X-Message-Number: 7681
Date: Wed, 12 Feb 1997 20:39:16 -0500 (EST)
From: Charles Platt <>
Subject: Cryopreservation Report

A couple of weeks ago, I started to post a detailed report by Mike Darwin
describing the cryopreservation of CryoCare member James Gallagher.  This
case history was first published in CryoCare Report, in two parts. For the
net, I divided Part One into subsections 1a, 1b, and 1c. These were posted
here on CryoNet. 

I intended to continue with Part Two, divided into subsections 2a and 2b. 
My plan was interrupted, however, by a trip to Arizona and New Mexico. 

Here, now, is subsection 2a. Subsection 2b will follow tomorrow. 

--Charles Platt


     The Cryopreservation of James Gallagher (subsection 2a)

     by Mike Darwin 

     Discussion of Transport Data 

     As was noted in Part One of this case report, the use of 
premedication, intracorporeal cooling, active compression-
decompression-high impulse CPR, and advanced reperfusion 
medication resulted in this patient experiencing less injury 
than any previous cryopatient as documented by serum tissues 
specific enzymes, blood gases, and clinical criteria (i.e., 
absence of pulmonary edema and good overall capillary 

     The impact of intracorporeal cooling in the form of 
colonic and peritoneal lavages with 0 degrees C buffered 
Normosol-R can be seen graphically in figure 1. As was 
previously noted, a cooling rate of slightly over 1.0 degrees 
C per minute was achieved for the first 10 minutes post 

     Close examination of this patient's cooling curve 
discloses what we believe to be additional very valuable 
information. For the first 50 minutes of CPR, rectal and 
tympanic temperatures smoothly track each other. However, at 
approximately the 50-minute post arrest mark there is a 
sudden reduction in the rate of tympanic temperature descent. 
This flattening of the tympanic temperature cooling curve 
continues until the start of extracorporeal support at which 
time there is a sharp decrease in tympanic temperature and 
resumption of "tracking" of the rectal temperature. 

     We believe this sudden slowing in the rate of tympanic 
temperature descent, which persisted until the start of 
femoral-femoral bypass, indicates a failure of cerebral 
perfusion. The author has repeatedly observed the same 
phenomenon in the dog lab with confirmation of failed 
cerebral perfusion obtained by intravenous dye administration 
Using a canine model and the standard ACLS drug protocol we 
typically see failure of cerebral perfusion following 10 to 
15 minutes of mechanical CPR. If the delay before starting of 
CPR is greater than 5 minutes after the onset of cardiac 
arrest it is uncommon to achieve any significant degree of 
cerebral cortical reperfusion during CPR (1). 
     In view of the canine data from our laboratory, the 
persistence of cerebral perfusion as indicated by continued 
decrease in tympanic temperature for the first 50 minutes of 
CPR in this patients is encouraging. However, it should also 
be noted that the presumed loss of cerebral perfusion 
occurred at approximately 24 degrees C (without further 
significant reduction in tympanic temperature) approximately 
110 minutes prior to the beginning of bypass, and associated 
resumption of both cerebral perfusion and cerebral cooling. 

     Clearly, it is critical to be able to take advantage of 
the relatively brief period of CPR-generated brain perfusion 
to achieve the maximum amount of cooling possible. In this 
case, another 2 to 3 degrees C of cooling could have been 
achieved with the addition of partial liquid ventilation by 
filling the patient's lungs to vital capacity with an 
appropriate heat exchange medium which is also capable of gas 
exchange (2).  Research currently underway suggests that an 
addition 4-6 degrees C of cooling could easily have been 
achieved during CPR with the use of continuous recirculation 
of the liquid ventilation medium through a heat exchanger and 
membrane oxygenator (i.e., sweep-flow liquid ventilation). 
     It is also apparent that further colonic and peritoneal 
lavages with 0 degree C fluid would have been useful during 
the first 50 minutes of CPR. 
  Finally, faster application of extracorporeal support is 
critically important and every effort should be made to 
initiate bypass within a _maximum_ of 45 to 50 minutes of 
cardiac arrest and sooner wherever possible. 

     As figures 2 and 3 show, venous pO2 and pCO2 improved 
steadily during CPR. Lactate levels rose steadily (figure 4) 
but remained impressively low during 142 minutes of CPR, 
peaking at 13 mM/L immediately prior to the start of bypass. 

(Figure 2 shows the _venous_ pO2 first measured at 
approximately 70 minutes post arrest measuring 38 mmHg.  
Venous pO2 to roughly 190 mmHg by 140 minutes post arrest.  
Venous pCO2 (figure 3) over the same time course ranges from 
28 mmHg to 23 mmHg.) 

     Serum glucose levels rose steadily during CPR (figure 5) 
indicating adequate hepatic perfusion (there was no 
exogenously administered glucose) but failure of glucose 
regulation, with serum glucose being above 350 mg/dl at the 
start of bypass. 

(Figure 5 shows serum glucose first measured at 70 minutes 
post arrest and increasing from 270 mg/dl to 370 mg/dl with 
all the points falling on a straight line.) 

     Venous pH was not aggressively raised to 7.4 in this 
patient, but rather was to be held in the range of 7.0 to 7.2 
during CPR. Control of pH was not as tight as was desired and 
the patient remained acidotic with a pH ranging from 6.95 to 
6.84, which is undesirably low (figure 6). The decision to 
keep pH in the range of 7.0 to 7.2 is based upon experimental 
evidence from our laboratory and elsewhere (3) that rapid 
correction of pH to normal levels can be deleterious to the 
brain and that low pH is somewhat protective during cerebral 

     In the future, it would be desirable to be able to 
measure pH dynamically in the patient during CPR and we are 
actively investigating means for doing this using 
percutaneously placed commercially available pH electrodes 
which are incorporated into 16 g needles (4). 

