Dilution is a process of mixing the contents of a vial of insulin with another liquid substance to lower the strength. This is done to make it easier to draw a very small amount of insulin, to more accurately draw a larger dose, or allow a larger volume of liquid to allow the caregiver to have a better “feel” that the syringe plunger was appropriately depressed when the shot is given.
Eli Lilly and Novo Nordisk make diluents for R/neutral and NPH/isophane insulins. A diluent contains both the suspension and preservative(s) found in the insulin type. It is important to use only a diluent that was made for that particular insulin. Mixing different suspensions and preservative(s) can destroy or render an insulin ineffective.
R/Neutral insulins contain no buffers. Lente-type insulins use acetate buffers, while NPH/isophane ones use phosphate buffers. Phosphates change the activity profile of lente insulins, making them work much like R/Neutral insulin.
You can obtain the diluent, as well as the vials in which to mix the insulin with the diluent, from the insulin manufacturer or through a pharmacy, and they should be free of charge.
- A notice dated June 27, 2005, indicates that Novo Nordisk has no insulin diluent available and that the company will not provide a reason for the shortage and cannot estimate a release date.
- A notice from Eli Lily dated April 12, 2004, indicates the company is no longer making available diluents for Humulin L and Humulin U.
You should refrigerate insulin diluent or otherwise keep it from extreme high or low temperatures. Handled in that manner, the diluent will remain useable until the expiration date on the box.
If you are unable to obtain the correct diluent for your insulin, it is possible to use sterile water or sterile saline solution. With either of these, a solution which is good for 2-4 weeks can be made. Your pet's vet can prepare it or advise you on the way to go about doing this.
Dilution supplies and method
You will need syringes to draw the insulin and the diluent out of their vials and to place the liquids into a mixing vial. You should consider using a syringe with a barrel larger than the one you use to give insulin shots, such as 3cc or 6cc tuberculin syringes. The fewer “syringe-fulls” of liquid you have to transfer to the mixing vial makes the process less prone to counting error. Tuberculin syringes have larger gauge needles than do insulin suringes. You should use a syringe with a gauge of 25 or finer so that the needles do not make too large a hole in the tops of the vials. You should have one syringe for the insulin and a separate syringe for the diluent.
Tuberculin syringes, unlike insulin syringes, usually have removable needles. Make sure that the needles are firmly screwed onto the barrels before use. Those syringes also may not have a plunger “stop” on them; determine the design of your syringes before you use them so that when you draw the insulin and diluent you do not pull the plunger all the way out of the barrel and end up with your liquid on the counter.
As explained in this wiki's article on syringes, when you draw a shot from an insulin vial, you need to first instill an equal amount of air into the bottle to maintain equilibrium in the vial. This is done while the vial is upright to avoid instilling air directly into the liquid and causing air bubbles. Because of the size of the barrels on tuberculin syringes, you will be instilling much more air into the insulin and diluent bottles, and creating more air pressure inside the vial, than you are used to when you are drawing an insulin shot. Do not take your finger off the plunger until you have turned the vial upside down or the vial will push the air back into the syringe. When you turn the vial upside down, make sure the needle, which is longer on tuberculine syringes, is well below the liquid line.
Some caregivers take advantage of this increased air pressure to help “move” the syringe plunger when they draw the insulin and diluent. In fact, they instill twice the amount of air into the vial to accomplish this, saying that when the vial slowly “pushes” the liquid into the barrel, there are fewer air bubbles. They retard the backwards movement of the plunger; slower movement of the liquid they say reduces the introduction of air bubbles into the liquid, and they stop the movement a few times as the syringe is filling to tap out the air bubbles, expel any air in the syringe back into the vial, and then continue filling. Removing air bubbles is important to make sure that the proper amount of insulin and diluent is drawn for the mixture. After they have drawn the proper amount of liquid, they keep their finger on the plunger as they draw the vial off the needle to make sure than any remaining air pressure in the vial does not change the amount of liquid they have just drawn.
Drawing insulin and diluent into the larger syringes without air bubbles can be a lengthy procedure; take your time.
Once you have drawn the proper amounts of insulin and diluent, you add them to the mixing vial. You can place a third syringe (a smaller insulin syringe) with the plunger removed in the top of the mixing vial to vent air as the insulin and diluent are added. Adding a “vent” eliminates the air resistance you would otherwise encounter when adding the liquid.
