Think back to your last severely hypoglycemic and lethargic patient presenting to the ED. What was the first treatment modality that came to mind? The initial knee-jerk reaction might be to reach for that big blue box of D50 if the patient has IV access. After all, top priority is to reverse hypoglycemia as fast as possible. But in the midst of stabilizing the patient, how often do we consider the potential aftermath of concentrated glucose?

Drawbacks of D50

1. Rebound hypoglycemia

After administration of D50 there is an excess amount of glucose available, leading to increased uptake and utilization by the tissues, which suppresses both gluconeogenesis and glycogenolysis. Without continued administration of dextrose-containing fluids, this may result in rebound hypoglycemia. Moreover, with the loss of IV access, a busy ED, and a subsequent fingerstick in the 200’s, the decision to initiate such fluids may be overlooked or delayed, thereby facilitating this risk of rebound hypoglycemia.

Unfortunately, the prevalence of rebound hypoglycemia from D50 is not well documented. One study reported subsequent hypoglycemic events occurring among 18% of patients who received both D50 and D10.1 Another study reported that glucose levels after administration of D50 returned to baseline within 30 minutes in a sample of healthy volunteers.2

2. Overshooting glycemic targets after treatment

Several studies have reported post-administration glucose levels between 160-250 mg/dL1,2; While this may be perceived as inconsequential during initial management, a recent retrospective, single-center study in the critically ill suggests that both rapid excursions in glucose and subsequent glycemic variability may be the best predictors of overall morbidity and mortality among these patients.3 It may be reasonable to consider other treatment approaches that may be less likely to complicate further glycemic management upon admission to the hospital, instead of one that can exacerbate glycemic variability.

3. Hypertonic toxicity

It is well known that intravenous administration of hypertonic fluids may result in harm to surrounding tissues. In fact, the osmolarity of D50 is even greater than that of 8.4% sodium bicarbonate (2500 mOsm/L compared to 2000 mOsm/L, respectively). Most would advocate for administration via a central line with osmolarities in excess of 900 mOsm/L.4 While the literature varies, rates of extravasation from such fluids have been cited to be as high as 10-30%.5 This risk can be mitigated somewhat by pushing D50 slowly over 2-5 minutes. Consider however, the osmolarity of 10% dextrose (D10) is 500 mOsm/L, and within range for safer peripheral administration.

Adverse effects of D50 include:

Local skin irritation

Thrombophlebitis

Extravasation with subsequent tissue necrosis

Evidence for use of 10% Dextrose (D10)

One small randomized controlled trial evaluated the effectiveness of D10 vs D50 for the treatment of hypoglycemia by EMS providers in the pre-hospital setting.1 The study included 51 profoundly hypoglycemic patients (median blood glucose of 26 mg/dL evenly distributed among both arms. The investigators pushed small 5 g aliquots of each (50 mL of D10 and 10 mL of D50), while waiting one minute in between doses to reassess the patient. The maximum cumulative dose of dextrose permitted was 25 g.

The primary objective of the study was time to Glasgow Coma Scale (GCS) score of 15. The investigators also took note of post-treatment glucose levels, and the total dose of dextrose administered. Here are the pertinent results:

Median pre-treatment GCS was 4 and 6 in the D10 and D50 arms, respectively.

Median time to GCS of 15 was 8 minutes in both groups .

. Median total doses administered were 10 g (100 mL) and 25 g (50 mL) in the D10 and D50 arms, respectively.

Median post-treatment glucose levels were also significantly different : 111 mg/dL in the D10 arm and 169 mg/dL in the D50 arm.

: 111 mg/dL in the D10 arm and 169 mg/dL in the D50 arm. Rates of rebound hypoglycemia were identical between both groups (18%).

