The Cryonics Institute’s 77th Patient : By Ben Best
The 77th patient of the Cryonics Institute was a 96-year-old CI Member who had been a CI Member since 1999. He had been a captain in the Army during the Second World War and among many subsequent management positions had supervised hundreds of engine inspectors, some of whom inspected engines used by the Apollo astronauts. Two of his three sons are also CI Members. Initially he had no interest in cryonics for himself, but he agreed to being cryopreserved to please his two sons. With time, however, he came to like the idea of cryonics. The third son was not interested in cryonics, and the third son's wife was vehemently opposed to cryonics -- as was the patient's brother.
The patient had a long history of arthritis. During the previous two years he had also been suffering from congestive heart failure, but was being stabilized with Lasix and Coreg. His vital signs had been monitored at least every half hour by his diligent sons (or a paid sitter) for the previous five years. During the previous three months his overall quality of life had been deteriorating significantly. A week prior to deanimation he had broken a hip (broken femur) and had gone to a hospital to have the femur pinned together. The physician said that the operation carried a 40% risk of death within 2 weeks of the operation, but the patient appeared to be recovering.
Although he seemed to be doing fine in the hospital, he was moved to a hospice on Monday, February 5th. The hospice was mainly interested in having terminal patients and therefore wanted to discontinue the Lasix and Coreg. Although the hospice agreed to continue the heart medications, they also gave narcotics and pain-killers. Once in the hospice the patient was comatose or sleeping most of the time, although he could hear and react on occasion. On Wednesday, February 7th the hospice decided that the patient was probably not terminal and discussed moving him to a nursing home, despite the fact that the patient was breathing with increasing difficulty. On Wednesday evening the patient deanimated in the hospice.
One of the sons had an Ambu CardioPump, bag mask valve and other equipment, but the hospice discouraged bringing cryonics equipment onto their property. They did, however, allow one of the sons to pack ziplock bags of ice around the patient's head -- which provided "maximum contact without a wet mess" (as they described it). Ironically, it was the son whose wife is vehmently anti-cryonics who packed the bags.
The hospice also allowed the local funeral director to inject heparin into the right carotid artery. The CI Michigan funeral director was concerned when he heard about this, worrying that the local funeral director could have damaged the vertebral in raising the carotid.
Because of the need to obtain a transit permit the patient could not be shipped until noon the following day. The shipment was via an intermediate airport, so the patient did not arrive at the Detroit, Michigan airport until Thursday evening at 8:30pm. Due to slow unloading and processing at the airport (and the drive from the airport) we did not receive the patient at the funeral home until 11pm.
Jim Walsh was the funeral director in charge of this perfusion, and he was assisted by his daughter, Sarah (who is also a licensed funeral director). This time we had a meticulous scribe who recorded the timing of all events. His notes are attached at the bottom of this case report. Perfusion of the head (brain) began at about midnight.
Mr. Walsh was able to isolate the carotid and vertebral arteries without much difficulty, so his fears of damage by the other funeral director injecting heparin were unfounded in this case (although it could happen). He did find the right vertebral to be small and scleroticized, but he managed to cannulate it with a small cannula.
Our intention this time was to take effluent samples from the jugular veins as well as from the Burr holes during perfusion, but that information had not been communicated to Mr. Walsh before he had cut the right jugular. He was, however, able to cannulate the left jugular.
Perfusion of the right side of the brain went much better than perfusion of the left side. Clots were seen to emerge from the left jugular, but not from the right side. Mr. Walsh reasoned, probably correctly, that an incomplete Circle of Willis in the old man meant that the heparin injected in the right
carotid had not reached the left side of the brain. Mr. Walsh argued that heparin should be injected directly into the heart rather than into a carotid -- both to ensure better circulation as well as to reduce the possibility of artery damage that could hamper perfusion.
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 solution (which is much more viscous than the 30% ethylene glycol which precedes it). In introducing VM−1 the first 0.2-0.3 liters were introduced at about 70-90 mmHg with a flow rate of about 0.37 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 (Vitrification Mixture one) -- with 120 mmHg perfusion pressure.
The objective is to perfuse the brain until the refractive index of the vein effluent and 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.
EG = Ethylene Glycol
RBHRI = Right Burr Hole Refractive Index
LBHRI = Left Burr Hole Refractive Index
LJVRI = Left Jugular Vein Refractive Index
Perfusion of the right side was halted when it became clear that the right side was approaching full saturation, but the left side was not. Halting perfusion of the right side forced more solution through the left side. Perfusion of the left side continued with perfusion pressure maintained at 120 mmHg until 3.0 liters of 70% VM−1 had been perfused. Then perfusion of both sides was resumed.
Perfusion of the head (brain) was stopped. Thermocouple probes were placed in the nasopharynx (proxy for deep brain temperature) and under the skin where the Burr holes had been drilled (after the Burr holes had been plugged).
