D50 or D10 to Treat Hypoglycemia?

One option favorably compares and is safer than its more commonly used alternative.

Hypoglycemia is commonly evaluated and managed in the emergency department. According to the CDC, there were 235,000 ED visits for hypoglycemia and 57,000 hospitalizations for hypoglycemia just among diabetic patients in 2016.^[1,2]

Compared to 7.6 million emergency department visits annually for chest pain, this number may seem miniscule in comparison. However, it is a costly diagnosis as the elderly and those with poor access to healthcare are more likely to require hospitalization and incur higher healthcare costs.

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This data does not account for non-diabetic patients, which is a much lower number but does add to the total number of ED visits and hospitalizations. The more troubling number is the mortality, which is anywhere between 4% and 20%, with a much higher mortality in non-diabetics. So, it is paramount that emergency physicians recognize and manage these patients in a timely fashion to prevent morbidity and mortality.

Background

Standard management of hypoglycemia in the emergency department includes providing glucose. If the patient is able to tolerate, it is almost certainly better to administer oral glucose, or better yet, a form of nutrition composed of carbohydrates, protein and fat to provide substrate for later storage and utilization.

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For the patient who is not able to tolerate oral preparations, parenteral dextrose is available. There are various concentrations of dextrose, ranging from 5% up to 50%. Often, when a patient presents with symptomatic hypoglycemia, a higher concentration of dextrose is chosen for administration in order to deliver sugar to the cells quickly and subsequently resolve any signs or symptoms. The concentration most frequently chosen in adult patients is dextrose 50% in water, otherwise known as “D50,” with an ampule of D50 coming in a 50mL luer-jet syringe. This will administer 25 grams of dextrose to the patient.

Is D50 the optimal choice in the management of these patients?  We have all had the experience of giving an ampule of D50 to a patient with hypoglycemia, observing the glucose concentration reach adequate levels, and the later the patient becomes hypoglycemic again. How does this rebound hypoglycemia happen?  Looking at the pharmacokinetics of D50, it has a half-life of about 25- to 30-minutes.

A 25-gram bolus of concentrated dextrose causes a huge spike in available glucose and, subsequently, in endogenous insulin secretion by the pancreas. Consequently, once that dextrose has worn off, there is residual insulin hanging around in the system that contributes to the rebound hypoglycemia that is often seen. Additionally, the spike in glucose causes the cessation of gluconeogenesis and glycogenolysis, which would maintain the patient in a euglycemic state.

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D50 Downside

In addition to its increased potential for rebound hypoglycemia, D50 can actually be harmful to patients. Some medications, such as calcium chloride and sodium bicarbonate, should not be administered via a peripheral line except in emergency situations. This is because these medications have a very high osmolarity making them caustic to veins, painful for patients during infusion and high risk for tissue damage if extravasated into the tissue.

Calcium chloride and sodium bicarbonate have osmolarities of about 2,000 mOsm/L. D50 has a greater osmolarity than both with an osmolarity of 2,500 mOsm/L. Yet, it is very commonly administered through a peripheral IV.

There are a few case reports of patients who received D50 through a peripheral IV, which extravasated and caused complications.Two recovered with hyaluronidase injections into the area of extravasation and made a full recovery.^[5,6]  Another one developed compartment syndrome and was taken to the operating room for a fasciotomy.^[7]

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Another Option

What alternative do we have for parenteral management of hypoglycemic patients?  The answer is 10% dextrose, also known as “D10.” In this dose, 250 mL of D10 is equivalent to 50 mL of D50 in that both give 25 grams of dextrose. There are some benefits to utilizing D10. First, the osmolarity of D10 is only 500 mOsm/L compared to the 2,500 mOsm/L of D50. Subsequently, with D10, there is much less risk of tissue damage if the infusion were to extravasate into the tissue. Second, it is much easier to infuse D10 than D50.

D50 must be pushed as an injection, which can sometimes be difficult, especially through a smaller caliber IV catheter. D10 can be run wide open as a bolus of 250 mL over however long it takes to infuse. Last, although the bolus of 250 mL of D10 administers the same amount of dextrose as 50 mL of D50, it is a less concentrated infusion. Therefore, there is not as much of a glucose spike inside the tissue, which leads to less of an insulin spike and allows gluconeogenesis and glycogenolysis to still occur. Result: less rebound hypoglycemia.

