The Cryonics Institute’s 91st Patient: By Ben Best
The 91st patient of the Cryonics Institute (CI) is Jackson (Jack) Zinn, a 65-year-old California lawyer with a long history of cryonics membership. Jack has had cryonics arrangements with the American Cryonics Society (of which he was once President), Trans Time, Alcor and most recently CI. He even tried to start his own cryonics organization (the International Cryonics Foundation). He involved himself in a number of cryonics-related legal cases, such as the fight to establish the legal right to cryonics in California. Jack may be most recently remembered for the "High Rollers" conferences that he organized in Laughlin, Nevada in the late 1990s.
Jack preferred to be a "neuro" (head-only) patient, but CI does not offer that service.
The patient had been suffering from congestive heart failure since the year 2005. In the months prior to the most recent hospitalizations CI received a number of phone calls (often in the middle of the night) either from the Member (because he was worried or upset) or in connection with his being in the emergency department of a hospital.
On October 2nd, 2008 CI received a phone call from the cardiac Intensive Care Unit (ICU) of a St. Joseph's hospital in Stockton, California because of the bracelet or necklace that the patient was wearing. This is probably the first case in the history of cryonics where jewelry has led to a phone call that assisted pre-mortem cryonics treatment. (In a previous case CI was informed post-mortem by a morgue that called because of jewelry they found on the patient.) A social worker associated with the case for the hospital was helpful in providing information. The hospital approved cooperating with the cryonics wishes of the patient.
Later, when I phoned the hospital ICU I was told that the patient was "awake, alert and stable", although confused. A few days later when I phoned I was told that he had been removed from the ICU and transferred to another wing of the hospital. When I phoned that wing they had no knowledge of the patient. For a couple of days I was unable to find anyone who knew of the patient's whereabouts. I had phoned the patient's home number many times, but it was always busy. I had begun to assume that the phone had been left off the hook. But after a few days it rang, and the man who answered told me that the patient was in the ICU of Dameron, a different Stockton hospital.
Dameron hospital confirmed that the patient was in the ICU, but because of strict adherence to HIPAA they would not provide health status information over the phone. I called their attention to the cryonics jewelry and the patient's desire to be cryopreserved. A couple of days later I was informed that the physicians & nurses by then all knew about the cryonics arrangements and that CI would be phoned if the patient died. The hospital ethics committee was not going to interfere with the patient's cryonics wishes, but I was told that no nurse or physician would place ice on the patient or otherwise become actively involved in cryonics treatment. The patient was being treated with Lovenox to prevent deep vein thrombosis which could have reduced the need to administer heparin — but heparin was nonetheless desirable.
The patient was unconscious and on a ventilator. The hospital had tried without success to remove the ventilator over a period of days. The patient had named a Power of Attorney for Health Care, Nolan PAHC — a partner in his law office. On Friday, October 17, 2008 the patient's prognosis was that he would not recover. Mr. PAHC as the patient's Power of Attorney had approved removal of the ventilator on the following Monday. At the suggestion of a nurse responsible for the patient at the time, removal was set for 9 am. There was an argument that the time should be set in accordance with airline schedules, but there was so much uncertainty about many issues that an early removal at a time with high staff availability seemed the best way to facilitate same-day shipment. Despite the fact that the previous attempts to remove the ventilator had failed, there was a chance that the patient would not deanimate immediately after the ventilator was removed.
There were enough friends and willing cryonicists in the area that a team of people assembled to volunteer to help with chest compressions and cooling when the ventilator was removed. Three of the initial friends/volunteers were Alcor Members and two were American Cryonics Society (ACS) Members. Two of the Alcor Members had signed "non-compete" agreements during Alcor Transport Training courses. Alcor kindly agreed to a temporary waiver agreement (drawn-up by one of the volunteers) to allow these Members to participate in this case. It was rightly viewed the field experience from this case could be of benefit for future participation by these volunteers in Alcor cases.