The head was placed in the plastic head-enclosure box to initiate cooling of the head. Dry ice was added to the enclosure box followed by addition of n−propyl alcohol. The smell from the n−propyl alcohol being added to the dry ice can be slightly unpleasent. Dr. Pichugin suggested using silicone oil rather than n−propyl alcohol. (Silicone oil has been ordered.)
Perfusion of the body was done with Ethylene Glycol (EG) flowing downward from the carotid arteries. There was no initial blood washout with m−RPS−2 carrier solution. With a constant perfusion pressure of 120 mmHg 4.2 liters of 4ºC 10% EG was introduced at a flow rate of about 1.0 liters/minute. Then 8.0 liters of 4ºC 30% EG was introduced at a flow rate of about 1.0 liters/minute. Finally, 2.0 liters of 4ºC 10% EG was introduced at a flow rate of about 0.57 liters/minute.
The body perfusion was stopped after not much more than 20 minutes of total perfusion time. There was extreme fluid accumulation in the abdomen, poor perfusion of the arms, and no sign of perfusion in the legs. This was very much like what had been seen the only other time a CI patient's body was perfused with EG (the 74th CI patient).
Another worrisome result of the body perfusion was the fact that (despite the head being in the dry ice filled plastic enclosure box) the nasopharyngeal temperature rose about 2ºC during the body perfusion -- indicating a back-flow from the body into the head. Mr. Walsh believed that this was due to flow through the trachea, which he suggested should be cut. More likely the backflow was through veins and lymphatics. Our scribe suggested applying a tight tourniquet to the neck. Another solution would be to not begin body perfusion until head temperature was low enough that solidification in the neck prevented backflow. Glycerol perfusion of the body would surely cause less edema than ethylene glycol.
A thermocouple probe was placed deep in the chest so that body temperature could be monitored and the chest was stitched closed by the funeral director. The patient, with his head still in the enclosure box, was transferred to a stretcher, loaded into the hearse and driven to the Cryonics Institute facility a few miles away.
At the CI facility the plastic enclosure was removed from the patient's head. The patient was then transferred to another stretcher so that he was lying on an open sleeping bag on top of a supporting backboard. Then he was placed in the computer-controlled cooling box. Cooling began shortly after 3am.
Upon arrival at CI the scribe had recorded a brain core temperature of −17ºC and a surface temperature of 1ºC. This makes no sense and did not agree with the values seen on the computer monitor -- which indicated a surface temperature just below −20ºC and a brain core temperature just below 0ºC -- ie, values reversed from those recorded by the scribe. The wires were a bit tangled while the head enclosure was removed so it is understandable that the values were reversed.
From the point of view of our computer-controlled cooling box equipment the timing of the arrival of our 77th patient was not good. A couple of months earlier I had ordered a second computer-controller for the cooling box and a software upgrade. The new system would provide for a warming capability (actually, a maximum rate of warming tempered by cooling) which could be used for annealing. The system is to also have an alarm to indicate excessive temperature deviations, notably a failure of liquid nitrogen injection. Two systems would also mean that Dr. Pichugin could keep one system in his lab for research and for pet cooling (he had perfused and cooled a pet in his lab two weekends before the arrival of our 77th patient). A human an a pet could be simultaneously cooled if the pet arrived while a human was being cooled.
The new software was not perfect when tested, although it seemed to do what was required. The main problem was that it would only display two steps (although it was still possible to program more than two steps) and the "EXIT" button was also cut off at the bottom of the screen. In practice, after the second step of patient/pet cooling manual intervention is required because the third step cannot begin until core brain temperature reaches surface brain temperature just above glass transition temperature (Tg). The timing of this event cannot be predicted. The older computer-controller had been taken to the manufacturer for installation of the new firmware while the programmers worked on the display problems.
The first two steps of cooling during the first six hours proceeded as desired, with core temperature eventually settling-at (and crossing) brain surface temperature at just below −120ºC. Oddly, body temperature leveled-off close to −60ºC.
Unfortunately, when I attempted to manually begin the third step, the system failed. After repeated failed attempts to resolve the problem with the help of the manufacturer's tech support I concluded that the only solution was to complete cooling the patient manually over a two day period. I did manual cooling for several hours, discovering by trial-and-error that a 3-minutes-on, 13-minutes-off cycle gave a reasonably tolerable protocol for an acceptable cooling rate.
I phoned tech support again and we spent more time experimenting and discussing the problems. Although the "EXIT" button was not displayed, I could exit the program by control-alt-delete. But when the program was re-started the process was still running in the background. We finally killed all background processes with the Task Manager. In retrospect it is obvious that rebooting the computer would have also began the program afresh, giving me two steps to complete cooling. On a positive note, my detailed discussions with tech support provided us with a depth of understanding of the software and its problems that would probably not have happened in the normal course of testing. The end result will be better software for our future patients.
