X-Message-Number: 7409
Date: 03 Jan 97 01:21:28 EST
From: Mike Darwin <>
Subject: Premedication of Cryopatients
The Following is the first in a series of BioPreservation, Inc (BPI) Technical
Briefs discussing the topic of
premedication of human cryopreservation patients.
Premedication of the Human Cryopreservation Patient, Part I
by Michael G. Darwin
"The physician must be able to tell the antecedents, know the
present, and foretell the future--must mediate these things, and
have two special objects in view with regard to diseases, mainly
to do good or to do no harm."
Hippocrates
Of The Epidemics
The Way It is
Because of the medicolegal constraints imposed upon cryonics
now, and most likely in the foreseeable future, cryopreservation
procedures cannot begin until clinical and legal death have
occurred. It is generally argued by proponents of human
cryopreservation that significant intervals of ischemic injury
need not be catastrophic, nor result in the irreversible
compromise of mentation and identity. These arguments are made
largely on the basis of laboratory experiments where global
ischemia is induced in healthy animals without prior pathology.
There can be no argument that such experiments have
contributed greatly to our understanding of the biology of
ischemia and to bounding the limits, as it were, of the
"theoretically possible" with respect to recovery of cryopatients
who experience ischemia. Clearly, the persistence of neuronal
membrane integrity and the conservation of central nervous system
(CNS) ultrastructure after significant periods of normothermic
ischemia is encouraging and provides a reasonable basis for the
hope that structures encoding human identity are still intact
after such insults. However, it is critically important to
realize that experiments conducted in the laboratory under
tightly controlled conditions are designed to answer highly
specific questions in fact, they are usually designed to answer
only a specific few questions. Such experiments cannot be
expected to tell us much about the condition and prognosis of
cryopatients who die in very complex and uncontrolled ways in the
real-world.
Unlike laboratory experiments, cryopatients do not typically
experience global ischemia from a well-timed jolt of electricity
to the heart after bounding into bed in previously good health.
Some will die from sudden, unexpected arrhythmias and do so free
from serious multiorgan or systemic disease which can cause
extensive antemortem brain damage. But such patients will pay for
the "scientifically clean" nature of their ischemic insult by
being subjected to uncontrolled reperfusion during futile
resuscitation attempts, long post-arrest delays attendant to
unwitnessed cardiac arrest, and/or medico-legal examination
(autopsy or seizure by the medical examiner (ME) or coroner).
While two-thirds of cryopatients will die "expected deaths"
(i.e., not from sudden cardiovascular compromise, suicide,
accident or homicide), only half of these will die in settings or
under conditions that make prompt high quality post-arrest
intervention possible.
Thus, approximately one-third of cryopatients will die from
degenerative disease in a setting that will allow for a
reasonably good chance of prompt post-arrest intervention.
However, this number is also misleading if it is taken to be an
indicator of an optimum chance at recovery or a laboratory-like
model of global cerebral ischemia.
The reality is that of this 35% or so of patients who
present for cryopreservation with adequate warning to mount a
full standby, somewhere between 7-10% of them will suffer from
some major pre-cryopreservation compromise to their brains. Many
of these patients will have organic brain syndrome from
Alzheimer's, multi-infarct dementia, HIV or HIV related CNS
infections (i.e., toxoplasmosis, tuberculosis, meningitis, etc.),
stroke, brain tumor (primary or secondary) or other causes. At
this time, little can be done to improve these patients' chances.
Of the remaining 25% of cryopatients without prearrest primary
brain pathology, most will suffer a prolonged period of agonal
shock characterized by hypoxia, activation of the immune-
inflammatory cascade, and regional cerebral ischemia. As a
consequence, these patients will experience global brain insult
before cardiac arrest ever occurs. Only a small minority of
cryopatients, perhaps as few as 2-10%, will present for
cryopreservation under conditions that allow for an optimum
standby and will experience legal death in a way which results in
little or no antemortem hypoxic-ischemic injury.
It should also be kept in mind that so far we have
considered only the effects of ischemia in a laboratory setting
as our guide to how we should visualize the condition of the
"typical" cryopatient. This scenario or model does not take into
consideration the behavior of the ischemically injured brain in
response to resuscitation (acute reperfusion), induction of
hypothermia, introduction of cryoprotectants during an extended
period of perfusion, and finally, the effects of cryoinjury
during cooling to -196oC.
All cryopatients, no matter how well or how poorly they
experience medicolegal death will, indeed must experience death
before cryopreservations procedure can commence. This fact alone
means that all patients presenting for cryopreservation will
experience some period of ischemic insult: even if the insult is
only 1-2 minutes of global ischemia and 3-5 minutes of inadequate
blood flow and gas exchange during the initial minutes of CPR.
This is the sad reality of how cryonics is practiced today,
and anyone who doubts this reality need only peruse the case
histories of those cryonics organizations that choose to publish
them in sufficient detail to allow a meaningful evaluation.
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