How much diluted insulin you can mix at one time depends on the dilution ratio (as discussed below) and the size of the mixing vial you use.
The amount of insulin and diluent that you add to the mixing vial depend on the starting strength of the insulin and the amount by which you want to dilute it. This involves great care to make sure you get the math right—not only in diluting the insulin but also in later administering it. If you feel you cannot get the math right in diluting the insulin, take it to a compounding pharmacy to have it done. If you feel you cannot get the math right in administering diluted insulin, do not dilute your pet’s insulin.
You have to decide the fraction of a unit in which you wish to be able to measure doses. This fraction you choose is affected not only by how “discretely” you need to administer insulin to your pet, but also by two practical considerations.
- The smaller the fraction of a unit to which you dilute the insulin, the more liquid you will have to inject into your pet for a given insulin dose. Some pets do not well tolerate large volumes of liquid in an injection. If you dilute, for example, U100 insulin to tenths of a unit, you will need to draw the diluted mixture into a U100 syringe to the 10 measure mark to administer a unit of insulin.
- A 3/10 cc insulin syringe, which measures to the 30 mark, will hold only 3 units of insulin diluted for tenths of a unit. If you needed to administer a dose larger than 3 units, you would either have to give more than one injection or use a larger insulin syringe.
To make this simple, let’s say you are using U100 insulin and U100 3/10cc syringes with single unit marks. You want to give your pet insulin in 1/4 unit doses. That would be simplest for you if you could draw to the 1U measure in the syringe to give 1/4 unit of insulin. To dilute your U100 insulin to 1/4 units, you would dilute at a ratio of 1 part insulin to 3 parts diluent. With that mixture, the maximum dose of of insulin you could put in the 3/10 cc syringe would be 7.5U. With this dilution ratio, you could use syringes marked for 1/2 units to administer as little as 1/8 unit.
If you want to dilute U100 insulin to administer in a U100 syringe:
|And want to administer this amount of insulin by drawing to the 1 measure mark on the syringe||Mix this amount of insulin||With this amount of diluent||Maximum diluted dosage you can get in a 3/10cc syringe|
Using diluted insulin
When you draw shots of diluted insulin, you must keep the dilution ratio in mind in measuring the dose.
The following table shows the measure of diluted mixture you should draw for various dosages.
|This measure on a U100 syringe|
|If you diluted U100 insulin in this ratio of insulin to diluent||Conversion ratio (divide marks by this number to obtain units)||1 mark||2 marks||3 marks||4 marks|
|Will give you this amount of insulin|
|1:1||2||1/2 U||1 U||1 1/2 U||2U|
|1:2||3||1/3 U||2/3 U||1 U||1 1/3 U|
|1:3||4||1/4 U||1/2 U||3/4 U||1 U|
|1:4||5||1/5 U||2/5 U||3/5 U||4/5 U|
|1:5||6||1/6 U||1/3 U||1/2 U||1/3 U|
|1:6||7||1/7 U||2/7 U||3/7 U||4/7 U|
|1:7||8||1/8 U||1/4 U||3/8 U||1/2 U|
|1:8||9||1/9 U||2/9 U||1/3 U||4/9 U|
|1:9||10||1/10 U||1/5 U||3/10 U||2/5 U|
Diluting using sterile saline or water
Some insulin can also be diluted by using a sterile saline solution or sterile water made for injections, available through your pharmacy. Insulin diluted with either of those liquids does not remain stable beyond 24 hours, and some insulins, especially Lantus, are absolutely not to be diluted in this way regardless. At best, such a dilution method is only appropriate for single shot purposes. See the further discussion of using those liquids for dilution below.
- Vetsulin Insulin FAQ's--Diluting Vetsulin/Caninsulin--Insulin Stability Loss
- Lilly Discontinues Diluent for all Lente & Ultralente Insulins
- Auburn University: Insulin Preparations-Lente Insulins
- Lente-Type Insulins & NPH/Isophane Insulins-A Bad Combination
- Novo Nordisk Diluent Shortage
- Lilly Discontinues Diluent for all Lente & Ultralente Insulins
- Dilution of Insulin With Sterile Water/Saline
- Using Sterile Water/Saline in Diluting Insulins