From Cryonics, May 1989
A SUSPENSION IN DETROIT
by Mike Darwin
On January 8th, a few weeks before I was to leave for Europe, an information request came into Alcor from a Detroit-area physician who informed us that he was terminally ill with cancer and giving serious thought to arranging for cryonic suspension. Mike Perry took the call, and aided by a handy copy of "The Cryobiological Case For Cryonics," he did a fine job of fielding a number of tough questions from the physician (whose name was Eugene Nalley) on the cryobiology of brains. A few days later Dr. Nalley called again to say that he had not received some follow-up information which he had requested from us. I called him back, apologized for the delay and ended up speaking to him at some length. It became apparent from our conversation that Dr. Nalley was anything but uninformed about cryonics and in fact had a long-standing interest in it and had been in touch with other cryonics groups.
He had given some consideration to making suspension arrangements, but was very up-front in stating that he just wasn't satisfied with what he had seen to date. At the time we spoke, he said he felt he had about six months to a year to go, depending upon how he responded to radiation therapy for his esophageal malignancy.
A few days later he received the material I sent and phoned for additional details. We spent several hours on the phone together and at that point it became apparent to me that his situation was a lot graver than he thought. I got some detailed medical history from him and ran it past a couple of Alcor members who are physicians. Their verdict was essentially the same as mine: three to four months at best.
A few days after that call my beeper went off. It was Dr. Nalley. He called to say that he was bleeding esophageally and felt he was deteriorating at a much faster pace than he had anticipated. His energy level was also low and he had decided that he wanted to put his youngest son, Jim Nalley, in charge of facilitating his cryonics arrangements. Would I talk to Jim, he wanted to know? I made the call to Jim from an auto store parking lot near an exit from the 91 Freeway.
I ended up speaking not just to Jim, but also to his wife Cindy. The starting conditions of the call were not good from any standpoint. I was at a pay phone in a noisy parking lot, there were two somewhat nervous (and I believe more than a little skeptical and suspicious) people 2,000 miles away in Detroit, and it was necessary for me to be on speaker phone on their end of the call. Their attitude was completely understandable considering the circumstances.
At that point I considered this just another one of those awful, longshot, last-minute calls that never materialize into a suspension. Here I was, talking to two people who were confronted with the fact that someone they loved very much was dying, and in addition to the usual stress of such situation there was now the issue of cryonics to consider.
As Jim and Cindy can now attest, talking with Mike Darwin about suspending (or facilitating the suspension) of a relative is not for the faint of heart. I graduated from the Curtis Henderson school of cryonics salesmanship, which consists of giving the person a large, undiluted dose of ruthless honesty followed by a number of worst case scenarios and harsh disclaimers to be chased with a tiny drop of optimism. The first thing I told Jim and Cindy after laying out the basics was: "Your father/father-in-law sounds very weak to me. From his description of his condition I think he has greatly overestimated the remaining time he has and unless he responds to treatment dramatically (which in my personal opinion is unlikely) he is going to be unable to make these arrangements himself. In order for him to have any chance of putting cryonics arrangements in place it is going to take every bit of courage and stamina you can summon. This may well be the most difficult and challenging thing you have ever undertaken. If, when you understand what is going to be involved you cannot manage it, then tell me immediately and save us both a lot of grief, expense and lost time."
I think this soliloquy impressed Jim and Cindy. I think the stream of details and information I supplied and the ready answers to their decidedly practical questions also helped. By the time that call was over, it was my impression that Jim and Cindy were "on the team."
A Trip To California
A lot had to be done. A huge stack of Alcor paperwork had to be filled out, funding had to be arranged and, most importantly, Jim and Dr. Nalley had to come and see the Alcor facility. We wanted to be very sure that they knew what they were getting into. We had already briefed them on all the "bad" things about Alcor: the litigation with the DHS, the Dick Jones case, the Dora Kent case. Now they needed to see for themselves what was available and meet a broader cross-section of Alcor's management.
The latter was especially important because I would be leaving for Europe in a few weeks. It was thus critical that the rapport we had built be transferred to someone else at Alcor so that communication would remain good and details such as hospital cooperation and shipment of the Alcor Remote Standby Kit could be worked out.
