X-Message-Number: 5983
Date: Sat, 23 Mar 1996 16:32:36 -0500 (EST)
From: Charles Platt <>
Subject: Bulletin from Mike Darwin

A Bypass On The Way to Bypass 

by Mike Darwin 

Introduction: The Problem 

One of the most frustrating problems in cryonics is the 
limitation that the procedure cannot start until legal death 
has been pronounced.  Even the recent Circuit Court decision 
ruling on the legality of assisted suicide does not alter the 
situation in this regard; whatever the "cause" and whatever 
the "mode"  of death, cardio-respiratory arrest, legal death, 
_must_ have occurred before cryopreservation procedures can 

There are, additionally, some reasons why, at least for the 
foreseeable future, cryonics organizations and their clients 
may want it to remain this way.  Chief amongst these reasons 
is the regulatory burden associated with procedures that 
would be considered under the "aegis" of medicine.  Any 
procedure done on a patient before legal death would 
certainly be considered a medical procedure -- even if such a 
procedure were to result in the patient's death.  An 
unfortunate corollary of this is that the full weight and 
force of the medical-industrial-regulatory-complex would come 
to bear on that part of the cryopreservation process carried 
out before legal death is pronounced.  In effect, this would 
be tantamount to a prohibition on the use of these 

Thus, patients confronting cryopreservation are still faced 
with the necessity of experiencing a period of cardio-
respiratory arrest before the procedure can begin, and this 
situation is unlikely to change in the foreseeable future. 

In practical terms what this means is the following: 

1) All cryonics patients will experience some period of 
interruption of blood flow to their brains (cerebral 

2) Methods used to restore blood flow and oxygenation must 
not result in return of spontaneous cardiac or respiratory 
activity in effect reversig clinical and thus _legal_ death. 

3) Currently, the best methods available for restoring blood 
flow after legal death that meet the criteria set forth in 2) 
above, are either very poor at restoring adequate circulation 
(CPR) or require a significant time-delay to implement 
(cardiopulmonary bypass; i.e., use of a blood pump and 
"artificial lung" to move and oxygenate blood). 

Of course, in many cases the patient will not be experiencing 
legal death under the controlled conditions allowed for in 
the scenario of medically assisted suicide many cryonicists 
envision as ideal.  Many patients will not choose active 
euthanasia, or will not be candidates for it (i.e., it will 
not be at all certain that the outcome of their medical 
crisis is a terminal one until such time as heartbeat and 
breathing cease, and resuscitation attempts are deemed futile 
or fail).  Many patients, even those dying or known to be at 
high risk of dying, will experience sudden de compensations 
and die with little or no opportunity for complex 
preparations  (both in terms of personnel and equipment) for 
cardiopulmonary bypass. 

The Most Desired Solution to The Problem 

Ideally, what is needed is a way to restore circulation and 
breathing in such patients _acutely_; immediately after 
pronouncement of legal death, in an efficient manner, which 
allows for cooling, oxygenation and blood circulation at 
rates of efficiency achievable with bypass, in a simple, 
straightforward and inexpensive way. To put it another way, 
we need a way to provide rapid cooling and circulatory 
support in cryopatients that can be applied by anyone with 
paramedic-level, or perhaps EMT-level training, with not much 
added training needed beyond that required to use the 
equipment currently used to achieve these ends during the 
transport of today's cryopatients (i.e., mechanical CPR using 

This is a tall order, and one which has occupied significant 
BPI and 21st research effort for the past two years.  The 
solution to this problem would, of course, result not only in 
tremendous potential benefit to cryopatients, but also to 
many other people who experience sudden cardiac death from 
heart attack, electrocution, drowning, and other causes, and 
who could similarly benefit from rapid induction of 
hypothermia _and_ efficient CPR. 

A little over two years ago, Mike Darwin came up with an idea 
that had the promise to solve this problem.  It would have 
all the necessary elements discussed above, and then some.  
It would be: 

*Easy to apply, requiring far less highly skilled personnel 
than are needed for bypass 

*Technically less demanding, requiring _fewer_ total 
personnel than bypass 

*Effective at achieving a rate of heat exchange in the brain 
comparable to or _better_ than that achievable with bypass 

*Effective at achieving good gas exchange even patients with 
severe lung disease/injury (pulmonary edema, Adult 
Respiratory Distress Syndrome (ARDS), space occupying lesions 
of the lungs such as tumor, etc.) 

*More effective than conventional closed-chest CPR at 
delivering good good flow 

*Relatively inexpensive to use 

While this technology would not replace bypass in ideal 
scenarios of patient transport, it could as a minimum act as 
a far more efficient bridge to it than do conventional 
transport techniques, and in those cases where bypass was not 
possible, this modality _would_ be available to insure rapid 
cooling and allow for prompt transport of the patient either 
to a facility where blood washout was possible, or to the 
facilities of the cryonics organization for definitive 
stabilization (cryoprotective perfusion and 

Well, what is this idea, how workable is it, and how soon 
will be available?  The answer to the first two questions is 
comparatively easy and straightforward, the answer to the 
third question is a little less definite. 

