26 replies to this topic

[Matthias]

Die gepackte Version

Edited by Matthias, 27 May 2008 - 12:09 AM.

[Matthias]

Instructions for Stabilisation for


Second edition (b)

Edited by Matthias, 27 May 2008 - 12:10 AM.

[Matthias]

Introduction

This will be a rather simplistic and I hope easy to understand introduction into a cryonic suspension. I hope to show how much your input can help make the journey to future technology as smooth as we know how at this time. A little training can make a BIG difference.

Edited by Matthias, 26 July 2008 - 06:03 PM.

[Matthias]

Stabilization Protocol


Assuming cooperation is available, make sure all intravenous lines (IV lines) are left in the patient; this will help later to administer the medications.

(1) Obtain permission to take charge of patient
(2) Contact the undertaker advised by Cryonics UK or chosen by the patient to arrange for them to collect the patient or for us to deliver to them.
(3) Place patient into portable ice bath, using the specially designed sling in the ice bath kit (or a sheet in a emergency). With the patient in the middle one person stands at each end (or one on each corner if four people are available) and lift making sure the ice bath is as close to the bed as possible.
(4) Start cardiopulmonary support (CPS) either by hand or with the aid of a heart-lung resuscitator -commonly known as a Thumper.
(5) Insert medications as per list and continue with CPS for at least 10 minutes after the last of the medications have been administered.
Place the squid Cooling Device in the ice bath to achieve even cooling and transport to a facility for cryoprotectant to be administered.

[Matthias]

Medication

It is always difficult to be precise when cardiac arrest is expected but the hospital staff will have had far more experience than us & will be able to help with the timing. Even if the patient arrests before expected you should have had enough training to be able to draw the medication in a few minutes.

It is recommended that you spend your time laying out and familiarising yourselves with the medications. No matter how much training you have, unless you are a trained nurse, or, as we recommend, have a nurse on hand, you will find it an entirely new ball game under pressure.

Keep as calm as you can, do your best; cock ups do happen & things do get forgotten. Even the most experienced people I know in cryonics make mistakes so don’t feel bad, just get on with the job and remember your training.
At a later stage I will go into greater depth about what the various medications do but at this stage I think just familiarising the names will be enough.
Medication and dosage table – will have to be maintained as supplies change

	Pk-No	Medications	DosageRequired (units/patients weight in kg)	Patients Weight/kg	Medication Suppliedconcentration (units/ml)	Vol To give/ml
1	1	Potassium Chloride	2*20ml Vials
2	1	Propofol (Dipridan)	20ml ampule
3	1	Vacuron	10ml
4	2	Sodium Heparin	2*4ml vials
5	3	Streptokinase	1000 U
6	3	Sodium Chloride	20ml vials
7	4	Epinephrine	1*30ml vial
8	5	Deferoxamine (Desferal)	4*500mg vials in all
9	6	Chlorpromazine (Thorazine)	1*10ml vial
10	6	Methylprednisolone or Solu-medrol	1 *8 ml vial
11	7	Gentamicin Sulphate	1*2ml vial
12	7	Bactrium	10 ml vial
13	7	Erythromycin	1 gram vial
14	8	Tagamet	2*2ml vials
15	9	Maalox	355cc
16	Sep	Tham	500 Ml
17	Sep	Mannitol	500 Ml
18	Sep	Dextran 40	500 Ml
19	Sep	Sodium Bicarbonate	6* 50ml syringes

To use the meds table to calculate the volume of medication to administer enter the patient’s weight in kilograms (2.2 pounds = 1kg, 14 pounds = 1 stone) and ensure that the medication supplied concentration column is up to date and correct (i.e. all in units/ml). Then multiply the dosage required by the patient’s weight and then divide by the medication supplied concentration: the answer should be the volume to give in millilitres.
You will however have ready-made tables in your medical case.

Edited by Matthias, 15 September 2005 - 06:32 PM.

[Matthias]

ABBREVIATED EMERGENCY INSTRUCTIONS

If pronounced for more than 60 minutes unattended


If the patient has been pronounced dead and has experienced a period of more than 60 minutes without cardiopulmonary support carry out the procedure below. (If rigor mortis is present do NOT administer medication and go to (3)

(1) Carry out sternal compression (or thumper) at the rate of 60 per minute during and for 5 minutes after the administration of the following medications.

(2) Administer the abbreviated medications

(3) Cool the patient as quickly as possible as per instructions.

