The Cryonics Institute’s 78th Patient: By Ben Best
The 78th patient of the Cryonics Institute was an 81-year-old German woman who had been made a Cryonics Institute Member by her daughter within days of the patient's deanimation. Although not highly educated the patient had worked as a secretary and was very talented as a craftsperson as well as musically.
The patient had been diagnosed as having Alzheimer's Disease nine years earlier. The patient's husband had been killed in an automobile accident a few days before the diagnosis of Alzheimer's Disease. Four years later the diagnosis was changed to Lewy body dementia. At the beginning of 2004 the patient suffered a stroke which left her bed-bound for the rest of her life -- requiring intensive care by her daughter.
The patient was in the hospital at the time of deanimation, suffering from aspiration pneumonia (the most common cause of death for Alzheimer's patients). The daughter had achieved what she felt was a sympathetic willingness to help by the attending physicians and nurses, but detailed instructions had been given in written form, but not reinforced verbally or given to all the responsible hospital personnel. Only 5,000 IU of heparin was administrated in the arm at the time of deanimation and this was not circulated by CPR/CPS. An hour later another 35,000-45,000 IU was administered, but this was not circulated either, so it was a somewhat fruitless exercise.
When the patient's daughter arrived she loudly vocalized expressions of hysterical despair & helplessness which resulted in help from attending physicians and nurses. An ice machine was discovered in the hospital which supplied abundant quantities of ice. The patient was wrapped in a water-proof sheet which was stuffed with ice and taped closed with sticky tape by attending physicans -- with special attention paid to the head. The daughter was extremely touched by the caring and attentiveness displayed by some of the nurses in packing with ice and doing whatever they could to help.
Later the daughter spoke privately with the chief physican, admitting to him that she had intentionally dramatized her hysteria in order to get help for her mother. She told him that she believed that the chances of her mother ever being reanimated were extremely small and she explained to him some of the intellectual background behind cryonics, including even a reference to the Aubrey de Grey Technology Review controversy. The physican shook her hand very warmly and expressed his desire to help her in any way that he could. At the end of the day the daughter passed the head nurse who somewhat tearfully told her that they had done their best to help with these cryonics procedures -- which they did not understand -- and that some of the nursing staff had been traumatized and exhausted in their efforts to do what needed to be done.
Fortunately for the patient, she lived near Frankfurt, which is the only German city with a direct flight to Detroit. Also fortunate is the fact that Barry Fowden, our cooperating German funeral director, lives near Frankfurt. He was able to send some of his staff to the hospital to render assistance. Barry speaks excellent English and is enthusiastic in his participation in cryonics cases. He is extremely helpful and competent.
Monday was a frantic day for the patient's daughter. She needed to arrange for funding based on equity in her house and she needed to find an English-speaking notary to help her with completion and signing of the Cryonic Storage Agreement. Both of the patient's daughters signed Next-of-Kin and Consent/Release agreements. The bank could not arrange a loan for the house on such short notice and the daughter was forced to obtain a personal loan from an acquaintance of an attorney who was her neighbor. Barry Fowden also required immediate payment. It took five hours for the bank to arrange for wiring the money.
The Cryonics Institute accepted the FAXed contracts and a FAXed statement from the bank that the money had been wired as proof of funded contract. (Although the money was wired on Monday, it did not appear in the CI bank account until Thursday.) This allowed Barry Fowden to get a consular mortuary certificate for shipment from the American Consulate near Frankfurt. Shipment was arranged for Tuesday. Because the flight to the USA leaves at 1:40pm and because of the necessary time for consulate approval, Barry does not think that shipment could have been arranged for Monday even if the contracts and funding had been in place.
The patient arrived in Detroit early Tuesday evening and was at the funeral home by 9:30pm, about 66 hours after the patient had deanimated. The patient had arrived in a metal shipping container that was completely sealed by welding -- which is how the other German CI patient had been shipped. Facilities manager Andy Zawacki opened the container with tin snips and a chisel, cutting his hand in the process. The patient was in a well-sealed body bag that still contained generous amounts of both ice and ice water.
Surgery for this case was done by Sara Walsh rather than by her father, Jim Walsh. Both are licensed funeral directors. Sara worked much more slowly than does her father, but her meticulous care produced good results: cannulation of both carotid arteries, both jugular veins and the right vertebral artery. The right vertebral artery was quite small and sclerotic, however, so perfusion through that vessel was probably poor or negligible. After cannulation, however, it became evident that there was a bubble that had not been removed from one of the lines. Rather than attempting recannulation we chose to watch the bubble which, as it turned-out, did not move during the perfusion due to its location at a high point in the line.
