The cryonic process

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The aim of cryonics is to stabilize critically ill patients after cardiac arrest, at cryogenic temperatures, in anticipation of future resuscitation. In Alcor, cryonics is considered a form of experimental critical care medicine, with members in biostasis considered patients. Because human cryopreservation is not available as an elective medical procedure, cryonics procedures can only be initiated after the pronouncement of legal death. The procedures to achieve this goal have been developed by Alcor for many years in consultation with external experts in brain resuscitation and cryopreservation of tissues and organs. Alcor offers cryopreservation of the whole body and neuroconservation. In both options, The preservation of the brain as the anatomical basis of the person has the highest priority. During the initial stages of cryonic procedures, the ideal goal of the Alcor protocol is to ensure the viability of the brain through contemporary biological criteria. This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation During the initial stages of cryonic procedures, the ideal goal of the Alcor protocol is to ensure the viability of the brain through contemporary biological criteria. This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation During the initial stages of cryonic procedures, the ideal goal of the Alcor protocol is to ensure the viability of the brain through contemporary biological criteria. This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation The ideal objective of the Alcor protocol is to ensure the viability of the brain through contemporary biological criteria. This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation The ideal objective of the Alcor protocol is to ensure the viability of the brain through contemporary biological criteria. This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation This means that the initial stabilization procedures of Alcor should not be harmful in themselves and that the reversal of these protocols should be possible in principle. During the subsequent phase, which involves cryoprotective perfusion and cooling below 0 degrees Celsius at cryogenic temperatures, this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the most modest goal of good ultrastructure. preservation this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the more modest goal of good ultrastructure. preservation this goal can no longer be achieved as a result of cryoprotective toxicity and structural injury associated with thermal stress, and is replaced by the more modest goal of good ultrastructure. preservation

Non-ideal cases

The procedures described in this document are what is attempted under ideal logistic and biological conditions. The circumstances under which legal death occurs can be very variable, and in many cases some or all of these procedures, except cooling, may be impossible. Unless members making cryopreservation arrangements express other written preferences, it is a general principle of cryopreservation that cryopreservation should be performed after legal death, even in deficient biological conditions, when standard protocol procedures can not be performed. This is done to preserve as much remaining biological information as possible,

Summary of cryonics procedures

The cryonics protocol of Alcor ideally consists of four different elements: (1) deployment and waiting, (2) stabilization, (3) cryoprotective perfusion, (4) cryogenic cooling.

(1) Deployment and standby. If a pending case or an emergency is notified to Alcor, a reserve team is deployed at the patient’s location to ensure prompt intervention after the legal death sentence.

(2) Stabilization. After legal death is pronounced, rapid cooling is initiated, circulation is restored, lungs can be ventilated, and medications are administered to protect against blood clotting and keep the brain viable. In cases of remote stabilization where transportation to the Alcor operating room can take up to 24 hours, the blood is ideally replaced with an organ preservation solution to improve cooling, prevent blood clotting and protect against cold ischemia.

(3) Cryoprotective perfusion. After the patient arrives at the Alcor facility, the patient’s blood (or the organ preservation solution) is replaced with a vitrification solution. Circulation of this solution through the blood vessels at cold temperatures partially replaces the water within the cells with chemicals that reduce or prevent the crystallization of the ice during additional cooling at cryogenic temperatures.

(4) Cryogenic cooling. After perfusion with cryoprotectant, the patient is gradually cooled to the temperature of liquid nitrogen for long-term care. In the future, as reliable equipment becomes available, cooling may be terminated and long-term maintenance may occur slightly below the transition temperature of the glass, to minimize structural damage.

Deployment and Standby

Alcor maintains a local emergency vehicle equipped with standby and stabilization equipment and at least one complete set of kits for remote deployment, and also has access to similar chronic emergency vehicles maintained by Suspended Animation, Inc., in Southern California and Florida. Alcor also makes an effort to maintain basic or complete kits in regional areas with a high number of cryonics members. The organization determines the allocation of reserve resources by periodically reviewing the demographics and regional distribution of its members. To minimize the possibility of late or last-minute implementation,

Alcor materials are available to family members, medical caregivers and third parties about their procedures to ensure an orderly and timely transition between the pronouncement of legal death and the initiation of cryonics procedures. Alcor will also request medical information about the terminal patient to help determine the time and scope of the deployment. Although Alcor does not participate in the pre-mortem treatment of the patient, Alcor can discuss with the family and the caregivers the medical management of the terminal patient. Alcor can also request permission for the placement of non-invasive monitoring devices.

Alcor maintains a Deployment Committee that normally includes its executive director, the Medical Response Director and the Chief Medical Advisor. The committee is responsible for evaluating and defining the comprehensive waiting policy for Alcor members, establishing waiting implementation guidelines and making real-time implementation decisions in emergency situations.

Unless the unforeseen circumstances (such as a remote last-minute case) do not allow full deployment, the Alcor Stabilization Protocol requires  four team members.Be present at the beginning of cryonics procedures. To avoid fatigue and errors, waiting team members rotate in pairs, in a 12-hour cycle, to allow enough rest and sleep. The stabilization team will normally be headed by the Medical Response Director of Alcor, who is a nationally certified paramedic. Additional team members may include other Alcor staff members with training in EMT (emergency medical technician), local volunteers trained in cryonic stabilization, or a Standby Team of Suspended Animation, Inc., which is composed of members of trained personnel and professional perfusion consultants and surgeons. If there is not enough notice for Alcor or Suspended Animation, Inc.

