U-shaped Association between Serum Calcium Levels and 28-Day Mortality in Patients with Sepsis: A Retrospective Analysis of the MIMIC-III Database

Abstract

Background Serum calcium levels disorder have been reported to be associated with poor prognosis in different diseases. Studies on the association between serum calcium and outcomes of septic patients remained limited. The aim of this study is to investigate the association between serum calcium and 28-day mortality in septic patients. Method Patients diagnosed with sepsis in the Medical Information Mart for Intensive Care III database were included. Patients were divided into five groups according to the quintiles of serum calcium levels, and their baseline characteristics were compared. Multivariate Cox regression models were employed to assess the association between serum calcium and 28-day mortality. Smooth curve fitting and segmented regression models were used to visualize the association between serum calcium levels and 28-day mortality risk. The 28-day survival probability between five groups was analyzed using Kaplan-Meier curves. Results A total of 3016 patients with sepsis were enrolled, and the 28-day mortality rate was 35.64%. After adjusting for confounders, compared with the reference quintile (Q4: 9.00–9.50), the lowest serum calcium level quintile (Q1: 5.70–8.20) was independently associated with an increased risk of 28-day mortality (HR: 2.12, 95%CI: 1.76-2.56). Smooth spline fitting revealed a U-shaped association between serum calcium and 28-day mortality. When serum calcium was <9.0 mg/dL, 28-day mortality risk increased by 58% per unit decrease in serum calcium (HR: 0.42, 95%CI: 0.37-0.48). When serum calcium was >9.0 mg/dL, the 28-day mortality risk increased by 12% per unit increase in serum calcium (HR: 1.12, 95% CI: 1.04-1.20). Conclusion A U-shaped association was observed between serum calcium levels and 28-day mortality in septic patients. Lower or higher serum calcium levels were associated with increased risk of 28-day mortality in septic patients.

Association between serum Calcium and 28-day mortality in Pediatric Pneumonia: Insights from a PICU Retrospective Cohort

“…In our study involving pediatric pneumonia patients in the PICU, serum calcium levels emerged as an independent prognostic factor for in-hospital mortality, aligning with ndings from other studies. [10,[20][21][22][23][24] Notably, research by Yan et al on sepsis and multiple myeloma, along with Yang et al's comprehensive cohort analysis, identi ed non-linear relationships. [21,22] Speci cally, in sepsis patients, a decline in serum calcium below 9.0 mg/dL signi cantly increased mortality risk.…”

“…[21,22] Speci cally, in sepsis patients, a decline in serum calcium below 9.0 mg/dL signi cantly increased mortality risk. [20] In contrast, for multiple myeloma patients, optimal survival correlated with serum calcium levels around 8.40 mg/dL, with both higher and lower levels indicating increased mortality [22]. Yang's extensive cohort studies in UK Biobank and NHANES also discovered a Ushaped correlation between albumin-adjusted calcium levels and all-cause or cardiovascular mortality, with linear association observed in cancer mortality.…”

Association Between Age and the 28-Day All-Cause Mortality in Tuberculosis Complicated by Sepsis in ICU Patients: A Retrospective Cohort Study [Letter]

“…This study did not consider information on patients’ medication use prior to admission; if this study had an analysis of medication use prior to admission in the included sepsis patients, this could have made the results more rigorous. In addition, Yan et al 4 found that the abnormal level of serum calcium sepsis in-hospital mortality increased significantly. Thus, lower or higher serum calcium levels were associated with an increased risk of 28-day mortality.…”

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

“…Hypocalcemia has been frequently observed in sepsis syndrome [9] , and several studies have reported a statistically significant negative correlation between serum calcium levels and mortality rates in patients diagnosed with sepsis [10–12] . However, other studies have reported that only extreme outliers of calcium levels are associated with sepsis mortality [13,14] , so what is the real role of calcium in sepsis?…”