From Cryonics, August 1981
by Jerry D. Leaf
Every case encountered in medical practice has its stamp of uniqueness, and so it is to be expected that every case of cryonic suspension will also be unique. It is hoped that each reported suspension case will provide helpful information to others, but equally important, that these reports will stimulate thinking beyond actual experience to possible problems in future suspensions.
The suspension patient, Mrs. K.V.M., was a suspension member of the Bay City Cryonics Society (BACS). Suspension arrangements were completed prior to clinical death. When I was advised of K.V.M.'s suspension status, she was in a community hospital being treated for chronic liver disease, etiology unknown. A nursing supervisor at the hospital agreed to co-operate in undertaking recommended emergency procedures in the event of her death. However, K.V.M.'s condition improved and she was discharged from the hospital as an outpatient.
K.V.M. lived alone, but was visited daily by a close relative. The relative had to leave town for a short business trip, and when he returned on November 3, 1978 he was informed that K.V.M. had just died. She died late at night, so that even if daily contact had been continued, it probably would have been hours before she would have been found. This points up the need for biomedical monitoring systems for suspension patients in similar situations. Fortunately, most people today are in a clinical setting when they have medical problems even when there is an unexpected problem, due to the paramedic services presently available.
The technology is available for physiological monitoring of patients in the home environment. Pulse transducers with built-in transmitters for activating automatic telephone dialers are needed. If such a system can be purchased, it would be advisable that cryonics organizations purchase them for lease to suspension patients.
I was able to get an abbreviated medical history in a telephone conversations with K.V.M.'s relative prior to the suspension procedure. After the suspension, we requested the relative acquire the complete medical records, including x-ray films, for K.V.M.'s suspension file. We have not received these records to date. I would like to emphasize the importance of acquiring medical records for each person who has made arrangements for cryonic suspension. The medical history has a direct bearing on the choice of surgical sites for perfusion and can be invaluable aid to interpreting problems that arise during the course of a suspension procedure. Every Suspension Member should insist that a copy of his medical records be kept on file by the cryonics organization responsible for his suspension. The importance of these records to a future medical team attempting reanimation can only be guessed at, but we can be sure that they will contain invaluable information.
K.V.M. was a female, caucasian, age 65, weight about 73 kg., height about 1.73 meters. Until 1963 her medical history was uneventful, at which time she underwent a laparotomy procedure for removal of an ovarian cyst. No other surgical procedures are known to have been performed. In 1973 she developed diabetes, possibly the lipoplethoric type, and was placed on regular insulin maintenance. The diabetes was easily controlled. In 1978 she was admitted to the hospital for evaluation and found to have a chronic liver disease, with probably hepatohemia. Exploratory surgery was ruled out, due to a coagulopathy in which her clotting capacity was subnormal, making any kind of surgery dangerous. While in the hospital she developed phlebitis and swelling of her lower extremities, with secondary infection. Her condition was brought under control during her hospitalization and she was released to continue recovery at home. She was placed on a special diet, but was receiving no regular medication. She had prescriptions for Dalmane (insomnia) and Valium (tranquilizer), to be used as needed. She was psychologically depressed by her health problems. She seemed to be in a stable condition until the time of her death.
Mrs. K.V.M. fell unconscious, on her front porch late at night. SHe was not discovered for several hours. The ambient temperature was -1 degree C. She was transported to the hospital where she was pronounced D.O.A. (dead on arrival). The cause of death was given as coronary occlusion. She was kept in a refrigerated room at the hospital until arrangements were made for her transport to Los Angeles, California, packed in ice. She was picked up at the Los Angeles International Airport and brought to the suspension facility in Fullerton.
The operating table (1) was padded using an egg crate foam rubber pad (2) to eliminate pressure occlusion of peripheral circulation. The O.R. table was moved to a position adjacent to the Ziegler case and the patient lifted out and transferred to the O.R. table. The body was covered with ice bags, zip-lock type (3), which minimize the thickness and weight of the ice pack. Chipped ice was used to reduce the possibility of pressure points that would be created by cubed ice. The head was placed in a three-sided plastic container (4), without a top, to insure the ice packs about the head were not displaced. Esophogeal and rectal thermistor temperature probes (5) were placed and temperatures monitored on a Yellow-Springs meter (6). The O.R. table was moved into the operating theater.
