Elevated serum magnesium levels are strongly linked to higher mortality in sepsis, suggesting a critical role for magnesium in assessing sepsis risk and guiding treatment strategies.

Study: High serum magnesium level is associated with increased mortality in patients with sepsis: an international, multicenter retrospective study. Image Credit: sfam_photo / Shutterstock.com

Sepsis refers to life-threatening organ dysfunction that develops following a dysregulated host response to infection. In 2017 alone, about 49 million cases of sepsis were reported worldwide, with about 19.7% of all mortality rates attributed to sepsis. Thus, an urgent need remains to quickly identify sepsis to initiate supportive and antibiotic management.

A recent report published in MedComm investigates the association between magnesium levels and mortality.  

The importance of magnesium

Magnesium is the second most abundant intracellular cation. This element is key to multiple enzymatic reactions involved in the synthesis of essential biomolecules like nucleic acids and proteins and energy metabolism.

Low magnesium levels correlate with a poor prognosis among patients with cardiometabolic disease and depression. In fact, previous studies have reported an association between hypomagnesemia and increased severity of illness and mortality rates among intensive care unit (ICU) patients.

Hypermagnesemia is also associated with higher death rates among severely ill children, those diagnosed with the coronavirus disease 2019 (COVID-19), and hospitalized patients.

The dose-response relationship between magnesium and sepsis

The current study included 9,099 patients from the Medical Information Mart for Intensive Care (MIMIC-IV) cohort in the United States and 1,727 patients from a Chinese cohort. All patients were classified into quintiles by increasing serum magnesium levels as Q1-Q5 and G1-G5, respectively.

The median serum magnesium concentrations in the American and Chinese cohorts were 0.86 and 0.87 mmol/L, respectively. Both groups exhibited increasing disease severity and worse laboratory readings with rising magnesium levels.

The MIMIC-IV cohort had higher complication rates. Comparatively, the severity of illness was greater in the Chinese cohort, accompanied by a higher sequential organ failure assessment (SOFA) score and poorer vital sign recordings.

In the MIMIC-IV cohort, 22.1% of patients died within 28 days, with Q5 associated with the highest mortality at 28% of the quintile. In the Chinese cohort, 16% of patients died in the same period, with the highest mortality rate of 20% observed in Q5.

In the Chinese group, G4 and G5 had the lowest survival rates, whereas G1 and G2 had the highest.

High magnesium and mortality risk

In both cohorts, the risk of all-cause death within 28 days doubled with elevated magnesium levels. After compensating for confounding factors, the highest quintiles in each cohort were significantly associated with a 47% increase in 28-day mortality risk. In Q4 and Q5, the risk was 19% and 27% higher, respectively, compared to Q2.

In the Chinese cohort, the 28-day mortality risk increased by 93% for every unit increase in serum magnesium levels, with G4 and G5 associated with a 38% and 52% increased risk, respectively. In the American cohort, the risk of 28-day mortality increased by 7.4-fold for every unit increase in serum magnesium levels.

Secondary outcome analysis indicated that, in the MIMIC-IV cohort, patients with higher magnesium levels had longer ICU stay durations, longer hospitalizations, and higher 90-day mortality rates, both overall and among hospitalized or ICU patients.

In the Chinese cohort, higher 90-day, ICU, and hospitalized patient mortality rates occurred in the highest quintiles as compared to G2, who were more likely to have more extended hospital and ICU stay durations.

In the MIMIC-IV cohort, males were at an increased risk of 28-day mortality by 172% compared to 47% for females. People 65 years and older in the Chinese cohort had a nearly five-fold increased risk, compared to a decline in risk by 36% among those younger than 65.

Mechanically ventilated patients in the American cohort were less likely to die at 46% as compared to the eight-fold increased risk of mortality observed among non-ventilated patients. In the MIMIC-IV cohort, ICU patients not on vasopressor therapy were at a three-fold increased risk of mortality as compared to 17% of those prescribed this treatment.  

Early sepsis is more likely to correlate with high magnesium levels. Although the mechanisms responsible for this association remain unclear, unstable hemodynamics due to magnesium’s vasodilator effects, as well as closure of myocardial potassium channels triggering malignant arrhythmias and heart failure, may be involved.

Impaired nerve transmission that causes respiratory muscle and diaphragmatic paralysis with respiratory failure and immunosuppression coupled with a dysregulated inflammatory response can also contribute to the relationship between magnesium levels and sepsis risk.

Conclusions

These findings suggest that serum magnesium at the onset of sepsis could be a practical parameter for risk stratification and potentially act as an independent risk factor for septic patients.”

Although these observations corroborate previous reports, the current study is the first to report the temporal relationship between hypermagnesemia at the onset of sepsis and increased patient risk. Both study cohorts yielded similar results, thereby providing validity to the observations and making these findings generalizable to Asian and North American populations.