Date: 20 Mar 96 00:50:41 EST From: Mike Darwin <> Subject: BPI TECH BRIEF #18, Part II Cryopreservation of CryoCare Patient #C-2150 (continued) by Mike Darwin Decision to Terminate Life Support At the beginning of December the patient became increasingly oxygen dependent and began experiencing a return of visual disturbances which were prodromal to his prior homonymous hemianopia. He also experienced a return of urinary incontinence. The patient expressed justifiable concern that the original brain metastases, or another, was again beginning to cause problems, or that structures adjacent to the tumor were experiencing the un-typical delayed death as a result of the high dose radiation to which they were exposed. Further, the nausea which had been present since shortly after the illness was diagnosed was now more or less constant with occasional vomiting. Attempts at pharmacologic control of the nausea using hydroxyzine, chlorpromazine, compazine, ginger, and tetrahydrocannabinol (THC) were unsuccessful. During the first days of December the patient repeatedly contacted BPI and expressed a desire to withdraw from palliative oxygen and to abruptly stop steroids and "get it over with." He explained that his quality of life was no longer acceptable, and that he wished to take action to end his life in a legal manner before the quality deteriorated further, and especially before he became unable to exercise choice in the matter. Unfortunately, while the patient had responded well to prompt anti-viral therapy for influenza, two of the team members were ill with the flu and with the non-bacterial bronchitis which accompanied it. Complicating matters further was the illness (again with the flu) of one of the team members' two small children. The patient was told that while we would respond if he was set upon immediate implementation of this course of action, optimum response would best be had by delaying a week or so longer in order to give team members time to recover and to permit final set-up of equipment in the home and last minute preparations to be made. When staff were largely recovered, a window of time was agreed for discontinuation of life support. The patient's private primary care physician (not involved with BPI) was closely involved in this decision, and advised BPI that he felt withdrawal of oxygen would result in rapid decompensation and cardiovascular collapse. He said he felt the patient was making an informed and "rational" choice (i.e., he saw no indication of compromising psychiatric illness, organic brain disorder, or undue influence). The physician commented that he was comfortable with the patient's decision since the patient had repeatedly told him he would have withdrawn from life support far earlier had it not been for his cryopreservation arrangements. The physician expressed a willingness to be present when the patient discontinued life support and to pronounce legal death. Further, the physician ordered that a Hickman catheter be implanted in the patient to facilitate administration of pain medication (his peripheral veins were "exhausted" from repeated sticks and catheter placement). BPI requested that the catheter be a large-bore Hickman to facilitate rapid, low resistance of transport medications, and the physician agreed to this request. During the weekend of 9-10 December the patient's home was fully prepared for standby and transport. The Mobile Advanced Life Support System (MALSS) was set up in the living room and the extracorporeal circuit strung. An operating room light was put in place, back tables were set up and instrument trays and ancillary supplies were laid out and readied. Specialized monitoring equipment for blood pressure, cerebral function, pulse oximetry, and acute lab collection (blood gases) was also put in place. The CDI point-of-care in-line blood gas system was also set up next the MALSS and the monitoring cells cut into the arterial and venous lines of the extracorporeal circuit to allow for continuous acquisition of blood gas data during initial bypass-assisted cooling, and during blood washout and replacement with 21CMBP-002 flush-store solution. The patient's physician was then consulted about the possibility of administering pre-cryopreservation medications to reduce the insult from the agonal hypoperfusion/hypoxia and post-pronouncement ischemia which would necessarily occur prior to mechanical restoration of circulation and breathing