X-Message-Number: 2958
Date: 02 Aug 94 21:17:51 EDT
From: Mike Darwin <>
Subject: SCI.CRYONICS Shock and Dr. Crippen

In response to Dr. David Crippen:

I have no idea who sent you the material on predicting agonal time course in
human cryopreservation patients.  It is understandable why such (unsolicited)

and out of context material would cause confusion.   I wrote it and thus will be
happy to answer your questions.  I am passingly familiar with your work on

shock, and am very well acquainted with the work of your colleague, Peter Safar,
on the pathopysiology of cerebral ischemia and cerebral resucitation.  Perhaps
someone  on Cryonet thought you might find the chapter from my book on standby
of interest -- or be able to add something to it relating to determining the
time course of terminally cryopreservation partients to cardiac arrest.

In answering your questions I will first start with some understandable basic

1) Some of us in the cryonics community do not see future medical science as an

unlimited genie capable of realizing all our deepest desires whether they happen
to be within the realm of physical law (as we currently understand it) or not.
I am one such person.  Therefore, wherever possible I strive to prevent injury
to the patients I cryopreserve.  

2) Injury to cryopreservation patients comes from three sources: the underlying
disease process, shock and global and trickle flow ischemia secondary to dying
and cardiac arrest, and finally cryoprotectant toxcicity and cryoinjury from
freezing.  Any of these injuries can prove lethal (even by the projected

capabilities of tomorrow's medicine).  For instance a patient may suffer from an
obliterative primary brain disease which destroys both mentation *and the
structure underlying it* long before legal or clinical death occur -- such
patient's will not benefit from cryopreservation.  Similarly, long periods of
normothermic or room temperature ischemia may render cryopreservation useless

(althought what the precise limits are here is more open to question).  Finally,
cryoinjury, especially in the absence of cryoprotectant drugs such as glycerol
do not do the patient any favors.  The less injury done to the patient the
likely the greater the fidelity of the restoration and perhaps the sooner the
restoration. Sooner where revival is concerned is always better.  Storage time
is risk time.

2) In order to replace roughly 50% of the patient's brain and/or body water with
glycerol it is necessary to have an intact capillary bed and a circulatory
system unobstructed by clots, leukocyte plugging, etc.  As you are no doubt
aware ischemic injury develops quite rapidly and, in the typically slowly dying
patient, the immune/inflammatory cascade is already activated and damage

underway.  Perfusing a patient with multimolar concentrations of glycerol over a
2-6 hour period is a challenge under the best of circumstances. Altered
capillary permeability, post mortem clotting, phospholipase activation, and so

on, can profoundly compromise the intruduction of cryoprotectant.  A patient who
is not rapidly stabilized in the field at the time of cardiac arrest will
experience clotting and will also experience the rapid development of cerebral
edema during cryoprotective perfusion which will bring perfusion to a halt
(cortical volume is monitored through burr-hole cranitomies and cortical

perfusion is evaluated with endoscopy and with intravascular dye (fluroscein) if

3) Our strategy for avoiding these problems is to attempt (ideally) to inhibit
or reverse all ischemic injury.  This ideal is rarely achieveable in practice,

but we can  certainly do better than letting our patient lie around for hours or
a day or two while s/he is transported  from where cardiac arrest occurred to a
facility for cryoprotective perfusion and freezing.  How do we do this?  The
terms we use to describe this process of stabilization are "standby" and

"transport."  What these consist of are preparing the location where the patient
is to experience cardiac arrest for immediate cardiopulmonary support using

machine delivered active-compression-decompression and high impulse CPR followed
by extracorporeal support via femoral-femoral bypass.  

4) Under good conditions I have started CPR within 1-2 minutes of cardiac
arrest.  Concurrent with beginning CPR we also administer a variety of I.V.
medications to reduce reperfusion injury and deal with the often inadequate
cardiac output achieveable with CPR.  While a complete presentation of the
protocol is beyond the scope of this response, suffice it to say that it is
multimodal and includes the use of high dose epi, nimodipine, deferoxamine,
sodium pentobarbital, acetyl-l-carnitine, THAM, heparin, and leupeptin.  CPR is

also carried out in a tub-like affair which is filled with crushed ice and water
at the time CPR is started (active pumping of the water goes on to facilitate
heat exchange)  for external cooling.  

5) At the same time that closed chest cardiopulmonary support is begun, surgery
is also undertaken to raise the femoral vessels for cannulation.  Generally,
cutdown and initiation of bypass takes about 60 to 80 minutes to complete.

During this interval the typical cachectic patient is cooling at a rate of about
0.2 C per minurte.  Bypass is initiated using a Normosol, mannitol and
Dextran-40 prime and the patient is cooled to approximately 15 C.  Typically
colling rates on bypass are in the range of 1 C per minute (we use the Sarns
Turbo hollow fiber oxygenator/heat exchanger).

6) At the time the patient reaches 15 C or therabouts the patient's blood is
washed out and replaced UW-Solution (we use Viaspan manufactured by DuPont
Pharmaceuticals). Viaspan is an intracellular type organ preservation solution
used for hypothermic preservation of the kidney, pancreas, liver, etc.  The
patient's core temperature is then further reduced to 2-4 C and the patient is
transported (often still on extracorporeal support via our own ambulance on a
special ECMO cart we have devloped) to a facility where cryoprotectant can be
introduced in a controlled and monitored fashion.

