Alcor 1997 Stabilization and Transport Manual
Table of Contents

Chapter 8: Medication Administration

Surface cooling, respiration, and the restoration of circulation do not provide complete protection for cells which have been deprived of oxygen. Any discontinuity in oxygen flow to the cells will cause the depletion of oxygen reserves and the consumption of other forms of available energy, like glucose. Once the oxygen reserves are jeopardized, the cell begins to search for addition sources of fuel. Some of the cell's systems will begin to fail, and since the resources aren't available to prevent or repair the new damage, each failure precipitates others. These failures spark a chain reaction of cell damage which becomes increasing difficult to stop. In some cases, simply restoring the flow of oxygen will be sufficient to reverse the damage. More extreme cases require medication. But in many cases, twelve minutes without oxygen is sufficient to cause currently irreversible brain damage to a living body [22, 23].

Every human being is constructed from trillions of cells. These cells need oxygen. If you learn even a little about how oxygen deprivation and other factors (like hypothermia) affect sensitive cell function, you will begin to understand the importance of this step in the transport procedure.

Cell Dysfunction

The cell membrane is only two molecules thick and is comprised of lipids and proteins. This tiny layer acts as a "gatekeeper" by controlling the composition of the cell, letting pass only those molecules it needs to survive. Lipids are fats, and anything that is fat-soluble may enter the cell. Various kinds of small molecules will also enter the cell.

Proteins in the cell membrane actually protrude through the lipid bi-layer and bond with nearby molecules. Bonding modifies the protein configuration, and when reconfiguration is complete, the nearby molecule will be "trapped" on the inside of a cell. Protein channels are very efficient regulators of ion concentration. They are capable of maintaining ionic concentrations of 10,000:1 between extracellular and intracellular fluid.

Ion Channels

One of the most important types of protein channel is one that regulates potassium and sodium. Potassium and sodium, along with calcium, maintain a rhythmic heartbeat, regulate the body's acid-base balance, and are responsible for the conduction of nerve impulses and muscle contraction. Because both potassium and sodium are plentiful in almost all foods, the body maintains few reserves. Potassium is more concentrated inside the cell, while sodium is found in higher concentrations outside the cell.

Another important channel regulates calcium levels. Normally, the extracellular to intracellular ratio of calcium is about 10,000:1. Disruptions in the sodium and potassium levels will cause the calcium channels to open haphazardly. Calcium will flood into the cell and cause the production of destructive enzymes.

A host of medications will help prevent calcium damage. Nimodipine inhibits smooth muscle contractions by blocking the influx of calcium into cells. Since destructive enzymes are created with excess calcium, they will be less abundant. Nimodipine is also involved in reducing damage caused by arterial spasms during ischemia. Because of its relaxative properties, patients will also experience a drop in blood pressure (which may be countered with epinephrine).

Because it is highly lipophilic, nimodipine may cross the blood-brain barrier to provide effective protection for the cerebral vasculature.

Diltiazem hydrochloride has comparable effects and is an alternative to nimodipine. The primary relevant distinction between the two is that diltiazem targets the heart, not the brain.

Sodium citrate is also used to prevent calcium damage. It binds calcium into a nondestructive, chemically-stable compound.

Another ion to neutralize is iron. Iron is essential to the structure of hemoglobin. When the red blood cells degrade, iron (Fe+2) is released to scavenge for oxygen. Deferoxamine hydrochloride chelates iron by forming a stable complex that prevents iron from being involved in further chemical reactions.

Hemoglobin

Hemoglobin comprises most of the volume of red blood cells, which constitute about half of the volume transported by blood. These are the cells in which oxygen will bind for delivery to the tissues. When blood flow stops, the blood cells fall heavily to the vessel floor. They settle. When blood flow begins again, the lighter, smaller objects and fluid above the hemoglobin "floor" will begin moving, but the densely packed blood cells won't. This effect is called sludging. Without enough red blood cells, the tissues will remain undernourished after an ischemic episode. Capillary sludging may be blocked by the administration of Dextran-40 [25].

In the absence of oxygen, red blood cells will bind with other red blood cells. These red blood cells will combine in seemingly haphazard patterns. Capillaries are tiny and will only allow structures about the size of single blood cells to pass. As structures formed of multiple red blood cells, they become lodged in the capillaries and restrict vessel flow severely or prevent it completely.

