Systematic Review of Pharmacologic Treatments for Hypochloremic Metabolic Alkalosis in Critically Ill Children

Metabolic alkalosis, characterized by an increase in serum bicarbonate (>28 mEq/L) and serum pH (>7.45), is associated with clinical complications including arrhythmias, mental confusion, and seizures. Non-pharmacologic measures are recommended first-line for treatment of hypochloremic metabolic alkalosis, but pharmacologic treatment may be needed. This review of the literature provides detailed descriptions of dosage regimens, efficacy, safety, and other considerations for use of pharmacologic agents. The literature search included published human studies in the English language from EMBASE and Ovid MEDLINE from 1946 to January 2025. A total of 11 studies representing 736 pediatric patients were included. Use of acetazolamide, hydrochloric acid, ammonium chloride, and arginine hydrochloride have been reported in the literature for pharmacologic management of hypochloremic metabolic alkalosis. Of these agents, acetazolamide and arginine hydrochloride are the only two available for use in the United States. Acetazolamide monotherapy was evaluated in 5 studies, representing 270 patients (36.6%). Arginine chloride monotherapy was evaluated in 2 studies, representing 427 critically ill patients (58.0%). Only 1 study compared the safety and efficacy of acetazolamide and arginine hydrochloride but was limited by variable dosing and undocumented routes of administration and duration of therapy. Adverse effects were reported in 7 patients (0.95%) in the studies included, all of which occurred with acetazolamide. Given that acetazolamide is a US Food and Drug Administration (FDA)-labeled commercially available medication for enteral and intravenous administration, it is the authors' opinion that it should be administered as a first-line pharmacologic agent for pediatric patients refractory to other interventions for hypochloremic metabolic alkalosis.