INSAKA: Insulin Plus Salbutamol Tops Monotherapy for Hyperkalemia

Adding nebulized salbutamol (albuterol) to intravenous insulin and dextrose lowered serum potassium more at 60 minutes than either therapy alone in adults treated for acute hyperkalemia in the emergency department (ED).¹ The combination outperformed both salbutamol alone and insulin and dextrose alone in the randomized INSAKA trial.

The findings were presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, by Emmanuel Montassier, MD, PhD, professor of therapeutics at Nantes Université and emergency physician at Centre Hospitalier Universitaire (CHU) de Nantes in France. Investigators described the added reduction as modest, and the trial was not designed to show whether a faster drop in potassium changes clinical outcomes, a question Montassier discussed in an interview with HCPLive.

Why Acute Hyperkalemia Management Varies Across Emergency Departments

“There is a huge variation in management of hyperkalemia in the emergency department,” Montassier said. “We have one observational prospective study in 14 emergency departments in the US, and the investigators identified 43 different strategies to manage hyperkalemia during the first 4 hours of ED management.”

Nebulized β2 agonists and intravenous insulin and dextrose are both commonly used to lower serum potassium, but their comparative effectiveness in the ED has been uncertain.¹ Previous research has largely been small, retrospective, or single center, Montassier noted.

To address this gap in research, the team compared insulin and dextrose, nebulized salbutamol, and the combination, hypothesizing that the combination would outperform either therapy alone.

INSAKA Trial Design: Salbutamol, Insulin and Dextrose, or Both

INSAKA was an investigator initiated, multicenter, open label, superiority randomized clinical trial. It was conducted in 13 French EDs from December 20, 2019, through December 31, 2025, and supported by a grant from the French Ministry of Health.¹,²

Adults ≥18 years with serum potassium ≥5.5 mmol/L were eligible. The threshold was lowered from 6.0 mmol/L by protocol amendment during the trial.¹

Participants were randomly assigned 1:1:1 to 1 of 3 arms:¹

• Nebulized salbutamol, 10 mg over 30 minutes
• Intravenous insulin, 10 units, with 500 mL of 10% dextrose over 30 minutes
• Both therapies at the same doses

The outcome of interest was the mean change in serum potassium from baseline to 60 minutes, a timepoint chosen to capture the early effect of each treatment, Montassier said. Secondary outcomes included change at 180 minutes and 24 hours, normokalemia, retreatment or dialysis, and adverse events.¹

Combination Therapy Lowered Potassium More Than Insulin or Salbutamol Alone

Of 410 patients randomized, 398 were analyzed: 133 in the salbutamol arm, 133 in the insulin and dextrose arm, and 132 in the combination arm. The median age was 76 years, 131 (33%) were women, and median baseline serum potassium was 6.2 mmol/L.¹

Mean decreases in serum potassium at 60 minutes were:¹

• Salbutamol: 0.8 mmol/L
• Insulin and dextrose: 1.1 mmol/L
• Combination: 1.3 mmol/L

The combination produced a greater reduction than salbutamol alone (adjusted difference, 0.44 mmol/L; 95% CI, 0.28-0.59; P <.001) and insulin and dextrose alone (adjusted difference, 0.22 mmol/L; 95% CI, 0.06-0.39; P = .008). Adverse events did not differ materially across groups, except that hyperglycemia was less frequent with salbutamol.¹

Whether Faster Potassium Lowering Improves Patient Outcomes Remains Unknown

Investigators concluded that the combination produced a modestly greater reduction in serum potassium at 60 minutes, and that whether this biochemical difference improves clinical outcomes remains uncertain.¹

“Our study was not powered for patient-oriented outcomes, so maybe we need to include more patients,” Montassier said. “To see if this rapid decrease in [potassium] is also associated with low mortality and low adverse outcomes, it will be interesting.”

Editor’s Note: Montassier reported no relevant disclosures.

References

1. Montassier E, Rossignol P, Legrand M. Acute treatment of hyperkalemia in the emergency department: a randomized clinical trial. Abstract FR-OR108. Presented at: American Society of Nephrology Kidney Week 2026; October 21-25, 2026; Denver, CO.

2. Montassier E, Lemoine L, Hardouin JB, Rossignol P, Legrand M. Insulin glucose infusion versus nebulised salbutamol versus combination of salbutamol and insulin glucose in acute hyperkalaemia in the emergency room: protocol for a randomised, multicentre, controlled study (INSAKA). BMJ Open. 2020;10(8):e039277. doi:10.1136/bmjopen-2020-039277