Tag: Mike Darwin

The case against cryonics

What is striking about cryonics is that those who have taken serious efforts to understand the arguments in favor of its technical feasibility generally endorse the idea. Those who have not made cryonics arrangements usually give non-technical arguments (anxiety about the future, loss of family and friends, etc), lack funding or life insurance, or are (self-identified) procrastinators. In contrast, those who reject cryonics are almost invariably uninformed. They do not understand what happens to cells when they freeze, they are not aware of vitrification (solidification without ice formation), they think that brain cells “disappear” five minutes after cardiac arrest, they demand proof of suspended animation as a condition for endorsing cryonics, etc.

This does not mean that no serious arguments could be presented. I can see two major technical arguments that could be made against cryonics:

1. Memory and identity are encoded in such a fragile and delicate manner that cerebral ischemia, ice formation or cryoprotectant toxicity irreversibly destroy it. Considering our limited understanding of the nature of consciousness, and the biochemical and molecular basis of memory, this cannot be ruled out. Cryonics advocates can respond to such a challenge by producing an argument that pairs our current understanding of the neuroanatomical basis of identity and memory to a cryobiological argument in order to argue that existing cryonics procedures are expected to preserve it. An excellent, knowledgeable, response of this kind is offered in Mike Darwin’s Does Personal Identity Survive Cryopreservation? Cryonics skeptics in turn could produce evidence that existing cryonics procedures fall short of this goal.

2. The cell repair technologies that are required for cryonics are not technically feasible. This argument should be presented with care and rigor because the general argument that cell repair technologies as such are not possible contradicts existing biology. A distinct difference from the first argument is that it is harder, if not impossible, to use existing empirical evidence to settle this issue. After all, making cryonics arrangements is a form of decision making under uncertainty and such decisions are not straightforwardly “correct” or “incorrect,” “right” or “wrong.” What can be done is to provide a detailed scientific exposition of the nature and scope of the the kind of repairs that are necessary for meaningful resuscitation and to argue that both biological and mechanical cell repair technologies are not conceivable – or are conceivable.

One thing that becomes immediately clear from this exercise is that there is no single answer to the question of whether cryonics can work because the answer to this question depends on the conditions and technologies that prevail during the cryopreservation of a patient. This introduces a set of more subtle distinctions concerning the question of what kind of cryonics should be assessed. It also produces an argument in favor of continuous improvement of cryonics technologies, and standby and stabilization services.

This short examination of technical arguments that could be made against cryonics gives advocates of the practice two talking points in discussion with skeptics or hostile critics:

(a) If a critic flat-out denies that cryonics is technically feasible, it is not unreasonable to ask him/her to be specific about what (s)he means by cryonics. This simple question often will reveal a poor understanding of existing cryonics technologies and procedures.

(b) A decision made on the basis of incomplete knowledge cannot be “right” or “wrong” and should be respected as one’s best efforts to deal with uncertainty.

Case reports in cryonics

This article was originally published in Cryonics magazine, 4th Quarter, 2010.

Introduction

The most important reasons for writing case reports are:

1. To provide a transparent and detailed description of procedures and techniques for members of the cryonics organization and the general public. A cryonics organization that never writes anything about its cases and procedures should be treated with more caution than an organization that does.

2. To validate current protocol and procedures in general, and its actual implementation in particular. A case report should not only record what happened but should be used for guidance as to what should happen in the future. A detailed case report, especially when a variety of physiological data has been collected, contains a wealth of information that can be analyzed for the team members’ and patient’s benefit. Cryonics cases are relatively rare (compared with other medical procedures), so we should try to learn as much as we can from the cases we perform.

3. To serve as a medical record to assist with future attempts to revive the patient. Although advanced future medical technologies may make it possible to determine the physiological condition of the patient down to the molecular level, it is important to provide as much medical information as possible to help in efforts to revive patients. Having a detailed record of the patient’s condition prior to pronouncement, subsequent stabilization, and cryoprotection, may also help the organization in establishing the desired sequence of revival attempts.

4. To gain more scientific credibility. If we want scientists and physicians to take us seriously, we need to convince them that we attempting to cryopreserve our patients in a scientific manner.  Professional case reports can provide this kind of credibility.

This article will mainly concern itself with the general question of how a case report can help a cryonics organization in improving protocol, techniques and skills.

Protocol

To be able to assess the quality of patient care in a cryonics case, it is important to specify what the intended protocol was prior to writing about the case. Only if we know what the organization was supposed to do will we be able to assess how successful the care was. For example, if there is no mention of collecting (and analyzing) blood gases during a case this may have been because it is currently not a part of the organization’s protocol, but it may also be the result of a shortage of skilled personnel, defective equipment, or other problems or deficiencies. Unless the writer of the report specifies what should have happened, it is difficult to assess the quality of preparation and performance. If preparation for the case was poor and there was no (functional) extracorporeal perfusion equipment available, the case report should not simply state that the organization attempted to do a

case without substituting the blood with an organ preservation solution, but also why the blood washout was not attempted.

In reality there will be many deviations between the organization’s protocol and what actually happens. Human cryopreservation cases are not controlled laboratory experiments, and as many people who have extensive experience doing cases know, unique situations present themselves, including frustrating events that are beyond the control of even the most skilled medical professional. Nevertheless, the inherent unpredictability and uniqueness of cryonics cases is too often used as an excuse or justification for failing to follow established protocol, or for serious errors and omissions in the care of the patient. Documenting the prospective protocol will help us to gain a more systematic understanding of what is possible (or essential) and within our control, versus that which is not.

Detail

The importance of writing detailed descriptions of the procedures and techniques employed during a case cannot be overestimated. This not only enables the reader to gain a comprehensive understanding of the techniques used, it also allows detailed analysis of the difficulties that were encountered during a case that would not have been noticed if there is only a brief mention of it. For example, instead of simply noting that medications were administered, providing comprehensive details is essential. There are many reasons why this is the case.

Case reports should be prepared with the possibility in mind that what may seem mysterious, or inexplicable, to the writer may be crystal clear to an expert or perceptive reader when provided with sufficient detail.

Providing as much detail as possible also serves to allow for replication of the techniques used by others. This is a critical component of the scientific method. Other investigators or practitioners must be able to duplicate the procedures and obtain the same outcome. Yet another consideration is that factors not now perceived or considered to be important may become so in the future. There are many examples of this in the history of cryonics that have proved essential to improving patient care. For example (1), in the early days of cryonics bags of ice were used to facilitate external cooling. It was not until comprehensive and consistent core cooling data were collected that it became apparent that this technique required 6-8 hours to cool a patient to ~ +20°C (room temperature!) with the patient cooling at a rate of 0.064°C/min. Documentation of these appallingly slow cooling rates provided powerful incentive to develop stirred water ice baths which increased cooling rates to between 0.15°C/min  and 0.33°C /min, allowing cooling to ~15°C within 90 minutes to 2 hours after the start of cardiopulmonary support (CPS) (see graph below).

Comparison of Cooling Methods: Above are actual cooling curves for three adult human cryopreservation patients on Thumper support, using ice bags, the Portable Ice Bath (PIB), and the PIB augmented by SCCD (squid) cooling. Patient A-1133 weighed 56.8 kg, patient A-1169 weighed 57.3 kg, and patient A-1049 weighed 36.4 kg. As this data indicates PIB cooling is approximately twice as efficient as ice bag cooling. The SCCD appears to increase the rate of cooling by an additional 50% over that of the PIB (roughly adjusting for the difference in the patients’ body mass).

This example is even more instructive because continued diligent and comprehensive monitoring of cooling in multiple patients made clear other factors that were critically important to good outcome or, conversely, prohibited it. A large-framed obese male with heavy fat cover and a large amount of thermal inertia will not cool at anywhere near the rate that an emaciated, petite woman will. Evaluating the patient for fat cover and body mass index before deanimation allows reasonably accurate prediction of the cooling rate and may suggest the need for the addition of other cooling modalities such as peritoneal lavage with chilled fluid. Favorable results from application of peritoneal cooling in turn will suggest that even greater rates of cooling are possible for all patients and lead to the addition of the modality as a standard part of the protocol.

Failure to gather and promptly analyze data as basic as cooling rate precludes realization that problems exist as well as any possibility of solving them.

It is important to note that an incomplete case report doesn’t necessarily indicate failure on the part of a cryonics organization. In a case where the number of team members is limited, all resources may have to be devoted to doing the case, instead of collecting data, or assigning an essential person to the job of taking notes. In the case of limited personnel it is better to do a good case without documentation than to document a bad case. To some degree this conflict between tasks can be avoided by having some of the team members (the team leader, paramedic, etc.) use a voice recorder with a clip-on microphone. But if the number of team members is insufficient, and data collection is not possible, this should be reported in the case report and recommendations should be made and implemented to prevent this situation from occurring again in the future. Good data acquisition and scribe work are essential for a good case report and, if feasible, should be a full-time job during a case.

Analysis

Specifying the protocol and describing the case in great detail is necessary but is not sufficient. A critical review of the information and data culminating in a list of desired changes and specific plans to address them should complement this. Ideally every discrepancy between protocol and reality that has been observed during the case should be discussed. Even in a case where stabilization started promptly after pronouncement, and the protocol was followed to the letter, there is still a lot of (physiological) data that, once analyzed, may require a change in the protocol in future cases.

To assess skills, identify critical failures, formulate solutions, and compare cases in a meaningful and valid way, a consistent and systematic format of reporting cases is essential. A typical case report should be divided into sections describing protocol, patient assessment, preparation and deployment of standby assets, the details of the case (divided in sections such as  airway management, cardiopulmonary support, external and other cooling methods, blood washout, cryoprotective perfusion, and cooling to storage temperature), analysis, recommendations, and a variety of (public or non-public) appendices. Such appendices should include time-lines and graphic presentation of data, medications, cryoprotectants, and statistical analysis and comparisons to other cases.

Each case report should not only present solutions, or suggest tests and experiments to identify solutions, but provide a plan of action as to how these things can be accomplished. One approach to ensure that research and tests to validate solutions are implemented, and appropriate remedial action is taken, is to appoint an officer in the organization who is responsible for quality assurance and quality control. This individual’s job will be to ensure that case reports are written in a manner consistent with the guidelines as outlined by the organization, as well as to ensure implementation of required changes.

