New information about U-100/U-40 syringes.

This is from the blog of Dr. Peterson, who is a widely known expert in veterinary endocrinology. It seems to say that U-40 syringes are more accurate at doses under 8 units than U-100's. I don't know why, but I find that hard to believe; in addition to which, they list all the reasons why you can't actually easily use a U-40 syringe with a U-100 insulin. (Lack of diluents, for example.) It even says that they found that the pen needles were more accurate than the U-100's. :shock:

Insights into Veterinary Endocrinology
Thursday, June 19, 2014

Top Clinical Endocrinology Research Abstracts Presented at the 2014 ACVIM Meeting: Diabetes


Last week, I spent a week in Nashville, Tennessee attending the the 2014 American College of Veterinary Internal Medicine Forum. As part of that meeting, a number of research abstracts were presented (oral and poster presentations) that dealt with various aspects of canine and feline endocrinology. I plan to take the next four blog posts to discuss some of the newest and best research findings featured at the ACVIM meeting.

Of all of the excellent endocrine research abstracts presented, I've selected a "top 12 list" of the ones that have the most potential to change what I do in my clinical practice. To do this, I've enlisted the help of Dr. Rhett Nichols, a well-known expert in endocrinology and internal medicine whose day-job is senior member of the veterinarian consulting service for Antech Diagnostics, the world's largest laboratory dedicated to animal health. However, since Rhett also serves as a consultant for the Animal Endocrine Clinic (my practice), it was not that difficult to get him involved in this project!

In this post, we will review 3 of these top 12 abstracts, followed by the remaining 9 abtracts in the upcoming 3 posts. We hope you agree with our selections, but if you don't, remember that you can always post a comment and add your opinion.



Borin-Crivellenti S, Bonagura, JD, Gilor G. Comparison of Precision and Accuracy of U100 and U40 Insulin Syringes. J Vet Intern Med 2014;28:1029.

Day-to-day variability of insulin action is an important factor in attaining glycemic control in diabetics. In part, this variability is caused by imprecise dosing of insulin.

We hypothesized that a U40 insulin syringe (U40) would be more precise than a U100 insulin syringe (U100). We dispensed 1, 2.5, and 4 international unit (IU) of insulin using 24 syringes for each dose from a BD Ultra-Fine 0.3-cc U100 (1⁄2 Unit Markings) and a VetOne 0.3-cc U40. Each dose was weighed on an analytical scale, and accuracy (mean [± SD] of actual dose–target dose*100/target dose) and precision (the coefficient of variation [SD/Mean] of the actual dose) were calculated. The proportions of CID (clinically important deviation: ≥ ± 20% off target) outcomes were compared between syringe types.

U40 was more accurate for 1, 2.5 and 4IU (13.2 ± 8.7%; 6.0 ± 2.76%; 3.2 ± 1.6%, respectively) than U100 (28.2 ± 15.4%; 10.7 ± 8.0%; 4.6 ± 2.9%, respectively) (p < 0.05). Precision was lowest for 1IU but improved with increasing dose (U40: 1IU = 15.8%, 2.5IU = 6.4%, 4IU = 3.5%; U100: 1IU = 15.1%, 2.5IU = 8.1%, 4IU = 3.3%). U40 was more precise than U100 for dosing of 2.5IU (p < 0.05) despite the 1/2-unit markings on U100. CID outcomes were more frequent in U100 vs. U40 in 1IU (16/24 vs. 8/24 respectively, p = 0.02) and 2.5IU (3/24 vs. 0/24 respectively, p = 0.07) but did not occur in 4IU.

For administration of small insulin doses, U40 are more accurate and precise than U100 and are less likely to result in clinically important over- or under-dosing. These results favor the use of U40 for administration of small doses of insulin.

Comments— Although the administration of low doses of U100 insulin (e.g., glargine, detemir, NPH) is common practice in veterinary medicine, this study reveals remarkably high dose error when doses of 4 units or less of U100 insulin are administered. Since similar findings were reported in human pediatric patients given low doses of insulin (1-3) one to two decades ago, the results of this study should not be all that surprising. The use of U100 syringes can be dangerously inaccurate with administering very low insulin doses, and the use of syringes with 1/2 unit markings has not been shown to improve accuracy or precision (3).

Most human diabetologists recommend diluting the insulin when low doses of U100 insulin must be given (1-3). However, one must remember that there are many problems associated with dilution of these U100 insulins (4,5). First of all, glargine should never be diluted under any circumstances. Other U100 insulins, such as NPH or detemir, can be diluted, but this may alter the absorption kinetics of the insulin. For NPH (Humulin N), one can obtain the special diluent from the insulin manufacturer (Eli Lilly) or the pharmacy. For detemir (Levemir, Novo Nordisk), the insulin manufacturer has a special diluting medium, but the company generally will not provide the diluent to veterinarians. Detemir can be diluted with sterile water or saline, but this dilutes the insulin's antimicrobial additive and increases the risk of bacterial contamination. Therefore, because of the risk of bacterial contamination and changes with efficacy, diluting detemir is not generally recommended (5).

In both human patients and dogs, the use of insulin pen devices have consistently shown to be more accurate than dosing with insulin syringes (2,3,6). In one recent veterinary report (6), an insulin pen device was found to be more accurate than the insulin syringes when low doses (<8 units) of insulin were administered. In that study, insulin syringes tended to over-deliver by approximately 20-25% for very low doses (1 unit). However, for higher doses (16 units), the insulin pen and insulin syringe were comparable in accuracy.

The Bottom Line—Administration of low doses of insulin can be very inaccurate and imprecise, especially when using a U100 insulin and syringe. Use of U40 insulin improves accuracy but still is far from perfect. Either dilution of U-100 insulin (if possible) or use of an insulin pen device will help to improve accuracy when low-dose insulin administration is required.

References:
Casella SJ, Mongilio MK, Plotnick LP, et al. Accuracy and precision of low-dose insulin administration. Pediatrics 1993;91:1155-1157.
Gnanalingham MG, Newland P, Smith CP. Accuracy and reproducibility of low dose insulin administration using pen-injectors and syringes. Arch Dis Child 1998;79:59-62.
Keith K, Nicholson D, Rogers D. Accuracy and precision of low-dose insulin administration using syringes, pen injectors, and a pump. Clin Pediatr (Phila) 2004;43:69-74.
Pet Diabetes: Diluting insulin. http://petdiabetes.wikia.com/wiki/Diluting_insulin
Roomp K, Rand JS. Management of diabetic cats with long-acting insulin. Vet Clin North Am Small Anim Pract 2013;43:251-266.
Burgaud S, Riant S, Piau N. Comparative laboratory evaluation of dose delivery using a veterinary insulin pen (abstract 121). Proceedings of the WSAVA//FECAVA/BSAVA Congress; 12-15 April 2012;567.

 

Yes, the pens are more accurate than syringes, especially at low does
http://www.ncbi.nlm.nih.gov/pubmed/20515311
http://care.diabetesjournals.org/content/22/1/137

Yes, it would be expected that U40 syringes (when used with U40 insulin) would be more accurate since there is more volume per unit with U40's. Thus inaccuracies in markins, especially the zero marking, would have less effect