:

  Medication		Dosage		Patient 	Medica-		Volume 

			required	weight /kg	tion		to give 

			(units/patient 	concentration	supplied	/ ml

			weight in kg)	(units/ml)



1 Sodium Heparin	2*4Ml vials			

2 Streptokinase		30,000 U 			

  			(2,250,000 in all)

3 Deferoxamine HCl	4*500mg vials			

4 Chlorpromazine	1*10ml vial			

5 Methylprednisolone 	1*8ml vial 			

  (by slow injection)

6 Erythromycin or Keflex1*1gram vial			

8 Maalox or Riopam 	355cc			

  or Titralac

Full training is given to the transport team in all aspects of the recovery and patient’s care and this is only a broad outline of requirements.

Edited by Matthias, 15 September 2005 - 06:53 PM.

[Matthias]

Equipment

For a local cryonics group to provide adequate assistance for members and in many cases friends can seem a daunting task.

Keeping a local kit supplied with up-to-date medications and gas bottles for the thumper is not an easy task, and may seem fruitless when they are so rarely used but it is essential and at C/UK we have a very comprehensive kit which must be checked on a regular basis.

The "perfectionist" mentality of many cryonicists leaves them feeling that since they cannot afford all the necessary equipment, it is preferable to do nothing and hope that a slow death and a flown-in remote standby team can handle the situation.

I think this VASTLY understates the value of temperature-reduction in light of the enormous decrease in ischemic damage, which also occurs, with a lowering of temperature (see ischemic damage).


In den USA wird Kryonik von gemeinnützigen Gesellschaften (Alcor, Cryonics Institute) angeboten. Dort können sich Menschen nach dem eigenen Ableben in Kryostase begeben. Die erste kryonische Suspension wurde am 12. Januar 1967 an James Bedford durchgeführt, der heute bei Alcor aufbewahrt wird.[2] In Russland gibt es neuerdings (2006) den kommerziellen Anbieter KrioRus. In Deutschland hingegen gibt es wegen des Friedhofszwangs keine rechtliche Grundlage dafür.[3] Folglich wird diese Dienstleistung in Deutschland lediglich für Tiere (üblicherweise Haustiere) angeboten.

Good capabilities would seem to require an awesome commitment of time & money for equipment & training.

Edited by Matthias, 26 July 2008 - 06:05 PM.

[Matthias]

How cold is cold enough?

Please note there is a full explanation of these calculations a latter version but I thought for those who are not mathematicians it would be advisable to have a pocket size version.

Deterioration starts the moment ischemia begins. The colder the patient, the slower they deteriorate.

This chart shows the relationship between time and deterioration and shows `once again how important it is to have a standby team.


Time = deterioration

Temperature Time Equivalent to

Celsius Kelvin 1 Second 1 Hour
At 37 C (body temperature) Remarks
___________________________________________________________
37 = 310.16 1 second 1 hour Body Temperature
20 = 293.16 1.9 sec 1.9 hours
0 = 273.16 4.7 sec 4.7 hours Water freezes
- 20 = 253.16 13 sec 13 hours
- 40 = 233.16 43 sec 43 hours
- 60 = 213.16 2.9 min 6.5 days
- 65 = 208.16 4.4 min 11 days Limit of a domestic freezer
- 79.5 = 193.66 15 min 39 days Dry Ice
- 128 = 145.16 4.7 days 46 years Freon boils
- 195.8 = 77.36 22 million years 79 billion years Liquid nitrogen

[Matthias]

Understanding Ischemic Damage

At the beginning I told you I hoped it would be easy to understand, well for anyone new this may stretch the little grey cells a little but don’t get despondent it will all make sense eventually.

Most cryonics patients are victims of some degree of ischemia, i.e., tissue damage as a result of oxygen & nutrient deficiency following failure of blood circulation.

This may happen during the dying process or following cessation of heartbeat often both.

Even under the best circumstances, it is difficult to restore circulation to levels provided by a normal heartbeat.

An ideal cryonics patient would suffer no ischemic damage.

Such a patient would be in good health prior to a sudden-onset of the fatal event, no brain tissue would have been affected.

The event would not be sudden; a cryonics transport team would be on site at the moment of legal declaration of death.

Upon legal death, cool down and restoration of circulation would begin immediately, followed by blood washout, perfusion with cryoprotectant solution and cooling to liquid nitrogen temperature, so this must be our goal.

It has been shown that when a patient was cryopreserved with up to 60 minutes of global ischemia they showed good ultra structure.

