X-Message-Number: 2867 Date: 09 Jul 94 03:02:55 EDT From: Mike Darwin <> Subject: CRYONICS Case Report (1/3) BPI Tech Brief #9 The following is case history of an ACS patient cryopreserved by Biopreservation. In accordance with the patient's wishes his name has been disclosed in this report. Wherever XXXX, XXXX appears it means that an individual did not wish (or we were unable to reach or otherwise get authorization to disclose) his/her name and we are respecting that individual's wishes and/or erring on the side of caution. A number of caveats about this report need to be made at the start: 1) Graphic data is usually critical to understanding what went on and it cannot easily be presented here -- in the case of this author it cannot be presented at all. Individuals who wish a copy of this report with the graphic data (charts, diagrams, etc.) may obtain one by contacting either BioPreservation or ACS. The report in its rough form (i.e., without photographs) will be furnished at the cost of duplication and handling (probably around $25.00). Copies of the finished report will be available through both ACS and BPI at a lower cost (larger press run, less administrative time) although when this final version will be ready it is not now possible to say. 2) This report will be presented in two parts: an initial almost exclusively descritive part, and a second and much shorter part which will contain some conclusions, discussion, and suggestions as to how this case might have been optimized and how future cases might be better handled as a result of what was learned here. Thus, I have deliberately avoided (wherever possible) drawing conclusions or making comments in the first part. Readers may find this frustrating but I believe it is important, in an area as speculative as cryonics, to try and carefully delinerate between simple observations and conclusion, opinion, and speculation. 3) This is technical case report. No translation or brief summary for the casual reader is provided. It will be tough sledding for anyone who does not have either a lot of patience and a couple of good reference books and/or a medical background. I do not apologize for this, merely caution the reader. I believe there is a need for reports such as this because they lay down, with some precision, what is being done and what results. I hope to routinely (in the future) begin correlating the gross and laboratory results observed in human patients with histological and ultrastructural results. To this end BPI has spent considerable time and money acquiring clinical biopsy equipment which allows for tissue sampling with minimum invasiveness. 4) An added frustration in viewing this report will probably be the hashing-up and/or omission of symbols such degree, micron, and so on. There may also be the loss of regularity in some of the tabular data. I regret that I do not have either the time, or in some cases the expertise, to go into the text and correct or otherwise replace characters which will be deleted by conversion to ASCII. I ask the reader to bear with me and/or to request a paper copy. ---Mike Darwin Cryopreservation Case Report: Jerome Butler White American Cryonics Society ID #: ACS 9577 Patient Name: Jerome B. White Date of Birth: 10-31-1938 Social Security #: 525-88-9577 Cryopreservation Date: 02-05-1994 Transport Staff : Michael G. Darwin, C.T.T., C.R.T., Team Leader, Surgeon Naomi Reynolds, C.T.T., Transport Technician (Medications) Shawn Shermer, B.S., C.T.T., Perfusionist Jim Yount, C.T.T., Transport Technician (Thumper, Logistic Support) XXXXX, XXXXX, C.T.T. (Scribe) Cheryl Heisler, Videographer Cryoprotective Perfusion Staff: XXXXX, XXXXXX, Ph.D., Surgeon Faye Smith, R.N., Scrub Nurse Michael G. Darwin, C.T.T, C.R.T., Team Leader Naomi Reynolds, C.T.T., Scribe Shawn Shermer, B.S., C.T.T., Perfusionist Sandra Russell, B.S., Assistant Perfusionist, Laboratory Analysis, CPA Ramp Technician Paul Wakfer, B.Sc., CPA Ramp Technician, Logistic Support Jim Yount, C.T.T., Videographer/Photographer Allen Lopp, B.S., Logistic Support Michael Fletcher, R.T, Equipment Technician, Logistic Support Mark Connaughton, B.S.M.E., -79 C Cool-Down Technician Candy Wood, Circulator Larry Wood, M.S., Logistic Support Biographical Background and Social History Mr. White became involved in cryonics shortly after the publication of Robert Ettinger's book The Prospect of Immortality in 1964. He was one of the founders of the American Cryonics Society (ACS) (then the Bay Area Cryonics Society) in 1968. From 1968 through 1982, and from 1990 through 1992, he served as an Officer, Governor and committee member for ACS. Mr. White was the second President of ACS serving from 1971 through 1982. Mr. White was also a frequent spokesman