This was not an easy thing for me to do. Dr. Nalley and I had built a relationship which involved a certain amount of bonding. He trusted me, and I cared a great deal about him. He was a good, sincere, and intelligent man who obviously wanted to stay alive very much. I admire that. What I admired even more was his courage. Just three months earlier he had lost his wife (whom I could tell he dearly loved) to a long battle with cancer. He had been unsuccessful in persuading her to opt for suspension. He was 71 years old, in failing health, and none of his children had expressed much interest in cryonics either. As he said to me during one of those first phone calls, "It looks like I am going to be going into the future alone, but I still want to do it. I just don't see any other course of action that makes any sense at all." Spoken like a true cryonicist.
Jerry Leaf agreed to take over for me as the "primary" and on Friday, February 3rd, Jim and Dr. Nalley flew out to Southern California to look things over and meet with Jerry and me. Dr. Nalley was weak enough by this time that he needed a wheelchair to be taken through the facility (although he could stand and walk short distances). As soon as I saw him I revised his estimated survival time downward considerably. He had lost over 60 pounds and was markedly emaciated.
Jim and Dr. Nalley were satisfied (perhaps even impressed) with what they saw at Alcor, they had completed the paperwork sent to them a few days before (breaking the record formerly held by Dave Pizer for fastest Alcor sign-up) and Dr. Nalley was issued a bracelet and suspension coverage at the end of the tour. They flew out of Ontario Airport and back to Detroit the next day. I left for Europe the following Tuesday.
While I was in Europe, a constant worry was that Dr. Nalley would not survive long enough for me to get back. I had promised him that I would cut short my trip to come back at a moment's notice, and he promised me he would try to hang on till I got back.
He kept his promise, so fortunately I didn't have to keep mine. I had been back only a few days when the call came in. Dr. Nalley's quality of life was very poor. He had not responded to radiation therapy nor had he gained any weight after a feeding gastrostomy (opening made through the stomach and abdominal walls to facilitate tube feeding) had been made and tube feeding started. His weight was down to 126 pounds from a pre-illness average of 250. He was bedfast, in considerable discomfort, and "wanted to get it over with." In conjunction with his physician, his hospice nurse, and his children he had decided to refuse further tube feeding and go ischemic. We would be called to fly out and stand by when his condition warranted it.
While I was in Europe, Jerry Leaf and Jim Nalley had done a magnificent job of planning. An apartment had been rented in Ann Arbor, in Washentaw County, and Dr. Nalley was to be moved there when it became apparent that he would require nursing care and was in imminent danger of death. This was done because Washentaw County has an excellent hospice program and allows the hospice Registered Nurse to pronounce death in the home without the physical presence of the attending physician being required at the moment of death. A hospice service with 24-nursing personnel was selected, the arrangements were cleared with the local coroner's office, and a cooperating mortuary with a good-sized prep room was located a few blocks away.
Another important contribution to readiness was made by Alcor member Dave Pizer, of Phoenix, Arizona. One of the things which the previous few suspensions had made obvious was the inefficiency of ice bags as a heat exchange medium. The plastic bags do a nice job of containing the ice, but they also act to dramatically decrease its heat removal capability. Not only does the plastic act as an insulating layer, it prevents the ice-cold water generated from the melting ice from flowing over the patient and carrying away heat. What is ideally needed is an ice slush bath, something that would simulate cold-water drowning, where very high rates of heat removal are known to be both possible and cerebroprotective. Ice in plastic bags simply cannot deliver the kind of heat removing capacity that ice in direct contact with the patient can or that an ice water bath can deliver.
The Pizer Tank
The problem with using such a "direct contact" scheme or an ice water bath is obvious: the mess. The only advantage to ice bags is that they keep water and ice off the floor (with varying degrees of success). What would be needed if we were to use a direct contact approach would be some kind of tub or tank which the patient could be placed in. Additional requirements would be that such a tank would have to be affordable, lightweight and above all portable.
This is where Dave Pizer entered the picture. Among other businesses, Dave and his wife Trudy own and operate a chain of auto upholstery shops in Phoenix. Dave has done a tremendous amount to help Alcor in the past both in terms of time and money, and he had previously volunteered to do any custom upholstery we needed. It didn't seem like a service Alcor was likely to be needing at the time it was made, but then along came the idea of the "portable ice river," as Steve Harris calls it.
Dave seemed the man for the job. He didn't disappoint us. I rang him up, told him briefly what was needed, and followed up with a sketch which was sent off a day or two before I left for Europe. When I returned I learned that he had built the tank from the drawing and sent it along a week or so after I'd left.
The Pizer Tank, as it is called, is a 6'2" long (inside) framework of 1- 1/4" PVC pipe to which a flexible Naugahyde tank is attached with snaps. The tank as executed by Dave is nearly ideal: it is inexpensive, breaks down into easy-to-transport components, is extremely rugged, and can hold a full load of 75 gallons of water without leaking or disintegrating.
