X-Message-Number: 7451 Date: 08 Jan 97 02:59:24 EST From: "Steven B. Harris" <> Subject: Cryopreservation Premedication, pt 3 The following is a BioPreservation, Inc. (BPI) technical briefing on premedication of human cryopreservation patients to mitigate the injury associated with antemortem and post mortem hypoxia/ischemnia. Contents copyright 1997 by BioPreservation, Inc. All rights reserved. ------------------------------------------------- Premedication of the Human Cryopreservation Patient Part III by Michael Darwin Psychosocial Considerations As the above discussion should make clear, premedication carries with it risks which are determined to a large degree by the patient's medical condition, and psychological and social situation. Determining the most beneficial (or lowest risk) approach can only be done after the patient is carefully assessed in all these areas. Psychosocial evaluation and intervention are covered in considerable detail elsewhere in this text. However, a few words specific to premedication are in order. Patients who have family and/or primary caregivers who are hostile to cryonics are generally not candidates for premedication. The same is true of patients who have diminished capacity, diagnosed psychiatric problems or who are obviously not fully capable of giving informed consent. The only exceptions to this rule are situations where: * Patients who are no longer competent have left an advanced directive or have a Durable Power of Attorney for Health Care (DPAHC) which specifies premedication. * The patient's medical surrogate (as appointed in their DPAHC) is aggressively supportive of premedication. * The spouse or parent(s) or guardian of the patient are cryonicists and are aggressively supportive of premedication. Situations where unresolved hostility, paranoia and mistrust exist on the part of any of the key players in the patient's personal, social or medical milieu, whether directed at cryonics or not, are absolute contraindications to premedication. Ideal situations are ones where the patient and family are long-time cryonicists, or where the patient has been pursuing alternative treatments that involve self administration of unapproved parenteral or category 6 medications. The latter situation, such as is often the case in HIV patients and younger patients with cancer or other unexpected degenerative diseases, almost invariably implies a person and caregiver(s) who have become knowledgeable about the mechanics of administering parenteral drugs, are willing to take risks, and are generally (but not always) capable of independent judgment and the ability to absorb and draw conclusions from the primary biomedical literature. Such a patient and caregiver(s) will be able to use the Internet and access biomedical databases and illness-specific special interest groups (SIGS) and thus get a wide range of independent information. The ability to critically evaluate the peer-reviewed scientific literature supporting premedication for ischemia-reperfusion injury is a strong plus in favor of providing the patient with information on premedication. Medical Considerations In addition to the psychosocial situation, the patient's medical condition and treatment will determine whether premedication is appropriate and if it is, what its specifications will be. Clearly a patient who is dying in a hospital will not be a candidate for intervention with category 4, 5 or 6 drugs. Similarly, a patient with gut failure, GI obstruction, or other contraindications to p.o. medication will not be able to benefit from many of the drugs likely to be of use in premedication. Beyond these logistical considerations come more subtle and potentially dangerous ones. An exhaustive medical evaluation of the patient by his personal physician and by a physician knowledgeable about premedication (including the pharmacology of the drugs to be used) is absolutely essential. The purposes of such an evaluation are to: 1) Rule out the possibility that the patient has a potentially treatable illness and is not terminally ill in the first place. 2) Rule out underlying medical conditions which may contraindicate premedication in general or the use of specific agents. 3) Provide medicolegal documentation of the appropriateness (i.e., anticipated benefits and lack of contraindication) of a given premedication protocol for the patient. 4) Provide a sound basis for determining the appropriate medications as well as their dose and route of administration. The medical evaluation of the patient prior to premedication should include the following elements without exception: 1) A comprehensive gathering, duplication (and retention) by the Cryonics Organization's Medical Director (COMD) of all of the patient's available medical records. 2) A thorough medical review of the records gathered by the attending physician and the COMD with specialist consultation as necessary. 3) Evaluation by a clinical laboratory (which the COMD has confidence in) of the patient's CBC, clotting status, TSH level and serum chemistries, at a minimum. 4) Evaluation of current and projected nutritional status, caloric intake, assessment of macronutrient intake (with special attention to fat intake), and assessment of dietary micronutrient intake. 5) Determination of baseline serum antioxidant levels and redox status (Pantox Profile). 6) Infectious disease screen including testing for HCV, HBV, HIV, TB and other etiologic agents as circumstances may indicate. Pantox Panel Determining the patient's antioxidant status is a crucial first step in formulating a plan for premedication. In some cases, patients may already be supplementing with vitamins or trace minerals which are central to the basic premedication protocol discussed below. In all cases it is desirable to titrate the dose to the desired levels. This will be especially important in cases of compromise to the gut, malabsorbtion syndrome, noncompliance, and poor nutritional status. Poor nutritional status will mean low intake of macronutrients including fats, which act as facilitators of absorption for lipid soluble medications. Pantox Profile The patient's serum antioxidant profile will serve several functions in addition to establishing a baseline for premedication. It serves as a marker for overall nutritional status and it provides easy to understand visual feedback for the patient, showing him graphically where he is now versus where he needs to be. Response to premedication as evaluated by serum antioxidant levels also contributes to our understanding of the effectiveness of premedication both in acutely raising blood levels of these drugs and in moderating ischemic injury. Below is a table giving the normal range of serum antioxidants and pro-oxidants (such as serum ferritin) evaluated by Pantox testing. [Pantox Laboratories, San Diego CA (619) 272-3885]. Lipid Soluble Antioxidants Normal Range Units Coenzyme Q10 (Ubiquinol) 0.33 - 4.37 *M Alpha-tocopherol (Vitamin E) 23.0 - 78.0 *M Gamma-Tocopherol 1.50 - 7.50 *M Lycopene 0.07 - 0.66 *M Beta-Carotene 0.25 - 4.20 *M Alpha-Carotene 0.04 - 0.50 *M Vitamin A 1.60 - 3.51 uM Lipid Protection Ratio 4.70 - 15.8 Water-Soluble Antioxidants Vitamin C 22.0 - 137 *M Uric Acid 246 - 569 *M Total Bilirubin 1.71 - 20.5 *M Direct Bilirubin 0.00 - 5.13 *M Iron Status Serum Iron 7.17 - 26.8 *M Iron Binding Capacity 44.8 - 71.6 *M Percent Saturation 11.2 - 51.7 % Available Binding Capacity 32.9 - 75.0 *M Serum Ferritin 27.0 - 450 ng/ml Table 7-1: Normal limits for serum antioxidants and pro-oxidants. The results of an individual's Pantox panel are displayed graphically so that the patient can meaningfully evaluate where s/he stands and see progress towards reaching predetermined goals. Below are graphic examples of a Pantox profile on a typical 51 year-old smoker with end-stage primary adenocarcinoma of the lungs. The "ideal" levels shown on the graphics for antioxidants are the lower limits considered desirable for premedication for cerebroprotection. End of Part III To be continued. BioPreservation, Inc. 10743 Civic Center Drive Rancho Cucamonga, California 91730 (909)987-3883 (N.B.: For those following Usenet's sci.cryonics, it will be noted that the partitioning of this article is not the same on Cryonet and Usenet. On Cryonet, due to space limitations, this article will eventually be presented in 7 parts, whereas on sci.cryonics it has already been posted in 4 parts.) Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=7451