Introduction 

• 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.

Pharmacology

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
Administration	IV push
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%)

Conclusions

• 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

References 

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.