X-Message-Number: 33369 From: Date: Mon, 28 Feb 2011 01:23:09 EST Subject: Melody Maxim's Distorted Reality 4 However, beyond these immediate practical considerations flow, in the context of pressure and other variables of the case, provides critically important insight into the pathophysiology of the cryopatient. We want to understand what is causing these things, why they happen, and how they respond to our interventions. Does SVR improve when we use a hyperoncotic perfusate, a hyperosmotic perfusate or a combination of both during TBW? Is this improvement lasting and does it come without adverse effects? Are vasoconstrictors such Neosynephrine or vasopressin effective in cases where the SVR is extremely low and the flow rate is astronomically high: and yet acceptable (i.e., required) physiological perfusion pressure cannot be obtained? How much actual capillary perfusion is occurring in such cases as opposed to flow that is shunted around the capillary beds? Beyond these examples it is important to understand that accurate measurement of as many physiological parameters as is possible leads to fundamentally new insights; often insights into important phenomenon which we did not even know existed. If we dont collect the data we will not be able to learn and make progress. The history of scientific, evidence-based medicine is a testimony to the criticality of vigorously collecting data which is consistently and ACCURATELY collected. That means precision in quantification. Ms. Maxim seems not to grasp this. Roller pumps are heavy, bulky and shed particles of tubing (spallation) into the blood or perfusate they pump. They are also harder on blood (more damaging to the cells) and they cause more activation of immune-inflammatory cascade (IIC) than the latest generation of centrifugal pumps. Depending upon the design of the system they unequivocally carry a greater risk of macro air embolization. Everyones preference in cryonics was to use centrifugal technology. However, a number of factors argued against this: 1) Knowing flows with precision and accuracy (indeed knowing them at all!) was critically important. It is absolutely essential in cryoprotective perfusion because flow rate is the primary perfusion parameter that determines cryoprotective agent equilibration in the patient. Flow is also the primary determinant of cooling rate (along with heat exchanger efficiency and the temperature of the wall water) during in-field CPB of cryopatients. Knowing when the patient will be cold enough to come off the pump is often really important since it can mean catching or missing a commercial flight. Roller pumps give a very consistent flow regardless of temperature, pressure, viscosity or perfusate composition. RPM can be converted directly into flow. 2) It is possible to design TBW systems so that no macro air can be perfused using roller pumps. This was done with the ATP. The ATP, properly set-up (a given in any system including centrifugal circuits) cannot pump macro air. The ATP was NOT designed for extended closed-circuit operation and ALL of my advice to SA was in the (stated) context of simple open circuit flush of the patient. 3) The notion that centrifugal pumps cannot cause physiologically devastating over-pressure injury is incorrect. While centrifugals cannot generate an infinite head of pressure under occluded conditions as can roller pumps, the static pressure of most medical centrifugals under no-flow (occluded arterial or venous line) conditions varies from ~500 to well over 700 mm Hg. Such pressures will NOT rupture the extracorporeal circuit (i.e., explode oxygenators, filters, or blow apart circuit connections) but they can cause tremendous damage to patients. Just try occluding the venous (outflow) line on a CPB circuit employing a centrifugal pump on a human (or animal) and wait until the flow goes to zero from back pressure. You will have one very, very dead patient. The much touted safety against over-pressure with centrifugals in CPB is primarily to the circuit and thus indirectly to the patient because if the arterial leg of the circuit explodes due to a clamped line, bypass is interrupted until a new circuit can be brought on-line and the patient is now virtually guaranteed not only ischemic time, but very likely the need for transfusion as well (with all its attendant risks). 4) No cryonics patient, to my knowledge, has ever been air embolized during in-field TBW due to a roller pump or due to pumping the venous reservoir dry. When in-field air embolization has occurred it has been due to improper connections on the arterial line: between the arterial line and the cannula (Venturi effect) or due to failure to de-bubble and aspirate the arterial line and arterial cannula/vessel prior to going on bypass. 5) Low level and bubble detection equipment with auto-shut-off and line-clamp features are highly effective at prevent air embolization and should be used on ALL CPB circuits. 