by Ben Best
The 86th patient of the Cryonics Institute is a 27-year-old European University student of nanotechnology who was afflicted with acute myelogenous leukemia. The patient had been diagosed eight months prior to his deanimation. He had failed to respond adequately to a vigorous effort to provide him with bone marrow transplants.
I was contacted by email about the case by CI Scientific Adviser Dr. Klaus Sames about three weeks before the patient deanimated. Shortly thereafter I was phoned by the patient himself, who gave me his credit card number to become an Option One CI Member. On the telephone the patient's voice sounded strained, as he struggled with his disease condition as well as with his attempts to speak English. During my last conversation with him he said that he would see me soon, a comment for which I did not have a ready answer. Completing the contracts for cryopreservation was an ordeal for the patient because of his illness, and he may not have succeeded were it not for the fact that his brother was strongly supportive of his efforts. The patient was able to sign the documents, and the $28,000 was wired to CI's bank account.
Dr. Sames was also quite supporting, traveling to the location of the patient to be of direct assistance and advising on medications as well as pre-medications. The list he emailed to me included heparin (I.V.), aspirin (30 milligrams), streptokinase, desferoxamin (2 grams I.V.), methylprednisolone (I.V.), melatonin (10 milligrams), selenium (100-250 micrograms) and CoEnzyme Q10 in Vitamin E oil. Dr. Sames sent me a report of his involvement in this case. I have slightly edited his report, mainly by removing identifying information about the patient:
################### BEGIN REPORT BY DR. KLAUS SAMES ##############
In the morning of Sunday, February 3rd, 2008 I visited the patient. His wish had been that we would still meet each other. He was tachypnoic and his sight was impaired and he felt that his end was near. On this day all members of the family met him. Ali had got the diagnosis of an acute myelogenic leukaemia in summer 2007. During his disease with the help of his family he founded a committee to find bone marrow donors for himself and other leukaemic patients. He did not find a donor with compatible bone marrow for himself, but was able to help 5 other patients. Therefore his contact with physicians had developed very positively. When I asked him in the weeks before if I should speak with the physicians he wanted to do this himself. Initially they found this to be a strange idea, but he convinced them to help him in spite of this. They promised to respect his last will and give him all the legal medical help he needed.
Following my visit we had a little conference with the head physician, another doctor and a paramedic person, the patient's brother and myself. His brother stated that the patient was studying nanotechnology as a mean of lifespan extension and cryonics. The logical consequence for him had been to choose cryonic suspension when his prognosis became so negative. He mentioned the strong effort of the whole family to help him cure the disease, which however did not lead to success. He introduced me as his confidential person.
Then the chief physician reported about all efforts made to cure the patient. He stated the department to be informed about all new developments in leukaemia treatment including new cytokines, growth factors, inhibitors etc. Now after exhaustion of all means the patient had no further chance of living. I told them that I am anatomist and have worked in the Institute of Anatomy of the University Hospital in Hamburg. I further told that I have worked in life span extension in agreement with the patient's ideas but with negative result and therefore support cryonics and have signed a contract myself. I explained the scientific basic and the idea of cryonics in a few sentences.
Then I was asked, how the medical staff could assist us. First I concentrated in anticoagulation. I asked if the coagulation state of the patient was reduced by the leukaemia or allows the application of heparin in vivo. I was informed about a critical reduction of thrombocytes, the coagulation still functioning normal: they feared heparin could further impair coagulation and cause intracerebral bleeding. In this situation I proposed to apply it post mortem during some rounds of heart massage. They promised to take this procedure in account, but should discuss the ethical aspect with their colleagues to come to a decision. I stressed the importance of early cooling and asked if we are allowed to surround the head of the patient directly after pronouncement of dead in his bed. The paramedic resisted and told us the patient would be in the cooling room in time of 2 minutes, where the paramedic of the pathology would arrive immediately after pronouncement. If he would be called following the cessation of breathing he would have 30 min. to come in. Then he should drive the patient to the Institute of Pathology situated nearby, where he could use the ice machine. (I did not trust in this timing and later urged the brother to ask his family to produce as many ice bags as possible in their refrigerators. They should take these to the bed room and urge the medical person to apply it immediately after pronouncement). I then proposed that I should apply all medicals which could not be given during life following transportation of the patient into the cooling room, this being no medical treatment but a preparation of the conservation of the "cadaver". They agreed to provide me with the medicaments which they would take to be efficient for tissue stabilisation or to apply them themselves. The medical persons asked for the indications of the other medicaments, I mentioned antioxidants, methyl prednisolone to protect cell membranes and antacids for protection of the stomach mucosa. They told me that antacids had been already given. At the end I stated that cryonics may have contributed substantially to the psychic stability of the patient. Then the discussion was finished in a friendly atmosphere.