Since no pre-treatment transport protocol had been used, the possibility of intravascular coagulation was considered in the choice of operative approach (7). A median sternotomy approach was used to maximize access to the major vessels. The chest and abdominal areas were prepped using a disposable surgical prep kit (8) with iodine based prep solution. The surgical team scrubbed (9), gowned (10), and gloved (11). The sternal operative site was defined by draping with sterile towels (12) and an adhesive skin drape (13) was placed over the sternum. A cardiac drape (14) was placed over the patient, extending to the anaesthetic screen at the head, down over the feet and down over the sides at least 24 inches below the operative field.
The incision wa made over the midline of the sternum with a #10 scalpel blade (15). Fascia and connective tissue were cleared down to the sternum. A median sternotomy was accomplished with a Stryker oscillating sternal saw (16). The edges of the sternotomy were padded with laparatomy sponges, a self-retaining retractor placed, and the sternotomy retracted open. Blunt and sharp dissection was used to expose the pericardium. The brachio-cephalic vein was so obscured by fat and connective tissue that it was inadvertently cut into. As a temporary repair we place #2 silk ties (17) proximal and distal to the veinotomy. A 2 cm. long piece of 1/4" ID tubing was inserted into the vein. This temporary repair would allow venous flow through the brachio-cephalic vein during the course of the perfusion.
A ventral midline pericardiotomy was made using Metzenbaum scissors. Four stay sutures of 3-0 silk (18) were placed in the margins of the pericardiotomy. These sutures were tied to the sternal retractor, thereby reflecting the pericardium away and exposing the heart and aorta for cannulation. This technique creates a pericardial cradle that helps stabilize the heart. A Sarns cardiotomy sucker (19) was used to suction away the pericardial fluid.
An aortic clamp was placed on the ascending aorta for partial occlusion. A 3-0 Ticron (20) purse string suture was placed in the aorta and a snare (21) applied. An aortotomy was made with a #11 scalpel blade (22). A 22 Fr. aortic perfusion cannula (23) was filled with Normosol (24) and a tubing clamp placed on the distal end. The aortic clamp was removed and the aortic cannula introduced into the aorta. The cannula was snared in place with a hemostat. A Satinsky partial occlusion clamp was placed on the right atrium, just below the apex. A purse string suture of 2-0 Ticron (25) was placed in the atrium and a snare tube applied. An atriotomy was made by removing the apex of the right atrium with Metzenbaum scissors. Single cannulation was used to save time, using a 40 Fr. venous return cannula (26). A tube clamp was placed on the distal end and the cannula introduced into the right atrium through the atriotomy, as the Satinsky clamp was removed. The venous cannula was snared in place with a hemostat and secured with umbilical tape (27). A third, small, purse string suture of 5-0 silk (28) was placed in the left lateral aspect of the ascending aorta and an aortotomy made with a #11 scalpel blade. A 3-way stopcock (29) was fitted to an Aloe arterial pressure monitoring catheter (30). A snare (31) was placed on the 5-0 suture, the Aloe catheter flushed with Normosol, then introduced into the aorta and snared into place.
The sterile perfusion tubing (32) was brought up to the surgical field and secured in the Travenol tubing holder towel clamped to the drapes. The arterial-venous loop (see circuit diagram) of the perfusion circuit was clamped and divided by cutting out the 1/2"-3/8" adaptor with Mayo scissors. A connector with stopcock (33) was used to attach the 1/2" ID venous return line to the venous cannula. Air was cleared from the system with a 100 cc. glass syringe. A 3/8" ID connector was used to attach the arterial perfusion system with a syringe. An 8 ft. pressure monitoring line (34) was fitted to the arterial pressure catheter, flushed with Normosol, and handed off the field to be connected to the pressure transducer (35), (36). The perfusion process was now ready to begin.
No Phase 1 perfusate was used because the core body temperature was already low enough for introduction of cryoprotective agents and further delay was not warranted. All perfusates were prefiltered through a clean 0.2 micron Pall filter (37) and passed through a sterile 0.2 micron Pall filter in line from the clean perfusate reservoir to the sterile perfusate reservoir (38). Arterial line perfusate and vein line effluent samples were taken at the end of each phase of perfusion for osmolarity, onconicity, and refractometer determinations (see data).
