Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025 Date: August 6, 2025 Guest Skeptic: William Toon is a paramedic who, this past May achieved over 50 years of continuous EMS certification. His professional path has taken him from front-line paramedic to national presenter, expert witness, flight medic, EMS program director, and senior training executive with a doctorate in Higher Education. Case: A 65-year-old patient presents to the emergency department (ED) with general weakness, mild abdominal cramping, and nausea over the past 12 hours. The patient has poorly controlled type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease stage 4 on hemodialysis. The patient missed their last dialysis appointment two days ago. The patient takes several medications for kidney disease and blood pressure, including a potassium-sparing diuretic. His ECG shows peaked T-waves. Stat chemistry reveals a serum potassium of 6.5 mmol/L. He is not yet oliguric and is hemodynamically stable. The team must initiate pharmacologic treatment immediately while preparing for possible escalation to dialysis. Background: Hyperkalemia is a potentially life-threatening electrolyte abnormality frequently encountered in the ED. It’s common in patients with chronic kidney disease, diabetes, or those on renin-angiotensin-aldosterone system (RAAS) inhibitors. While treatments like insulin, beta-agonists, and calcium gluconate are well-known, the comparative efficacy and safety of pharmacologic agents used to rapidly reduce serum potassium remain uncertain. Clinicians must balance rapid action with safety when choosing treatment for hyperkalemia. Understanding which pharmacologic interventions work best and how quickly they act is vital to optimizing care. Unfortunately, much of the existing data on hyperkalemia treatment is derived from small or methodologically limited trials. Clinical Question: What is the effectiveness of pharmacological interventions in the acute treatment of hyperkalemia compared to standard care, placebo, or other interventions in adults? Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025 Population: Adult patients with hyperkalemia (typically defined as serum potassium ≥5.0 mmol/L). Studies included varied populations such as those with CKD, dialysis patients, and acutely ill inpatients. Exclusions: Patients under 18 and those receiving non-pharmacologic interventions (dialysis) were excluded. Intervention: Any acute pharmacological intervention to mitigate the harmful effects of hyperkalemia or to lower potassium levels. Comparison: Placebo, standard care, or head-to-head comparisons of other pharmacologic interventions. Outcome: Primary Outcome: Change in serum potassium from baseline at specific time points (1, 2, 4, and 6 hours). Secondary Outcomes: Proportion of patients achieving normokalaemia, adverse events (hypoglycaemia), need for rescue therapy (dialysis), and all-cause mortality. Type of study: Systematic review and meta-analysis Authors’ Conclusions: “Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous salbutamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable. Yes The search for studies was detailed and exhaustive. Yes The primary studies were of high methodological quality. No The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. No The treatment effect was large enough and precise enough to be clinically significant. Yes Who funded the trial? No financial support was provided for the study. Did the authors declare any conflicts of interest? No relevant conflicts of interest disclosed. Results: Studies included adult patients with hyperkalemia from EDs, inpatient wards, and dialysis units. Ages ranged widely, with a predominance of patients with chronic kidney disease (CKD) and cardiovascular comorbidities. Key Result: Sodium zirconium cyclosilicate and insulin-glucose regimens were most effective in lowering serum potassium within four hours, while other agents had limited short-term impact. Primary Outcome: At four hours, insulin-glucose reduced potassium by an average of 0.8 mmol/L, and sodium zirconium cyclosilicate by 0.67 mmol/L. SPS (sodium polystyrene sulfonate) and patiromer showed smaller and delayed effects. Secondary Outcomes: Hypoglycemia occurred in 17% of insulin-treated patients. Dialysis was needed in 6.2%. Mortality rates were not significantly different among treatment groups. Substantial Clinical and Methodological Heterogeneity: O
