and shown in the photographs below. That is principally the use of a hard-shell venous reservoir as opposed to a compliant bag. I like hardshell reservoirs and started out pumping them; the very first was the late 1970s era Bentleys, and of course Kay-Cross disc oxygenators before that.

When we first started doing in-field CPB and blood washout in cryonics we used the dominant technology of the time which was bubble oxygenators. Below is a photo of a typical 1980s in-mortuary cryopatient washout using a Shiley S-100A bubble oxygenator. The gentleman in the picture is professional perfusionist and cryonics pioneer Jerry Leaf (now deceased).



The picture of an in-field femoral cutdown (below) is included simply because it shows me (almost 20 years ago) using the same technology (Im the guy to the right, opposite Jerry):



I include these images because I want to provide historical context and to hopefully demonstrate that I am conversant with hard-shell reservoirs and am comfortable using them.

Both Melody and Boon are correct in the advantages they cite for hard-shells and what I am about to say will probably seem incredible to both of them.

The Alcor Foundation is the largest and most medically oriented of the existing cryonics organizations. Indeed, both of the case photos you see above are of Alcor patients. In September of 1991 Jerry Leaf entered cryopreservation and a year later I was dismissed from Alcor. A young woman with no prior medical, biology, or basic science background, was given control of the cryopreservation team and transport operations at Alcor. A veterinary surgeon with no prior experience in CPB was brought in to do the thoracic surgery.

Almost all basic elements of safe (or rational) technique were either severely degraded or disappeared at this time. Rational selection of cannula size and even the use of venous cannula during femoral-femoral washout vanished. Mortuary embalming pumps were used when convenient (often because something was missing from the washout field kit which disabled it). Proper securing of cannula via the use of properly anchored tubing holders and securing the red Robinson snares to the tubing with umbilical tape stopped. An immediate consequence of this was that arterial cannula began to pop-out of the aortic root in about one in three cases. Since no one knew to clamp the venous line when this happened, and the patients had little intravascular pressure (MAP ~ 35 mm Hg), there was massive air entrainment in the aortic root where it could not be seen with the consequence being massive air embolization of these patients.

In one case (a dear friend of mine), the arterial line was mistakenly placed in the femoral vein and a very small bore venous cannula was placed in the femoral artery and bypass was initiated at near physiologic flow rates. The result was massive splanchnic edema and epistaxis due to rupture of vessels in the sinuses: one can only imagine what the effect on the brain capillary bed was.

Standard practice at Alcor has been to use a very small in-house fabricated hard-shell reservoir for cryoprotective agent (CPA) perfusion which is run with only 100cc to 200cc of volume in it. Air is routinely entrained into the arterial leg of the circuit and it is dogma that the air separation membrane on the 40 micron Pall filter will remove this air. This reservoir is also stirred continuously, using a magnetic stir bar to create vortex stirring, with accompanying creation of massive quantities of microbubbles. The CPA perfusate is at least twice as viscous as blood and has multiple polymers that create very stable foams and delay the gravity-mediated removal of microbubbles for many minutes far beyond the design constraints of arterial filters used for blood in CPB circuits. I have written extensively on this; http://www.cryocare.org/index.cgi?subdi ... =tech5.txt

However, despite identifying this problem and creating a solution, no changes have been made in the subsequent 12 years.

The young woman I mentioned previously returned to Alcor several years ago and continues to be the dominant technical presence.

The quote below is from a brief case summary of a patient perfused in Alcors facilities in August of 2005 (http://www.alcor.org/Library/html/alcornews043.html):



"Once at the lab, the open heart surgery for this whole-body
patient was begun, followed by the introduction of the
newest cryoprotection protocol. At around 30-40 percent of
our target concentration, the system filled with foam,
which was subsequently pumped into the patient. Perfusion
was stopped, and the foam was methodically removed from the
cannula and the aorta, to the best of our ability to do so.
This incident highlighted many problems, not the least of
which was that the perfusionist had stepped away from his
station without providing for a replacement. Other problems
contributing to the foam were the ice blockers themselves
(X-1000 makes a rather stable foam); the cardiotomy suction
system was introducing bubbles into the mixing reservoir;
and the mixing reservoir was being run low. It took us a
full hour to de-foam as much as we did.

Cryoprotection was terminated after refractive readings in
both arterial and venous samples remained above the target
for a half hour. The patient experienced severe edema, and
we have several theories about what contributed; changes
will be made to the whole-body protocol as a result.

The patient, Alcors 64th, was pronounced in the early
morning of May 13, the expected medications were
administered, and she was then removed to a funeral home.
Because of extensive sclerosis in the femoral vessels, the
patient was washed out using the right carotid, but this
fact was not communicated to the operating room team and
precipitated an early cryoprotective ramp. Because the neck
was obscured by ice bags and drapes, we failed to locate the
additional source of leakage in an already difficult
surgery. Despite the problems during surgery, the
cryoprotection went fairly well."

I think it likely that the above quote will stun both Boon and Melody. I am long past that point. If you are an Alcor patient receiving extracorporeal support you have (based on this womans past performance) a ~ 1 in 5 chance of being perfused with massive amounts of air at some point during your care (either in the field or in the facility). This does not include microbubble embolization, which happens during every case, and which they neither check for, nor apparently are sensitive to as a problem

Not stated in the quote above, or the case summary it came from, was that this patient was massively edematous and was unrecognizable at the end of CPA perfusion (described by one person present as looking like the Michelin tire man).

Paradoxically, some of Alcors in-field coordinators are far better at CPB than are Alcor central staff. They are much more afraid and concerned about their limitations, and thus more cautious and vigilant.

Having said that, none of these people have ever pumped a survival case on either an animal or a human, and the enormous mass of acquired knowledge and experience which both of you (Melody and Boon) have, is completely absent. Both of you are aware of basic things such as the effect of tubing diameter on flow and pressure. You know the safe levels required for the reservoir you use and you are intimately aware of your response time versus flow and reservoir volume. I could easily write a textbook about all the things you know, and know viscerally, leaving aside things like pharmacology, acid-base balance, and basic physiology all which act to make you safe and competent perfusionists.

I am writing this to give you a perspective that this will not be the case with SA, Alcor, or other cryonics organization perfusionists who will operate the ATP in the field. No matter how thoroughly these sincere people master didactic training, they will not have any real clinical experience, and will not have the instincts and embedded hand knowledge that even a marginally competent perfusionist will have. This reality trumps all other considerations in circuit design. These people will necessarily be like a person who has been taught the basics of operating an automobile on a closed course. They can drive it forward and avoid hitting the walls at low speeds. However, they have no crash avoidance skills, will freeze up at intersections, will often reach for and activate the wrong control, have no instinctive feel for the vehicle or its control console, and will be unable to backup, let alone parallel park. No one with even vestiges of sanity would put such a person into a high performance racecar and turn them loose in a NASCAR race, let alone Indycar racing!

The obvious solution to this would be to hire a professional perfusionist. This is simply not economically possible nor is it really practical given the low volume of cases (less than 20 a year) even at Alcor, or even in cryonics worldwide (less than 40 a year). And remember, of these cases, many will not be perfusable due to delay, autopsy, sudden death, financial constraints, or geographical remoteness.

The next best thing is to train appropriately skilled and motivated people in an animal research environment where they can pump survival animals (typically dogs) and gain the enormous array of both intellectual and manual skills required to be a safe, competent, and flexible perfusionist. Alas, this kind of training stopped some years ago and has been repeatedly rejected as an option for SA personnel. Only such extensive in-house training on relevant models will do the job. This is not going to happen. Please integrate this fact into your thinking.

_Hardshell vs. Bags_

First, a caveat: I may be seen as biased since the current Alcor ATP was reconfigured by me prior to its clinical implementation. The basic platform was designed by Alcor and I want to make clear that most of the credit for this system, including the critical idea of modularizing it in a Pelican case, is the work of Steve van Sickle and Hugh Hixon at Alcor.

Given logistic constraints, and lack of training of personnel, recirculating in-field CPB will be a relatively rare thing and, frankly, something I would rather not see done solely due to skills issues. A patient who has been safely washed out and cooled is vastly better off than a patient who has been embolized with macro air in an attempt to cool a few more degrees or provide metabolic support in ultraprofound hypothermia.

To this end, I configured the system to have almost no potential for administering macro air. This was done by drawing from a collapsible perfusate reservoir (Alcors idea) and using a collapsible venous reservoir which was to be kept largely purged of air. Since the ATP cannot be moved there is always a sharp time constraint on how long a patient can be maintained on CPB. This is so for at least the following reasons:

1) Most cryopatients have major compromise to systemic capillary integrity. In particular, most patients will have experienced massive pulmonary edema and alveolar flooding. Many patients will have active GI bleeds due to erosion of the gastric mucosa by hydrochloric acid during agonal hypoperfusion (shock). Gastric blood flow is negligible in many patients during the last few hours of agonal hypotension. The effect of this is that perfusate rapidly leaves the extracorporeal circuit either as pulmonary transudate or via hemorrhage of compromised gastric mucosa. Even if gastro-protection has been undertaken prior to cardiac arrest, there is usually massive pulmonary transudation of perfusate, including the colloid. You will see this in the intubated patient as a steady flow of blood-tinged perfusate existing the ET tube at a rate of up to 20 ml/min. This will limit the time on the pump unless a reserve of 10 to 20 liters of perfusate has been provided to make up for this loss. Contemporary cryonics personnel are oblivious to this as a problem and assume that, the patient is bleeding internally. If a reserve of perfusate is on hand and MAP is kept to ~35 mm Hg it is possible to perfuse such patients continuously for over 12 hours (Ive done it). It is also physiologically desirable given the limitations of the current perfusate (MHP-2).

2) Many mortuaries that cooperate with cryonics organizations specialize in embalming for air shipment, or are otherwise busy with their usual case load. They cannot afford to have the prep-room tied up for long periods of time and frequently balk at the time constraints imposed by even a simple blood washout. While not always the case, the mortuary frequently wants the cryonics personnel out of there, if for no other reason than to free up their personnel. A cryonics case requires more total personnel time than a regular embalming, including application of cosmetics and clothes. Further, their personnel are a limited resource and if they use them extensively on a cryonics case they may be unwilling to handle a case from the community on a timely basis and/or charge overtime.


3) It is usually imperative to catch the next available commercial flight and this means that the patient must be prepared for transport as soon as possible. Since the ATP cannot be moved the patient must be disconnected from extracorporeal support. Typical air transport of a cryopatient is shown below:



The solution to this problem for local (within 4 hours drive time) cases was to develop a mobile CPS platform that included ECMO capability:








Note (below) the CDI on the right and the Tektronix monitor under the lamp (on the left) for invasive monitoring of MAP and CVP:



This system allowed for continuous perfusion and metabolic support of patients. However, it requires several skilled personnel to use this kind of equipment and, at its core, a skilled perfususionist (professional or otherwise) who is familiar with the peculiarities of asanguineous perfusion in the patient with MSOF and fulminating pulmonary edema. For the time being this system is not being used by SA and is only used by Alcor for acute blood washout.

Which brings us back to the SA ATP as it was configured by Alcor: the ATP is very hard to pump macro air with. If you empty the bulk perfusate reservoir bag and then accidentally empty the patient (venous) reservoir bag, even if the venous reservoir has 500 cc of air, none of it will reach the patient before the pump begins to make that unmistakable thuwmp, thwump, thwump, sound that indicates that it is pulling a vacuum on the inlet side of the pump shoe. Flow drops off to nil and the bleed-line on the arterial filter provides additional protection. If this happens it means that all perfusate in the reservoir bag has been expended (the patient has been successfully washed out) or there is a kink in the feed line to the venous reservoir. There is thus no infinite reservoir of atmospheric air to draw upon.

I was careful to specify arterial tubing lengths and filter volume such that even if the venous reservoir had 500 cc of air in it, it would not reach the patient (this in addition to using an air separating filter). This is the reverse of what is done clinically (and especially in dog work) where every centimeter of tubing is a curse of hemodilution which may have to be overcome by transfusion on the pump (a major problem in the dog because we do not have in-house blood banks).