Urged by the patient's brother, I gave the paramedic a call to ask him how many time he would need to reach the hospital from his home, if ice is at hand and if there is a transportable tube to take up the patient with water ice as the funeral director had announced it to me. He confessed that he has only a plastic body bag.
At around 1.10−15 a.m. on Monday I got a call from the patient's brother and the information that the patient had died. We ran together into the hospital. The patient had died around 12.15−18 p.m. on Sunday. At 12.22 the pathological paramedic was informed.
I found the patient in his bed, the head and part of the chest covered by bags of thin plastic material filled with ice cubes. At that moment transportation into the hospitals cooling room with the patient in his bed started. I was told that the physicians had given heparin, but I don't actually know the dosage (my proposal had been 100,000 U of sodium heparin). The patient's brother gave me an ampule with 125 mg methyl prednisolone. Since the cooling room had to be closed up to the arrival of the paramedic around 10 min later, I applied it somewhat later in the pathology, hoping that anticoagulation has worked over the maintained venous catheder, while a relative performed cardiac massage. We applied 6 pails of ice. The patient had ordered an sump pump and I spent some time with the help of a relative of the patient to fill enough water into the bag to set the sucker of the pump in action, Meanwhile patient's brother was busy ordering more ice until the patient was covered, but he remained concerned about the feet being not totally covered. I sprinkled ice water over the head and neck of the patient, but had to stop it after around ten minutes since the parents arrived to see the patient. After the parents visit I decided to fill in some more ice and bring the patient into the cooling box to stop the rapid melting of ice. The helper of the funeral director arrived at around a quarter to 12 a.m. by car and transportation started after a little ceremony with all the relatives around 1 hour later to Airport.
Later I asked myself if my presence has made sense. It was useful for the discussion with the medical staff. The patient set trust in my presence. I could accentuate the most important parts of the procedure. As an anatomist I was familiar with treatment of bodies in hospitals and pathology. Last not least: even very strong persons are grateful if there is a cryonic helper giving the psychic stabilization they need. I underestimated this fact in foregoing cases.
################### END REPORT BY DR. KLAUS SAMES ##############
Dr. Sames later informed me that the physicians had given the patient 30,000 U of sodium heparin, and no other medications. When I had spoken to the patient on the phone I had recommended that he take Vitamin E and fish oil for pre-treatment. I was trying to keep my recommendations simple enough that he could understand and comply (mixed tocopherols would be much better than just alpha tocopherol, but this would have been too complicated to explain, and I don't think mixed tocopherols are readily available in Europe.) The patient believed that heparin from doctors is what really matters, and he spoke dismissively of my "home remedy" recommendations. I did not attempt to argue with him or persuade him. He did not follow my advice.
Unfortunately, it is not possible to clear the American Consulate and ship the patient on the same day, so he was held in a cooler at a funeral home packed in ice. The patient was put on a flight for Michigan early Tuesday morning. He was shipped in a metal box filled with ice and soldered shut so that it was totally sealed. There was still adequate ice on the patient when his metal box was opened at the funeral home of Jim Walsh in Michigan.
|New Perfusion Equipment|
In late December the Cryonics Institute had been visited by Melody Maxim, a professional perfusionist who advised on means of upgrading our perfusion system. We replaced our old Sarns pump with a COBE that gives digital readouts of flow rate, and a filter to trap bubbles and particulate matter. But the new perfusion system was still incomplete. In particular we were still struggling to get a digital pressure monitor and cannulae for pressure detection. Medtronic company had refused to give the Cryonics Institute an account, evidently because we are a cryonics organization. So we were trying to arrange a purchase from a Medtronic client, but progress was slow. In the meantime we had to rely on our "transducer" pressure gauge, which converts water pressure to air pressure.
Other complications were that the patient disclosed having hepatitis B and had requested that his body be perfused. The hepatitis B caused me considerable concern until I realized that it is not really such a dangerous virus for North American adults who have a healthy immune system. All members of the perfusion team had previously received hepatitis B shots, but I was under the misconception that boosters are required. A few extra precautions were taken such as hoods, visors, extra gloves and extra bleach, but it is undoubtedly true that many past patients have borne many undisclosed pathogens. I have a nightmarish vision of a rash of new cryonics patients bearing highly infectious new diseases.
