Retrospective analysis of previous studies has shown that hypomagnesemia can prolong ventilator support and hospital stay and increased mortality in critically ill patients (5). Animal studies have demonstrated the involvement of magnesium ions in the immunomodulatory response of sepsis patients, and intriguingly, magnesium ion supplementation may contribute to the prognosis of sepsis patients (6). Nevertheless, relatively little is known about the exact effects of hypomagnesemia and magnesium supplementation on the outcomes of sepsis patients. Therefore, we used the MIMIC database to retrospectively analyze the effect of hypomagnesemia on sepsis patients.
This study found that the patients with hypomagnesemia were younger (63.2 vs 68.7), had a higher proportion of septic shock (71.34% vs 73.27%, P = 0.03), and also had lower levels of serum potassium, serum calcium, and creatinine at admission (all P < 0.01). Preliminary analysis revealed that the duration of vasoactive drug use and mechanical ventilation and the length of ICU stay and the total hospital stay of patients with hypomagnesemia were longer. The ICU mortality of patients with hypomagnesemia was higher (P = 0.04), but no statistical difference was observed between the two groups after multivariate regression analysis. Similarly, there were no significant differences in 28-day mortality, hospital mortality, 14-day mortality, or 60-day mortality between the two groups, even after multivariate regression analysis. According to K-M survival curve analysis, there was no statistical difference in 28-day mortality, the main endpoint of the study, between the two groups (Fig. 2), which is inconsistent with the previous study on critically ill patients (7). A retrospective study involving 10 clinical studies has indicated that hypomagnesemia serves as a risk factor for increased mortality in critically ill patients, but it does not exert any effect on the risk of sepsis (8), which may reflect the particularity and complexity of sepsis patients compared with critically ill patients. Multivariate regression analysis demonstrated that the patients with hypomagnesemia had a higher incidence of hypokalemia (P < 0.01). The decrease of serum potassium level caused by low magnesium is attributed to a combination of multiple mechanisms, one of which is that magnesium modulates the activity of the ROMK channel (potassium channel in the outer renal medulla), leading to increased potassium excretion from the kidney (9). C. Thongprayoon has found that hypomagnesemia on admission increases the incidence of acute respiratory failure during hospitalization (10). Consistently, we found that the duration of mechanical ventilation in patients with hypomagnesemia was significantly longer than that in patients without hypomagnesemia (70.1 vs 26.3, P < 0.01). This may be related to respiratory muscle weakness caused by hypomagnesemia (10). In addition, magnesium regulates the contractibility of smooth muscle cells, and hypomagnesemia leads to bronchospasm, which in turn prolongs mechanical ventilation (11). Our study found that the duration of vasoactive drug use in patients with hypomagnesemia was longer than that in patients without hypomagnesemia, however, the pathological mechanism remained unclear. Intriguingly, magnesium ions are also involved in endothelium-dependent and non-endothelium-dependent vascular tone regulation mechanisms in the microcirculation, and hypomagnesemia can lead to heart failure and severe arrhythmia (12), which may be one of the possible reasons. Patients with hypomagnesemia had a longer duration of mechanical ventilation and vasoactive drug use, which seemed to explain the longer ICU stay and hospital stay of patients with hypomagnesemia (P < 0.01). Also, the length of ICU stay and hospital stay was decreased with the increase of serum magnesium level (Fig. 3), indicating that the serum magnesium level had an impact on some prognostic indicators of patients with sepsis. Magnesium supplementation in patients with hypomagnesemia is no longer controversial. However, it is not clear whether magnesium supplementation in patients with normal serum magnesium levels can affect the prognosis of sepsis patients. In view of this, we assigned these patients with normal serum magnesium levels to the non-magnesium supplementation group (group A) and magnesium supplementation group (group B) according to whether they were supplemented with magnesium during hospitalization. Despite the differences in basic conditions between the two groups, multivariate regression analysis showed that the 28-day mortality and 14-day mortality of group B were significantly lower than those of group A, but there was no statistically significant difference in 60-day mortality between the two groups. The duration of mechanical ventilation and vasoactive drug use of group B was shorter than that of group A. Similarly, Afsaneh Noormandi performed magnesium supplementation in sepsis patients with normal serum magnesium levels and elucidated that patients with magnesium supplementation had a faster lactic acid clearance and a shorter hospital stay. Although there was no significant difference in 28-day mortality between the two groups of patients, the 28-day mortality of the two groups was significantly lower than that of the placebo group. The average survival time of patients with magnesium supplementation was significantly longer than that of patients treated with placebo [25.85 vs 22.19 days (P = 0.001)] (4). Magnesium ions act as a cofactor of thiamine triphosphatase and participate in lactic acid metabolism. Magnesium iron deficiency may result in the accumulation of lactic acid, which may be the reason why magnesium supplementation improves the prognosis of sepsis patients. These findings suggested that magnesium supplementation for sepsis patients with normal serum magnesium may improve the prognosis.
This study still has some shortcomings. Firstly, the serum magnesium data of all patients were obtained after hospitalization, and there was no fixed specimen collection time. Hence, it failed to analyze the serum magnesium level and the duration of low magnesium before admission, which may affect the results to some extent. Secondly, the reasons, timing, methods, dose, and target magnesium value of magnesium supplementation in patients with normal serum magnesium were not counted. The causal relationship between magnesium supplementation as an intervention and prognosis is not clear, which needs to be further confirmed by high-quality randomized controlled studies.