How does insulin lower serum potassium in acute hyperkalaemia and what is the recommended intravenous insulin and glucose regimen?

How Insulin Lowers Serum Potassium

Insulin drives potassium from the bloodstream into cells by activating sodium-potassium ATPase pumps on cell membranes, effectively lowering serum potassium by approximately 0.5–1.2 mEq/L within 30–60 minutes of administration. 1, 2

Cellular Mechanism

Insulin binds to cell surface receptors and triggers a cascade that activates Na-K-ATPase pumps, which actively transport potassium ions from the extracellular space into the intracellular compartment 1. This transcellular shift does not eliminate potassium from the body—it simply redistributes it, which is why the effect is temporary, lasting only 2–4 hours 1.

The onset of potassium-lowering begins at approximately 30 minutes after insulin administration, with peak effect occurring within 30–60 minutes 1. Because this is a redistribution rather than elimination, additional interventions (such as potassium binders or dialysis) are needed for sustained potassium control in patients with ongoing hyperkalemia 1.

Clinical Application: The Standard IV Insulin-Glucose Regimen

Recommended Dosing Protocol

For acute hyperkalemia treatment, administer 10 units of regular insulin intravenously with 25 grams of dextrose (50 mL of D50W) to lower serum potassium while preventing hypoglycemia. 1, 2

• The standard regimen produces a potassium reduction of 0.65 ± 0.09 mmol/L when insulin is given with glucose 2
• Combining insulin with nebulized albuterol (10–20 mg) produces an additive effect, lowering potassium by approximately 1.21 ± 0.19 mmol/L—significantly greater than either agent alone 2
• The hypoglycemic effect of insulin is attenuated when albuterol is co-administered, making combination therapy both more effective and safer 2

Timing of Glucose Administration

Administer hypertonic glucose (25 grams IV over 5 minutes) before the insulin bolus, not after, to minimize hypoglycemia risk while maintaining efficacy. 3

This sequence—glucose first, then insulin—is clinically effective, well-tolerated, and avoids the hypoglycemic complications seen when insulin precedes glucose 3. The approach induces a significant fall in plasma potassium while causing a transient rise and then normalization of plasma glucose, with no hypoglycemic side effects 3.

Dose Considerations

Use the full 10-unit dose of regular insulin for patients with serum potassium >6.0 mEq/L, as reduced doses (5 units) are significantly less effective in this range. 4

• A post-hoc analysis revealed that reduced-dose insulin (5 units) produced 0.238 mmol/L less potassium reduction compared to conventional dosing (10 units) when baseline potassium exceeded 6.0 mmol/L 4
• At lower potassium levels (5.5–6.0 mEq/L), there was no significant difference between doses, but the conventional dose remains standard practice 4

Critical Safety Considerations

Hypoglycemia Risk and Monitoring

Hypoglycemia occurs in 6–44% of patients treated with insulin-glucose for hyperkalemia, with severe hypoglycemia (<54 mg/dL) occurring in 1–10% of cases. 5, 6

• The wide range in reported incidence reflects differences between retrospective (lower rates) and prospective studies (higher rates), suggesting hypoglycemia is often underrecognized 6
• The median time to hypoglycemia onset is 2 hours (range 1–2 hours), but it can occur throughout the 3-hour post-treatment window 6
• Low pretreatment blood glucose (<100 mg/dL) is the single most significant predictor of post-treatment hypoglycemia 5, 6

Monitor blood glucose hourly for at least 3 hours after insulin administration, regardless of whether the patient has diabetes or received adequate dextrose. 6

• Age, sex, renal function, diabetes diagnosis, and previous insulin treatment do not reliably predict hypoglycemia risk 5
• Even with an infusion protocol combining insulin plus glucose, 6.1% of treatments resulted in hypoglycemia 5
• Patients with impaired renal function (AKI or non-dialysis CKD) remain at risk despite adequate glucose co-administration 5

Special Context: Diabetic Ketoacidosis and Hyperglycemic States

In DKA and HHS, patients typically present with normal or elevated serum potassium despite massive total body potassium depletion of 3–5 mEq/kg body weight. 1

This paradox occurs because acidosis and insulin deficiency drive potassium out of cells into the serum 1. Once insulin therapy begins, three mechanisms rapidly drive serum potassium dangerously low:

• Insulin-mediated cellular uptake 1
• Correction of acidosis (which shifts potassium intracellularly) 1
• Volume expansion with fluid resuscitation (dilutional effect) 1

If presenting potassium is <3.3 mEq/L in DKA/HHS, delay insulin therapy until potassium is repleted to prevent life-threatening arrhythmias, cardiac arrest, and respiratory muscle weakness. 1

Once serum potassium falls below 5.5 mEq/L during DKA/HHS treatment (and adequate urine output ≥0.5 mL/kg/hour is confirmed), add 20–30 mEq potassium per liter of IV fluid using 2/3 potassium chloride and 1/3 potassium phosphate. 1

• This mixed formulation simultaneously restores phosphate stores, which are also depleted in hyperglycemic crises 1
• Monitor potassium levels every 2–4 hours during active treatment 1
• Hypokalemia develops in approximately 50% of DKA patients during treatment, and severe hypokalemia (<2.5 mEq/L) is associated with increased inpatient mortality 1

Common Pitfalls to Avoid

• Administering insulin without glucose in non-hyperglycemic patients: Even patients with normal baseline glucose can develop severe hypoglycemia 5
• Giving insulin after glucose instead of before: This sequence increases hypoglycemia risk without improving efficacy 3
• Using reduced insulin doses (5 units) for severe hyperkalemia (K+ >6.0 mEq/L): This produces significantly less potassium reduction 4
• Failing to monitor glucose for the full 3-hour window: Hypoglycemia can occur late, with median onset at 2 hours 6
• Assuming diabetic patients are at higher risk for hypoglycemia: Diabetes status does not predict hypoglycemia risk; low pretreatment glucose does 5, 6
• Starting insulin in DKA/HHS before verifying potassium ≥3.3 mEq/L and adequate urine output: This can precipitate fatal arrhythmias 1
• Not adding potassium to IV fluids once serum K+ drops below 5.5 mEq/L in hyperglycemic crises: This leads to dangerous hypokalemia in 50% of cases 1