The Idea 

The idea for this technology came about from making the 
following simple observations: 

1) _All_ of the blood that flows out from the heart to the 
various organs of the body flows through the lungs first, 
where it is oxygenated and carbon dioxide is removed. 

2) The lungs are soft, compliant sacks which are easily 
compressed during CPR and act to absorb a lot of the 
mechanical energy or "pumping" force exerted during the 
downstroke of compression on the chest. 

3) Air, oxygen, and other gases make terrible heat exchange 
media;  since they are roughly a thousand times less dense 
than water, they will remove heat at only roughly one 
thousandth the rate! 

The Solution to the Problem 

With a little further thought it becomes apparent that the 
thing to do is _get rid of the gas_ in the lungs and replace 
it with fluid.  Preferably a fluid that could deliver oxygen 
and carbon dioxide as well as or better than air--or even 
high concentration oxygen. It would also be desirable if this 
fluid were nontoxic, and if it were not soluble in water, or 
in fats, so that it would not get into the tissues.  It 
should also be a reasonably good heat transfer medium.  
Ideally, it should be possible to fill large mammals' lungs 
with this fluid  (such as dogs) and have them recover 
uneventfully after being ventilated with it for an extended 
period of time.  

To summarize, the _simple_ answer to the problem of efficient 
gas exchange, rapid cooling, and improved hemodynamics during 
CPR is _liquid ventilation._ 

Initially, when we began this work, we started with 
hemoglobin solutions.  There were many problems with this 
approach which neither time nor space will permit discussion 
of here; and we knew such problems would occur.  The 
important thing was that this early work (conducted starting 
two years ago) established the feasibility of liquid 
ventilation in achieving the rates of cooling and increase in 
mean arterial pressure and cardiac output in CPR that were 
needed for both cryonics and non cryonics applications. 

We then looked to perflurodecalin and mixtures of other 
flurocarbons such FX-80, the breathing medium used by Leland 
Clark and his associates in the late 1960's. Clark and his 
colleagues were able to briefly keep mice alive, submerged 
and breathing in FX-80 until they died from exhaustion from 
the increased work of breathing _and hypothermia._  However, 
the physical characteristics of this agent including its 
viscosity, spreading coefficient, and relatively poor gas 
transfer capabilities (as well as its long-term pulmonary 
toxicity) made it an unacceptable choice. 

A great deal of time and effort has been focused on 
developing a suitable working fluid and developing a usable, 
simple technique for applying total liquid ventilation in the 
setting of cryonics transport.  These problems have now 
largely been solved. 

A proprietary working fluid that results in long term 
survival of animals ventilated with it has been found by BPI 
and 21st Century Medicine.  Just as importantly, a way of 
using this fluid has been developed.  Two ways in fact. 

The one which will be discussed here is simple, 
straightforward and, we believe, very elegant. It is called 
sweep flow total liquid ventilation (SFTLV). It works as 
follows.  A large tube is placed in the patient's windpipe 
(trachea) by either endotracheal intubation (passage of the 
tube down the mouth and into the trachea past the vocal 
cords) or preferably by tracheotomy (wherein the trachea is 
surgically opened through the skin of the neck and a tube 
placed directly in it). 

The tube used for liquid ventilation using this technique 
differs from a conventional tracheal tube in several ways.  
First, it is a double-lumen tube; in other words one tube 
inside the other.  The "inside"  tube extends beyond the tip 
of the "outside" tube by about 15 mm.  Second, the lower 
2/3rds of the outside tube has numerous holes or 
fenestrations in it, from the point where the end of the tube 
is positioned (at a level just above the location where the 
trachea divides into the two main-stem bronchi [the carina]) 
to the point on the outer tube where a balloon is inflated to 
prevent the liquid ventilating medium from escaping in any 
space between the tube and the trachea. The smaller, inner 
tube is connected to a reservoir-pump-oxygenator-heat 
exchanger assembly (the liquid ventilator) and carries 
oxygenated and chilled liquid breathing media down the tube 
where it is delivered into the trachea at a point just above 
that of the carina.  The larger outer tube picks up the fluid 
from the trachea and returns it (under gravity or pump 
assisted flow) to the reservoir. (See Illustrations 1 and 2). 