Thus, until skill level improves dramatically and consistently in personnel who operate the ATP, I am unalterably opposed to hard-shell or otherwise open venous reservoirs. The changes I wish to see made the most are the addition of an ultrasonic macro/micro air bubble detector to the arterial line between the oxygenator and the filter, and high pressure (arterial and venous) alarms which will shut the pump down and clamp the arterial line. The presence of a closed venous reservoir will also prevent venous return in a no-(arterial) flow situation from over-topping the hardshell reservoir something that happened at least once after I left Alcor and which air-locked the hardshell oxygenator (something which they had no idea what to do about).

My specific comments are below:


_Changes to Suspended Animations Perfusion Circuit,
As of May 29, 2006_

Melody Maxim:


1. Replaced bag with hardshell reservoir.

A hardshell reservoir offers many advantages over a soft bag reservoir, including less resistance to venous return, higher volume capacity and better air handling.

Can you provide more information on better air handling?
The venous reservoir serves as a high-capacitance (i.e., low-pressure) receiving chamber for venous return, facilitates gravity drainage, is a venous bubble trap, provides a convenient place to add drugs, fluids, or blood, and adds storage capacity for the perfusion system. As much as 1 to 3 L of blood may be translocated from patient to circuit when full CPB is initiated. The venous reservoir also provides several seconds of reaction time if venous return is suddenly decreased or stopped during perfusion.

Reservoirs may be rigid (hard) plastic canisters ("open" types) or soft, collapsible plastic bags ("closed" types). The rigid canisters facilitate volume measurements and management of venous air, often have larger capacity, are easier to prime, permit suction for vacuum-assisted venous drainage, and may be less expensive. Some hard-shell venous reservoirs incorporate macrofilters and microfilters and can serve as cardiotomy reservoirs and to receive vented blood.
Air handling of hardshell reservoirs is better than the softshell bags for the fact that the rigid plastic canisters are open types, or what we call an open system vs. the closed system of the collapsible plastic bags. When you have lots of air entering the softshell bag, you will need to manually purge the air out the top of the bag whereas air in the hardshell reservoir is vented out automatically without your interventions. Hence, in this sense, we say hardshell reservoirs can handle air better than the softshell bags.

It also provides for filtering of the venous return, a feature that should be highly desirable compared to the non-filtered bag reservoir, as the presence of clots in the venous return during a cryonics procedure is likely.

This isnt necessarily an argument against filtering venous return, but to the extent that a clot may have gotten past the arterial pump, the clot filter prevents it from getting into the patient. Im not aware of any cases where the clot filter clogged and had to be swapped out. Aside from any potential concern of the arterial filter getting clogged, are there any other reasons to take into consideration? Could you provide more information on the filtering of the venous return? The reason why I ask is because I learned at Mechanisms that the cardiotomy reservoir has become the scourge of perfusionists because it is a major source of micro bubbles, so Im curious to know if it is an internal filter or separate from it, and to what extent it might introduce micro bubbles. At a minimum, I recommend that the waist dump line be split off prior to reaching the filter to help ensure that the filter does not become clogged during washout, similar to the way you currently have it setup on the training pack.

***Mike Darwin: Clotting should not be a problem in any cryopatient who is a candidate for closed-circuit perfusion (recirculation. I have occasionally seen cast clots of the femoral artery or vein in patients who were cutdown within 45 minutes of arrest and who were also promptly heparinized, medicated, and given closed-chest CPS and cooling. These clots appear to be antemortem due to profound shock and accompanying peripheral hypostasis. Despite this ominous finding, Ive never seen macro clotting beyond this. In cases where such a clot is found it is simply extracted with clot forceps; in all cases these have been well formed, dark, retracted clots._

If visible clotting (as opposed to cold agglutination) is observed during blood washout, then the patient is not a candidate for recirculation barring the presence of a skilled perfusionist.

Mathew is right on target about air bubbles and debris from cardiotomy reservoirs and hard-shell venous reservoirs and there are additional considerations which are unique to cryonics cases:

1) The higher (beyond safety constraints) that you run the perfusate level in a reservoir the more microbubbles you will typically form. This is especially true in hardshell reservoirs because they have a large column of poorly stirred fluid with a debubbler column of open cell urethane foam covered with nylon tricot. The big column of poorly stirred fluid is the first problem because it is cold. Because it is both cold, and far below ambient temperature, it will out-gas, or fizz. Unlike solids, gas solubility in water is directly related to temperature: the colder the perfusate is, the more dissolved gas it will hold. Any uninsulated standing reservoir of cold fluid will warm up and will generate microbubbles. Soft drinks go flat very fast at ambient temperature for this reason.

2) An added problem is that the urethane and nylon tricot serve as fantastic nucleating sites for bubbles. Thus, they actually favor microbubble formation. You can see the same effect in soft drinks if you note that most of the bubbles form on the interior of the glass and on the ice cubes; the latter being far colder than the glass.

3) Compared to plasma the MW of the colloid used in current washout solutions is astronomical (250,000 to (preferably) 500,000 KD versus 40,000 KD for plasma proteins, principally albumin). In the near future I expect MHP-2 to be replaced with a solution containing polyglycerol, polyvinyl alcohol, and possibly polyethylene glycol (the latter in MWs as high as 100,000 KD). These molecules inhibit cellular edema in hypothermia and ischemia (cold and warm) but are also profoundly effective at both facilitating the creation of, and stabilizing foam.

The air-liquid interface of the large surface area, open cell urethane foam column, will facilitate the generation of bubbles as the liquid level rises and falls dynamically. In blood, antifoam-A is used to inhibit this effect, and indeed, the large surface area of the urethane foam is designed to serve as a matrix for the Antifoam-A and maximize the surface area of blood foam exposed to Antifoam A. However, perfusate is not blood and the kinetics of air bubble movement and the ability of Antifoam-A to uniformly reverse foaming are untested at best, and in doubt at worst. Even with blood under clinical conditions near normothermia, the presence of the de-foaming column is not completely effective and we all know that cardiotomy and hard shell reservoirs are a source of microbubbles during conventional bypass.

Beyond these unusual problems, there is currently an inviolable rule in CPB which has been in effect since I started using extraporeal equipment in the mid-1970s; more surface area equals more debris. Prebypass filters were invented to deal with the ever-present load of plastic debris that comes out of even the most carefully washed extracorporeal circuit. I have seen oxygenators/tubing/filters being cleaned at Gish prior to sterilization and even washing with hundresof liters of ultrapure water leaves a lot of debris. While not a major issue in cryonics (given the other horrors) I dont like the idea of adding yet more debris.

Finally, there is yet another problem unique to cryonics which really demands discussion on its own. Cryonics started out relying heavily on expired products. Those of us in the vanguard of this use were very concerned about this: actually, terrified would be a better adjective.

By the application of both reason and experience we identified which drugs and devices could be used beyond expiry, and for how long. Ultimate validation was in the animal lab and often we had help on this from other investigators who were using outdated supplies: this was once the way most research got done. This practice is now illegal, so a vast reservoir of data shared between labs and by manufacturers is now no longer available.

Most hollow fiber oxygenators and dilyzers are good indefinitely if they are stored under reasonable conditions. This is amazing. However, this is most emphatically not the case for bubblers or for cardiotomy reservoirs, and storage conditions are critical.

The urethane column in hardshell reservoirs is subject to oxidation and disintegration over time. Some of you may have observed this effect with old urethane bed pillows which have become crumbly and non-elastic. The urethane foam column inside a reservoir stored under uncontrolled conditions or past its expiry becomes a crumbly, embolizing mess. It begins to shed large numbers of particles in 1 to 10 micron range long before this deterioration is visible to the naked eye. High ambient temperature and humidity can greatly accelerate this process (as does UV light, which not a consideration here). It is important to remember that these reservoirs (ATPs) will be stored under uncontrolled conditions; no guaranteed, monitored, ISO 900X environments.

I have seen relatively stable in-field PVC items become sticky from plasticizer elution due to long storage times, and especially due to storage under uncontrolled conditions. Not surprisingly, Florida is where I have observed this the most (there used to be a permanent Alcor perfusion facility in FL which was established in the early 1980s and decommissioned in the late 1990s. I both implemented and decommissioned it). I am thus very wary of components that fail catastrophically with extended storage.

I agree that the waste dump line should come before the venous return line enters the cardiotomy reservoir. This not only guards against clots, but also reduces contamination with red cells and with agglutinated RBCs.

Disadvantages of hardshell reservoirs include the use of silicon antifoam compounds, which may produce microemboli, risk of microembolism, and increased activation of blood elements. Soft bag reservoirs eliminate the blood-gas interface and by collapsing reduce the risk of pumping massive air emboli. Because of the concerns on microemboli and increased activation of blood elements, some perfusionists have switched back to using softshell bags again.
See my commens above. I would also add that the current (Alcor) ATP components retain their utility and safety even when stored under extreme ambient conditions. I am reluctant to give this up. It has been hard-won experience. I actually made a complete tubing pack of tubing and connectors out of polymer that does not have plasticizers and should have had an indefinite shelf life. This was packed for shipment to SA. I have no idea whether it ever got there. It used polypropylene connectors and the tubing was resistant to the solvents in the vitrification solutions.

[As an aside, I am very concerned about plasticizer leaching from PVC tubing during CPA perfusion, especially with the addition of dimethylformamide. Both DMSO and DMF raidly degrade PVC components at room temperature. Contamination of perfusate with dissolved plastics and housing failure on oxygenators under pressure seems quite possible; for example, the Sarns oxygenator housings are a clamshell with a glue joint holding the two halves together.]
The reservoir currently available at SA is a cardiotomy reservoir, rather than a venous reservoir, which would be more desirable. The cardiotomy reservoir is designed for blood collection, such as that from general suction lines that are used in the field. Hence, the cardiotomy reservoir has a very effective filter designed to remove debris. One undesirable effect of this feature is reduced flow rate, due to the time it takes the perfusate to traverse across the filter. (SAs existing cardiotomy reservoir is rated at a maximum flow of 5LPM.) Another disadvantage of the cardiotomy reservoir is that it does not have a 1/2" port for the venous return line, therefore requiring a 1/2-3/8 reducer in the venous return line. Nor does it provide for a venous luer lock for the sampling manifold, thus requiring an additional luer lock connector to be placed in the venous line for this purpose.***

Melody Maxim: I agree that we dont want to use a cardiotomy reservoir because of the high flow rates, but the bottom connection is tapered and will hold both a 3/8 and ½ tubing. At Alcor we used to reduce the tubing down to a ¼, and ran the tubing coming from and going to the reservoir through a pumphead, but changed this to a gravity drain with larger tubing to reduce the amount of air being pumped into the mixing reservoir during cryoprotection in hopes of avoiding pumping micro bubbles into the patient.

Boon: For your portable circuit (have never seen the actual circuit, just some photos that Charles sent a while back) I dont know whether a hardshell cardiotomy-venous reservoir will fit in the carrying-case or not. Obviously the soft bag will have no issues.

Mathew Sulivan: Modifications will have to be made to accommodate SAs level detection system, as discussed.

Melody Maxim: I agree.

ANY decrease or restriction in diameter largely defeats the advantage of using a larger line. In other words, if you are using a ½ line (as you should) to facilitate venous return and you put a 3/8 connector in that line you have dramatically reduced your flow and increased your resistance (and thus your CVP under high flow conditions).


2. Moved oxygenator recirc line to top of reservoir.
Should air need to be evacuated from the oxygenator, (this should be unlikely, provided a watchful eye is kept on the reservoir), the air is handled without effort, unlike in the previous SA circuit where the removal of air from the oxygenator would have led to filling the bag reservoir with air that was somewhat difficult to expel.

Boon: I agree.

Melody Maxim: Thats the beauty of hardshell reservoirs, they handle air better than the soft bags.

Mike Darwin: ***I cant comment on this change without seeing the circuit. I will make comments via the pictures and Boons comments below.***

3. Deleted reservoir vent line to waste bag line.
No longer necessary. If volume is excessive, it can easily be diverted to the waste bags via the Y-connector in the venous return line. Parallel clamps have been placed on the branches of the venous line, past the Y-connector, so they are easy to see and manipulate, while continuing to monitor the reservoir.

Boon: I agree the vent line is no longer necessary, but I may need some clarification on the volume you speak of are we still talking about air? Until I see the proposed reservoir, Im not sure to what extent this might be an issue. With the cardiotomy reservoir as it stands now there is more than enough capability to vent any amount of air we will likely see.