This study suggests that higher concentrations of dextrose-containing fluids do not expedite reversal of hypoglycemia as compared to lower concentrations, and that lower concentration formulations are more likely to achieve normal glycemic targets. However, because the investigators used aliquots of dextrose to permit intravenous pushing of both formulations, concern may arise over the study’s external validity- -as lower-concentrations of dextrose are typically given as piggybacks or continuous infusions in the Emergency Department. Additionally, no information was provided regarding rates of administration in either arm.

More recently, the California Contra Costa County EMS system revised their current protocol adopting the use of a 100 mL bolus of 10% dextrose for treatment of hypoglycemia in the field.6 An observational cohort of 162 patients treated after protocol implementation demonstrated the feasibility, safety and efficacy of this treatment modality. The median initial blood glucose of patients in the cohort was 38 mg/dL, and median post-treatment glucose levels were 98 mg/dL. The median time to second recheck of blood glucose was 8 minutes. Of those treated, 18% required an additional 100 mL bolus. There were no adverse events or deaths reported. Interestingly, a linear regression analysis of the elapsed time between initial and subsequent glucose values suggested minimal short-term decay in blood glucose after administration – a frequently cited concern with administration of D50.

Infusion Misconceptions

A common over-simplification made during acute situations is that medications need to be given by intravenous push for rapid administration. While this may be true in many cases, it may not be when dealing with vesicant substances, such as dextrose. Although D50 is intended to be given via intravenous push, it still requires slow administration. Another misconception is that administration via piggyback is “too slow.” While flow rates will vary depending upon the cooperation of the patient and the intravenous access obtained, even small, 22 gauge catheters can achieve flow rates of between 35-40 mL/min. Additionally, small amounts of pressure applied to the bag may effectively double the rate of administration.7 Thus, a 200 mL bolus of D10 (20 g) can be administered about just as fast as an amp of D50 should be.

Potential Scenario

“Our hypoglycemic patient is much more alert and oriented after 25 grams of D50, however, we completely blew the IV line in their hand, we can’t get another line in, and the repeat fingerstick is now 250 mg/dL. Is there a way to avoid these complications in the future?”

Suggested Approach

If intravenous access has been obtained:

Hang a 250 mL bag of 10% dextrose, and administer a bolus of 100-200 mL.

If a very small catheter has been used (22-24G), may apply light pressure to bag to facilitate administration.

Clamp tubing between boluses, and reassess for improvements in mental status. Re-check the fingerstick glucose.

Repeat boluses as needed until the patient becomes alert and oriented, and/or until normoglycemia is achieved.

The aforementioned approach may be most applicable when:

A patient has a poor-quality line

A patient is a known brittle diabetic

Ongoing drug shortages preclude access to D50

References

Emerg Med J. 2005;22(7):512-515. PubMed] Moore C, Woollard M. Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial.. 2005;22(7):512-515. Acad Emerg Med. 1998;5(7):691-694. PubMed] Balentine J, Gaeta T, Kessler D, Bagiella E, Lee T. Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers.. 1998;5(7):691-694. Crit Care Med. 2008;36(11):3008-3013. PubMed] Krinsley J. Glycemic variability: a strong independent predictor of mortality in critically ill patients.. 2008;36(11):3008-3013. Nutrition. 1998;14(6):496-501. PubMed] Kuwahara T, Asanami S, Kubo S. Experimental infusion phlebitis: tolerance osmolality of peripheral venous endothelial cells.. 1998;14(6):496-501. Am J Emerg Med. 2010;28(2):257.e1-2. PubMed] Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation.. 2010;28(2):257.e1-2. Prehosp Disaster Med. 2014;29(2):190-194. PubMed] Kiefer M, Gene H, Alter H, Barger J. Dextrose 10% in the treatment of out-of-hospital hypoglycemia.. 2014;29(2):190-194. Emerg Med J. 2011;28(3):201-202. PubMed] Reddick A, Ronald J, Morrison W. Intravenous fluid resuscitation: was Poiseuille right?. 2011;28(3):201-202.