Alcor offers education and training to its members and medical professionals interested in basic procedures of human cryopreservation. In addition, anyone who feels motivated to actively participate in the cases can look for more advanced training. A network of volunteers and trained members can be requested to help in remote cases or basic logistics or stabilization tasks.

Cryonics keeps “Frozen Heads”

What is known as “Neuro” or head suspensions are, in fact, available in the cryonics industry today, but you will not find that option in CI. CI is interested in preserving people and our policy is the preservation of the whole body just so that our patients can be revived in their entirety and in the future.

The argument in favor of head suspensions only is that the brain is the only truly critical organ for preservation, since it is the source of a person’s memories and identity. Following this reasoning, it is assumed that a vitrification only for the head can be done more quickly and that long-term liquid nitrogen storage of a head is more efficient than a complete body.

We agree that the brain is a critical organ, and our vitrification process perfumes the head and body simultaneously, so there is no appreciable advantage to only perfuse the head and discard the body in terms of time or effectiveness. We simply feel that it is our duty to preserve the whole person, not just the head.

To argue against the economic savings of head-only storage, the IC prices for full-body suspensions are actually lower than the only neuro option in competing companies. This is because the philosophy of CI from the beginning has been to offer our members the services of cryonics suspension of the highest quality at affordable prices.

Stabilization

The goal of stabilization is to maintain the viability of the brain according to contemporary biological criteria after the legal pronouncement of death. To achieve this purpose, four different procedures are ideally used:

1. Cardiopulmonary support. The circulation is restored to provide oxygenated blood to the brain and to improve cooling. Depending on the specific circumstances, the lungs can be ventilated.

2. Induction of hypothermia. The temperature of the patient is reduced to just over 0 degrees Celsius to depress the metabolism.

3. Administration of medicines. Medications are given to improve circulation, inhibit blood clotting, and protect the brain.

4. Replacement of blood. If the patient is far from the Alcor facilities, and if it is logistically possible, the patient’s blood is replaced by an organ preservation solution to improve cooling, prevent coagulation and protect against cold ischemia.

Cardiopulmonary support, the induction of hypothermia and the administration of medications are initiated as soon as possible after the death is pronounced. In practice, none of these procedures alone is enough to keep the brain in a viable state. To ensure that these interventions are carried out simultaneously, a minimum number of four team members will be present at the start of the stabilization. Their tasks will include the collection of data for further review and analysis.

Stabilization procedures end when the patient’s temperature has been reduced near the freezing point of the water or when the blood is being washed to prepare the cryoprotective perfusion. In remote chronic cases, blood replacement is an option before transport to cryonic facilities.

Induction of hypothermia

External cooling of the patient should be started immediately after pronouncement of legal death to depress metabolism. The patient is moved from the bed to a portable ice bath (PIB) that contains ice and cold water to facilitate cooling during transport, and increase cooling rate. The patient should be completely immersed in ice and water with a primary emphasis on the head and areas with major surface vessels such as the neck, axilla and groin. Because the total area of ​​contact between dry ice cubed and the patient is unavoidably limited, some water is essential, to maximize heat transfer. It should cover as much of the patient’s skin as possible, and is circulated via a system of perforated tubing to a submersible pump. Water is flowed rather than sprayed over the patient,

The simultaneous initiation of aggressive cardiopulmonary support increases the rate of cooling by moving warm blood from the patient’s core to the surface for heat exchange. The goal of all these procedures is to achieve the rapid cooling rates observed in immersion in cold water without sacrificing cardiopulmonary support and medication administration.

A lower degree of internal cooling can be achieved during stabilization by cooling medications and liquids before they are administered.

Patient cooling should continue without interruption during transport to the funeral home or during surgical procedures. The recording of the patient’s temperature is important to monitor the effects of the cooling efforts and for the subsequent notification of the case.

Because even the fastest cooling rates can not preempt ischemic injury without the circulation of oxygenated blood and the administration of neuroprotective drugs, the induction of hypothermia can not be a substitute for these interventions. This is particularly important during the start of stabilization procedures because energy depletion is running faster than cooling can depress the metabolism.

If an ice bath is not available, a heavy body bag can be used to surround the patient with ice without spilling or dripping.

In typical cases, the patient should not be cooled below the freezing point of water (0 degrees Celsius). The patient can only cool below the freezing point of water if Alcor has made the decision that prolonged delays before stabilization, or that are expected during transport, will make cryoprotective perfusion impossible. In such cases, the patient should be kept at the temperature of dry ice (-78.5 degrees Celsius), with the understanding that this will cause a very serious brain injury as a result of freezing. If a patient is frozen, special care must be taken to avoid thawing and freezing, which will cause even more damage.

Medicine administration

Administration of medication should be started as soon as the patient has been placed in the portable ice bath. If the patient already has an intravenous patent line in place, or if there is no portable ice bath available, administration of the first medications may begin earlier. Under no circumstances should members of the Alcor team begin or authorize the administration of medication prior to the pronouncement of legal death.