Because the hospital had told me that the patient has Methicillin-resistant Staphylococcus aureus (MRSA), I told the volunteers that we cannot risk the chance that they would contract MRSA while in the process of giving chest compressions. So while friends, family and volunteers were to be on hand when patient's ventilator was removed, the most help that they could give would be in cooling and moving the patient. The hospital would attempt to ensure that a physician or nurse was on hand to give quick pronouncement before the ventilator was removed.
This was a difficult case, not only because of the MRSA, but because the patient is 5−feet 4−inches tall and weighs nearly 300 pounds. I don't mean to discourage heavy CI Members in making this comment, but I had not previously dealt with a patient this size and shape, and it posed new challenges — especially with the MRSA. I believe that what we learned from this case will assist us in providing good service to CI patients who are much heavier than this one was.
I was given mistaken information that the patient had lost a great deal of weight, and was down to 200 pounds. I told our funeral director that an oversized shipping box was not needed. Fortunately, the Inman funeral director got the patient's height and weight — proving me wrong for trusting hearsay. There was not time to get an oversized Ziegler case for the patient. The Inman funeral director had a bioseal system that reportedly could be used with a large shipping box to contain the MRSA and ice. I did not understand the details.
The local funeral director for this case was selected by CI funeral director Jim Walsh's Inman funeral director network. The Inman funeral director was nearly two hours drive away from the hospital where the patient was staying. Jim Walsh told me that because death was not a certainty upon removal of the ventilator that the Inman funeral director would only come after death had been pronounced. I arranged to have the Inman funeral director paid to wait at the hospital at the time the ventilator was to be removed. The negotiation process was made difficult because Inman does not even allow direct communication between funeral directors (fearing that they will "cut a deal" that leaves Inman out). Anything that I wanted to say to the Inman funeral director would have to go through Jim Walsh talking to the Inman representative who would talk to the Inman funeral director. Direct communication between the Inman funeral director and volunteers was obviously impossible.
At 9am on Monday, friends, family (ex-wife) and volunteers were ready, but the funeral director's driver did not arrive until an hour later. But after some delay the hospital decided against removing the ventilator, so the lateness of the driver was not critical — although it could have been. Jim Walsh had phoned me and told me to tell the volunteers to go home because they were bothering the Inman funeral director's driver. Jim also raised the issue of liability. With Inman representatives like this there is no hope for help from cryonics volunteers for remote CI Members.
The liability issue is a genuine one and if we are to worry about it fully, then that is the end of any possible involvement of volunteers for any cryonics case. We could adopt a policy of "no volunteers-ever" for the Cryonics Institute and that would certainly be the safest thing that we could do, but it would be a great blow for patient care. Or perhaps we could make an exception for relatives — or would the liability issues be different? Alcor has a long tradition of using volunteers, although in many cases they have had the volunteers sign contracts disclaiming any responsibility. My understanding is that CI had a tradition before my time of using volunteers when the occasional standby was done. Since my involvement in CI the cases in which volunteers have been involved were the Toronto case (in which I led a standby), the 72nd patient, and the more recent cases in Europe and Australia.
If we follow this "no volunteers" principle then CI must issue a "hands-off" ruling against any involvement to the Cryonics UK group, the Australian group or any other local group anywhere in the world that wants to have volunteer local help. I don't mean to be dismissive of the legal liability issue, but somehow that must be weighed against the possibility of self-help by cryonicists and the benefit for patient case that volunteers can provided.
Although the patient was still unconscious on 9am Monday, a physician saw improvement and thought there was a possibility that the patient could recover. The hospital was also concerned about what the patient had put in his Advanced Health Care Directive. It was in this Directive that the patient named his law partner as his Power of Attorney for Health Care (whom I will call "Mr. PAHC"). Mr. PAHC had notarized the Directive. A few people told me that this had raised a question about the authority of the law partner to be Power of Attorney for Health Care and to authorize removal of the ventilator. But Mr. PAHC told me that his notarization only certified that the signature on the Directive was that of the patient. The entire Directive had been filled-out by the patient by hand.