Another complication was that Dr. Pichugin (CI's cryobiologist) had gone and Mr. Walsh's funeral director daughter Sara is pregnant and did not assist. The main negative consequence of fewer perfusion team members, however, is that note-taking was not as good as it had been. Compensating for this somewhat was our acquisition of a Testo temperature monitor which can automatically log temperatures for uploading to a computer by a USB port.
Since CI has begun vitrifying patient's brains, body perfusions have been done after perfusing the brain, when they have been done at all. Because of concern that collateral circulation from the body perfusion may contaminate the head perfusion, this time the body was perfused first. Dr. Pichugin had also recommended before he left that the next patient receiving a body perfusion should have the body perfused before the head.
In the past we have had only one person always operating the perfusion pump. It is bad policy to be too dependent on the skills of a single person, so this time another person (who had practiced using the new equipment) ran the pump. The body was perfused with glycerol because glycerol causes less edema in the body than does ethylene glycol. Perfusion began with 2 liters of 10% and 3 liters of 20% glycerol at 0.85 liters per minute followed by 4 liters of 40% at about 0.5 liters per minute. There appeared to be no clotting and the body perfusion was proceeding better than any body perfusion that has been done since CI began the use of vitrification.
Near the end of the 40% glycerol perfusion a few bubbles entered the line, passing through the filter and entered the patient. Perfusion then became more difficult. When the 75% solution was poured into the reservoir the more experienced person pointed-out that the manner of pouring was generating the bubbles. Glycerol is much more viscous than our vitrification solution, and 75% glycerol is so viscous that the bubbles created by pouring had no chance of rising in a reasonable amount of time. Perfusion of the body was terminated.
There were also difficulties with the pressure gauge, which had not been primed with fluid. Even when it was primed, however, it did not appear to operate reliably. Melody Maxim had pointed-out that the gauge is only measuring line pressure, but line pressure is probably higher than patient pressure -- thus provides an upper limit for patient pressure.
Putting bubbles in a patient is a mistake that must not be repeated. At least these bubbles entered the body rather than the brain. This patient received a better body perfusion than any patient perfused within the last four years. Most of those patients had no body perfusion at all, and were probably better off. Glycerol alone can do no more than reduce ice formation, not eliminate it. The DNA of the body is not destroyed by freezing, and most of the body will need to be replaced by future science, anyway. Future engineered organs should be better than organs we have today (especially those afflicted by age or other diseases). Building a scaffolding in which new tissues, organs and limbs can grow has already been done in medicine. None of this is an excuse, however, for allowing bubbles to enter a patient. This MUST NOT happen again.
To minimize the chance of more bubbles, the more experienced person ran the pump for the perfusion of the head. He was able to pour the perfusate in a manner that did not appear to create bubbles. Again, it is a bad practice (if not dangerous) to be very dependent upon the manual skills of a single person. Technical means must be found to allow others to flawlessly perform the same task. In this case, a tube and siphon effect may be a safer way of introducing perfusate into the reservoir without bubble formation.
In attempting to cannulate vessels for the head, Mr. Walsh complained that the glycerol used to perfuse the body had caused extensive shrinkage of the upper vessels. He was unable to cannulate either vertebral artery (which he said were very small). So only the carotid arteries received perfusate. He told me afterward that perfusion of the right subclavian artery is a better way to ensure right vertebral perfusion (the method we had adopted as a standard), but I don't know if he meant that the body perfusion had prevented him from using the subclavian. He severed the left jugular, so was unable to cannulate or open it with forceps for sampling of effluent. There was no problem with the right jugular.
Mr. Walsh argued that when the body is perfused in the future, it should be done after perfusing the head. I am concerned that the glycerol or other body fluids may contaminate the brain vitrification, based on rising core temperature seen during body perfusion. Mike Darwin (who has considerable medical knowledge and cryonics experience) says that the neck has many collateral vessels that can allow for flow that bypasses major vessels. Whether the head is perfused first or second, the head must wait for well over an hour in ice or dry ice while the body is being perfused. For the case where the body is perfused second, the vitrified brain spends time in dry ice when it could be cooling more quickly to glass transition temperature and thereby reducing the risk of devitrification. Closed circuit whole body perfusion does not improve matters because the brain must wait for the rest of the body to be saturated rather than receive optimum treatment. I believe that every attempt to perfuse the body compromises brain perfusion. I recommend that CI Members not request body perfusion.
