Written by Amanda Mathews
Spoon Feed
When comparing IV insulin lispro versus IV insulin regular for hyperkalemia in the ED, lispro was associated with a significant decrease in potassium but an increase in hypoglycemic events.
Is one insulin too regular for hyperK treatment?
This was a retrospective cohort study of adults in two academic emergency departments treated for hyperkalemia with 5 units of IV insulin. Site A used insulin regular and Site B used insulin lispro. The remainder of their order sets for hyperkalemia treatment were similar. The dose of 5 units was chosen based on pre-populated department order sets. 237 patients met study criteria, of which 129 received insulin regular and 108 received insulin lispro.
The primary endpoint of the study was change in first post-insulin serum potassium result within 6 hours. An additional primary safety endpoint was the frequency of hypoglycemia (defined as <70 mg/dl) or supplemental dextrose administration within 6 hours. There was a larger decrease in potassium with lispro compared to regular (unadjusted mean difference -0.24, 95%CI -0.42 to -0.06). While the first blood glucose reading post-IV-insulin administration was similar between the two groups, more patients had hypoglycemia in the lispro group (16%) compared to the regular group (7%). Odds of hypoglycemia were greater among those who received lispro versus regular (unadjusted OR 2.49, 95%CI 1.08 to 6.09).
While not a primary object of the study, authors found that patients who were given albuterol in addition to IV insulin had an increased reduction in potassium, and there was a larger proportion of patients that also received albuterol in the insulin regular cohort which could confound results.
How will this change my practice?
While this study is not immediately practice-changing, it could be a realm for further study. It seems that both insulin lispro and regular could be safely used in an order set for hyperkalemia treatment; however, one must be cognizant of hypoglycemia post insulin administration and ensure that blood glucose checks are included in any order set being used.
Editor’s note: A retrospective cohort study should never be called a “trial.” The AJEM editors should not have allowed this title. ~Clay Smith
Source
Comparison of Single-Dose Intravenous Insulin Regular vs. Insulin Lispro for Hyperkalemia Treatment in the Emergency Department: The SIR-LISPRO Trial. Am J Emerg Med. 2025 Dec 26;101:92-98. doi: 10.1016/j.ajem.2025.12.031. Epub ahead of print. PMID: 41477935; PMCID: PMC12810486.
View JournalFeed Critical Appraisal
Critical Appraisal
Study Identification
Background
Study Question
Study Design & Conduct
Prospective / Retrospective: Retrospective
Multicenter: Yes
Unit of Allocation: Not applicable
Unit of Analysis: Patients
Randomization Method: Not applicable
Allocation Concealment: Not applicable
Blinding: Not applicable
Follow-up Duration: 6 hours
Population
- Adults admitted to the ED
- Treated for hyperkalemia with 5 units of IV insulin
- Not reported
Number Enrolled: 237
Number Analyzed: 237
Key Baseline Characteristics
Sex: Not reported
Disease Severity: Not reported
Care Setting Distribution: Emergency Department
Exposures / Interventions
Description: Intravenous insulin lispro
Definition / Dose: 5 units
Timing: Upon ED admission for hyperkalemia
Classification Method: Not reported
Protocolized / Discretionary: Discretionary
Description: Intravenous insulin regular
Definition: 5 units
Outcomes & Results
Primary Outcomes
Definition: Change in serum potassium within 6 hours following IV insulin administration
Time Point: 6 hours
Measurement Method: Standard laboratory methods
Results: uMD: -0.24; 95% CI: -0.42, -0.06
Secondary Outcomes
Definition: Proportion of patients with blood glucose <70 mg/dL or requiring supplemental dextrose
Time Point: 6 hours
Measurement Method: Standard laboratory methods
Results: uOR: 2.49; 95% CI: 1.08, 6.09
Risk of Bias
Risk of Bias - ROBINS-I
- Confounding (Some concerns): Potential confounders not fully adjusted due to retrospective design.
- Selection of participants (Low): Clear inclusion criteria for ED patients treated for hyperkalemia.
- Classification of interventions (Low): Interventions were clearly defined as insulin lispro or regular.
- Deviations from intended interventions (Low): No deviations reported as interventions were standard practice.
- Missing data (Low): Outcome data were available for all included patients.
- Measurement of outcomes (Low): Outcomes were objectively measured using standard laboratory methods.
- Selection of the reported result (Some concerns): Potential for selective reporting due to retrospective nature.
Transparency
COI Statement Present: TRUE
