X-Message-Number: 7414 Date: 03 Jan 97 19:09:18 EST From: Mike Darwin <> Subject: Premedication of the Human Cryopreservation Patient II UY-ernative 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. Risks 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 contraindicated. 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 uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=7414