Each medication falls into one of three categories:

        1. Small-volume medications (such as heparin and streptokinase)

        2. Large volume fluids (such as hydroxyethyl starch)

        3. Fluids that require gastric administration (Maalox).

        4. Medications to add to the blood wash solution.

The administration of small-volume medications and large-volume liquids should start at the same time. This is particularly important if the patient is severely dehydrated at the beginning of the stabilization procedures. Simultaneous administration of small-volume medications and large-volume fluids can be achieved by pushing the small drugs on the line or establishing a second IV line.

If there is no delay between the pronouncement of legal death and the start of stabilization procedures, the full set of medications must be administered.

Small volume medications

(1) Propofol (200 mg – fixed dose)

Propofol is a general anesthetic and is used for two reasons. The first reason is to reduce the metabolism of the brain to reduce oxygen and glucose requirements, and the second is to prevent the theoretical possibility of recovery of consciousness due to aggressive cardiopulmonary support.

(2) Sodium citrate (10 grams for patients <40 kg, 20 grams for patients> 40 kg)

Citrate is an anticoagulant that prevents the formation of blood clots that can interfere with blood circulation and cryoprotective perfusion. When chelating calcium, it also prevents the heart’s self-induction and functions as a neuroprotector. It is administered as a custom formulation of 20% sodium citrate in water, packed in 50 ml sterile vials.

(3) Heparin (50,000 IU – fixed dose)

Heparin is an anticoagulant that prevents the formation of blood clots that can interfere with blood circulation and cryoprotective perfusion. Heparin loses effectiveness at a low pH (pH <6.7), so pH control is important during cryonic stabilization. That is why other anticoagulants are also important.

(4) Vasopressin (40 IU, fixed dose – second dose of 40 IU concurrent with Vital-Oxy)

Vasopressin is a vasopressor that is used to increase blood pressure during cardiopulmonary support. There is no need to administer vasopressin if the patient’s temperature is close to or below +20 ° C at the time of administration, as it is not effective at low temperatures.

(5) Minocycline (200 mg – fixed dose)

Minocycline is a broad spectrum bacteriostatic antibiotic and a free radical scavenger with good tissue and brain penetration that possesses a wide variety of neuroprotective properties, including inhibition of metalloproteinases, iNOS, PARP, mitochondrial cytochrome release and apoptosis .

(6) SMT (S-metilisotiourea) (400 mg – fixed dose)

SMT is a neuroprotector (iNOS inhibitor) that is used to protect the brain from ischemic injury. SMT also increases blood pressure.

Large volume medications

(7 and 10) Decaglycerol / THAM (2 x 200 ml – 

Fixed dose) Deglycerol is a glycerol polymer used to osmotically inhibit a cerebral edema similar to mannitol. THAM is a buffer used to mitigate acidosis. Decaglycerol / THAM is administered as a customized formulation of 20% w / v decaglycerol and 4.5% w / v THAM (tromethamine) in water, packed in 2 sterile 200 ml vials. The first dose of 200 ml should be administered (IV injection) after completing the administration of small-volume medications, and the second dose of 200 ml should be administered after the completion of all other medications.

(8) Vital-Oxy (formerly known as Oxynil) (approximately 700 ml – administer 6 ml / kg)

Vital-Oxy is a patented emulsion from Critical Care Research, Inc., of the antioxidants melatonin, vitamin E (such as D-alpha tocopherol), PBN (alpha phenyl t-butyl nitrona) and the anti-inflammatory agent carprofen.

Fluids that require gastric administration.

(9) Maalox (250 ml – fixed dose)

Maalox is an antacid that is used to stabilize the pH of stomach contents to prevent erosion of the stomach wall by hydrochloric acid at low temperatures. Failure to prevent this can lead to contamination of the circulatory system with stomach contents and abdominal swelling during subsequent perfusion.

Optional (only occurs when the patient is dehydrated)

(11) Hetastarch (250 ml – fixed dose)

Hetastarch is a volume expander that is used to restore volume in dehydrated patients and increase cerebral perfusion during CPS.

Wash medication (add to the wash solution before remote blood wash or the first cryoprotector wash in the operating room)

(12) Streptokinase (250,000 IU – fixed dose)

Streptokinase is a thrombolytic that is used to break existing blood clots that can interfere with blood circulation and cryoprotective perfusion. 
If there is a delay of more than one hour after the cardiac arrest, an abbreviated list of medications must be administered.

        1. Sodium citrate (10 grams for patients <40 kg, 20 grams for patients> 40 kg)  
        2. Heparin (50,000 IU – fixed dose)  
        3. Tempol (5 g – fixed dose – dissolved in 20 ml of normal saline ). Tempol is a low molecular weight superoxide scavenger that is used to mitigate the damage caused by free radicals induced by ischemia. It is used only in the abbreviated protocol. 
        4. Minocycline (200 mg – fixed dose)  
        5. Decaglycerol / THAM (200 ml – Fixed dose)  
        6. Maalox (250 ml – Fixed dose – for gastric administration) 
        7. Streptokinase (250,000 IU – fixed dose – add to the wash solution before remote blood wash or the first injection of cryoprotection in the operating room)

The administration of these medications must be followed by at least ten minutes of chest compressions to distribute the medications, accompanied by cooling of the surface.