Heparin will prevent the formation of new clots, but it won't reverse those clots already formed. For this reason, it is essential that heparin be the first transport medication administered to a patient.

Lysosomes and Peroxisomes

Floating freely within the cell are two further dangers. Lysosomes and peroxisomes are essentially sacs of poison awaiting the signal to burst. These are dangerous substances which cause complex molecules to break down into simpler forms.

The lysosomes and peroxisomes won't self-destruct until more than an hour after cardiac arrest occurs [25, 26, 27]. Rigor mortis is an indication that these sacs have begun bursting, and the stabilization protocol (with the exception of cooling) will not be administered to patients displaying evidence of rigor mortis.

Rigor mortis refers to the stiffening of muscles that occurs after death. It starts three to four hours after pronouncement and is usually complete within twelve hours. This stiffness will gradually disappear over the next 48-60 hours. Other factors affect the onset of rigor mortis, including the amount of physical exertion occurring before pronouncement. If signs of rigor are observed sooner than expected, they will recede sooner as well.

In cases where rigor is present, cardiopulmonary support and subsequent perfusion may be attempted, but decisions will be made on a case-by-case basis. For those patients where rigor has come and gone, no attempts should be made to restore circulation. Transport team members will simply prepare for shipment to Scottsdale in such circumstances.

The extent of ischemic damage may be partially assessed using complex chemistry and blood gas analyses. These analyses are routinely performed in hospitals for heart attack victims. Complex chemical analysis is beyond the capacity of an Alcor transport team, but testing the pH of a patient's blood is a simple way to gain useful information.

pH

This is the symbol used to express the degree of acidity or alkalinity of an aqueous solution. A more precise definition is that pH is the negative logarithm of the hydrogen ion concentration, relative to water. Acids are those substances which break down and release hydrogen ions, while bases (alkaline solutions) break down and release hydroxyl ions. On a scale of 0-14, a solution with a pH=7 is neutral; one with a pH=0 to 6.99 is acidic, and one with a pH=7.01 to 14 is alkaline (or basic). In humans, pH falls between 7.3 and 7.5.

As a patient's body temperature is reduced, the pH may be expected to fall by 0.07pH PER °C [28, 29]. This drop in pH is overshadowed by ischemia's effect on pH: expect the transport patient's pH to drop (become more acidotic) significantly. When lysosomes or peroxisomes burst, the toxins released into the blood will begin breaking the bonds of complex molecules to form more simple molecules. Many of the simple molecules form acids of various sorts.

Sodium bicarbonate and tromethamine are two medications which will help regulate acid/base levels in a transport patient. Each of them buffers against the buildup of acid in the blood. Tromethamine is part of the medication protocol, and sodium bicarbonate is used in cases where the transport team has the personnel available to monitor and regulate pH changes once all other medications have been administered.

Glucose

Glucose in the body is converted to energy by all the cells. The glucose concentration in the blood will determine the amount of insulin produced by the pancreas. Insulin is a hormone which promotes the absorption of glucose by the liver. Normal metabolic levels for glucose should be maintained during a transport, if personnel are available. If not glucose levels aren't regulated, they will break down into lactic acid, which is damaging to the cells.

The administration of dextrose, which is another name for glucose, will increase glucose levels in the blood. Normal serum glucose levels range from 90-110 mg/dl. If dextrose (50% concentration) is used, blood glucose levels will rise by approximately 2 mg/dl per ml administered.

50% dextrose (ml)  = [required glucose level (mg/dl) - measured glucose level (mg/dl)]
                                                                                2

Medication Packaging

There are a variety of ways a medication can be stored prior to use. Solutions may be stored in vented or unvented glass bottles, plastic bladders, vials, or ampules. Bottles and bladders are used for medications administered in volumes generally exceeding 50m1. They require an intravenous line. Vials and ampules are generally used in cases where the volume is less than 50m1. Small bottles and ampules may also contain a powder which must be hydrated prior to administration. Most packages also contain slightly more than the label indicates. Be certain to measure out only the amount needed for the patient.

