The Cryonics Institute’s 81st Patient: By Ben Best
The 81st patient of the Cryonics Institute was a long-time cryonicist who had switched from CryoCare Foundation to CI when CryoCare was going out of business in 1999. A chemical engineer by profession, the patient was 77 years old at the time of his deanimation.
On Sunday, June 3, 2007 we were notified that the patient had suffered a hemorrhagic stroke and had been placed on a ventilator. Depending on the severity of the hemorrhage, remaining on the ventilator could have increased brain damage. The physician estimated that only one-fifth of the brain had been affected. The family was determined, however, that the ventilator would not be removed until family members had been assembled to witness the event together. If the patient died the instant the ventilator was removed, that would be a sign that remaining on the ventilator had probably increased brain damage. As it turned-out, the patient did not deanimate until an hour after the ventilator was removed on the afternoon of Monday, June 4th, a promising sign that remaining on the ventilator may not have increased brain damage.
Only a few weeks earlier the patient had attended a Suspended Animation, Inc. conference in Florida with his son. However, for reasons that are clear only to the patient, the patient did not sign up with Suspended Animation for their services. It occurred to me that Suspended Animation might offer cryonics rescue procedures for reduced cost, especially in light of the fact that there would be no standby. I saw this as a benefit for both the patient and for Suspended Animation. I contacted the patient's son and Suspended Animation to confirm that this could be done. Both parties agreed that this would be worthwhile and that the costs were acceptable.
Suspended Animation the patient's funeral director were waiting by the bedside when the ventilator was removed. The patient had spontaneous heartbeat and ventilation of his own for nearly an hour after ventilator removal until he experienced cardiac arrest and pronouncement of death was made. Immediately after a prompt pronouncement of death, Suspended Animation then rapidly began application of anti-ischemic medications, cool-down and cardiopulmonary support. Suspended Animation did a blood washout, used a heat exchanger for more rapid cooling while doing bypass perfusion and replaced the blood with organ preservation solution. The blood washout was done through the femorals so it did not interfere with the neck surgery required for cryoprotectant perfusion. The patient was then packed in ice and shipped to the funeral director near the CI Facility where the brain perfusion with vitrification solution occurred. Suspended Animation has written its own case report of the cryonics rescue procedures they applied when the ventilator was removed.
The patient was located near enough to the CI facility to be driven to CI, but not near enough for our funeral director to directly pick-up the patient. The patient's local funeral director drove half the distance and the CI funeral director and CI Facilities Manager Andy Zawacki drove the remaining half of the distance. Neither of them had any sleep that day, or night, and Andy was concerned that if our funeral director went alone he may doze off and get into an accident so he went along to keep him company and share the driving, though our funeral director drove most of the way himself. The shipping box containing the patient packed in ice was exchanged between vehicles at the half-way point.
The CI local funeral director was Jim Walsh, assisted by his funeral director daughter Sara. At 7:40am on the morning of Tuesday, June 5th surgery on the 81st patient began in the Walsh's funeral home. A semicircular incision was made below the neckline to expose arteries and veins. Typically the vertebral artery on the right side is too small for cannulation and the vertebral artery on the left side is large enough, but for this patient the opposite was true. He was also atypical in that the branching of the carotid and vertebral from the subclavian artery on the right side was below the clavicle (breast bone). Mr. Walsh did not have a bone cutter to cut through the clavicle, but by reaching below the clavicle with his fingers he was able to pull the subclavian artery upward enough to cannulate it. Because of the blood washout the jugular veins were difficult to locate (blood in the veins makes them easier to find).
After about half-an-hour all vessels had been properly cannulated, so that perfusion could begin at 8:10am. Core brain temperature at that time was +3.7ºC. The effluent from the left jugular vein was clear and there was initially no effluent at all coming from the right jugular. Soon thereafter blood clots and blood began to emerge from the right jugular. The hemorrhagic stroke had apparently been in the right side of the brain, and the blood washout by Suspended Animation had not removed the blood from the stroke.
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 liter was introduced at about 70-90 mmHg with a flow rate of about 0.64 liters/minute. 70% VM−1 is more viscous than 30% ethylene glycol, but the first portion of VM−1 mixed with the ethylene glycol thereby increasing the net flow rate above what would be expected from 70% VM−1.
Insofar as the patient had already been washed-out by Suspended Animation, there was no need to begin the blood washout with m−RPS−2 (modified Renal Perfusion Solution two) carrier solution (we had skipped beginning with wash-out solution in a recent case, anyway). In this case we began perfusion with 10% ethylene glycol and ended with 70% VM−1 -- all perfusates were introduced at about 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
When the burr holes were placed in the skull there was no evidence of blood. However when the first burr hole sampling was made, some blood was seen in the left burr hole, but not the right burr hole. This seems odd insofar as the blood had come from the right jugular and not the left. When the second burr hole sampling was made there was still blood coming from the left burr hole, but not the right. On the suggestion to only perfuse on the left side (in the hope of washing away the blood) Mr. Walsh closed the right cannulas, thereby increasing perfusion on the left side. This popped the cannulas on the left side, and it was not possible to recannulate the left jugular. Soon there was blood flowing from both burr holes. After about fifteen minutes Mr. Walsh turned on his suction pump and suctioned blood from both burr holes using tubing. After several minutes of suction most of the blood appeared to have been removed, particularly on the right side. The fluid was clear for both burr holes at the time of the last two samplings. No samples were taken from the jugular, presumably because the last samples had been high enough. Core brain temperature had dropped to +0.5ºC. Perfusion was stopped at 9:30am.