Another critical role of case reports is to educate the organization’s staff as well as consultants and, where appropriate, the patients’ physicians and other health care providers about protocol, procedures and techniques. Although case reports are not and should not be a substitute for comprehensive written protocols, standard operating procedures (SOPs), and thorough training of personnel, sometimes solutions to problems can only be found in case reports where a team member was presented with an unusual problem. Consistent and systematic organization of case reports will greatly enhance the utility of case reports for this purpose. For example, if a reader wants to know about surgical techniques, and problems encountered in gaining access to the circulatory system for blood washout, consulting a case report will be far easier if they’re organized in a consistent and predictable manner.

Answering Objections

One objection to writing up a case report is that it is not a controlled experiment and at best provides only anecdotal evidence. This is not the case for the following reasons.

Not all the mistakes and issues identified are of a hypothesis testing nature. For example, if a patient presents the human cryopreservation team members with a problem that could not be managed with the equipment at hand, the cryonics organization doesn’t necessarily need a larger number of cases to decide to make a change to their equipment, and to start teaching employees the necessary skills.

Similarly, what may be perceived as anecdotal evidence for the cryonics organization may be a consistent finding in nearly identical settings in mainstream medicine. For example, some issues during a human cryopreservation case may be well known in hemodynamic management of potential organ donors in hospitals, or, for example, a medication in the protocol that is undergoing trial as a stroke therapy may demonstrate the same adverse effects observed during transport of a cryonics patient.

Of course, such lessons are impossible to learn without both broad and deep knowledge of medicine and the relevant research literature. Considering the ever growing number of publications and hyper-specialization, case reports may increasingly become collaborations between numbers of people with expertise in diverse areas. The individuals with the most valuable input do not necessarily have to be the ones who did the case. A physician dealing with similar issues in a neuro-intensive care unit may identify problems and propose solutions not obvious to those delivering cryonics care to the patient.

Monitoring

We don’t know how our patient is going to fare in the future but we can know a lot about how our patient fared up to the point of long term low temperature care if we monitor his condition continuously. This starts from collecting detailed pre-mortem medical data to monitoring fracturing events during cooldown.

It is tempting to say that a case went very well if all the steps of the protocol were followed in a timely manner. This is not unreasonable because one would expect a strong correlation between an evidence based protocol and optimal care. But it is important to keep in mind that the goal of stabilization and cryopreservation is to treat the patient and not the book (as a saying in emergency medicine goes).

Without comprehensive monitoring of the patient through all parts of the procedures a case report will only document a predictable series of mechanical steps and some crude visual indicators of (relative) success at best. The things we are really interested in, like (quantitative) end-tidal CO2 measurements, cardiac output, pH, and cerebral oxygenation, cannot be observed without sophisticated equipment.

Not only do we want to know how the patient is doing after the fact, we would also like to be able to intervene during a case if we observe a trend that suggests (alternative) treatment. Only in-depth reporting and analysis combined with a sound understanding of the physiopathology and available treatments will enable us to do so.

Presentation

A comprehensive list of dos and don’ts in writing case reports is not something that can be explored in this article, but some things are worth mentioning. Stylistically, a human cryopreservation report should resemble a medical or research report rather than a sensationalized adventure for the patient or the standby team. This should apply to the organization of the material as well as the choosing of words. As a general rule mainstream medical terminology should be used instead of cryonics jargon. Editorializing should be limited, and if perceived necessary, be moved to the proper section of the report. For example, jumping from a technical description of procedures to quarrelling among relatives or complaining about government regulation doesn’t look very professional.

Protocol, procedures and techniques should be the subject of the report, not people. Cryonics preparation and procedures are very demanding and exhausting for all people involved and mistakes are made and will be made. Errors should be presented as dispassionately as possible to avoid a culture of blame and personal conflict. Experience also teaches that (potential) participants are more open to transparent reporting if a case report will not single out individuals in describing procedures.

No matter how competent the writer of the report is, each report should be proofread by most or all individuals who were involved in the case and, if possible, a variety of outsiders with appropriate technical and medical knowledge, before it is released to the general public.

Patient Care

Writing case reports as presented in this article may be more demanding and time-consuming than generally has been done in human cryopreservation, but the results may improve patient care to a degree not previously seen.  Ultimately, the most ambitious use of case reports will be one in which the case reports are analyzed as a series, measurements are compared, and patterns are established. Reading (and evaluating) a series of case reports in a systematic manner  will even enable us to answer some very fundamental questions as to whether, or the degree to which, protocol, procedures and techniques  have improved over the years.

Providing the best patient care possible for current and future patients is the reason why cryonics organizations exist, and considering how powerful a tool a good case report can be, a responsible cryonics organization should devote considerable resources and time to writing them.

As our members and resources increase, and human cryopreservation gradually becomes a part of mainstream medicine, the successful transition from basic algorithm, volunteer driven case to evidence-based cryonics will be an important mandate.

Case reports and increasing caseload

One of the biggest challenges facing a growing cryonics organization is that the organization will be faced with a growing number of cases per year. This challenge is further amplified if all these cases need to be documented. As a consequence, a cryonics organization will find itself allocating an increasing amount of time to writing case reports and falling behind publication schedule. One of the most unfortunate responses to such a development would be to make an attempt to keep writing case reports in the old style but to lower standards and take short cuts.

An alternative approach is to develop a new format for case reports that allows for a shorter report but still captures the essential objectives of case reporting. One approach is to eliminate all the narrative that is not essential for following the mechanics of the case and evaluating the quality of care. In the past there have been a number of case reports with excessive narrative but little technical reporting or analysis. For a cryonics organization with a growing caseload the opposite approach should be followed. Another approach is to eliminate detail about procedures that were performed without deviations from past protocol and expectations, provided that this is made explicit in the report. As a result, case reports will increasingly read as a description and commentary on events that diverged from protocol or new observations about existing procedures.

To establish a template for such case reports the following approach can be followed. First, it is established what kind of information is essential for doing a meta-analysis of all cryonics cases. Then these parameters are reverse-engineered to create a template for writing case reports that reconcile the need for economy of expression and documenting all the relevant aspects of a case.  One important advantage of producing such case reports is they permit easier consultation of the technical details of the case and still meet the fundamental objectives of writing case reports.

The history of case report writing in cryonics shows an erratic potpourri of approaches and styles. One of the most unfortunate victims has been the objective of using case reports to improve the practice of human cryopreservation and to formulate meaningful research questions for the sciences that inform cryonics. But if systematic thought is given to the objectives of case reporting outlined in this document, steps can be taken to leave this unsatisfactory situation behind while meeting the needs of a growing cryonics organization.

Notes

(1) I am grateful to Mike Darwin for this example and for reviewing earlier drafts of this article.

The RhinoChill: A New Way to Cool the Brain Quickly

We scientists are difficult, cranky, and above all, maddeningly frustrating people. Want to turn lead into gold? No problem, we can tell you how to do that, and in fact have even done it already: the only catch is that the cost of such ‘nuclear transmutation’ is many times that of even the most expensive mined gold. You say you want to travel to the moon? Done! That will be ~$80 billion (in 2005 US dollars). Want to increase average life expectancy from ~45 to ~80 years? Your wish is our command, but be mindful, you will, on average, spend the last few of those years as a fleshpot in the sunroom garden of an extended care facility.

And so it has been with an effective treatment for cerebral ischemia-reperfusion injury following cardiac arrest. Thirty years ago, laboratory scientists found a way to ameliorate most (and in many cases all) of the damage that would result from ~15 minutes of cardiac arrest, and what’s more, it was simple! All that is required is that the brain be cooled just 3oC within 15 minutes of the restoration of circulation. The catch? Well, this is surprisingly difficult thing to do because the brain is connected to the body and requires its support in order to survive. And the body, as it turns out, represents an enormous heat sink from which it is very difficult to remove the necessary amount of heat in such short time. Thus, the solution exists and has been proven in the laboratory, but it has been impossible to implement clinically.  This may be about to change as a variety of different cooling technologies, such as cold intravenous saline and external cooling of the head begin to be applied in concert with each other. Separately, they cannot achieve the required 3oC of cooling, but when added together they may allow for such cooling in a way that is both effective and practical to apply in the field.  A newly developed modality that cools the brain via the nasal cavity may provide the technological edge required to achieve the -3oC philosopher’s stone of cerebroprotection.

Read the complete article in PDF here.

At last, a sure-cold way to sell cryonics with guaranteed success!

A humorous romp through a promising new technique in aesthetic medicine from one cryonicist’s (warped) point of view.

Figure 1: Before cryopreservation (L) and after cryopreservation (R).

As everyone involved in cryonics for more than a fortnight is sadly aware, cryonics doesn’t sell. Indeed, if we were pitching a poke in the eye with a sharp stick, we’d more than likely have more takers than we’ve had trying to ‘market’ cryonics to the public. To see evidence that this is so, you need only wander around a shopping mall on a weekend and observe all the (painfully) stainless steel lacerated and brightly colored needle-pierced flesh sported by the young and trendy and increasing by the old and worn, as well.

Yes, it’s clear; we misread the market, to our lasting detriment.

It’s true that we’ve tried the ‘you’ll be rich when you wake you up line,’ and heaven knows we’ve beaten the ‘you’ll be young and beautiful forever’ line, well, virtually beaten it to death. And while people are certainly interested in great fortune and youth, both of these things share the same unfortunate shortcoming, namely that they are things that people either don’t have but want, or do have and don’t want to lose. As anyone who is really savvy at marketing will tell you, the best way to sell something is to promise (and preferably be able to deliver) that you can get rid of something that people have and really don’t want – something that is ruining the quality of their life, destroying their health, draining their pocketbook and, worst of all, making them really, really ugly.

So, it turns out that for onto 50 years now, we’ve missed the real selling point of cryonics that’s been there all along: IT WILL MAKE YOU THIN! Guaranteed!

Can such a claim be true? Well, surprisingly, the answer would seem to be an almost unqualified, “Yes!”

Recently it’s been discovered that adipocytes, the cells responsible not only for making you fat, but for making you hungry, as well, are particularly susceptible to a phenomenon in cryobiology that has proved a nettlesome (and only recently (partially) overcome) barrier to solid organ cryopreservation: chilling injury. Quite apart from freezing damage due to ice crystals forming, adipocytes are selectively vulnerable to something called ‘chilling injury.’ 1-5 Chilling injury occurs when tissues are cooled to a temperature where the saturated fats that comprise their cell membranes (external and internal) freeze. You see, saturated fat, which is the predominant type of fat in us humans, freezes well above the temperature of water – in fact, it freezes at just below room temperature. That’s why that big gash of fat on the edge of your T-bone steak is stiff and waxy when it is simply refrigerated, and not frozen.