Mr. PAHC told me that the reason the ventilator was not removed was because a physician had said the patient could recover and because in the Instructions for Health Care section of the Directive, the patient initialed "Choice to Prolong Life" rather than "Choice to Not Prolong Life". In the "Other wishes" section, the patient wrote "I wish the treatment that best contributes to the cryonic preservation of my remains". It seemed possible to me that if an affidavit could be written by an authoritative person that certified that the patient's wish to be cryonically preserved under the best condition was being compromised by remaining on the ventilator, the latter instruction might take precedence.
Before the Monday when the ventilator was removed, the hospital had been giving health status updates to the patient's ex-wife, who was very supportive of the patient's desire to be cryonically preserved. After the Monday, the hospital would only give health status information to the Power of Attorney. An appeal by next-of-kin was unlikely. On his Member Questionnaire the patient had named his elderly aunt as next-of-kin, rather than his 26-year-old daughter — as if he could choose his next-of-kin. He had written in the questionnaire that his daughter might oppose the cryopreservation. The patient's ex-wife confirmed that the daughter is anti-cryonics and that to involve the daughter in the case could result in trouble.
Belatedly, I did a MapQuest search for funeral directors located close to the hospital. A funeral director located within a few blocks of the hospital — Matt Bryant of Wallace-Martin Funeral Home — agreed to take the case. The people at this funeral home were extremely dedicated to helping people fulfill their wishes, however unusual those wishes might be. They had a special shipping box built that would handle someone this patient's size, and this box was built within one or two days.
When I asked Matt Bryant how big a person needs to be before they would be shipped in an oversized Ziegler container he told me 300 pounds, but width is very important. Jack is 5'4" and 300 pounds, which makes him much wider than someone who would be 6'4". Height only becomes a problem above about 6'4" because the Ziegler's are 6'5". The company who manufactured an oversized Ziegler box for another of CI's patients told me that anyone over 250 pounds should have an oversized shipping box, but they may be biased by the fact that they manufacture shipping boxes for oversized corpses. Our 81st patient was 6'2" and 250 pounds and we had no trouble shipping him in an ordinary Ziegler box.
Wallace-Martin Funeral Home was agreeable to having volunteers help with cooling and ice packing. And they provided me with emergency phone numbers and said that with proper pre-arrangement they could ship the patient on a weekend if the patient deanimated on a weekend — something I had not thought was possible in California. I informed Jim Walsh of this change of funeral directors and I put Jim in contact with Wallace-Martin Funeral Home.
Mr. PAHC, the patient's Power of Attorney for Health Care, attempted repeatedly to get the hospital to inform him which physician would sign the death certificate. This information is essential if the patient deanimates on a weekend because the funeral home can ship on a weekend if they have causes of death and the name of the physician signing the death certificate. Normally shipping of a patient on a weekend is not possible in California, but a woman who works at the Stockton funeral home told me that she has personal phone numbers of people who work in the health department and that because of this she has been able to ship on weekends many times. She did not know what the availability of this service is to others.
Mr. PAHC tried in vain to speak with a physician, but could only manage to get nurses to speak with him. It would have been best if a neurologist could have evaluated the patient. The fact that the patient was responsive to pinpricks and had not been removed from the ICU would seem to indicate that no one thought he was brain-dead. The patient's ex-wife told me that the patient had never experienced a stroke or heart attack, which increased the chance that no neurodegeneration was occurring while the patient was on the ventilator. But why was he unconscious/sleeping all of the time? In retrospect, as Power of Attorney for Health Care Mr. PAHC could have gone to the hospital administration and demanded a neurological assessment. Also, if the patient had named an alternate medical surrogate who was a medically-knowledgeable cryonicist, the access to medical information could have been better. Choosing a medical surrogate or alternate who is a Cryonics Institute Director would definitely NOT be a good idea because of the potential for conflict of interest — especially if life-support is to be removed.