during transport by BPI. The physician reviewed the medications suggested and agreed to prescribe all those available in the U.S. and Mexico. The patient had made arrangements through an AIDS buyers' club to obtain other medications which he believed would be efficacious in helping to ameliorate ischemic injury. These were largely drugs which 21st Century Medicine animal research had shown to be cerebro-protective if given before the ischemic insult. The following schedule of pre-cryopreservation medication was begun by the patient on 10 December, 1995: Medications for 10 December: aspirin, 1.25 grain, p.o., daily ascorbic acid, 1 g t.i.d. N-t-butyl-a-phenylnitrone, 500 mg, p.o. with evening meal sodium selenite, 1000 mcg selenium p.o. co-enzyme Q10, 100 mg p.o. t.i.d. dexamethasone, 4 mg p.o. t.i.d. doxycycline, 100 mg p.o. d-alpha tocopherol, 1,000 IU, t.i.d. phenytoin (Parke Davis), 100 mg, t.i.d. morphine sulfate by IV pump p.r.n. for pain. 50 mg thalidomide, p.o. before retiring 10 mg melatonin, p.o. before retiring Medications for 11 December: aspirin, 1.25 grain, p.o., daily ascorbic acid, 1 g t.i.d. piracetam 800 mg p.o. at 10:00 N-t-butyl-a-phenylnitrone, 1g mg, p.o. with evening meal sodium selenite, 1000 mcg selenium p.o. co-enzyme Q10, 100 mg p.o. t.i.d. dexamethasone, 4 mg t.i.d. doxycycline, 100 mg, t.i.d. d-alpha tocopherol, 1,000 IU , t.i.d. phenytoin (Parke Davis), 100 mg, t.i.d. morphine sulfate by IV pump p.r.n. for pain. 50 mg thalidomide, p.o. before retiring 10 mg melatonin, p.o. before retiring Patient agreed to take no solid food after 11 December at 2400 since it was his decision to withdraw life support the following afternoon. Medications for 12 December: aspirin, 1.25 grain, p.o., daily ascorbic acid, 1 g t.i.d. N-t-butyl-a-phenylnitrone, 1 g, p.o. with evening meal sodium selenite, 1000 mcg p.o. co-enzyme Q10, 100 mg p.o. t.i.d. dexamethasone, 4 mg t.i.d. doxycycline, 100 mg , t.i.d. d-alpha tocopherol, 1,000 IU , t.i.d. phenytoin (Parke Davis), 100 mg, at 100 and 1600 morphine sulfate by IV pump p.r.n. for pain. misoprostol, 100 micrograms at 1600 melatonin, 50 mg, p.o. at 1900 prilosec, 20 mg, p.o. at 1900 800 mg ibuprofen at 1900 phenytoin, 500 mg, p.o. at 1900 Maalox, 60 cc p.o. immediately before discontinuing oxygen. The patient obtained on his own, and self-administered without assistance at about 2100 through his implanted Hickman catheter, 250 cc of Dextran 40 in normal saline (Baxter, Irvine, CA) containing 1 mg of Nimodipine (A.G. Bayer, Germany), 40,000 IU of sodium heparin and 5 grams of a proprietary agent developed by 21st Century Medicine. This latter agent will be hereinafter referred to as 21CM-006; it was developed to protect against ischemic injury, up-regulate the efficacy of anaerobic metabolism, and ameliorate V/Q mismatch (where blood flows through unventilated area of lung and thus does not get oxygenated) and prevent loss off normal vasomotion (where blood delivered to the tissues is not distributed to the capillaries properly resulting in "shunting" and failure of delivery of oxygen and nutrients to the tissues in shock) concurrent with discontinuing high flow oxygen support (8-10 LPM by mask with reservoir bag: FIO2 was ca. 80-90%). A final conversation was had with the patient at about 1900 at which time he was repeatedly advised that he could change his mind without any problem to BPI and that he should feel no pressure to pursue this course of action. His response was: "You don't understand. This is easy. The hard thing would be taking one more day of life like this." The patient appeared in good spirits and laughed and joked with family and team members. He explained that he had accepted he was either to die or recover from cryopreservation, and that either way he was fully prepared and psychologically ready. He had played a card game with family and friends that afternoon, and explained that while he was a little apprehensive, he intended to take some alprazolam (Xanax) and get ready for the journey ahead. Several BPI team members spoke with the patient privately and said their good-byes. Cardiopulmonary Arrest At the request of the patient and his family (for reasons of intimacy; saying farewells etc., and basic privacy) the entire BPI team withdrew to the BPI transport vehicle parked outside the patient's apartment. The patient's attending and primary care physician remained with the patient and the patient's family to supervise