Mathew Sullivan: I dont think Melody is referring to air when she talks about excessive volume. The volume shes talking about is fluids. I do agree with her in putting a Y-connector in the venous return line instead of having a vent line from the cardiotomy reservoir connected to a waste bag.

Mike Darwin: ***Since I am opposed to using hard-shell open reservoirs I wont comment here beyond saying that Boons interpretation is correct.***

4. Deleted excess connectors from AV loop.
Its best to have only the two cannulae connectors most likely to be used inserted in the AV loop, with others available.

Charles Platt: As mentioned during the meeting, I recommend that we universalize our cannulae connections by inserting any appropriate fittings deemed necessary to our cannulae and re-sterilize them. This ensures no matter if we are working on a full sized adult or a small child that we can connect the cannulae to the tubing without having to make any last minute adjustments. The most obvious example of this might be to insert a ¼ x ½ connector into a venous cannulae, then re-sterilize it. This may seem strange to perfusionists out in the real world considering they would use a small tubing circuit with the interest in a small circuit volume for a child, but our tubing packs are one size fits all and this is okay in our situation because we do not have the same concerns associated circuit volume and the need for blood.

We should also consider or debate the possible use of quick disconnects made by Qosina that Medtronic was using at Mechanisms.'

Mathew Sullivan: Question is what are the percentages that you will be working on a small child, my guess is probably not often. The quick disconnects that Medtronics Resting Heart System circuits are using may be a good solution.

Mike Darwin: ***Unfortunately, I dont have the text at hand, but Alcor recently (last 12 months or so) pumped a patient full of air in the field because they did not have the right sized connector and the mortician tried to jury-rig something which, as best I can tell, created a venturi at the connection between the arterial line and the arterial cannula thus allowing for sustained and undetected (until foam came out the venous line) air embolization. In several cases perfusion was either not possible, or mortuary cannula and/or equipment had to be used because there was a missing connector. One of these cases was the mother of a world-renowned biomedical researcher. I have been criticized for calling people who do this kind of things IDIOTS, but I honestly dont know what else to say. The first time it happens is inexcusable, but to have it go on, and on, over 15 years is sheer idiocy. Nevertheless, this is the way it is. An inexperienced person digging through lots of supplies on a tray or in a kit-box may be unable to find or recognize the right sized coinnector. I know that seems impossible to you (and me) but it has happened. I used to keep every conceivable sized connector in my goat so that when I filled the goat with saline I would empty out my pile of connectors onto the cutdown or major thoracic tray thus they were always at hand and in the sterile field. And, of course, I could tell a ¼ x 3/8 connector from a 3/8 x 3/8 connector on sight. You only get that ability by handling these things on a near daily basis.

While you may well know in advance that you are doing a child, and the odds may be low, you cant count on that. No child has been cryopreserved since the early mid to late 1970s. However, there are children signed up and there may well be a pediatric at-need case. You need to at least be able to go from 3/8 to ¼.

What is more, I kept a selection of stainless steel cannula on my tray (maximum size 6 mm OD) which I could use on very atherosclerotic patients. The femorals of some elderly patients will only accommodate a small cannula and these all have ¼ tubing barbs. You can easily deliver 5 LPM a minute through such a cannula (I did it all the time on dogs) albeit at the price of a high back-pressure between the pump and the cannula.***

Charles Platt: The venous cannula currently being used has an incorporated 3/8 connector.

Melody Maxim: I dont know that we have come to any firm conclusion on which cannulae we will be using, but if or when this becomes the standard, the tubing should not go past the first barb to make for easy removal of the tubing. Speaking thereof, the AV loop on the training pack has both of its cannulae connections past both barbs and if this were done on a real tubing pack, expect the surgeon to complain a lot. Tubing or connectors meant to be removed to make way for cannulae connections should not go past the first barb to make for easy removal.

The arterial cannula does require a 3/8 connector, so one with a luer lock has been included.

Charles Platt: Discuss whether this luer lock is acceptable to replace the previous manometer port connector.

Melody Maxim: My assumption here is that we will be going with the arterial cannulae with pressure manometers built within unless someone can think of a reason not to; therefore, the 3/8 LL connector will need a one-way stopcock to allow for the removal of large amounts of air, sampling for those who will insist on taking a sample there, or even for those who might want to use a florescent die to look at patient circulation as an example as has happened in the past. We used to have this type of connection next to the cannulae at Alcor, but the surgeons complained enough that we moved it back a few inches to allow for better handling and making the cannulae connection.

Boon: I think the purpose of having a luer lock on the 3/8 connector for the arterial cannula is to allow air (if any) to purge out when connecting to the arterial line from the pump. I do not agree with putting a one-way or a 3-way stopcock there to allow for taking an arterial blood sample or for measuring the arterial line pressures. You dont want to mess around with the arterial cannula once it is in place. Instead put a 3-way stopcock on top of your arterial line filter to have access for blood sampling and checking your arterial line pressures is a better way to go.


Mike Darwin: ***This has been an endless source of frustration for me. No one has listened to me over this issue for the last 15 years so I hardly expect them to start now. (Forgive my cynicism.)

Pressure cannot accurately be measured in back of the arterial cannula at all but the lowest flows with the largest diameter cannulae. In order to measure pressure via the arterial cannula it is necessary to pass an intracath beyond the tip of the cannula and then hook this up to a pressure transducer. Yes, it can be a manometer, but this is pretty pathetic and very dangerous. Solid-state disposable pressure transducers and portable, compact, battery powered (NiMH no less!) monitors are now available. USE THEM! Use them not only to monitor MAP but to monitor CVP or even venous line pressure at the venous cannula, if nothing else is available.

What you are measuring when you measure pressure behind the arterial cannula is the back pressure generated by the constriction of flow represented by the arterial cannula. The long fluid filled line leading to the manometer is just air embolism machine waiting to spring into action.

The idea of the 3/8th connector near or on the arterial cannula being used to work air out of the system before going on bypass is not understandable to any professional cryonicists now engaged in perfusing people (that I know of). They assume that if you dribble fluid out of the arterial cannula when you insert it into the arteriotomy that you MUST therefore have no air. It is impossible to convence them that AFTER the arterial cannula is placed and secured that you must draw back blood and work out any bubbles. If they dont see any air in the line when the insert the dripping cannula into the artery, they dont believe there can be any. The fact that air may have entered the artery via the arteriotomy and be present between the arteriotomy and the proximal arterial ligature appears to be an impossible concept for them to wrap their minds around. Of course, in the real world, if you fail to do this you will pump air and you will usually have a detectable neurological deficit to contend with.

Similarly, if you simply do the rote exercise of aspirating the vessel after the proximal tie is released you will almost always SEE air. However, if you always refuse to do this you will never see the air and therefore you will never remove it. And, since your patient never wakes up, you never see any harm in this Indeed, after you have completely filled a patient up with air and blown him up like a balloon you can confidently state: Despite the problems during surgery, the cryoprotection went fairly well.


So, yes, you need a 3/8 connector with 4-way stopcock at the arterial cannula to remove air prior to going on bypass.***


5. Removed a 3/8-1/4 reducer, as well as a tube inside a tube connection, from the AV loop recirc line and changed the tubing from 1/4" to 3/8.

Melody Maxim: Im not sure about the 3/8 x ¼ connector, since the new tubing packs under construction do not have this item in the AV loop.

Increasing the tubing size eliminates the need for the two extra connectors, (especially the extremely undesirable tube inside a tube connection),

Boon: Because I have not seen the circuit, I dont know what she means by tube inside a tube connection. However, I have to agree with her on eliminating any unnecessary extra connectors, if you can.

Melody Maxim: There may have been a legacy item leftover in the training pack in regards to the tube inside a tube, but if you look at the other tubing packs on the table you wont find any solvent bonded connections. I know some people have expressed concern about solvent bonded connections (calling it a glued connection which it is not) sighting they have never seen it before, but I have purchased tubing circuit products that had tubing bonded to products and you have also mentioned the use of bonded products, so Im a bit confused when I hear statements such as extremely undesirable. The only thing that I wonder about is some form of unwanted reaction as a consequence of using the solvent, but I possess no knowledge to make such an assertion and can only speculate as to why some here are objecting to it. I expressed concern about this while working at Alcor, but I was told that it was a solvent and not a glue, so there wasnt anything to be concerned about. If I remember correctly, I was informed that the solvent evaporates away.

Mike Darwin: ***Solvent bonds are achieved by solventing (dissolving) the two tubing segments into each other using cyclohexane. As Mathew notes, they are widely used by manufacturers and often used to join large PVC and acrylic components together. After EO sterilization and out-gassing there is virtually no cyclohexane residue in the circuit. Cyclohexane joints must never be used in the field only before sterilization and out-gassing.

Solvent bonds are undesirable only in that if they are facing the direction of flow they tend to create turbulence which damages formed blood elements. Connectors do this too, but usually to a much smaller extent because they are designed to minimize turbulence and do not have the un-tapered surface of the solvent joint.

Aside from the irreversibility of the joint, they are of no special consequence. Done properly, I have never seen one fail and they are not difficult to do well. By contrast, Ive seen plenty of tubing come off connectors, albeit not on tubing packs assembled by medical manufacturers. The reason in-house tubing connections may blow-off is due to the effects of sterilization on the tubing and the connector. Heating of the tubing pack during EO sterilization and out-gassing (heated aereation) can cause tubing to relax and connectors to shrink slightly. Manufacturered tubing packs get around this problem by electronically welding the tubing to the connector for all but those joints that need to be broken to go on bypass.

My comments here are educational; I have no strong feelings one way or another. I used solvent bonds mostly when I had a tight space or otherwise wanted to avoid kinking from a connector. Solvent joins are much less likely to kink on tightly coiled tubing, or on short-lengths of tubing such as the recirculating connector line near the end of the AV loop (a feature common to all ultraprofound hypothermic asanguenious perfusion circuits).***

Charles Platt?:and provides for recirculating at a higher flow rate.

Mathew Sullivan: Higher flow rates through the bypass are not necessary. All that we need is a reasonable flow rate to maintain the temperature while on bypass.

Mike Darwin ***Mathew is correct. The purpose of the bypass loop near the end of the AV loop is to prevent warming of the perfusate (or blood) and consequent out-gassing and bubble formation during any pause in bypass. If you leave perfusate that has been cooled to near 0 degrees C in a line to warm up it will fizz and form bubbles as the gas solubility of the perfusate decreases with warming. This is true of the entire circuit and is why it is critical to maintain flow so that bubbles will be swept into the filter and so that the circuit and perfusate temperature can be maintained at a constant and low temperature to avoid out-gassing in the first place.***

Charles Platt?:The tubing length seems adequate for positioning the tubes in any desirable position.

Mathew Sullivan: We used to use the 3/8, but after sufficient complaining on the part of the surgeons we switched to a 1/4, since it offers a greater amount of flexibility, is less inclined to resist adjustment, and offers a lower probability of having a permanent kink as a result of packaging and sterilization.

The Keck clamp has also been replaced which means we will have to put the old screw clamp back on in addition to the clamp that is on there now. This means subtle adjustments in bypass can no longer be done with a single hand easily with any degree of precision in the event the surgeon what it during their procedures, to training events were we have demonstrated backpressure.

Boon: If your arterial line is 3/8 and venous line is also 3/8, why would you want your AV loop shunt line to be ¼? I would use 3/8 for my shunt.

Mathew Sullivan: If you use 3/8 tubing for the bypass line you will find it stiff and difficult to position. It is also much more difficult to occlude completely, especially when cold. The use of ¼ tubing is a lesson hard-learned and should not be reversed.

Mike Darwin: ***Restore the Keck clamp! Screw type (Hoffmann compressor) clamps are completely unsuitable for use anywhere in a CPB circuit. They are especially dangerous with cold PVC tubing (remember the shuttle Challengers O-rings?) because they do not reliably occlude in the cold and if applied when the tubing is warm they may allow flow when it cools.

In addition to the Keck Clamp, I always applied a metal occluder to the line; I dont trust plastic clamps of any kind for bypass, or even dialysis; Ive seen several (living) human patients killed by those damn things.***



6. Shortened tubings to perfusate bags and waste bags.
Having all clamps within reach is a safety feature, as it allows the person operating the perfusion circuit to stay in close proximity to the reservoir and pump. (Shortened lengths should still be adequate to position perfusate and waste bags in a variety of position in the event of cramped quarters.)