for ACS, and for the promotion of cryonics, appearing on radio and television shows and speaking to schools, educational and civic groups. Mr. White was also a one of the founders of Trans Time, Inc., a commercial cryonics services organization. Mr. White had a varied professional and educational background. He received his B.A. in philosophy from the University of New Mexico in 1966 and continued his education at the University of California at Berkeley where he studied Computer Science and education with special emphasis on the psychology of learning, programmed learning, and computer aided learning. From 1983 to 1992 Mr. White was lead designer for software for Sterling Federal Systems, Inc. a contractor to NASA Ames. While at Sterling Mr. White worked on a variety of NASA projects including participating in the development of software to analyze the Martian atmosphere. He also participated in design work on a variety of programs to develop tilt-wing aircraft. Mr. White was also responsible for the first paper describing a detailed and scientifically plausible approach to the repair of cryopreservation-induced damage: "Virus-induced repair of damaged neurons with preservation of long-term information content" which was presented at the First Annual Cryonics Conference in Ann Arbor Michigan in 1969. Over the course of his nearly three decades of active involvement with cryonics Mr. White repeatedly updated and re- executed legal and financial paperwork to provide for his cryopreservation, including a Consent for Cryonic Suspension (cryopreservation) executed on 27 August, 1985 and Durable Powers of Attorney for both finances an healthcare executed in August of 1993. Mr. White's academic background, his long years of active involvement in cryonics, and his first-hand participation in every aspect of a number of human cryopreservations establishes his informed consent. Medical History The patient is a 55-year-old Caucasian male homosexual who was diagnosed with HIV (Human Immunodeficiency Virus Type I) disease in 1989. The first CD4 cell count noted in the patient's medical record was 465 per cmm on 01-24-1992. The patient experienced an atypical precipitous decline in CD4 count from 386 per cmm on 01-31-1992 to 114 per cmm on 04-29-1992. A formal diagnosis of AIDS (Acquired Immune Deficiency Syndrome) Related Condition (ARC) was made on 08-10-1989. Prior to that time the patient had enjoyed good health with a medical history remarkable only for long-standing seasonal allergic rhinitis and hepatitis B, the latter of which ran its course without complications in 1977. At the time of his diagnosis with ARC the patient was begun on Nizoril for onychomyocosis. On 08-28- 1989 the patient was started on an antiretroviral treatment consisting of 100 mg Zidovudine q. 4 hours. On 06-11-1991 the patient was begun on 300 mg Nebupent (aerosolized pentamadine for pneumocystis carinii prophylaxis) q.d. and the antiretroviral ddC (2',3'-dideoxycytidine) was added to his regimen at a dose of 500 mg t.i.d. As of 03-31-1992 the patient was described as doing well and all organ systems were negative for pathology with the exception of the skin which presented a rash thought to be due to ddC (ddC was discontinued for this reason on 02-28-92). Record of an office visit to his primary care physician Dennis McShane, M.D. on 05-28-1992 notes the following: ddC restarted on 05-14-1992 without complications, the development of simple bronchitis on 04-29-1992, complaint of depression on 04-29-1992, and the presence of hairy leukoplakia on 05-08-1989. The patient's Karnofsky score at the time of the 05-28-1993 visit was 80%. During an office visit on 07-02-1992 the patient noted the beginning of intermittent diarrhea, some decrease in energy level, and slight numbness in the feet. By 09-10-1992 the patient was experiencing chronic watery diarrhea on a daily basis and his Karnofsky score had declined to 70%. Medications were transiently discontinued to evaluate for their possible effect on diarrhea. By 10-15-1992 the patient had experienced considerable weight loss as a result of chronic diarrhea (down to 65 kg from a normal baseline of 75 kg), consistent daily fatigue, and his CD4 count had declined to 45 per cmm. At that time, 1 tbs. of Metamucil b.i.d. and 400 mg Trental t.i.d. (the latter as an inhibitor of tumor necrosis factor/treatment for AIDS wasting syndrome) were added to his daily medications. On 10-29-1992 the patient's condition was noted to be continuing to deteriorate with a further decline in his CD4 count as well continued deterioration in the patient's subjective condition. At that time 200 mg of ddI (2',3- dideoxyinosine) b.i.d. and 250 mg Azithromycin q.d. (for mycoplasm avians intracellularae (MAI) prophylaxis) were added to the patient's regimen with concurrent discontinuation of the zidovudine and ddC. The ddI resulted in exacerbation of the diarrhea and was discontinued with a return the zidovudine/ddC protocol resulting in lessening of the diarrhea. On 11-11-1992 a flexible sigmoidoscopy was performed in an attempt to determine the cause of the diarrhea. The results of sigmoidoscopy were unremarkable. By 02-25-1993 the patient's weight had declined to 59 kg and his Karnofsky score to 60%. Stavudine (2'3'- didehydrodideoxythymidine) (d4T), 4 ea., b.i.d. was begun 02-05- 1993. On 05-05-1993 the patient's weight had declined to 57.7 kg with diarrhea, cachexia and marked temporalis muscle wasting noted. On 02-06-1993 a peripherally inserted central venous catheter (PICC line) was placed and the patient was started on total parenteral nutrition (TPN) at 2000 cc per day with 10% lipids at a rate of 167 cc/hr over 12 hours. Due to persistent abdominal pain a CT of the abdomen was performed on 05-14-1993 which disclosed fatty infiltration of the liver, mild to moderate splenomegaly, and a 2 cm non- contrast filling mass just below the cecum. Cefelexin was added to the patient's antibiotic regimen to cover for the possibility that the abdominal mass was an abcess. On 05-20-1993, 50 mg pyridoxine q.d. and 50 mg thiamine q.d. were added to his treatment program. The patient's weight was stable at 57.7 kg and his Karnofsky score was 80% at that time. On 06-18-1993 the patient was noted to have markedly increased pain secondary to ddC neuropathy with unexplained reluctance to take analagesics in the prescribed way (possibly indicative of early neurological deficit secondary to his illness). Medications added on 06-03-1993 were as follows: 25 mg Elavil, h.s., Vicodin, 1 q. 4 hrs., 100 mg Diflucan (fluconazole) q.d. Elavil was increased to 50 mg h.s. on 06-18- 1993. The patient continued to do fairly well with some weight gain on TPN (62 kg) until 08-11-1993 at which time the patient was seen with complaints of falling due to lack of balance. Neuro exam disclosed intact cranial nerves, PERRLA, ability to rise from seated position without assistance, oriented x 3 (but with verbal responses slightly slowed), negative Romberg, unsteady gait without ataxia, and inability to stand on tiptoe or hop on each foot. A CT scan of the head was performed 08-12-1993 at Standford Medical Center which revealed a mass in the right thalamus with surrounding edema which involved the thalamus, right internal capsule, posterior limb and globus pallidus. Post contrast scan disclosed a mass approximately 12 mm in diameter. Following the CT scan the patient was admitted to Sequoia Hospital in Redwood City, California for stereotactic biopsy to discover the etiology of the thalamic mass and begin appropriate medical treatment of the lesion. At the time of this admission, in addition to the acute thalamic mass, the patient was noted to be suffering from AIDS wasting syndrome, oral thrush, AIDS and/or antiretroviral peripheral neuropathy, myopathy due to AIDS and zidovudine, and depression due to his underlying poor condition. At the time of his admission the patient's mentation was noted to be intact, but with some slowness and thickening of speech. Thalamic lesion biopsy results reported on 08-13-1993 disclosed the presence of toxoplasmosis gondii, and initial treatment consisting of pyremethamine and sulfadiazine was commenced. On 08-24-1993 the patient developed an erythamatous mobiliform rash which was believed due to sulfonamide sensitivity. Sulfonamide was discontinued and the patient was begun on I.V. clindamycin. He slowly improved and was discharged on 08-12-1993 on maintenance doses of 75 mg pyrimethamine, 600 mg clindamycin q. 6 hrs, and 10 mg leucovorin b.i.d. all administered p.o. for treatment of the toxoplasmosis. The patient was readmitted to Sequoia Hospital on 08-16- 1993 following an episode of prolonged confusion, possible (unwitnessed) seizure, fever (39.3 C) and rapidly progressive debilitation. A CT scan revealed an increase in the size of the right thalamic lesion with involvement of the head of the right caudate nucleus. The patient was begun on broad spectrum antibiotics (ceftazidine and vancomycin) for the possibility of sepsis. Because of the presumed progression of his CNS toxoplasmosis he was begun on high dose pyrimethamine in addition to clindamycin and atovaquone. On 10-16-1993 the patient was again admitted to Sequoia Hospital with recurrent seizures. At that time it was determined that the patient had become noncompliant in taking his medications (discontinued taking his medications 2-3 weeks prior to this admission) due to depression and deteriorating mental state. The