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. Plans had been made to attempt a body perfusion with this patient using 80% ethylene glycol (as had been attempted with the 74th and 77th patients). The rapid cooling and blood wash-out by Suspended Animation -- along with the relatively short cold ischemic time during shipment -- should have made this patient an ideal candidate for the third attempt. But his swollen abdomen and the general edematous appearance of his body was too discouraging.
The patient's head was lifted into the plastic enclosure box which was filled with dry ice pellets. This time we used 100% isopropyl alcohol rather than silicone oil or n−propyl alcohol as the fluid for the dry ice slurry. Pure isopropyl alcohol resulted in neither the acrid stench of n−propyl alcohol nor the sticking-together of dry ice pellets seen with silicone oil.
The patient was transferred from the funeral home to the CI facility and placed in the cooling box. Cooling in our computer-controlled cooling box began at 10:44am. The software problems associated with our recent upgrades have been resolved, as far as we can tell.
Brain surface (skull) temperature was −25ºC and brain core temperature was +2.5ºC when cooling began. The effectiveness of the dry ice slurry in cooling the head was evident by the low skull temperature, but even with that surface cooling (and even without perfusion of the body) the brain core temperature had risen 2ºC. We have been concerned about backflow of perfusate into the brain from the body as a result of perfusion pressure in the body. But even without perfusing the body the high osmolality of the vitrified brain apparently draws enough fluids from the body to elevate brain core temperature.
In the hope of reducing the amount of fluctuation of brain surface temperature I made the controlling thermocouple temperature be the ambient temperature. It soon became evident, however, that having the controlling thermocouple on the skull surface produces faster cooling, which is of greatest importance in the initial cooling phase. I quickly switched to making skull surface temperature the controlling thermocouple.
On Friday, June 8 there was a 30 second power outage, probably associated with heavy raining. This was enough to kill the cooling box controller. The laptop's battery prevented the laptop being used for cooling box control from being affected (an advantage over a desktop, which would not have a battery). I was forced to reboot the entire system and re-start the programs from where they had left off.
The fact that the cooling box controller was rendered non-functional by the power outage meant that the controller alarm had been rendered non-functional also. After all of the efforts I had put into attempting to ensure an alarm would warn of problems, a new vulnerability was exposed. But it was to get worse.
The next day there was a power outage lasting nearly half-an-hour. When the power went off initially we had no way of knowing how long it would last. Andy got the generator running and plugged it into the power bar for the cooling box, cooling box controller and laptop. When the power was restored the program was again halted while converting back to the standard power. With so many interruptions there is no single cooling curve -- only fragments.
Andy pointed out that we had an Uniterruptible Power Supply (UPS) in the office and thought it may be useful in case of another power outage. I disconnected our office computers from the UPS and connected it to the power bar used for the cooling box controller. The battery would at least protect the system from short power outages. I have placed an order for another cooling box controller upgrade. This time I would like a built-in UPS that triggers the alarm if there is a power outage. If there is an extended power outage the UPS/alarm system would give us warning and time to get the generator running.
Another issue of some (but not great) concern is the amount of temperature fluctuation that occurs with the opening and closing of the valve, allowing liquid nitrogen to flow into the cooling box spray bars. With each opening of the valve there is an initial increase in temperature, apparently due to warming in the pipes. I spoke to the cryogenics engineer who built our small cooling box about this matter and he told me that a vacuum box around the valve could address the problem. But the fact that the problem is mostly in the pipes was demonstrated when Andy filled the cryostats that Saturday. The continuous flow of liquid nitrogen in the pipes during filling considerably reduced the temperature variation we saw on the cooling curves.
I used ambient temperature for part of the final cooling stage and brain surface temperature for another part. I thought that using ambient for most of the slow cooling phase would reduce temperature fluctuation on the brain surface, but I am not convinced. Ambient temperature as the controlling temperature was most useful in the final stage because it was higher than brain surface temperature, which was the first to hit −195ºC.
By the morning of Monday, June 11th the patient's brain surface, brain core and body temperatures all had reached −195ºC, the lowest temperature I have yet seen in the cooling box. This is a testament to the improved cooling box sealing Andy has created. The patient was removed from the cooling box and became the third patient in HSSV−6−8 cryostat.
(The Suspended Animation version of the case report for this patient can be found in the Case Reports section of the Suspended Animation website: SA Procedures for Patient CI-81. This document is a PDF file, so Adobe Acrobat is required to read it.)