7)  As you may surmise it takes a team of about 6 people to carry out initial

stabilization and transport of a patient.  Typically I work with a team of three
skilled people; myself, a perfusionist, an R.N. and or/a respiratory therapist
and/or a physician (intensivist).  Three of the six team members are usually

less skilled local people who have either basic training at the EMT level or are
medically unskilled people who are used to get ice, lift the patient, run
errands, etc.

8) As you may also surmise this is not either a) cheap, or b) logistically

"easy."  Once deployed in the field, often a thousand or two thousand miles from
"home" I do not have a fresh supply of equipment or personnel to draw on and
housing six people in a patient's home on in an ambulance (or cry-room of the
hospital or nursing home) is not easy.  People become fatigued and wear out

physically and emotionally.  They also cost a lot -- about $1000 a day (and that
is a bargain because that includes airfares, 14 large crates of equipment; an
entire OR and bypass capability pluse,  Dinamapp, pulse oximeter, Ektachem, and
a load of other equipmet).  Keep in mind that it takes time to prime and
debubble the extracorporeal circuit.  When the patient arrests every skilled
person is busy establishing an airway, doing a jugular cutdown for IV support,

starting the Thumper,  optimizing end-tidal CO2s, beginning external cooling and

so.  That means that ideally the circuit should primed when it is clear that the
patient is no more than hour or two away from arresting.  This is NOT easy to
determine.  And I only have on circuit, so if I "blow" it and prime a day too
early, I'm in trouble unless FedEx can bail me out!  I'm also out $800.00!

9) As a consequence I try to know as precisely as possible when the patient is
going to arrest.  This is terribly important for a whole host of reasons.  As
I've previously noted there is the issue of cost.  The average length of a
standby is about 7-days.  Physicians, especially critical care physicians, are
notoriously unreliable in predicting time course to cardiac arrest in terminal
patients.  I believe this is so largely because they do not monitor such

patients or even pay very close attention to them.  All labortory monitoring has
been dc'd and the physician doesn't even examine the patient crticically any

My personnel must also be conserved.  Long standbys mean personnel sitting by
the bedside for days on end getting worn down and losing their responsiveness.
They also mean the necessity of housing staff off-site much of the time.  Thus,
the standby team needs to be able to predict the time course to cardiac arrest
with reasonable precision so that the team can be brought together when the
patient is frankly agonal.  Also, just drawing up the transport meds takes two

skilled people about 15 minutes (these things don't come packaged in Bristojects
like code meds!  Many of them are prepared in-house since they are not FDA
approved).  Similarly, 300 pounds of ice doesn't last forever....

Phasing all these things is critical to being ready when the time comes.
Knowing when the last turn in that spiral of decompensation is happening is not
as easy as it seems.

10) Finally, understanding if the patient is dying dehydrated or wet is also
important.  CPR stinks under the best of circumstances and a hyperviscous and
hypovolemic patient is not going to respond well.  Promptly rehydrating such a
patient will be critical to minimizing post pronouncement ischemic injury and
restoring adequate perfusion.  The same is also true of the importance in
knowing whether a patient is "wet."  Under the best of circumstances prolonged
CPR results in rapid compromise of gas exchage due to the development of
pulmobary edema (PE).  A patient with nascent or full-blown PE at the time of

arrest is not going to benefit from excessive fluid administration and in such a
situation a more concentrated dose of THAM would be used and volume expansion

with Dextran-40 and/or Noromsol would not be undertaken.  We would also probably

user higher ventilation pressures on such a patient as well as aggressive PEEP.

Knowing the patient's pre arrest condition is thus important not only to
determine time-course to the arrest, but also to determine management

11) Finally, a few words about death.  I can tell from the tenor of your remarks
that medical death to you is something which has real meaning.  It is important
that you understand that to me and to other cryonicists this is not the case.
Most of the people you pronounce dead are still (brain) viable by *current*
criteria. The typical cancer or AIDS "no-code" patient who experiences
cardiorespiratory arrest and is pronounced legally dead could often be restored
to consciouness with vigorous enough support if intervention comes soon enough.
This is not done (and quite rightly so) because contemporary medicine cannot

treat the underlying cause of the arrest or restore the patient to an acceptable
quality of life.   It is no accident that barbiturate is present in our
protocol: it is used not only to reduce cerebral metabolic demand (bringing it
more into line with what CPR can deliver), but also is present  to prevent
recovery of consciouness in patient's which physicians have pronounced "dead."
It is a little difficult for me to accept your criterion for death as very
absolute  when one of "your" (i.e., contemporary medicine's) dead patients
begins to recover consciouness.

Further, the limitations of tommorrow's medicine may arguably be different than
those of today's.  Defining death in the future will in my opinion have little
to do with immediate ability to restore function or acceptable quality of life,
but rather will be determined by whether or not the patient still retains the
structural elements of memory and personality which constitute that patient's
identity.  These things can exist as *information* long after they cease to
exist as a functional operating system.  When we freeze people we are trying to
preserve that information with as much fidelity and as little damage as
possible.   The price of ischemic injury is one we would prefer to keep as low
as possible.

My book chapter which you were sent was written for EMT level people and for
field transport technicians with little experience in the care of dying
patients.  Actually, it could serve some physicians in good stead too, from
what I've seen.

Thank you for your questions.  And by the way, who did send you this
information?  I would be curious to know.

Mike Darwin

[ Mike, my apologies for not appending an explanation at the end of
  Dr. Crippen's message, because I think that I know what happened.
  Your message #2948 was long enough to make the CryoNet software chop
  it into two parts and apparently only the second part reached
  Dr. Crippen.  Unless the email failed again, he should have
  received your entire message by now. - KQB ]

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