We had been advised (and we have learned the hard way) that there can be blood or fluid flow from the body into the head, although the vessels involved are somewhat mysterious. There may be small arteries, backflow through veins or perhaps a rich network of lymphatic vessels in the neck that can allow fluid to enter the head from the body even when the carotids, vertebrals and jugulars have been ligated or cannulated. Cryoprotectant is very thick and the very high osmolarity of a brain saturated with cryoprotectant compared to the relatively lower osmotic pressure of body fluids means that body fluids entering the brain could cause neurons saturated with cryoprotectant to swell and rupture. To oppose this osmotic pressure the head end of the operating table was elevated about 30º. CI Director Alan Mole suggested that the body could be prevented from slipping down by the use of mesh foam rubber high-friction material. A "Rub Grabber Plus" pad foam from Lowes costing $7 performed admirably in this regard.
Insofar as no heparin had been circulated to the patient's head we were quite concerned that there could be severe clotting which would prevent perfusion. In fact, there was very little clotting, certainly less than was observed in the previous patient who had received a heparin injection into the right carotid. It is hard to make sense of this, but it is a common phenomenon. Andy Zawacki has said that he has observed clotting much more frequently in the body than in the head, and this perfusion was centered on the head. There is a natural anti-clotting action that happens with the passage of time.
The only scientific paper I can find that addresses this question is an old one:
This paper describes the activity of plasminogen activator released from vacular endothelial cells which controls the level of plasma plasmin which degrades fibrin and/or fibrinogen. Fibrinolysis is activated by stress, and those who die a sudden death or who otherwise have higher levels of catecholeamines in their bloodstream at the time of death have the highest fibrinolytic (anti-coagulant "clot-busting") activity. Fibrinolytic activity and catecholeamine levels are also high in cases of death from oxygen deficiency. The cause of death listed on the death certificate of this patient was "respiratory failure", so she would have been a good candidate for high catecholeamine levels and high fibrinolytic activity.
The patient's daughter did, however, later inform me that she had been giving her mother very low dose aspirin (25 mg) every day along with daily doses of Vitamin E (800 mg/day) and CoEnzyme Q10 (120 mg/day) -- which could be expected to reduce clotting.
Just because we do not see clots and just because there appears to be good blood flow in the brain is no guarantee that there has not been clotting. It is possible that some regions of the brain are receiving no blood flow because of a clot that is totally blocking vessels -- with blood shunting selectively through vessels that are open.
On the other hand, the cryoprotectants that we use in our (vitrification perfusion assists in blood washout. Pure washout solution that contains no cryoprotectant does not remove residual blood as well as a washout solution containing some cryoprotectant.
Perfusion pressure was maintained at 120 mmHg throughout the perfusion, while flow rates declined with the increasingly viscous perfusate. The only exception to this was the first introduction of 70% VM−1 (Vitrification Mixture one) vitrification solution (which is more viscous than the 30% ethylene glycol which precedes it, at least partially because it is at a lower temperature). In introducing VM−1 the first 0.2-0.3 liters were introduced at about 70-90 mmHg with a flow rate of about 0.36 liters/minute. Otherwise, perfusion data for the head (brain) can be presented in tablular form, beginning with the blood washout with m−RPS−2 (modified Renal Perfusion Solution two) carrier solution and ending with 70% VM−1 -- with 120 mmHg perfusion pressure.
The objective is to perfuse the brain until the refractive index of the Jugular vein effluent and/or the burr hole samples matches at least matches the refractive index of 60% VM−1. The refractive index of 65% VM−1 is 1.422 and the refractive index of 60% VM−1 is 1.416. A 60% VM−1 solution is deemed adequate for stable vitrification. (A perfect vacuum has a refractive index of 1.000 and water has a refractive index of 1.333 at 20ºC.)
m−RPS−2 = modified Renal Perfusion Solution two (washout/carrier solution)
EG = Ethylene Glycol
VM−1 = Vitrification Mixture one
RBHRI = Right Burr Hole Refractive Index
LBHRI = Left Burr Hole Refractive Index
RJVRI = Right Jugular Vein Refractive Index
LJVRI = Left Jugular Vein Refractive Index
Perfusion was halted based on the refractive index of the left jugular vein. All refractive indexes were above that of 65% VM−1. Perfusion had begun at 11:04pm and was stopped at 12:06pm. Thermocouple temperature probes were placed deep in the chest, in the nasopharynx (proxy for brain core temperature) and under the skin of the skull near a burr hole.