Mr. PAHC was being told different stories by different nurses, and he was my only source of medical information. One nurse said that the patient had awakened, but was not responsive to hand-holding or spoken commands. The patient was being given been given diuretics. Mr. PAHC told me that the patient was accumulating fluid (probably ascites associated with the patient's congestive heart failure) which was being suctioned four times per hour. The patient's blood count dropped, but a blood transfusion had no lasting effect on keeping the blood count from dropping.
A nurse also told Mr. PAHC that the patient was mostly breathing on his own, but not enough to be removed from the ventilator. She said that the patient was too unstable to be moved to a chronic ventilation support facility. He had already been in this ICU for over two weeks, but they were not giving an impression of rushing the patient out as long as he was unstable. (All the ICU expenses were covered by the patient's Medicare.)
If the patient was moved to a chronic ventilation facility he would probably not have lasted long. His fluid would not have been drained and he could easily have died of pneumonia (I am told this happens often in those places). Deanimation would be at an unpredictable moment and the chronic ventilation facility people might not be very friendly to the idea of volunteers. If a decision was made to move the patient to a chronic ventilation facility that would have been a signal to try to get the ventilator removed at a scheduled time.
On Friday, October 31st, the patient was producing so much fluid that the hospital was having trouble suctioning. A decision was made to remove life support, with approval from Mr. PAHC. The patient had still been apparently unconscious/asleep all of the time, although his eyes sometimes opened. The hospital agreed to remove life support on the following Monday — November 3, 2008 at 9am — a time scheduled to allow for cryonics volunteers to be assembled and other preparations to be in place.
The "Other wishes" section of the patient's Advanced Directive ("I wish the treatment that best contributes to the cryonics preservation of my remains") did not seem to affect the decision. Apparently neither the hospital nor Mr. PAHC had been able to read that section. Only on Friday the 31st did Mr. PAHC tell me the "Other wishes" section was illegible to him. But I could read it fairly clearly. I don't see how the words could be anything other than what I read them to be.
On Sunday the patient had kidney failure, and the hospital again affirmed to Mr. PAHC that life support would be removed the next day.
The Stockton funeral home people seem to be willing to go to great lengths to accommodate our wishes, but they had limits. On the Friday, Mr. Bryant told me that the funeral home would not allow volunteers to be involved once the patient was in their possession because of liability concerns associated with the MRSA. He said that if it were not for the MRSA they would allow the volunteers to work in a room at their funeral home. Mr. Bryant told me that he personally had a bad experience with MRSA. He said that he got an insect bite, and because he probably had gotten MRSA in association with his job the insect bite got infected, was lanced and diagnosed as MRSA — and he was sick for a month. He said that he would arrive at the hospital at 8:45 am on Monday and would wait outside — but he would not go inside the hospital before the patient was pronounced dead. It is the funeral home's policy not to enter the hospital pre-mortem because it makes them look like vultures, and upsets family members.
As things stood Friday it appeared that the volunteers would have no place to work and would be unable to touch the patient because of the MRSA. Some CI advisors suggested that the risk from MRSA is overblown or misguided. Reportedly 0.8% of the American population is colonized with MRSA and 32% with ordinary methacillin-sensitive Staphylococcus aureus ("Staph") [JOURNAL OF INFECTIOUS DISEASES; Kuehnert,MJ; 193(2):172-179 (2006)], mostly on the skin and in the nose. Hand-shaking is a common practice that can spread Staph, especially because over 90% of people pick their nose. In most cases, neither form of Staph causes harm to healthy people having healthy immune systems.
Hospitals are cesspools of infection, which is easily spread among people with compromised immune systems. The proportion of Staph that is MRSA in the American ICUs increased from 2% in 1974 to 64% in 2004 [CLINICAL INFECTIOUS DISEASES; Klevens,RM; 42(3):389-391 (2006)]. But staff typically do not suffer from MRSA — it is the sick patients that are unable to resist the effects. And hospital-based MRSA is less virulent than community-based MRSA, which is a different strain of bacteria. Unlike the hospital-based MRSA, the community-based MRSA sometimes has the appearance of an insect bite and causes considerable infection-related illness to affected persons [EUROSURVEILLANCE; Vandenesch,F; 9(11) (2004)].
