X-Message-Number: 16170 From: Date: Wed, 2 May 2001 03:26:53 EDT Subject: Kryos News # 3 Kryos News # 3 A PARK OF YOU OWN One of the biggest fears of people signed up for cryonics is that they may suffer an unexpected health emergency or catastrophic accident, allowing no time to notify their cryonics organization in advance. Even in situations where a patient is known to be terminal, legal death often occurs much sooner than expected. In fact, cancer patients and elderly, chronically ill patients have a far higher risk of sudden death than a patient recovering from a serious heart attack. There are several reasons for this. Among the more obvious are that such patients often have compromised immune function as a result of treatment and/or the disease process. Chemotherapy can cause sudden overwhelming infection that can result in death in hours (sepsis). Several cryopatients have died unexpectedly in this way. Similarly, depressed immune function and increased susceptibility to infection in the elderly and others with bladder catheters or other invasive appliances can result in sudden death from infection. Patients with chronic obstructive pulmonary diseases (COPD) such as emphysema and asthma are also at risk of rapid decline and cardiac arrest. Closer monitoring of these patients' immune function, often with something as simple and inexpensive as a complete blood count (CBC) test, could greatly reduce the frequency of this kind of rapid and unexpected death. Another cause of sudden death in cancer patients, particularly in advanced stages, is hypercoagulability. This is a big word for a simple problem: such patients tend to develop lethal blood clots in the vessels supplying their hearts (heart attack) or develop clots in the veins of their legs or elsewhere, which break off and partially or completely close off blood supply to the lungs. Cancer-associated hypercoagulability appears to be a result of activation of the immune-inflammatory cascade as a direct effect of the cancer cells, as well as due to ischemia in tissues being compressed by the expanding tumor mass. Terminally ill cryopatients should be monitored for this kind of change in blood clotting by doing prothrombin (PT) and partial thromboplastin time (PTT) tests. These tests are inexpensive, and, if they do indicate hypercoagulability, either Coumadin or a newer and safer drug, Plavix, can be given on a chronic basis to normalize clotting times. While this treatment isn't for every ill person, it could definitely help to reduce the incidence of sudden or very rapid death in patients at risk. Still, these interventions cannot save everyone from the cryonics nightmare of sudden death. In cases where a healthy person suffers an accident, the patient frequently is autopsied by a coroner or medical examiner, but there are exceptions. Even if death occurs naturally, paramedics or morticians seldom have immediate access to heparin, which is a vital drug to prevent the blood clotting that will impede perfusion. Conventional medical personnel are even less likely to possess, or be willing to administer, other medications which a cryopatient needs. In the past, Alcor addressed these problems by creating Regional Standby Kits which were placed with volunteers at key areas across the United States (and later in Europe and Australia). At Kryos we believe this is still a viable approach, although still not adequate in many situations. How can each Kryos client have guaranteed, _immediate_ access to the critical molecules that could make the difference between a good cryopreservation and a very bad one? This question has become of even greater urgency with the advent of vitrification technology. Successful application of vitrification requires even the smallest brain vessels to be open and unobstructed. This is best achieved by rapid postarrest anticoagulation and the administration of compounds to inhibit biochemically mediated ischemic damage and inhibit cell swelling. Unfortunately, such compounds are not on any hospitals' shelves anywhere in the world. And, getting them to a patient in a timely fashion is all too often impossible. We at Kryos have what we believe is a major advance that will go a long way toward solving this problem. We call it the Past Arrest Response Kit or PARK for short. PARKs would be issued as part of a client's completion of arrangements with Kryos. The kit would consist of a cocktail of compounds for administration AFTER PRONOUNCEMENT OF LEGAL DEATH to inhibit ischemic injury, including blood clotting. The PARK would also contain a disposable Active Compression-Decompression CPR device to facilitate much improved circulation/delivery of the ischemia-protective chemicals. We have developed an inexpensive prototype device which uses an adhesive pad to stick it to the chest. The instructions are simple: peel off the "wax paper" cover from the adhesive pad, place the sticky pad of the device midline on the patient's chest between the nipples, and begin cardiopulmonary support (CPS) by pushing down on the device with enough force to depress the chest wall by 2" and pulling up after each compression with enough force to almost lift the patient from the floor, at a rate of 60 times a minute. An added advantage is that the use of this device eliminates the need for ventilation, since each upstroke of the device pulls air into the patient's lungs, much as the negative pressure in an iron lung was used to ventilate people in the past. Blood circulation