There was no attempt to perfuse the body. Perfusion of the body of the 77th patient with 80% ethylene glycol had achieved little other than loading the abdomen with cryoprotectant. Worse, the core temperature of the brain rose more than the surface temperature of the head in the 77th patient -- indicating flow of fluid from the body into the head and brain. The potentially destructive effect of body fluids entering a perfused brain osmotically (which caused us to elevate the head of the operating table for this patient) is all the more a threat as a result of the pressure generated in perfusing the body with cryoprotectant. There is no justification for perfusing the body when there is so much evidence of a destructive effect upon the brain as a side effect. Until some solution to this problem is found, it is much better to straight-freeze the body. A straight-freeze of the body does not mean that information is lost, there should still be plenty of information in the body which future nanotechnology and molecular repair technologies could utilize in reconstruction, rejuvenation and reanimation.
The patient was slid from the operating table to a stretcher that contained her backboard and sleeping bag. Her head was then placed in the head enclosure box and surrounded with pellets of dry ice. On the suggestion of Dr. Pichugin silicone oil rather
than n−propyl alcohol was used as the the fluid added to the dry ice. This worked as well and did not create the toxic stench that had been generated with the n−propyl alcohol in previous cases.
We arrived at the CI facility at 1:40am. The deep nasopharyngeal (core brain) temperature was 0.8ºC. The head enclosure was removed and the patient was placed in the cooling box, still lying on her sleeping bag and backboard. When cooling box cooling began at 2am the core brain temperature was −2ºC, the temperature under the skin of the skull was −8ºC, body temperature was +3ºC and ambient temperature was 10ºC.
The computer-controlled cooling box software problems had still not been resolved, but these problems only arose upon reconfiguration of the program -- and erratic behavior could be eliminated by rebooting -- although this would mean a loss of discontinuity of the plot. I decided to program the the entire first seven hours without manual intervention, such that the temperature of the probe under the skin of the skull would drop to below glass transition temperature (Tg) and then rise slowly in an "annealing" step.
Normally the body has a very high thermal momentum, but in this case the body probed indicated that the body was cooling faster than the skin under the skull or deep in the brain. The body had less rather than more thermal momentum than the head probes. This makes no sense. Probably Sara's placement of the body thermocouple did not put it in the center of the chest, as I requested. Possibly it went so deep as to touch the bottom the chest or a side wall of the chest. If the body probe was close to where the sleeping bag was being soaked with liquid nitrogen, it would cool more rapidly and warm more rapidly with evaporation. This is more in keeping with what was observed.
The brain probes went a bit further below Tg than I would have preferred, but not so far (I believe) as to create excess thermal stress and cracking. The rise in the body temperature began to disturb me, so I halted the process at about −106ºC body temperature, rebooted the cooling box and began the hundred-hour cooling from approximately Tg to liquid nitrogen (LN2) temperature.
For the hundred-hour cooling I used the ambient temperature as the controlling thermocouple. It wasn't really "ambient", however. The thermocouple was in a box (to prevent it from being sprayed with liquid nitrogen) and in a small block of thermal insulation (to reduce excessive cycling). This did not work so well because the controlling temperature was a fair bit higher that the head or body temperatures. Again, the body temperature was the lowest, because of closer contact with liquid nitrogen, I suspect. As the head temperatures approached liquid nitrogen temperature I manually intervened again and held the skull and brain temperature at about −192ºC until we were ready to do the transfer. Then I manually dropped the temperature to −194ºC (the lowest temperature obtainable in the cooling box) in preparation for removal.
This patient was the sixth and last to be put into the HSSV−6−6 cryostat (HSSV−6−7 was filled before HSSV−6−6). The ropes on the other five patients already in that cryostat were tied to the sides in such a way to assist in the placement of the final patient in the remaining "hole" between the other patients. The final stages of tying and inserting into the cryostat cannot be done quickly enough. Years of experience have given Andy the expertise to move with speed and efficiency.
The cooling box was opened at 8:58am on the morning of Monday, March 12th, the patient was removed at 9:04am and the patient was in the cryostat by 9:18am.