Melody Maxim recommended that the chest be opened and that cannulation be through the largest vessels -- the aorta and superior vena cava. This would eliminate many of the problems associated with trying to cut and cannulate smaller vessels such as the jugular and vertebrals -- both of which had failures in this case. Moreover, it would allow for the use of a Medtronic cannula which is equipped to measure patient perfusion pressure directly. We still had not received Medtronic cannulae so were unable to use the open chest technique. Mr. Walsh agreed to open the chest in the future. We had enough new experiences to deal with on this case, so it was probably best that we did not add the complication of trying to open the chest this time.
PERFUSION DATA ABBREVIATIONS:
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
In previous vitrification perfusions the burr holes were created after ethylene glycol perfusion and before perfusion with CI−VM−1. This time the burr holes were not created until five liters of 70% CI−VM−1 had been perfused, on the assumption that saturation would not be evident until after more perfusion, anyway. This is true, but there is something to be said for watching the refractive index rise to its terminal value. The top of the patient's head had many visible cancerous nodules which were particularly evident when the burr holes were created.
The flow rates and volumes are estimates, partially because more effort was devoted to tasks other than record-keeping. The temperatures given for the ethylene glycol are probably about right insofar as the containers are stored in the CI refrigerator and placed in coolers with ice shortly before use. The −7ºC for CI−VM−1 is a figure I have been uncritically accepting from the data Dr. Pichugin would supply, and it is undoubtedly wrong. Perfusate temperature is not measured during perfusion at all -- we only measure naso-pharyngeal temperature (which reflects the temperature of perfusate along with latent body temperature and applied ice). Warming surely occurs during transport of the VM−1 from the CI freezer to the funeral home and due to the wait (patient preparation, surgery, and, in this case, body perfusion) prior to use.
Several days after the perfusion I put some VM−1 into CI's freezer and subsequently compared the temperature with that of VM−1 from the freezing compartment of CI's refrigerator (where it is normally stored). The freezer VM−1 was just below −22º, whereas the freezing compartment VM−1 was just below −17º. It appears we would do better to store VM−1 in the freezer.
It is not possible to determine all refractive indexes at once, so their appearance on a single line should not be given too much substance. It was difficult to get samples from the burr holes until the head was lowered to the table rather than being in an elevated position. Sampling from the left jugular seemed questionable because the vessel had been cut and the pool of fluid associated with the remains of the vessel could easily be diluted with fluid other than most recent effluent. Trying to sample through forceps from the right jugular seemed to have similar problems.
|Naso-pharyngeal temperature |
during head perfusion
and dry ice cooling
After perfusion the patient's head was placed in a box
of dry ice, with his neck resting on the edge of the box. Isopropyl
alcohol was added, which allowed for greater cooling of the
head. The patient's naso-pharyngeal temperature (surrogate for
core brain temperature) had been monitored with the Testo 175-T3 temperature
data logger since the beginning of head perfusion and continued to be
monitored until the patient was placed in the cooling box at the
Cryonics Institute facility. As can be seen from the graph of data
downloaded from the Testo data logger, the patient's naso-pharyngeal
temperature remained just above 0ºC during the head perfusion, but
increased after the perfusion while the temperature probes were being
stitched to the patient and the patient was being
moved from the perfusion table. After placement of the dry-ice
cooling box naso-pharyngeal temperature decreased to nearly
−50ºC while the patient was being driven to the CI Facility.
At the CI facility the patient was transferred to the computer-controlled cooling box for cooling to liquid nitrogen temperature. Cooling began shortly after 9 pm on the evening of Tuesday, February 5th, 2008. Naso-pharyngeal (core brain) temperature had risen to above −30ºC between removal of the dry-ice cooling box and the beginning of liquid nitrogen vapor cooling. I used the skin skull temperature (red in the charts) as the controlling temperature. Within the first hour I was able to get naso-pharyngeal temperature (green in the charts) down to −80ºC, and it was clear that I could have cooled even more rapidly. Most of the first 18 hours was spent holding the head temperature near −120ºC (to achieve temperature uniformly before solidification) while the body cooled.