Vasopressors, such as epinephrine or vasopressin, should be administered intermittently to ensure greater cerebral blood flow. SMT also increases blood pressure. The effects of these medications can be assessed through the use of final tidal CO2 monitoring. The protocols can reduce the administration of vasopressors to a limited number of discrete injections to simplify.

Maalox is not introduced into the circulatory system but into the patient’s stomach. This requires the placement of the King LTS-D double lumen airway or a designated gastric tube. Unless it is not possible to place the King LTS-D airway, the King LTS-D airway is the preferred method for the administration of Maalox because it allows simultaneous ventilation. Maalox should only be administered through the gastric tube inserted into the posterior channel of the KING LTS-D airway if the team leader has received confirmation that the KING LTSD has not been accidentally placed in the trachea. A gastric tube should only be placed by an experienced medical professional.

If Alcor fails to persuade the patient’s caregivers to leave an intravenous line in place, the preferred method of drug delivery is intraosseous infusion. If intraosseous infusion is not available or is contraindicated for the patient, a member of the experienced team should place a peripheral IV line. Central IV lines should only be placed by qualified medical professionals. Techniques such as pressure infusion should only be used by people with extensive experience such as paramedics.

The preparation of the drugs must begin at least one hour before the estimated time of circulatory arrest or on the way to the patient if it has already been pronounced. The compounds that have been prepared in the company in Alcor must be sterilized by filtration before its administration.

In cases where team members are not sure of the dose, administration methods or other problems, they can contact the Alcor medical adviser, who must be available by phone at all times during the wait, stabilization and recovery. patient transport. Team members should not improvise on their own initiative.

The initiation of blood wash or cryoprotective infusion should not be delayed to complete the administration of medications. If the administration of the remaining drugs is still considered desirable, they can be added to the organ preservation solution during the perfusion.

Streptokinase should be added to the wash solution in the case of a remote wash or during the first discharge before the cryoprotective perfusion in Alcor.

Remote blood substitution

In remote cases, the replacement of blood with an organ preservation solution prior to transport at hypothermic temperatures is desirable unless it is logistically impossible to do so. The remote replacement of blood has the following objectives:

        1. Rapid induction of ultra-deep hypothermia.

        2. Prevention of coagulation, accumulation of red blood cells and “no reflow.”

        3. Maintain the viability of the brain during transport.

Alcor uses an air-transportable perfusion circuit (ATP) or, if available, the Stockert SCPC portable clinical perfusion system, to replace the patient’s blood. The organ preservation solution of choice in Alcor is MHP-2. MHP-2 is an intracellular hyperosmolar asanguine whole body preservation solution.

To facilitate rapid cooling, MHP-2 should be kept as close as possible to the freezing point of the water (0 degrees centigrade). An integrated heat exchanger in the ATP circuit is designed to reduce the temperature to near freezing, if necessary, before the solution enters the patient. Heparin and insulin should be added to MHP-2 during extracorporeal circulation. At this point, any remaining stabilization medication (with the exception of Maalox) can also be injected into the circuit.

Remote blood washing should only be performed in the absence of contraindications to this procedure. The contraindications for the remote replacement of the blood vary from pathologies of the patient “pre-mortem” to practical and logistical challenges:

Contraindications for remote blood replacement

  • More than six hours since the legal death occurred.
  • Failure to substitute blood remotely will significantly reduce transport time.
  • Arriving at the nearest funeral home or other place that allows blood replacement will result in excessive cardiopulmonary support times
  • There are no team members with extensive experience and knowledge of cardiopulmonary bypass present in the case
  • Inspection of blood organ preservation solution (MHP2) reveals bacterial growth
  • Inspection of the composition of the blood organ preservation solution suggests errors in the composition of the perfusate
  • The presence of systemic edema (accumulation of fluid throughout the body) that may have occurred during cardiopulmonary support
  • Active gastrointestinal hemorrhage at the time of cardiac arrest.
  • Prolonged splanchnic ischemia or severe abdominal swelling
  • Severe pulmonary edema
  • Severe cerebral edema
  • Prolonged periods of warm cerebral ischaemia

To facilitate a smooth transition from cardiopulmonary support to blood replacement, Alcor will normally attempt to deploy a team of at least two people to a funeral home that cooperates to set up and prime the perfusion circuit. These team members must also obtain additional ice to further cool the patient and to use it as a means of heat exchange during blood washing. In some cases (eg, home hospice), remote blood replacement at the bedside is possible. This option should be discussed in advance with the patient, the patient’s medical substitute, and the medical caregivers.

Remote blood replacement requires surgery and cannulation of the patient’s main blood vessels. The preferred procedure in Alcor is the femoral-femoral cannulation. Most surgical alternatives to femoral cannulation can cause complications during cryoprotective perfusion and should only be performed by experienced surgeons in the absence of contraindications for remote blood replacement.

The interruption of circulation should be minimized during surgery. This is particularly important if the surgery starts when the patient’s core body temperature is still close to body temperature. If prolonged interruptions of circulation are expected during surgery, the procedure should not be initiated until the patient’s core body temperature has been reduced to 20 degrees centigrade. The cooling should never stop during surgery; The patient must remain surrounded by ice.