But I had little hope that I could use this material to influence the attitudes of the funeral directors or hospital staff involved in this case.
Because I had the impression that it was unlikely that either the hospital or the funeral home would allow non-staff to touch the patient on their facilities I spent many hours Sunday phoning ambulance companies in the Stockton area. My plan was to have an ambulance company take the patient and do cooling and CPS in their vehicle in the parking lot of the funeral home under the direction of the funeral director. A few of the companies might have been willing to help if I had called a few days earlier. Pro-Transport-1 told me that they would need time to check with their legal department and study possible liability of a cryonics case. None of the ambulance companies had such a request before and they were a bit weirded-out about the whole thing. Some were quite friendly, though. Hughson Ambulance Paramedics told me that they would have helped if I had called sooner, but that there was not time enough to get the necessary staff together. American Medical Response may have had a similar issue -- they told me that they might change their mind on Monday morning. Eight a.m. Monday morning is the busiest hour of the week for heart attacks, so this may have been a factor.
The patient was overfunded by insurance policies above the minimum cryopreservation fee, so I felt that I had some leeway to incur extra expenses. (The patient had not been paying his premiums recently, but there was enough cash value in the policies that the premiums were covered.) I cannot say that I could have made these efforts on behalf of CI Members who fund at the bare minimum. I may not even have been able to change funeral directors, because the Inman funeral director would have been much less expensive. The special shipping box alone cost a few thousand dollars, an expense we would have avoided with the Inman funeral director. CI Members are advised to fund above the minimum for this and other reasons (such as protection against future uncertainties, and access to future services which may be available at extra cost).
When I called Mr. Bryant on Sunday evening, however, he told me that the volunteers could come to the funeral home. He provided his cell phone number to one of the volunteers. The funeral home had decided that despite the MRSA that the volunteers could do chest compressions in a room of their funeral home so long as the patient remained completely sealed in the body bag.
At 9 am on the morning of Monday, November 3, 2008 four volunteers, Mr. PAHC and another long-time lawyer friend of Jack's were waiting in the hospital for life-support to be removed. Two funeral home staff people were waiting with a vehicle at the loading dock of the hospital. But the physician in charge of removing life support did not arrive until an hour later. During the wait, Judy Segall arrived and was able to spend about ten minutes alone with Jack in the ICU. At 10:10 am the ventilator and a heart catheter was removed. All drugs were discontinued except morphine. An oxygen mask was also used to improve patient comfort (some of the volunteers questioned whether this is a good practice). Nurses kept predicting that the patient would only remain alive another 15 or 20 minutes, but his heart did not stop until 11:28 am.
Pronouncement of death had been prompt because nurses had the authority to pronounce. A nurse administered 40,000 IU of hospital heparin after pronouncement. The volunteers were impressed by how well the nurses did chest compressions post-mortem. The patient was placed in a body bag supplied by ACS (the hospital's body bag was too small) and the volunteers added 50 pounds of ice. (In a debriefing later, the volunteers joked that a cryonics party needs lots of ice and is BYOBB — Bring Your Own Body Bag.) The funeral home staff wheeled the patient to their vehicle and drove him to the funeral home.
At the funeral home the volunteers wore gloves and protective coveralls ("bunny suits"), which were supplied by ACS. At the hospital they had donned "bunny suits" provided by the hospital. Another 50 pounds of ice — along with bleach — was added to the body bag and then the volunteers took turns giving chest compressions through the body bag for an hour. I later learned that the volunteers had added the bleach for the protection of those of us in Michigan who would be opening the body bag. But it had been my intention that they use the bleach to protect themselves from infection.