With the decreased concentration of dextrose in D10, one would assume that it is not as effective as D50 in cessation of hypoglycemia or its symptoms. However, the literature would suggest otherwise. The prehospital literature has three studies looking at D10 vs. D50 in the prehospital setting. The first was a randomized controlled trial done in 2005 where only profoundly hypoglycemic patients (glucose of 4 mmol/L or less) were chosen.^[8]

EMS administered either D10 or D50 to these patients through a peripheral IV in small aliquots and measured the time for the patient to achieve a GCS of 15, how much dextrose was administered, and glucose concentrations after treatment. It was a small study with only 51 patients, however, there was no statistically significant difference between the groups in terms of the time to get to a GCS of 15 (eight minutes for both groups).

There was a significant difference in terms of the dextrose administered, much less with the D10 (10 grams vs. 25 grams in the D50 group), and a difference in the post-treatment glucose levels, again, less in the D10 group (6.2 mmol/L vs. 9.4 mmol/L in the D50 group).

Both groups had the same incidence of rebound hypoglycemia. The second study evaluated an EMS system switching from D50 to D10 after D50 went on shortage and increased in price.^[9]

The system wanted to assess the feasibility and safety of using D10 as an acceptable alternative in hypoglycemic patients. Overall, they managed almost 164 patients with D10. No adverse events or deaths were reported. About 18% of the patients required a second dose of D10. It was found that D10 was feasible and safe to use in the management of hypoglycemic patients.

From this study, it appears that D10 is at least as effective as D50 in abating symptoms in hypoglycemic patients. The last study, a retrospective study published in 2021, again showed there was no statistically significant difference between D10 and D50 in hypoglycemic patients.^[10]

Conclusion

Therefore, the proposed algorithm is as followed. If a patient is able to tolerate oral nutrition, give them oral glucose or a meal with carbohydrates, protein and fat. If a patient is not able to tolerated PO, establish an IV and administer 100 to 250 mL of D10. Both of these medications can be administered IO as well so don’t forget that as an alternative route.

Bottom Line: D10 is a safer alternative to D50 in the management of hypoglycemic patients in the emergency department.

References:

1. HCUP Nationwide Emergency Department Sample (NEDS). Healthcare Cost and Utilization Project (HCUP). 2016. Agency for Healthcare Research and Quality, Rockville, MD. hcup-us.ahrq.gov/nedsoverview.jsp
2. HCUP National Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2016. Agency for Healthcare Research and Quality, Rockville, MD. hcup-us.ahrq.gov/nisoverview.jsp
3. Glynn N, Owens L, Bennett K, et al. Glucose as a risk predictor in acute medical emergency admissions. Diabetes Res Clin Pract. 2014 Jan;103(1):119-26. Epub 2013 Nov 4.
4. Tsujimoto T, Yamamoto-Honda R, Kajio H, et al. Prediction of 90-day mortality in patients without diabetes by severe hypoglycemia: blood glucose level as a novel marker of severity of underlying disease. Acta Diabetol. 2015 Apr;52(2):307-14.
5. Lawson SL, Brady W, Mahmoud A. Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment–a clinical report. Am J Emerg Med. 2013 May;31(5):886.e3-5.
6. Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med. 2010 Feb;28(2):257.e1-2.
7. Chinn M, Colella MR. Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report. Prehosp Emerg Care. 2017 Jan-Feb;21(1):79-82.
8. Moore C, Woollard M. Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial. Emerg Med J. 2005 Jul;22(7):512-5.
9. Kiefer MV, Gene Hern H, Alter HJ, Barger JB. Dextrose 10% in the treatment of out-of-hospital hypoglycemia. Prehosp Disaster Med. 2014 Apr;29(2):190-4.
10. Weant KA, Deloney L, Elsey G, Combs D, French D. A Comparison of 10% Dextrose and 50% Dextrose for the Treatment of Hypoglycemia in the Prehospital Setting. J Pharm Pract. 2021 Aug;34(4):606-611.