withdrawal of life support, assure adequate palliation of air hunger and discomfort, and promptly pronounce legal death. BPI personnel were to be summoned immediately after pronouncement by cell phone (four BPI personnel had cell phones!). At approximately 22:50, the patient discontinued oxygen. He had taken approximately 3 mg of alprazolam about an hour before discontinuing oxygen, and he had access to self- administered morphine (pump limited boluses) to ease air hunger. It was reported that the patient rapidly lost consciousness on withdrawal of oxygen and experienced cardiopulmonary arrest at 2311 on 12 December, 1995. Transport Phase 1: CPR, Medication, External, Initial Cooling Intubation was accomplished at 23:13 by Dr. Harris, and "Active Compression-Decompression-High-Impulse CPR" (ACDC- HICPR), using a custom built Michigan Instruments "Thumper" mechanical chest compressor, was initiated at 23:14. A standard Ambu ACDC silastic suction cup was used on the Thumper to achieve the ACDC component of the ACDC-HICPR. Placement of a tympanic temperature probe was achieved concurrent with intubation (during securing of the endotracheal tube). The initial tympanic temperature reading was 36.8 degrees C. Tympanic (eardrum) temperatures were used in this patient because it is well established that tympanic temperature reflects true brain temperature since the blood supply for the eardrum and midrain and cerebral cortex are the same. Typmanic temperature is thus a much more reliable measure of the temperature of the iorgan we are *most* interested in preserving (the brain) than are esophageal or rectal temperatures. Further, work with dogs at 21st has established a far closer correlation between tympanic temperature and actual measured brain temperature (via invasive probes) than esophageal or rectal temperatures Family and friends had begun icing the patient at the time of pronouncement (legs, abdomen and lower thorax; leaving the head unencumbered so that airway management could be instituted before icing) and the head, thorax and axilla were iced concurrent with the start of cardiopulmonary support. Simultaneous with the start of external cooling, a Darwin rectal thermocouple probe was placed in the descending leg of the double barreled colostomy and the 60 cc balloon inflated to anchor it in place. A Darwin colonic lavage tube with a 60 cc silastic balloon and fenestrated tip was also inserted in the stoma of the ascending end of the colostomy, and the balloon on the lavage tube was also inflated to anchor it into the ascending colon. Immediately thereafter a stab wound was made (using sterile technique) through the medial aspect of the right external oblique muscle 3 cm to the right of the navel, at the level of the iliac crest. The stab wound was rapidly extended in depth by blunt dissection with Metzenbaum scissors (Mets) until the peritoneum was reached, and a 1 cm incision was made in the peritoneum with Mets and a Darwin peritoneal lavage tube was inserted and its 60 cc silastic balloon rapidly inflated to seal and anchor it in place. Once all lavage tubes were in place the patient's ascending, transverse colon, and terminal ileum were irrigated with 2 liters of iced Normosol-R, pH 7.4, and the peritoneal cavity was irrigated with 4 more liters of this solution (Abbott Pharmaceuticals, Chicago, IL). Reservoirs connected to the colonic and peritoneal lavage tubes were placed on the floor and the lavage fluid was allowed to drain into the respective bags by gravity. The first pulse oximetry and end-tidal CO2 readings were obtained at 23:16 and were 95% and 5% respectively. Wave form acquisition on the pulse oximeter was excellent and the pulse rate of 80 per minute correlated exactly with the action of the Thumper. At 23:19 the patient's tympanic and descending colon temperatures had declined to 29.8 degrees C. By 23:20 the descending colon temperature had rebounded to 34 degrees C. At 23:21 the peritoneum was lavaged with 2 additional liters of iced Normosol. At 23:22 the tympanic temperature was 28.7 degrees C and the descending colon temperature was 28.6 degrees C. Oxygen saturation at that time was 93%, and End tidal CO2 (EtCO2) was 4%. Administration of Transport Medications began at 23:12 and was as follows: Epinephrine 12.6 mg, 23:12, IV push (given to support blood pressure during CPR). The drug 21CM-005 3.15 g, IV push, 23:16, (This drug is a proprietary compound given to inhibit lactic acidosis and increase the efficacy of anaerobic metabolism). 