As a general rule, Alcor refrains from remote blood replacement if there are no experienced clinical or research surgeons on the team (unless it is determined that the director of a local funeral has the necessary experience to perform the surgery and cannulation ). Alcor paramedic personnel have received the necessary surgical training and qualified surgeons for cryonic vascular access can also be provided by Suspended Animation, Inc., or Critical Care Research, Inc., under contract with Alcor. If there is uncertainty or debate about the presence of any of the contraindications, Alcor will refrain from remote blood substitution.

Remote blood replacement should only be started when there is a functional ATP or a conventional perfusion circuit present. The use of embalming pumps is not allowed because such pumps do not allow adequate control and monitoring of the pressure.

The purpose of the initial stage of blood replacement is to wash the patient’s blood. When the patient’s venous effluent indicates that the blood has been washed (as evidenced by a light color or no change in color), the ATP goes from “open circuit” (wash) to “closed circuit” (recirculation) mode , and MHP-2 continues to circulate through the heat exchanger until the patient’s core temperature approaches the freezing point of the water. In general terms, the ATP stops when the core patient’s temperature falls below 5 degrees Celsius, although the procedure can be aborted before this point if there is a special advantage in doing so, such as the need to coincide with air transport schedules available

If it is practical to do so, the patient should be weighed before and after completing the blood replacement if this capacity is available in a funeral home.

Transport of patients

For cases where the patient’s location can be accessed more quickly, in general, by land than by air, Alcor employs an emergency vehicle that maintains at least all the equipment available for remote stabilizations. Periodic inventory checks and driving tests should ensure that the emergency vehicle is always available for case work. In a typical local case, the Alcor vehicle is parked near the patient’s location. During standby mode, the vehicle can also be used to draw medicines and assemble equipment. The vehicle is equipped with a lift gate to transfer the portable ice bath to the vehicle. The parking should allow enough space for the elevator door to work.

If the patient is outside the practical range of the Alcor emergency vehicle, the patient will be transferred to the Alcor operating room by a scheduled airline or, if the appropriate financial arrangements have been made, by air ambulance. The patient is placed in a case for sending “corpses” (often a “Ziegler” case). The Ziegler case is insulated and placed in a box that is normally used for air shipping and must be available in any morgue.

The reserve team must be very careful to ensure that the case does not leak water or body fluids, as these events may cause the shipment to be removed from the aircraft and be retained for inspection. To prevent leakage of body fluids, the patient should be placed in a body bag surrounded by ice inside the Ziegler case. To prevent the water from melting from melting, ice should be placed in large Zip Loc bags (2.5 gallons).

The amount of ice must be sufficient to allow at least 48 hours of transport. This amount will vary according to the patient’s weight and body temperature at the time of shipment, subject to the different ice restrictions imposed by different airlines. A table can be provided for guidance on this topic.

If the ice has been stored in a freezer, care should be taken that it has warmed to 0 degrees Celsius and is actively melting before packing with a cryonics patient. If an ice pack has visible white frost, it is too cold to use. Bags that are suspected of being too cold should be heated with water until all the ice inside is visibly moist and melting.

If the airline regulations do not allow the patient to send water ice, hypothermia can be kept in cold packs. Alternatively, Terra-Sorb hydrogel crystals can be mixed with ice in bags, using 2 teaspoons of hydrogel crystals per gallon of ice. This will turn the liquid water into a gel that can not be filtered. Like ice packs, cold packs and hydrogel ice packs should always be warm enough so they do not have frost. The condensation of liquid water in bags or ice bags in the air of the room is normal and expected.

At least one member of the team must be on the same plane as the patient to intervene with the airline personnel and act as the patient’s advocate if delays or unexpected complications occur. The patient’s temperature must be recorded during transport. This temperature recorder should not be the same as the one used during the stabilization, to avoid losing data during transport or handling.

Monitoring of stabilization procedures.

A reserve team must include a designated scribe. The main task of the scribe is to collect data and record observations during the case. At a minimum, the scribe must record and describe all relevant events during a case, including the following:

Deployment and case preparation. 
Medical data of the patient obtained from caregivers. 
Legal death pronouncement time. 
Start and end of stabilization procedures. 
Start and end of cardiopulmonary support. 
Start and end of the initial cooling. 
Time of placement IV 
Time of administration of all medications and fluids. 
Intermittent temperature data 
Start and end of surgery. 
Start and end of blood replacement. 
Intermittent pressure data during blood replacement. 
Any interruption of unusual procedures and events.
Start and end of patient preparation for transport. 
The nasal and rectal temperatures should be recorded from the beginning of the stabilization procedures until the stabilization procedures are completed.

Final measurements of tidal CO2 should be collected during cardiopulmonary support. If available, a final digital CO2 should be used because more detailed information is provided on the effectiveness of cardiopulmonary support.

If sufficient personnel and experience are available, blood samples (blood gases and electrolytes) should be collected immediately after the declaration of legal death and at intermittent points during the stabilization procedures. These samples should be sent to a laboratory for independent analysis.

Before the start of blood substitution, a sample of the organ preservation solution must be collected for internal quality assurance purposes.