Some signed-up cryonicists may not be so lucky, but as a transport team we must do our very best to reduce damage,

THIS WILL WORK BEST IF WE WORK AS A WELL OILED MACHINE, training, training and when we are really fed up with training yes more training until we can do a stand by without thinking.

Cryonicists have focused a great deal of attention on freezing damage and the potential of future science to repair that damage.
The rationale for this argument is good, namely, that freezing damage is much like a broken window, the pieces are still there, and molecular repair technology may be able to re-assemble them.

But ischemic damage could be potentially much more serious leading to such degradation of structure that no future technology could possibly reconstruct.

It may be that the prevention of ischemic damage may be the key critical factor toward future reconstruction of cryonics patients.
Concern with freezing damage could fatally distract attention from this fact.

With this in mind, it is worth discussing what happens to brain tissue during ischemia.

[Matthias]

MECHANISMS OF BRAIN-TISSUE ISCHEMIC DAMAGE

Ischemia results in lowered oxygen & glucose delivery to brain tissue. As a result, cells have less ATP production, (Adenosine Tri Phosphate) i.e., less available energy.

This not only damages the membrane, it releases the toxic free fatty acid arachidonic acid, which forms substantial amounts of oxygen free radicals.
Calcium can enter a cell through voltage-controlled ion channels of the L-type (long-lasting) or the N-type. Calcium can also enter a cell through agonist-controlled ion channels the agonist in question being the neurotransmitter glutamate.

Zur Lagerung wird der Organismus bzw. das Organ üblicherweise bei −196 °C in flüssigem Stickstoff gekühlt. Dies führt zur Frakturierung des Gewebes bei −150 °C. Da es sich hierbei lediglich um wenige, makroskopische Brüche handelt, werden diese – zumindest von den Anbietern – als prinzipiell reversibel eingeschätzt. Kryoforscher suchen zur Zeit nach einem geeigneteren Medium, so dass nicht mehr unter −150 °C gekühlt werden muss und somit keine Brüche mehr entstehen.
Platelets release arachidonic acid, adding to that formed by cell membrane breakdown. Extracellular arachidonic acid contributes to glial cell swelling and increases permeability of the blood-brain barrier.

Moreover, arachidonic acid potentiates the formation of eicosanoids, which increase aggregation of blood cells and constriction of blood vessels. Polymorphonuclear leukocytes further occlude microcirculation and release reactive metabolites.

Edited by Matthias, 26 July 2008 - 06:06 PM.

[Matthias]

REPERFUSION INJURY

It seems desirable to re-initiate cerebral blood flow for the purpose of perfusing brain cells with cryoprotectant. But this can result in a phenomenon known as "reperfusion injury".

Indeed, in the absence of oxygen & glucose (i.e., without reperfusion), no histological damage to cells is evident for more than an hour, and most of the structural damage seen in the first 2 hours is to mitochondria and ribosomes.

Rather than resuscitating cells, the re-entry of oxygen by reperfusion may enhance free-radical damage. We will not do reperfusion for normothermic ischemia in excess of one hour.

Instead an abbreviated stabilisation procedure will be used. An attempt to re-start the circulation may meet with a resistance known as the "no-reflow" phenomenon.

Increased blood pressure is required to overcome "no-reflow" due to vasospasm, increased blood viscosity and oedema.

For cryonics purposes, the increased permeability of the blood-brain barrier due to arachidonic acid and other ischemic damage may actually facilitate perfusion of cryoprotectant.

Even cell membrane damage may be advantageous for an analogous reason.

[Matthias]

Die erste kryonische Suspension wurde am 12. Januar 1967 an James Bedford durchgeführt, der heute bei Alcor aufbewahrt wird.[2] In Russland gibt es neuerdings (2006) den kommerziellen Anbieter KrioRus. In Deutschland hingegen gibt es wegen des Friedhofszwangs keine rechtliche Grundlage dafür.[3] Folglich wird diese Dienstleistung in Deutschland lediglich für Tiere (üblicherweise Haustiere) angeboten.

Edited by Matthias, 26 July 2008 - 06:06 PM.

[Matthias]

Ramping of Cryoprotectant in Closed-Circuit Perfusion

At this time we use undertakers who will do the preparation and perfusion (the replacement of blood with cryoprotectant “antifreeze”) because the method used by undertakers to embalm is similar in many ways to that used in cryonics. Undertakers have much to offer us but whilst they give an excellent and professional service with the equipment they have, with co-operation we can improve on this by introducing closed circuit perfusion. Leave the undertaker to do the cut down and connections and our expertise and equipment to improve the suspension.

