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 CryoCare ----------------------------------- 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 integrity). 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 arrest. 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 ischemia. 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 oxygenator.) 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 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=7681