The Positive and Negative Effects of Calcium Supplementation on Mortality in Septic ICU Patients Depend on Disease Severity: A Retrospective Study from the MIMIC-III

Abstract

Background. Calcium administration in septic patients with hypocalcemia is a controversial issue. The present study preliminarily investigated the effects of calcium supplementation on the length of hospitalization and mortality in septic ICU patients with different severities of hypocalcemia and disease. Method. A total of 5761 eligible septic patients, including 2689 who received calcium supplementation and 3072 who did not receive calcium supplementation, were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The cofounding covariates between the calcium supplement and nonsupplement groups were balanced using the propensity score matching model. We compared the length of stay (LOS) in the ICU and hospital with 28-day and hospital mortality and stratified the analysis according to the sequential organ failure assessment (SOFA) score and ionized calcium (iCa) at the first ICU admission in the matched groups. Results. The results showed that iCa at the first ICU admission was associated with mortality in sepsis patients (HR: 0.421; 95% CI: 0.211∼0.837), but the lowest mortality rate was observed in patients with mild hypocalcemia. A total of 993 paired patients were included in the analysis after propensity score matching. Regardless of the SOFA score or presence of iCa, the LOS in the ICU was higher in the calcium supplement group than in the nonsupplement group. The survival analysis was stratified by the SOFA score and showed that calcium supplementation reduced mortality when the patient’s SOFA score was ≥8 ( p = 0.002 ), and it worsened the outcome when the patient’s SOFA score was ≤4 ( p = 0.010 ). It had no significant effect on patients with SOFA scores ranging from 5 to 7 ( p = 0.911 ). Conclusion. Our results showed that mild hypocalcemia may be protective in septic patients, and calcium supplementation may have positive and negative effects on mortality depending on disease severity. The SOFA score may be a valuable clinical index for decisions regarding calcium administration.

Nonlinear relationship between ionized calcium and 28-day mortality in patients with sepsis: A retrospective cohort study from MIMIC-IV database

“…This suggests that mild hypocalcemia may be protective against sepsis. A retrospective study [27] found that mild hypocalcemia may have a protective effect in septic patients, and calcium supplementation may have both positive and negative effects on mortality depending on the severity of the disease. Aberegg also suggested that low iCa levels may be protective in critically ill patients, whereas attempts to correct low levels may be harmful [6] .…”

Management of hypocalcaemia in the critically ill

“…In a subset of this cohort of sepsis patients, He et al . [29] found a longer ICU and hospital length of stay (LOS) after calcium supplementation was given. Furthermore, a higher 90-day mortality was found following calcium administration in patients with iCa 1.01–1.20 mmol/l, while in patients with iCa levels below 1.01 mmol/l, it might be beneficial [29].…”

“…Despite the absence of an evidence-based threshold for calcium supplementation and its inefficacy in restoring serum calcium levels, as well as the transient nature of hypocalcaemia, calcium administration occurs frequently in the ICU. In 18-79% of the ICU patients included in observational studies, calcium was administered [7,25,29,32,52,53] (M. Melchers, H.P.F.X. Moonen, T.S.…”

“…The laboratory definition of hypocalcaemia varies by institution. However, it is generally defined as an iCa of less than 1.15 mmol/l, which is reported to occur in 55-88.5% of critically ill patients [4,7,[25][26][27][28][29], making it a focus of research interest.…”

“…[29] found a longer ICU and hospital length of stay (LOS) after calcium supplementation was given. Furthermore, a higher 90-day mortality was found following calcium administration in patients with iCa 1.01–1.20 mmol/l, while in patients with iCa levels below 1.01 mmol/l, it might be beneficial [29]. These findings align with results from our observational study that septic patients with iCa between 1.06 and 1.14 mmol/l when calcium was administered and had worse long-term survival rates (M. Melchers, H.P.F.X.…”