Enteral When Compared With IV Magnesium Replacement in the Critically Ill: A Noninferiority Randomized Clinical Trial

Enteral magnesium replacement may be as effective as IV replacement while being a cheaper and more environmentally sustainable intervention. The primary objective was to evaluate whether enteral magnesium is noninferior to IV administration in correcting hypomagnesemia.

Prospective, open-label, parallel-group, electronic medical record-embedded, randomized, noninferiority trial.

Single-center mixed medical-surgical-trauma ICU.

Patients with serum magnesium concentration between 0.35 and 0.7 mmol/L.

Enteral or IV magnesium replacement.

The primary outcome was serum magnesium concentration at 24 hours after enrollment, with a noninferiority margin of 0.1 mmol/L. Secondary outcomes included dose of administered magnesium, urine magnesium excretion, costs of intervention delivery, waste, bloodstream infections, new atrial fibrillation, duration of admission, and mortality. Between June 2023 and May 2024, 360 patients were included. Baseline magnesium concentrations were comparable. At 24 hours, mean ( sd ) magnesium concentrations were 0.80 mmol/L (0.19 mmol/L) in the enteral arm and 0.92 mmol/L (0.23 mmol/L) in the IV arm, with a mean difference of -0.12 mmol/L (95% CI, -0.16 to -0.07 mmol/L) indicating inconclusive results about noninferiority. Enteral replacement substantially decreased urine magnesium concentrations compared with IV replacement (median difference of area under the curve, -46.2 mmol·hr/L), cost (median difference, -6.48 Australian dollars; 95% CI, -7.40 to -5.56 Australian dollars), waste (median difference, -55 grams; 95% CI, -58 to -51 grams), C o2 footprint (median difference, -946 grams; 95% CI, -996 to -896 grams), and additional IV fluid administration (median, -100 mL; interquartile range, -200 to -100 mL). There were no between group differences for other outcomes.

Enteral magnesium replacement for mild-to-moderate hypomagnesemia did not establish noninferiority to IV replacement at a margin of 0.1 mmol/L but it reduced urinary concentration of magnesium, cost, environmental waste, carbon emissions, and IV fluid administration.