On resumption of computer-controlled cooling the body temperature dropped fairly rapidly to below the temperature of the brain surface or core. I believe the reason for this is that as the temperature in the cooling box gets lower the vaporization of the liquid nitrogen spray declines. Eventually, increasing amounts of liquid nitrogen soak into the open sleeping bag upon which the patient rests, thereby cooling the body closer to liquid nitrogen temperature. Although still attached to the body, the head is more independent and continues to be mainly cooled by the ambient air temperature in the cooling box.
I ended-up maintaining the patient at around −191ºC for an extra day. I did not want to lower target temperature below −191ºC because I did not want to flood the cooling box with liquid nitrogen.
When Andy returned on Monday I dropped the temperature to as low as it would go -- somewhere between −194ºC and −195ºC. Previously we had not been able to get ambient temperature in the cooling box below −192ºC, indicating that the work Andy has done to improve sealing of the box has been effective.
After removing the patient from the cooling box we could see a deep pool of liquid nitrogen below the cot, the obvious result of the very long period at very low temperature. In accordance with our usual procedure the sleeping bag was wrapped around the patient prior to removal. Soaked with liquid nitrogen, the sleeping bag helps maintain the patient at low temperature during the transfer from the cooling box to the cryostat. The sleeping bag is tied tightly to the backboard with ropes which are threaded through holes at the bottom of the backboard so that the patient can be lowered head-first into the cryostat.
The final stages of tying and inserting into the cryostat cannot be done quickly enough. Years of experience have given Andy the expertise to move with speed and efficiency.
Perfusion Timeline Notes for the 77th Patient Perfusion
February 8/9, 2007
23:00 Patient arrives at funeral home
23:04 Start unpacking patient container
23:07 Start setting up perfusion equipment in prep room
23:07 Unscrewing of Ziegler case
23:09 Ziegler is opened ice in garbage bags had been placed on the patient
Bag with ice is left on head
23:10 Emptying ice bags in buckets
23:14 Gowning / gloves
23:23 Patient moved to prep room
23:25 Patient lowered to table
23:28 Preparation of tubing
23:28 Body bag removed
23:30 First incision / pacemaker removed
23:34 Observation of vertebral: very sclerotic
23:35 Both carotids and vertebral raised
23:41 Cannulation of all vessels
23:43 Opening cannulae for flow
23:45 Raising right jugular vein for cannulation. Failed.
Funeral director states that he prefers to cannulate jugulars earlier during the procedure.
A tube is placed in the left jugular vein.
23:55 Start burr holes preparation: expose dura
23:56 Observation of cerebral dehydration
23:57 Venous effluent clear on left jugular vein.
Right jugular vein more difficult to determine because of collateral blood (?) from the rest of the body.
Body weight: estimated 135
00:03 Clots observed on left side of the head, right side of the head more dehydrated
00:07 Yuri takes first sample for refractometry
00:10 Some edema observed on right side of the head, dehydration on both side getting equal
00:14 Drilling of left burr hole. Changed bit because it didn't went through
00:17 Drilling of right burr hole
00:25 Clots observed coming from left jugular vein
00:31 Increasing edema observed in the patient's face
00:46 Left side: relatively poor uptake of CPA: less rebound on left side
00:53 Left eye is rehydrating; not longer looks "collapsed".
00:58 Stopped perfusion of both sides to achieve better perfusion of left side of the head.
01:14 Resuming perfusion of both sides again
01:25 Edema getting progressively worse during last 25 minutes
01:27 Stopped perfusion brain
01:27 Clamping off flow to brain, removal of vertebral cannula
01:27 Placement of thermocouples: - T1 Burr Hole (surface brain) - T2: Nasal
01:30 Start perfusion of the rest of the body
01:34 Head placed in enclosure
01:35 Adding dry ice to enclosure
01:38 T1 = 0.1ºC
T2 = 1.4ºC
01:41 Added alcohol
01:43 T1 = 1.4ºC
T2 = 1.1ºC
01:46 Increasing abdominal edema observed
01:47 T1 = 1.0ºC
T2 = 2.4ºC
01:50 T1 = 0.3ºC
T2 = 2.8ºC
01:52 T1 = −0.3ºC
T2 = 3.1ºC
01:53 Stop perfusion of rest of the body because abdominal edema is getting worse,
almost no venous return and backflow of fluids through the esophagus to the brain is suspected.
01:58 Incision closed by funeral director.
02:00 Placement of thermocouple deep in the chest
02:05 Incision closed
02:12 Patient moved to stretcher
02:18 Leaving funeral home
02:30 Patient arrives at CI
02:48 T1 = 1.0ºC
T2 = −17.0ºC
02:51 Head enclosure removed
02:53 Labeling thermocouples
02:55 Moved patient to CI stretcher
02:57 Patient lowered into cool down box
03:00 Running thermocouples through box
03:05 Box closed
03:10 Start cool down