The perfusates were mixed as 5%, 10%, and 15% DMSO v/v concentrations (see perfusate composition). Staged increase of DMSO concentration is used to prevent osmotic shock. Perfusion with the first reservoir of 5% DMSO perfusate was begun. Poor venous return was noted at this time and it soon became obvious that the abdomen was distending. Perfusion was temporarily terminated and an examination of the diaphragm showed compression of the inferior vena cava at the point where it passes through the diaphragm. The compressive force was due to the weight of the fluid in the peritoneal cavity. The single venous cannula in the right atrium was removed. Venous cannulas (39) 26 Fr. and 32 Fr. were introduced into the superior and inferior vena cavas, respectively. This would allow separate monitoring of inferior and superior venacaval drainage. The superior cannula was introduced through an atriotomy in the atrial wall and snared in place, after placement of a second purse string suture. The inferior caval cannula was introduced through the original apical atriotomy and advanced to the diaphragm, but could not be advanced beyond. This demonstrated the complete occlusion of the inferior cava at that site.
At this time it became necessary to decompress the inferior vena cava by removing fluid from the peritoneal cavity. The cardiotomy suction tip was introduced into the peritoneal cavity through a stab wound made in the upper right quadrant of the diaphragm with a #11 scalpel blade. A large volume of fluid, mostly blood, was suctioned from the peritoneal cavity. An estimated 2.0 to 3.0 liters of blood was removed. This blood volume represents 1/2 to 2/3 of the patient's total calculated blood volume. We can only speculate that either K.V.M.'s fall caused a massive intraperitoneal hemorrhage, or the hemorrhage precipitated the fall. The hemorrhage probably resulted in the expenditure of clotting factors at the site, which explains why we observed no sign of intravascular coagulation. The degree of hemorrhage was probably determined by her coagulopathy -- as well as the severity of the lesion.
The inferior vena cava was successfully decompressed and the inferior venous cannula easily passed beyond the diaphragm and snared in place. The venous cannulas were connected to the venous return line with a Y-connector with stopcock (40), and air cleared with a syringe. Reinstitution of perfusion showed good venous return from both superior and inferior vena cava cannulas. However, continued accumulation of perfusate in the peritoneal cavity indicated we should keep it drained during the course of the perfusion. To accomplish the latter, without intermittent use of the cardiotomy sucker, a 22 Fr. (41) venous cannula was introduced through the diaphragm and connected to the general venous return line by use of an additional Y-connector (see circuit diagram). Continued perfusion showed good venous return, and slow clearance of the peritoneal cannula indicated a hemorrhage site somewhere on the venous side of the vascular system. As stated previously, the probable site of the lesion was though to be the hepatic system, from her medical history. I considered doing a laparatomy to identify the specific site of the lesion and do a repair, but decided the expenditure of time was not justified as long as we were able to provide adequate perfusion.
Perfusion continued with 5% DMSO concentration. A total of 10 liters of 5% DMSO perfusate was delivered with a peak arterial pressure of 65 mm. Hg and a peak pump flow rate of 1.7 liters/min. Ten liters of perfusate having 10% DMSO concentration followed, with a peak arterial pressure of 90 mm. Hg and peak pump flow of 2.5 liter/min. The final portions of the perfusion procedure consisted of 40 liters of perfusate with 15% DMSO concentration. A peak arterial pressure of 50 mm. Hg with an average pump flow of 1.5 liter/min. was used. The perfusate temperatures ranged from 4 degrees C to degrees C with an average of 6 degrees C. Near the end of the perfusion it was evident that the tissues were taking up perfusate, as evidence by a general appearance of edema. The degree of edema could not be quantified; however, it never reached the stage that it interfered with perfusion. edema can be related to the condition of the vascular bed as a result of the circumstances of death. The skin had the typical coloration seen after DMSO perfusion. No problems with intravascular coagulation were encountered, and perfusion of a total of 60 liters of perfusate was completed.
The venous and arterial cannulas were clamped with tube occluding forceps. Snares were removed from the inferior and superior vena cava cannulas. As each cannula was removed, the corresponding atriotomy was closed with the purse string suture and tied. The same procedure was used to remove the arterial perfusion cannula and the diaphragm was closed with 2-0 Ticron. The tubing was removed from the brachio-cephalic vein, and distal and proximal ends were closed with Weck clips (42). Seven sternal wires (43) of 22 ga. stainless steel were used to close the median sternotomy. The skin was closed with 2-0 Ticron on a cutting needle (44). The suture line was protected by a spray-on plastic bandage (45) by Parke-Davis. The pump tubing was removed from the surgical field and the surgical drapes removed from the patient.
