BioPreservation: Suspension Technology Report by Mike Darwin That past few months have seen rapid growth not only in Biopreservation Inc.'s (BPI's) basic cryopreservation capability, but also in innovations to transport procedures. Some of these innovations are simple and straightforward such as the reorganization of our Remote Standby Kit (RSK), while others involve profound changes in the very fabric of the transport procedure. We have made several of what we would call "breakthrough" advances in patient care. Unfortunately, we will be somewhat delayed in communicating very much detail about these advances until our patent applications are filed (a process which will take months; preliminary steps are now underway). Most of this article will thus focus on what we CAN tell you about, and frankly, that's plenty enough in itself. ACS/BPI Training On Memorial Day weekend Jim Yount of ACS and Naomi Reynolds of BPI drove down from the Bay Area for a weekend of INTENSIVE one on two training. The facility was deliberately emptied of EVERYONE but Mike Darwin, Jim and Naomi. The objectives were tough ones: Jim and Naomi would perform 4 jugular cutdowns on a dog and two femoral cut downs. They would pass small and large bore cannula on the jugular cutdowns to simulate getting vascular access for administration of Transport medications during human cryopreservations. They would then (using the femoral- femoral approach) go on cardiopulmonary bypass, hemodilute the dog to a hematocrit of less than 20 (diluting its blood by about half) and then come off bypass. They would do ALL of this WITHOUT any significant physical assistance from Mike Darwin. (I didn't even scrub in; I just stayed in my street clothes and put on a mask and cap.) We started at noon on Saturday and by 4:30PM they had two jugular cutdowns done. The long hours of performing the femoral cutdown and going on bypass lay ahead (I should add that they had also set up the heart-lung machine and primed it.) At that point I proposed we abandon the jugular cutdowns and go on to working on the femoral cutdowns and getting on with bypass. To their credit BOTH Naomi and Jim immediately said in effect "No, we've come all this way and we damn well intend to get all the practice we can!" So, they did two more jugular cutdowns, picking up considerable speed and then went to work on the groin. About 12 hours after starting the dog had been put on bypass and cooled to 13*C at which point hearbeat had ceased. At about 15*C I left the facility to buy food for man, woman and beasts and when I came back over an hour later Naomi and Jim were rewarming the dog. Aside from a close call where Naomi almost pumped air while I was away (a valuable learning experience) and a blow-off on the arterial line where it joined the cannula (this SHOULD NOT have happened and thus was an even MORE valuable learning experience) bypass was uneventful. The dog's heart started beating on its own and she (the dog) came off bypass with minimal bleeding and an activated clotting time of 130 sec. (prebypass was 80 sec.). By 7:00 AM she had kicked out her endotracheal tube and by noon she was standing up. When I arrived at 5:00 PM she was waiting for me by the door of the facility (no kidding)! She has done very well, required minimal pain medication and has suffered NO complications from 3 hours of cardiopulmonary bypass surgergy/perfusion conducted by two "rank amateurs" who did pretty darn well. In addition to serving as a training dog she also served as something of a control on BPI/21sts basic bypass technique (pretty darn good too!). The dog's name, by the way, is Gouda. In case you are wondering, she got this name when the kind soul who brought her back from the airport let her out of the shipping crate and fed her some cheese. She then (a short while later) vomited up this 1/2 pound of cheese all over the interior of our kindly volunteer's BRAND NEW Nissan Pathfinder. He has of course learned his lesson: let air-shipped crated dogs lie -- and don't feed them Gouda Cheese en route. Also by the way, Gouda is a very sweet collie mix dog who weighs about 40 pounds and would love to have a home. Any takers out there? BPI/21st Century tries to place all good tempered surviving research/training animals. Upgraded Remote Standby Capability The first major improvment in Remote Standby Capability (RSC) came when the American Cryonics Society decided to purchase an RSK from BPI. This RSK is a full capability kit designed to allow for field surgery, total body washout and near 0 degrees C shipping of patients to BPI or other cryonics organization's facilities for cryoprotective perfusion. The ACS kit will be available for use by BPI to service ACS clients and thus frees up the BPI kit. Also, in a critical emergency it is possible the ACS kit might be dispatched to "fill the gap" (and the same is true for the BPI kit if ACS has TWO emergencies at the same time -- a situation which HAS happened in the past). The BPI kit has been radically upgraded and restructured. The weight of all the critical modules has been kept below the airline minimum