3.15 g of 21CM-005 contains approximately 40 mEq of potassium, an amount sufficient to preclude restoration of spontaneous cardiac activity. Soporate (21CM-004) 6.30 g IV push, 23:12 (Soporate is a proprietary compound given to inhibit excito-toxicity in a class of brain receptors found to be critical in mediating cerebral re-perfusion injury in dogs following 12+ minutes of global cerebral ischemia using a cardiac arrest model. The drug also acts as a general anesthetic preventing patient's from regaining consciousness during cardiopulmonary support.) 21CM-005 6.30 g IV push, 23:12 (see above for explanation of the pharmacology of this agent). Oxynil (21CM-003) 630 mg IV push, 23:13 (Oxynil is a proprietary agent which has been shown to ameliorate brain ischemia in dogs by its free radical trapping ability. It is useful primarily as an adjunct and potentiator of other antioxidant medications). 21CM-002 100 ml; 50 ml IV push, 50 ml over ca. 10 minutes. Push dose given at 23:15, infusion completed at 23:28. (21CM-002 is a cremophor emulsion (micellized) mixture of two proprietary antioxidants which rapidly cross the blood brain barrier. One of these antioxidants crosses mitochondrial membranes rapidly and prevents failure of high energy metabolism in neuron and glial cells following re- perfusion after global ischemic injury in dogs of 12+ minutes duration). Deferoxamine 2g was added to the mannitol infusion (126 g mannitol as 20% solution in water). Mannitol infusion was begun at 23:32 and concluded at 23:40. Exiquell (21CM-005) 315 mg IV push. (Exiquell is a proprietary agent used to inhibit the quaint-quisqualate receptor system which is a significant source of excito- toxicity following global cerebral ischemia in the dog.) THAM (tromethamine) 15.75 g in 250 cc (50 cc IV push), with the balance by IV infusion, 23:18 Mannitol (see Deferoxamine above). Pavulon (pancuronium bromide) 2 mg, 23:16, to inhibit shivering and prevent return of spontaneous respiration. Methylprednisolone 1 g IV infusion over a minimum of 5 minutes, begun 23:16, ended, 23:20. Cipro IV (ciprofloxacin; antibiotic causing no cold agglutination) 400 mg IV infusion given slowly between 23:16 and 23:30. Dextran 40 (Gentran) in 10% saline, 500 cc. Administration of all transport medications to this patient was completed at 23:40. The first blood sample for gases, chemistries and electrolytes could not be collected until after the conclusion of medication administration. A central venous sample was collected via the patient's Hickman line at 23:50 on 13 December and yielded the following results: RESULTS: NORMAL RANGES Tympanic Temperature: 25.7 degrees C, Descending Colon Temperature 19.0 degrees C pH 7.34 7.35 (mean) pCO2 52.4 mmHg 45-55 pO2 37.0 mmHg 40-50 O2 Sat 89% 70-75 BUN 15.0 mg/dl 7-25 Creatinine 1.1 mg/dl 0.7-1.4 Sodium 120 mEq/l 135-146 Potassium 5.5 mEq/l 3.5-5.3 Chloride 82 mEq/l 95-108 Magnesium 1.7 mEq/l 1.2-2.0 Calcium 7.2 mg/dl 8.5-10.3 Phosphorus 7.8 mg/dl 2.4-4.5 Protein, Total 5.8 g/dl 6.0-8.5 Glucose 251 mg/dl 70-125 Bilirubin,Total 0.8 mg/dl 0.0-1.3 Alk Phosphatase 76 U/L 20-125 LDH, Total 227 U/L 0-250 GGT 58 U/L 0-65 AST 101 U/L 0-42 ALT 69 U/L 0-48 Uric Acid 0.5 mg/dl 4.0-8.5 Iron, Total 138 mcg/dl 25-170 Iron Binding Capacity 748 mcg/dl 200-450 % Saturation 18 12-57 HCT 26% 41-50 The next central venous blood sample collected during CPR at 0020 on 13 December, yielded the following results: Tympanic Temperature: 23.0 degrees C, Descending Colon Temperature13.8 degrees C pH 7.115 7.35 (mean) pCO2 27.8 mmHg 45-55 pO2 35.1 mmHg 40-50 O2 Sat 88% 70-75 BUN 17.0 mg/dl 7-25 Creatinine 1.1 mg/dl 0.7-1.4 Sodium 132 mEq/l 135-146 Potassium 4.3 mEq/l 3.5-5.3 Chloride 91 mEq/l 95-108 Magnesium 1.8 mEq/l 1.2-2.0 Calcium 7.8 mg/dl 8.5-10.3 Phosphorus 9.9 mg/dl 2.4-4.5 Protein, Total 3.4 g/dl 6.0-8.5 Glucose 300 mg/dl 70-125 Bilirubin, Total 1.1 mg/dl 0.0-1.3 Alkaline Phosphatase 92 U/L 20-125 LDH, Total 376U/L 0-250 GGT 69 U/L 0-65 AST 182 U/L 0-42 ALT 126 U/L 0-48 Uric Acid 0.5 mg/dl 4.0-8.5 Iron, Total 177 mcg/dl 25-170 Iron Binding Capacity 779 mcg/dl 200-450 % Saturation 18 12-57 HCT 26 41-50 At 0050 another central venous sample was collected from the Hickman catheter and revealed the following results: Tympanic Temperature: 21. degrees C, Descending Colon Temperature 9.9 degrees C pH 7.087 7.35 (mean) pCO2 25.2 mmHg 45-55 pO2 