Mathew Sullivan: I agree and this helps to bring us in better alignment with Alcors tubing pack.

Mike darwin ***Agreed.***

7. Shortened accessory lines to avoid tangling and confusion.

Boon: Not sure what this is?

Mike Darwin: ***Not sure what this either, but the shorter the better for most lines. It makes hand-over-handing much easier and less necessary.***

8. Removed manometer port at AV loop.
Patient pressure is best monitored in vivo,

Melody Maxim: I agree.

Mike Darwin ***This problem (monitoring arterial and venous pressures) must be dealt with definitively and effectively. In the clinical setting of fem-fem CPB the radial artery would typically be used to monitor pressure. However, expecting SA personnel to reliably place radial artery lines is unrealistic and too time consuming. Creating a routinely useable (prefabricated) through-the-arterial-catheter monitoring line (using an intracath), or buying Biomedicus arterial cannula with built in pressure monitoring lines, is the best I can suggest. You may be able to get a reasonably good static (non-dynamic) arterial pressure by placing an intraflow-equipped line distally into the femoral artery and ligating it there. Femoral collateral circulation is very poor in humans, but it should be sufficient to give you a static arterial pressure.

Whenever a central venous line is present (subclavian, Hickman, portal cath, dialysis cath, etc.) you can use that for a reliable CVP. Monitoring CVP will alert you to insufficient venous drainage, kinked or occluded venous line, or an obstructed venous catheter..

All pressure lines must be equipped with intra- (angio) flows to allow for flushing and for priming of the lines prior to insertion. Virtually all disposable pressure transducers have this feature incorporated into them; all that is needed is an IV of saline and a pressure infuser. There are many compact, reliable, self-calibrating pressure transducer-monitor systems out there. Buy a good one and learn to use it.

but if necessary, pressure can be monitored via the luer lock on the arterial cannula connector.

Provided a three-way stopcock is already in place before the circuit is primed.***

Discuss. Is this acceptable for SAs purposes? What was the purpose of the 3-way connector on the manometer port?

Melody Maxim: It is a multi-use port that allows for anything from the removal of large amounts of air in the event there is a major problem, sample taking, to injection of chemicals.

Mathew Sullivan: I want to make sure I understand you correctly. So you have a 3-way stopcock connected to the luer lock on the arterial cannula connector, right? And you are saying this is a multi-use port that allows for removal of air, sample taking, and for injection of chemicals (drugs). In perfusion we are taught to NEVER inject anything through the arterial side because of risk of introducing air. You always inject chemicals/drugs into your venous reservoir. I believe trying to manipulate the 3-way stopcock while on bypass to either drawing blood sample or injecting drugs is not a smart thing to do. Putting a purge line off the top (3-way stopcock) of your arterial filter will allow you to draw arterial blood sample and connecting another pressure monitoring line to a side port of the 3-way stopcock to your manometer will allow you to measure the arterial line pressure. See the photo below:




Mike Darwin: ***Melody is right. You should not be using this port for anything in the field except to remove air prior to going on bypass. ALL samples and drugs are added via the 5-gang stopcock. Addition of dye is for CPA perfusion and must be done by an expert that is the only exception to the rule and the only reason it is done is because there is no other way to get a clean signal (the arterial filter dilutes the dye). NEVER use any port on the arterial line (after the filter) for anything other than removing air. Samples must also ALWAYS be taken from the stopcock assembly. There is no reason to do otherwise since an arterial or venous sample withdrawn from the stopcock assembly is not going to be any more or less accurate than one taken from the arterial line near the patient. Taking a sample from the arterial line is DANGEROUS and IRRESPONSIBLE. It is also guaranteed to result in air embolism sooner rather than later.***

9. Removed most 3-way stopcocks and syringes.
These are very easy to break off when packing, or setting up, the circuit, and should be added after setup.

Mathew Sullivan: Some things can be assemble at the last minute such as syringes and vacutainer ports, but Im against not pre-attaching stopcocks. Ive been a party to more than one heated debate over who forgot to attach the stopcock and the consequences resulted in anything from concerns associated with the introduction of air after the start of procedures to not being able to get a sample at the last minute with the start of washout.

Having everything in place was done so at the request of Tanya because she did not understand the kits well enough to know where to get everything and put it together in the field. People such as Tanya will blame those who make tubing packs for not making them complete, resulting in unwanted problems in the field.

Mike Darwin:***Melody is right but Mathew is more right . The stopcock assembly must stay in place or it will, a) placed incorrectly (highly likely) or b) forgotten altogether with people then going to the connectors on the arterial and venous lines at the cannula to draw samples. Better to have a broken stopcock assembly which they can see how to replace than none in place at all. BTW, they will also not know to hook the arterial filter vent line to the venous reservoir since most people in cryonics are relying solely on the air separator on the filter. I was overjoyed when air separators were first introduced on the Lekoguard because I saw cryonics personnel not have any (bleed) line from the arterial filter to the venous reservoir. Instead, they ran a monitoring line from the top of the filter to the waste bag and they would only open the arterial bleed-line to remove macro-air that had accumulated in the filter (and of course to let air out during priming)!!!!!!!! Too incredible for words.***

Changes not yet implemented:
1. Incorporate parallel tubing paths to permit perfusion with, or without, flow through the oxygenator.

Mathew Sullivan: Same as the bypass line on the clot filter?

Charles Platt: As previously discussed and agreed upon, it is best to avoid flow through the oxygenator during procedures in which oxygenation is not desirable.

Mathew Sullivan: Im not aware of this agreement. For my own edification, are you saying that an oxygenator that is under pressure on the liquid side and at atmospheric pressure on the gas side will uptake O2? If the answer is yes, then we could cap off the gas connections.

Charles Platt: This also provides for continued flow in the event of oxygenator failure.

Melody Maxim: As mentioned in the meeting, the only time Im aware of an oxygenator failing is during training when the HEX is permanently wet and can go for weeks or month between use. Washouts are much shorter then cryoprotection and I have perfused a patient for I believe up to 12 hours. Charles mentioned that washouts take approximately two hours. He could be right, but Im still a bit surprised based on my experience washing patients out in the OR. My guess is that it shouldnt take more than 45 minutes to do a washout and recirculation to 10C or lower, unless the patient is compromised. I have a vague recollection of core body temperatures dropping to reasonable levels in about 20 minutes, and bringing the patients temp down those last few degrees takes longer as the temperature descent curve flattens out.

I dont know too much about the washouts and the cryoprotection procedures, if the incidence of having to change-out the oxygenator is quite frequent during bypass, then it is a very good idea to incorporate a shunt line for your oxygenator. (Please see attached file on PRONTO Procedure)

Mike Darwin: ***It would be nice to skip the oxygenator in simple washout cases and there was a day when this was possible when the old Sarns non-disposable heat exchangers were still around (all three of mine never made it to SA or were otherwise lost). However, with the advent of modern disposable oxygenators there is, at least to my knowledge, no free standing heat exchanger that has the necessary efficiency to allow for this (HEX co-efficient of ~0.6). The oxygenator is thus serving as the heat exchanger. You must never bypass the oxygenator while perfusing a patient for this reason.

I have run Sarns, Capiox, Gish, and a variety of other hollow fiber oxygenators in the dog lab (survival) and on cryonics cases. I have routinely run all of these oxygenators in excess of 12 hours without failure. The failure Melody is referring to here is transudation or weeping of plasma or plasma ultrafiltrate across the hollow fiber membrane. All current hollow fiber oxygenators are not true membrane oxygenators (like the Kolobow silastic membrane). Rather, they consist of a microporous fiber which is wetted by blood or other high-surface tension liquid. The pores (more like spaghetti laid out on a plate) dont leak liquid water or plasma because of the surface tension the water forms over the microporous lattice. Its the same principle that you see when you wet a piece of fine hardware cloth, like a window screen; the water is held in the screen holes by surface tension.

After extended operation plasma proteins and salts begin to accumulate on the gas side of the fiber and these deposits both decrease the effectiveness of gas exchange and defeat the surface tension, water-retaining capacity of the micropores in the fiber. The result is that water starts flooding out of the fibers under hydrostatic pressure and the fibers become a plasma ultrafilter. At that point the gas exchange efficiency is lost.

Under normothermic or mild hypothermic conditions in a clinical situation this a serious problem and requires that the oxygenator be switched out per protocol.

Such failures do sometimes occur early in oxygenator use and they are not the only failures possible. On the Gallager case I had a Sarns oxygenator (cosmetic defect reject) housing split into two pieces shortly after going on bypass! Fibers can also be damaged resulting in gas bubbling into the blood, but this is usually caught during priming.

Aside from the catastrophic failures I note above, failure of the oxygenator from fiber compromise is the only likely scenario. This is a non-issue in cryonics cases as far as Im concerned. It is very unlikely to happen and if it does you can simply turn off gas flow to the oxygenator and keep running it. If the drip of fluid out the gas ports is annoying you can put a short section of ¼ tubing on the ports and clamp them. This assumes that the patient is in ultraprofound hypothermia (< 10 degrees C) and that you want to continue recirculation. There are many reasons why you might want to do this on an ECMO (MARC) cart, but they are beyond the scope of this commentary.<br>
To summarize, the oxygenator is mostly there because of the heat exchanger. In most cryonics settings the ATP will be used no more than 2 hours and oxygenator failure due to wetting of the fibers is unlikely to be a material be a material consideration.

Typical (actual) washout and cooling times range from 15 minutes to 60 minutes on CPB. Much depends upon how much the patient has cooled externally before going on bypass.

In the future, if we ever return to 1980s style cryonics with prompt and effective CPS and capable personnel, the issues of prolonged gas exchange, appropriate FiO2, sophisticated monitoring (gases and pH), and oxygenator failure will need to be addressed. However, IMHO, that time is not now. For now, primum non nocere (first, do no harm) should be the goal. That means pressure alarms, air bubble detectors, and as intrinsically safe a system possible.***

2. Incorporate independent heat exchanger.
Discuss Heat Exchanger Performance Factor

Charles Platt: As mentioned in the meeting, Im not sure this is necessary based on the above discussions.


3. Replace current oxygenator.

Charles Platt: Unfortunately, nearly all currently available oxygenators in the U.S. come with an integral heat exchanger, with the exception of an independent silicone membrane oxygenator that is generally only used for ECMO procedures. The silicone membrane is expensive and difficult to manage, due to the flexibility of the membrane.

Mathew Sullivan: There are several comparable oxygenators available that would be more than satisfactory for Suspended Animations perfusion circuit, but this decision is best made after choosing the heat exchanger, for which there are several recent leads that deserve further investigation.

As mentioned in the meeting, I think we are better off sticking with an integrated system. I believe there was universal agreement from all of us that the product which is most desirable will be one with the highest cooling efficiency.


Mike Darwin: ***See my comments above. I do not favor scrapping the oxygenator at this point even though in most cases it functioning only as a heat exchanger. Ive had extensive experience with the Sci-Med Kolobow and do not recommend its use in this application.

I strongly suggest you abandon the Sarns oxygenators you are using. These are no longer manufactured and are not well configured for this use. This is the third time I have suggested this, and second time in print. You need to use an oxygenator that is going to be manufactured into the foreseeable future. The Sarns is history. and if they were stored in Florida under uncontrolled conditions I would NOT use them to pump a human. Every Sarns I had (and that you now have) is either a diverted return from a hospital, or a cosmetic defect reject. I took meticulous care of them and never stored them in high humidity environments nor did I ever expose the overwrap to shelves or handling. A small hole in that overwrap and, with varying barometric pressure, high humidity, and spores, and you have a nonsterile oxygenator and possibly one with actual microbial overgrowth. These oxygenators were dispensed in corrugated cardboard boxes to protect the sterile packaging. I would use these for animal (survival) training runs, but even then only after careful vetting.

The Monolith is is many ways ideal (size wise), but is being discontinued. I suggest you look at a format like the Gish or Medtronic which is broadly similar to the Monolith. If you want a good home for the excess Sarns oxygenators I can tell you who to send them to.***



Boon: Hi Aschwin,

In your email you wrote, Please focus on what you believe are the most important issues. Our short term goal is having basic capability, not the most sophisticated circuit in the world. OK, let me break it down to different points.

