The Cryonics Institute’s 88th Patient: By Ben Best
The 88th patient of the Cryonics Institute is an 89-year old cancer victim from Ohio who was cryopreserved by her son and daughter. The patient had breast cancer that spread to her bones, kidney and the base of her skull.
The patient's daughter had vaguely known of cryonics, but became inspired to cryopreserve her mother after seeing the April 1st TV program on the subject with Barbara Walters. She had paid money to Alcor, but balked when Alcor asked for even more money on the grounds that it is a "last minute" case (terminal within six months of joining Alcor). The daughter was considering using Suspended Animation, Inc. or having her mother brought to Michigan by ground ambulance when her mother took a turn for the worst, and she was forced to sign-up her mother with CI without any provision for standby.
The staff at the nursing home where her mother was being held were extremely interested and helpful. They were so interested that many of them were hopeful that the patient would deanimate during their shift, so that they could participate in cryonics emergency medical procedures. The patient deanimated at 2:55 am in the morning of Thursday, May 29, 2008. The nurse in charge had phoned me at the beginning of her shift asking for detailed instructions, which she followed scrupulously. Between 30,000 to 40,000 IU of heparin was injected into a vein in the wrist after a speedy pronouncement of death, and the nurse administered chest compressions for a full fifteen minutes. The patient's head was placed in a pan of ice and water.
The Ohio funeral director is a personal friend of the patient's daughter, and was eager to be as helpful as possible. I told her that when she retrieved the patient from the funeral home that she should use a body bag and fill it with as much loose ice as possible. She drove the patient half-way from Ohio to meet our funeral director, which halved the amount of driving time which would have been required if our funeral director had driven the entire distance. We were able to begin perfusion within seven hours of the time of deanimation.
Jim Walsh, CI's funeral director, complained about the mess of melted water and ice in the body bag. He would have rather that ziplock bags had been used, but this would have increased the amount of time required to cool to ice temperature. Water has 25 times the thermal conductivity of air, and the more water that can directly contact the skin, the better the cooling. The presence of melting ice directly in water assures that the water remains at the temperature of melting ice. The sad truth is that the best cooling requires messy methods. The excellent perfusion and lack of edema seen in this patient can be partly attributed to the messy, effective cooling she received -- along with the speediness of delivery.
When perfusionist Melody Maxim consulted with CI in December, she recommended the use of a large cannula into the ascending aorta, rather than perfusion into the carotids and vertebrals. Our funeral director has often had problems getting cannulae into the vertebrals. Sampling venous return from the jugulars has also been a problem, because it is difficult to intubate the jugulars. Often effluent from the jugulars was sampled only after it mixed with a pool of other fluid. Sampling from the superior vena cava would avoid these problems.
|Aorta||Superior vena cava|
The third reason for perfusing with the large cannula into the aorta is to get better control of perfusion pressure. Melody had noted that the metal cannulae we have been using could cause a large pressure drop. As an experiment I took pressure readings with and without the metal cannulae at a flow rate of about one liter per minute (using VM-1 and a test system in CI's perfusion room). With the cannulae I got readings of about 100 mmHg, whereas without the cannulae I got readings of about 40 mmHg. In attempting to get physiological perfusion pressures during perfusion we had been aiming for 120 mmHg to 140 mmHg, but if my experiment is right, those line pressures corresponded to patient perfusion pressures of about 50 to 60 mmHg. Over-pressurizing the patient is a worrisome danger, but the danger of under-pressurizing is that capillaries are not sufficiently opened to allow for good perfusion. The greatest worry we had was that it might be difficult to properly secure the cannula in the ascending aorta. Melody suggested retrograde perfusion of a means of avoiding this problem.
Direct access to the heart required opening the chest. I had obtained a sternal saw for this purpose. But instead of using the saw to cut the sternum, Mr. Walsh cut along the ribs. He argued that this is standard procedure in autopsies. That may be true, but there is little concern for blood vessel integrity during an autopsy. Much blood accumulated in the pericardium, probably due to severed arterioles. There was no sign of clotting, however, which may be a testament to the heparin administration and the fifteen minutes of chest compressions given in the nursing home.
The cannula was inserted into the ascending aorta and held in place with a rubber ring on the cannula which was distal to the suture. The diameter of the ascending aorta is considerably larger than the diameter of the cannula -- which has much to do with the risk of the cannula not remaining secured. As it happened, during perfusion the cannula did slip out of the aorta once, but this proved not to be the disaster I had feared. The cannula was immediately restored, ligated tightly below the suture ring and remained in place for the rest of the perfusion. I believe that by using three rather than one sutre ring that the cannula can be well-secured without future worry.