Figure 2: Chilling injury is thought to result from crystallization of cell membrane lipids.

Chilling injury isn’t really well understood. In the days before both cryobiology and indoor heating, humans used to experience a very painful manifestation of it in the form of chilblains – tender swelling and inflammation of the skin due to prolonged cold exposure (without freezing haven taken place). In the realm of organ preservation it is currently thought that chilling injury occurs when cell membranes are exposed to high subzero temperatures (-5oC to -20oC), again, in the absence of freezing.

There is evidence that the lipids (fats) that make up the smooth, lamellar cell membranes undergo crystallization when cells are cooled much below 0 deg C. Since the crystals are hexagonal in shape and have a hole in the middle, this has the effect of creating a pore or hole in the membrane. Cells don’t like that – those holes let all kinds of ions important to cells keeping their proper volume and carrying on their proper metabolic functions leak in and out, as the case may be. This isn’t merely an inconvenience for cells, it’s downright lethal. Without boring you with technical details, it is possible to partially address this state of affairs in organ preservation by adjusting the ‘tonicity’ of the solution bathing the cells: oversimplifying even more, this means by increasing  the concentration of salts to a concentration higher than would normally be present

Figure 3: Contouring of the skin in a pig subjected to brief, subzero cooling of subcutaneous fat.

But, to return to our chilled adipocytes and the promise not only of weight loss, but of a fat-free future; adipocytes are killed, en masse, when their temperature is dropped to between 0 and -7oC. Within a few days of exposure to such temperatures they undergo programmed cell death (apoptosis) and within a couple of months they are phagocytized by the body; and all that ugly and unwanted fat is carted off to be used as fuel by the liver. Now the rub would seem to be that this effect is most pronounced when the temperature of the tissue is cooled to below the freezing point of water and held there – preferably for a period of 10 minutes or longer.

That sounds dire, doesn’t it? What about the skin, the fascia, blood vessels, and the other subcutaneous tissues that will FREEZE (in the very conventional sense of having lots and lots of ice form in them)? Well, the answer, as any long-time experimental cryobiologist will know (even if he won’t tell you) is: pretty much nothing. Way back in the middle of the previous century, a scientist named Audrey Smith and her colleagues at Mill Hill, England found that you could freeze hamsters ‘solid’ – freeze 70+% of the water in their skin and 50% of the water in their bodies – and they would recover from this procedure none the worse for wear. Similarly, those of us who have carelessly handled dry ice for a good part of our lives will tell you that we see parts of our fingertips turn into stiff chalky islands of ice all the time, with the only side effect being a bit of temporary numbness that resolves in a few days to a week – certainly a side effect well worth it to avoid the considerable inconvenience of rummaging around to find a pair of protective gloves.

Figure 4: The Zeltiq Cool Sculpting Cryolipolysis device.

But alas, we scientists (most of us, anyway) are not a very entrepreneurial lot, and so we never thought either of inventing the ZeltiqTM cryolipolysis system, or using ‘the thin-new-you’ as a marketing tool for cryonics.

Yes, that’s right; some very clever folks have found a way to make a huge asset out of a colossal liability – to organ preservationists, anyway. Around 2004 a Minneapolis dermatologist named Brian Zellickson, MD, who specialized in laser and ultrasonic skin rejuvenating procedures, made a not so obvious connection. Both laser and skin ‘face-lifting’ and skin ‘rejuvenation’ procedures rely on the subcutaneous delivery of injuring thermal energy to the tissues of the face, or other treated parts of the body (cellulite of the buttocks and thighs are two other common areas for treatment). These energy sources actually inflict a second degree burn in a patchy and well defined way to the subdermal tissues.

Now this may seem a very counterintuitive thing to do if you are trying to induce ‘rejuvenation’ or ‘lift’ a sagging face. But if you think about it, it makes a great deal of sense. As any burn victim will tell you, one of the most difficult (and painful) parts of recovery is stretching the highly contracted scar tissue that has formed as a result of the burn injury. Indeed, for many patients with serious burns over much of their body, the waxy, rubbery and very constricting scar tissue prevents the return of normal movement, and can lock fingers and even limbs into a very limited range of motion. Many burn victims must do painful stretching exercises on a daily basis to avoid the return of this paralyzing skin (scar) contracture.

And it must be remembered that aged skin – even the skin of the very old – can still do one thing, despite the many abilities it has lost with age, and that thing is to form scar tissue in response to injury. Thus, laser and ultrasonic heating of normal (but aged) skin induces collagen proliferation and large-scale remodeling of the skin. For all the bad things said about scar tissue it is still a remarkable achievement in that it does constitute regenerated tissue. Regenerated tissue which does the minimum that normal skin must do to keep us alive: provide a durable covering that excludes microbial invasion, and prevents loss of body fluids. By injuring the tissue just below the complexly differentiated layer of the dermis (with its hair follicles, sweat glands and highly ordered pigmentation cells) much of the benefit of ‘scarring’ is obtained without the usual downsides.

The injured tissues respond by releasing collagen building cytokines as well as cytokines that result in angiogenesis (new blood vessel formation) and widespread tissue remodeling. And all that newly laid down collagen contracts over time, tightening and lifting the skin – and the face it is embedded in. These techniques may justly be considered much safer versions of the old fashioned chemical face peel, which could be quite effective at erasing wrinkles and achieving facial ‘rejuvenation,’ but was not titrateable and was occasionally highly unpredictable: every once in awhile the result was disastrous burning and accompanying long term scarring and disfiguration of the patient’s face.

St some point Dr. Zellickson seems to have realized that the selective vulnerability of adipocytes to chilling offered the perfect opportunity for a truly non-invasive approach to ‘liposuctioning’ by using the body’s own internal suctioning apparatuses, the phagocytes, to do the job with vastly greater elegance and panache than any surgeon with a trocar and a suction machine could ever hope to do. Thus was invented the Zeltiq Cool SculptTM cryolipolysis machine.6

Figure 5: The cooling head of the Zeltiq devive equipped with ultrasonic imaging equipment and a suction device to induce regional ischemia and hold the tissue against the cooling surface.

The beauty of cryolipolysis is that it is highly titrateable, seems never to result to in excessive injury to, or necrosis of the overlying skin, and yields a smooth and aesthetically pleasing result. Not unjustifiably for this reason it is marketed under the name Cool SculptingTM. The mechanics of the technique are the essence of simplicity. The desired area of superficial tissue to be remodeled is entrained by vacuum in a cooling head equipped with temperature sensors, an ultrasonic imaging device, and a mechanical vibrator. The tissue in the cooling head is sucked against a conductive surface (made evenly conductive by the application of a gel or gel-like dressing to the skin) where heat is extracted from it. The tissue is cooled to a temperature sufficient to induce apoptosis in the adipocytes, while at the same time leaving the overlying skin untouched. The depth of cooling/freezing is monitored by ultrasound imaging and controlled automatically by the Zeltiq device.  At the appropriate point in the cooling process the tissue is subjected to a 5 minute period of mechanical agitation (massage) which helps to exacerbate the chilling injury, perhaps by nucleating the unfrozen fat causing it to freeze.7 When the treatment is over, the device pages an attendant to return to the treatment room and remove it.

The tissue under vacuum is also made ischemic – blood ceases to flow, and this has the dual advantage of speeding the course of the treatment by preventing the blood borne delivery of unwanted heat – and more importantly, by making the cooling more uniform, predictable and reproducible. It also has the effect of superimposing ischemic injury on top of the chilling injury which is something that seems to enhance adipocyte apoptosis. The whole treatment, in terms of actual cooling time, takes about 60 minutes. In the pig work which served as the basis for the human clinical treatments, the duration of treatment was only 10 minutes: but the cooling temperature was also an ‘unnerving’ -7oC. The degree of temporary and fully reversible peripheral nerve damage (that temporary numbness us ‘dry ice handlers’ know so well) was more severe at this temperature, although it resolved in days to a week or two, without exception.

As previously noted, cryolipolysis causes apoptosis of adipocytes and this results in their subsequently being targeted by macrophages that engulf and digest them. This takes time, and immediately after treatment there are no visible changes in the subcutaneous fat. However, three days after treatment, there is microscopic evidence that an inflammatory process initiated by the apoptosis of the adipocytes is underway, as evidenced by an influx of inflammatory cells into the fat of the treated tissues. This inflammatory process matures between seven and fourteen days after treatment; and between fourteen and thirty days post-treatment, phagocytosis of lipids is well underway. Thirty days after treatment the inflammatory process has begun to decline, and by 60 days, the thickness of interlobular septa in the fat tissue has increased. This last effect is very important because it is weakness, or failure of the interlobular fat septae that is responsible for the ugly ‘cottage cheese’ bulging that is cellulite. Three months after the treatment you get the effect you see below on the ‘love handles’ of this fit, and otherwise trim fellow. Thus, it is fair to say that Cool SculptingTM is in no way a misnomer.

Figure 6: Art left is a healthy, fit young male who has persistent accumulation of fat in the form of ‘love handles’ that are resistant to diet and exercise and the same man 3 months after cryolipolysis.

Does cryolipolysis really work? The answer is that it works extremely well for regional remodeling or sculpting of adipose tissue – those pesky love handles, that belly bulge around the navel, that too plump bum, or those cellulite marred thighs. So far it has not been used to try and ablate large masses of fat – although there seems no reason, in principal, why this could not be done using invasive techniques such as pincushioning the fat pannus with chilling probes, as is done with cryoablation in prostate surgery. However, this would be invasive, vastly more expensive, and likely to result in serious side effects.

And that was one of the really interesting things about the research leading up to FDA approval of cryolipolysis: it seems to cause no perturbation in blood lipids, no disturbance of liver function (the organ that has to process all that suddenly available fat) and no global alterations in immune function. It seems to be safe and largely adverse effect free. There is some localized numbness (as is the case in freezing of skin resulting from handling dry ice) but it resolves without incident with a few weeks of the procedure.8

So, all of this makes me wonder, since human tissues tolerate ice formation and respond to it in much the same way as they do to laser or ultrasound ‘rejuvenation’ (depending upon the degree of damage) a logical question is, “would it be possible to use partial freezing of the skin – just enough to provoke the remodeling response – as a method of facial rejuvenation?” It should be safer than a chemical people and it is, like laser and ultrasound therapy, titrateable.

Figure 7: “Gad darn it, this shiny gold stuff keeps getting into the silt I’m tryin to git out of this here river!”

