Background
Magnesium is an essential mineral involved in nerve function, muscle contraction, heart rhythm, and energy production. In critically ill patients, low magnesium levels, or hypomagnesemia, are common because of poor intake, gastrointestinal losses, diuretics, kidney dysfunction, sepsis, and the stress of critical illness. Even mild deficiency can matter in the intensive care unit because magnesium disturbances may contribute to arrhythmias, weakness, and difficulty correcting other electrolyte problems such as low potassium or low calcium.
The usual way to replace magnesium in critically ill patients is intravenously. IV magnesium is fast and familiar in intensive care, but it has drawbacks. It requires infusion equipment, nursing time, and often extra IV fluid. Much of the administered magnesium may also be lost in urine, especially when kidney handling of magnesium is altered. An enteral approach, meaning magnesium given through the gastrointestinal tract by mouth or feeding tube, could be simpler, cheaper, and potentially more sustainable. However, it has been unclear whether enteral replacement corrects magnesium deficiency as effectively as IV treatment in the ICU.
This randomized clinical trial was designed to test whether enteral magnesium replacement is noninferior to IV replacement for mild-to-moderate hypomagnesemia in critically ill adults. Noninferiority means the investigators were not trying to show that enteral therapy is better, only that it is not unacceptably worse than IV therapy by a pre-specified margin.
Study Design
This was a prospective, open-label, parallel-group randomized trial embedded in the electronic medical record. The study took place in a single mixed medical-surgical-trauma intensive care unit. Patients were enrolled between June 2023 and May 2024.
Adults with a serum magnesium concentration between 0.35 and 0.7 mmol/L were eligible. This range represents mild-to-moderate hypomagnesemia. Participants were randomly assigned to receive either enteral magnesium or IV magnesium replacement.
The main outcome was the serum magnesium concentration at 24 hours after enrollment. The study used a noninferiority margin of 0.1 mmol/L, meaning enteral therapy would be considered acceptably effective if it did not lower the 24-hour magnesium level by more than 0.1 mmol/L compared with IV therapy.
Secondary outcomes included the total magnesium dose administered, urinary magnesium excretion, treatment cost, waste generated, bloodstream infections, new atrial fibrillation, length of admission, mortality, carbon emissions, and additional IV fluid use.
Key Results
A total of 360 patients were included in the trial. Baseline magnesium levels were similar between groups, which is important because it suggests the randomized groups started from a comparable point.
At 24 hours, the mean serum magnesium concentration was 0.80 mmol/L in the enteral group and 0.92 mmol/L in the IV group. The mean difference was -0.12 mmol/L, with a 95% confidence interval from -0.16 to -0.07 mmol/L. Because the lower bound of the confidence interval crossed the noninferiority threshold of -0.1 mmol/L, the study could not establish noninferiority for enteral magnesium at the chosen margin.
In practical terms, IV magnesium raised the blood magnesium level somewhat more by 24 hours. The difference was statistically informative but not enormous. The key finding is that enteral treatment did not meet the trial’s strict criterion for being considered noninferior to IV treatment.
At the same time, enteral magnesium had several important advantages. It substantially reduced urinary magnesium concentration compared with IV therapy, suggesting less magnesium was wasted through the kidneys. Enteral replacement was also associated with lower intervention costs, less waste, a smaller carbon footprint, and less additional IV fluid administration.
The trial reported the following median differences favoring enteral therapy: cost was lower by 6.48 Australian dollars, waste was lower by 55 grams, carbon dioxide footprint was lower by 946 grams, and additional IV fluid use was lower by 100 mL. These differences are clinically interesting because they show that the route of administration can affect not only laboratory values but also hospital resource use and environmental impact.
There were no meaningful between-group differences in the other measured outcomes, including bloodstream infections, new atrial fibrillation, duration of admission, and mortality.
How to Interpret the Findings
The trial does not mean enteral magnesium is ineffective. Rather, it means that for the specific patient group studied and the specific noninferiority margin used, enteral replacement did not prove that it performs close enough to IV replacement in improving serum magnesium at 24 hours.
A few points are important when interpreting this result:
First, the difference in serum magnesium was relatively modest. Both approaches raised magnesium levels, and enteral therapy still corrected many patients’ hypomagnesemia to some degree.
Second, the clinical importance of a 0.12 mmol/L difference may vary depending on the patient’s condition. In a patient with a life-threatening arrhythmia or severe deficiency, faster and more predictable correction with IV magnesium may be preferable. In a more stable patient with mild hypomagnesemia, enteral therapy may still be reasonable, especially if preserving IV access, reducing fluid load, or limiting waste is a priority.
Third, the study focused on a 24-hour endpoint. It does not fully answer whether enteral magnesium might perform similarly over a longer period, whether repeated enteral dosing could narrow the gap, or whether certain subgroups of ICU patients benefit more from one route than the other.
Clinical Implications
For intensive care teams, the trial adds useful evidence to a common bedside decision: should magnesium be given by mouth or tube, or by IV infusion?
IV magnesium remains the preferred option when rapid correction is needed, when gastrointestinal absorption may be unreliable, or when the patient cannot tolerate enteral medications. This is especially true in severe symptomatic hypomagnesemia, malignant arrhythmias, or situations where controlled and prompt repletion is essential.
Enteral magnesium may still have a role in selected critically ill patients with mild-to-moderate deficiency, particularly when the gastrointestinal tract is functional and the patient is already receiving medications or nutrition through a feeding tube. Its advantages in cost, waste reduction, and lower IV fluid exposure may be meaningful in busy ICUs and in health systems focused on sustainability.
This study also highlights a broader concept in modern critical care: the environmental and resource burden of common treatments matters. Even small changes in route of administration can reduce consumables, fluid exposure, and greenhouse gas emissions when applied across many patients.
Strengths and Limitations
This trial has several strengths. It was randomized, prospective, and embedded in routine clinical workflow, which improves real-world relevance. It also assessed not only biochemical efficacy but also resource use and environmental impact, giving a more complete picture of the intervention.
However, there are limitations. The study was open-label, so clinicians and patients knew which treatment was being given. It was conducted at a single center, which may limit generalizability. The noninferiority conclusion depended on a specific margin of 0.1 mmol/L, and different clinicians might judge that threshold differently. The trial also included only patients with mild-to-moderate hypomagnesemia, so the findings should not be applied to severe deficiency without caution.
In addition, serum magnesium is only one measure of treatment success. Tissue magnesium balance, symptom relief, and longer-term clinical outcomes are harder to measure and were not fully resolved here.
Bottom Line
In critically ill adults with mild-to-moderate hypomagnesemia, enteral magnesium replacement did not prove noninferior to IV replacement for achieving serum magnesium targets at 24 hours. Still, enteral therapy reduced urinary magnesium loss, costs, waste, carbon emissions, and extra IV fluid administration. For stable ICU patients with a working gastrointestinal tract, enteral magnesium may remain a practical and more sustainable option, but IV replacement is still the safer choice when rapid or reliable correction is needed.