Hypertonic glucose vs insulin–dextrose to prevent hypoglycaemia following treatment for hyperkalaemia (HIGH-K): protocol for a double-blind randomized controlled trial

BACKGROUND: Hyperkalaemia is a life-threatening electrolyte abnormality commonly managed with intravenous insulin-dextrose therapy (IDT). Although effective, IDT frequently causes hypoglycaemia, particularly in patients without diabetes. Glucose-only therapy, which leverages endogenous insulin production, may offer comparable potassium-lowering effects with reduced hypoglycaemia risk. However, evidence remains limited. METHODS: The HIGH-K Trial is a single-centre, double-blind, randomised controlled trial in adult, non-diabetic patients presenting to an Australian Emergency Department with hyperkalaemia (>5.5 mmol/L [99 mg/dL]). Ninety-five participants are randomised 1:1 to receive either glucose-only therapy (100 mL 50% dextrose bolus followed by 250 mL 10% dextrose infusion over 2 h) or standard IDT (10 units IV insulin with 25 g dextrose followed by 250 mL saline infusion). The primary safety outcome is the incidence of hypoglycaemia (<3.9 mmol/L [70 mg/dL]) within six hours. The primary non-inferiority outcome is the mean change in serum potassium from baseline to two hours, using a non-inferiority margin of -0.5 mmol/L (-9 mg/dL). Secondary outcomes include severity of hypoglycaemia, rescue insulin requirements, and serum insulin/C-peptide levels. DISCUSSION: This is the first double-blind, randomised controlled trial to directly compare the safety and biochemical non-inferiority of glucose-only therapy versus standard insulin-dextrose therapy in the emergency department. By utilising a continuous glucose infusion following a bolus, the protocol aims to sustain endogenous insulin release and optimise intracellular potassium shift while preventing hypoglycaemia. If non-inferiority is demonstrated, this approach could provide a safer alternative in high-acuity or resource-limited clinical settings. CONCLUSION: Results will be disseminated in peer-reviewed journals and at national and international conferences. Findings may inform future research and clinical practice guidelines regarding glucose-only therapy for hyperkalaemia.