The Cryonics Institute’s 79th Patient: By Ben Best
The 79th patient of the Cryonics Institute (CI) is an 88-year-old man who had been a CI Member for nearly ten years and had been a cryonicist much longer. Neither of his two daughters have a personal interest in cryonics, but both are fully supportive of their father's desire to be cryopreserved. Because of his deteriorating health he has long had arrangements in place with his local cooperating funeral director. Because he lived within a 7 hour drive from the Cryonics Institute his funeral director was prepared to drive him to CI as a means of avoiding airline scheduling and airport delays.
The man had a stroke in August 2005 and another in the Fall of 2005. He had been recovering somewhat until he got pneumonia in December 2006. At that time he was placed under home hospice care and remained under home hospice care even after his December recovery. On February 20, 2007 he was having contortions that an attendant interpreted as being another stroke. He was sent to the hospital where the stroke was not confirmed, but a heart attack was diagnosed (the daughter suspects that he had a heart attack in the ER). He was released from the hospital on February 23rd, but home hospice care had been ended by the hospital trip.
The daughters had hoped that their father could recover some function through physical therapy and occupational therapy, which are not available to people who are under hospice care. But there therapies were subsequently abandoned as being hopeless. On Friday evening, March 23, 2007 CI was phoned by one of the patient's daughters who told us that her father had stopped eating. She had been informed that after eating has stopped deanimation is expected within two weeks. The patient had been given a Do Not Resuscitate (DNR) bracelet in the hospital, which he was still wearing and which may be of assistance in getting a speedy pronouncement of death. Pronouncement at home would either be by 911 or by a home hospice nurse. If it was 911 then the police and Medical Examiner (ME) would get involved. If the patient was under hospice care then the nurse could pronounce.
CI Facilities Manager Andy Zawacki had spoken to the ME and he said that she sounded like she would help in a cryonics case, respecting the wishes of the patient and (hopefully) arriving on the scene quickly if 911 were called. We were told by one of the daughters that the doctor who had placed the patient under home hospice care in December was refusing to do so again without a personal examination -- and that an examination seems unlikely until Monday, but fortunately this had been misinformation she had been given by someone associated with the hospice. On Saturday morning the physician placed the patient under hospice care again. The hospice nurse requested that she be called immediately if the patient's breathing became labored. That very evening the patient's breathing slowed and the nurse was able to arrive quickly and give a speedy pronouncement of death after breathing stopped completely.
The patient arrived at the CI Funeral Director's Funeral Home not long after 8am Sunday morning. Sara Walsh was the funeral director in charge of the surgery. Although the operating table was tilted 30º to elevate the patient's head (preventing flow from a hypoosmolar body), Sara did not think that a rubber mesh mat was necessary to prevent the patient from sliding. (She was correct.) An attempt was made to build a crushed ice pillow for the patient's head.
As before, Sara's surgery was careful and meticulous. Sara had reservations about attempting to cannulate the right vertebral artery because of its smallness and fragility. Instead she cannulated the right subclavian artery as a means of perfusing through the vertebral without risking injury to the vessel.
Sara attempted to cannulate the right and left jugular veins so that effluent refractive index could be evaluated. She was unable to isolate the left jugular vein because it had been too damaged by the patient's funeral director in the failed attempt to inject heparin on the left side. She did, however, locate and cannulate the right jugular vein. She is still opposed to the idea of a funeral director attempting to inject heparin through a peripheral vein like the femoral because of the poor condition of veins in the elderly. Although she says that she and her father are capable of injecting heparin directly into the heart, she does not believe that most funeral directors can do this. Her recommendation is for other funeral directors to cut the skin along the right clavicle, look for the subclavian vein and inject heparin into the subclavian.
The heparin injected into the right jugular apparently was very effective because there was no evidence of clotting. Dehydration was expected because the patient had not been eating. Under this circumstance it was deemed better to begin perfusing with 10% ethylene glycol rather than with the carrier/washout solution.
