Clinical value of serum calcium in elderly patients with sepsis

a b s t r a c t

Purpose: To explore the clinical value of serum calcium (Ca) in elderly patients with sepsis. Materials and methods: The clinical data and laboratory data of elderly patients with sepsis (n = 165) and elderly population for physical examination (n = 67) in a tertiary hospital from January 2020 to November 2020 were col- lected. We analyzed serum Ca levels in sepsis and septic shock firstly, and then continued to investigate them in the survival group and the death group. Meanwhile, we also assessed the correlation between serum Ca and PCT. Results: The serum Ca levels of the elderly patients with sepsis were lower than that of the control group (median 1.98 vs 2.31 mmol/L, P < 0.001), and the more severe the sepsis, the lower the serum Ca levels. Sepsis patients with decreased serum Ca had higher shock rate and mortality. There was a negative correlation between serum Ca and PCT (r = -0.2957, P < 0.001).

Conclusion: Serum Ca has a certain value for the early recognition of elderly patients with sepsis and the judgment of the severity of the disease.

(C) 2021

  1. Introduction

Sepsis is a very dangerous disease with a high morbidity and mortal- ity rate. It is a fatal organ dysfunction caused by the uncontrolled re- sponse to infection [1,2]. As sepsis has the characteristics of high morbidity and mortality, its early diagnosis and intervention are of great significance to improve the quality of life of patients.

At present, the most common Serum marker applied in sepsis is

procalcitonin [3]. The plasma level of PCT will increase when se- vere infection and sepsis occur [4]. However, the increase of PCT level can only last for 1-4 days [5]. For patients who can’t get medical treat- ment in time, PCT detection has some limitations. What’ worse, it may not increase significantly in sepsis caused by virus infection [6], which is likely to be ignored by clinical doctors, leading to missed diagnosis. And in some autoimmune Disease states, on the contrary, PCT will also increase [7], which will also interfere with the doctor’s judgment.

Patients with sepsis often have electrolyte disturbances [8]. Clini- cians pay more attention to the levels of serum potassium and sodium, but not to the serum calcium (Ca). Ca ions have many important phys- iological functions. For example, it can promote and regulate the activity of certain enzymes in the body [9]; Ca ions also participate in the activ- ities of nerves and muscles and the release of neurotransmitters, and regulate hormone secretion [10]. At the same time, blood coagulation, cell adhesion, and muscle contraction also require Ca ions [11]. What’s more, Ca ions also play an important role in controlling inflammation

* Corresponding author.

E-mail address: [email protected] (P. Zhang).

and edema, as well as maintaining acid-base balance [12]. Many clinical studies have suggested that critically ill patients are particularly prone to abnormal Ca metabolism [13]. We speculate that elderly patients with sepsis also have abnormal Ca metabolism, and the serum Ca levels may be related to the severity of the disease.

In this study, we analyzed the serum Ca levels of elderly patients with sepsis, and preliminarily evaluated the correlation between serum Ca and sepsis of different severity.

  1. Materials and methods
    1. Study population

A total of 232 elderly subjects were recruited in this study, including 165 cases in disease group and 67 cases in control group. The disease group were elderly patients with sepsis, and the elderly patients were defined as patients older than 60 years old. All subjects were recruited from a tertiary hospital from January 2020 to November 2020. According to the severity of the disease, patients in the disease group were divided into sepsis group (n = 124) and septic shock group (n = 41); then they were divided into survival group (n = 125) and death group (n = 40) according to their survival after 28 days of hospitalization. We used the Third International Consensus Definitions for Sepsis and Septic Shock [2] as the standard for sepsis patients. According to the consensus, sepsis was defined as life-threatening organ dysfunction caused by a dys- regulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis- related] Organ Failure Assessment (SOFA) score of 2 points or more.


0735-6757/(C) 2021

Septic shock was be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. The diagnosis criteria of septic shock were hypotension with blood pressure at or above 65 mmHg under the action of vasoactive drugs, and blood lactic acid level of more than2 mmol/L after sufficient fluid resuscitation [2]. The patients who met the above conditions were included in the septic shock group. Exclusion criteria: used immunosuppressants, Ca, vitamin D preparations and other drugs that may affect the electrolyte level in re- cent 3 months; combined with diabetes, cancer, chronic renal insuffi- ciency, rickets, thyroid diseases and other basic diseases that affect bone metabolism. The control group was the same-period healthy elderly pop- ulation for physical examination, the inclusion criteria was the physical examination reports are all qualified. While the exclusion criteria was the same as the sepsis group. All subjects were over 60 years old.

This study was a retrospective analysis and approved by the ethics committee of Renmin Hospital of Wuhan University (No. WDRY2020-K223).

