The Cryonics Institute’s 97th Patient
The 97th patient of the Cryonics Institute (CI) has been a CI Member since 1986, and was active in cryonics since its inception. The patient came to many of the annual CI meetings, and had been meticulous in ensuring that his physician, funeral director, and others were well informed and well prepared concerning his cryonics wishes.
At the time of his deanimation the patient was recovering from illness he had contracted during travel overseas (possibly a virus, no sign of bacterial infection was found). He was found by his wife collapsed in their home on the morning of Saturday, June 26th. His wife phoned 911. The ambulance and police were on the scene. No attempt was made at resuscitation, and he was pronounced dead. Ice was packed around the patient's head. When the funeral director arrived, more ice was packed all around the patient.
Although the patient had a history of hypertension, he had no previous heart problems. There was no autopsy and no request for an autopsy. Based on inspection by the funeral director, a few hours had passed between the time of collapse and the time of discovery.
The patient is a classic example of why I have worked so hard to develop vital signs alarm systems for cryonicists. Millions of dollars have been spent developing standby equipment and procedures, while a significant number of cryonicists receive no standby because of sudden death (usually cardiac), and remain undiscovered for varying lengths of time.
Thanks to the patient and Andy Zawacki the patient's funeral director already had a shipping case ready for use in such a contingency. The patient's funeral director was able to arrange shipment to Michigan that very day, which was all the more remarkable given that it was a Saturday. The patient had arranged with the funeral home and his physician that verbal approval would be acceptable for shipment of human remains outside of the state, as Florida does not require a signed death certificate.
The flight was scheduled to arrive in Detroit at 8:44PM, but was delayed a couple of hours. With air cargo closing at 11PM it was all CI's funeral director could do to get the body released and not held overnight. The patient arrived at Faulmann & Walsh Funeral Home shortly before midnight.
I am still struggling to decide upon the best surgical approach for our patients. Before the 69th patient and vitrification, perfusion was a simple matter of glycerol up and down the carotid arteries. With increasing focus on brain perfusion, we have made efforts to ensure that the brain is perfused through the vertebral arteries as well as the carotid arteries. This is especially important in our more elderly patients where the chances of an incomplete Circle of Willis is much greater. For some of our patients, funeral director Jim Walsh has been able to individually cannulate the two vertebrals as well as the two carotids. But the cannulae used for the vertebrals are much smaller than those used for the carotids. It is likely that the smaller cannulae create so much resistance that perfusate takes the path of least resistance — into the carotids, with little passing into the vertebrals.
My preferred solution is to perfuse with an aortic cannula into the ascending arch of the aorta while clamping the descending aorta along with the subclavian arteries — taking effluent from the superior vena cava. An aortic cannula is large compared with the steel embalmer's cannulae used for the carotids and vertebrals — and it offers negligible back-pressure resistance. Opening the chest, however, is not a simple procedure, and it can make clamping the subclavian arteries difficult. In the 92nd patient it was too hard to access the right subclavian for clamping, so the right arm was perfused along with the head.
In this case, the patient wanted his body perfused as well as his head. I finally decided that the best approach would be to perfuse into the ascending aorta, clamp the descending aorta, and perfuse both the arms along with the head using CI−VM−1 vitrification solution. CI−VM−1 is too chemically harsh for body perfusion because of the fragility of blood vessels in the gastrointestinal tract. Unless glycerol is used, a body perfusion will quickly end with all of the fluid going into the abdomen. The arms, however, seem to tolerate vitrification solution much better. But if the whole upper body is being perfused, assessing refrective index through effluent in the superior vena cava does not give as good an evaluation of brain perfusion.
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.)
CI's funeral director Jim Walsh did the surgery, assisted by his daughter Sara, who is also a licensed funeral director. Doing a median sternotomy and opening the chest led to a big surprise. The aorta was broken and the chest was filled with blood. The patient had evidently died of an aortic aneurysm or an aortic dissection. Even if the patient had died under observation, any attempt to do chest compressions to restore circulation or circulate heparin would have been futile.
|Steel Carotid Cannulae||EOPA CAP Aortic Cannula|
The aortic cannula [Elongated One-Piece Arterial (EOPA) Central Arterial Pressure (CAP) cannula] was quickly replaced by two steel embalmer's cannulae on the perfusion circuit. Mr. Walsh cannulated the brachiocephalic trunk and the left common carotid artery, meaning that there would be no perfusion of the left arm or of the brain through the left vertebral artery. He also exposed the jugular veins for drainage and effluent sampling, as he had been evidently been planning to do. In his opinion, taking drainage from the superior vena cava resulted in filling the chest cavity with fluid. From my point of view, sampling from the jugular would be preferable because if provides more precise data on the saturation status of each side of the brain. But cannulating a jugular is considerably more difficult than cannulating the superior vena cava. Cannulae are sold in large volumes for each size, and I have been reluctant to order when I have been so uncertain what an appropriate size would be. The good folks at Suspended Animation, Inc. had given me an assortment of cannulae of various sizes, however. Mr. Walsh inserted a 22 French aortic cannula int the right jugular. For the left jugular, which was smaller, he used a 14 French venous cannula. Flow became poor from both cannulae, and both cannulae were removed after a while — resulting in jugular samplings being diluted with an uncertain amount of nearby fluids.