Which returns me to the whole subject of cryonics: fat is very poorly perfused and it seems unlikely that things done to moderate or abolish chilling injury will be nearly so effective for the adipocytes in fat (if it they are effective at all). That means that we might well all come back from our cryogenic naps not only young, via the magic of nanotechnology and stem cell medicine, and rich via the miracle of compound interest (which none other than Albert Einstein once remarked was “the most powerful force in the universe”), but also THIN! For all these years organ cryopreservationists, like Fahy and Wowk, have been panning for the mundane silt of a way around a chilling injury9 all the while discarding the gleaming nuggets of gold that were persistently clogging up their pans.

We cryonicists should not repeat their error and should realize a good thing when we see it. Now, for the first time, we can credibly claim that if you get cryopreserved you’ll come back not only young and rich, but young and rich and beautiful and thin!

Methinks there must be very few in the Western World today, man woman or child, who can resist a product that has all that to offer – and which, by the way, bestows practical immortality in the bargain.

Ok, Ok, maybe we shouldn’t mention that last part about immortality; it might scare the children.

REFERENCES:

1)     Wiandrowski TP, Marshman G. Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. Australas J Dermatol 2001;42:207–10.

2)     Diamantis S, Bastek T, Groben P, Morrell D. Subcutaneous fat necrosis in a newborn following icebag application for treatment of supraventricular tachycardia. J Perinatol 2006;26:518–

3)     Lidagoster MI, Cinelli PB, Levee´ EM, Sian CS. Comparison of autologous fat transfer in fresh, refrigerated, and frozen specimens: an animal model. Ann Plast Surg 2000;44:512–5.

4)      Wolter TP, von Heimburg D, Stoffels I, et al. Cryopreservation of mature human adipocytes: in vitro measurement of viability. Ann Plast Surg 2005;55:408–13.

5)      Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR. Selective cryolysis: a nivel method of noninvasive fat removal. Lasers Surg Med 2008;40:595–604.

6)     Avram MM, Harry RS. Cryolipolysis for subcutaneous fat layer reduction. Lasers Surg Med. 2009 Dec;41(10):703-8. Review. PubMed PMID: 20014262.

7)     Zelickson B, Egbert BM, Preciado J, Allison J, Springer K, Rhoades RW, Manstein D. Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model. Dermatol Surg. 2009 Oct;35(10):1462-70. Epub 2009 Jul 13. PubMed PMID: 19614940.

8)     Coleman SR, Sachdeva K, Egbert BM, Preciado J, Allison J. Clinical efficacy of noninvasive cryolipolysis and its effects on peripheral nerves. Aesthetic Plast Surg. 2009 ul;33(4):482-8. Epub 2009 Mar 19. PubMed PMID: 19296153.

9)     Fahy GM, Wowk B, Wu J, Phan J, Rasch C, Chang A, Zendejas E. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology. 2004 Apr;48(2):157-78.

Cryonics, trans-temporal communism and future squatters

Cryonics advocate Eugen Leitl puts forward some hard-hitting and thought-provoking observations about cryonics (reminiscent of Mike Darwin’s more recent thoughts on the subject):

Cryonics, like Natural Selection, or the theories of General and Special Relativity, is core-smashing in character, and in the case of cryonics, the idea is so antithetical to the existing order of civilization that it can it only be advanced by insurgent means. This is so because cryonics overturns the Vitalistic view of life, challenges the conventional definition of death, invalidates the core tenets of contemporary medicine, erodes the need for a mystical afterlife, radically redistributes capital (disrupts inheritance, bequests, and mortuary customs), mandates a complete change in reproductive behavior, perturbs generational succession, requires space colonization, requires (and supports) profoundly disruptive technologies such as cloning, regenerative medicine, nanotechnology, artificial intelligence, and finally, ends the species and enables, if not requires Transhumanism. As a consequence, cryonics creates adverse emotional and intellectual states within the existing culture such as survivorship guilt, indefinitely extended anxiety and uncertainty accompanying life-threatening illness (the cryonics patient remains ‘critically ill’ for decades or centuries), prevents the psychological closure that accompanies “true” death with disposition of remains, creates indefinite anxiety about the well being of cryopreserved loved ones, disrupts the intimacy of family interactions during the “dying” process, may bitterly divide family members who are opposed to cryonics versus those who are in favour, and blocks or disrupts deeply held mechanisms for coping with death and bereavement that are inculcated from childhood by eliminating the customary wake, funeral, and other comforting rituals.

In particular, he opines that “the idea that cryonics was just an extension of medicine and is compatible with religion and existing social and political institutions, while superficially satisfying, is both mistaken and bound to fail.” After this observation one would expect him to advocate some radical form of transhumanism as a vehicle to promote cryonics. But he further believes that:

Distinct from initialization failures, there are inherent in cryonics several corrosive and self destructive ideas that have grown over time until they have virtually overwhelmed cryonics today. The first of these is “temporal load shifting,” or more colloquially, the problem of ‘our friends in the future…his causes cryonicists to increasingly shift the burdens, technological and financial, present and future, onto the people (supermen) who we believe will revive us from cryopreservation, a concept that may fairly be called Trans-Temporal Communism: from cryonicists now according our ability (none); and from our ‘supermen friends in the future’ according to our needs (infinite). Trans-Temporal Communism leads to the creation of ‘Future Squatters; people who believe that technological advances will happen when conditions are right for them to occur. This is a brilliant position because it is never wrong; it is the perfect piece of circular reasoning that justifies doing nothing. This creates a perverse situation wherein intelligent and talented people who enter cryonics do not, as might at first be thought, find it impossible to believe that cryonics, vast extension of the human life span, or, for that matter, many of the transformational technologies of Transhumanism are impossible, but rather they that find it not only believable, but inevitable that these developments will occur within their lifetimes (i.e., Kurzweil and deGray)….The Future Squatters who have come to dominate contemporary cryonics are not merely parasites content to sit and wait until robots show up at their doors with immortality on a silver platter, all too often they are actively contemptuous and dismissive of the (fewer and fewer) people working hard to build a practical, sustainable and robust cryonics that withstand the tests of time and deliver its patients to a future they have created; a future not only technologically capable of restoring them to life; but morally and financially impelled to do so, as well.

If one rejects both cryonics-as-medicine and the futurist / transhumanist vehicle to communicate the idea of cryonics, one wonders what the correct approach should be. The observation that “the core problem in cryonics is the absence of a philosophical and moral basis for cryonics and the accompanying ethics and dogma required to enforce it” does not seem to follow from the preceding observations.  Most importantly, what is this “philosophical and moral basis for cryonics” that is required, and why is it separate and different from the general moral conduct that social interaction and reason generate?

It is becoming clearer and clearer that demonstrating the technological feasibility of cryonics is not sufficient for the acceptance of cryonics. There seems to be a growing consensus that “fear of the future” and lack of closure are among the biggest hurdles for giving the idea a charitable hearing.  But little thought is being given to this topic, and it is quite correct that this omission can be squarely attributed to a kind of simplistic futurism that is circulating in cryonics circles. If  even most self-identified transhumanists cannot bring themselves to make cryonics arrangements, why would one expect the rest of the population to embrace the idea?

Cryonics advocates often seem to believe that if they refute the common scientific and technical objections to cryonics (which is not that hard to do because the psychological resistance to the idea prevents critics of checking even the most basic facts about the rationale and practice of cryonics) the social and psychological reservations will take care of themselves. This is not just incorrect, such reservations are often the most fundamental.

One would be surprised if an invasive, experimental medical procedure would lack detailed information about post-procedure care, responsibilities of  the hospital and family members, and reintegration. Considering that for many people cryonics constitutes a solitary leap into an unknown and far-away future, is it reasonable that providers of such care, and advocates of cryonics, think about doing a better job of responding to these concerns. This is mostly unexplored territory because even the most alienating events in human life as we know it cannot capture this aspect of cryonics.  It is doubtful that such concerns can be removed by altering the philosophical and moral basis of cryonics.

The pursuit of cryonics as medicine

The biggest obstacle to the acceptance of cryonics is medical myopia; the idea that someone who has been pronounced dead by contemporary medical criteria will still be considered dead by future criteria. Advocates of human cryopreservation strongly argue against this. There are few things more discomforting than the idea that medical professionals of the future will look back in horror and wonder why we gave up on people who still possessed the neuroanatomical basis of their identities and memories.

But there is another kind of myopia in the public discussion of cryonics that warrants consideration. It is taken for granted by some critics of contemporary cryonics that cryonics has always been framed as a form of medicine. Nothing could be further from the truth. The history of cryonics is replete with debates between advocates of the medical model and those who believe that timely transport of the patient to a cryonics facility for low temperature storage should be adequate for future resuscitation by advanced nanotechnology. It is only because  cryonics advocates with medical and research backgrounds such as Mike Darwin and Jerry Leaf vigorously argued for adopting conventional medical techniques and protocols that today’s cryonics organizations can even be criticized  for falling short of these criteria.

There is a silver lining to a lot of the controversy that surrounds today’s cryonics . Critics now adopt the premise that cryonics is a form of medicine to make a case against practices they consider suboptimal.  It was not long ago that public critics of cryonics simply dismissed the whole idea as pseudo-science. This was never a sophisticated response but ongoing advances in cryobiology (such as vitrification of the central nervous system) and synthetic biology/nanotechnology have made this position even more of a showcase of ignorance. When people read the news about animals being cloned from straight frozen DNA they will be less receptive to tendentious claims that existing cryonics technologies are hopelessly inadequate to preserve the identity of a person.

The current development in which cryonics is being criticized from a clinical framework should have positive effects on how cryonics will be approached from a regulatory framework. It does not make sense to argue that cryonics is a pseudo-science and offering false hope but at the same time insist that cryonics organizations adopt high standards of medical care. The acceptance of the concept of “patient care” in cryonics would be incoherent without (implicitly) embracing the premise that cryonics patients have interests and deserve legal recognition of that fact. As more public information is disseminated about the quality of brain vitrification that is possible today, the need to recognize cryonics as an elective medical procedure will receive more attention from bioethicists and medical professionals.

There are those who believe that the acceptance of cryonics itself is being held back by amateurism. If this is the case there should be unexploited profit opportunities for cryonics providers that pursue the highest standards of medical care.