One thing all medication packages have in common is that there is a plastic protective cap covering the port from which the medication is re-moved. These caps are easily removed from the package. Once removed, these caps cannot be replaced, so they should only be removed when the medication is being drawn up for administration. Once the caps are removed, the seal underneath should be swabbed with alcohol. In the case of multi-dose vials, this should be done every time medication is withdrawn.

When medications are withdrawn into syringes, there may be tiny air bubbles attaching to the insides of the syringe. Simply tap the syringe gently to allow the bubbles to rise to the tip, and depress the plunger until all bubbles are removed.

Bottles

Glass bottles are divided into two categories: those which are vented and those which are not. This characterization is important to the choice of an IV line, as IV lines also come with a venting option. If the medication is stored in a vented bottle, an unvented line must be used, and with the unvented bottles, a vented IV line. In cases where no vented IV line is available to use on an unvented bottle, an IV needle may be spiked through the seal and used to introduce air. (This is risky. Bottles should never be left unattended during pressure infusion to avoid air being introduced into the IV line.)

Medications degrade when exposed to air. Placing a medication on ice will reduce the rate of degradation, but this deterioration will begin once the sterility or vacuum of a container is breached and applies to all forms of packaging, including syringes. Once spiked for administration, a medication must be used within 24 hours. If the medication isn't used immediately, it should be stored on ice in an ice chest or refrigerator.

Bottles must be hung (spiked end down) from an IV pole or similar high structure. Gravity will provide the necessary pressure to infuse the solution, and because of this, bottles must be hung as far above the chest of the patient as is possible (preferably at least 2-3 feet, and the length of the IV line will generally determine the upper limit).

Glass bottles pose a serious risk of air emboli, and must be constantly attended to avoid the accidental introduction of air into the patient.

Bladders

Flexible bladders are used for large volume medications, and they are all unvented containers. For rapid infusion, an inflatable pressure cuff may be used. Using the pressurization technique will pose a serious risk of air emboli here as well, and pressurized bladders must be constantly attended to avoid the accidental introduction of air into the patient.

Solutions contained in bladders may be administered without venting, as the flexible sides of the bladder may be compressed to force the fluid into an IV line. For best results, all of the air should be removed from the bladder prior to hanging it for infusion. This is accomplished by spiking the bag with an IV line, opening the line to fluid flow, turning the bag upside down, and squeezing the air out through the line. A pressure cuff may then be placed around the bladder (for rapid infusion) and both are hung from the IV pole. Once hung, the inflation bulb of the pressure cuff is squeezed several times. This will begin the rapid flow of fluid out of the bladder.

The use of bladders and pressure cuff is preferable to using glass bottles. With the air removed from the bladder before it is connected to the patient, there is less chance that air will accidentally be administered to a patient. The pressure cuff also enables faster infusion of medication than gravity will provide.

Vials

Vials are essentially small bottles which contain medication in either liquid or powder form. These small bottles generally have a rubber stopper at the top which must be pierced by a needle to access the medication. They are also vacuum-sealed for sterility. Rubber stoppers are designed for one injection only or for multiple dose administration. Labels on the vial and any associated box will provide this information. Only a "multi-dose" vial may be punctured more than once and still maintain the sterility of the solution.

Vials which contain powder must be rehydrated with the appropriate solution (usually sterile water). The packaging slip stored with the vial will provide full details about reconstitution of the powder. Required amounts of rehydrating solution are pulled into a syringe and then injected through the rubber stopper. The syringe is then removed and the vial is gently turned to dissolve the medication. Once the powder is completely dissolved, the medication may be removed for administration.

There is another type of vial which deserves mention: Mix-O-Vial. This is an ingenious container which has two separate chambers for powdered medication and the reconstituting solution. Simply depress the plunger to combine the powder and fluid, invert gently until the powder is dissolved, and withdraw from the vial using a needle and syringe.

Before fluid medication may be removed from a vial, the transport team member must be wearing gloves and have assembled appropriate sterile needles and syringes. Remove the plastic cap and swab the rubber stopper with an alcohol pad. Attach a needle to the tip of the syringe. No fluid may be removed from a vial without first injecting some air through the rubber stopper.

Fill the syringe with a volume of air identical to the amount of fluid you will withdraw. Insert the needle through the stopper. Inject a quantity of air into the vial and, without removing your thumb from the syringe, release the pressure on the plunger. Fluid should flow into the syringe easily, as the pressure in the vial rises with the injection of air. The tip of the needle should remain below the fluid line to avoid simply filling the syringe with air.