    1. Data collection

The levels of white blood cells , hemoglobin (Hb), C-reactive protein (CRP), PCT and Ca were the first Laboratory test results after ad- mission. It is understood that in laboratory tests, WBC and Hb were an- alyzed by Sysmex XN-9000 automatic blood cell analyzer. Serum PCT was detected by Cobas 8000 e 801 automatic chemiluminescence im- munoassay analyzer produced by Roche diagnostic company. CRP was detected by H780-3 automatic specific protein analyzer produced by Xilaiheng company (Shenzhen, China). Serum total protein (TP), albu- min (Alb) and Ca were detected by Siemens ADVIA 2400 biochemical analyzer. And we have access to information that could identify individ- ual participants during or after data collection.

    1. Statistical analysis

Statistical analysis was performed with the SPSS 25.0 (IBM, Armonk, NY, USA) and GraphPad Prism 6.0 (GraphPad Software, La Jolla, CA, USA). Single sample Kolmogorov-Smirnov (K\\S) method was used to test whether the data of each group conformed to the normal distribu- tion. The normal distribution data was expressed by mean +- SD, the comparison between two groups was conducted by student’s t-test. The non-normal distribution data was represented by median (P25, P75), Mann-Whitney U test was used for comparison, and Spearman cor- relation coefficient was used to represent the correlation between the two groups. The P value <0.05 indicates statistical significance.

  1. Results
    1. Characteristics of study population

The clinical data of all subjects were as follows (Table 1). There was no significant difference in gender and age between the two groups

(P > 0.05). The WBC, CRP, PCT and HR levels of the sepsis group were higher than those of the control group (P < 0.001), while the Hb, TP and Alb levels were lower than that of the control group, and the Ca levels were the same (median 1.98 vs 2.31 mmol/L, P < 0.001). Among the pathogens, multiple pathogens infection accounted for the most, followed by Gram-negative bacteria. As to the primary Infection sites in the sepsis group, the respiratory system was the most common.

    1. Analysis of serum Ca in sepsis and septic shock

According to the severity of the disease, elderly patients with sepsis were divided into sepsis group and septic shock group. The two groups of patients had no statistical significance in age and gender (P > 0.05). The levels of Ca in the sepsis group and septic shock group were 2.02 (1.91, 2.11) mmol/L and 1.88 (1.69, 1.98) mmol/L, respectively. The more severe the sepsis, the lower the Ca levels (Fig. 1A). Moreover, our results showed that the probability of septic shock in the group with decreased serum Ca level was significantly higher than that in the group with normal serum Ca level (41.94% vs 6.45%, P < 0.05, Fig. 1B).

    1. Analysis of serum Ca levels in survival group and death group of sepsis

Similarly, we also analyzed the serum Ca levels of sepsis patients with different hospitalization outcomes. The results showed that the serum Ca level of the death group was lower than that of the survival group (P < 0.05, Fig. 2A), and the mortality rate of the serum Ca de- creased group was higher than that of the normal serum Ca group (P < 0.05, Fig. 2B).

    1. Serum Ca in elderly patients with sepsis was negatively correlated with PCT

As shown in Fig. 3A, the PCT levels of patients with sepsis in the serum Ca decreased group were significantly higher than those of the serum Ca Normal group, in order to further analyze the correlation be- tween serum Ca and PCT, we performed spearman correlation analysis between the two indicators and found that serum Ca in elderly patients with sepsis is negatively correlated with PCT (r = -0.2957, P < 0.001, Fig. 3B).

  1. Discussions

Sepsis is a disease of Multiple organ dysfunction caused by the un- controllable infection, with a very poor prognosis [14]. As a special group, the elderly usually has more basic diseases, degraded organ func- tion and lower immune status [15]. Especially for some elderly patients with poor cardiopulmonary function storage or long-term bed rest, they are vulnerable to severe infections, which can lead to sepsis. The elderly is of poor tolerance and rapid disease evolution, which makes the treat- ment of sepsis in the elderly more difficult [16]. Early recognition and intervention are of great significance to improve the quality of life of

Table 1

Clinical characteristics of the participants

Sepsis(n = 165)

Healthy control(n = 67)


P value

Gender (male/female)





Age (years)

72.18 +- 8.53

72.03 +- 7.64



WBC (x109/L)

10.55 (7.34, 17.27)

5.79 (5.04, 7.03)



Hb (g/L)

109 (91, 126)

131 (143, 156)



CRP (mg/L)

89.64 (34.78, 175.19)

0.5 (0.5, 2.73)



PCT (ng/mL)

4.15 (0.99, 14.55)

0.05 (0.03, 0.07)



Ca (mmol/L)

1.98 (1.89, 2.08)

2.31 (2.23, 2.38)



TP (g/L)

56.60 (50.50,61.85)

66.60 (63.40,70.40)



Alb (g/L)

32.10 (27.80,35.70)

43.80 (43.20,46.44)



HR (time/min)

92 (78,106)

87 (78,102)



Gender using Chi-square test; Age using student’s t-test; WBC, Hb, CRP, PCT, Ca, TP, Alb and HR using Mann-Whitney U test.