6) Loss of prime on centrifugal pumps in the presence of high molecular weight colloids creates large numbers of very stable and difficult to remove micro-bubbles. This also often happens during priming when air is enrtrained into the pump. 7) Centrifugal pumps are not acceptable for CPA perfusion and personnel MUST learn how to reliably and safely use roller or other occlusive positive displacement pumps. This can only be achieved by extensive didactic and hands-on training in a feedback driven model. Translated, that means you must pump living animals under demanding conditions (i.e., that produce major physiological derangements) with SURVIVAL as the outcome and with EVALUATION of the quality of that survival (i.e., end organ function, neurological outcome, etc.). I (and Jerry Leaf when he was alive) have been saying this for 20 years!!!!!! Melody Maxim writes: "The misunderstandings that are going on, here, are one of the inherent reasons medical professionals should be used to perform medical procedures in cryonics. We never had these types of disagreements, when I worked in heart surgery, because we all had the same basic educations, with our specialties layered on top that. In other words, we "spoke the same basic language," and we had all been educated regarding each other's specialties, to some degree. (All of the perfusionists in my class did hospital rotations assisting the anesthesiologist, and scrubbing in with the surgeons, and we had classes related to every aspect of heart surgery, not just perfusion.) Mike Darwin: This is quite true and, in point of fact, neither Jerry nor I had any such problems with the many medical professionals, including professional perfusionists, with whom we interacted or collaborated with over the years. In fact, Ms. Maxim is the first such person with whom Ive had this difficulty." Melody Maxim writes: "These questions are not pertinent to the situation at SA. SA is not starting out with blood, and they are not using cryoprotective perfusate of varying concentration. The last I heard, they are washing out the patient's blood with a specified volume of washout solution that has a consistent concentration." Mike Darwin: See my extensive comments above. Melody Maxim writes: "Precisely measuring the flow is nowhere near as important as preventing the introduction of air to the patient. An occlusive pump will continue to pump at the set rate, regardless of whether the tubing is filled with fluid, or air, while a centrifugal pump will not." Mike Darwin: This is true, but it is not the whole story (see above). The solution is to have *only properly trained/skilled personnel perform TBW*. Clinical perfusionists are the ideal (with additional training) but the fact is that any intelligent, motivated person with the right temperament and reflexes can be trained to operate an open circuit TBW system (with the proper safeguards) with a high degree of safety. That does not mean a weekend of training but rather extensive, outcome-based training using the identical system that is to be employed in the field. The reality is that in much of the world, and for the foreseeable future, cryonics is going to be performed by non-perfusionists. There was a time when that was done both safely and effectively (if you count me as a non-perfusionist). But it was NOT done easily. In fact, actual real-world experience has demonstrated that I am even more conservative on this point than is Ms. Maxim. I refused to provide CI with a more complex circuit absent extensive training to a level where I was satisfied that the personnel using the system would be reasonably safe. Every additional complexity in the procedure or the circuit design creates distractions with the potential for error (absent through training and vetting). There was a time in cryonics (1981 to 1997) when at least in SOME cryonics operations these standards applied and in those operations *air was never pumped to any cryonics patient (with no exceptions and no qualifications)*. Meklody Maxim writes; "An equally critical, related issue, (which isn't even being discussed by Mike), is the importance of maintaining proper patient pressures. After reading SA's "CI-81" case report, I accused SA of over-pressurizing a patient whose cerebral vasculature was already compromised. The occlusive pumps that have been used in cryonics are NOT sensitive to pressure and will continue to deliver the selected flow rate, no matter how high the patient's pressure gets. (In other words, an occlusive pump will continue to pump at the same rate, in the presence of increasing pressure, until something blows apart.) A centrifugal pump will respond to increasing patient pressure with a decreasing flow rate, and to a decreasing patient pressure with an increasing flow rate, at a constant RPM. Placing an amateur behind an occlusive pump is almost certain to result in: a.) Air being introduced to the patient b.) Inappropriately high perfusion pressures that may result in vascular insult to the patient c.) Inappropriately low perfusion pressures that may result in the inadequate perfusion of the patient's tissues (some of the patient's tissues won't be perfused with the cryonics solutions) d.) Any combination, or all, of the above" Mike Darwin: Countless CPB cases have been pumped worldwide with roller pumps with a microscopic incidence of air embolism due to the presence of the roller pump, per se; and with excellent outcomes. This was true even before the introduction of safety features such as macro/microbubble detectors, low-level