of 65 pounds and the boxes are are all equipped with handles to facilitate handling as baggage rather than as freight. This is an important capability because often freight space is NOT available on the same flight the Transport Technicians are going on, and even if it is, it means that the RSK must be processed through the *airfreight offices* of the carrier and picked up at a location remote from the passenger terminal: a delay that can mean hours lost in a critical situation where a patient is profoundly unstable or already down. A major element in achieving this weight reduction (aside from modularization) was the procurement of "state-of-the- art" industrial instrumentation transport containers made of PLASTIC! These rugged new plastics can take baggage handling stresses and still hold up. Some of the modules (for less sensitive equipment) are heavy-gauge aluminum. In addition to reconfiguring and modularizing the kit we have also made it easier to use. The medications box is no longer a gray Flambeau tool chest but rather a suitcase type affair with a large, lift-out panel on which ALL the medications are mounted, in the order to be given, in clear acrylic boxes secured to the panel with Velcro. Meds needing refrigeration are in color-coded overpacks to key personnel to insert them onto the panel just prior to use. Incompatible meds are also color-coded. Many other changes to the rest of the kit, of the same nature, designed to facilitate both user-friendliness and speed of use, have also been incorporated, but space prevents us from detailing them here. Three major functional advances have been made in the BPI RSK. The first is the addition of extra patient monitoring/telemetery equipment. We now have a Dinamap automatic, osscilographic, nonivasive blood pressure monitor (boy that's a mouthful, isn't it?). This device allows us to monitor the patient's blood pressure using a cuff, but far more accurately and reliably than by using a cuff with a microphone or by listening with a stethescope. This unit thus allows us to continue to monitor blood pressure NONIVASIVELY (i.e., without cutting into or sticking the patient and placing a catheter or sensor in his/her body) and with far greater accuracy than with conventional blood pressure equipment. The unit has several other features which are very important to us: * It operates automatically and can be set to take blood pressures at any arbitrary interval desired. * It automatically displays pulse and calculates/displays mean arterial pressure. The latter is a critical value in evaluating how long a patient will "last" while agonal (i.e., is in the last stages of the dying process before heartbeat ceases). * It has adjustable "High" and "Low" alarm limits on both systolic and diastolic pressures so that family or personnel can be alerted to any significant changes in the patient's status. This is VERY important since it is all too easy for exhausted standby personnel or family members to drift off to sleep. Our first experience with pulse oximetery in the field has clearly indicated a need for another modality of measuring patient "instability". The Dinamap is old, reliable technology which is used by hospitals everywhere to monitor critically ill patients. In fact, the new units (we have a new one) are increasingly replacing invasive blood pressure monitoring in the ICU since they have been found to be just as reliable for most applications and carry less risk and COST. The down side to this of course is that used Dinamaps, even older ones, are very costly because they are now very much in demand (the lowest used price we've seen is $1200). We have also added EKG and stethephone capability allowing us to transmit EKGs and breath and heart sounds to consulting clinicians remote from where the patient is. This allows us to put experts "on site" via telemedicine. We are investigating the use of videophones which will transmit modest quality images (Such as the AT&T Picturephone), but which could be of critical importance in assisting the consulting physician(s) in evaluating the patient's condition. As we are learning from hard experience, even a crummy picture is worth a lot of words. Inclusion of this equipment in the kit (if we decide it is cost effective) would also allow less skilled personnel to be guided through equipment set-up in an emergency in a situation where the kit is on-site with the patient but highly skilled BPI personnel are not (we increasingly send out the kit well in advance of anticipated need). Perhaps the most dramatic upgrades to the kit are the additions of a complete mini-clinical lab (MCL) and the capability for on-site preparation of the new 21st Century Medicine/BPI perfusate which has been shown effective in inhibiting cold-rigor mortis after blood washout (this solution will probably soon replace Viaspan for most remote uses). The MCL is actually pretty sophisticated and will allow us to do the following evaluations: hematocrit (% of blood as red cells), hemoglobin, serum total protein, osmolality (blood/urine/perfusate), chemical urinalysis (ketones, glucose, bilirubin, blood, etc.) urine specific gravity (along with urine osmolality a critical indicator of the patient's fluid balance status or degree of dehydration-- very important if the patient is dying secondary to dehydration (either as a direct result of the disease process or by consciously choosing to refuse all food and fluid). Blood/perfusate pH is also on line in the kit. Within the next 6 months (hopefully sooner) we plan to add capability for serum ammonia and total bilirubin (indicators of certain kinds of liver failure), BUN and creatinine (indicators of renal function), amylase (indicator of pancreatic disease), as well as serum phosphorus and cholesterol and triglycerides (these last three tests are of little clinical relevance in the standby setting, but will come as part of the package capability). Several questions probably come to mind about the addition of this clinical laboratory capability: * First, why? The answer is simple; we often find ourselves in field situations where we are unable to tell what is happening to the patient and/or what the patient's likely time-course to cardiac arrest is because medical consultants (remote and/or on site) do not have access to needed laboratory information. This has been intensely frustrating, and was especially a problem in the last (and first) cryopreservation BPI did. * Second, why not just send the sample in to a local clinical lab for analysis? Not only is this not only costly (up to $200 for each "stat" run) it is often logistically difficult. The sample has to be drawn, containerized, run down to the lab and then you WAIT for results. Monitoring rapid deterioration of a patient's condition is not cost effective or practical when using an outside lab. Also, since the information is not for "theraputic" purposes physicians will not usually order it because insurance won't reimburse the cost and setting up with the local lab ( i.e., one near the PATIENT as opposed to the one across town the doctor uses) on pay-per-use basis is very problematic. An on-site lab lets the treating or consulting physician order labs effortlessly and allows everyone to get near instantaneous feedback. Most test results are available within 5 minutes or less! * Tests can be repeated at frequent intervals without draining the patient of blood. A normal clinical analyzer requires about 3-5 cc of serum which means they need about 7-10 cc of blood. The Ektachem and other equipment we use requires about 1 cc of blood to perform ALL the tests we need to do! * Why is it so critical to know what is going on medically with the patient when the end-point (legal death) is always the same? Here the answer is simple: preparedness and cost containment. Every day of remote standby is a minimum of 1K! If medications are prepared too early and have to be discarded another 1-2K goes down the drain and what's more the meds might not be there when the patient needs them! We believe that better in-field diagnostic capability will prove effective in containing standby costs AND giving better care to the patient. Also, as we start to monitor these parameters we'll learn which values signal real trouble and build a database of "crisis" values which will improve our predictive skill. For instance, we know for our in-lab work with dying dogs that serum lactate and ammonia levels show a predictable pattern of increase right before an animal becomes agonal. We need to build a similar series of curves for humans dying slowly too! The MCL is not a luggage-able item so it must be air- shipped. But then, it is likely to be needed only in longer cases of standby anyway so we don't see this as a problem. New CPR Equipment By the time you read this BPI should have taken delivery on a new system for delivering CPR which should DOUBLE our cardiac outputs over the previous high-impulse system now used by Alcor. In others words, this unit should allow us to deliver nearly NORMAL baseline cardiac output (blood flow) in many patients. This system has been months in the designing/engineering and has required a great deal of innovation and a lot of effort on both our part and on the parts of our British colleagues who have worked with us to make this system possible. We cannot give you the details yet, but we can tell you that this is only the "first half" of a revolution in suspension patient care centering on transport. This new CPR unit is computer driven and preliminary in- house tests (using a prototype of this system) indicate that we may at long last be on the threshold of solving many of the problems associated with conventional closed-chest CPR (pulmonary edema, grossly inadequate cardiac output, and rapid loss of brain perfusion). A major problem has been getting a workable (portable) power supply since this unit, unlike Michigan Instruments Thumpers and Brunswick HLRs uses solid state logic and computer driven solenoids to move the chest. Incidentally, the price tag on this unit was a "mere" $10,074.63! Upgraded Cryoprotective Perfusion Capability One innovative upgrade to cryoprotective perfusion has been the acquisition of fiber-optic