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 0.2-0.3 liters were introduced at about 70-90 mmHg with a flow rate of about 0.36 liters/minute. Otherwise, perfusion data for the head (brain) can be presented in tablular form, beginning with the blood washout with m−RPS−2 (modified Renal Perfusion Solution two) carrier solution and ending with 70% VM−1 -- with 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
Perfusion was halted based on the refractive index of the right jugular vein (with an additional 0.3 liters for good measure). All refractive indexes were above that of 65% VM−1. Perfusion had lasted about an hour. 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. Cotton was stuffed into the burr holes and the skin around the burr holes was sewn shut. There was no attempt to perfuse the body.
After perfusion was complete the patient was moved to a stretcher on top of a backboard and sleeping bag. Then the patient's head was placed in the plastic head cooling enclosure, dry ice pellets were added to the enclosure and silicone oil was poured-in. The patient was then loaded into the funeral director's Chevrolet Suburban and driven to the CI facility.
At the CI Facility the dry ice was carefully chipped-away from the patient's head in the plastic head enclosure. We had switched from using n−propyl alcohol to silicone oil as the dry ice slurry cooling fluid because of the toxic fumes emitted when n−propyl alcohol is added to the dry ice (and because of the general toxicity/flammability of n−propyl alcohol). But the silicone oil makes the dry ice pellets stick together and troublesome to remove from the patient's head. Andy expressed his opinion that we should return to using the n−propyl alcohol, despite the protests of Sara and others. Perhaps the solution is to give adequate warning and to turn the fan on high while adding the n−propyl alcohol. Sara also complains about the pungent garlic-like odor of the DMSO in CI−VM−1.
The patient was placed into CI's computer-controlled cooling box and cooling began at around 11am. Brain core temperature was about −15ºC when cooling began, indicating the effectiveness of the dry ice/silicone oil slurry in cooling the head.
It quickly became evident that the cooling box software would not open the valve which releases liquid nitrogen into the cooling box. Less than two weeks earlier I had spent an entire day in our research lab with two Wineman Technology (our cooling box hardware/software provider) engineers ironing-out all the bugs in the software, so this problem was inexplicable. I tried switching cooling box controllers and laptops, but this was no help.
Although it was possible to manually open the valve, and the valve would necessarily remain open for a few hours of initial rapid cooling, manually regulating the cooling after the initial stage seemed like a horrific undertaking. It seemed all the more horrifically diabolical because of the annual CI Directors/Advisors meeting scheduled for 2pm that Sunday. Caring for our patients was our first priority so preparation for the meeting has been severely disrupted.
About half of the Directors attending were planning to do so by telephone conference call, but the conference call service we had reliably been using suddenly became unreliable. The meeting was delayed nearly a half-hour while we struggled with technical problems with the cooling box and conference calling. It was suggested that the meeting be cancelled, despite the fact that one Advisor (York Porter) had driven from Kentucky.
I gave handouts to Directors/Advisors attending the meeting and asked them to do their best to work their way through the agenda items. I flitted in-and-out of the meeting while manually controlling the cooling box and doing everything I could to contact Wineman Technology engineers on the Sunday. Wineman has no emergency weekend support. E−mail messages sent to their engineers and even phone calls to home numbers of engineers (which I found from paid internet services) were fruitless. Somehow the agenda items were mostly discussed and manual cooling-box control proceeded without problems.
After the Directors/Advisors meeting Immortalist Society President York Porter was helpful in relieving Andy and me in manual control of the cooling box during the first 24 hours of cooling. I was able to give my lecture about Sex Hormones to the ten or so people who came to the Potluck Dinner.
The standard cooling protocol was followed during the first 8 hours in which the brain surface temperature was cooled to just below below glass transition temperature (Tg), held there until brain core temperature also fell below Tg and then doing some "annealing" in which brain surface temperature was elevated above core temperature -- and both elevated to just above Tg before the final slow cooling to liquid nitrogen temperature. We settled into a cooling rate of 1ºC per hour, which was easiest to manage.