Go with the hardshell cardiotomy/venous reservoir for its better air handling and volume capacity.
Stick with the integrated system (oxygenator with integrated heat exchanger).
Dont put a 3-way stopcock at the arterial cannula connector, instead put one on top of the arterial line filter as shown in the photo above.

I dont know whether my advice is good enough to help you in deciding how to proceed.

Thank you for the opportunity to give my 2 cents worth of comments.

Sincerely,

Boon

ATP Circuit



Boon: Out in the field, are you going to have enough height differentials between the patient (in supine position) and the inlet of your venous reservoir to create adequate gravity venous drainage?

Mike Darwin: ***I agree with Boon, this is not enough fall. The reservoir needs to be as low as possible to the ground..This is another reason I dont like hardshells because you cant get them as close to the floor. You need 30 cm of fall on the venous line. Also, you must not snake the venous line up over the top of the PIB. If you look at the photo below we have unsnapped the side of the PIB at groin to allow for the venous line to fall directly from the groin wound to the venous reservoir. In the OR we simply raised the table top to get the desired fall (see below). It would have been very desirable to design the PIB so that it could be raised or lowered. In the field we achieved this with the old PIB design by placing the PIB on a mortuary table. All mortuary tables can be raised or lowered either hydraulically or by a bar-and-ratchet. Thus, we were not constrained by height. When the ECMO cart (MALSS) was designed we were stuck with a fixed height due to engineering constraints. This caused endless problems as the oxygenator and the venous line literally had to rest on the floor. In order to move the patient from home or mortuary to the ambulance we had to discontinue CPB and pull up the Sarns oxygenator holder.

Can the new PIB be adapted so that the ice bath (patient) can be raised up to a higher level?

As you can see from the two photos below I ran the venous reservoir bag virtually on the floor in dogs and humans. I kept the reservoir bag nearly full in this model because the dogs had been in normothermic cardiac arrest for 16 minutes and vascular tone went from nothing to fully vasoconstricted in a matter of seconds as various drugs were given. This was the only way to avoid pumping air. Lower bag volumes are desirable when doing hypothermic asanguineous recirculation to avoid warming and microbubble formation in stagnant blood.***







Boon: It looks to me like you are using a Terumo Capiox Cardiotomy. I know its cheaper than using an integrated cardiotomy-venous reservoir. However, with cardiotomy-venous reservoir there is a ½ venous inlet right on top of the hardshell, therefore you dont have to use a ½ x 3/8 reducer. This will create some resistance to your venous flow coming down from ½ in tubing to 3/8 in tubing. Your purge line is not connected to the venous inlet tubing, hence, does not have the venous sampling capability.

Mike Darwin: ***I agree with Boon. If you decide to use a hard-shell use a proper venous reservoir. Do NOT put flow restrictions in line: it does not matter that a port is set up to take either 3/8 or ½ tubing; if you reduce the diameter, however transiently, you increase back pressure and decrease flow.***



Boon: This is the integrated cardiotomy-venous reservoir that we currently use.

Mike Darwin: ***While I dont recommend hardshells this would be the way to go. Note all the ports on top of this reservoir! This is a recipe for confusion and disaster in unskilled hands.***


Boon: Another view of our cardiotomy-venous reservoir during bypass:



Boon: This must be a Peristaltic Pump. Im curious how high of the flow it can generate.



Mike Darwin: ***This is a commercial Cole-Parmer persistaltic pump. Youd love the ease of loading the pump shoe. It can easily produce 10 LPM flow with a ½ ID pump shoe. It also automatically occludes eliminating the need for in-field occlusion***

Boon: Do you really need a five-gang sampling manifold?



Mike Darwin:***They probably do not. I used two 5 gang manifolds of the cerebral ischemia dogs because we needed to give nearly a dozen drugs in very rapid succession. I have suggested that SA use a 5- or 6-gang manifold in the IV line during initial external CPS to facilitate rapid administration of transport meds. Here it is likely to be confusing, and perhaps a 3-gang should be used.***




Melody Maxim: We find a three-gang sampling manifold is more than adequate to inject drugs or draw samples.

Mike Darwin: ***Agreed.***

Boon: Why do you need to have two manometers to measure your arterial line pressure?



Mike Darwin: ***As I understand it, one is back up. These things and the isolators just creep me out completely. One big pressure excursion and you have intra-arterial air! I think it is also important to point out here that this set-up is to monitor filter back pressure (loading), not monitor arterial pressure. If the pressure in back of the filter begins to rise without an increase in flow then you know the filter is loading or clotting. This has never been a problem in asanguineous perfusuion in humans or dogs since the HCT is always <5%. Obviously, in whole blood clinical perfusion, monitoring pressure drop across the arterial filter is essential.***<br>


Boon: It would be nice to reduce the number of connectors you have.



Mike Darwin: ***This is the bypass loop and the A-V loop. I would substitute the arterial line 3/8 x 3/8 x 3/8 Y connector with a 3/8 x 3/8 x ¼ Y connector and the ½ x ½ x ½ connector on the venous line with a ½ x ½ x/ ¼ connector. This will let you create your bypass line out of 1/4 tubing with no reducing connectors. Yes, they do make a ½ x ½ x/ ¼ Ys, and they are configured so that the ¼ luer is parallel to the other (3/8) barb making this a very smooth configuration.

Absent this, I would use a solvent bond to unite a piece of ¼ tubing with a short stub of 3/8 tubing on one end, and the same thing with ½ tubing on the other.

There needs to be a 3/8 connector with port and 3-way stopcock on the arterial line where it will connect to the cannula to debubble the line and the vessel. Similarly, there needs to be a ½ connector with port and 3-way-stopcock on the venous line where it will connect to venous cannula.***

Boon: Hi Aschwin,

Here are some of my concerns:
1. Height differentials between the patient and the venous reservoir.
2. Is it feasible to use integrated cardiotomy-venous reservoir instead of just cardiotomy reservoir?
3. How good is the Peristaltic Pump? Is it going to generate enough flow?

4. Too many connectors in the circuit.

I hope these pictures are helpful. Let me know what you think.

Thank you.

Boon

Mike Darwin: ***1)Per the above, it would be good if you can adapt the PIB to be raised up like the top an Ferno-Washington embalming table.
2) I strongly suggest sticking with a compliant bag-type venous reservoir.
3) This pump is a proven workhorse and will deliver more than adequate flows. It is easy to set up and to operate and vastly safer for the operator than the traditional Sarns configuration (with the roller on top). You cannot crush fingers or entangle hair or clothing in this pump.
4) I agree that connectors should be minimized. I cant do this very well without a hands-on.
5) Arterial and venous temperatures should be monitored on the oxygenator and not with ports on the lines. A Cu+/C load type thermocouple should be secured into these ports directly as opposed to using the commercially available sensors because these sensors leak too much heat down the probe; they are not designed to run at a delta T of more than 5 degrees C. This also avoids long runs of TC line, simplifies the operative field, reduces the possibility of snagging a line and pulling a cannula out, and reduces the risk of contaminating the sterile field.
6) I can explain how to configure the TC probes so that they fit directly into the temperature monitoring ports on the oxygenator as opposed to using manufacturers probes which will read consistently 3-5 degrees to high with a large delta T.

Thank you for allowing me the opportunity to comment on this very interesting set of problems.

Mike Darwin***

END OF COMMUNICATION TO SA
------------------------

In a message dated 11/20/2008 9:18:31 A.M. Pacific Standard Time, perfusion333@comcast.net writes:

I originally wasn't going to respond to Mike's post, because I'm really just sick and tired of butting heads with non-professionals, in regard to perfusion, in cryonics. However, I don't think it's productive for the cryonics community to have Mike Darwin come here making certain (perhaps misguided) assumptions, and criticizing CI for consulting with a medical professional, as it is only likely to reinforce the negative attitude that prevails in conventional medicine in regard to cryonics, and vice versa.

MIKE DARWINS RESPONSE:

Melody,

I have never criticized any cryonics organization for consulting with medical or other professionals. In fact, on this list-serve I recommended (some months ago) that CI contact the AMSECT (American Society of Extracorporeal Perfusionists) chapter in the Detroit metro area to see if there were perfusionists interested in working with CI and learning what was required to be of material assistance in cryonics. I have also offered to put CI in touch with intensivists and others in medicine that might provide advice and assistance.

The only negative attitude I know of in cryonics towards medicine is that of Charles Platt and, in a different way, Bob Ettinger. As I understand it Bob sees much of medicine as it has been applied to cryonics as gilding the lily, superfluous, or not worth the cost, or not affordable. If I have any of this wrong (vis a vis Bobs position) Im sure hell correct me.

You write:

I find it somewhat confusing that Mike recognizes the need for someone with a "working knowledge of perfusion at Board Certification level - at a bare minimum," and then acts like such a person is too ignorant to participate in developing perfusion protocols for cryonics. With all due respect, (and recognizing that Mike Darwin may know a lot more about medicine, in general, than I do), I think his knowledge regarding clinical perfusion, and perfusion equipment, (especially recent developments in perfusion equipment), is somewhat limited.

Now, I am puzzled! I have, at least to my knowledge, never had any exchanges or communications with you beyond a very brief (3-5 min) chat on the phone when you were employed at SA; Charles put you on the phone with me and we exchanged some pleasantries. Beyond that, I dont believe you have communicated with me.
As to my current state of knowledge in terms of hardware and consumables; I would hazard Im fairly current. I have e-subscriptions to just about every perfusion/extracorporeal medicine journal, and I read them including the adverts. I also count a number of working clinical perfusionists as friends and colleagues, and I visit centers of cardiovascular surgical and perfusion excellence all over the world; I just spent time at the premier institute for cardiovascular surgery in Russia in Moscow. I also read a great deal of the primary literature on cutting edge developments in extracorporeal medicine; I have a longstanding interest in LVAD (left Ventricular assist Device), TAH (Total Artificial Heart) and bioartificial organ technology. I am a device nut and have a reputation as a medical technophile. I introduced the Novametrix CO2SMO into cryonics (sadly no one knew how to use it properly) and have tried to introduce cerebral function monitoring (onto 15 years now; since Aspect first started its clinical development of the BIS monitor) into Transport operations, to no avail.

I pumped some of the first centrifugals and I pumped the very first pseudo-membrane oxygenators (the horrible Travenols) as well as the first successful hollow fiber membrane (Bentley). I started research perfusion when Pemco discs were still in use a (I own both a pediatric and adult disc oxygenator and I still know how to disassemble, clean and Siliclad them ). Other than Charles Platt, you are the only person I know who has ever accused me of not being enthralled with, and knowledgeable about the very latest in perfusion or medical hardware (or related technology). Im not sure my passion in this area is a good thing, but nevertheless, it is very real.

So, again, Im puzzled by your remarks. I hope you are not mistaking the madness you saw at SA during your tenure there in any way for my work-product or advice. In fact, my advice to SA, in almost every respect, was not followed. To name just a few areas/items related to CPB: use of the wrong size arterial pumps, a jury-rigged high-low level sensor for the venous reservoir which was made of corrodible metals rather than using highly reliable and physiologically compatible off-the-shelf integrated level detection and marco/micro-bubble detection system equipped with pump shut off and line clamp features, failure to use Biomedicus flat wire cannula for femoral venous return, failure to use gravity assisted drainage... I could go on for pages...and did. I recently totted up the raw pages of correspondence from me to SA and it was over 900 pages long.

You continue:

I came to this conclusion a long time ago, after reviewing many of Mike's documents about perfusion, and having had a series of exhanges with him, regarding perfusion equipment, when I first began working with SA.
Again, I have no record of any exchanges with you and I have published nothing related to perfusion vis a vis cryonics in at least a decade. About the only things I can think of you that you may have seen from me were my advice to SA against Charles ideas of:

* using centrifugal pumps (in the field or for CPA perfusion),
*vacuum assisted drainage in the field (in unskilled hands)
*and a moderately strong recommendation against hard-shell reservoirs; again for in-field use in unskilled hands.

SA may have followed my advice about centrifugal pumps, but certainly didnt with respect to hard-shell reservoirs or level/pressure/bubble alarms; at least not until long after I had no further input, if then.

