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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=7409