Inexplicably, brain core (naso-pharyngeal) temperature initially rose to nearly
−112ºC as I held the skull skin temperature at just below −120ºC.
|First hour||First 18 Hours|
|Flowers for the 86th patient|
The patient's father and female cousin flew from Europe in order to visit the CI Facility. On Wednesday they arrrived at the CI Facility with five other family members who life in North America. I never learned the exact relation of the other relatives because I was too preoccupied with other matters. I saw no anti-cryonics sentiment expressed by any of the relatives. The youth of the patient may have removed many of the standard concerns about death and religion. This was a talented young family member of great potential who had been tragically deprived of life (more obviously than many of the rest of us).
The father did not speak English, but the cousin was quite fluent. If she had been skeptical, it may have been concerning whether the Cryonics Institute actually exists. She said that our organization couldn't exist in Europe. The father warmly shook my hand with both of his hands. The others showed friendly curiosity about our operation. Many of the family members took photos, and flowers were placed in the flower receptacle for the 86th patient.
With some ambivalence I agreed that the family could return and watch the patient being placed into liquid nitrogen on Saturday. Facilities manager Andy Zawacki later expressed concern that I had done this. I invited CI Members Drew Simpson and Richard Medalie to help on Saturday, and they agreed to do so.
After 16 hours of cooling I elevated skull skin temperature to nearly
in order to get an "annealing" effect and improve brain temperature
uniformity before beginning the slow cooling to liquid nitrogen temperature
intended to reduce cracking after solidification. (Solidification should occur
a few degrees below −120ºC.) Brain core temperature remained
below skull temperature for the cooling beyond the first 30 hours,
probably because of liquid nitrogen adjacent to the head. After about
50 hours the body temperature also fell below skull skin temperature,
probably due to the liquid-nitrogen-saturated sleeping bag under the patient.
|15 to 30 hours||30 to 70 hour|
Between the 84th and 85th hour of cooling Andy filled some cryostats. The constant flow of liquid nitrogen through the pipes had a smoothing effect on the controlling thermocouple temperature (red in the graph).
In the same
hour the controlling thermocouple temperature plummeted to about −194.8ºC,
joining the temperatures of the brain and body. The computer controller
was set to a target temperature of −195ºC, a temperature the cooling
box can not attain. So the valve was constantly on, flooding the patient and
the box with liquid nitrogen. It would have been a good time to move the patient
into liquid nitrogen, but we needed to wait for the family and our assistants
to arrive. After a while I figured-out that by adjusting target temperature
to −194.7ºC I could get the valve to open-and-close, thereby
reducing the flooding effect of a continuously open valve spraying liquid
|84th to 85th hour||Last 2 hours|
Seven family members arrived shortly before noon on Saturday, at about the same time as CI Members Drew Simpson and Richard Medalie. Drew agreed to help move the patient, and Richard agreed to help keep an eye on the family. With Andy, Drew, and me so focused on moving the patient from the cooling box to the cryostat -- and with so many family members around -- Richard was very helpful by ensuring that there weren't people in wrong places or doing wrong things (although the family all seemed honest and non-malicious).
|Full cooling box cooling curve|
I allowed the family members to see the patient in the cooling box, but asked them not to photograph him because of my concern of the reaction if photos of the patient appeared on the internet. I ran a continuous spray of liquid nitrogen in the box to clear the vapor that would diminish visibility. It was quite a moving experience to watch the family members, one-by-one, look into the cooling box and see the patient.
After the viewing, Andy closed the sleeping bag around the patient and removed him from the cooling box. I poured liquid nitrogen onto the patient while Andy strapped and tied the patient to his board. Drew and Andy loaded the patient onto the forklift, lifted the patient to the level of the top of the cryostat, and then manually lowered the patient into the cryostat. I stood near the end of the catwalk watching the patient being lowered -- with his father right behind me and other family members watching (and photographing and filming) from the catwalk and below.
Allowing the family -- and so many family members -- to view the body and have such a close presence during the move is probably not a good general policy. It is a very vulnerable time for both CI and the patient, and many things can go wrong under these circumstances. If we do it enough times something will go very wrong. In this case, I am glad to have given the family such a meaningful experience, and to have allayed any concerns they may have had that we stuff blankets into sleeping bags and do not really cryopreserve patients. (I have heard such concerns on several occasions, considering that patients in sleeping bags and cryostats are not directly visible.)
I experienced nothing but cooperation and appreciation from the family. Only once did a family member raise a religious issue. One of the men asked me what "churches" think of cryonics. I told him that different views are expressed by others, but that from our point of view we are practicing a form of medicine -- and that there is no conflict between medicine and religion.