The Cryonics Institute’s 75th Patient: By Ben Best
The 75th patient of the Cryonics Institute had many things in common with the three patients that preceded her. She was a mother cryopreserved on the initiative of her son, the signup occurred with the mother in a terminal state (post-terminal for the 73rd) and payment was in cash.
Five weeks previously the son had phoned to say that his mother was in the hospital, that he would get a loan on some land to pay for cryopreservation and that his father approved of cryopreserving his mother if she became legally dead. On a Saturday morning at 4:30am the son phoned and told me that his mother was in the ICU. He paid the $1,250 Option One Membership fee by credit card and FAXed the membership application to lock-in the $28,000 rate.
Fifteen hours later we got a call from a physician in the ICU saying that the mother had coded and was getting defibrillations to restore regular heartbeats, but said that he couldn't keep her alive much longer. The physician was aware that the mother was a cryonics patient and he wanted information on how a cryonics case should be handled. I explained that we wanted heparin injected as soon as possible and that the heparin would be most effectively circulated if it could be given pre-mortem. The physician requested that we FAX our hospital instructions, which we did. The mother was given heparin pre-mortem and ice was packed around her head immediately post-mortem (post-pronouncement). She was transferred to the hospital morgue and kept in a refrigerated unit with ice packed around her head.
The patient had been hospitalized for nearly a year and had been in a semi-coma for at least the last month. She had a history of untreated type 2 diabetes and she had experienced multi-organ failure. Early in the year she had a liver transplant due to autoimmune hepatitis. She was given immune suppressant drugs. She had kidney failure and was on dialysis. She suffered from multiple infections which she had acquired as a result of spending so much time in hospitals, notably MRSA. This resulted in bacterial growths in her heart that had been removed and a mitral valve had been replaced. She never got off the ventilator following the heart operation. She had some mini-strokes which reduced her spontaneous speech and increased her sleeping.
The son wired $22,111 Monday morning and was still scrambling to raise the rest from his father's credit cards and other means. But the greatest delay factor proved to be the fact that his mother was in a Chicago hospital and the laws of Chicago and the hospital procedures are horrible in terms of permitting rapid shipment. Only her physician was permitted to sign the death certificate and he did not do so until Monday afternoon. But Chicago regulations do not permit the hospital to release the body until the death certificate has been filed, and filing was not completed until Tuesday. Avoid Chicago hospitals!
We received the patient late Tuesday evening and began perfusion a few minutes before midnight. The patient had experienced about 80 hours of cold ischemia. She was edematous and had a generally bad appearance. She was a rotund woman, which was exacerbated by the edema. On the positive side the heparin made the blood washout uncomplicated.
As we have done with all perfusions since our CI's 69th patient, we perfused through both the vertebral and the carotid arteries. The carotids alone do not perfuse the whole brain for about 15% of people and for about 50% of stroke victims. To make our surgery more clear I have made a more careful drawing of the relevant arteries, which is shown.
Our funeral director gains access to the blood vessels by incisions just below the clavicle. Slits (incisions) are made in the arteries for the insertion of the cannulation tubes (blunt needle-like cannulas) required for perfusion. The vessels are clamped below the incisions. The cannula on the left side of the drawing (right side of the patient) perfuses both the vertebral and the carotid. The right side of the drawing (left side of the patient) illustrates that the carotid and vertebral are independently cannulated and perfused. On a previous perfusion our funeral director indicated that we could cannulate the carotid and vertebral independently on the left side (patient's right side) as well, but he did not want to do this when it came to perfuse this patient, saying that the vertebral was too small. Andy Zawacki had prepared the tubing to allow for independent perfusion of four arteries, but we ended-up only using three cannulae.
This patient was perfused longer than any patient previously had been perfused, in an effort to reach a refractive index of Burr hole (holes drilled in the skull -- one on the right side and one on the left side) samples that matched the refractive index of 70% VM−1 (Vitrification Mixture). As usual, perfusion was begun with m−RPS−2 washout/carrier solution (the solution that "carries" the vitrification cryoprotectant). Then VM-1 was perfused in increasing concentrations, 10%, 30% and finally 70%. Although the refractive index rose, it would not rise high enough to indicate complete brain saturation. To test whether slow diffusion into brain tissue was occurring, there were two five-minute pauses.