Interestingly, SA became fixated on vacuum assisted drainage for a truly amazing reason which had nothing to do with prior (competent) experience with either in-field TBW or extended duration extracorporeal support of cryonics patients at ~4-6 deg C. This is the story, written for another person (non-perfusionist; an engineer) at another time:

I was in Peacehaven (UK) staying with Alan & Sylvia Sinclair circa 2003. I picked up a copy of The Immortalist from their coffee table and on the cover was the Mobile Advanced life Support System (MALSS: the MALSS was the forerunner of the MARC a la Alcor) that Saul Kent had purchased from me when Kryos folded. It had been modified for operator convenience such that the venous reservoir was at eye level! This will probably mean nothing to you for the moment (long explanation to follow), but the practical effect is devastating. The blood returning to the heart from the body is conducted through two very large diameter tubes called the superior and inferior vena cava (SVC & IVC). The SVC drains the head and upper trunk and the IVC the lower body. Each is about 25 mm in diameter under resting conditions and they easily distend under pressure. Normal central venous pressure (CVP) is about 5 torr, and anything above 15 torr causes rapid development of (interstitial) edema. Above 20-30 torr and you blow the pulmonary alveolar capillary tight junctions and the lungs not only flood with fluid; fluid will start pouring out the ET tube inexorably! Nothing you can do will fix this; it is an irreversible injury which, at very least, is going to make CPA perfusion (whole body) very difficult because perfusate will escape the circuit from the lungs at an enormous rate, even under low flow and low pressure conditions and this perfusate cannot be returned to the blood circuit via cardiotomy suction as would the case with capillary ooze from transacted small caliber vessels in the chest.

This issue of tolerable CVP is relevant because flow through the cavae obey Poiseuilles Law. In laminar fluid flow through a tube or pipe frictional (viscosity) energy losses occur and these cause a pressure drop along the length of the pipe as a function of the pipe size, the type of fluid, and the mean flow velocity or flow rate.

The central formula in the laminar flow model is the Poiseuille equation:

R = (8hL)/pr4.
or Poiseuille law:
Q = (pDPr4)/(8hL),

where P = pressure, n = mean flow velocity, Q = volumetric flow rate, L = tube length, h = fluid viscosity, and r = tube radius.
The underlying assumption of laminar flow is the condition of uniform viscosity across the diameter of the tube; each fluid molecule within the tube is exerting a similar force against each adjacent molecule towards the periphery. This means that fluid adjacent to the conduit wall is motionless (no = 0), maximum fluid velocity (nmax) is in the center of the conduit, and fluid velocity is related to distance from the center (ni) by a parabolic function. Resistive losses (pressure drops) linearly are related to flow rate and flow resistance. While flow resistance linearly relates to conduit length, it is inversely related to the fourth power of the radius (or diameter of the tube or pipe). For example, a 1-cmdiameter tube has 16 times the flow resistance of a 2-cmdiameter tube of the same length and carrying the same fluid. Stated another way, 16 tubes of 1-cm diameter are needed to handle the same fluid flow at the same pressure as a single 2-cmdiameter tube. So, when you put someone on femoral-femoral bypass (CPB) in the field you are forcing ALL the flow that would normally go through TWO tubes each of which has a nominal diameter of 25 mm (=50 mm combined) through one tube with an absolute diameter of 12.5 mm! If you do the math you will see that this will result in a large and physiologically unacceptable increase in pressure. This difficulty is overcome only by the expedient of gravity-assisted drainage. You have to put the patient at least 30 cm above the venous reservoir and be certain to never allow the blood/perfusate in the venous line to become air-locked.

What is being done to make low CVP drainage possible through such a comparatively tiny tube is to use the siphon effect; negative pressure is being generated by gravity. The experts hired by SA were idiots. They knew nothing of even the most basic physiology, let alone the mechanics of venous return in CPB! When I saw that picture on the cover of THE IMMORTALIST I rang up Saul in the US (at Alans expense) and frantically told him of this error and its consequences. I then sent him and Bill Falloon a follow-up email. This wretched set-up was nevertheless subsequently used on a cryonics patient and they could not get venous return and there was massive edema. The mortician (wisely) decided to hook the venous return line to his water aspirator and suck on the venous line. They were able to complete washout but only after causing unimaginable injury to the systemic and pulmonary vasculature.

The people at SA were apparently never able to wrap his mind around this concept and he complained to a competent perfusionist they subsequently hired (a woman named Melody Maxim) about not getting adequate venous return with fem-fem CPB and Mike Darwins set up. What he didnt tell this consultant was that the venous reservoir was (arguably) 15 cm above the patients right heart!!!!!! This may have lead the consultant to suggest centrifugal pump assisted venous drainage which is not typically necessary and which is very technically challenging to implement; it requires great operator skill compared to what is available in the form of non-professionals who are trained in-house. It is also expensive. Also, unlike in the clinical setting, you can always put in another femoral venous cannula and return line. We have to do this in dogs:



The proper set-up of the MALSS is shown below. These photos are from a case where emergent CPB was undeertaken in the patients living room. CPS was started within ~2 min of arrest and CPB was started ~140 min post arrest; I had to cut down the contralateral vessels:

The Mobile Advanced Life Support System (MALSS) in use in a patents home in the mid-1990s. The red arrows in the photos show the venous reservoir bag:


SET UP PRIOR TO ARREST:



CLOSED-CIRCUIT PERFUSION UNDERWAY AFTER TBW:




groin because the patient had an anatomically anomalous right femoral vein that could not be cannulated (tumor invasion). Fortunately, he had great perfusion with the high impulse ACDC Thumper during the first 60 minutes post-arrest and he had cooled to ~ 23-24 deg C by the time bypass initiated.
CPS supported perfusion was probably very low past this point in time; you can see the tympanic temperature cooling rate go flat in the graph below at about 60 min post arrest). BTW, EVERY little back box or red dot on that graph was collected BY HAND and in real time by a fully dedicated data acquisition person. She literally collected data as fast as she could physically take it down. This is an important point: if we did not have that high sampling rate (now achievable with hand held temp. Monitors like the DualLogger) we would never have seen the flattening of the cooling curve that probably indicates the end of CPRs utility in moving blood (this data agreed with our dog data).



END OF EXCERPT.

You write:

Yes, I understand Mike's done a lot of perfusion, in cryonics, but "a lot of perfusion" in cryonics isn't equivalent to "a lot of perfusion" in conventional medicine. He's may have done dozens of actual cases over the years, while clinical perfusionists would do hundreds, (if not thousands), of cases, in the same amount of time. As Mike points out, there's no substitute for clinical experience. I pretty much cut off my exchanges with Mike, (about perfusion equipmjent), in a relatively short time, because I felt like it was some sort of "pissing contest," as my father would say. (Pardon me, but that's what it felt like, and I can't think of a more accurate, but polite, term.) I have a feeling this discussion could become much the same thing, in light of Mike's criticisms of CI, for consulting with me, so don't expect this to be a "back-and-forth," on my part. This will probably be a "one-shot rebuttal"...

If all I had was perfusion experience in cryonics Id have had essentially no experience at all. At one time I was a Board eligible perfusionist, but I never sat for the Boards and quite honestly, I did very comparatively little clinical perfusion. I started out in extracorporeal medicine doing acute (ICU) hemodialysis and working in the dog lab doing CPB. My guess would be that Ive pumped ~1,000 animals in my career; this is a trivial case load compared to that of a profession perfusionist over the same span of years. On the other hand, they call it a learning curve because it does plateau and after a certain amount of experience, animal or human, you do reach a level of knowledge and experience I liken to having learned to ride a bicycle.

Having said, make no mistake about it, it has been 8 years since Ive done CPB and I would require substantial re-education in terms of my procedural skills and knowledge; reflexive behavior and immediately accessible knowledge and judgment. And this brings up THE critical point I was trying to make: there are two kinds of knowledge in a craft: didactic (book or factual knowledge) and procedural or hands-knowledge. To some extent it is almost impossible for most people to master didactic knowledge in a discipline like surgery, perfusion, or operating an automobile without also having procedural knowledge; actually DOING the tasks involved, like driving an automobile under real-world conditions if you want to be able to drive a car. Once you have mastered both the didactic and procedural aspects of a craft or profession, you can usually maintain the didactic portion of your competence, and currency in the field, by diligent reading, interaction with colleagues, attending seminars and conferences and observing your discipline being practiced (preferably at centers of excellence). However, you will NOT be able to do procedures without interning and retraining your hands and reflexes. Indeed, it goes deeper than just hands skills because you will make procedural errors such as clamping or unclamping the wrong line, taking too much time to make a decision, or even making the wrong decision given only a short time to react.

I know about this first hand because I have experienced it several times during prolonged lay-offs from pump work. I learned to actually budget in several dogs as screw-up runs when the team had been away from CPB for more than 3 months.
So, my point was (and is) that I would not have, and in fact did not do what Ben asked me to do, because I felt very confident CI would pump air. My recommendations to Ben were essentially the same as yours (judging from the photo and text that appeared in Long Life): digital roller pump, medical grade tubing that is preferably discarded or properly reprocessed, combination oxygenator (to be run with 100% N2; He would be preferable but cost was an issue) and heat exchanger, auto-venting 40 micron filter, purpose-built reservoir with fluid addition baffles to prevent air entrainment and a perfusate addition port below the liquid level for adding perfusate, connector with port and 4-way stopcock at the arterial cannula to allow for aspiration of bubbles in the aortic arch or other vessels, large caliber cannula with an Intracath pressure monitoring line or a separate arterial line, heater cooler (easily and cost effectively fabricated in house to allow for subzero chilling of perfusate via the HEX) I strongly recommended, and have done so for over 20 years (!!!!), that CI use median sternotomy and RA drainage assisted with the appropriate venous cannula and gravity. Since they have refused (for 20 years) my last suggestion was stenting the RA and draining the thorax with an array of several cardiotomy suckers. And my best advice, if they insisted on using the carotids and vertebrals for vascular access, was to measure pressure with a set-up like this coupled to a robust and easy to operate transducer and monitor set-up:



In fact, Ive tried repeatedly to argue that they can successfully perfuse most whole body patients who want body perfusion solely via the femoral approach by using properly sized Biomedicus flat-wire venous cannula; Ive perfused 7.5M glycerol via this route! I even offered to let them use this equipment at no charge to see if they could work with it effectively.
But all of this requires more than just a few days training. We had to pump dogs on a regular basis using a survival model to maintain the necessary procedural skills. In fact, this level of activity was necessary for people to even be able to find the necessary supplies on the shelves. Once you move from extreme simplicity you begin to need to lots of things and those things require organization and familiarity; neither of which can occur absent experience. I was thus unwilling to create an environment where there would be some benefit at the risk of enormous harm. Primum non nocerum.

The set-up I saw CI using horrified me; and Bens unwillingness to substitute cable ties for corroding old hose clamps both baffled and disgusted me. Metal hose clamps are impossible to sanitize, can easily cut gloves and protective clothing, and can (and often do) cut through tubing. I actually pressured Ben to take me to a home improvement store and buy cable ties and cheap applicator tool; although he said he could see no reason to use them!

That kind of lack of understanding and behavior shouts to me that under no circumstances should I introduce complex and not well understood elements into CIs practice absent extensive teaching and training; if not from me, then from someone locally, perhaps found via AMSECT. I used to teach basic dog CPB to cardiothoracic surgeons and my experience with those (mostly) arrogant SOBs was that they had to kill a few dogs before they would listen to me. These were highly intelligent people with an excellent head for medicine and extensive background knowledge in physiology and pharmacology. When someone argues with me endlessly over cable ties for securing the connections on extracorporeal circuit tubing or about the advisability of using heparin or other anticoagulants post-arrest, I KNOW they have no business running even the arterial leg of a CPB circuit.
Beyond the experience at CI, I have had what is now onto 2 decades of horrible experience at Alcor and SA. Some of the people at Alcor are bright and seemingly technically knowledgeable.

However, all you have to do is watch the Discovery Channel documentary Immortality on Ice (1996) and see Alcor patient Stanley Penska being washed out in a mortuary with a PortiBoy embalming pump and NO VENOUS CANNULA!!!!! The venous return is geysering out of his femoral vein; periodically Hugh Hixon or Tanya Jones reposition the mortuary clot forceps and out comes another jet of pink fluid. Unlike me, Hugh can do the math that underlies the Poiseuille equation and can calculate the resistance to flow and the pressure that will develop in any length of tubing as a function of diameter, viscosity and flow rate. So, why are such errors continually being made??????