Revival of cryonics patients literature

There is a growing literature that discusses the technical aspects of revival of cryonics patients. The following list of the published literature was compiled by Ralph Merkle and Robert Freitas and published as an appendix of their article on molecular nanotechnology in Cryonics Magazine 2008-4:

Robert C.W. Ettinger, The Prospect of Immortality, Doubleday, NY, 1964

Jerome B. White, “Viral Induced Repair of Damaged Neurons with Preservation of Long-Term Information Content,” Second Annual Cryonics Conference, Ann Arbor MI, 11 April 1969

Michael G. Darwin, “The Anabolocyte:  A Biological Approach to Repairing Cryoinjury,” Life Extension Magazine (July-August 1977):80-83

Thomas Donaldson, “How Will They Bring Us Back, 200 Years From Now?” The Immortalist 12 (March 1981):5-10

K. Eric Drexler, Engines of Creation:  The Coming Era of Nanotechnology, Anchor Press/Doubleday, New York, 1986, pp. 133-138

Brian Wowk, “Cell Repair Technology,” Cryonics 9(July 1988)

Mike Darwin, “Resuscitation: A Speculative Scenario for Recovery,” Cryonics 9(July 1988):33-37

Thomas Donaldson, “24th Century Medicine,” Analog 108(September 1988):64-80 and Cryonics 9(December 1988)

Ralph C. Merkle, “Molecular Repair of the Brain,” Cryonics 10(October 1989):21-44

Gregory M. Fahy, “Molecular Repair Of The Brain: A Scientific Critique, with a Response from Dr. Merkle,” Cryonics 12(February 1991):8-11 & Cryonics 12(May 1991);  “Appendix B. A ‘Realistic’ Scenario for Nanotechnological Repair of the Frozen Human Brain,” in Brian Wowk, Michael Darwin, eds., Cryonics: Reaching for Tommorow, Alcor Life Extension Foundation, 1991

Ralph C. Merkle, “The Technical Feasibility of Cryonics,” Medical Hypotheses 39(1992):6-16

Ralph C. Merkle, “The Molecular Repair of the Brain,” Cryonics 15(January 1994):16-31 (Part I) & Cryonics 15(April 1994):20-32 (Part II)

Ralph C. Merkle, “Cryonics, Cryptography, and Maximum Likelihood Estimation,” First Extropy Institute Conference, Sunnyvale CA, 1994

Ralph Merkle, “Algorithmic Feasibility of Molecular Repair of the Brain,” Cryonics 16(First Quarter 1995):15-16

Michael V. Soloviev, “SCRAM Reanimation,” Cryonics 17(First Quarter 1996):16-18

Mikhail V. Soloviev, “A Cell Repair Algorithm,” Cryonics 19(First Quarter 1998):22-27

Robert A. Freitas Jr., “Section 10.5 Temperature Effects on Medical Nanorobots,” in Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999, pp. 372-375

Ralph C. Merkle, Robert A. Freitas Jr., “A Cryopreservation Revival Scenario using MNT,” Cryonics 30(Fourth Quarter 2008).

CPR and the breath of death?

And the Lord God formed man of the dust of the ground, and breathed into his nostrils the breath of life; and man became a living soul. Genesis 2:7

For breath is life, and if you breathe well you will live long on earth.  – Sanskrit Proverb

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In the Beginning…

Since the beginning of modern resuscitation over 40 years ago the sequence of interventions, and to a great extent their importance, has been determined by the ABCs of cardiopulmonary resuscitation (CPR): Airway, Breathing and Circulation. [1] Without breath there is no life and the most obviously and easily detected sign that life is fleeing is the absence of breath. What’s more, in many in whom breathing has newly ceased, simply opening the airway, or giving a single rescue breath will restore spontaneous respiration. We are told that breath is life and there is great truth in this saying.

Negative Pressure Ventilation

The physiology of the vertebrate chest is a truly amazing thing and it can take very bright men years to master its implications. One of the hardest concepts for me to grasp was that under normal conditions the pressure inside the pleural space (the space around the lungs) and the mediastinal spaces (the space that surrounds the heart and the great vessels of the chest) is always negative relative to both the atmospheric pressure and the pressure in the rest of the body (more on this later). [2] In other words, there is always a slight vacuum in those parts of the chest. Mostly this is a result of the fact that we breathe using our diaphragms and the muscles of our chest wall to create a low grade vacuum inside the chest into which air rushes via the trachea to fill our lungs.  When we relax those muscles, the natural elasticity, or recoil of the chest wall and diaphragm acts to squeeze the air out [I], and the cycle is then repeated. We thus breathe by means of negative pressure ventilation.

Naturally enough, when medicine began to try to restore breathing when it had ceased, most of the attempts that were made were attempts to simulate the natural process whereby air is moved in and out of the lungs; principally by negative intrathoracic pressure. [3]

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Above: an illustration of the Silvester method of artificial respiration circa 1880. (Silvester HR., A new method of resuscitating still-born children, and of restoring the persons apparently drowned or dead. BMJ 1858;2:576-9.)

Understandably, trying to mimic the complex action of the diaphragm and accessory muscle of the chest wall in normal negative pressure ventilation were difficult, cumbersome and often ineffective.  By 1959 rescue breathing using the mouth-to-mouth technique had become the mandated medical standard. [4]

There is no question that mouth-to-mouth resuscitation is vastly more effective than the medically endorsed methods that preceded it. What’s more, the class of ventilation to which mouth-to-mouth belongs, intermittent positive pressure ventilation (IPPV), has become essentially the only modality for assisting or replacing breathing in humans.  IPPV long ago displaced negative pressure ventilation (NPV) in the form of the iron lung and the cuirass shortly after polio was vanquished in the 1950s.

Below: Polio patients suffering from respiratory paralysis in iron lungs during an epidemic in the early 1950s.

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Below: A contemporary cuirass ventilator; this new breed of machines uses a biphasic approach that employs negative pressure on inspiration and positive pressure assisted exhalation. The Hayek biphasic cuirass ventilator is capable of  delivering higher tidal volumes (negative inspiratory tidal volume and positive expiratory tidal volume),  greatly increased frequency of ‘breaths’ from 6 to 1200CPM, and allows control of the inhalation to exhalation ratio without depending upon the passive recoil of the patient’s chest. Courtesy of United Hayek Medical: http://www.unitedhayek.com/products/mrtx

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While IPPV has many advantages over NPV, it is un-physiologic in one way that turns out to be of crucial importance in the setting of CPR. IPPV dramatically reduces the return flow of blood from the body to heart. The physics and physiology of this are complex, and even the shortest and most lucid tutorials run to many pages of text; often studded with equations and difficult to interpret graphs and charts. Among the many reasons IPPV’s effects are so complex in the human with a beating heart is that the body can respond to changes in venous blood flow, ventricular volume, and so on by dynamically adapting; heart rate can be increased, vascular tone can be altered, and even the amount of fluid retained by the body can be altered. [5]

The Danger of Positive Pressure Ventilation in CPR

For the patient in cardiac arrest none of these adaptive changes is possible. That makes discussion of the problems posed by IPPV much simpler, while at the same time making the adverse consequences more serious and potentially life threatening.

To understand why IPPV is so dangerous in the setting of CPR it is necessary to understand the concept of preload. Most simply, preload can be defined as “the load to which a muscle is subjected before shortening.” If this doesn’t leap out at as a point of great significance it is because this definition needs to be understood in connection with a physiological principle named after the two great physiologists who discovered it, the Frank-Starling Law of the Heart [II]. The Frank-Starling law of the heart (also known as Starling’s law or the Frank-Starling mechanism) states that the greater the volume of blood entering the heart during diastole (the period between cardiac contractions or the end-diastolic volume), the greater the volume of blood ejected during systolic contraction (stroke volume). This may seem pretty obvious: what you put into the heart before it contracts determines what you’ll get out of it after contraction is complete. But, as it turns out, this relationship is rather more complex than simple double entry bookkeeping would suggest.

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Above: Frank-Starling Cardiac Function Curve. Courtesy of Wikimedia Commons.

In the diagram above the Y-axis shows the cardiac output and the X-axis shows right atrial pressure. While the above diagram shows only one line, a classic Frank-Starling plot often shows three separate lines, each roughly the same shape, one atop of each other, to illustrate that shifts on the same line indicate a change in preload, while shifts from one line to another indicate a change in afterload or contractility. This allows the cardiac output to be synchronized with the venous return and with the cardiac output; without depending upon external regulation to make changes. For our purposes this diagram does the job in that it shows that the relationship between venous return from the body to the right heart has a powerful effect not only on how much the blood the heart pumps, but also on the efficiency with which it pumps that blood.

As the heart is increasingly loaded with blood it becomes better and better at pumping it out to the body (up to a point) by contracting more forcefully and emptying the cardiac chambers more completely with each heartbeat. However, as the graph also shows, there is a threshold of filling or stretching of the ventricles beyond which further filling, or preload, causes no further improvement in cardiac output and (not shown) ultimately causes a decrease in pumping efficiency with a corresponding decrease in cardiac output.

Special attention needs to be paid to the Y-axis on the graph because the huge change in cardiac output shown on X-axis happens due to a change in right atrial pressure of just 3 mm Hg, or 4.1 cm H20. [6]

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To put this change in right atrial pressure in context it is only necessary to look at the graphic above to realize that a change in pressure of 3-4 mm Hg is the maximum that occurs over the course of the whole respiratory cycle. Even more importantly, as is also illustrated above, is the seeming impossibility that the pressure inside the pleural mediastinal spaces, the latter of which which contains the heart and the great vessels, is always negative throughout the entire respiratory cycle. Put another way, the areas inside the chest that conduct blood away from and back to the heart always operate under a low vacuum: ~ -6.8 cm H2O during the height of inspiration, and ~ -2.0 cm H2O at the end of exhalation. [7] This continuous negative intrathoracic pressure serves to aid venous (and lymphatic) return from the body to the heart and thus to facilitate preload and optimize cardiac output.

By contrast, a quick glance at the graphic below, which is an actual pleural pressure tracing from a patient undergoing mechanical IPPV, shows that the thoracic viscera, including the vena cavae and right heart, are subjected to positive pressures throughout the respiratory cycle which, at their peak, are typically 30 to 40 times higher than those experienced during normal (negative) pressure breathing! In fact, the situation is even worse than it seems at first glance because not only does the intrathoracic pressure never go to zero (let alone to a negative value), it is deliberately kept positive, in this case by about 8 cm H2O. This is done because in the absence of lung expansion under the influence of the intrathoracic vacuum, the alveoli, the small air sacs of the lungs, begin to collapse and stick to each other. Collapsed alveoli are very difficult to re-open and restore ventilation to. Thus, it is necessary to keep them inflated at the end of exhalation by maintaining some positive pressure in the airways. Since this pressure is applied and maintained at the end of a breath (and between breaths) it is called positive end expiratory pressure, or PEEP, for short. [8]

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Intrapleural pressure tracing of a patient with acute respiratory distress syndrome unergoing intermittent positive pressure mechanical ventilation wih a PEEP of 8 cm H2O

The graphic below shows the effect of only 3 cm of H2O PEEP on blood flow from the head and upper body through the superior vena cava (SVC). Just 3 cm H2O of PEEP reduces superior vena cava (SVC) blood flow by 25%! [9]  A patient with a spontaneously beating heart can (and does) usually compensate for this reduction in return blood flow from the body in many ways, none of which are available to the patient in cardiac arrest.