patient was started on Dilantin (phenytonin) which was subsequently discontinued due to skin rash and substituted with Phenobarbital (120 mg at bedtime, 60 mg in the a.m., both given p.o.). During this admission the patient also developed Staph cellulitis at the site of his PICC line with culture of the catheter tip revealing coagulase negative Staphylococcus. The patient was treated with vancomycin and the catheter was removed. A new PICC line was placed prior to discharge. The patient was discharged on 11-04-1993. By 11-08-1993 the patient's mental state had deteriorated to the point that the reliability of self-care of his PICC, and of his self-medication were questionable (the patient had formerly been meticulous in his self-care). On a follow-up visit by the home healthcare nurse on 11-11-1993 it was determined that the patient had become incapable of further medical self-care and at this point I.V. medication and TPN treatments were administered by his Primary Caretaker and medical and financial power of attorney, Margaret Bradshaw (a close friend). At this time the patient's Karnofsky score was 50% with the patient requiring full-time assistance and considerable medical care. On 11-22-1993 the patient was seen in his primary care physician's office emergently for acute pain and swelling of his left arm apparently secondary to infection of his PICC line. The PICC line was removed and the patient was continued on 1 g vancomycin q. 12 hrs. At this time the patient was also started on 2 mg dilaudid q. 4 hrs for pain. Following the discontinuation of TPN the patient lost 5.45 kg and decided to restart TPN. A PICC line was again placed and TPN was restarted on 12-15-1993. Medications at this time were as follows: Table I: Medications as of 12-15-1993 Drug Dose Frequency Start Date Nebupent 300 mg q.d. 06-11-91 Trental 400 mg t.i.d. 10-15-92 Pyridoxine 50 mg q.d. 05-20-93 Thiamine 50 mg q.d. 05-20-93 Vicodin tablet q. 4hr, p.r.n. 06-03-93 Riopan 1-2 tab q.i.d. 07-12-93 Leucovorin 10 mg b.i.d. 08-15-93 Haldol 2 mg h.s., p.r.n. 08-31-93 Diflucan 50 mg q.d. 08-20-93 Azithromycin 250 mg q.d. 09-23-93 Zantac 150 mg b.i.d. 08-31-93 Pyramethamine 25 mg q.d. 11-11-93 Phenobarbital 120 mg h.s. 11-01-93 Clindamycin 600 mg q.i.d. 11-11-93 Dilaudid 4 mg q. 4hr 01-06-94 (+ 2 mg from11-22) Testosterone 100 mg q.m.o., I.M. 12-23-93 By 01-20-1994 the patient was severely disabled with a Karnofsky score of 30%. Ms. Bradshaw noted that the patient was increasingly somnolent and bed-bound and there was discussion of discontinuing life-supporting treatment in the near future (i.e., TPN, antibiotics, etc.). Diagnoses at this time were as follows: Table II: Diagnoses as of 01-20-1994 Diagnosis Start Date Hairy Leukoplakia 05-08-89 Depression 04-29-92 Diarrhea 07-02-92 Weight Loss 01-08-93 AIDS 02-16-93 AIDS Wasting Syndrome 05-05-93 Peripheral Neuropathy 05-20-93 Myopathy 07-29-93 CNS Toxoplasmosis 08-11-93 Impotence 10-07-93 Knowledge Deficit 11-11-93 On 01-28-1994 the patient experienced an acute febrile episode (39.6 C) with pulmonary congestion (rhonchi present bilaterally), labored respirations. Pulse oximetery was instituted on the afternoon 01-28-1994 using Criticare Model 503 pulse oximeter. Oxygen saturation at that time was 85% and the patient was obtunded with a Glasgow Coma score of 4. The patient was started on 4LPM oxygen and given 1 g vancomycin b.i.d. under advice from a consulting physician, Ronit Katz, M.D. Due to the patient's poor quality of life and the advanced stage of his disease (multisystem organ failure) it was determined by Ms. Bradshaw (his medical power of attorney) in accordance with the patient's previously expressed wishes concerning what constituted an acceptable quality of life to him, and in consultation with his primary care physician Dennis McShane, M.D., that hospitalization was medically inappropriate. It was the opinion of both of his physician and his attending home healthcare R.N. that death was imminent. Standby personnel from both Northern and Southern California were deployed. Shortly after the arrival of Standby personnel the patient's condition stabilized and improved markedly. There was considerable improvement in breath sounds, return of responsiveness, and decrease in fever to 38.0 C. By 01-13-1993 the patient was able to take fluid by mouth and was able to be assisted to a chair for short periods of time. The patient's mental state was one of confusion and apraxia/aphasia although he did seem to recognize friends and caretakers, and was able to respond to verbal commands/interrogation by nodding his head appropriately. The Standby Team stood down at this time. Agonal Course -- To Be Continued -- Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=2867