detectors and arterial line clamps. Of necessity, neonatal and adult ECMO are STILL carried out using compliant bags with these features (plug a push-plate type bag volume sensor/controller) and I believe many canters still use roller pump for this days to weeks-long CPB procedure. The fact is that BOTH systems are used clinically with acceptable safety and excellent outcomes. Outside of cryonics, in the world of clinical medicine, I have almost no doubt that centrifugal pumps will become the standard of care and, what is more, that minimal CPB using integrated centrifugal pump-oxygenator- heat exchanger-cardiotomy and venous reservoir systems is the future of CPB (and that eventually, when/if true membrane hollow fibre oxygenators are manufactured, this will be the case for extended duration ECMO, as well). These systems are compact, have less immune-inflammatory cascade activating surface area (and the surface area that is present can be better treated to minimize such activation), and are less damaging to both the formed elements of the blood and to the plasma proteins than are conventional CPB circuits andthey require less priming volume thus conserving blood and reducing the need for transfusion. They are also just more elegant and aesthetically physiological: in the body the heart is not positioned in the pelvis, but rather is adjacent to the lungs with the shortest possible lengths of connecting tubing (blood vessels). Whats more, if the flow problem can be solved I believe that minimal CPB systems will be ideal for use in cryonics cases including cases where prolonged (8 to 24 hours) extracorporeal support is indicated. Of course, this presupposes they are affordable. Much of what we actually used in cryonics from day one was a function of what we could gain access to - and that was in large part a function of money. (The righ 'connections' and favors also played a critical role). SA is an other-worldly affair subsidized by LEF and not, as far as I can tell, sustainable in its current form. Ms. Maxim speaks of inappropriately high perfusion pressures in cryopatients. I concur, but would go further and ask these questions of her: 1) What are the safe and appropriate pressures to use in cryopatients during both blood washout and subsequent asanguineous recirculation? Please explain why you have chosen the value(s) you provide. 2) What are the absolute and relative medical contraindications to in-field TBW for cryopatients? 3) What are medical indications and contraindications for extended (> 1 hour) asanguineous extracorporeal support of cryopatients? What are the likely complications and how should they be managed? 4) What are the expected pressures (MAP & CVP) and flows in both acute TBW and ECMO treated cryopatients? 5) What colloids can be used in TBW/ECMO of cryopatients and for what reasons? What colloids are known to be contraindicated and on the basis of what evidence? 6) What FiO2 should be used during TBW and/or ECMO in cryopatients? Why? Melody Maxim writes: "Mike Darwin: "So, again, I ask: has SA done the simple experiments necessary to validate the SCPC flowmeter? An easy place to start is to pump tap water from a reservoir and measure the flow/min by capturing the pump output in a graduated cylinder while using a stopwatch to determine elapsed time." I've been waiting all day for someone to ask the obvious question, but it seems to have slid right past everyone on this forum. Since Mike claims to be concerned with the accurately measuring the flow of SOLUTIONS USED IN CRYONICS, why is he suggesting using TAP WATER for the experiment, rather than the actual washout solution??? This makes no sense, whatsoever. Regardless, as Mike, himself, points out, it is simple to determine whether the flow transducer is accurate for SA's washout solutions, and I'm quite sure the perfusionists associated with SA learned this simple task, (just as I did), in perfusion school. Mike Darwin: I suggested tap water because it is cheap and readily available. If the flowmeter reads tap water flows accurately then it is worth proceeding to test it with perfusate (really expensive) under real-world conditions. I suggested tap water for the same reason you used it in training circuits: it is a cheap liquid which you can pump and which behaves enough like blood for the purpose at hand. If the SCPC flowmeter gives an invalid number for tap water, particularly if it is misleadingly close to a believable flow, then you should proceed with real caution if you proceed at all. CPB ultrasonic Doppler flow meters and electromagnetic flowmeters will NOT read water or TBW asanguineous perfusates at all. This is a blessing in that you are not likely to mistake a random number generator for a truly accurate flowmeter. If a flowmeter reads tap water with reasonable accuracy (or can be calibrated to read such) then there is a good chance it will read perfusate accurately; after all, we know for sure it reads blood accurately and tap water is one extreme of a continuum between distilled water and blood, with perfusate being in-between in terms of viscosity and ion content. Content-Type: text/html; charset="US-ASCII" [ AUTOMATICALLY SKIPPING HTML ENCODING! ] Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=33369