With a patient in ice water, chest compressions cool the body by improved conduction/convection. But cooling of the head will be slowed by warm blood from the body — especially in this case where the patient has such a large, round body. That effect will be compensated if the brain can receive nutrient & oxygen from the blood to retain viability. But as the blood becomes increasingly depleted of nutrient & oxygen, chest compressions become increasingly disadvantageous to the extent that they slow head cooling with no compensating benefit. I had originally suggested that they do chest compressions for an hour, but even that may have been too long.
The volunteers were very pleased with the cooperation and competence of Wallace-Martin funeral home staff. One volunteer commented very favorably on the design of the large, strong, zinc-lined, silicone-sealed waterproof shipping box. He had worked on other cryonics cases (with Alcor) and rated Wallace-Martin as far superior to the other funeral directors — adding (jokingly) that every time he dies in the Stockton area he will be sure to use Wallace-Martin.
The volunteers stopped at about 1 pm, Pacific Time. The patient had to arrive at the airport three hours before departure, which was about 9:30 pm. There was evidently no delay in obtaining the death certificate and transit permit. The death certificate was signed by the attending ICU physician. Apparently whomever was the attending ICU physician at the time of death was to be the one to sign the death certificate. The hospital could have saved us much frustration by telling us this.
I was phoned by a Stockton journalist who was evidently well-acquainted with Jack Zinn. At Jack's request, that journalist had written an article about Jack's cryonics interests in the January 7, 2004 issue of his newspaper. Jack told another lawyer in his office that when he is cryonically preserved that he wanted the lawyer to phone the same journalist with the story. The journalist told me that he had long admired Jack for his work to help immigrants and homeless people. The journalist had quite a bit of information about the case already. All I added was details about the Cryonics Institute & its operation — and my hopes. I had not been planning to disclose Jack's identity, but there was no longer any reason not to. Jack was always very public about his cryonics involvement — no less than I am. On Wednesday a newspaper article describing the case appeared in THE RECORD — a newspaper local to the Stockton area: Attorney's final wish: to chill out.
The patient arrived at the Detroit airport at about 5 am, Eastern Time — and did not arrive at Jim Walsh's funeral home until about 7:30 am. Jim Walsh had gone to Florida, so his funeral director daughter, Sara, was in charge of the surgery.
Another funeral director had been called-in to assist, but when he found out about the MRSA he said that he would have to leave because recent surgery had weakened his immune system. He did stay to help remove the patient from the shipping box, which was no simple task. The box was lifted to the ground and then turned on its side. Water flooded out. The body bag was cut, and more water flooded out. A couple of ziploc bags contained mostly water along with a few pieces of ice. The 100 pounds of ice (the amount I had suggested) had been inadequate for a patient this size, for the time delays, and for the amount of insulation used. (A partial roll of wool insulation had been provided by the volunteers.) I had told the Stockton funeral director to use insulation, but he told me that the box provided adequate insulation on its own. That clearly was not correct. There would have been ample room in the shipping box for additional ice and insulation. I blame myself for this mistake, but some of the voluneers blame themselves as well. Hopefully, there will not be a future CI case in which less than ample ice and insulation is used.
The patient was loaded onto a gurney, wheeled into the funeral home and transferred to the operating table, all with the assistance of the other funeral director. He handed strings to Sara while she did surgery before he left — thereby remaining longer than he had intended.
Because of the MRSA, Jim Walsh said that he would not go through the chest, so his daughter reverted to perfusion through the carotids and vertebrals. Instead of cannulating the subclavian artery on the patient's right side (left side in the diagram), she cannulated the right carotid — missing the right vertebral. On the left side, however, she cannulated both the carotid and vertebral arteries, as usual. To overcome past difficulties in cannulating the jugular veins, I had placed a ring of glue a few millimeters from the end of the cannula to act as a sutre ring. That cannula did not fall out — as so many have in the past — so my idea may have been a good one. Unfortunately, Sara severed the left jugular vein during her surgery, so there was no possibility of cannulating that vessel.