Image of Fig. 1 Image of Fig. 3

Fig. 1. Analysis of Ca in sepsis group and septic shock group. (A) Comparison of Ca levels between sepsis group and septic shock group; (B) Incidence of septic shock with different levels of Ca. *P < 0.05.

Fig. 3. Correlation between serum Ca and PCT in elderly patients with sepsis. (A) The PCT levels of patients with sepsis in the Ca decreased group and Ca normal group; (B) Scatter plot of correlation between Ca and PCT. *P < 0.05.

elderly patients with sepsis [17]. It is recommended that scholars exca- vate more early serum markers to improve the early diagnosis of sepsis and help clinicians to intervene in the disease as soon as possible.

During the hospitalization of critically ill patients, they are usually accompanied by electrolyte disturbances, sepsis patients are the same [18]. Clinicians often ignore the serum Ca levels of patients with sepsis, and hypocalcemia is more common [19]. The cause of hypocalcemia in patients with sepsis is not yet fully understood, and its possible mecha- nisms are very complex [20-25]. The incidence of hypocalcemia in pa- tients with sepsis ranges from 36.0% to 86.5% [26]. The study of serum Ca levels may provide certain value for the early diagnosis and progno- sis of sepsis. This paper analyzed the serum Ca levels of the elderly pa- tients with sepsis, and found that the serum Ca levels of them were lower than those of the physical examination population, which was con- sistent with the theory above. At the same time, this study also showed that the serum Ca levels of sepsis group and septic shock group were dif- ferent, and the serum Ca levels were lower with the increase of disease se- verity, this trend was consistent with other studies [27]. It was suggested that the serum Ca levels was also of reference value for the disease sever- ity classification for elderly patients with sepsis. What’s more, the serum Ca levels of death group were also lower than those of survival group, which suggested that serum Ca may be a prognostic factor for elderly pa- tients with sepsis. The incidence of shock and mortality were higher in el- derly patients with sepsis in the serum Ca decreased group, it also provided evidence that serum Ca can be used as a biomarker, which may be an indicator of the deterioration of sepsis.

PCT is the most common indicator applied in the diagnosis, medica-

tion guidance and prognosis of sepsis. The PCT content in the normal body is extremely low [28]. When the body is infected, the PCT levels will rise rapidly. In this study, the PCT levels in the sepsis group were much higher than those in the control group, which was consistent with previous studies [29]. In this study, we found that the PCT levels of the elderly patients with sepsis in the serum Ca decreased group were higher, and PCT could reflect the degree of sepsis infection [30], which indicated that the infection degree of the elderly patients with sepsis in the serum Ca decreased group may be more serious, which was consistent with the above results. Correlation analysis also proved this point above, the results showed that serum Ca and PCT had a

Image of Fig. 2

Fig. 2. Analysis of Ca levels in survival group and death group of sepsis. (A) Comparison of Ca levels between survival group and death group of sepsis; (B) sepsis mortality with different levels of Ca. *P < 0.05.

negative correlation, which might suggest that Ca and PCT participated in the development of sepsis together, and could reflect the severity of sepsis, which further indicated that serum Ca levels had certain refer- ence value for the preliminary diagnosis and severity classification of sepsis.

However, there were also some limitations with the study. Firstly, our research object only came from a single hospital in a single region, and there may be accidental errors between regions and different hos- pitals; Secondly, we only analyzed the elderly patients as the research object, and didn’t include patients of other ages, so the results of this study have little reference significance for sepsis patients of other ages; Thirdly, the control group in our constituency is the population of physical examination. It may be more rigorous to select patients with infectious symptoms but not sepsis as the control group. We will consider this in the follow-up study; Fourthly, this study is only a small sample size study, and the follow-up needs to expand the sample size for in-depth analysis.

  1. Conclusions

In summary, serum Ca has a certain value for the early recognition of elderly patients with sepsis and the judgment of the severity of the dis- ease. However, there is no accepted answer as to how serum Ca partic- ipates in or affects the occurrence and development of sepsis. We suggest that scholars can expand the sample size for more in-depth re- search to clarify the specific pathway and mechanism of serum Ca af- fecting the occurrence and development of sepsis, which may be more conducive to guide clinical diagnosis and prognosis judgment.

Author contributions

Li Huan designed and performed the study and wrote the manu- script, Zhang Ping’an was responsible for the revision and review of the paper, Chen Juanjuan provided the ideas of the manuscript, Hu Yuanhui and Cai Xin were responsible for collecting data, Tang Dongling participated in the discussion part and provided financial support. All authors contributed to the article and approved the submitted version.

Funding statement

This research was funded by National Natural Science Foundation of China (81773444).

Declaration of Competing Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Not applicable.


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