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The effect of a 3cm H2O water change in PEEP on the flow of venous blood returning to the right heart from the upper body via the superior vena cava. [9]

During conventional closed chest CPR, or in the case of the cryonics patient cardiopulmonary support (CPS), the patient experiences truly massive increases in intrathoracic pressure that last longer and reach extremes never seen in IPPV. The largest and most deleterious source of this pressure results from the physical compression of the thoracic contents during the down-stroke of chest compressions. This raises the intrathoracic pressure to between 80 and 110 cm H2O for roughly 50% of the CPR duty cycle – in other words, the pressure inside the chest is about the same as the normal averaged (mean) blood pressure in a healthy adult for half of the time the patient is undergoing CPR/S! Added to this pressure is the additional pressure of IPPV and the PEEP (usually 5 cm H2O) required to keep the small airways open. The effects of these profoundly un-physiologic pressures on the return of venous blood to the heart and consequently on cardiac output during CPR are devastating. [10]

Overcoming Increased Intrathoracic Pressure and Preserving Cardiac Output

Following the development of active compression decompression CPR (ACD-CPR) by Cohen, et al., in 1992  [11] the critical importance of maintaining negative intrathoracic pressure during the decompression phase of the CPR duty cycle has become increasingly understood. [12, 13, 14]  There is a rapidly growing body of both animal and clinical CPR research documenting improved survival and decreased neurological morbidity when the intrathoracic pressure is kept negative during the decompression (release of chest compression) phase of CPR by the use of inspiratory impedance threshold devices, such as the ResQPod, and ACD-CPR. [15, 17, 18]  An instructive video demonstration of how the ResQPod works can be seen at: http://www.advancedcirculatory.com/

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ResQPod impedance threshold device. Courtesy of Advanced Circulatory systems, Inc. http://www.advancedcirculatory.com/

Similarly, there is accumulating evidence that the increased intrathoracic pressure that results from excessive IPPV during CPR dramatically reduces cardiac output (CO) and causes increased morbidity and mortality. [19, 20, 21].

In 2004, Yannopoulos, et al., reported the development of a device which allows for the continuous application of negative intrathoracic pressure by applying controlled suction to the airway. [22] This device combines an ITD with a vacuum source and a negative pressure regulating valve to maintain an intrathoracic vacuum of between 5 to10 mm Hg (6.8 to 13.6 cm H2O), while allowing IPPV to proceed normally. This device, called the intrathoracic pressure regulator (ITPR) allows IPPV to be delivered as needed during ACD-CPR, while maintaining negative intrathoracic pressure when PPV is not being administered. The device effectively restores the intrathoracic space to its natural state as a low negative pressure (vacuum) chamber; increasing venous return from the body and consequently increasing preload and cardiac output. The ITPR also markedly increases coronary perfusion pressure (CPP) [III] while at the same time decreasing intracranial pressure (ICP). In CPR ICP is typically elevated from the basal value of 12-16 mm Hg to 22-30 mm Hg (as the result of pressure transmission by blood in non-valved veins and by transmission of intrathoracic pressure via the cerebrospinal fluid) further compromising already inadequate cerebral perfusion. [23] Reduction of ICP during CPR has been shown to improve both survival and neurological outcome in an animal model of CPR. [24]

Prototype ITPR (Advanced Circulatory Systems, Inc.) in position in a typical bag-vale resuscitator – ET tube set-up.

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The ITPR has been shown to dramatically improve gas exchange, hemodynamics, cardiac output, vital organ perfusion, and short-term survival during ventricular fibrillation (VF) cardiac arrest in a porcine model of sudden cardiac arrest and CPR. [25] The ITPR is able to not only overcome the high intrathoracic pressures associated with CPR (45 to 55 mmHg or ~61 to 75 cmH20 [26]) but to both create and sustain negative intrathoracic pressure (determined indirectly by measuring the ET tube pressure) continuously during prolonged periods of ITPR-CPR, even in the presence of induced hypovolemia. [27]  In hemorrhaged (hypovolemic) pigs, Yannopoulos, et al., were able to sustain CPP at >15 mm Hg (the accepted threshold for successful defibrillation in human sudden cardiac arrest) and the isovolemic VF animals in the study maintained CPP at >25 mm Hg throughout the full 15 minutes of ITPR-CPR. In both groups, the ETCO2 was consistently maintained above 25 mm Hg, and the 1-hour survival was 100%, as contrasted with 10% in control animals receiving AHA standard CPR (P = 0.0001).

By comparison, after 3 minutes of conventional CPR the control animals had a mean coronary perfusion pressure of less than 15 mm Hg and all had developed pseudo-respiratory alkalosis indicative of the ventilation/perfusion mismatch of standard CPR. [28] Blood gases in VF animals were strikingly preserved during ITPR-CPR; paO2, which was 96±2 mm Hg at baseline, was 214±12.37 mm Hg after 10 min and 198±6.75 mm Hg after 15 min of ITPR-CPR. These findings would seem to suggest that ITPR-CPR may be reducing or eliminating the pulmonary edema that accompanies CPR and the high intrathoracic (and thus pulmonary arterial and venous pressures) generated during CPR.  ITPR is similarly effective at improving both hemodynamics and survival in a swine model of severe hypovolemic hypotension. [29]

The Breath of Death?

However, even with the use of the ITPR, each ventilation transiently raises intrathoracic pressure and decreases CO. In the setting of CPR/S it might be said that each breath is potentially a ‘breath of death’ in terms of its impact on perfusion.

In 2007 the author began experimenting with ways to eliminate tidal ventilation during CPR/S using simple mechanical systems to simulate the lungs and thorax. Based on this preliminary work it appears that it will be possible to eliminate tidal ventilations completely while at the same time maintaining a negative intrathoracic pressure during the non-compression portion of the CPR/S duty cycle. This is possible by the simple expedient of connecting the patient’s airway to a regulated vacuum source while at the same time delivering the desired minute volume of ventilating gas to the carina of the trachea. This scheme is illustrated in the schematic below.

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Above: Experimental implementation of continuous negative pressure ventilation in CPR/S. A conventional endotracheal tube is modified by passing a fenestrated suction catheter down the lumen to the level of the carina through a side opening in the tube through which ventilating gas is continuously delivered at the desired minute ventilation volume. Negative intrathoracic pressure and removal of waste gas is achieved by applying continuous, regulated suction to the 15 mm adapter on the end of the ET tube. Movement of gas to and from the distal airways is achieved by the action of the ACD chest compressor-de-compressor operating at 100 cycles/min on the ventral thorax.

Continuous Non-Tidal Negative Pressure Ventilation

A (negative) airway pressure regulator is attached to the 15 mm connector of a modified endotracheal tube. Continuous negative airway pressure is generated by connecting the airway pressure regulator to a vacuum/suction source. Ventilating gas of the desired composition (i.e., oxygen concentration, therapeutic additives, etc.) is continuously delivered to the patient’s lungs by a ventilation gas delivery catheter that can be advanced or withdrawn through the lumen of the ET tube. The ideal position for the ventilation gas delivery catheter is at the point where the trachea bifurcates into the main-stem bronchi; the carina. Movement of the ventilating gas to the distal airways is achieved by the dynamically varying force on the chest resulting from cardiac compressions, with or without  active decompressions. The desired minute volume is determined by the flow rate of ventilating gas delivered to the carina.

In cases where pulmonary edema is preventing adequate gas exchange and it is deemed necessary to apply positive intrathoracic pressure (at the expense of cardiac output) it is easy to do this by adjusting the pressure on the airway pressure regulator to the desired positive pressure setting; as would be done with the application of positive end expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) as is done for the treatment of pulmonary edema by a different means with the Boussignac tube. [30, 31]

breath11

The illustration above shows a possible configuration of a dual-lumen endotracheal tube that would accomplish continuous non-tidal negative pressure ventilation in conjunction with an attached airway pressure control valve.

breath12

Prototype Active Comnpression-Decompression square-wave HLR constructed to the author’s specifications by Michigan Instruments, Inc., of Grand Rapids, MI. The device incorporates a continuous ventilation gas flow meter (red arrow) which allows for delivery of air blended oxygen at the desired oxygen concentration and minute volume.

In 1996 a prototype heart–lung resuscitator capable of delivering non-tidal continuous negative pressure ventilation in conjunction with ACD-square wave-CPR was fabricated by Michigan instruments of Grand Rapids, MI (shown above). Unfortunately, this device was never evaluated in a canine or porcine model of CPR in cardiac arrest. Bench testing with a sophisticated test lung did demonstrate that the unit could deliver adequate minute ventilation while maintaining operator specified negative (or positive) intrathoracic pressure throughout the decompression phase of the CPR/S duty cycle.

If animal research confirms that this mode of ventilation (which is an extension of the ITPR) is both safe and effective it should be possible to apply it to cryonics patients without the years-long wait for regulatory approval. In the case of CPR in the clinical environment, non-tidal continuous negative pressure ventilation using this scheme will likely remain one of the many intriguing and potentially useful ideas in CPR that await another time and place, or perhaps more accurately, a different universe in order to find application.

The End of the Thumper Era?

With clinical advent of ACD-CPR, and the experimental debut of the ITPR and negative intrathoracic pressure CPR delivered via the trachea, it would seem that the days of the Michigan Instruments, Inc. (MII) Thumper CPR devices, which have been the dominant technology used in cryonics transport operations, are over. Despite the very low cost of used Thumper HLRs ($150 to $500 US) the capability of doubling or trebling cardiac output (and sometimes quadrupling cerebral blood flow during CPR) would seem to mandate the expense of either custom fabricated MII equipment, or purchase of a  LUCAS or LUCAS 2 device ($20,000 US).

