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Hypokalemia in children following cardiac surgery occurs frequently, placing them at risk of life-threatening arrhythmias. However, renal insufficiency after cardiopulmonary bypass warrants careful administration of potassium (K+). Two different nurse-driven protocols (high dose and tiered dosing) were implemented to identify an optimal K+ replacement regimen, compared to an historical low-dose protocol. Our objective was to evaluate the safety, efficacy, and timeliness of these protocols.A retrospective cohort review of pediatric patients placed on intravenous K+ replacement protocols over 1 year was used to determine efficacy and safety of the protocols. A prospective single-blinded review of K+ repletion was used to determine timeliness.Pediatric patients with congenital or acquired cardiac disease.Twenty-four-bed cardiothoracic intensive care unit in a tertiary children’s hospital.Efficacy was defined as fewer supplemental potassium chloride (KCl) doses, as well as a higher protocol to total doses ratio per patient. Safety was defined as a lower percentage of serum K+ levels ≥4.8 mEq/L after a dose of KCl. Between-group differences were assessed by nonparametric univariate analysis.There were 138 patients with a median age of 3.0 (interquartile range: 0.23-10.0) months. The incidence of K+ levels ≥4.8 mEq/L after a protocol dose was higher in the high-dose protocol versus the tiered-dosing protocol but not different between the low-dose and tiered-dosing protocols (high dose = 2.2% vs tiered dosing = 0.5%, P = .05). The ratio of protocol doses to total doses per patient was lower in the low-dose protocol compared to the tiered-dosing protocol (P < .05). Protocol doses were administered 45 minutes faster (P < .001).The tiered-dosed, nurse-driven K+ replacement protocol was associated with decreased supplemental K+ doses without increased risk of hyperkalemia, administering doses faster than individually ordered doses; the protocol was effective, safe, and timely in the treatment of hypokalemia in pediatric patients after cardiac surgery.