When this system was first developed we were focused on 
mimicking the normal process of breathing: inspiration and 
expiration.  We soon found this problematic.  While it was 
possible to successfully meet the gas exchange demands of an 
animal in this fashion, we were limited on  our ability to 
carry out heat exchange, and the control of inhalation and 
exhalation of the liquid was demanding and equipment-
intensive.  Due to the very high viscosity of liquid, as 
compared to air or other gases, we were constrained to limit 
the number of ventilations to no more than 5 to 7 per minute  
(normal is 12 for air) and the total flow rate of liquid in 
and out of the lungs to no more than  2000 ml/min for an 
average adult (65 kg) (a comparable normal tidal volume in 
air would be about 4200 ml/min).  While these tidal liquid 
volumes and ventilation frequencies provide adequate gas 
exchange, they limit us undesirably on heat exchange.  This 
is particularly the case because the liquid breathing medium 
we are using, CryoVent (TM, BPI) carries only about a quarter 
of the amount of heat per unit volume as does water. 

The solution to this problem was to use a "sweep flow" 
system, wherein CryoVent is continuously pumped into the 
trachea at relatively high flows (about 4-6 liters per 
minute) and continuously returned to the oxygenator-heat-
exchanger.  Movement or exchange of chilled, oxygen rich 
CryoVent from the large aiways (the trachea and bronchi) to 
the small airways (the alveoli) where gas and heat exchange 
takes place is achieved by the use of Active Compression 
Decompression CPR (ACD-CPR) (with or without a high impulse 
component to the wave of force delivered to the chest on 
downstroke).  Thus, each up stroke of the suction-cup plunger 
on the ACD-CPR machine pulls chilled oxygen rich liquid into 
the alveoli of the patient's lungs (See Illustration 3)  This 
means, in effect, that the patient is ventilated not once 
every 5 chest compressions with gas as in conventional CPR, 
or once every 12-14 compressions with conventional "tidal-
volume" (inspiration-expiration) liquid ventilation, but 
rather _after, or rather during, each  upstroke and 
downstroke of CPR!_ 

Thus, the large airways serve as a reservoir, or sump, of 
chilled, oxygenated fluid which is rapidly changed out during 
each upstroke and down stroke of ACD-CPR.  The sump is kept 
"fresh" by the fast flow or "sweep" of chilled oxygenated 
CryoVent through the large airways. 

This system is highly effective at facilitating rapid cooling 
and good gas exchange even when used without external (ice 
water immersion) cooling and colonic and peritoneal lavage 
with cold solutions.  It is _much_ more effective when 
combined with them.  Indeed, we anticipate being able to 
achieve cooling rates in the average adult male (65 kg) of 
1.5 to 2.0 C/min!  The solubility of oxygen in CryoVent at 
both 0 C and 25 C is approximately 50 ml/100 ml..  The 
solubility of carbon dioxide is over three times that of 
oxygen at room temperature; 170 ml/100 ml of CryoVent, and 
roughly four times that of oxygen at 0 C; or, 200 ml/100 ml 
of CryoVent.  The use of the sweep flow system greatly 
improves the rate of heat exchange, indeed, even the CryoVent  
liquid _not_ moved in and out of the alveoli still 
contributes powerfully to heat exchange by cooling the large 
airways and the rich supply of blood which flows both into 
and out of the lungs adjacent to them (the hilar arteries and 

The efficacy of ACD-CPR at circulating blood is also greatly 
increased due to the vast reduction in lung compliance 
associated with replacing the normally present gas with 
liquid.  The underlying biomechanics of this is shown in 
Illustration 4, where the compliance curve for both the air 
and CryoVent  filled lung are shown.  As can be seen, air is 
far more compliant than CryoVent and the lung thus dissipates 
energy, or "compresses" when it is squeezed, decreasing the 
pressure or pumping force delivered to the heart and large 
blood vessels of the chest, the so called "thoracic pump" of 

As in the film THE ABYSS, the answer is to replace the gas 
with liquid, albeit for different reasons.  The solution is 
just that simple. 

Unexpected Benefits 

An unexpected benefit of CryoVent was its ability to rapidly 
and effectively restore gas exchange in the wet edematous 
lung.  On X-ray, it first appeared as though CryoVent was 
reversing pulmonary edema and re-inflating liquid filled lung 
within minutes of being given down the endotracheal tube!  It 
took us quite a little while to understand what was 
happening.  The clue came from the pioneering work of an 
Italian Intensivist by the name of Gattinoni (Anesthesiology  
1991;74:15-29).  What Gattinoni discovered was that when 
patients were turned prone the "water-logged" or consolidated  
"dependent" part of the lung quickly moved from the lower 
lobes on the posterior side, to the newly dependent anterior 
part of the lung lobes.  This quick reappearance of 
consolidated lung occurred too rapidly to be explained by a 
shift of water through the airspaces, or through the tissue 
itself (i.e., migration of fluid between the cells from 
"high" to "low" areas). 

