Insulin remains one of the cornerstones of early severe hyperkalemia management. Insulin works via a complex process to temporarily shift potassium intracellularly. Though insulin certainly lowers plasma potassium concentrations, we often underestimate the hypoglycemic potential of a 10 unit IV insulin dose in this setting. The purpose of this post is to highlight the need for proper supplemental glucose and blood glucose monitoring when treating hyperkalemia with insulin.

This is such an important medication safety issue, the Institute for Safe Medication Practices (ISMP) highlighted it in a February 2018 Safety Alert.

Incidence of Hypoglycemia

One of my favorite articles on the management of hyperkalemia was written by Dr. Weisberg in Critical Care Medicine.1 A 10 unit dose of IV regular insulin has an onset of action of about 5-10 minutes, peaks at 25-30 minutes, and lasts 2-3 hours (the Weisberg article actually lists subcutaneous kinetics). Herein lies the problem in that IV dextrose only lasts about an hour (at most). Allon et al reported up to 75% of hemodialysis patients with hyperkalemia developed hypoglycemia at 60 minutes after insulin administration.2 A retrospective review of 219 hyperkalemic patients reported an 8.7% incidence of hypoglycemia after insulin treatment.3 More than half of the hypoglycemic episodes occurred with the commonly used regimen of 10 units of IV insulin with 25 gm of dextrose. A 2014 study of 221 end-stage renal disease patients who received insulin for treatment of hyperkalemia reported a 13% incidence of hypoglycemia.4 A more recent study in 409 ED patients reported 17% of patients developing hypoglycemia (glucose < 70 mg/dL) after insulin for hyperkalemia.5

The overall incidence of hypoglycemia appears to be 10-15%.

Risk Factors for Developing Hypoglycemia

The study by Apel et al identified 3 factors associated with a higher risk of developing hypoglycemia:

No prior diagnosis of diabetes [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.0–5.1, P = 0.05] No use of diabetes medication prior to admission [OR 3.6, 95% CI 1.2–10.7, P = 0.02] A lower pretreatment glucose level In mg/dL : mean 104 ± 12 mg/dL vs 162 ± 11 mg/dL, P = 0.04 In mmol/L : mean 5.8 ± 0.7 mmol/L vs 9.0 ± 0.6 mmol/L, P = 0.04

Renal dysfunction, in and of itself, may also be a risk factor for developing hypoglycemia. Some evidence suggests that insulin is metabolized by the kidneys to some extent. Furthermore, patients with acute kidney injury have clinically relevant changes in insulin metabolism, as evidenced by increased hypoglycemic events and lower insulin requirements upon developing AKI.6

A higher insulin dose (10 units vs. 5 units) caused more hypoglycemia (28.6% vs. 19.5%, 95% confidence interval [CI] -16.8% to -1.3%).7

The 2018 study by Scott et al, identified that lower glucose prior to insulin (adjusted odds ratio [aOR] 0.90; 95% confidence interval [95% CI] 0.85 to 0.96), higher doses of insulin (aOR 1.07; 95% CI 1.01 to 1.15), and lower doses of D50 (aOR 0.98; 95% CI 0.97 to 0.99) were independently associated with hypoglycemia in the multivariate analysis.5 Age, history of diabetes, and history of renal failure were not independently associated.

Strategies for Avoiding Hypoglycemia

Preventing hypoglycemia is important. Some clinicians use up to 20 units of IV regular insulin as the hypokalemic effect is dose-dependent.8 Here is a suggested strategy for administering enough dextrose to counter the initial insulin bolus of 10 or 20 units. It is loosely based on the Rush University protocol.4 Other strategies include q30 minute glucose checks for the first 3 hours with as needed supplemental glucose orders or lower insulin doses.

Initial [glucose] Initial Dextrose Dose Supplemental Dextrose ** Glucose Monitoring > 200 mg/dL (> 11.1 mmol/L) None 25 gm (50 mL) of D50 if blood glucose < 70 mg/dL Hourly up to 3 hours 100-200 mg/dL (5.6-11.1 mmol/L) 25 gm (50 mL) of D50 25 gm (50 mL) of D50 if blood glucose < 70 mg/dL Hourly up to 3 hours < 100 mg/dL (< 5.6 mmol/L) 50 gm (100 mL) of D50* OR

25 gm (50 mL) of D50 + D10 infusion 250 mL/hr for first hour 25 gm (50 mL) of D50 if blood glucose < 70 mg/dL q 30 minutes for first hour, then hourly up to 3 hours D50 = dextrose 50%; D10 = dextrose 10% * There are drawbacks to administering 100 mL (50 gm) of D50. Adam Spaulding, PharmD discusses D50 vs. D10 for severe hypoglycemia in the ED. 50 mL (25 gm) of D50 + infusion of D10 might prevent rebound hypoglycemia and hypertonicity issues with an initial 100 mL (50 gm) dose of D50. ** A supplemental D10 infusion may be needed beyond one hour depending on blood glucose concentrations.

What about using dextrose only?

Theoretically, administering dextrose should stimulate insulin release (if the patient has a functioning pancreas) and thereby lower serum potassium concentrations. Early reports recommend against this technique for 2 reasons.9

Endogenous insulin levels are unlikely to rise to the level necessary for a therapeutic effect There is a risk of exacerbating the hyperkalemia by inducing hypertonicity.

On the flip side, a randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia.10 Administration of 10 units of insulin with 100 mL of 50% glucose (50 g) was compared with the administration of 100 mL of 50% glucose only. Infusion of a glucose-only bolus caused a clinically significant decrease in serum potassium by 0.5 mEq/L without any episodes of hypoglycemia. The insulin/glucose group saw a drop in potassium of 0.83 mEq/L at 60 minutes.

Bottom Line: Based on conflicting data, and considering that many patients have ESRD plus diabetes, this approach has potential but may not be ready for mainstream use. Also, hyperglycemia may be undesirable in some patients.

Take Home Points

The hypoglycemic effects of IV insulin last longer than a bolus of dextrose. More than one dextrose dose is often needed when treating hyperkalemia.

One ‘amp’ (50 mL, 25 gm) of D50 is not enough to counteract the hypoglycemic effect of insulin in patients with normoglycemia to start.

Make sure to check glucose at the 30-minute and hour mark after administering IV insulin. Insulin’s peak effect by this route occurs within 30-60 minutes and this period is when hypoglycemia has most often been reported in the literature.

Order sets are key to preventing this common medication error.

Dr. Scott Weingart and I discuss this issue on his EMCrit podcast 101: Avoiding Resuscitation Medication Errors – Part 1.

Last updated: August 23, 2018

Editor’s note: Reference 1 indicates that the kinetics for IV regular insulin are as follows: onset 20 minutes, duration 4-6 hours. That is actually the subcutaneous insulin kinetics. The corrected IV kinetics are reflected in the post.

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