The Cryonics Institute’s 92nd Patient: By Ben Best
The Cryonics Institute's 92nd patient is a PhD in Mechanical Engineering in his early 60s who had worked in the Aerospace Industry. He joined CI as a Yearly Member in the Fall of 2007, quickly completing his contracts and funding. His urgency was associated with a case of esophageal cancer. He later allowed his Membership to lapse, possibly because he thought the cancer had been cured.
On April 17, 2009 we received a frantic call from the patient's wife who made a payment to restore his Yearly Membership. The patient's esophageal cancer had spread to his liver, and he was not expected to live more than a few weeks — a couple of months at most. The patient's wife told me that she was holding-off getting hospice status because she wanted to get antibiotics. She told me that her husband would probably deanimate at home.
Less than a week later the patient's wife phoned again, this time saying that her husband's condition was deteriorating rapidly. She was rushing to ensure that the Cryonics Institute was a beneficiary for some of her husband's life insurance policy. Shortly before midnight on the evening of Wednesday, April 22nd she called to tell me that the hospice nurse had said that her husband would not survive the night. Only two days earlier her husband, although in a wheelchair, had seemed quite normal.
I phoned CI's funeral director, Jim Walsh, to appraise him of the situation. The patient lived in California and Mr. Walsh had earlier arranged for an Inman funeral director living within 20 minutes of the patient to handle the case. But Mr. Walsh learned that the Inman funeral director's cooler was full, and Mr. Walsh was forced to get another Inman funeral director quickly — this one 60 minutes from the patient.
Shortly after 6:30am Eastern Time (3:30am California time) I received a call that the patient had deanimated. I had instructed that ice be packed around the patient's head — preferably sticking the patient's head in bag filled with ice. The hospice nurse told me that this was emotionally difficult for the patient's family to deal with. I told her to pack ice around the head in the best way that she could. I asked the CI funeral director to inform his Inman funeral director to pick up the patient. The nurse and the patient's wife phone several times asking when the funeral director would arrive. It seemed more like two hours than one hour before the funeral director arrived.
The patient's wife had been assured by an insurance agent the previous day that CI would be the beneficiary of a $40,000 portion of the patient's insurance policy, but CI still lacked documentary proof. The California office of the insurance company opened at 6am California time, and within a couple of hours I was able to get FAXed confirmation of CI's beneficiary status on the insurance policy.
CI should have received the patient by Thursday night, but we did not receive the patient until early Saturday morning. The death certificate had been completed in advance and I could see no reason why a transit permit could not be obtained promptly. In attempting to get an explanation from our funeral director for the delays, he told me that there were new administrative regulations, and that the physician saw no urgency in signing documents. Even if there are new California regulations, the idea that the physician and/or the California funeral director had no sense of urgency seems like the most plausible explanation for the delays.
The patient was well-packed in ice. CI's funeral director, Jim Walsh commented on how hard the patient's body was to the touch, saying that the patient felt frozen. The patient was somewhat hard, but not rock-hard. If the patient had not been placed in a freezer, he may have been frequently packed with ice that had been taken from a freezer. Freezing could have potentially caused blood vessel damage, at least on the superficial vessels. A temperature probe placed in the nasopharynx at 8:08am measured 2.8ºC, but five minutes later it was down to 0.9ºC.
|Electric sternal saw||Chest spreader|
This was the first CI patient for whom the chest was opened using an electric sternal saw and chest spreader. The aorta was abnormally large and fragile. Mr. Walsh accidently poked a hole in the aorta with the plastic EOPA CAP cannula in the process of cannulation, which tore easily due to the fragility. He pointed to another hole in the aorta and expressed the opinion that the patient may have died from an aortic aneurysm rather than cancer. As a fallback, Mr. Walsh used two steel carotid cannulae to cannulate the brachiocephalic trunk and the left common carotid artery coming off of the aortic arch. This meant that the left vertebral artery received no perfusion and the patient's brain, head and right arm were all being perfused. Mr. Walsh did not want to do more surgery to clamp-off flow to the right arm, for some reason. The superior vena cava was too damaged to cannulate for drainage (as had been done for the 88th and 89th patients), but Mr. Walsh was able to lift the vessel with tweezers so that good effluent samples could be obtained.
In testing the perfusion apparatus at the CI Facility, CI Facility Manager Andy Zawacki had determined that the steel carotid cannulae caused a 90 mmHg pressure drop. To be conservative, line pressure was assumed to be 80 mmHg greater than patient arterial pressure during the perfusion. To stay within a physiological range, line pressure was kept at around 200 mmHg (to approximate 120 mmHg arterial pressure).
Perfusion was begun at 8:38am with a hyper-osmotic, iso-oncotic 10% ethylene glycol solution. The solution was made iso-oncotic with PolyEthylene Glycol (PEG, 20,000 Molecular Weight) and made hyper-osmotic by adding an extra 100 milliOsmolal of glucose to m−RPS−2 carrier solution. The added oncotic and osmotic support is intended to dehydrate the patient initially and reduce the potential for edema. Normal osmolality is about 300 milliosmoles, so an additional 100 milliosmoles is not much, especially in light of the fact that 10% EG in carrier solution is nearly 2,000 milliosmoles, 30% EG is over 4,000 milliosmoles, and 70% CI−VM−1 is over 10,000 milliosmoles. Admittedly, the effect is transient, but it takes at least 5 minutes for enough cryoprotectant to enter cells to significantly reduce the differential between osmolality outside a cell and osmolality inside the cell. (Hypertonic solutions are not very damaging to cells that are not to be returned to isotonic, normothermic conditions — as is the case in cryonics.)