Ampules

These are the final category of medication packaging, and they provide the greatest risk for injury of the transport team member. Ampules are small containers with neither lid nor injection port. They are glass and must be broken before the medication can be withdrawn. Ampules contain a single dose of medication.

The ampule is generally tapered at one end to provide a hand-hold for breaking off the top. Before breaking open an ampule, make certain to wear gloves and wrap the tapered part of the ampule with gauze. Snap sharply to break the top. While holding the ampule with one hand and a syringe with the other, withdraw the medication.

Medication Preparation

All of the medications to be administered to a patient must be prepared before they are needed, if possible. It takes some time to calculate the dosages and withdraw them for injection. If done in advance, transport team members must make certain that all syringes, bottles, and bladders are labeled. Bottles and bladders are labeled by the manufacturers, but syringes must be labeled with the medication name (or recognizable abbreviation) using a semipermanent marker. Once labeled, syringes may be stored for later administration.

If a patient is clearly agonal, medications may be drawn up, but transport team members must be aware that predicting time of death is an extremely inexact science. Past Alcor patients have historically exceeded their physicians' estimates for time of death and have experienced agonal declines that were hours (and in one case, days) longer than anticipated. The reason for this is that medical professionals concentrate on making people well. Little time has been spent on the mechanics of death. As a result, predictions are often wrong. This is important, because there is generally only one set of medications in each local emergency response kit. If medications are drawn up and the patient lingers, the medications will degrade and become unusable within 24 hours. Margins of 24 hours are usually sufficiently close that a second set of medications is rarely needed, but if this happens, more medications may be shipped from Alcor Headquarters.

Intravenous Access

An IV provides a portal to the circulatory system through which large-volume medications may be pushed. IVs are always placed into veins. Using an artery to administer medications to a patient is dangerous, because of the high pressures of arterial circulation and because the arterial side of the vascular system is unfiltered. (The lungs act as an emergency filter for emboli.) Improper IV technique causes damage to the vessels and could result in irreparable damage to the vessel, as where a needle is driven through a vessel instead of eased into it.

Primary access points for transport patients include the basillic or axillary veins in the arm, the saphenous vein in the leg, and the jugular vein in the neck. The jugular vein, and indeed any central IV (like a subclavian), is a less-desirable IV site for the transport patient, because the displacement of blood caused by the high pressures of the heart-lung resuscitator will reduce the amount of fluid transported by these vessels. Femoral vessels are less desirable because that is where surgical access for blood washout is likely to occur. Placing an IV into the femoral area may also cause damage to the vessel and make access to this area during the blood washout difficult or impossible.

Medications should be administered to a patient as soon after pronouncement as possible and concurrent with both surface cooling and the initiation of cardiopulmonary support.

While some medications may be administered using an intramuscular (into the muscle) or subcutaneous (under the skin) injection during a routine hospitalization, these administration methods are not used on a cryonic suspension patient. During bouts of ischemia and severe trauma, the body will shunt blood away from the skin and muscles and redirect it to the vital organs. This reduces the efficiency of intramuscular or subcutaneous medication absorption. Absorption into the blood is fastest when medications are injected directly into the circulatory system.

There are four primary failure modes for IV therapy which must be avoided: air emboli, hematoma, infiltration, and clotting. Because IV placement requires training and practice, it should only be done by experienced personnel. However, this does not eliminate the responsibility of transport team members to observe the condition of the patient or the IV. Any transport team member observing problems with an IV line should tell the transport team leader or other delegated individual immediately.

Clotting

Clotting is the easiest complication to avoid, and one of two failure modes which may be avoided with simple diligence. An IV line, when in the patient but not being used momentarily, should be filled with heparinized saline and flushed occasionally to prevent blood in the line or needle from clotting. If a line cannot be flushed, the tubing is first replaced without removing the needle from the patient. Attempt another flush, and if it also fails, place a new IV.

Air Emboli

An embolus (plural: emboli) is a plug within a vessel which floats, or migrates, freely until blood vessels narrow and it becomes lodged. Once lodged, the embolus will obstruct circulation. An embolus could be a blood clot, an air pocket, a fatty deposit, or a tumor [2]. Air emboli are air bubbles which have been administered to the patient, bubbles which block blood flow.