It is important to keep in mind that a scribe should go beyond simply writing numbers. All kinds of observations are valuable and, in fact, can be crucial, at a later date, to understand what happened during a case and why. In addition, we strongly believe that photographs and videos of procedures should be created to document a case, provided that interested parties, such as family members, medical staff and funeral home staff, allow it. While some people have expressed concern that visual materials may be stolen or placed in public forums, we believe they can protect the cryonics organization and its staff by demonstrating that the procedures were carried out in a thorough manner. If there is anxiety about possible theft of records, Surely the answer to this problem is to protect the records against theft, instead of stop creating records. Alcor’s registration documents clearly establish that cryonics is an experimental procedure. Any experimental procedure should be documented as completely as possible, so that others can learn from it and procedures can be improved.

At a minimum, the team leader must be equipped with a voice recorder to document important events as they occur. Record notes and voice recordings are essential to build a correct timeline of the case. A separate record sheet is available for data collection during the terminal phase. All record sheets and voice recordings must be turned in to designated Alcor representatives after the case is completed, and a signed formal acknowledgment of receipt must be obtained.

Cryoprotective perfusion

Cryoprotective perfusion is the central procedure of the Alcor human cryopreservation protocol. Without the introduction of a vitrification solution, extensive damage to the brain must be expected. To achieve a good morphological conservation of the brain, the blood (or organ preservation solution) in the patient is replaced by a vitrification solution. The Alcor vitrification solution, M22, is licensed by 21st Century Medicine, Inc. It is the least toxic vitrification solution known in the peer-reviewed literature for its concentration, and provides strong protection against the formation of ice at low speeds. cooling.

The concentration of these solutes of LM5 is the same in the perfused base (perfusate of initiation), and the M22 solution that is added to the perfused base, so that the concentration of these solutes of the LM5 carrier solution remains constant throughout the cryoprotective perfusion process.

After arriving at the facilities of Alcor, a median sternotomy will be performed to cannulate the great vessels of the heart (aorta and right atrium) for patients throughout the body. Vascular access surgery for the whole body or neuropatients in Alcor is usually performed by a contracted surgeon.

If cardiopulmonary support (CPS) should be stopped during surgery, it is desirable that the patient be cool enough for the brain to suffer minimal additional injury during the interval of interruption of blood circulation. The usual rule during the years 2013 to 2018 has been to continue with the CPS until the patient’s temperature reaches + 20 ° C or the cooling rate of the brain decreases to approximately 0.1 ° C / minute, whichever comes first. This is a temperature cold enough for the brain to suffer minimal injury according to current medical criteria, even if the circulation stops for 30 minutes. The fastest surgical methods to reduce the times of circulatory arrest to just ten minutes may allow the CPS to stop and the surgery to begin,

Once the surgical cannulation is completed, the first step is to wash the blood (or the previous organ preservation solution) with base perfusate B1. B1 consists of LM5 plus 1 mM dehydrated calcium chloride, plus 2 mM magnesium chloride hexahydrate, plus a patented additive that reduces edema.

Once this step is completed, the concentration of M22 solutes in the carrier solution should be increased slowly in a linear manner by progressively adding “M22 concentrate” (1.25 times the normal concentration of non-carrier solutes M22 in the LM5 carrier solution) to the circulation . Perfuscated base B1. The objective is to linearly increase the concentration of cryoprotectants in the circulating perfusate so that the arterial concentration of the M22 solutes reaches 50% of the target concentration in 100 minutes. The target concentration is the concentration of M22 solutes shown in the previous M22 composition table, a concentration that can be created in the laboratory to calibrate the refractometer by diluting a sample of M22 concentrate (1.

When the concentration of arterial cryoprotectant reaches 50% of the target concentration, the rate of addition of the concentrate should be reduced to maintain the arterial concentration close to 50% while the venous concentration is recovered. During this time, the arterial perfusion temperature should fall from about +3.5 degrees Celsius to -3 degrees Celsius. When the M22 venous effluent approaches 50% of the target nominal concentration of M22 measured by the manual inspection of the refractive index, the concentration of M22 should be increased rapidly between 100% and 105% of the target concentration. The cryoprotective perfusion is completed when the concentration of the venous effluent reaches 100% of the target and there is little fluctuation in the refractive index of the venous effluent.

In neuro patients, only the head is perfused through the carotid arteries. This procedure allows for faster cooling rates, bilateral monitoring of the brain and has been observed to produce reduced hole drainage and facial edema. If there is evidence that the Circle of Willis is incomplete or damaged, the vertebral arteries must also be cannulated. Otherwise they are fastened. During the isolated perfusion of the head, the head is secured in a cephalic chamber and the venous return is filtered before being partially returned to the patient.

The perfusion pressure during cryoprotective perfusion should not exceed 100 mmHg for both neuro and whole body patients, measured in the arterial line. Because the cryoprotectant concentration and the lower temperatures increase the viscosity, the speed of the pump must be reduced several times during the course of the perfusion. . Not exceeding 100 mm Hg is particularly important in patients with ischemia and patients with cerebral inflammation. Infusion pressures below 80 mmHg should be avoided.