For the 88th and 89th patients perfusion was into the aorta and drainage was from the superior vena cava. No burr holes were made in those cases, partially because I was feeling confident about reading refractive index values from the superior vena cava effluent. With reversion to the old surgical method — and with our previous experiences of unreliable effluent from the jugulars — I felt the need to have burr holes again to assess brain saturation with vitrification solution. I also requested that burr hole size be increased. So the burr holes were three-eighths rather than one quarter inch in diameter. Burr holes are intended to relieve pressure in the brain when cerebral edema occurs, but not once has brain tissue been observed to protrude from a burr hole during a CI perfusion — which would imply that cerebral edema has not occurred since the use of burr holes. The extreme facial edema of the 87th and 89th patients was quite disturbing to me, however. I thought that a larger burr hole would be better for brain visualization, even if not for pressure relief.
Rather than interrupt perfusion, burr holes were made before surgery began, at my request. This was probably not a good idea because of the bleeding. It is probably best to make the burr holes after a few liters of CI−VM−1 have been perfused — and well after blood has been washed out. The brain should have shrunk somewhat by that time.
My concern about the extreme facial swelling (edema) in the 87th and 89th patients also motivated me to increase the osmolality — and add oncotic support — to the 10% EG (ethylene glycol) perfusate. I added enough KCl to increase osmolarity by 100 milliosmoles and enough polyethylene glycol (PEG 20,000 Mwt) to provide the oncotic support (ie, blood vessel rather than cell membrane osmotic pressure) of normal blood albumin (28 mmHg). Instead of KCl I could have used glucose or mannitol. Cells already swollen with sodium (due to sodium pump failure) would not be expected to absorb more potassium. Any potassium that enters a cell might actually drive out sodium. But the major effect of extra extracellular potassium and chloride would be to draw water out of cells. Normal osmolality is about 300 milliosmoles, so an additional 100 milliosmoles is not much, especially in light of the fact that 10% EG in carrier solution is nearly 2,000 milliosmoles, 30% EG is over 4,000 milliosmoles, and 70% CI−VM−1 is over 10,000 milliosmoles. Admittedly, the effect is transient, but it takes at least 5 minutes for enough cryoprotectant to enter cells to significantly reduce the differential between osmolality outside a cell and osmolality inside the cell. (Hypertonic solutions are not very damaging to cells that are not to be returned to isotonic, normothermic conditions — as is the case in cryonics.)
Eight liters of hyperosmotic 10% EG solution was perfused into the patient. The dehydration of the head and face was dramatic, but there was little sign of rehydration by the time perfusion was completed. Nor was there any sign of either shrinkage or swelling of the brain from visual inspection of the burr holes.
When the patient was placed on the operating table his nasopharyngeal temperature was about 10ºC, which I expect was not much above the temperature of the rest of his body. Some ice was placed on his head, but temperature nonetheless rose to about 11ºC during surgery. Once perfusion began, the temperature started dropping. Temperature continued to drop until it was between 0ºC and 1ºC during the last 20 minutes of perfusion.
The perfusion began at 9:08 am with the addition of the 8 liters of the hyperosmotic 10% EG solution, followed by 6.5 liters of 30% EG solution and 16.5 liters of 70% CI−VM−1. We were fortunate to have a burly funeral home assistant who helped with moving the patient and who took excellent notes (there has generally not been enough staff to have good note-taking for these case reports). Data from the 70% CI−VM−1 perfusion can be presented in table form. Flow rates were in the range of 0.7 to 0.8 liters per minute. Line pressures were measured in the 140 to 150 mmHg range, which is probably about 40 mmHg above pressures in the patient's arteries.
70% CI−VM−1 perfusion began at 9:30 am. Recording of refractive index values began at 9:35 am.
The objective is to perfuse the brain until the refractive index of the effluent at least matches the refractive index of 60% VM−1. The refractive index of 65% VM−1 is 1.422, the refractive index of 60% VM−1 is 1.416, and the refractive index of 55% VM−1 is 1.410. 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.) The jugular vein effluent should be the most important. The meaning of the burr hole effluent is less clear.