There are several ways these bubbles could be administered to a patient. Each of them should be avoided. If air is administered to the patient, it must be recorded in the transport notes. Include the circumstances and an estimate of the volume of air administered.

Some medications are stored in IV bags or sealed bottles. Both the bags and the bottles frequently contain some air. Air can easily be removed from an IV bag, because of its flexible sides, and indeed should be removed before the IV lines are connected. Proper sterile techniques should be observed at all times. During a transport, the transport team member who is administering medications is responsible for making certain that no IV bag is hung for the patient with air inside. It is rarely possible, during a transport, to arrange for constant supervision of an IV line, so prevention is key to avoiding this threat to perfusion.

Bottles are another matter—the air cannot be removed from the container. If a bottle is allowed to run dry without the line being clamped, air will enter the patient's circulatory system. The IV line must be clamped before the bottle runs dry. During a transport, the transport team member who is administering medications is responsible for making certain that no bottle runs dry.

IV lines may be a source of emboli if they aren't primed with fluid prior to starting the infusion.

Safety Precautions

No transport team member will prepare or administer medications without wearing gloves.

Once the plastic covering has been removed from a needle, do not recap that needle. Carefully remove the needle from the syringe and place it into the Sharps container. Once all sharp objects have been collected, seal the container for shipment with the patient.

A completed Incident Report Form should be included in the transport notes if any transport team member is exposed to infectious material, as would happen with a needle-stick.

Intravenous Cannulation

There are three basic types of needles and catheters used in peripheral lines for administering medication. First, a winged infusion set consists of a needle with plastic wings and tubing with an adapter for IV lines and syringe tips. Then, there are two catheters. One is "over-the-needle" and the other is "inside-the-needle". Over-the-needle catheters are preferable to inside-the-needle catheters, as placement is easier.

Catheters are preferable to winged infusion sets, as it is generally possible to infuse larger volumes of fluid into the patient more quickly. Catheters may also be more securely fastened to the patient. Use the largest size possible. (Note: needles, cannula, and catheters are sized such that the lower numbered sizes are the largest needles.)

If a patient has been pronounced in the hospital or while under the direct supervision of a physician, there may already be catheters in place. If so, request that they be left in place after pronouncement. Before using any lines that have been left in place, make certain that the injection port is compatible to any medications which will be administered through it. Also make certain that any blood in the line has not clotted. This can be avoided by pushing a low concentration Heparin solution (10U/50m1) through the line every few minutes.

Generally, IV lines will only be placed by transport team members who have experience and training. However, all team members must be familiar with the types of IV lines and needles available and how to manage an IV.

Catheter Placement Using Cutdown

1. Once a vessel has been located (usually through palpation) and the skin cleaned with Betadine, an incision may be made into the skin.

2. Blunt dissection is used to isolate the vessel from the surrounding fatty tissue (fascia) and muscle. Avoid cutting any blood vessels in the area. (Cauterize or clamp as needed and able.)

 
Step 3
3. Once the vessel has been cleared of any connective tissue, slide forceps underneath and pull sutures underneath. (At least one proximal and two distal.) Tie off the distal end as far down as the incision will allow.
 
 
Step 4
4. Use the proximal suture to elevate the vessel (to prevent undue bleeding). Use a Bulldog clamp to hold in place. use forceps to hold the vessel in place. Using a #15 blade, cut the vessel with an upward stroke beginning about half way down.
 
 
Step 5
5. Use the forceps to stabilize the hole and hold it open. With the other hand, insert the catheter. Remove the clamp and advance the catheter as far as it will go. Tie the proximal suture. Use the second distal suture to secure the catheter.
 

IV Management

Most medications will be administered through an IV line. There are several kinds, including vented and unvented or filtered and non-filtered. Be certain to use the appropriate line with each medication.

All IV lines have clamps to stop the fluid flow. Most have ports for administration of medication from a syringe, in addition to a bottle or bladder. Other ports may allow for the addition of another IV line into the loop.

If a needle and syringe are used to add medication to an IV line, clamp the line above the port and inject the new medication. Never administer air. Never let an IV run dry.