39.2 mmHg 40-50 O2 Sat 91% 70-75 BUN 17.0 mg/dl 7-25 Creatinine 1.0 mg/dl 0.7-1.4 Sodium 134 mEq/l 135-146 Potassium 4.9 mEq/l 3.5-5.3 Chloride 91 mEq/l 95-108 Magnesium 1.9 mEq/l 1.2-2.0 Calcium 7.9 mg/dl 8.5-10.3 Phosphorus 10.6 mg/dl 2.4-4.5 Protein, Total 3.5 g/dl 6.0-8.5 Glucose 308 mg/dl 70-125 Bilirubin, Total 1.1 mg/dl 0.0-1.3 Alkaline Phosphatase 91 U/L 20-125 LDH, Total 366 U/L 0-250 GGT 69 U/L 0-65 AST 204 U/L 0-42 ALT 140 U/L 0-48 Uric Acid 0.5 mg/dl 4.0-8.5 Iron, Total 179 mcg/dl 25-170 Iron Binding Capacity 778 mcg/dl 200-450 % Saturation 23 12-57 HCT 26 41-50 The final central venous sample taken during CPR was at 01:20 on 13 December and yielded the following results: Tympanic Temperature: 19.3. C, Descending Colon Temperature 7.5 degrees C pH 7.047 7.35 (mean) pCO2 23.7 mmHg 45-55 pO2 110.4mmHg 40-50 O2 Sat 98.1% 70-75 BUN 17.0 mg/dl 7-25 Creatinine 1.0 mg/dl 0.7-1.4 Sodium 133 mEq/l 135-146 Potassium 5.7mEq/l 3.5-5.3 Chloride 92 mEq/l 95-108 Magnesium 1.9 mEq/l 1.2-2.0 Calcium 7.9 mg/dl 8.5-10.3 Phosphorus 11.3 mg/dl 2.4-4.5 Protein, Total 3.5 g/dl 6.0-8.5 Glucose 364 mg/dl 70-125 Bilirubin, Total 1.2 mg/dl 0.0-1.3 Alkaline Phosphatase 92 U/L 20-125 LDH, Total 380 U/L 0-250 GGT 69 U/L 0-65 AST 214 U/L 0-42 ALT 148 U/L 0-48 Uric Acid 0.5 mg/dl 4.0-8.5 Iron, Total 178 mcg/dl 25-170 Iron Binding Capacity 777 mcg/dl 200-450 % Saturation 23 12-57 HCT 22 41-50 Intermim Interpretation and Comment On Cooling From the laboratory and temperature data above, several important conclusions can be drawn, particularly when taken in the context of the protocol used in this case, in comparison with results obtained in two previous cases which compare with this one closely (Alcor patient A-1260, and ACS patient 9577). Direct comparisons of many of the parameters in these two cases is not possible owning to absence of data in the previous cases. For instance, in patient A-1260 no temperature data was acquired until 32 minutes after cardiac arrest. Thus, a direct comparison between cooling rates during (say) the critical first 10 minutes post arrest is not possible here. However, comparisons can still be made where data does exist at corresponding intervals. These three patients are of particular interest to compare because they match each other closely in sex, weight, fat distribution, and body surface areas, and they are of reasonably close ages. All patients were cooled at a minimum using a portable ice bath and ice-water circulating pump/distribution assembly (two with identical equipment). All patients had cooling and CPR begun within 2-4 minutes of cardiopulmonary arrest, and all were promptly medicated using the specified protocol. It is also important to note that all patients died of illnesses, two of AIDS and one of disseminated cancer, which left them cachectic and which involved compromise to multiple organ systems. One notable difference was the prolonged agonal course of ACS-9577 compared to the other two patients, and the poor response to cardiopulmonary support this patient exhibited, probably as a result of the antemortem ischemic injury and pulmonary compromise. Data from one other patient, A-1049, a 32.8 kg severely wasted patient who arrested from dehydration secondary to end-stage adenocarcinoma of the lung, is also relevant. This patient is included since her mass and fat content/distribution and response to cardiopulmonary support were the most favorable of any patient cryopreserved by comparable methods available to this author. This patient thus serves as "best-case" for the efficacy of previously used methods of cooling, medication and CPR. The number of asterisks after the case number indicates the overall score, from zero to ****, for response to cardiopulmonary support as evaluated by EtCO2, skin-color, femoral pulse, and other parameters when available. A critical determining factor in how well a patient will cool during transport in addition to surface area, mass and fat quantity and distribution (fat is a good insulator) is the adequacy of blood circulation. Warm blood being delivered to the surface of the body and to structures with good surface to volume ratios that facilitate good exchange (such as fingers, toes, arms, and legs) will clearly be superior in patients with good cardiac output. The patient's antemortem condition will be a major factor in determining how well s/he will respond to CPR. However, also of great importance is the use of highly efficient