After perfusion with 30.0 liters of 70% VM−1 the refractive index was no higher than it was after 19.5 liters. Although this may be partly due to the fact that the VM−1 needed to saturate into tissues, seeing little progress the perfusion was terminated. Possibly brain edema was part of the problem, but that would not explain why the refractive index rose so well during the early part of the perfusion. There was no shrinkage of brain evident from the burr holes.
After having perfused the brain and head it was decided that the patient was too already too edematous to even attempt to perfuse the body. The funeral director drained some fluid out of the abdomen, which should have reduced some bulk ice formation and hastened cooling.
Andy has built a head-cooling box, which we used for cooling the head while we perfused the body of CI's 74th patient. Even though we did not perfuse the body of this patient, we used the head cooling box to accelerate head cooling during transport of the patient from the funeral home to the CI Facility.
Previous discussions of the head-cooling box invariably provoke concern that we are removing the patient's head from the body, which is untrue. The policy of the Cryonics Institute does not allow for neuropreservation, much less separation of the head. To clarify the use of the head-cooling box some photos of a mannequin in the box may better illustrate its use than words alone.
The head is placed in the box while the neck is cradled on the edge of the cutout in the side of the box and the body remains attached. The body lies outside of the head-cooling box. A slider in the notch for the neck makes a complete seal around the neck so that the head-cooling box can be filled with dry ice and n-propyl alcohol.
(Much as a slurry of water ice and ice water in a portable ice bath greatly accelerates cooling of a cryonics patient's body, a slurry of dry ice and n-propyl alcohol in a head-cooling box accelerates cooling of a cryonics patient's head. As a proof in principle I cooled two golf-ball sized spheres of hamburger in two cottage cheese containers filled with dry ice. Without n-propyl alcohol a hamburger sphere cooled from 7.7ºC to −56.9ºC in 32 minutes, but the container with dry ice in n-propyl alcohol slurry cooled from 7.7ºC to −56.9ºC in 7.25 minutes -- more than four times faster. Although n-propyl alcohol is more expensive than isopropyl alcohol, it has a wider range of liquid state temperatures: −127ºC to +97.2ºC versus −86ºC to to +82.4ºC for isopropyl alcohol. Insofar as the sublimation temperature of dry ice is about −79ºC n-propyl alcohol may be overkill, and we may try using isopropyl alcohol in the future.)
After the patient was transported to the CI Facility she was placed on a sleeping bag, the head-cooling box was removed, she was placed on a backboard and she was cooled in our computer-controlled cooling box and was cooled for six days.
Andy had put a great deal of work into trying to adapt the cooling box so it was controlled-flow in the sense of only allowing a flow of gas out of the box through a pipe with a one-way valve. But his efforts failed quickly. Nonetheless, the cooling box does prevent entry of water vapor and deposition of ice crystals on the patient, which is what is most important.
Our funeral director had placed thermocouple probes under the skin of the skull (the controlling thermocouple), just under the skull on the surface of the brain (through the Burr hole) and deep in the nose (brain core temperature). As the first five hours of cooling indicate, the red probe and the green probe tracked each other closely. This leads me to conclude that in the future a probe in the Burr hole should not be necessary.
Although the time is not indicated on the graph, about 25 hours were spent on an "annealing" stage, where the brain surface temperature was first held at −130ºC and then elevated until it was briefly above the core brain temperature. As is shown in the "annealing detail" plot, the surface temperature was above the core temperature for about an hour in the range of −116ºC to −114ºC. Achieving thermal uniformity of the brain just above glass transition temperature (Tg) is a means of reducing thermal stress (cracking) during the slow cooling over several days to −196ºC (−191ºC, actually, insofar as our cooling box will not reach −196ºC).
On Monday, six days after receiving the patient, she was placed in liquid nitrogen in a cryostat. The son requested Roman Catholic rites for his mother in the cryostat. I told him that if his mother is a patient in biostasis that last rites would not be appropriate, but that we have made various accommodations for people of different religions in our cryostats. The son said that he figured that he gave a 50% chance for cryonics and a 50% chance for last rites, and he wanted to cover all the bases.