X-Message-Number: 7414
Date: 03 Jan 97 19:09:18 EST
From: Mike Darwin <>
Subject: Premedication of the Human Cryopreservation Patient II


	So, what can be done? Even in the best of cases there will 
be a period of ischemia which reaches or exceeds the current 4-6 
minute envelope of clinical recovery. The problem of mitigating 
ischemic injury upon reperfusion and after the declaration of 
legal death is dealt with in great detail elsewhere. And, as has 
been previously noted, it is not possible to start 
cryopreservation procedures on people not yet legally dead. So, 
it would seem that this discussion might well end here. And so, in 
effect, it will for many cryopatients for diverse reasons that 
will be discussed below.

	But this need not always be the case. The common event which all 
cryopreservation patients experience is hypoxia-ischemia. Whether 
global or incomplete, whether in the presence of underlying 
systemic disease or not, all will experience ischemia. And so we 
can, as Hippocrates admonishes us to do, "tell the antecedents, 
know the present, and foretell the future." And with such 
knowledge of the past, present and future comes the power to act.

	While it is certainly the case that postmortem aspects of 
cryopreservation (induction of hypothermia, cryoprotective 
perfusion, and cooling and solidification) cannot be undertaken 
before legal death, much of what determines the likely utility of 
these "postmortem" procedures will occur prior to medicolegal 
death. Furthermore, many of the physicochemical events that will 
result in ischemic injury after cardiac arrest and upon 
reperfusion can best be moderated or even inhibited by pre-insult 
pharmacological intervention.

Defining Premedication

	The basic definition of premedication in the context of this 
text is pharmacologic intervention during the patient's terminal 
illness to moderate or inhibit ischemia-reperfusion injury that 
would otherwise occur as a result of cardiac arrest and the 
delays attendant to the pronouncement of legal death.

	Encompassed by this definition is a wide range of behaviors 
ranging from providing the patient with nonspecific information 
that pharmacological intervention is an option, to providing the 
patient with detailed verbal or written information, all the way 
through to establishing a specific protocol for dispensing drugs. 
Please note that all biologically active compounds, including 
nutrients in excess of the Reference Daily Intake (RDI), which 
are taken by or given to the patient with the intent to modify 
the patient's response to ischemia-reperfusion injury or the 
dying process will be considered, for the purposes of this text, 
to be medications or drugs.  


	Is antemortem premedication of patients to inhibit agonal 
and postmortem injury legal? Is it moral? Will it harm the 
unequivocally living patient in order to provide supposed benefit 
for the equivocally dead one? These two questions must be asked 
and answered before we proceed further.

Legal Risks to Patient and Staff

	Ironically, the legality of premedication is an easier 
question to address than the question of "will it do no harm?" To 
be sure, neither question has a black-or-white or all-or-none 
answer. The answers come in shades of gray, and as with all such 
gray-state answers, there is the associated hazard of mistaking 
dusk for dawn.  

	In the United States (the only country in which I will 
consider here) there are six broad classes of pharmaceuticals: 

1) Vitamins, nutrients, and minerals (i.e., vitamins E and C, 
selenium, magnesium)
2) Over the counter (OTC) drugs (aspirin, naproxyn, cimetidine)
3) Ethical prescription drugs approved by the US FDA (l-deprenyl, 
Dilantin, misoprostol)
4) Ethical drugs available in non-US countries which may be 
legally imported 
	for personal use (Zileuton, piracetam, ketotifen)
5) Unclassified drugs and drugs approved for veterinary but not 
human use (PBN, FBP)
6) Underground or contraband drugs (Thalidomide, GHB)

	The legal risks associated with thoughtful and prudent use 
of drugs in categories 1 and 2 (vitamins and OTC drugs) with the 
patient's informed consent under the direction of a physician and 
with the knowledge and consent of the patient's personal 
physician and caregivers, are minimal (but not nonexistent).

	The legal risks associated with thoughtful and prudent use 
of drugs in category 3 (ethical US FDA approved drugs) under the 
direction of the patient's physician are somewhat greater but 
still probably small.

	Risks associated with thoughtful and prudent use of drugs in 
category 4 (ethical non-FDA approved drugs) imported by the 
patient for personal use under the direction of a physician and 
with the knowledge and consent of the patient's personal 
physician and caregivers is considerably greater.

	Use of drugs in category 5 with the knowledge and consent of 
the patient's personal physician is high. Without the involvement 
of the patient's primary care physician, use of such agents is 

	Any use of drugs in category 6 is normally contraindicated 
and always carries with it the risk of autopsy of the patient and 
serious legal repercussion for any cryonics personnel involved in 
such activity.

	More detailed considerations of the legal risks involved in 
premedication will have to await discussion of specific drugs and 
specific medical and social scenarios later in this discussion.

Medical Risk to the Patient

	The issue of medical and psychosocial harm to the patient in 
the context of premedication is a far more difficult one. At 
first glance it might seem a simple issue. Some drugs like 
aspirin and vitamins E and C which might provide substantial 
cerebroprotection if given in advance of the ischemic insult 
would seem to carry no downside. They are commonly ingested by 
healthy people, are widely endorsed by physicians in moderate 
amounts, are essential nutrients found in food, and are freely 
available OTC without a prescription.

	However, the hidden caveat in the above paragraph is the 
qualifier "they are commonly ingested by healthy people." In 
patients with iron overload from hemochromatosis or with 
diminished urine output, moderate doses of vitamin C could cause 
serious injury or death. In the patient who is platelet depleted 
or suffering from bleeding secondary to cancer or 
gastrointestinal (GI) ulceration, vitamin E or aspirin may 
precipitate a hemorrhage causing morbidity or mortality.

	Thus, even the most seemingly innocuous agents may cause 
direct physical harm. Beyond the issue of physical injury or 
death are the even thornier issues of social cost (impact on the 
quality of remaining life) and economic cost, both of which may 
feed back in unexpected ways to affect the patient's physical 
well-being. Thus, as with all medicine practiced upon living 
people, the admonition to "first do no harm" looms large and 
weighs heavy on its practitioners.

	The point of this discussion is very simple: premedication 
of cryopreservation patients carries with it cost, uncertainty, 
and the potential for considerable harm as well as some benefit 
(to both the patient and the cryonics personnel). The cost-
benefit ratio will be something that can only be established on a 
case-by-case basis with careful and thoughtful interaction 
between all of the parties involved. Such parties will 
necessarily include the patient and the Standby personnel, but 
may (and usually should) include the patient's family, 
physician(s), intimate friends, and others involved in the 
patient's care.

	In some situations it will be an imperative for the 
patient's physical and psychological well being (quite apart from 
any advocacy or involvement of cryonics organization or Standby 
staff) to use category 6 drugs and this will be undertaken by the 
patient with the full support and active cooperation of all 
caregivers (including the physician) and the family. Ironically, 
such a situation may pose only the most minimal risk to the 
patient and staff where, by contrast, the use of a single 
category 1 drug such as vitamin E in a situation involving a 
hostile physician or family member may result in a medicolegal 
disaster. There are no hard and fast rules and good judgment is 
the only protection. Good judgment, however, is hardly an assured 
commodity and it must be stated clearly and without qualification 
that premedication of any patient with any drug carries with it 
risk which cannot be eliminated. Be forewarned!

End of Part II


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