In all cases, Alcor introduces its vitrification solution by increasing the concentration of the cryoprotective components in a linear fashion to avoid the osmotic lesion that would occur when the cells are hit with a solution of high molar strength. The M22 concentrate is gradually introduced into a mixing tank where the solution is continuously mixed with the perfusate base B1 previously perfused before it is introduced to the patient. The venous effluent is partially discarded (to maintain the volume of the mixing tank when the M22 concentrate is added) and is partially returned to the mixing tank to ensure a linear increase of the ramp and to reduce the volumes of M22. In patients of the whole body, the circuit should also include a cardiotomy suction device to recover the lost perfusion of the patient’s thoracic cavity. A sub-zero heat exchanger should be used to lower the perfusion temperature below 0 degrees Celsius. In Alcor, LabView software monitors perfusion behavior.

Cryoprotector perfusion monitoring

The tracing and monitoring continue during the cryoprotective perfusion. The collection of important data is automated, but the scribe must make an effort to document the flow of the case and record the data manually, including all events that may be relevant. At a minimum, the scribe must record the following:

Preparation and start-up of the cryoprotective perfusion circuit. 
Time of arrival of the patient. 
Start and end time of the surgery. 
Start of blood wash / perfusion 
Start of cryoprotective perfusion. 
Intermittent pressure 
readings Intermittent flow readings Intermittent 
patient temperature and perfusion data. 
Manual measurements of the refractive index. 
Any interruption of unusual procedures and events. 
Completion of the cryoprotective perfusion.
Visual data is even more important, during cryoprotective perfusion, than during field work. Alcor maintains a video camera that monitors events from a fixed position, but its record must be complemented with photographs and videos of handheld cameras that show details of the first surgical procedures, cannulation, visible brain shrinkage through holes and other data .

The state of the brain is visually monitored through two small holes in the skull (hole holes) made with a standard neurosurgical tool (Codman driller of 14 mm). This allows observation of the osmotic response of the brain. A brain with a substantial ischemic lesion becomes inflamed, indicating an interruption of the blood-brain barrier, damage to endothelial cells or compromise of water regulation of cells.

During cryoprotective perfusion, LabView software collects cryoprotectant concentration data from in-line refractometers. These measurements can be consulted to observe trends, but they should not be used to make decisions. Protocol decisions should be guided by manual refractive index measurements that are analyzed by desktop refractometers or digital hand-held refractometers.

If it is practical to do so, in cases of neuropreservation, the cephalon should be weighed before and after the completion of the cryoprotective perfusion.

Cryoprotective perfusion is the central procedure of the Alcor human cryopreservation protocol. Without the introduction of a vitrification solution, extensive damage to the brain must be expected. To achieve a good morphological conservation of the brain, the blood (or organ preservation solution) in the patient is replaced by a vitrification solution. The Alcor vitrification solution, M22, is licensed by 21st Century Medicine, Inc. It is the least toxic vitrification solution known in the peer-reviewed literature for its concentration, and provides strong protection against the formation of ice at low speeds. cooling.

The concentration of these solutes of LM5 is the same in the perfused base (perfusate of initiation), and the M22 solution that is added to the perfused base, so that the concentration of these solutes of the LM5 carrier solution remains constant throughout the cryoprotective perfusion process.

After arriving at the facilities of Alcor, a median sternotomy will be performed to cannulate the great vessels of the heart (aorta and right atrium) for patients throughout the body. Vascular access surgery for the whole body or neuropatients in Alcor is usually performed by a contracted surgeon.

If cardiopulmonary support (CPS) should be stopped during surgery, it is desirable that the patient be cool enough for the brain to suffer minimal additional injury during the interval of interruption of blood circulation. The usual rule during the years 2013 to 2018 has been to continue with the CPS until the patient’s temperature reaches + 20 ° C or the cooling rate of the brain decreases to approximately 0.1 ° C / minute, whichever comes first. This is a temperature cold enough for the brain to suffer minimal injury according to current medical criteria, even if the circulation stops for 30 minutes. The fastest surgical methods to reduce the times of circulatory arrest to just ten minutes may allow the CPS to stop and the surgery to begin,

Once the surgical cannulation is completed, the first step is to wash the blood (or the previous organ preservation solution) with base perfusate B1. B1 consists of LM5 plus 1 mM dehydrated calcium chloride, plus 2 mM magnesium chloride hexahydrate, plus a patented additive that reduces edema.

Once this step is completed, the concentration of M22 solutes in the carrier solution should be increased slowly in a linear manner by progressively adding “M22 concentrate” (1.25 times the normal concentration of non-carrier solutes M22 in the LM5 carrier solution) to the circulation . Perfuscated base B1. The objective is to linearly increase the concentration of cryoprotectants in the circulating perfusate so that the arterial concentration of the M22 solutes reaches 50% of the target concentration in 100 minutes. The target concentration is the concentration of M22 solutes shown in the previous M22 composition table, a concentration that can be created in the laboratory to calibrate the refractometer by diluting a sample of M22 concentrate (1.

When the concentration of arterial cryoprotectant reaches 50% of the target concentration, the rate of addition of the concentrate should be reduced to maintain the arterial concentration close to 50% while the venous concentration is recovered. During this time, the arterial perfusion temperature should fall from about +3.5 degrees Celsius to -3 degrees Celsius. When the M22 venous effluent approaches 50% of the target nominal concentration of M22 measured by the manual inspection of the refractive index, the concentration of M22 should be increased rapidly between 100% and 105% of the target concentration. The cryoprotective perfusion is completed when the concentration of the venous effluent reaches 100% of the target and there is little fluctuation in the refractive index of the venous effluent.