     Other indicators of the efficacy of CPR in meeting this 
patient's metabolic demands are the patient's serum sodium, 
potassium, and chloride levels which are presented in figure 
7. Note that the patient's serum potassium remains stable at 
under 5 mM/L throughout 120 minutes of CPR. Similarly, serum 
sodium is constant at between 130 and 135 mM/L. 

     Graphic data for arterial pressure during bypass and 
total body washout (TBW) are presented in figure 8 and again 
reflect the good physiologic state of the patient. 

                   Cryoprotective Perfusion 

     Patient Assessment 

     Following transport of the patient to BPI's facilities 
in Southern California for cryoprotective perfusion and 
freezing (arrival time 0545 on 13 December, 1995) the patient 
was moved from the portable ice bath and onto the operating 
table. Assessment of the patient at that time disclosed 
evidence of good cutaneous blood washout and no evidence of 
rigor mortis.  Also remarkable was the absence of the typical 
depression and deformation of the midsternum and the absence 
of flail chest ( chest morphology was normal without the 
typical "caved-in" appearance typically invariably seen after 
prolonged mechanical CPR).  Following assessment  the patient 
was repacked in ice. 

     The patient was evaluated for the presence of pulmonary 
edema radiologically and by measuring peak and mean 
inspiratory airway pressure. The chest film disclosed lungs 
clear to the bases bilaterally and peak airway pressure was 
36 cm H2O when inflated with 10 cc/kg of air. This was 
consistent with absence of clinical evidence of pulmonary 
injury which has previously invariably occurred as a result 
of antemortem shock, CPR and TBW during Transport. 

     Determination of lung water status (i.e., the absence of 
pulmonary edema) was critical in this case because of our 
desire to carry out cryoprotective perfusion using femoral-
femoral vascular access, as opposed to performing a median 
sternotomy and achieving vascular access via the aortic root 
and right atrium. Work done at BPI over the past two years 
has established the safety and efficacy of this approach to 
cryoprotective perfusion utilizing newly developed flat-wire, 
high-flow, low-resistance, femorally placed venous cannulae 
(Biomedicus 29 Fr. x 60 cm.) which allow for caval drainage 
at the level of the right atrium. However, for this approach 
to be used safely it is essential that the patient not 
develop high intra-thoracic pressure from lung edema which 
could impede venous return. 

     In the past, all patients undergoing cryopreservation in 
the authors' experience have developed marked edema of the 
lungs during transport which has invariably progressed to 
massive edema of the lung parenchyma with alveolar 
transudation and filling during cryoprotective perfusion 
(5,6,7). Often this edema is so severe that closure of the 
chest wound over the distended lungs is problematic. Such 
massive fluid accumulation and accompanying increase in 
intrathoracic pressure would be unacceptable and lead to 
compartment syndrome and consequently failed caudal perfusion 
in a patient with a closed chest.  Rapid development of 
pulmonary edema is a well established sequelae of 
conventional closed chest CPR (8). 
     Assessment of lung compliance during cryoprotective 
perfusion was carried out by measuring peak inspiratory 
pressure using the same tidal volume at several intervals 
during cryoprotective perfusion. (Peak inspiratory pressure 
increases during cryoprotective perfusion as a result of 
reduced lung compliance due to cryoprotective-associated 
stiffening of the pulmonary parenchyma and this must be taken 
into account during evaluation). Radiologic evaluation can 
also be used to determine lung edema status dynamically. 

     Final Preparations For Cryoprotective Perfusion 

     Final preparation of the patient for cryoprotective 
perfusion consisted of the application of occluding 
tourniquets to all four limbs (metal hose clamps were used) 
and re-establishment of the extracorporeal circuit by 
connection of the femoral arterial and venous cannulae to the 
cryoprotective perfusion circuit (figure 20). Care was taken 
to avoid introduction of any air into the tubing/cannulae 
during re-establishment of the extracorporeal circuit. 

(Figure 20 shows a schematic of the cryoprotective perfusion 
circuit.  The circuit contain a recirculating loop through 
the patient to which concentrated cryoprotectant solution is 
added and dilute venous effluent is removed in a controlled 
fashion.  The circuit is also remarkable for a variably 
buoyant floating lid atop the liquid column of the 
recirculating reservoir and a de-aerator positioned between 
the recirculating reservoir and the intake of the arterial 
(i.e., patient loop) pump.  The purpose of the floating lid 
is to prevent air entrainment into the viscous perfusate by 
the mixing magnetically driven stir bar in the bottom of the 
recirculating reservoir.  The de-aerator acts as a bubble 
trap to capture any entrained air before it can enter the 

     In parallel with reestablishing the bypass circuit, the 
patient underwent aseptic preparation and draping for 
craniotomy. Scalp incisions were then made 2 cm from the 
midline over each parietal lobe, and a DePuy pneumatic 
perforator was used to make two burr-holes ca. 10 mm in 
diameter in the cranial bone. The dura was opened in each 
burr hole using a dura hook and iris scissors and was 
dissected away to the edge of the burr hole using the iris 
scissors. The brain was noted to be slightly dehydrated and 
retracted from the margin of the burr holes bilaterally by 2 
mm. A silastic and teflon clad, copper-constantan 
thermocouple probe (22 gauge) was placed on the cortical 
surface at the level of the temporal lobes by advancing the 
thermocouples through the burr holes over the cortical 
surface. Initial temperature readings were 1.8 C for the 
right temporal and 2.0 C for the left temporal lobes. 


End of part 2a

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