All medications administered to a patient must be recorded for the patient's permanent record (time administered, medication name, and amount given). Another tenant of medical practice is applicable to cryonics: "if it wasn't recorded, it wasn't given." This will be the assumption in post-suspension evaluation of both the team's performance and the quality of the suspension received by the patient. The transport coordinator's Emergency Response Manual contains forms designed for the recording of this information. Use them.

It is easiest, in situations where transport personnel are plentiful, to assign one individual scribe duties and another medication administration duties. It is the responsibility of the individual giving the medications to en-sure that the appropriate information is recorded.

Conclusion

A great deal of information is contained in this chapter, and much of it will be useful to the transport team member during a standby or transport situation. Many physicians and nurses are interested in the types of medication administered to Alcor patients. Demonstrating an understanding of the purpose of medication and the damage it mitigates will help enhance the credibility of cryonics in the medical community. Recognizing the failure modes of medication will help a team member prevent damage to the suspension patient, which is the goal of a transport.

Medication, in conjunction with cooling and cardiopulmonary support, will provide the optimal structural protection for a patient, within current constraints. The transport team which can accomplish these steps will have performed admirably. Only a blood washout remains as a protective measure. That is the subject of the next chapter.

Calculating the Volume of Medication to Administer

Volume to give is calculated with the formula:
dosage x weight of patient in kilograms ÷ package concentration

MEDICATION
DOSAGE
(units/kg)
Weight of Patient
(KG)
Package Concentration
(units/ml)
Volume to Give
(ml)
HEPARIN  420U      
POTASSIUM CHLORIDE (OR)  1mEq      
SODIUM PENTOBARBITOL  30mg      
DEFEROXAMINE HCL  2g in all      
EPINEPHRINE  0.2mg      
NIMODIPINE (OR)  10ug      
DILTIAZEM  300ug      
SODIUM CITRATE  120mg      
ASCORBIC ACID  125mg      
TROMETHAMINE  250mg      
CHLORPROMAZINE HCL  3mg      
METHYLPREDNISOLONE  1g in all      
MANNITOL  2g      
METUBINE IODIDE  0.07mg      
GENTAMICIN SULFATE (OR)  1mg      
ERYTHROMYCIN  1g in all      
BACTRIM  10ml in all      
DEXTRAN-40  500cc at most      
MAALOX  250cc      
STREPTOKINASE  1,000U      
VERAPAMIL  0.30mg      
  • HEPARIN: is an anti-coagulant (prevents new clots from forming, doesn't affect clots already formed.)
  • POTASSIUM CHLORIDE: reduces cerebral metabolic demand.
  • SODIUM PENTOBARBITOL: reduces cerebral metabolic demands and electrical activity in the brain.
  • DEFEROXAMINE HCL: binds excess free-iron into a non-destructive, chemically stable compound and reduces free radical damage.
  • EPINEPHRINE: supports blood pressure and helps to counter the relaxative properties of nimodipine and diltiazem.
  • NIMODIPINE: inhibits smooth muscle contraction by blocking the influx of calcium into an injured cell, reduces arterial spasms during ischemia, and provides protection against cerebral "no reflow."
  • DILTIAZEM: has similar effects to nimodipine.
  • SODIUM CITRATE: binds excess calcium into a non-destructive, chemically stable compound and reduces cerebral reperfusion injury.
  • TROMETHAMINE: combats acidosis.
  • CHLORPROMAZINE HCL: stabilizes the cell membrane and protects against cold ischemic injury.
  • METHYLPREDNISOLONE: functions similar to chlorpromazine.
  • MANNITOL: reduces free radical damage and prevents cerebral edema.
  • METUBINE IODIDE: paralyzes the muscles to inhibit shivering and reduces overall metabolic demand.
  • BACTRIM: prevents microbial overgrowth. An anti-bacterial agent.
  • ERYTHROMYCIN: has similar effects to Bactrim.
  • GENTAMICIN SULFATE: has similar effects to Bactrim.
  • DEXTRAN-40: minimizes capillary sludging and supports blood pressure in volume-depleted patients.
  • MAALOX: prevents gastric acid accumulation and reduces the chance for gastric hemorrhage.
  • STREPTOKINASE: dissolves clots.
  • VERAPAMIL: reduces intracellular calcium loading.

 

Go to Chapter 9 or Table of Contents