endoscopy equipment (along with the expertise to use it!). Endoscopy means to look inside the body and this area of medicine has been undergoing explosive developments since the late 1960's. The pace has quickened in recent years and it now possible to perform major abdominal surgery such as gall bladder removal via endoscopic means. BPI has acquired a reasonably sophisticated endoscopic capability. We have a Sony high resolution CRT (Tv monitor) with accompany videorecorder, a Storz endoscopic television camera, an ACMI halogen, and a Storz Xenon light sources, as well as related suction and irrigation equipment. We have also acquired a variety of endoscopes including a gastroscope, a colonoscope (both made by Olympus) a rigid hysteroscope (which allows visualization of blood vessels well under .5 mm in diameter on the brain surface and even slightly (1-2 mm) BELOW the brain surface using our Xenon light source), and two ultrathin (1.5 and 2.5 mm diameter x 1 M length) flexible "vascular" scopes (the latter has an irrigating/working channel down which an instrment can be passed) which allows us to visualize almost the entire brain surface through burr holes opened over each cerebral hemisphere. We can thus snake these scopes between the tough dura mater which covers the brain and the brain surface and look at the pial blood vessels to assess the degree of blood washout or continued perfusion (via injection of dyes). These two scopes can also be passed through blood vessels (the largest is the size of a Swan- Ganz catheter for those with a medical bacground) and used to look inside carotid arteries and other vessels for retained clots after washout has taken place in patients who did not receive good transport/blood washout in the field. Added capabilities are the ability to inflate the abdomen with carbon dioxide(CO2) (we have a Wolff CO2 insufflator) and examine the abdominal viscera with our rigid scopes. This is a very important capability to have if we see abdominal distension (indicating possible perfusate leakage) during perfusion. These instruments also have "working channels" and we have biopsy equipment which can be passed down the working channel allowing us to biopsy abdominal organs on whole-body patients for evaluation of their response to cryoprotectuive perfusion/freezing -- something that could be done in the past only by making a large abdominal incision (clearly unacceptable for data gathering purposes in whole body patients). We can also examine the gastric mucosa (inside of the stomach) for lesions that may cause loss of perfusate (ulcerated mucosa from shock during the agonal period or absent post arrest stabilization) as well "treat" these lesions to a limited extent (and thus stop loss of perfusate) by cauterizing the lesion or distending the stomach and compressing the leaking area with a gastric baloon filled with CO2. Yet another added capability is pulsatile perfusion of the patient's circulatory system which is especially useful in facilitating perfusion of patients with extended post-arrest ischemic injury. ACS MiniKits Deployed On Memorial Day Weekend 2 minikits were deployed in the Bay Area. The Minikit concept has been rattling around for about 6 months and Jim Yount deserves the credit for really pushing them into being. ACS bought two of them for Northern California (in addition to two simpler ones which Jim had put together himself). The Minikits have basic drugs, basic IV-start equipment, a bag-valve resuscitator, a cut down tray, paramedic holster (superscissors, etc.) and Zip-Loc bags. The temperature sensitive meds (i.e., those that can't be left in the car) are packed in a fanny pack so they can be carried around with the person on-call. The need for more minikits was brought home during the last ACS suspension when an overturned tanker cut-off staff with equipment from reaching the patient's nursing home in Walnut Creek, CA. Since ACS was nice enough to buy the minikits, BPI decided to meet them half-way and deployed another Thumper (cardiopulmonary resuscitator) with regulators, wall adapter and 2 aluminum E-cylinders, with BPI Transport Tech Naomi Reynolds. Naomi also has one of the ACS minikits so she is now a walking 1-woman cryonics Transport capability. BPI to Deploy Transport Kit on East Coast Due to the rapid growth of CryoCare membership on the Eastern Seaboard BPI will be deploying a full ER kit, possibly including blood pump/washout capability towards the first to middle part of July of this year. Stay tuned for more details. Portable Ice Bath (PIB) Redesign Underway BPI is also redesigning the PIB so that it will be: a) very lightweight b) collapsible into an automobile/airline luggage cartable size c) easier to set-up (just unfold it!). We should have a couple of these on-line in about a month. We feel confident that these upgrades will go a long way towards improving patient care and we look forward to reporting on even more exciting ones in the near future. If you have any questions about BPI's services, feel free to give us a call (909)987-3883. Copyright 1994 by BioPreservation, Inc.