Edited by Matthias, 26 July 2008 - 06:07 PM.

[Matthias]

Cannula type

It will be very important to use special flat-wire femoral drainage
cannula that extend up the femoral almost to the level of the heart.

In fact, he will probably be able to place these cannula without instructions, but better to have them than not.

These are very easy to insert and the mortician can do this for you. He will simply need to follow two simple instructions, which he can get, from a 1 or two pages illustrated written sheet. These are very easy to insert and the mortician can do this for you. He will simply need to follow two simple instructions, which he can get, from a 1 or two pages illustrated written sheet.

Edited by Matthias, 26 July 2008 - 06:07 PM.

[Matthias]

Closed Circuit Perfusion

Outside the patient, some of the drainage is discarded, but most is returned to a circulating (stirred) reservoir connected to a concentrated reservoir of glycerol.

The circulating reservoir is initially Ringer's solution (an aqueous solution of the chlorides of sodium, potassium and calcium isotonic with blood & tissue fluid) or a similar isotonic mixture, which gradually becomes increasingly concentrated with glycerol as the stirring and recirculation proceed.
The circulating reservoir is stirred from the bottom by a magnetic stir bar on a stir table and/or from the top by an eggbeater-type stirring device.
The stirring will draw glycerol from the glycerol reservoir, and pumping of the perfusate should also actively draw liquid from the glycerol reservoir. Gradually a higher and higher concentration of glycerol is included in the perfusate and the osmotic shock of full-strength glycerol is avoided.

Zur Konservierung bedient sich die moderne Kryonik (seit Beginn des 21. Jahrhunderts) der Vitrifizierung, um die Bildung von Eiskristallen zu vermeiden. Eiskristalle führen ansonsten zu einer Vielzahl mikroskopischer Verletzungen, welche nach heutigem Kenntnisstand als irreversibel einzustufen sind.
The next page gives a lot of information on vitrification but it is worth pointing out a great deal of work is going on at 21Centry medicine and methods of using it at Alcor, Alcor US already use it on neuro patients but there are still many problems to overcome before this method can be used in the UK but we are working on it.

Edited by Matthias, 26 July 2008 - 06:07 PM.

[Matthias]

Vitrification in Cryonics
by Ben Best

There is a great deal of research into vitrification at this time and C.I will be carrying out its own research later this year, headed by one of the leading authorities on vitrification, Dr Pichugin, but I thought it worth while introducing you to the subject through this very well written article by Ben Best.

Unfortunately some of the original supporting diagrams have been lost, so the text is not as clear as in the original.

[Matthias]

s.o.

Edited by Matthias, 26 July 2008 - 06:08 PM.

[Matthias]

THE PHYSICAL CHEMISTRY OF VITRIFICATION

At Tg there is a sudden increase in viscosity (usually many orders of magnitude), but there is no comparable sudden decrease in volume. In fact, Tg is characterized as a temperature-range where the rate of decrease of volume decreases, although volume does continue to decrease (and viscosity continues to increase) linearly below Tg. Tg could be a temperature critical to cracking because the sudden increase in viscosity would be likely to affect heat conduction as well as stress.
A good carrier solution will be non-toxic, and by reducing the amount of cryoprotectant needed to vitrify will reduce toxicity from cryoprotectant.

Edited by Matthias, 26 July 2008 - 06:08 PM.

[Matthias]

ICE BLOCKERS

The other source of assistance for vitrification comes from ice blockers. While cryoprotectants slow ice-crystal growth and formation, ice blockers act specifically against the formation of the ice-nuclei which are necessary for freezing to begin.
siehe Beispiel:
Although the melting temperature of water is 0ºC, water that is absolutely pure will not freeze above -40ºC because water requires nucleating agents to begin crystal growth. This is called "the devitrification problem". Before the use of ice-blockers it was believed that only radio-frequency rewarming technology could possibly achieve rewarming rates rapid enough to avoid ice-crystal formation upon devitrification.

Edited by Matthias, 26 July 2008 - 06:09 PM.

[Matthias]

Beispiel
<pre>

OH OH OH
| | |
-CH2-C-CH2-C-CH2-C-CH2-C-CH2-C-CH2-C- (POLYVINYL ALCOHOL)
| | |
OH OH OH

</pre>
Although these percentage differences may seem small, the benefits from ice-blockers are actually very great. Toxicity increases exponentially as the cryoprotectant concentrations reach the high levels needed to vitrify. Of particular relevance to cryonics, however, is the fact that cryoprotectants become too viscous to perfuse well at high concentrations, whereas ice blockers add little to viscosity. Thus, ice-blocker plus cryoprotectant can produce a solution that can both perfuse and vitrify.

