• Insulin with dextrose is an effective method to lower potassium levels quickly in acute hyperkalemia. • Literature shows ranges of potassium reduction by 0.5-1.0 mEq after administration of a single dose. • Patients with renal insufficiency and end stage renal disease (ESRD) have a higher incidence of hypoglycemia after treatment with insulin for hyperkalemia due to:
o Reduced insulin clearance (prolonged insulin action)
o Reduced hepatic glucose production
o Reduced renal gluconeogenesis
• The appropriate dose of insulin to minimize hypoglycemic events when using for the treatment of hyperkalemia in patients with renal insufficiency is still debated.
|Medication||Insulin (human regular)|
|Mechanism||Cause an intracellular shift of potassium via exchange of sodium ions via the Na+/K+ ATPase pump|
|Dose||5-10 units Doses of 0.1 units/kg (max 10 units) have also been considered|
|PK/PD||Onset: 15-30 minutes for initial potassium lowering effects Duration: 4-6 hours, prolonged duration in ESRD|
|Adverse Effects||Hypoglycemia, hypokalemia, hypersensitivity|
|Compatibility||Can dilute in normal saline to increase volume for ease of administration|
|Pearls||Must be given with dextrose (25g IV) to prevent hypoglycemia – Some patients require repeated dextrose; rare exceptions for those already extremely hyperglycemic The most common used product is regular human insulin given IV to ensure fast onset of potassium lowering effects and prevent variable absorption|
Overview of Evidence
|Author, Year||Design (Sample Size)||Intervention & Comparison||Outcomes|
|Verdier et al., 2021||Single center, retrospective (n =174)||5 units vs 10 units IV regular insulin in ICU patients||• Hypoglycemia was more frequent with 10 unit vs 5 units of IV insulin (19.5 vs 9.2%, p=0.052) • No difference in rates of severe hypoglycemia or change in serum potassium|
|Moussavi et al., 2020||Retrospective, observational (n=700)||10 units vs <10 units IV regular insulin||• Significantly lower frequency of hypoglycemia with lower insulin doses (11.2 vs 17.6%, p=0.008) • Greater reduction in serum potassium with insulin doses <10 units (mean reduction 0.94 vs 0.8, p=0.008)|
|Keeney et al., 2019||Single center, retrospective (n=442)||5 units vs 10 units IV regular insulin||• Hypoglycemic events in patients with reduced eGFR were higher in patients receiving 10 units of insulin (17.4 vs 7.9%, p=0.02) • Similar potassium reductions in both groups|
|McNicholas et al., 2018||Single center, retrospective (n=99)||Evaluate hypoglycemia risk based on usage of hyperkalemia protocol||Subgroup analysis showed trend towards hypoglycemia with higher doses of insulin in ESRD. (5 units: 28% vs 10 units: 54%)|
|LaRue et al., 2017||Single center, retrospective (n=675)||5 units vs 10 units IV regular insulin||• Hypoglycemia was significantly increased in patients receiving 10 units of insulin (28.6 vs 19.5%, 95% CI -16.8% to -1.3%) • No significant difference in potassium decrease|
|Pierce et al., 2015||Single center, retrospective (n=149)||5 units vs. 10 units with low eGFR||No significant difference in hypoglycemia between those receiving 10 units or 5 units of inuslin (19.7 vs 16.7%)|
|Apel et al., 2014||Single center, retrospective (n=221)||Hypoglycemia risk in patients receiving IV regular insulin (4- 10 units) in patients with ESRD on HD||• 90% of patients received 10 units of insulin • 13% of patients experienced hypoglycemia (IV insulin doses not specified) • Patients who were not diabetic had a higher risk of hypoglycemic events (OR 2.3, 95% CI 1.0–5.1, p=0.05)|
|Schafers et al., 2012||Single center, retrospective (n=89)||Evaluated evidence of hypoglycemia in any patient receiving 5 -10 units regular insulin||• 61 patients had renal insufficiency (69%) • 19 patients had hypoglycemia (21%) |
• 15/19 patients who became hypoglycemic had renal insufficiency (79%)
• Hypoglycemia risk seems to be elevated in those patients with renal insufficiency, especially those who are insulin-naive
• Consideration should be made to lower the initial dose of IV insulin for patients with AKI or CKD
1. LaRue, et al. Pharmacotherapy. 2017;37(12):1516-1522.
2. Moussavi, et al. Crit Care Expl. 2020;2:e0092.
3. Allon, et al. Kidney Int 1990;38 (5):869–72. 7.
4. Allon, et al. Am J Kidney Dis 1996;28(4):508–14.
5. Li, et al. Clin Kidney J. 2014;7:239-41.
6. Schafers, et al. Journal of Hospital Medicine. 2012;7(3):239-42.
7. Pierce, et al. Annals of Pharmacotherapy. 2015;49(12).1322-26.
8. McNicholas, et al. Kidney Int Rep. 2018;3:328-36,
9. Apel, et al. Clin Kidney J. 2014;7(2)248-50.
10. Keeney, et al. Am J Emerg Med. 2019; doi.org/10.1016/j.ajem.2019.158374
11. Insulin Human Regular. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2020, February 8. from http://www.micromedexsolutions.com/
12. Insulin human regular. Lexicomp [online database]. Hudson, OH. Woltes Kluwer Clinical Drug Information, Inc. Accessed 2020, February 8. http://www.online.lexi.com
13. Verdier, et al. Aust Crit Care. 2021;S1036-7314(21)00070-9.