means of CPR and the use of drugs which prevent shunting of blood away from tissues that need it, and which prevent shunting of blood through parts of the lung which are fluid filled or not able to exchabfe oxygen. No doubt part, but by no means all of the superior cooling results observed in this patient were as a result of better perfusion during CPR. As can be seen from the table above, patient C-2150, the subject of this report, cooled at a rate of approximately 1 degree C/min during the first ten minutes post arrest, and at a rate of 0.56 degrees C/min for the entire 30 minute period after arrest. This is a rate twice that of a patient with roughly half his mass and with far less subcutaneous fat during the first 10 minutes post arrest, and twice that at 30 minutes post arrest. It is also interesting to note that the 30-minute post arrest cooling rates of all three other patients are well below 0.5 degrees C/min., and are in close agreement (0.24 and 0.21) for the two patients whose mass, fat distribution and surface area most closely approximate those of this patient. We believe that this patient experienced such superior rates of cooling--indeed, rates achieveable in a patient of his surface area only with extracorporeal (blood/body core) cooling--because of the following factors: * Superior perfusion due (blood circulation) during CPR as a result of: a) cardiac arrest in the absence of a long period of agonal shock. b)pre-arrest medication which reduced cold agglutination, prevented loss of c) normal vasmotion and adequate control and distribution of blood flow. d) greatly improved cardiac out, mean arterial pressure (MAP) and decreased venous pressure as a result of ACDC-HICPR e) improved oxygenation due to ventilation with each compression upstroke using ACDC-CPR f) in hibition of oulmonary edema as a result of lower central venous pressures and better mitral valve function as a result of ACDC-HICPR *Superior cooling due to the use of colonic and peritoneal lavage with ice cold solution in addition to external cooling using the portable ice bath (PIB) and a circulating water system to pump ice cold water over the patient's body. The use of these modalaties and the cooling rates achievable with them was established in dog lab. Further, other cooling approaches such as the use of ice-slush lavages in stomach, inaddition to the colon and peritoneum, and the addition of liquid ventilation (using perfluburon chilled to 0-2 degrees C) or subzero jet gas ventilation, are currently under investigation (and patent) and may provide for cooling rates approach 1.5 to 2.0 degrees C per minute if added to the modalities used in this patient. Administration of all transport medications to this parient was completed at 2340. Transport Phase 2: Initiation of Extracorporeal Support and Total Body Washout Surgery to raise the right femoral artery and vein was begun at 23:30 following standard prep of the right groin with Betadine scrub/solution, and creation of a sterile field with sterile muslin towels and disposable drapes. Two femoral arteries of 3-5 mm in diameter were rapidly located and a pressure line was placed in one at 23:55 (initial pressure measured was MAP 47 mmHg). However, despite extensive further dissection of the right groin no femoral vein could be located. Dissection along the tissue plane of the femoral arteries failed to reveal the femoral vein (although the sciatic nerve was identified) and the femoral arteries appeared to bifurcate within the abdomen. (Subsequent autopsy disclosed that the patient had no femoral vein and a right iliac artery that bifurcated into two femoral vessels at the terminus of the abdominal aorta). Several small veins (3-5 mm in diameter) were located and one of these opened to determine feasibility of cannula placement for venous return. While this was deemed not possible, it was noted that the venous blood was free-flowing and arterial red in color, indicating adequate oxygen delivery to the patient (the patient's tympanic temperature at that time was approximately 23 degrees C, colonic temperature 14.5 degrees C). By 00:15 a decision had been made to abandon the right groin wound and proceed with surgery to raise the left femoral artery and vein. Prep of the left groin was made at 00:21 and the femoral artery and femoral artery and vein were rapidly identified. The femoral vein was cannulated with a Biomedicus Carmeda-coated, 21 Fr. x 50 cm