I have seen this over and over and over again, ad nauseum. Alcors replacement surgeon (for me) actually asked me why we could not use a patients Hickman central venous catheter for the venous return line on cardiopulmonary bypass (CPB) instead of going to all the trouble of putting a purse string in the right atrium and placing a two-stage venous return cannula! This was a professional who was a practicing veterinarian and who had supposedly had extensive experience with CPB in dogs, sheep and pigs!!!???!!!!! She was holding the Hickman catheter in her left hand while palpating the tip of it in the SVC; this is a tube with an external diameter of perhaps 3 mm and through which it is very hard to force 500 cc at 300 torr pressure in 10 minutes! You could have knocked me over with a feather. I couldnt make this stuff up if I tried!

You write:

The only way to "assume a working knowledge of perfusion at Board Certification level," is to hire properly educated and trained perfusionists. SA and Alcor can certainly afford to hire qualified perfusionists, (or at least retain a small pool, to rotate call), but I'm not sure CI can do this. If not, they must work with what they have.

I couldnt agree more with the caveat (to which I gather you do not subscribe) that cryonics is a discipline within medicine that requires specialized mentoring and training. A cardiothoracic surgeon is NOT competent to do perfusion without extensive training in perfusion; particularly training to develop split second judgment, rapid responses and a complete awareness of the circuit he is operating: as if it were an extension of his body. People who know how to drive well have a constant awareness of the position and likely behavior of the other drivers around them; they are constantly alert to likely (and unlikely) deviations in other drivers behavior, as well as in road conditions, and the behavior of their own automobile.

When I am in an OR I can immediately sense a wide range of things being right or being amiss; I know the normal sound of a ventilator cycling properly, of roller pumps or centrifugals operating smoothly, of the appropriate level of tension in the voices of every person in theatre, of the sound of a pump that has run dry or has an occluded line; the sound of bearing starting to fail on a pump, the sound of an uncoupled impeller on a centrifugal pump... You dont get these things in a day or a week, and if you cant get them at all then DO NOT DO COMPLEX PROCEDURES that can deprive a patient of cryoprotection. Nothing that CI can add to their technological base will undo the harm of a patient who is massively air embolized and cannot be cryoprotected as a consequence. This has happened at Alcor again and again...

Alcor had a perfusionist for a year or so to whom I carefully explained that in patients who have had substantial cold ischemia, the aorta will be under very slight negative pressure. This is totally counterintuitive unless you understand the pathophysiology of ischemia. Absent ion pumping, large amounts of vascular water move into the cells under the influence of the Gibbs-Donan effect. Every bit of mechanically and osmotically accessible vascular water will end up trans-located into the intracellular compartment. Starting about 15 min post arrest the CVP actually goes slightly negative (if you have a highly sensitive and properly zeroed pressure transducer to measure it). When you do a median sternotomy on such patients the evidence that the vascular volume has been depleted is that the aorta is concave. The aortas normal configuration, if cut out of the body and placed on a table top or in a basin of liquid, is NOT concave it is cylindrical. Why is this? The short answer is because the aorta has elastic fibers arranged in such a way as to make it cylindrical. The take home message is that the instant you make your aortotomy with that #11 blade in a concave aorta air will enter the aortic root/arch: air which you cannot see and which it is virtually impossible to evacuate because of the physical structure of the vessel. The first time Jerry Leaf and I saw a concave aorta we were smart enough to realize that we needed to do something; but it took us about 10 minutes to figure out what to do; should we cannulate a femoral vessel and pressurize the aorta? That would take a lot of time, but would certainly work. We ultimately decided to fill the thorax with perfusate and do the aortotomy and cannula insertion under water. We were smart enough to identify that truly unique to cryonics problem and deal with it. Unfortunately, even after being cautioned about this, the perfusionist that Alcor had on staff paid no heed with the expected results.

What I do have is 30 years of experience doing perfusion under demanding conditions that most perfusionists will never encounter. And I am not speaking of cryonics cases, but rather of the years of research work with models such as Peter Safars dog model of CPB reperfusion after many minutes of global normothermic ischemia. I have trained skilled perfusionists in this model and they do not learn it easily; one described it as a combination of his worst perfusion experiences all rolled into one; no volume, enormous demand for flow, sky high CVP, severe acidosis, totally deranged blood gases, no SVR and then, in seconds, massive SVR as a result of vasopressin and epi administration; and then almost instantly a tight venous reservoir bag which required draining into accessory reservoirs the volume of which could not be returned to the animals for HOURS after CPB was over!

Below are photos taken during one of these experiments (circa 1998). Most of the equipment you see was owned by me and maintained by me and I could reliably operate all of it:





I could also manage intensive care of the animals (including vent management and set-up and basic servicing of the vents of we used). That expertise extended to a wide range of ancillary equipment; IV pumps, syringe pumps, gas blenders, anesthesia machines (everything from tearing down a vaporizer to reworking gas regulators). The only thing I couldnt operate in the pictures above was the computer control system; we were in the process of automating CPB and Brian Wowk was the only one who understood that hardware and software.

ICU care was extensive for all of our models (TBW and ischemia-reperfusion) and we had to take a 12 hour shift alone:




You write:

Mike: "In fact, they require a lot of accessory knowledge that many contemporary perfusionists will not have; such as solvent bonding techniques, detailed knowledge of in-house ethylene oxide sterilization procedures, interaction of circuit components (polysulfone pseudomembranes, arterial filters, etc.) with cryoprotective chemicals, thermal (mis)behavior of some circuit components at near 0 deg C and on and on and on."

While Mike is correct in regard to the interaction of circuit components with cryoprotective chemicals, (something I am still kicking myself for, for not immediately recognizing the issue, when I first became involved in cryonics), I think he is making too much of other issues. Things such as solvent bonding techniques and detailed knowledge of in-house ethylene oxide sterilization procedures are unnecessary, in my opinion, and it was my observation at SA and CI, that ordinary perfusion circuit components performed exceptionally well at near-zero temperatures. The only thing I remember being solvent bonded on the SA circuit, (prior to my revisions), was an undesirable tube-inside-a-tube connection, below the venous reservoir, and I believe Mathew told me this was Mike's design. This was totally unnecessary, as there were reducers readily available to accommodate the connection, and it isn't necessary to solvent bond anything on the venous side, as it is an area of negative pressure. It isn't really necessary to solvent bond anything on the arterial side, either, though perfusion manufacturers do routinely solvent bond the connections around the arterial filter, as that is the highest pressure area of the circuit, and a disruption there could be difficult to deal with. In fact, when using occlusive pumps, (as is usually the case in cryonics), it is wise not to have all of the connections be "bulletproof," as it would be a heck of a lot better to blow apart the circuit, than over-pressurize the patient to the point that would be required to rupture a bonded connection. Even if solvent bonding, or ethylene oxide sterilization procedures were necessary, these procedures are EXTREMELY easy to learn. Certainly, anyone who is capable of having "a working knowledge of perfusion at Board Certification level," can master either of these tasks in one day, or less.

Please dont make the mistake of picking any one issue out of context; my point was that solvent bonding IS used by some cryonics organizations and rather than give it up and use reducing connectors, or subcontract to a manufacturer as Mathew Sullivan has suggested, they have demanded that it be used, and be used by people who are unfamiliar with it. A short précis of fuck-ups Ive personally observed:

Attempting to bond PVC tubing to polypropylene or polyethylene fittings; you cannot do this because those plastics are impervious to cyclohexane and most other solvents.
Bonding to plastics that are degraded by cyclohexane resulting in a plastic connector or component fracturing or breaking in two after sterilization.
Making connections with bubbles in them that are unreliable.
Trying to bond the WRONG SIZES of tubing together with resultant failure under pressure; or entrainment of air in the negative pressure areas of the circuit.
Bonding and then using the tubing/connectors/joins before the solvent has cured and been baked out with resulting hemolysis.

Contractors and hired experts want very much to please, and they have no way of knowing they are dealing with people who are often colossally ignorant, or worse, ignorant, stupid and arrogant; the worst possible combination. I gather it took you awhile to come to this realization during your tenure at SA. You are to be commended that you were honest enough to walk away. My point (yet again) is that all too many such experts, including some people I otherwise respect a great deal do not do that; they stay and take the money, or mistakenly believe that things are better off with them than without them. This is never the case. All they do is to serve as legitimizing beards which allow the incompetence (now morphed in fraud) to continue. I have no patience with such behavior.

You write:

Mike: "This is but one of countless examples that cut across the full spectrum of doing cryonics on a medical-model, or in a technologically complex way. It is THE major source of disaster when medical professionals or technologists are 'brought in to provide expertise. These well-meaning folks believe they know cryoprotective perfusion or even TBW perfusion because they are Board Certified perfusionists or cardiac surgeons. And, without exception, they are trusted completely by the people who hire them - even when cold, hard, logical and well documented objections to the specific dangerous things they do, or recommend be done, are made."

The "dangerous things" I've done, or suggested, in regard to perfusion in cryonics, can't even BEGIN to compare to the level of "dangerous things" that have done, and are STILL BEING DONE by the non-professionals amongst the cryonics organizations. For Mike to put forth that it is disasterous to consult with medical professionals is extremely offensive, and promotes a mentality that is sure to keep cryonics right where it is...in the dark ages, with golf pros and fabricators, and other laymen, performing complex medical procedures.

I said no such thing and implied no such thing. I simply said that cryonics is a professional discipline like any other in medicine and that a frequent mistake (endlessly repeated) by cryonicists and people in other professions, is to assume that an allergist is the same as a neurosurgeon or even that a cardiothoracic surgeon is a perfusionist. This is NOT so. I am a professional in cryonics, perhaps the only one left that co-created and used the medical paradigm with evidenced based decision making. I could just as easily say I resent your assertion that I am no such thing. What good would that do me, or you or anyone else?

No one is more aware of, or has railed more loudly or for any greater length of time than I have, at the utter incompetence that has overtaken the biomedical sphere of cryonics. I spent years of my life publicly pointing out the same issues that you are apparently pounding away at to no avail.

I learned that public criticisms are generally and are perceived as attacks. Worse than that, they completely alienate the community and destroy your reputation. The your Im speaking of here is not you, but rather me. However, I believe that that shoe may very well fit your case too. I stopped engaging in such behavior almost ten years ago and avoid being drawn into.

I do strongly believe there is a time and place for public criticism of the fraud and shenanigans that are going on in cryonics; but that time and place have to be carefully leveraged and chosen and, above all, there has to be an alternative. We are in the unfortunate position of atheists arguing to the believing saved; they may be crazyor fioolish for believing that nonsense (virgin births, golden tablets...), but given their alternative, who can blame them? Blaise Pascal was not a fool... Before Jerry Leaf arrested we were well on our way to creating an environment where thorough documentation, teaching, training, and mentoring of the proper people to become professionals in cryonics could be undertaken. We realized that you had to have the right people; you cant make anybody into a perfusionist, a surgeon, or even a good auto mechanic. It takes the right mixture of temperament and talent.

Until that environment is recreated there will be only failure. It is not possible to take a physician or a perfusionist or a neurosurgeon and throw them into cryonics and have them perform. This only causes heartache all around; and it is not just the technical issues but the ethical issues, liability issues, licensing issues and many others. Cryonics is a unique and uniquely dangerous environment, and it is unfair to subject an unsuspecting professional to that environment without extensive training and mentoring.

You write:

Mike: "Case in point: Ben Best had me come out to CI to make recommendations on how to improve CI's perfusion capability. I put together a basic circuit and explained to Ben what kind of accessory equipment would be required to achieve the ends he had in mind. This included a heater cooler, electronic (auto-zero) pressure monitoring equipment, digital pumps, and a rack assembly to hold and organize this instrumentation. For instance, the pressure transducer has to be at the level of the right atrium or you get garbage data..."

I hate it every time I see someone in cryonics remark about the level of the pressure transducer, as if knowing this makes one an expert in the monitoring of perfusion pressures. I criticized Platt for this very same remark, in his review of the SA case report. He appeared to be patting himself on the back for telling the team to put the transducer at the level of the patient, but that was it...no instructions on how to prime and zero the pressure set-up, much less how to trouble-shoot pressure issues, when the SA team was having extremely high pressures at extremely low flows. It's simple physics that if your pressure transducer is not at the same height of the pressure you want to monitor, the pressure reading will not be accurate. WHAT'S MORE IMPORTANT is something everyone in cryonics seems to have overlooked, (or to have been ignorant of), for decades in cryonics, is that the pressure Mike is referring to, is NOT a patient pressure, it's a CIRCUIT pressure, (unless the pump is turned OFF and the transducer is open only to the patient...a practice that is of no use in cryonics). At best, during cryogenic perfusion, the circuit pressure can be used to note trends in pressure. For example, if your flow is staying the same, but the circuit pressure is increasing, the patient's pressure may be increasing, (or someone may be kinking the arterial line, or the solution is becoming more viscous as it cools, or any of a dozen other things).

