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."

    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 

	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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