Another change in technique used in Dr. Nalley's transport was the substitution of the new calcium channel blocker nimodipine for Verapamil, which we have previously used. Nimodipine has been shown to be far more effective in a variety of animal models in protecting against reperfusion injury following extended periods of cerebral ischemia. One investigator has recovered pig-tailed monkeys from up to 17 minutes of total cerebral ischemia using nimodipine administered starting five minutes after the animals were resuscitated. The use of Nimodipine in cryonic suspension patients was not straightforward. It took several weeks of on-again, off- again effort just to develop a vehicle solution that the drug would dissolve in. Nimodipine is also very photosensitive and degrades rapidly when exposed to white light. Thus it must be packaged and delivered in photosafe vials and administration equipment. All of these problems were overcome: the last of them only a few days before Jerry and I left for Detroit.
On March 11th, Jim called and informed us that his father was starting to slip badly and had requested that we come. Jerry flew out the following morning. After some consultation it was decided that I should keep my speaking engagement at the California Coroner's Convention the morning of the 15th and then fly directly from Sacramento to Detroit. Jerry Leaf arrived on the morn- ing of the 12th.
If Dr. Nalley had proven too optimistic about how long he had to live, he proved equally pessimistic about quickly he would "die." Death from dehydration is a slow, unpleasant process.
The only bright spot was that Dr. Nalley was surrounded day and night by all four of his biological children (and visited frequently by his step- children) throughout the ordeal. Jerry and I have never observed such love and care on the part of all the children in a family. They were there with him through almost every minute of what was, to put it mildly, a painful and stressful experience.
Jerry and I spent six days with the Nalley family in very close quarters. It was an enriching experience for us and one we are very grateful to have had. They are extraordinary people, each and every one of them. Just how extraordinary we were soon to find out.
On March 19th, it became apparent to everyone that Dr. Nalley was in the final 48 hours of his illness. He was severely dehydrated and had an overlying case of pneumonia. Steve Bridge, Alcor's Midwest Coordinator, was summoned from Indianapolis to serve as an extra hand. A few weeks earlier Steve had flown up to Detroit to meet with the Nalley family and to act as our eyes and ears in checking out the mortuary and the Remote Standby kit to make sure that everything was in order.
On the night of the 20th, Dr. Nalley's breathing became very labored and it was apparent that he was at most a few hours from cardiac arrest. We spent a rocky night, sleeping fitfully with several false alarms. Around 8:00 AM CST on the morning of the 21st, the hospice nurse notified us that he was frankly agonal and that he would arrest at any minute. We got out of bed and began readying the resuscitation equipment and medications. We did not have long to wait this time. At 8:19 AM Dr. Nalley experienced respiratory and cardiac arrest and was pronounced legally dead by the attending nurse. At 8:25 AM CPR was begun by Jim, followed by support with a Brunswick heart-lung resuscitator.
Then the first, and thankfully the last, major problem occurred: We had requested that a "heparin-loc" intravenous catheter be put in place in Dr. Nalley while he was still alive. The hospice nurse was not comfortable with this request and gently refused it. Even though Dr. Nalley had excellent peripheral veins we were concerned about our ability to insert an IV catheter if he was badly dehydrated. As it turned out, our worries were justified. Despite vigorous efforts by myself, Jerry Leaf and Cindy Nalley (who is an expert at sticking small vessels in dehydrated animals: she is a veterinary medical technician) we could not get a catheter in. After a number of frustrating minutes of failure we decided to move Dr. Nalley from the back bedroom where he had arrested into the living room where we had our Pizer tank set up and considerably more room to work. Once he was positioned in the Pizer tank we managed to do a cut-down and start our IV medications at 8:57 AM. Luckily, Cindy had her animal emergency kit in her car and we were able to fashion a makeshift cut-down tray on the scene. We have since modified the Alcor medications kit such that it contains a field cut-down kit so that we are never in that situation again.
Once he was in the Pizer tank, Dr. Nalley began to cool rapidly. In fact, his rate of temperature descent during external cooling was roughly twice that of the last patient Alcor suspended under similar conditions (Alice Black, see Cryonics 9(11) November 1989). By 11:30 AM his esophageal temperature was down to 24.5°C from a post-arrest temperature of 39.5°C at 8:55 AM. This works out to an average cooling rate of 6.4°C per hour. With further refinements such as the use of a battery-operated pump and a sump reservoir of ice water we think we can increase the rate of core cooling using such a bath to 10°C to 12°C per hour in selected patients (i.e., those who are thin or wasted secondary to disease and who thus have little insulating fat and low body mass).