As it turns out, the dependent areas of the lung are 
collapsed, and appear fluid laden not because they have more 
fluid in them, but because they have less gas.  By carefully 
calculating the Hounsfield number for each cubic centimeter 
of lung tissue, Gattinoni showed that the lung water content 
did not vary significantly from the consolidated to the non 
consolidated area in edematous lung. Water content in 
edematous lung did however, differ radically from that of 
normal lung.  The consolidation of the lower lobes, or the 
most dependent part of the lung occurs as a result of the 
increased weight and thus the increased pressure exerted by 
the water-logged lung sitting atop the equally water-logged 
dependent lung. Normal lung tissue is very light and weighs 
alomost nothing. Injured lung is dense with fluid and the 
weight of this fluid filled tissue exceeds the ability of the 
gas pressure and the mechanical strength of the small airsacs 
(the alveoli) to resist it.  Thus, the alveoli in the 
dependent lung collapse and the lung takes on its wet, liver-
like appearance. 

It is doubly unfortunate that most of the blood flow to the 
lung in the prone position is to those very same dependent 
lobes that  are water-logged and whose alveoli are collapsed 
and inaccessible to gas exchange.  Thus, _most_ of the blood 
leaving the heart goes through lung where no gas exchange is 
possible and proceeds to be distributed to the tissues 
without oxygenation and without removal of carbon dioxide.  
This phenomenon is known as ventilation/perfusion mismatch, 
or V/Q mismatch for short. 

Because CryoVent is about 1.8 times the density of water, it 
rapidly re inflates these collapsed dependent alveoli and 
"recruits" them to gas exchange and heat exchange.  In fact, 
CryoVent opens up consolidated edematous lung within 10 
minutes of administration! 

CryoVent has other advantages as well; it displaces alveolar 
mucus and fluid and stops these fluids from acting as 
cesspools of free radical and proteolytic enzyme activity: 
CryoVent will not support either biologically meaningful free 
radical chemistry or catabolic biochemistry.  CryoVent is as 
inert as liquid teflon. 

One other advantage not at first appreciated: nitric oxide is 
readily soluble in CryoVent.  Nitric oxide is not be confused 
with _nitrous_ oxide (so-called laughing gas used in dental 
anesthesia).  Rather, nitric oxide is a powerful blood vessel 
dilator and is currently being used to selectively up 
regulate blood flow through areas of lung which _are_ being 
ventilated with gas by addition of nitric oxide in the ppm 
range to the breathing gas in patients with severe ARDS to 
correct V/Q mismatch. We are currently getting the capability 
of nitric oxide administration and it should be feasible to 
use nitric oxide in combination with CryoVent to more quickly 
and _selectively_ improve blood flow to lung tissue which 
CryoVent reaches. 

The Problems with the Solution 

So, as we said before, the solution is just that simple: 
ventilate with liquid. Unfortunately, _life_ is never quite 
that simple.  CryoVent is definitely ready to move from the 
laboratory and into the field for clinical application to 
human cryopreservation patients.  How soon will this happen?  
Well, that is a more difficult question to answer.  Currently 
we are hopeful that this technology will be ready for 
implementation within the next 60 to 90 days.  Most of the 
hardware exists or is under construction.  The working fluid 
is being produced now.  What we are waiting on is for _all_ 
of these elements to fall into place.  

We expect to take delivery on our first in-field Thumpers 
capable of delivering the kind of CPR we need in about 60-90 
days.  We have a similar timetable for obtaining 20 liters of 
CryoVent.  We have a prototype ventilator now, but it has not 
been refined into the compact and easy to transport unit that 
we would like.  Indeed, THAT is one of our weakest links; 
rapid and cost-effective implementation of final, "user 
ready" hardware for sweep-flow liquid ventilation.  This will 
not be an easy task.  Many of the normal benchmarks used to 
monitor the efficacy of CPR (such as end tidal CO2 
measurement) are rendered inapplicable by sweep-flow liquid 
ventilation.  Indeed, just the engineering of the system into 
a compact, easy to use system will take many months.  But, we 
are on our way.  In the meantime, we should shortly have the 
capability to apply this technology using bulkier equipment, 
and we will certainly be able to apply a unique variant of it 
which requires almost no equipment and little expertise, but 
which is not as effective at achieving good heat exchange. 

The nice thing about CryoVent is that it stable indefinitely 
at room temperature.  It will not expire, go bad or need to 
be restocked, except after use. 

We apologize for not telling you about this sooner, but as we 
said, life is never that simple.  We have been in the process 
of patenting CryoVent and related technology.  If its any 
comfort, it has been very hard for us to keep this secret.  
We are excited  about this technology and we think it is 
about to revolutionize cryopatient transport. 

Our patent work is in and the time for disclosure is right 
since CryoVent will soon be applied to BPI client patients.  
In fact, we sincerely hope to have CryoVent and sweep flow 
total liquid ventilation available for the next patient BPI 
cryopreserves.  Wish us luck! 

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