On Monday morning I was able to reach the engineers at Wineman Technology, but the engineer who has done most of the programming was attending a funeral. I spent much of the day intermittently working with his assistant making efforts to solve the problem while continuing manual control of the cooling. The change to Daylight Savings Time had occurred between the day of extensive testing and Sunday, so a number of attempted fixes were made based on the idea that this may have caused the problem. After a day of failed efforts the Wineman engineers told us to send them the unused cooling box controller by overnight express courier so they could directly test the unit.
Andy and I took turns maintaining a 24−hour vigil of manual control. I sat with a set of magazines and Andy had the TV next to the laptop. It was difficult to read or get too engrossed in anything because of the necessity of manual control every few minutes.
We observed that the temperature would increase at the moment the valve was opened, probably because the valve released relatively-warmed nitrogen gas before releasing liquid. The proportion of gas was greater for longer periods of time since the previous opening. This caused me to reflect on the desirability of being able to control threshold of temperature deviation for valve opening (I had asked the engineer to reduce the threshold from 1ºC to 0.5ºC). Somewhat inexplicably the core brain temperature was consistently lower than brain surface temperature, and there was a high responsiveness of core temperature to surface temperature changes. My guess is that thermal conductivity of the brain increases as the temperature becomes lower -- especially in the solid state.
Late in the day on Tuesday I was called by a Wineman engineer and given a simple instruction to change a PID parameter which immediately fixed the problem and allowed us to finish the cooling in automatic mode. The Wineman engineer who had supervised most of the software development and debugging let me know that he had negligently changed the settings at the end of our day of testing. He apologized for this error and assured me that it would not happen again. Admitting to a mistake of such catastrophic consequences might be an opening for a lawsuit, so it would be understandable why such an admission might be avoided if it were feasible to do so.
Unfortunately this was not the end of our software problems. Several hours later a dialog box appeared indicating that there was no more memory. I had seen this problem before and knew that it could be solved by rebooting the cooling box controller, although this meant starting a new graph for the final 18 hours of cooling. The Wineman engineers were informed of this problem and were able to locate the cause in their software.
Sara Walsh had been more careful to place the temperature probe for the body into the center of the chest than she had done with the previous patient. So we got a more reliable cooling curve for body temperature. As we had seen in our previous cases, at around −186ºC the body temperature dropped below brain temperature. I believe that this may be due to contact of the body with the liquid-nitrogen-soaked sleeping bag as well as due to the high thermal conductivity (and high thermal momentum) of the body at low (solid state) temperature.
As horrific as this experience had been, we all learned a great deal about the controller software and the cooling process. Eliminating the bugs will make the software more robust and our knowledge of the potential problems and fixes ensures better problem management in the future -- and greatly reduced problem likelihood. We also learned that as a last resort we can manually control the cooling box for an extended period with a high degree of fidelity to what we would achieve with automated control. It give confidence to know that we can do this, but I think it is highly unlikely that we will have to do such manual control again. I believe that we are attaining some very excellent hardware and software for computer-controlled cooling.
We were able to cool the patient to −194.6ºC in the cooling box -- within 2ºC of liquid nitrogen temperature. This is a testament to Andy's diligent efforts to improve insulation in the cooling box.
I had resolved to try to get a good look at the patient when we opened the box, despite not wanting to do anything that might interfere with patient care. I thrust my head into the fog coming from the cooling box and was surprised to see what a clear sight of the patient that I had when my head was below the level of the fog. I observed a somewhat chalky dust on the patient's face, but saw no indication of ice. I did not keep my head there very long, however, and I am not skilled in knowing what to look for. I could probably photograph the patient's face, although it is an awkward position and I don't know to what extent the temperature might affect the camera.
We removed the patient from the cooling box while he was still on his backboard and in his sleeping bag. The sleeping bag was zipped shut (the zipper is remarkably able to endure liquid nitrogen temperature). I soaked the sleeping bag near the patient's head with liquid nitrogen from a bucket while Andy secured the patient to his backboard with ropes and straps. The 79th patient became the first patient in HSSV−6−8 cryostat.