However, the reality is that the ITPR offers the older generations of conventional CPR machines a new lease on life. The raison d’être for ‘suction cup’ CPR is to create negative intrathoracic pressure by forcefully pulling up on the ventral chest wall between compressions. This method of creating negative intrathoracic pressure was developed as a consequence of the case of a successful resuscitation from cardiac arrest having been carried out by a layman using a lavatory toilet plunger; not as a result of systematic academic or medical laboratory investigation. [32]

It is the principle that is important, and in this case the principle is negative intrathoracic pressure; something that can be applied by surrounding the thorax with a vacuum in a cuirass, or by using a suction cup to decompress the chest wall. Importantly, it can also be accomplished by the ITPR and without the use of complex pneumatic or electromechanical machinery to move a suction cup to and fro. [IV] The ITPR and continuous negative pressure ventilation suggest a number of novel ways that may allow for the continued use of costly first and second generation mechanical CPR equipment – perhaps with even greater efficacy than is possible with the latest generation HLRs. But, alas, that is a subject for another article.

REFERENCES

1) Eisenberg MS., Cardiac Arrest. The science and practice of resuscitation medicine. In: Paradis NA, Halperin HR, Nowak RM, editors. The quest to reverse sudden death: a history of cardiopulmonary resuscitation. Baltimore: Williams and Wilkins; 1996.

2) West, JB., Pulmonary Physiology and Pathophysiology, Lippincott Williams & Wilkins, Philadelphia, 2000.

3) Baskett, FF., The Holger Nielsen Method of Artificial Respiration Resuscitation (2007) 74, 403-405.

4) Acierno LJ, Worrell LT., Peter Safar: father of modern cardiopulmonary resuscitation. Clin Cardiol. 2007 Jan;30(1):52-4.

5) Luecke , T, Pelosi, P., Clinical review: Positive end-expiratory pressure and cardiac output. Critical Care 2005, 9:607-621 (DOI 10.1186/cc3877).

6) JE, A.D., Carlson CJ, et al., Continuous positive-pressure ventilation decreases right and left ventricular end diastolic volumes in the dog. Circ Res, 1980. 46: p. 125-132.

7) West, JB., Pulmonary Physiology and Pathophysiology, Lippincott Williams & Wilkins, Philadelphia, 2000.

8) Acosta, E, Varon, S. The Use of Positive End-Expiratory Pressure in Mechanical Ventilation. Critical Care Clinics, Volume 23, Issue 2, Pages 251-261.

9) de Waal, KA, Evans, N. Osborn, DA, Kluckow , K, Cardiorespiratory effects of changes in end expiratory pressure in ventilated newborns. Arch Dis Child Fetal Neonatal Ed 2007;92:F444–F448. doi: 10.1136/adc.2006.103929.

10) Jellinek, H., Krenn, H, Oczenski, W, et al., Influence of positive airway pressure on the pressure gradient for venous return in humans. J Appl Physiol, 2000. 88: p. 926-932.

11)  Cohen, T., Tucker, KJ, Redberg, RF, Lurie, KG, Chin, MC, Dutton, JP, Scheinman, MM., Active compression-decompression resuscitation: a novel method of cardiopulmonary resuscitation. Am Heart J, 1992. 124: p. 1145-50.

12) Jellinek, H., Krenn, H, Oczenski, W, et al., Influence of positive airway pressure on the pressure gradient for venous return in humans. J Appl Physiol, 2000. 88: p. 926-932.

13) Aufderheide, T., Sigurdsson, G, Pirrallo, RG, et al. , Hyperventilation-induced hypotension during cardiopulmonary resuscitation. Circulation, 2004. 109: p. 1960-1965.

14) Cheifetz, I., Craig, DM, Quick, G, et al., Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model. Crit Care Med, 1998. 26: p. 710-716.

15) Cabrini, L., Beccaria, P, Landoni, G, Biondi-Zoccai, GG, Sheiban, I, Cristofolini, M, Fochi, O, Maj, G, Zangrillo, A., Impact of impedance threshold devices on cardiopulmonary resuscitation: a systematic review and meta-analysis of randomized controlled studies. Crit Care Med, 2008. 36: p. 1625-32.

16) Plaisance, P., Lurie, K, Payen, D., Inspiratory impedance during active compression decompression cardiopulmonary resuscitation: a randomized evaluation in patients in cardiac arrest. . Circulation, 2000. 10: p. 989-994.

17) Wolcke, B., Mauer, DK, Schoefmann, MF, Teichmann, H, Provo, TA, Lindner. KH, Dick WF, Aeppli D, Lurie KG., Comparison of standard cardiopulmonary resuscitation versus the combination of active compression-decompression cardiopulmonary resuscitation and an inspiratory threshold device for out-of-hospital cardiac arrest. Circulation, 2003. 108: p. 2201-2205.

18)  Lurie, K., Voelckel, W, Plaisance, P, et al., Use of an inspiratory impedance threshold valve during cardiopulmonary resuscitation: A progress report. Resuscitation, 2000. 44: p. 219-30.

19) O’Neil, J., Deakin, CD., Do we hyperventilate cardiac arrest patients? Resuscitation, 2007. 73: p. 82-85.

20) Chandra, N.C., et al., Observations of hemodynamics during human cardiopulmonary resuscitation. Crit Care Med, 1990. 18: p. 929-34.

21) Aufderheide, T., Lurie, KG., Death by hyperventilation: A common and life-threatening problem during cardiopulmonary resuscitation. Crit Care Med, 2004. 32(No. 9 (Suppl.)): p. S345–S351.

22) Yannopoulos, D., Nadkarni, VM, McKnite, SH, Rao, A, Kruger, K, Metzger, J, Benditt, D, Lurie,KJ., Intrathoracic pressure regulator during continuous-chest-compression advanced cardiac resuscitation improves vital organ perfusion pressures in a porcine model of cardiac arrest. Circulation, 2005. 112: p. 803-81.

23) Guerci, A., Shi, AY, Levin, H, Tsitlik, J, Weisfeldt, ML, Chandra, N., Transmission of Intrathoracic Pressure to the Intracranial Space during Cardiopulmonary Resuscitation in Dogs. Circ Res, 1985. 56: p. 20-30.

24) Srinivasana, V., Nadkarnia, VA, Yannopoulosb, D, Marinoa, BS, Sigurdssonc, G,  McKnitec, SH, Zookc, M, Bendittc, DG, Lurie, KG., Spontaneous gasping decreases intracranial pressure and improves cerebral perfusion in a pig model of ventricular fibrillation. Resuscitation, 2006. 69: p. 329-334

25) Yannopoulos, D., Nadkarni, VM, McKnite, SH, Rao, A, Kruger, K, Metzger, J, Benditt, D, Lurie,KJ., Intrathoracic pressure regulator during continuous-chest-compression advanced cardiac resuscitation improves vital organ perfusion pressures in a porcine model of cardiac arrest. Circulation, 2005. 112: p. 803-81.

26) Chandra, N.C., et al., Observations of hemodynamics during human cardiopulmonary resuscitation. Crit Care Med, 1990. 18: p. 929-34.

27) Lurie, K., Zielinski, T, Voelckel, W, et al., Augmentation of ventricular preload during treatment of cardiovascular collapse and cardiac arrest. Crit Care Med 2002. 30: p. (Suppl):S162-5.

28) Weil, M., Rackow, EC, Trevino, R, Grundler, W, Falk, JL, Griffel, MI., Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med, 1986. 315: p. 153-156.

29) Sigurdsson, G., Yannopoulos, D, McKnite, S, et al., Lowering of intrathoracic pressure improves blood pressure and survival rates in a porcine model of hemorrhagic shock. Resuscitation, 2006. 68: p. 399-404.

30) Srinivasana, V., Nadkarnia, VA, Yannopoulosb, D, Marinoa, BS, Sigurdssonc, G,  McKnitec, SH, Zookc, M, Bendittc, DG, Lurie, KG., Spontaneous gasping decreases intracranial pressure and improves cerebral perfusion in a pig model of ventricular fibrillation. Resuscitation, 2006. 69: p. 329-334.

31) Weil, M., Rackow, EC, Trevino, R, Grundler, W, Falk, JL, Griffel, MI., Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation. N Engl J Med, 1986. 315: p. 153-156.

32) Leman P, Greene S, Whelan K, Legassick T., Simple lightweight disposable continuous positive airways pressure mask to effectively treat acute pulmonary oedema: Randomized controlled trial. Emergency Medicine Australasia, 2005. 17 p. 224 – 230.

33) Templier F, Dolveck F, Baer M, Chauvin M, Fletcher D., ‘Boussignac’ continuous positive airway pressure system: practical use in a prehospital medical care unit. Eur J Emerg Med, 2003. 10 P.87-93.

34) Malzer R, Zeiner A, Binder M, Domanovits H, Knappitsch G, Sterz F., Laggner AN. Hemodynamic effects of active compression-decompession after prolonged CPR Resuscitation, Volume 31, Issue 3, Pages 243-253

[I] While most exhalations are passive and do not require muscular  assistance, we do sigh, cough and sometimes forcibly assist air out of our lungs and these instances of assisted exhalation are important to health.

[II] The German Otto Frank and Briton Ernest Starling.

[III] In the setting of resuscitation from cardiac arrest as opposed to CPS in cryonics Transports, the  coronary perfusion pressure during CPR  is the single most important predictor of successful defibrillation and thus of successful  resuscitation.

[IV] It is important to note that this applies only in situations where the chest still possesses its basic structural integrity. In cases of rib fracture or ‘flail chest’ where the thorax has lost its rigidity, only ACD-CPR or the application of an integrated chest compressor and cuirass device would be effective in generating blood flow.

ACD-CPR & the rise of the machine?

If conventional cardiopulmonary support (CPS) in cryonics is difficult to perform adequately, and impossible to sustain for more than brief periods (30-60 min) before exhausting even a 3-man standby team, this is even more the case for active compression-decompression CPS (ACD-CPS) using the ResQPump (formerly the Ambu CardioPump). Even in the conventional medical setting of comparatively brief periods of CPR before defibrillation ACD-CPR is difficult to do, let alone do well. Indeed, if ACD-CPR (in conjunction with an impedance threshold device such as the ResQPod) continues to show superior results in terms of outcome (as it is now doing in recent and ongoing clinical trials) it may be the advance that makes heart-lung resuscitators both medically acceptable and cost effective. There is some evidence that this may actually be happening; while not yet profitable, the LUCAS CPR device is gaining in popularity and continues to be the subject of consistently favourable laboratory and clinical studies.