Nasopharyngeal temperature was 1.6ºC when perfusion began, and continued to rise to a maximum of 4.3ºC until perfusion with cold 70% VM−1 solution (which had been in the freezer) was begun. Nasopharyngeal temperature was back down to 1.1ºC when perfusion was completed. A graphical representation of temperature was produced by a Testo 175-T3 temperature data-logger, although the data-logger was on standard rather than daylight savings time, and absolute temperatures (other than 0ºC) are not shown in the vertical axis. Perfusion data is given in the table below.
Refractive Index values taken during CI−VM−1 perfusion
|9:11||4.2||Inserted Burr Holes|
No edema was evident in perfusing with the hyper-osmotic, iso-oncotic 10% ethylene glycol solution, of which a total of nine liters was added. Nine liters of 30% ethylene glycol was also added, at the end of which the lips were becoming visibly edematous. The 30% ethylene glycol carrier solution had no oncotic additive and was iso-osmotic. Considering the amount of cold ischemia (and possible freezing) the patient had suffered, a hyper-osmotic, iso-oncotic 30% ethylene glycol solution — and less total volume of the 30% EG — may have been advisable.
After a few liters of 70% CI−VM−1, edema in the patient's head and face became increasingly evident. Burr holes were made in the right and left sides of the skull not long after the 70% VM−1 perfusion had begun. But bone in the right burr hole evidently blocked efforts to measure brain shrinkage/swelling. Between the perfusion of 8.5 and 12 liters of 70% VM−1 the brain on the left burr hole shrunk one millimeter, but did not change (shrink or swell) with further perfusion.
Refractive index of the effluent from the superior vena cava was slow to rise. Perfusion was stopped at 10:10am after a full 27 liters of 70% VM−1 had been used, the most that has ever been given to a CI patient. We had to stop because we had run out of 70% VM−1, despite the fact that the refractive index was still rising and was not stable. The final refractive index indicated a tissue saturation between 60% and 65% VM−1. Much of the 70% VM−1 had gone into the right arm, which had become significantly larger than the left arm.
At the end of the perfusion a box was placed around the patient's head, and then the box was filled with dry ice pellets followed by isopropyl alcohol, to get the rapid cooling effect of an ice slurry. The patient was wrapped in a sleeping bag and transported to the CI Facility. At the CI facility at 11:10am the nasopharyngeal temperature had only dropped to −1.8ºC, but the skull temperature was closer to −10ºC.
After removal of the patient's head from the box containing the dry ice slurrry, the patient was placed into the computer-controlled cooling box for cooling to liquid nitrogen temperature.
|First 22 hours||"Annealing" step|
Brain surface (skull) temperature was cooled to −115ºC in just over two hours, cooled more slowly for another half-hour to −120ºC, cooled slowly for an additional half-hour to −122ºC, and then held at −122ºC for about eighteen hours while the brain core temperature dropped more slowly to approach −118ºC. The purpose of this was to avoid thermal stress while solidification temperatures are approached. Even though vitrified tissue should still be liquid above −122ºC, the viscosity is so great that the danger of freezing ( de-vitrification) is very small.
After holding skull surface temperature at about −122ºC for about 15 hours brain temperature became more uniform. The "annealing" step consisted of raising skull surface temperature to −115ºC over a period of about an hour, which allowed nasopharygeal temperature to rise to nearly −116ºC. Subsequent cooling allowed the brain surface temperature to drop back below the nasopharyngeal temperature and then rise toward the nasopharyngeal temperature. This step was intended to increase uniformity of brain temperature so as to minimize thermal stress during the long, slow cooling to liquid nitrogen temperature. This is not actually "annealing", because annealing involves warming a solid to just below melting temperature as a means to relieve thermal stress in a solid.
|Final 4.5 hours||Full 127.5 hours|
After about 155 hours, the body temperature dropped below the brain surface and nasopharyngeal temperatures, possibly the result of the sleeping bag being soaked with liquid nitrogen. At about 125 hours the body temperature reached a lower limit of just below −192ºC, and approaching 126.5 hours the brain surface and nasopharyngeal temperatures approached the same lower limit. The 91st patient had also approached a lower temperature limit of just below −192ºC, but we were able to cool the 84th patient and the 86th patient to nearly −195ºC. No explanation can be given for these differences.
Facility Manager Andy Zawacki transferred the patient from the cooling box to liquid nitrogen in the HSSV−6−10 crystat with the assistance of his brother-in-law, Dave Fulcher (who is now a part-time employee at the Cryonics Institute). Dave poured liquid nitrogen on the patient to keep him cold, while Andy tied the patient to a plywood backboard. Then the patient was elevated by forklift to the level of the cryostat tops, and placed into the cryostat.
|Out of cooling box||Being tied to board||Raised to cryostats|