The patient was perfused with 5 liters of 10% and 12 liters of 30% ethylene glycol at flow rates of about 1.5 liters per minute. These are large volumes, but much of this went into the body rather than just the head. Only after perfusing a while did Mr. Walsh ligate the descending aorta and axillary vessels. Despite these ligations there was still evidence of body perfusion, even after perfusion with 70% CI−VM−1 was begun. Most remarkably, there was no evidence of edema anywhere in the body, even at the end of perfusion.
Burr holes were inserted into the skull, and perfusion with 70% CI−VM−1 was then begun. Refractive index was determined using a Reichert AR200 Handheld Digital Refractometer rather than the old glass plate refractometer -- a vast improvement in speed, simplicity and reliability. Placing a tube for sampling into the superior vena cava was clean and simple, allowing for excellent sampling of effluent.
A full eighteen liters of CI−VM−1 was perfused into the patient, much of which apparently went into the body. Flow rates got up to 2 liters per minute and pressures of about 100 mmHg were recorded. These pressures where still line pressures, but with the wide-mouthed cannula the line pressure would be much closer to patient pressure than was the case with the metal cannulae. Earlier pressure readings were so much lower when using lower flow rates and the less viscous ethylene glycol that we had reason to question the accuracy of those readings.
There was no effluent from the left burr hole, and very little from the right burr hole. The first sample from the right burr hole gave a refractive index of 1.383 and a sample five minutes later gave 1.391 (below saturation). Samples from the superior vena cava rose to 1.417, which is barely over the refractive index for 60% CI−VM−1.
Jim Walsh and Andy Zawacki have expressed skepticism that burr hole effluent is anything other than an index of vascular damage. Cryonicist Mike Darwin mainly used burr holes to monitor brain swelling or shrinkage, but the burr holes we make are too small for visualization of the brain and we have only used them for refractive index sampling. Mike Darwin attempted to determine the source of burr hole exudate, with inconclusive results. But the vascular damage does not fit with Darwin's observation that the most burr hole effluent was seen in the patients with the least ischemic damage. I have examined the case reports, and only in the case of our 84th patient does it seem that burr holes were useful in deciding that perfusion was finished. If the problems of jugular sampling are eliminated through sampling from the superior vena cava, the disruption of perfusion and the compromise of head cooling associated with burr holes may never be necessary.
Record-keeping for this perfusion was not great, in no small part because of the attention devoted to the new methods and equipment. Nasopharyngeal temperature rose to 10.7ºC by the end of perfusion. Cryoprotectant toxicity is higher at higher temperatures, but diffusion in and out of tissues is faster.
At the end of the perfusion the patient's head was covered with dry ice and isopropyl alcohol was added to have the benefit of an ice slurry. By being in a box around the head, however, the slurry did not seem so messy.
The patient was driven to the CI facility from the funeral home and was placed into the computer-controlled cooling box for cooling to liquid nitrogen temperature. The dry ice slurry had driven brain (skull) temperature down to about −35ºC, but the temperature rose to nearly −21ºC before cooling-box cooling began driving-down the temperature. Naso-pharyngeal temperature rose from −36ºC to −35ºC before being driven-down.
|First 2 hours||Slower initial cooling|
Brain surface (skull) temperature was cooled to −115ºC in just over one hour, cooled more slowly for another half-hour to −120ºC, and then held at −120ºC for about fifteen 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 −120ºC, the viscosity is so great that the danger of freezing ( de-vitrification) is very small.
After holding skull surface temperature at about −120ºC for about 15 brain temperature became more uniform. The "annealing" step consisted of raising skull surface temperature to −117ºC over a period of about an hour, which allowed naso-pharyneal temperature to rise to nearly −118.5ºC. In immediate subsequent cooling, skull surface temperature fell below naso-pharyngeal temperature, as step designed to help minimize thermal stress during the long, slow cooling to liquid nitrogen temperature.
When the patient brain temperature reached about −155ºC I increased the rate of cooling somewhat so as to finish by Monday evening. Faster cooling at lower temperatures produces less thermal stress than the same rate of cooling at higher temperatures because thermal expansion with temperature is less per degree Kelvin at lower temperatures.
The patient was removed from the cooling box on Monday, June 2, 2008 at around 5 pm and placed in liquid nitrogen. Unlike the case with the previous patient, there had been no problems with false alarms coming from the Uninterruptible Power Supply (UPS) and cooling box controller alarms. Between cases facilities manager Andy Zawacki had wired an extension cord into the wall-plug. I believe that a plug not securely in its socket had been at the root of the false alarm problem, and that this problem will not happen again.