Predictive value of ionized calcium in critically ill patients: an analysis of a large clinical database MIMIC II

Abstract

Background and objective: Ionized calcium (iCa) has been investigated for its association with mortality in intensive care unit (ICU) patients in many studies. However, these studies are small in sample size and the results are conflicting. The present study aimed to establish the association of iCa with mortality by using a large clinical database.

Methods: Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was used for analysis. Patients older than 15 years were eligible, and patients without iCa measured during their ICU stay were excluded. Demographic data and clinical characteristics were extracted and compared between survivors and non-survivors. iCa measure on ICU admission was defined as Ca0; Camax was the maximum iCa during ICU stay; Camin was the minimum value of iCa during the ICU stay; Camean was the arithmetic mean iCa during ICU stay.

Main results: A total of 15409 ICU admissions satisfied our inclusion criteria and were included in our analysis. The prevalence of hypocalcemia on ICU entry was 62.06%. Ca0 was significantly lower in non-survivors than in survivors (1.11 ± 0.14 vs 1.13 ± 0.10 mmol/l, p<0.001). In multivariate analysis, moderate hypocalcemia in Ca0 was significantly associated with increased risk of death (OR: 1.943; 95% CI: 1.340-2.817), and mild hypercalcemia was associated with lower mortality (OR: 0.553, 95% CI: 0.400-0.767). While moderate and mild hypocalcemia in Camean is associated with increased risk of death (OR: 1.153, 95% CI: 1.006-1.322 and OR: 2.520, 95% CI: 1.485-4.278), hypercalcemia in Camean is not significantly associated with ICU mortality.

Conclusion: The relationship between Ca0 and clinical outcome follows an "U" shaped curve with the nadir at the normal range, extending slightly to hypercalcemia. Mild hypercalcemia in Ca0 is protective, whereas moderate and mild hypocalcemia in Camean is associated with increased risk of death.

Figure 1. Relationship between initial iCa (upper panel) and logit transformed mortality by using Lowess smoothing technique.

The figure shows that the relationships are non-linear. The lowest mortality rate occurs within the normal range of iCa (1.15–1.25 mmol/l). For the initial iCa, the “U” shape curve indicates that both hyper-and hypocalcemia are associated with equally increased risk of death. However, for the mean iCa, hypocalcemia was associated with more death than hypercalcemia.

Figure 2. Receiver operating characteristic curve (ROC) shows that the areas under ROC are approximately 0.78 for the four fitted models.