Mixing two different types of insulin into a single syringe is common practice for people managing diabetes, reducing the number of daily injections. This technique combines a fast-acting insulin with a longer-acting one to provide both immediate blood sugar control and sustained coverage. Because different insulin types interact chemically, the specific order in which they are drawn into the syringe is a safety measure. Following a precise sequence prevents one insulin from contaminating the other’s vial, which could alter its effectiveness and lead to unpredictable dosing.
Understanding Insulin Compatibility
Insulins typically combined in one syringe are a short or rapid-acting type and an intermediate-acting type to achieve a dual effect. Short-acting insulins, like Regular insulin or rapid-acting analogs (e.g., Aspart or Lispro), provide quick coverage for meals. Intermediate-acting insulin, such as Neutral Protamine Hagedorn (NPH), offers a slower onset and longer duration to manage blood sugar between meals and overnight.
Long-acting insulins, including Glargine or Detemir, must never be mixed with any other insulin in the same syringe. These insulins are formulated to maintain a steady, peakless release over many hours. Mixing them disrupts their chemical stability, altering their time profile and making their action unpredictable. For example, Glargine is formulated at an acidic pH, and mixing it with a neutral-pH insulin causes immediate precipitation, compromising its long-acting function.
The Critical Mixing Rule: Clear Before Cloudy
The rapid or short-acting insulin, which is visually clear, must be drawn up first, before the intermediate-acting NPH insulin, which is cloudy. This is known as the “clear before cloudy” rule, a fundamental safety procedure in insulin administration. The mnemonic “RN” (Regular/Rapid to NPH) helps remember the correct sequence for withdrawal.
This strict order prevents contamination of the clear insulin vial by the cloudy NPH insulin. NPH is a suspension containing protamine and zinc, which slows its absorption and gives it its cloudy appearance. If a small amount of NPH suspension enters the clear, short-acting insulin vial, the protamine proteins can bind to the clear insulin. This contamination alters the clear insulin’s chemical environment and rapid action profile, potentially delaying its onset and reducing its peak effect.
A contaminated clear insulin vial delivers an unreliable dose that does not act quickly enough to cover meals, potentially leading to uncontrolled blood sugar spikes. Drawing the clear insulin first ensures that if any insulin is accidentally pushed back into the vial, it is the clear insulin itself, protecting the remaining supply. The cloudy NPH vial is protected because its contents are already a suspension, and a small addition of clear insulin does not significantly change its time-action profile.
Step-by-Step Guide to Drawing Up Mixed Insulin
The process begins by preparing the cloudy NPH insulin vial, which requires gentle mixing. Roll the NPH vial carefully between your palms until the suspension is uniformly milky white. Avoid shaking the vial, as this creates air bubbles that affect dosing accuracy. Next, clean the rubber stoppers of both the NPH and the clear insulin vials with alcohol and allow them to dry fully.
Draw air into the syringe equal to the dose of the cloudy NPH insulin needed. Insert the needle into the NPH vial and inject this air, then withdraw the needle without drawing any liquid. This equalizes the pressure within the vial, making it easier to withdraw the NPH dose later.
Next, draw air into the syringe equal to the dose of the clear insulin needed. Insert the needle into the clear insulin vial and inject the air. Keep the needle in place, turn the vial upside down, and pull the plunger to withdraw the exact dose of clear insulin. Check carefully for air bubbles, and then remove the needle from the clear vial.
Finally, insert the needle into the cloudy NPH vial. Turn the NPH vial upside down and slowly pull the plunger back to withdraw the required dose of NPH insulin, stopping precisely at the total combined dose mark on the syringe. Be careful not to push any clear insulin already in the syringe back into the cloudy vial during this final withdrawal step.
Safety Considerations and When Not to Mix
Always confirm the labels on both vials to ensure the correct type and concentration of each insulin. Failing to roll the NPH vial is a common error, resulting in an inaccurate dose because suspended particles settle at the bottom. Rolling properly re-suspends the contents and slightly warms the insulin if it was refrigerated, without introducing air bubbles that shaking would cause.
Once the two insulins are drawn into the syringe, they must be injected immediately, ideally within five minutes of mixing. The clear, rapid-acting insulin begins to interact with the protamine in the NPH insulin as soon as they are combined. Delaying the injection causes the clear insulin to bind to the protamine, altering its intended quick-action effect and leading to unpredictable blood sugar management.
The need to mix insulin is avoided when using a pre-mixed insulin pen or cartridge, which contains the two insulins already combined in a fixed ratio. Individuals using an insulin pump only use rapid-acting insulin, making manual mixing irrelevant to their therapy. Always consult with a healthcare professional before making any changes to an insulin routine or attempting to mix insulins.