Two copper-constantan temperature probes were placed, one in the esophagus and a second at the feet. Temperature probes were secured with umbilical tape. An Ace bandage wrap served to keep the arms close to the torso. The ice packs were removed and the patient placed in double polyethylene bags (46). The temperature cables -- esophageal and rectal thermistor, and esophageal and foot copper-constantan -- were brought out of the opening of the bags and the bags sealed.
The patient was placed in a polyurethane insulated container with isopropyl alcohol pre-cooled to 2 degrees C. Dry ice and alcohol were gradually added to lower the bath temperature to -79 degrees C. When rectal temperature reached -72 degrees C. the alcohol was removed and the patient completely covered with dry ice and layer of insulation. The insulated container was sealed and shipped by air to the Trans Time facility in Emeryville, California, where the patient was placed in LN2 capsule storage at -196 degrees C.
The K.V.M. suspension presented us with some unique problems which we were fortunate to correctly analyze and solve. However, one can always see room for improvements, in retrospect. Anatomical variations can always lead to errors, such as accidentally cutting into the brachio-cephalic vein, which was obscured by a heavy layer of connective tissue. In the future I would be inclined to do a laparotomy if there is any perfusate leak in the peritoneal cavity. This would insure that no arterial lesions are present.
In the future I would like to take biopsy samples that would be representative of strongly and weakly circulated tissues, to determine the uptake of cryo-protective agent. I am also trying to acquire a fluoroscopy unit so we can use dye injection techniques to view the vascular distribution of perfusates during perfusion. This will allow us to select the minimum necessary arterial pressure required for good perfusion of the entire vascular bed, or determine if any areas are underperfused.
The samples of arterial perfusate were taken from the vent port of the arterial line filter. Unfortunately, an analysis of these samples indicated that significant quantities of 5% and 10% DMSO perfusate remained trapped in the filter. Therefore, our 10% and 15% DMSO perfusate samples represented mixed rather than discrete samples. Without definitive arterial samples to compare to our venous effluent samples, we are unable to make a reasonable estimate of DMSO uptake in the tissues. In the future we will collect arterial samples directly from the arterial line.
1. Operating table, Scanlan, Type A4000.
2. Eggcrate pad, Bio-Clinic, Catalog No. 357AE.
3. Ziploc bags, plastic, Size 26.8 cm x 1.75 mil, Dow Co.
4. Plastic box (3 sides), Rubbermaid, Catalog No. JDI 2969.
5. Esophageal and rectal thermistor temperature probes, Yellow Springs Instruments, Model 401.
6. Tele-Thermometer, Yellow Springs Instruments, Model 42SL.
7. "Cryonic Suspension of Sam Berkowitz: Technical Report," LONG LIFE MAGAZINE vol. 3, no. 2, March/April, 1979.
8. Disposable surgical prep kit, Desert Pharm. Co., Cat. No. 212.
9. Disposable scrub brush, E-Z Scrub, Desert Pharm. Co., Cat No. 4103.
10. Disposable surgical sterile back gown, Tekna-Med, Cat. No. 4103.
11. Disposable surgical gloves, Triflex, Travenol Labs., Size 7 Cat. No. 2D7153, Size 7 1/2 Cat. No. 2D7154.
12. Disp. surgical towels, Tekna-Med, Texas Medical Products, Cat. No. 0035.
13. Plastic adhesive skin drape, Vi-Drape Surgical Film, 24" x 22", Parke-Davis, Cat. No. 30-1056-12.
14. Disp, cardia pack, Tekna-Med, Texas Medical Products, Cat. No. 0001.
15. Scalpel blade #10, Bard-Parker, Cat. No. 1110.
16. Sternal saw blade, Stryker, Cat. No. 1101.
17. #2 silk ties, 2x60", Davis & Geck, Cat. No. 1037-81.
18. 3-0 silk, Deknatel, Cat. No. 743.
19. Cardiotomy suction tip, Sarns, Cat. No. 9999.
20. 3-0 Ticron, Davis & Geck, Cat. No. 3085-41.