Another unexpected problem was defective operation of the digital pressure display box. During testing at the CI facility a few hours earlier, I had zeroed the pressure display box and had seen that it was functional, and had assumed that it would work at higher pressures. But it did not. Fortunately, there was a backup pressure display box on hand which proved to be fully functional. (In subsequent testing, it appears that the defect in the display box is nothing as simple as a battery problem, unfortunately.)
Because the patient had suffered so much ischemic damage, I decided to minimize ramping in an effort to get higher tissue saturation of cryoprotectant as soon as possible. Too often with ischemic patients, perfusion has become impossible because of edema. Ice damage is a worse problem than osmotic damage.
Perfusion began with a mixture of about 2 liters of 30% ethylene glycol with 3 liters of 70% VM−1 solution. The patient's right arm and head was perfused with an additional 19.5 liters of 70% VM−1 solution. The patient's body was perfused with 4 liters of 40% glycerol and 9 liters of 75% glycerol. Record keeping was spotty (given the limited staff), but was adequate to give a reasonable picture of what was happening.
Perfusion pressures are given as 60 mmHg less than the actual readings — as an estimated allowance for the pressure added by the steel embalmer's cannulae. Higher perfusion pressure for an ischemic patient is a means of overcoming no reflow , but should not be so high as to risk damaging blood vessels. Temperatures recorded were from a thermocouple inserted into the nasopharyngeal region (through the nose) as a proxy for central brain temperature.
RJVRI = Right Jugular Vein Refractive Index
LJVRI = Left Jugular Vein Refractive Index
Refractive Index values only taken during CI−VM−1 perfusion
|TIME (AM)||TEMP (ºC)||
|1:52||Upper Body Perfusion Halted|
|2:00||Lower Body Perfusion Begun|
|Lower Body Perfusion Halted|
|Dry Ice Slurry Added to Head|
No burr holes were made in this case. The best time to have made the burr holes would have been at the beginning of the perfusion, but it seemed like there were enough complications that the team was dealing with at that time without adding another. Burr holes could have been made later, but would not have given a full sense of the effects of vitrification solution. In general, burr holes and assessment of brain shrinkage is a good practice that should be part of every perfusion.
The patient received no heparin, and was not receiving any anti-coagulant medication at the time of his death (although he took a baby aspirin daily, along with fish oil and other supplements). As our current research and much literature has shown, although clotting contributes to "no reflow", it is probably not the main source of the phenomenon. Although clots were visible in the blood, they were mostly small. Flow was never halted the way edema has halted flow in other ischemic patients. The use of high concentration cryoprotectants likely helped prevent edema.
Although refractive index rose more slowly in the right jugular effluent than in the left jugular effluent, the right side of the face showed more evidence of good perfusion. An initial shrinkage of the right face was followed by a swelling, although the swelling was at least partly edematous. There was less visible change on the left face.
The body was perfused with the high percentage glycerol solutions through the descending aorta. Mr. Walsh initially had a cannula in the left subclavian to perfuse the left arm, but the left subclavian was soon clamped out of concern that glycerol might go up the left vertebral. There was not good evidence of dehydration of the body, but if there was filling of the abdomen, it was minimal.
Upper body perfusion was nearly an hour and lower body perfusion was 35 minutes.
As usual, dry ice pellets 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 head enclosure and dry ice was removed. Patient cooling in the new Omega computer-controlled cooling box began at about 3:30AM Sunday morning.
With the 95th patient we adopted a new cooling protocol based on principles outlined by a cryobiologist. This includes the idea that holding periods ten or twenty degrees above glass transition temperature can provide significant stress relief because the viscosity and thermal stress can be very high at those temperatures. Also, cracking at higher temperatures results in larger, but fewer cracks than cracking at lower temperatures. So if cracking is inevitable, it is better to force cracks at higher temperatures by rapid cooling. Unlike with the previous controller, however, the Omega controller cannot cool any slower than one degree Celcius per hour. Thus, the modified cooling protocol of the cryobiologist was:
cool as fast as possible to −100ºC
hold at −100ºC for 20 hours (stress relief)
cool from −100ºC to −110ºC in 30 minutes (10ºC/hour)
hold at −110ºC for 20 hours (stress relief)
cool from −110ºC to −120ºC in 30 minutes (10ºC/hour)
hold at −120ºC for 20 hours (stress relief)
warm from −120ºC to −116ºC in 1 hour (annealing)
hold at −116ºC for 2 hours (annealing)
cool from −116ºC to −145ºC in 30 minutes (rapid-cooling cracking step)
cool from −145ºC to −196ºC in 51 hours (1ºC/hour)
(For a more detailed explanation of these principles, see STRESS & STRAIN AT LOW TEMPERATURE and COOLING PROTOCOL NEAR Tg FOR VITRIFYING CRYONICS PATIENTS.)
|Cooling curve for the CI's 97th patient|
The cooling took under 7,000 minutes, or less than five days. Cooling was finished at about 10PM on Thursday, July 1st.
CI's 97th patient became the sixth and last patient to occupy cryostat HSSV−6−10. This required careful arrangement of the other five previous patients in order to fit him into the cryostat.
|Ropes holding five patients||Five patients await the sixth|
|Patient inserted into cryostat||Ropes for all patients tied together|