of compounds administered IV is superior to conventional CPR using this approach. Ventilation with room air during such CPS is actually less injurious than ventilation with high concentration of oxygen as is typically done during resuscitation efforts using CPR. What's more, the longer the patient has been ischemic (in cardiac arrest), the more beneficial room-air ventilation is, and the more harmful high concentration or pure oxygen ventilation would be. As for protective compounds, the PARK "cocktail" will be packaged in a kit that will allow for either professional administration by a paramedic, nurse, physician, or mortician (a mini-cutdown kit will be provided for morticians) who can gain IV access, or where IV access is not possible administration via injection into the liver. The latter may sound difficult but really isn't. Fortunately, the liver is in about the same place in everyone and is very easily located by obvious external anatomical markers. Obesity will be the main problem, since overlying fat will increase the depth to which the administration stylette must be inserted. The prototype is a sheathed device that protects the operator from the exposed sharp end of the stylette at all times and would remain in the patient after delivery of the chemicals. The latter has several advantages: 1) It prevents a biohazardous "sharp" from being generated, 2) it allows us to determine if the positioning was correct, and 3) it will likely also contain a temperature probe which will allow for monitoring of the patient's core cooling using an inexpensive logging thermometer. The stylette assembly would attach to the patients' skin using cyanoacrylate (a chemical similar to SuperGlue). Cyanoacrylate is a water-catalyzed adhesive and sticks even to moist skin very rapidly and very securely. If the operator misses the liver, no harm will be done, but no benefit will be received. However, since the patient has no other recourse, this strategy is still better than nothing, and in most cases the liver will be accessed. We have not quantified to what extent drugs delivered by this route will be distributed in patients, depending on the post-arrest time. Our guess is that distribution will be adequate in newly arrested patients, considering that injection of dye into the liver or kidney of animals during CPR gives excellent and rapid distribution. Once Kryos has operational laboratory facilities, we will quantify and validate this approach in a relevant animal model. For those who want them, and are willing to pay the extra cost, more advanced versions of the PARKs will be available for exclusive use by medical professionals or paramedics. Either way, PARKs will go a long way towards eliminating the sense of utter helplessness and vulnerability which most cryonicists feel. In many instances there will be paramedical, medical, or mortuary personnel available who can be persuaded to administer the compounds intravenously, obviating the need for trained Kryos personnel to be on site. Just having a lot of PARKs out there will allow us to use existing clients as an emergency distribution source of PARKs for at-need cases. For instance, if we get a call that someone is going down near another client in Denver or Orlando, the client can ferry over a PARK to the hospital or mortician faster than we can get one there by courier or Federal Express. The other part of the PARK will be a beefed up "body bag" and a special holder to facilitate packing the head in ice. Conventional body bags leak like a sieve. We will be using rugged water-tight material to eliminate this problem. The head icer will allow for much improved cooling of the brain. For those willing to pay extra we can also supply enough "instant ice" (KwikKold) to fill up the head icer. KwikKold is a product that produces a sustained endothermic reaction which soaks up a lot of heat. It isn't cheap (though the ingredients are!) but it would be very effective as a first response until ice could be obtained. Just packing someone's head in KwikKold will reduce temperature in the brain fairly rapidly if the hair is wetted--and we will be providing a bottle of surfactant containing wetting solution for the hair. We are also looking into producing a KwikKold equivalent that would cost far less. Finally, the PARKs will pack a lot of pharmacologic punch. Advisors associated with Kryos have learned how to get a lot of protective compounds into a small volume with a long, stable shelf life. If the PARK is refrigerated, its shelf life will be even longer. Refrigeration will have the additional advantage of reminding people about Kryos and their cryopreservation arrangements every time they open their refrigerator at home. Granted, it will take up some home fridge space and lead to some family "discussions." But we think it will be a net benefit. A final concern is security and liability. The part of the PARK containing the cocktail of ischemia protecting compounds will be designed so that it can be opened without destruction of the contents only after an authorized Kryos representative has given the access code and determined it is legal and biomedically appropriate to proceed with use of the PARK. This is one of many innovative solutions which Kryos plans on delivering to its clients. We're enthusiastic about the potential of the PARK to help dramatically improve the quality of care for a significant number of cryopatients. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=16170