venous cannula (#34284). However, a further complication occurred in that the femoral artery was invaded with malignancy; apparently between the tunica media vasorum and the intima of the vessel. The vessel also was moderately atherosclerotic (soft yellow atheroma). This complicated arterial cannulation and required extensive further dissection of the groin to avoid a dissecting aneurysm of the entire arterial tree secondary to cannula placement. Thumper support was discontinued at 01:07 at a tympanic temperature of 20.2 degrees C and a colonic temperature of 8.4 degrees C. MAP had dropped to 35 mmHg at this time, and it was felt that further Thumper support was not productive. Both cannulae were in place by 01:18 and closed circuit femoral-femoral bypass was begun at about 01:18, using a prime consisting of 750 cc Dextran 40 in Normal saline, 1500 cc of Normosol-R pH 7.4, 500 cc 20% mannitol in water, and 50 cc (1 mEq/cc) of sodium bicarbonate solution. At 01:21 a "popping sound" was heard, and the polycarbonate housing of the Sarns 9444 Turbo oxygenator was noted to have developed a leak at the joint between the two halves of the housing. This occurred at a pressure of 260 mmHg, well below the 760 mmHg pressure this unit is rated for. The problem (popping sound) was noted at exactly 01:20 and the pump was shut down and lines were clamped at 01:21. The circuit was carefully inspected for air from the oxygenator through the filter and up to the patient, and none was noted. The oxygenator was changed out of the circuit and replaced with a fresh one and the bypass line was used to prime the new oxygenator and debubble the circuit. Bypass was resumed uneventfully at 01:33, 12 minutes later. Closed circuit bypass was continued at a MAP of 45 mmHg and flow rate of 2-3 liters per minute (LPM). When the patient's tympanic temperature reached approximately 16 degrees C (colonic , 6.2 degrees C) the patient was progressively hemodiluted with 10 liters of Viaspan using 2 liters of open circuit flush at a MAP of 45- 50 mmHg. At the conclusion of the Viaspan flushes, the patient was flushed with 10 liters of 5% (v/v) glycerol in 21CM-BPI-002 base perfusate. Glycerol-containing flush was introduced slowly in two liter aliquots. Flushing with 5% glycerol began at 01:42 and was followed by flushing with 10 liters of 10% w/v glycerol perfused in the same fashion. Flushing with 2 liter aliquots of 10% w/v glycerol was completed at 02:35. Flushing proceeded more slowly than normal due to partial cold and chemical-induced rupture of both plastic bags containing the flush solution, with leakage which required a great deal of effort to contain. At 02:02 the tympanic probe was replaced with a frontal sinus probe to facilitate movement of the patient at the conclusion of bypass. It is interesting to note that frontal sinus and tympanic temperatures agreed to within 0.2 degrees C. Frontal sinus temperature at the conclusion of flushing/glycerolization was 5.5 degrees C, colonic, 1.6 degrees C. Following the conclusion of total body washout and phase I glycerolization, the patient was disconnected from the extracorporeal circuit with care taken to avoid introduction of air into either the arterial or venous cannula (the cannulae were cross-connected with a short length of 3/8" x 3/32" bypass tubing which was filled with perfusate and carefully purged of air before the occluding clamps on the cannulae were removed). The patient was then removed from the PIB of the MALSS and placed in a more easily transportable PIB for transfer to the BPI/21CM facility for cryoprotective perfusion. Originally it had been planned that the patient would be moved with extracorporeal support on the MALSS continuing. However, the patient occupied a second story apartment with a stairway that became extremely slick and hazardous during what was the first (and unexpected) rain of the Los Angeles basin's winter season. For the safety of the patient and the personnel, a decision was made not to attempt to transport the 600 pound-plus MALSS, with the patient in it, down the stairs in heavy rain. The patient was transported by BPI ambulance from Huntington Beach to Rancho Cucamonga, CA starting at approximately 0350. Driving conditions were very poor with heavy rain and an earlier than usual morning rush hour traffic beginning by the time the freeway was reached at 0400. The patient arrived at the facility at 0545 on 13 December. End of PART II