Currently, mechanical CPS is viewed by paramedical personnel as not just dangerous (i.e., the myth of routinely broken ribs and lacerated lungs and livers) but also as ineffective and, perhaps just as importantly, as a potentially professionally demeaning or threatening piece of technology. In my 30 years of experience interfacing with EMTs and paramedics in both the US and UK regarding mechanical CPR, the most frequent remark I’ve heard is, “I can do better CPR than that machine can.” Since CPR is the most dramatic, and arguably one of the most defining practices in emergency medicine, it is perhaps understandable that many emergency medical system (EMS) personnel will equate replacement of manual CPR as equivalent to replacement of the people who perform it. Many paramedics perceive the heart-lung resuscitator (HLR) as a device that will make high quality CPR something anyone can do ‘with the push of a button.’

1

In reality, deploying and applying even the most automated and technologically sophisticated HLRs will require more skill and expertise on the part of EMS personnel, not less.

Mechanically delivered ACD-CPR is also more effective than conventional mechanical CPR, even when delivered per the new AHA standards. As an example, coronary and cerebral blood flows during LUCAS CPR are improved by 25-30% over those obtained with the Michigan Instruments Thumper HLR.

2

Steen S, Liao Q, Pierre L, Paskevicius A, Sjöberg T. “Evaluation of LUCAS, a new device for automatic mechanical chest compression and active decompression for cardiopulmonary resuscitation.” Resuscitation. 2002; 55: 289-299.

3

Rubertsson S, Karlsten R. “Increased cortical cerebral blood flow with LUCAS, a new device for mechanical chest compressions compared  to standard external compressions during experimental cardiopulmonary resuscitation.” Resuscitation 2005; 65: 357-363

But of even greater interest in the context of cryopatient Transport is the dramatic improvement in the durability of perfusion being demonstrated with ACD-CPR using the LUCAS, as opposed to what can be achieved with conventional CPR. While mean arterial pressure (MAP) and cardiac output (CO) are often adequate to maintain cerebral viability during the first minute or two of chest compressions, they rapidly fall to levels that are inconsistent with survival thereafter. Deterioration of cardiac preload, rapid and progressive loss of chest wall elasticity (and thus recoil) and possibly elevated intrathoracic pressure from ‘auto-PEEP’ (gas trapping at the end of expiration and dynamic hyperinflation of the lungs) all likely contribute to the rapid decay in mean arterial pressure (MAP) and perfusion seen in conventional CPR.

4

ACD-CPR using the LUCAS preserves MAP and perfusion, even during prolonged CPR; in one case up to 240 minutes. The representative waveforms above are from LUCAS CPR performed on 13 patients who experienced cardiac arrest during cardiac catheterization and who underwent CPR for times ranging from 45 to 245 minutes. Mean systolic and diastolic blood pressure were 81±23 and 34±21 mmHg, respectively; pressures fully compatible with preservation of brain viability and long-term survival.

Compressed Gas Bottles & the Autopulse

Aside from the problem of interrupting CPR while HLRs are applied, and the historically complex and clumsy nature of the devices, the other major barrier to the use of mechanical CPR has been the need for a bulky and heavy supply of compressed gas to power the devices. Typically, two E-cylinders containing 640 liters of oxygen or air will run an HLR for only 15 to 20 minutes. This is a major logistic hurdle in conventional emergency medicine which becomes far more serious in the setting of cryopatient Transport. Oxygen (compressed or in chemical form in ‘oxygen generators’ of the type used in commercial jetliners) cannot be transported on commercial aircraft nor shipped by common carrier because of the hazard it represents. As a result, cryonics Standby/Transport teams must find a way to acquire compressed gas immediately upon landing – something that is becoming increasingly difficult since the advent of electrically powered oxygen concentrators which have largely eliminated the need for 24/7 home delivery of oxygen in high pressure cylinders.

One solution to this problem was the development of the Autopulse (Zoll Medical Corporation) which is a battery powered HLR that delivers vest CPR. While vest CPR has been shown to be superior to conventional CPR in some studies, it lacks the ability of ACD-CPR to dramatically reduce intrathoracic pressure and to maintain MAP and CO during long duration CPR. An additional problem with the Autopulse for cryonics is that the device contains the electronics; control circuitry, motors and associated mechanical devices used to power and operate it which are located in the backboard that the patient rests upon.

5

Since cryopatients are immersed in ice water, this means that the device must be extensively re-engineered for this application. Suspended Animation, Inc., of Boynton Beach, FL has reportedly developed such a portable ice bath (PIB) compatible Autopulse which they have patented and plan to market to the cryonics community at a considerable mark-up over the Autopulse’s already high retail price of ~$20,000. Another problem facing the Autopulse is the increasing gap in the quantity and quality of both the published animal and human clinical research between the Autopulse and ACD-ITD-CPR. The strong selling point of the Autopulse has been its ability to operate on compact batteries for up to 20 minutes with the ability to rapidly and easily change out batteries without any interruption in CPR.

I Sing the LUCAS Electric!

A few months ago, LUCAS announced what has certainly been a long and desperately desired advance in HLR technology – in and out of the cryonics community. LUCAS is now marketing the LUCAS 2, which is a completely battery powered version of their pneumatically driven LUCAS 1 machine.

6

This second generation LUCAS uses the basic, the well-proven LUCAS 1 platform, with a number of potentially critical added improvements. In addition to using microprocessor controlled electronic actuators, the device contains a ventilation reminder; with plans to allow interface of the device to a sophisticated, compact ventilator in the near future. Most importantly, the LUCAS 2 operates for 45 minutes on the on the newly available lithium ion polymer (LiPo ) battery technology (with no test-cycles or reconditioning required) and may also be connected to and operated from electrical power points (wall outlets) or car outlets. The battery is neatly integrated in the hood of the HLR and it can easily and rapidly be changed out, making the LUCAS 2 a lightweight and compact device to store and carry (17 kg, complete).

7

Incredibly important to cryonics operations is the fact that the device uses a softer start during the initial adjustment to the patient’s chest, and is much quieter when in operation. This latter consideration is of critical importance in institutional settings where the noise generated by pneumatically driven HLRs has resulted in significant resistance (and even refusal to allow their use in a few cases) on the part of hospital, extended care facility, and hospice administrators. The LUCAS 2 should go a long way towards overcoming this problem since the noise level is actually less than that often encountered when conventional manual CPR is administered.

8

The LUCAS user interface remains very simple with fingertip access to all operating modes and 3-step, 3-button actuation. Delightfully, the LUCAS 2 can operate from wall current (100-240V / 50/60 Hz) or from an automobile car outlet (12-24V); if the engine is running to power the vehicle alternator, the unit can operate from the vehicle power supply indefinitely (or as long as the petrol supply lasts)!

Whatever happened to the future of medicine

Source: ExtroBritannia

Why the much anticipated medical breakthroughs of the early 21st century are failing to materialize

Saturday 30th May 2009, 2pm-4pm. Room 403 (fourth floor), Birkbeck College, Torrington Square, London WC1E 7HX. There’s no charge to attend, and everyone is welcome.

Speaker

Mike Darwin has 30 years experience in cutting edge medical research. Co-founder of the Institute for Advanced Biological Studies, 1977. President of Alcor Life Extension 1983-1988, Research Director 1988-1992. Described by Wikipedia as “Second only to Robert Ettinger as one of the most influential figures in the controversial field of cryonics”

Description of talk

The last half of the 20th Century was a time of explosive growth in growth in high technology medicine. Effective chemotherapy for many microbial diseases, the advent of sophisticated vaccination, the development and application of the corticosteroids, and the development of extracorporeal and cardiovascular prosthetic medicine (cardiopulmonary bypass, hemodialysis, synthetic arterial vascular grafts and cardiac valves) are but a few examples of what can only be described as stunning progress in medicine derived in large measure from translation research.

The closing decades of the last century brought confident predictions from both academic and clinical researchers (scientists and physicians alike) that the opening decade of this century would see, if not definitive cure or control, then certainly the first truly effective therapeutic drugs for cancer, ischemia-reperfusion injury (i.e. heart attack, stroke and cardiac arrest), multisystem organ failure and dysfunction (MSOF/D), immunomodulation (control of rejection and much improved management of autoimmune diseases), oxygen therapeutics and more radically, the perfection of long term organ preservation, widespread use of the total artificial heart (TAH) and the clinical application of the first drugs to slow or moderate biological aging.

However, none of these anticipated gains has materialized, and countless drug trials in humans based on highly successful animal models of MSOF/D, stroke, heart attack, cancer, and immunomodulation have failed. Indeed it may be reasonably argued that the pace of therapeutic advance has slowed. By contrast, the growth of technology and capability in some areas of diagnostic medicine, primarily imaging, has maintained its exponential rate of growth and, while much slower than growth in other areas of technological endeavor, such as communications and consumer electronics, progress has been impressive.

Why has translational research at the cutting edge of medicine (and in particular in critical care medicine) stalled, or often resulted in clinical trials that had to be halted due to increased morbidity and mortality in the treated patients? The answers to these questions are complex and multifactorial, and deserve careful review.

Renewed success in the application of translational research in humans will require a return to the understanding and acceptance of the inescapable fact that perfection of complex biomedical technologies cannot be modeled solely in the animal or computer research laboratory. The corollary of this understanding must be the acceptance of the unpleasant reality that perfection of novel, let alone revolutionary medical technologies, will require a huge cost in human suffering and sacrifice. The aborted journey of the TAH to widespread clinical application due to the unwillingness on the part of the public, and the now extant bioethical infrastructure in medicine, to accept the years of suffering accompanied by modest, incremental advances towards perfection of this technology, is a good example of what might rightly be described as a societal ‘failure of nerve’ in the face of great benefit at great cost. It may be rightly said, to quote the political revolutionary Delores Ibarruri, that we must once again come to understand that, “It is better to die on our feet than to live on our knees!”

Pre-meeting and post-meeting activities

Why not join some of the UKTA regulars for a drink and/or lunch any time after 12.30pm, in The Marlborough Arms, 36 Torrington Place, London WC1E 7HJ. To find us, look out for a table where there’s a copy of James Halperin’s book “The First Immortal” displayed. (This book is a well-researched and thought-provoking novel about cryonics.)

Discussion is likely to continue after the event, in a nearby pub, for those who are able to stay.

Room 403 is on the fourth floor (via the main lift) in the main Birkbeck College building, in Torrington Square (which is a pedestrian-only square). Torrington Square is about 10 minutes walk from either Russell Square or Goodge St tube stations.