X-Message-Number: 7594
Date: Wed, 29 Jan 1997 17:35:53 -0500 (EST)
From: Charles Platt <>
Subject: Cryopreservation report (part 1b)
Mike Darwin has asked me to post his report of the
cryopreservation of CryoCare's first patient, James
Gallagher.
Part One of this report was first published in CryoCare
Report number 6. Part Two appeared in issue number 9. Many
photographs and charts appeared in the printed version and
cannot be reproduced here.
Subscriptions to CryoCare Report are available for $9
(four issues) per year.
Because this text is long, I am dividing it into
subsections. Thus Part 1 will be posted as Part 1a, Part 1b,
and Part 1c. Part Two will be posted as Part 2a and Part 2b.
--Charles Platt
CryoCare
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Part 1b
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.
[missing figure]
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.
[missing figures]
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:
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End of Part 1b
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