Surely you jest? See my diagram above. I am thoroughly familiar with invasive pressure monitoring in the critical care and perfusion environment. I have never pumped a patient without an arterial line or an Intracath threaded through and beyond the tip of the arterial cannula which is in turn connected to a pressure monitor. I can also tell you that CPA viscosity will nail you to the wall in terms of measuring pressure if you are using a small bore arterial pressure monitoring catheter or line (18 g or smaller) because the high viscosity destroys the dynamic responsiveness of a system using small bore tubes (see Poiseuilles Law above: the part re viscosity); you can have massive overpressure occur before the monitor can register it.

You continue:

Mike can indirectly criticize my "cryonics expertise" all he wants, but the very first time I saw the CI perfusion pump circuit in action, I saw something everyone who has ever reviewed that circuit, before me, appears to have overlooked. Seeing high pressures in a circuit that wasn't connected to a patient, I almost immediately realized the "patient pressures" CI had been recording, for many years, were NOT patient pressures. They were perfusion circuit pressures that were SIGNIFICANTLY greater than actual patient pressures, due to the extremely restrictive cannulae that were being used. (My guess is that, when CI was recording patient pressures of 100mm Hg, the actual patient pressure was probably 40mm Hg, or less. I told Ben how to test the pressure drop across the cannulae, but I don't know if he ever got around to it, or not. If I had been there, longer, I would have done it myself.) I asked Ben if anyone had ever explained to him that this was not a patient pressure, and he said no one ever had. Mistaking a circuit pressure for a patient's pressure is a critical error ANY experienced perfusionist would immediately recognize, yet it's something that seems to have been overlooked, in cryonics, for decades. Either Mike, (who had been at CI not long before me), did not draw this critical aspect of pressure monitoring to Ben's attention, (and nor did anyone else), or Ben forgot. Either way, this is EXPONENTIALLY more important than having the transducer too high, or too low, which, at times, seems to be the only thing the "experts" in cryonics know about monitoring pressure.

Mike: "Ben did not like the fact that this system was too big; it could not fit in the tiny prep room of the cranky mortician CI uses. I told him that an integrated cart could be fabricated to replace the mortician's prep table that would include all of these things and more... The answer was still 'no': it was all too complicated..."

I received much the same answers..."Too big, too complicated." While I would certainly have liked to have seen more of my perfusion suggestions implemented, I understood that CI had their limitations. If you have to do your perfusion at a mortuary, and the mortician will only allow you a certain amount of space, that is what you have to live with. It's not like there's a funeral director willing to participate in cryonics on every street corner. And, if you can't afford a full-time perfusionist, or standby perfusion fees, you can't afford it.
Mike: So, Ben asked me to set CI up with what he saw as a very simple circuit that basically consisted of the arterial leg of a standard CPB AV-loop. I told him I would do this ONLY if he would accept the (free) training and teaching that MUST accompany this. He refused. I explained that the very simple (indeed crude) system CI used had one great advantage: it's simplicity reduced the chance of catastrophic errors. I told him bluntly and repeatedly that the instant large surface area devices are introduced into a circuit enormous knowledge is PRESUMED about how they will behave and how to de-bubble them. A simple glass bubble trap would be infinitely better for CI than even a good auto-venting arterial filter - absent extensive and VALIDATED training on how to use such equipment.

I cannot even begin to explain how strongly I disagree with this, as a trained and experienced perfusionist "with a working knowledge of perfusion at Board Certification level," and as someone who has watched the employees of SA use both a bubble trap and an arterial filter. They had difficulty priming the bubble trap, and filled it with air almost every time they turned the pump off, and then didn't know how to remove the air, in order to resume flow. They didn't have these problems, once I changed to an arterial filter. The arterial filters are much easier to use. They come preassembled, with a bypass loop and a purge line that includes a one-way valve. In addition, not only do they protect against air, but they remove particulate matter.

Mike: "Instead, he went out and hired a perfusionist to do what he wanted done. I'm sure this person did the best they could under the circumstances. But, what the expert forgot was that a perfusionist is not made in a day, or a week, or a year, and that hundreds of lab hours and clinical hours are clocked before they are turned loose - even as an intern on a human patient. During those 'invisible' hours the perfusionist soaks up an 'instinctive' knowledge of the craft."
Mike seems to mistakenly assume I didn't make certain suggestions, (some the same as his). In addition, Ben didn't hire me to "do what he wanted done," he asked for my professional opinions and suggestions, and some basic instruction, then he made decisions, based on CI's "comfort zone." It was ridiculous, and extremely presumptuous, for Mike to assume I forgot "a perfusionist is not made in a day, or a week, or a year, and that hundreds of lab hours and clinical hours are clocked before they are turned loose." I'm sure I know that much better than he does. A perfusionist isn't made in a couple of decades, by experimenting with perfusion equipment in cryonics, and relatively little actual clinical experience, either. I'm quite sure Ben would confirm that I must have said something akin to, "I can never teach you what you need to know, about perfusion, in these three days," dozens of times, while I was there.

Mike: "The result was that CI pumped air on the first patient on whom they used their 'new and improved circuit' which was, more or less, exactly WHY I told Ben I refused to do as he asked. CI returned to a 'simpler'circuit..."

CI pumping air was not the result of consulting with a perfusionist, or a "new and improved circuit" which was minimally changed from what they had before. I've been told it was the result of someone not being attentive to the reservoir, and to the introduction of a large amount of bubbles while pouring additional amounts of solution into the reservoir. I've also been told massive amounts of air get pumped in a very large percentage of cryonics cases, while this is an EXTREMELY RARE, (virtually unheard of, in this day and age), occurrence in conventional medicine, where professional perfusionists are used. Incidents like this are a result of amateurs performing perfusion, NOT a result of consulting with professionals. Whether you have a bubble trap or an arterial filter, when introducing large amounts of air into the circuit, you will, at some point, exceed the amount of air the device can handle. "LESSON ONE" for perfusionists is "Don't pump air," (in other words, "ALWAYS WATCH THE RESERVOIR"). In my opinion, for cryonics, "LESSON ONE," in regard to perfusion should be adapted to "KEEP THE RESERVOIR FULL. (In conventional medicine, this can't be done, because it's important to hemodilute the patient as little as possible, but this is not the case in cryonics.) When using large volumes of solution, such as is the case in cryonics, there are ways to introduce additional solution to the reservoir, without introducing air. I discussed at least two methods, with Ben, so I won't go into the technical details, here.

Sigh. Yes, I know all this. And I could foresee it and I did. But you have yet to explain why this happened at CI only after they got a new circuit? Why was the reservoir not baffled, or at a minimum why was this not done (these are instructions written 30 years ago for emergency (expedient) perfusion equipment):

4.0 Set-Up of the Circuit for Cryoprotective Perfusion:




4.1 The circuit consists of a minimum 5-liter reservoir with a bottom outlet (10 liters is preferred). TURN THE PUMP OFF AND CLAMOP THE LINES TO THE PATIENT WHEN FILLING OR REFILLING THE RESERVOIR! The reservoir should be filled, if possible, using a funnel with a short length of tubing attached. The end of the tubing can be positioned below the liquid surface when adding additional perfusate. This will reduce the amount of air introduced into the perfusate when additional volume is added. The tubing between the funnel and reservoir is clamped when the funnel is first filled and air is purged from as much of the line as possible. The clamp is then slowly released allowing air to be displaced as filling is continued. One reason it is desirable to have a larger reservoir is that it reduces the number of interruptions required in order to top-up or change cryoprotectant concentration.

The reservoir should be wrapped in some kind of insulating material if possible; a small blanket or a number of turns of fabric will do.

You conclude:

I've taken more time with this than I wanted to, and now I'm pretty much done with this discussion, other than to reiterate that I think it is extremely unproductive for Mike Darwin to discourage the use of professionals, all the while demanding a professional level of competence. Cryonics is going no where fast, for so long as the community is encouraged to shun medical professionals.

--Melody

Yet again, I have not done this; what I have done is to realize that existing cryonics organizations will misuse professionals; seeking them out selectively and using their input equally selectively and without acquiring the needed knowledge base and skills to truly address the problems. Professionals (mostly unsuspecting) who get suckered into this relationship are the ones who get hurt; the cryonics people just keep trucking on, indifferent to the misery they have caused, the iatrogenesis they have created, or the patients they have harmed. They get away with it because cryonicists believe time will heal all wounds and overcome all stupidity - and mostly because the patients cannot scream, or bleed, or otherwise show objective signs of the injury they have suffered.
Mike Darwin

--------------------------------------------------------------------------------
From: m2darwin@aol.com
Reply-to: CI_Sci@yahoogroups.com
To: CI_Sci@yahoogroups.com
Sent: 11/21/2008 12:38:42 A.M. Pacific Standard Time
Subj: Re: [CI_Sci] mixing reservoir

NAME REDACTED, et al.,

There is no doubt that ramping up the CPA concentration for the first part of CPA perfusion in the patient with little ischemic injury is ideal. However, even in such good cases (now vanished from cryonics) it is arguably not desirable to linearly ramp all the way up to terminal concentration; in fact this is not what is done at 21CM, or Alcor, for that matter. We did it in the early days because that's all we knew to do and even then we would sharply increase the slope of the ramp if we encountered edema (always the case in ischemically injured patients).
For the typical severely ischemically injured CI patient I would not support ramping, but rather believe that stepped introduction with a doubling of concentration with each 'pass' is the best approach.

As to how to handle switching from one concentration to another or how to 'refill' a reservoir without introducing air, this is best done by using TWO reservoirs which are set up as shown below:




This set-up allows you to switch from one concentration to another or to refill a reservoir without introducing air. This set-up was rejected several years ago as too complex. It completely avoids introducing air since you fill reservoirs ONLY when you are not pumping from them.

You can also use a baffled reservoir like this:





The baffle (you can have more than one if needed) diffuses the stream of liquid and channels or streams it down the sides of the vessel and this avoids entraining air in the liquid.

This can also be done with a slotted or perforated tube anchored to the side of the tank:



If you want to really equilibrate the patient with CPA and to introduce it at a suitably non-toxic (low) temperature you will have to close the circuit. This does not preclude fairly discrete steps up in concentration but it does blunt them a bit (which is probably good). Below is the protocol 21CM was using to introduce and remove CPA from kidneys. It consists of a linear ramp for the first part of the introduction procedure followed by a sharp step up followed by a smaller (but still abrupt) step-up in concentration. The step-ups are tolerable ONLY because the organ has first been loaded with at least half the concentration to be subsequently stepped. Organs tolerate gentle introduction of the first CPA much better than starting out with steps. In the case of M22 they've found that a linear ramp is necessary up to ~5M CPA; they very much want to go faster to minimize exposure time, but this was not a viable strategy.



Always remember that this is uninjured tissue under ideal conditions. The problem with CI patients is that you are trading off reduced osmotic injury for decreased cryoprotection (due to edema). Right now, that seems like a very bad trade off.
This is what Alcor shoots for, and at least in this case, achieved (courtesy of Brian Wowk):



Notice that it takes them 4+ hours to get to terminal (target) concentration! This isn't being done because they want to be gentle it is what is actually required to achieve equilibration under real world conditions; the steepness of the 'ramp' attests to this. Note that venous concentration take quite awhile to equilibrate with the arterial concentration - over 2 hours in fact. This may not be evident from the graph but what must be kept in mind is that during the whole 'flat' part of the graph above 'concentrate' is steadily being added to the system in order to maintain the desired 'target' concentration in the recirculating reservoir (and thus in the patient). This is very much my experience in ischemically injured patients and it is why I do not believe that CI is reaching CNV in their patients. Too much of the microvasculature is inaccessible to flow with the result being vastly decreased surface area and much longer diffusion/equilibration times.

--Mike Darwin

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