In neuro patients, only the head is perfused through the carotid arteries. This procedure allows for faster cooling rates, bilateral monitoring of the brain and has been observed to produce reduced hole drainage and facial edema. If there is evidence that the Circle of Willis is incomplete or damaged, the vertebral arteries must also be cannulated. Otherwise they are fastened. During the isolated perfusion of the head, the head is secured in a cephalic chamber and the venous return is filtered before being partially returned to the patient.

The perfusion pressure during cryoprotective perfusion should not exceed 100 mmHg for both neuro and whole body patients, measured in the arterial line. Because the cryoprotectant concentration and the lower temperatures increase the viscosity, the speed of the pump must be reduced several times during the course of the perfusion. . Not exceeding 100 mm Hg is particularly important in patients with ischemia and patients with cerebral inflammation. Infusion pressures below 80 mmHg should be avoided.

In all cases, Alcor introduces its vitrification solution by increasing the concentration of the cryoprotective components in a linear fashion to avoid the osmotic lesion that would occur when the cells are hit with a solution of high molar strength. The M22 concentrate is gradually introduced into a mixing tank where the solution is continuously mixed with the perfusate base B1 previously perfused before it is introduced to the patient. The venous effluent is partially discarded (to maintain the volume of the mixing tank when the M22 concentrate is added) and is partially returned to the mixing tank to ensure a linear increase of the ramp and to reduce the volumes of M22. In patients of the whole body, the circuit should also include a cardiotomy suction device to recover the lost perfusion of the patient’s thoracic cavity. A sub-zero heat exchanger should be used to lower the perfusion temperature below 0 degrees Celsius. In Alcor, LabView software monitors perfusion behavior.

Cryogenic cooling

After completing or terminating the cryoprotective perfusion, the patient will be prepared for cryogenic cooling. A “crackphone” is placed in contact with the surface of the brain to soundly detect subsequent fracture events. Patients from the whole body should be transferred to a large isolated cooling box, and neuro patients to a small dewar. The cooling process is controlled by software. Liquid nitrogen is injected into the cooling or warming box and vaporized, extracting heat from the patient. A fan circulates the steam to further improve cooling. The temperature drops rapidly to a temperature between -80 degrees Celsius and -110 degrees Celsius. That temperature is maintained at that plateau for 12 hours to allow the thermomechanical relaxation of the tension, and then descends more slowly for 100 hours to minimize thermal stress and fracture. In a neuro case, the final descent of around -190 degrees Celsius to -196 degrees Celsius is achieved by gradually filling the dewar with liquid nitrogen. In cases of the entire body, the patient is transferred to a Bigfoot dewar in a precooled sleeping bag for the final descent to the liquid nitrogen temperature. Because whole-body transfers are performed at room temperature, good logistical preparation and minimizing transfer time is essential. The final descent of around -190 degrees Celsius to -196 degrees Celsius is achieved by gradually filling the dewar with liquid nitrogen. In cases of the entire body, the patient is transferred to a Bigfoot dewar in a precooled sleeping bag for the final descent to the liquid nitrogen temperature. Because whole-body transfers are performed at room temperature, good logistical preparation and minimizing transfer time is essential. The final descent of around -190 degrees Celsius to -196 degrees Celsius is achieved by gradually filling the dewar with liquid nitrogen. In cases of the entire body, the patient is transferred to a Bigfoot dewar in a precooled sleeping bag for the final descent to the liquid nitrogen temperature. Because whole-body transfers are performed at room temperature, good logistical preparation and minimizing transfer time is essential.

If cryoprotective perfusion is not possible, ice formation will start below 0 degrees Celsius. As a result, a uniform and slow cooling speed (to minimize thermal stress caused by uneven cooling) can be maintained over the entire temperature range.

The software collects the temperature and crackphone data during the cooling process.

Long-term care

After cooling to the temperature of liquid nitrogen (-196 degrees Celsius), the patient is kept in a vacuum isolation war until a time in the future when resuscitation can be considered feasible. The long-term care dewars must be equipped with level sensors and alarms. Dewar recharges must follow a systematic and documented program.

Reports and reports of cases

After participating in the case, team members must send record sheets, recordings and other notes to Alcor. Alcor must schedule an informational session with all the participants and advisors of the case as soon as it is convenient after completing the case. The purpose of the report is to discuss the strengths and weaknesses of the case in an analytical way, without confrontation. The information session should be documented, and a transcript should be circulated among the participants to verify its accuracy and completeness. In general, the summary document should include a list of the action items that must be completed. A follow-up meeting must be scheduled to determine the progress of these elements. These elements of action and their completion must also be documented in the case report.

A case report must be generated, including all pertinent details. Alcor may decide to retain some information to protect the patient’s privacy. Case reports should be completed within 2 months of the case and should follow a general template to allow meaningful comparisons between cases and meta-analysis.

Once the case is completed, the reserve coordinator and other staff members should give priority to preparing Alcor for future cases. The equipment must be recovered, cleaned and restored, and consumable supplies must be replaced. This unattractive routine work is obviously vital to maintain the capacity for future response.

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