Edited by Matthias, 26 July 2008 - 06:09 PM.

[Matthias]

VITRIFICATION OF CELLS & TISSUES

In 1949 it was discovered that glycerol can be used to protect bull sperm against freezing injury. A year later, the same techniques were successfully applied to red blood cells. Since that time large industries have developed around the cryopreservation of bull sperm and human blood.
In 1959 the substance DiMethyl SulfOxide (DMSO) was demonstrated to be useful as a cryoprotectant.
Now being cryopreserved worldwide, but it is at least a million. And the number of living children who were once embryos at liquid nitrogen temperature is in the tens of thousands. (For an online review of human embryo cryopreservation technology see Human Oocyte and Embryo Cryopreservation.)

Edited by Matthias, 26 July 2008 - 06:09 PM.

[Matthias]

Cryopreservation of tissues & organs is much more difficult than cryopreservation of small collections of cells. Time is required for cryoprotectant to permeate an organ and also for temperature to penetrate. Tissue is subject to degradation if there is no blood circulation even if the temperature is very low, yet a very low temperature will slow the rate of cryoprotectant perfusion.

Crystallization is not an inevitable consequence of water cooling, however. A 68% v/v (volume/volume) glycerol/water solution will not crystallize at any subzero temperature -- it simply hardens like glass. But concentrations of glycerol greater than 50% v/v are too viscous & toxic for cryonics use. As mentioned above, the brain is an especially ice-crystal tolerant organ, insofar as 60% water as ice-crystals causes little gross damage.

Edited by Matthias, 26 July 2008 - 06:11 PM.

[Matthias]

The experiments of I.Suda [NATURE 212:268-270 (1966) and BRAIN RESEARCH 70:527-531 (1974)] indicate that cat brains cooled to -20ºC in 15% v/v glycerol (62% brain water as ice) for 777 days and 7.25 years, both show normal-looking EEG patterns upon re-warming -- although neurological activity is less for the 7.25-year brains. Haemorrhaging and cell loss of these specimens probably could have been prevented using several measures:

ie, 27.2% v/v glycerol (3.72 Molar) should be sufficient to prevent ice-crystal damage to brains cooled to any subzero temperature (including liquid nitrogen temperature, -196ºC). For years cryonicists believed that "the Smith Criterion" of a minimum of 3.72 Molar glycerol concentration might be adequate to prevent freezing damage in cryonics patients.

Edited by Matthias, 26 July 2008 - 06:11 PM.

[Matthias]

In the December 1991 issue of CRYONICS magazine, a cryobiologist described the results of an experiment with a single rabbit brain perfused at room temperature with 3.72 Molar glycerol, cooled to -130ºC, cut into slabs, and the resulting slabs stored at -78ºC for many months before examination under an electron microscope. He states: "...the pattern of ice formation seems to be potentially quite damaging. Everywhere one looks, thick sheets of ice are found stabbing their way through brain tissue with apparent abandon."
He goes-on to say, "It is almost miraculous how well the tissue organization re-establishes itself in general after thawing, even in areas where gaps are present. However, the likelihood of extensive damage existing below the level of resolution of the light microscope, but all too visible in the electron microscope, appears high."

Edited by Matthias, 26 July 2008 - 06:12 PM.

[Matthias]

Although a certain caution should be taken in accepting the results of a single preparation of a rabbit brain by a single experimenter, however, at high concentrations the glycerol perfuses poorly into cells and, in fact, osmotically draws water out of cells -- resulting in dehydration.

Edited by Matthias, 26 July 2008 - 06:12 PM.

[Matthias]

.......u.s.w ich bin jetzt auf Seite 31 von 107
d.h. komplett wäre das ganze Dokument noch 3 mal so lang

A) soll das bis Seite 107 hier komplettiert werden?

B) ist das so lesbar oder muß es noch besser formatiert werden?

C) dürfen wir das hier überhaupt?

[caliban]

das manual besteht teilweise aus reprints, teilweise aus irrelevantem gelaber, teilweise aus veraltetem Material. Wichtige Aspekte fehlen hingegen.
Besser waere, das ins Wiki zu stellen und gruendlich zu ueberarbeiten.

Lesbarkeit:
Bilder in thread muessen kleiner geschrumpft werden sonst muss man rechts scrollen.