RJVRI = Right Jugular Vein Refractive Index
RBHRI = Right Burr Hole Refractive Index
LBHRI = Left Burr Hole Refractive Index
Refractive Index values taken during CI−VM−1 perfusion
|TIME (am)||TEMP (ºC)||RJVRI||RBHRI||LBHRI|
After thermocouples were placed in the chest and under the scalp, the patient was removed from the operating table onto a gurney. The anti-coagulants had worked like a charm — there was no sign of clotting at any time. But moving the patient was messy & difficult, not only because of his weight & shape, but because his MRSA-infected blood would run out. The blood also spilled on the floor of the CI facility. Liberal amounts of bleach were used in cleaning blood from the floor of the funeral home and the CI facility. CI facilities manager Andy Zawacki suggested that doing a body washout might be a good way to reduce the mess and danger of infection. If CI resumes having perfusions through the chest, however, there should not be a problem of excessive blood still in the body when a head-only perfusion is done.
As usual, dry ice in an isopropyl alcohol slurry has been packed around the patient's head at the funeral home, and was removed at the CI facility. At the CI facility the patient was placed in the computer-controlled cooling box. When cooling-box cooling began at 12:06 pm the nasopharyngeal temperature was 3.5ºC and body temperature was 19ºC. Temperature under the skin of the skull was rising after removal of dry ice — rising from −22ºC to −17ºC in the first few minutes of cooling before dropping again.
The thermocouple in the skin above the burr hole is used as the controlling thermocouple by our LabVIEW computer control system. Cooling of vitrified tissue should be as rapid as possible to glass transition temperature (Tg) [solidification temperature — which is −121ºC for 70% (w/w) CI−VM−1 and −123ºC for 60% (w/w) CI−VM−1], but should not go much below that temperature in the first phase. Cooling must be done quickly above solidification temperature to prevent ice formation which might occur in areas which are poorly perfused. Below solidification temperature cooling must be done very slowly to minimize cracking due to thermal stress.
|Full 138 Hours|
The cooling strategy is to cool the surface of the brain as rapidly as possible to Tg and then wait until the temperature in the center of the brain approaches Tg. Once the center of the brain is close to Tg the surface is warmed slightly in the hope that the entire brain could be of uniform temperature in a highly viscous "liquid" state just above Tg. This is not actually "annealing", because annealing involves warming a solid to just below melting temperature as a means to relieve thermal stress in a solid. By remaining just above Tg for the entire brain and cooling very slowly through Tg we believe we achieve the greatest temperature uniformity and the least thermal stress, while relying on the very high viscosity to prevent devitrification.
I allotted six days for patient cooling. As mentioned above, at 5'4" and 300 pounds the patient was nearly round — meaning close to the smallest possible surface-area-to-volume ratio. By the use of surface cooling, body cooling was expected to be slower than usual. But core brain cooling also proved to be exceptionally slow, probably because of warming of the brain by heat conducted through the neck. It might have been better if I had targeted −122ºC rather than −120ºC for brain surface temperature at the second stage of initial cooling. That way brain core temperature could have been closer (if not below) brain surface temperature before the long, slow phase of cooling began.
Otherwise, cooling was relatively uneventful until the end. For some reason, skull, brain and body temperature would not drop below −192.5ºC, despite the fact that ambient temperature dropped to −195ºC. When we removed the patient at 8 am on the morning of November 10, 2008 the cooling box was flooded with liquid nitrogen.
As usual, I poured liquid nitrogen on the patient's head while Andy tied him down to a backboard and tied-on metal identification tags. To help safely move such a heavy patient Andy has installed an electric hoist on the ceiling above the cryostats — much like the one he had installed above the cooling box. We were able to get the patient into liquid nitrogen, but Andy's safety is highly dependent upon his sure-footedness. Something needs to be done about finding safer ways of getting our patient's into cryostats, but I don't see an immediate solution to this problem.
|Lift from pallet||Lower into cryostat||Hold the patient's ropes|