Another complicating factor which was beyond our control was Dr. Nalley's low blood volume due to dehydration. Even after administering nearly 1,500 cc of various transport medications he was still severely dehydrated and probably had an even lower than the average (inadequate) blood pressure while on CPR support. The ability to rapidly cool such patients thus becomes paramount since CPR is probably doing little to meet their metabolic needs and is probably useful primarily to circulate transport medications and prevent blood from clotting.
By 11:33 AM blood washout and perfusion of the tissue preservative solution (TPS) had begun. Perfusion was effective at rapidly reducing his core temperature; dropping it from 23.5°C to 3.5°C in 45 minutes.
Despite the probable poor cardiac output from the HLR, an arterial pulse with pressure was noted during cannulation and the first venous pH was 7.16, indicating that the THAM buffer had been circulated.
Blood washout went very well. At first, we were apprehensive that we had a serious problem, since when Jerry Leaf opened Dr. Nalley's femoral artery it was observed to be obstructed by a clot. We were immediately concerned that he might have clotted systemically. Fortunately, this was not the case and the clot in the femoral artery was the only one noted at any time during blood washout or subsequent cryoprotective perfusion. It had a "retracted" appearance indicating that it had probably occurred during the agonal period when his peripheral circulation was being shut down to conserve blood flow to the brain and core organs.
Blood washout was terminated at 11:58 AM at a venous pH of 7.80. This is the first time we've ever reached such a desirably high terminal pH and this was achieved, we believe, as a result of the addition of a modest amount of potassium phosphate to the perfusate to augment the organic HEPES buffer which we have used alone in the past.
We also think it possible that the addition of phosphate and ribose to the flush perfusate resulted in better metabolic support to the muscles (and presumably neurons and other body cells) during the subsequent cold ischemia of air transport. When the patient arrived at the facility rigor mortis was present only in the leg that had been unperfused as a result of being used for the femoral cut-down (since Dr. Nalley had elected for neurosuspension, no effort was made to perfuse the limb supplied by vessels used to carry out the blood washout). It is not possible to be certain that the absence of rigor was a result of these changes in perfusate composition, since the use of the Pizer tank almost certainly resulted in substantial protection of muscle energy reserves by facilitating more rapid cooling than has been achievable in the past.
Another change in procedure was the use of 20 liters of Dextran40- containing perfusate for initial washout, which was then "chased" with 10 liters of base perfusate in which hydroxyethyl starch (HES) was substituted as the colloid. Our experience with two previous patients had indicated that Dextran 40-containing flush solutions resulted in more complete blood washout and considerably less cold agglutination than we have previously observed. Unfortunately, Dextran 40 is undesirable to use for cryoprotective perfusion because it tends to leak from the capillary bed and it is somewhat toxic to the endothelial cells which line the capillaries. This latter effect is a consideration of some import when the exposure time of the capillaries to the agent will be many hours, as it is during air transport of patients like Dr. Nalley. It was for this reason that its concentration was greatly reduced by flushing the circulatory system with 10 liters of base perfusate containing HES.
From the beginning of the transport procedure, continuing through blood washout and preparation for shipping, Dr. Nalley's children, Jim, Gene Jr., Ray, and Diane were present and assisted every step of the way. Jim started manual CPR after legal death was pronounced until we could couple the patient to the heart-lung resuscitator. CPR was continued while transporting Dr. Nalley to the mortuary and setting up the circuit for blood washout. Cindy scrubbed in and assisted Jerry and me with the cutdown and blood washout.
Following the completion of blood washout, Dr. Nalley was prepared for air shipment by being placed in an insulated chest and completely packed in ice in Zip-Loc bags. We were fortunate that blood washout was completed in time to catch a direct flight leaving Detroit International Airport at around 3:00 PM and arriving at Los Angeles International at about 7:00 PM. Jim and Cindy had decided to accompany Dr. Nalley on the flight and, emotional state permitting, participate in the rest of the cryonic suspension procedure.
All of us at Alcor had real misgivings about the latter idea, but we also felt very strongly that it was important for purposes of both reassurance and accountability to let the family be present if they could handle it. As it turned out, not only did Jim and Cindy hold up well emotionally, they were two of the most useful people around.