21. Snare tube (5 cm long piece), All Purpose Catheter, 18-20 Fr., Davol, Cat. No. 9419.
22. Scalpel blade #11, Bard-Parker, Cat. No. 1111.
23. Aortic perfusion cannula, 22 Fr., Type 1966, USCI, Cat. No. 007195.
24. Normosol-R ph 7.4, Abbot Labs., Cat. No. 1570 (or use normal saline).
25. 2-0 Ticron, double armed, T-S needle, Davis & Geck, Cat. No. 3192-51.
26. Venous cannula, 40 Fr., Type 1967, USCI, Cat. No. 007215.
27. Umbilical Tape, 2x30", Davis & Geck, Cat. No. 731.
29. Pharmaseal 3-way stopcock K-75, American Hospital Supply, Cat. No. 17108-010.
30. Aloe arterial pressure catheter, 15" long, Argyle, Cat. No. 8888-153213.
31. Small snare tube (3 cm. piece), All-Purpose Cath., Davol, 10 Fr., Cat. No. 9140.
32. Tubing, all Tygon S-50-HL except pump shoes of Dow Corning Silastic.
33. Connector, straight 1/2" ID with Luer-lok port, Cobe Labs., No. 50-608.
34. Pressure monitoring line, 8 ft., Cobe Labs., Cat. No. 40-108.
35. Pressure transducer, Statham Instruments, Model P23db.
36. See pressure monitoring system diagram.
37. Pall filter, Ultipor DFA, 0.2 micron, Part No. DFA 3001 ARA.
38. Oxygenator, Temptrol, Bentley Labs., Model Q-100.
39. Venous cannula, 26 Fr., Type 1967, USCI, Cat. No. 007208; and 32 Fr., Type 1967, USCI, Cat. No. 007211.
40. Y-Connector with Luer-lok port, Bentley Labs., Cat. No. C345S, and a 3- way stopcock, Cobe Labs., Cat. No. 41-210.
41. Venous cannula, 22 Fr., Type 1967, USCI, Cat. No. 007206.
42. Weck clips, Hemo-Clip, Weck Co., Cat. No. 523-170.
43. Sternal wires, 22 ga., Davis & Geck, Cat. No. 2420-09.
44. 2-0 Ticron, cutting needle, Davis & Geck, Cat. No. 3092-51.
45. Spray bandage, Aeroplast Dressing, Parke-Davis, Cat. No. 30-5268-1.
46. Plastic bags for suspension patient, 30" x 90" x .00125" and 38" x 90" x .003" polyethylene, More Plastic Bags, custom made (36" x 90" x .006" EVA bags are now used).
The members of the Trans Time Suspension Team deserve the highest praise for their efforts, which made this a successful perfusion. To my knowledge, there is no more capable suspension team anywhere in the world.
Paul Genteman, 1st Assistant Surgeon
Betty Leaf, LVN Scrub Technician
Fred Chamberlain, Perfusionist
Laurence Gale, Physiological Monitoring
Reg Thatcher, Physiological Monitoring
Hugh Hixon, Laboratory Technician
Virginia Jacobs, O.R./Lab Assistant/Circulator
*Bill Jameson, Perfusionist
* Bill Jameson helped to prepare the perfusates, but was unable to stay for the suspension. My thanks to Bill for the help he was able to provide.
I am also grateful for the continued support of Trans Time, Inc. in its pursuit of excellence under the direction of Art Quaife.
2. Effluent reservoir
3. Sterile perfusate reservoir
4. Arterial roller pump
5. Pall filter, 0.2 micron
6. Roller pump to fill sterile reservoir
7. Clean perfusate reservoir
8. Roller pump for cariotomy sucker
9. Cardiotomy suction line
10. Sarns suction tip
11. Connector with stopcock
12. Connector, straight 3/8" I.D.
|13. Arterial cannula
14. Arterial-venous shunt
15. Venous cannulas
16. Peritoneal drainage cannula
17. Filter air vent line
18. Pall filter, 40 micron
19. Heat exchanger, arterial line, Brown-Harrison
20. Arterial perfusion line
21. Venous return line
22. Heat exchanger, venous line, Brown-Harrison
23. Water lines
MgCl2 6 H2O
Disodium glycerophosphate H2O
to one liter volume
15% v/v DMSO perfusate
Onconcitiy, measured: 46.7 mm. Hg. (Measured on an IL OOP head)
Osmolarity, measured: 2656 mOsm/kg H2O (Measured on a Wescor vapor pressure osmometer)
pH of perfusate (37°C)