Dr. Nalley arrived at the facility at about 10:00 PM and by 10:30 PM his rectal temperature had been measured at 2.0°C. Surgery was begun at 1:11 AM on the morning of the 22nd and perfusion was begun at 3:22 AM.
Blood washout of the brain, as evaluated though a 10mm burr hole over the parietal cortex, was excellent. The pial vessels on the cerebral cortex surface were free of blood, as were the tissues of the chest and head which were incised to gain access for vascular cannulation and opening of the burr hole (hematocrit at the end of blood washout was unreadable). The use of Dextran-40-containing flush seem ed to provide better blood wash out than has been observed with the use of HES flushes, extending the experience we have had with the last few suspension patients treated under similar circumstances.
The burr hole was opened prior to cryoprotective perfusion and the cerebral cortex was ob- served to be free of both blood and edema. Cryoprotective perfusion with glycerol in our sucrose-HEPES (SHP-1) perfusate began uneventfully. Approximately 40 minutes after the start of glycerol perfusion, a modest increase in brain volume was observed indicative of developing cerebral edema. We had anticipated cerebral edema secondary to ischemic injury as a potential problem because of the long agonal period and poor circulation during CPR. Our initial strategy in controlling cerebral edema consisted of increasing the slope of the glycerolization ramp from a rate of approximately 20mM per minute to 40mM/min. This was effective for awhile, but it soon became necessary to switch from continuous perfusion to pulsatile flow (with a ramp rate around 25mM/min.) in order to control edema.
Pulsatile flow was not effective in reducing the degree of edema, but it did stop its progression. The surface of the cerebral cortex was thus bulging into the burr hole only about 1-2 mm at the conclusion of perfusion.
Checking For Flow
Since we have no way of directly measuring intracranial pressure or performing brain perfusate flow studies, we were very anxious to know if we were in fact perfusing the brain, or if flow was shunted to bone, muscle, and other supportive tissues. To help resolve this question (this is not the first time we've been confronted with cerebral edema during cryoprotective perfusion) a bolus of 750 mg of fluroescein-labeled dextran70 was given into the arterial line. Immediately before the fluroescein-labeled dextran was given the lights in the operating room were turned off and the burr hole was illuminated with UV light, thus allowing the cortical surface to be observed for the presence of the fluorescent dye.
We were not disappointed. Within seconds of administration the dye appeared in the brain pial vessels under the burr hole; one pial vein which was approximately 0.5mm in diameter and whose path bisected the burr hole lit up like an oscilloscope tracing. Thus, we were reassured that cryoprotective perfusion was continuing in the brain despite the presence of some edema and consequent likely elevation of intracranial pressure.
Perfusion flow rates were excellent throughout perfusion with the flow rate being 1900 cc/min at the start of perfusion and 1200 cc/min near the end of perfusion (a decrease in flow rate occurs near the end of perfusion in all patients due to the increasing viscosity of the perfusate as the glycerol concentration increases).
Perfusion was terminated at 6:10 AM at a terminal glycerol concentration of 3.8 M -- very close to what we had been hoping for. Cephalic isolation was completed by 6:44 AM and cooling to dry temperature was started at 7:03 AM.
Seeing It Through
Throughout perfusion and cephalic isolation Jim and Cindy stood by and provided help where they could. After the completion of perfusion and the start of external cooling both Jim and Cindy pitched in with clean-up. Cindy's skills were particularly useful. Working almost single-handedly, she washed the surgical instruments and prepared them for resterilization -- another advantage to having a veterinary medical tech around!
Jim and Cindy remained in Southern California for the next several days -- long enough, in fact, to assist with the transfer of Dr. Nalley from the Silcool bath to the neurocan for cooling to liquid nitrogen temperature. Jim's photographs of this part of the suspension procedure are, to our knowledge, the first that have ever been made of this procedure. Jim also acted as the photographer during the transport of Dr. Nalley, and these pictures are the first ever made of an Alcor field resuscitation/blood washout.
The Long Sleep
On April 4, 1989 Dr. Nalley joined the other Alcor neuropatients in the cephalarium vault. He had told me repeatedly during our phone conversations that cryonic suspension as a ticket to seeing the future had been a dream of his for 20 years. Both of us had hoped that journey could have been deferred, even if only for six months or a year, but events proved otherwise, as they often do.
Near the end, his anxieties were only that he get suspended under the best conditions available. I believe that cryonics provided a substantial element of hope, although it was clear that he considered it a long shot.
My own perspective is not greatly different from his.
Good luck, Dr. Nalley. Au revoir, but hopefully not goodbye.