Influence of hypocalcemia on the prognosis of patients with multiple trauma

Abstract

BACKGROUND

Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications.

AIM

To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas.

METHODS

The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People’s Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups.

RESULTS

There was an association between serum calcium levels and the prognosis of patients with polytrauma.

CONCLUSION

Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

Key Words: Multiple trauma, Hypocalcemia, Prognosis, Intensive care unit, Influence

Core Tip: The research showed hypocalcemia has a high probability of occurrence in patients with multiple injuries, and blood calcium values are closely related to the prognosis. Prognosis is directly associated with blood calcium levels, which can be used as an indicator to judge the prognosis of patients with multiple injuries.

INTRODUCTION

With the rapid acceleration of human social development, urban construction, and the rapid rise in car ownership, the number of traumas has increased dramatically[1]. Patients with trauma are often multi-injured, and the condition of multi-injury is more complex and critical, with a poor prognosis and a high risk of death. Moreover, it is a burden to society and the family. Hypocalcemia is highly common in hospitalized patients, including those with trauma, and abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and left untreated, and certain factors may lead to serious neurological and cardiovascular complications[2]. In this study, we retrospectively analyzed the correlations between blood calcium values[3]. In addition, other factors are associated with the prognosis of patients with multiple injuries. All the patients included in the study were admitted to the intensive care unit (ICU). We aimed to provide a reference to make monitoring and treatment stronger. In addition, we aimed to improve the success rates for these multiple injuries. Multiple traumas refer to severe trauma to more than two anatomical sites caused by the same traumatic factor, at least one of which is serious and life-threatening[4]. With the development of society and transportation, there is an increasing number of patients with multiple injuries, and death and disability rates remain high, which puts forward higher requirements for clinicians. The factors causing multiple injuries are extremely complex, and electrolyte and internal environmental disturbances are likely to occur in the early stages. Clinical changes in serum calcium ion (Ca²⁺) levels are common and often manifest as hypocalcemia.

MATERIALS AND METHODS

General information

A retrospective analysis was conducted on 99 patients with multiple injuries admitted to the Department of Intensive Care Medicine, Fuyang People’s Hospital, from January 2020 to December 2021. Based on the results of blood calcium values, 81 patients were grouped into the hypocalcemia group and 18 were in the normocalcemia group, with a blood calcium range of 2.11–2.52 and < 2.11 mmol/L defined as normal and hypocalcemic, respectively.

The inclusion criteria were as follows: (1) Meeting the diagnostic criteria for multiple injuries; (2) Previously physically healthy without any disease affecting the patient’s prognosis; and (3) Multiple ICU admissions for the same patient; only the first time was included. The following were the exclusion criteria: (1) Previous abnormal blood calcium; (2) Various cancers and bone diseases; (3) Presence of parathyroid disease and hyperphosphatemia; and (4) Presence of renal failure and the need for dialysis.

Specimen collection

Blood was immediately collected from patients with trauma for emergency inspection after admission. Blood was collected from the control group to detect serum Ca²⁺, hemoglobin (Hb), and prothrombin time (PT). The age, sex, and injury status of the patients were recorded. Biochemical index detection: Serum Ca²⁺ was determined using a Beckman-Coulter K (Beckman Coulter, Inc; Fullerton; CA; United States). An automatic biochemical analyzer used for detection. Hb was detected using an automatic blood analyzer (XE-5000, Sysmex Corporation; Foshan Shunde Dewei Medical equipment Co., LTD; Foshan; China), and PT was detected using an automatic blood coagulation analyzer (CA-7000, Sysmex Corporation; Foshan Shunde Dewei Medical equipment Co., LTD; Foshan; China).

Injury severity score criteria

The injury to each organ was rated from 1 to 6 points according to the degree of injury and size of the life-threatening injury, as follows: (1) Mild injury; (2) Moderate injury; (3) Serious injury; (4) Serious injury, but not life-threatening; (5) Serious injury, with the possibility of death; and (6) Extremely serious, basically impossible to rescue. The highest injury severity score of 75 was automatically determined when a patient had 1 or more IIS scores of 6 points.

Statistical processing

SPSS 17.0 statistical software was used for data analysis, was the expression of measurement data and count data were expressed as a rate or constituent ratio; rank sum test, t-test, and χ² test were used. Statistical significance was set at P < 0.05.

The dangers of hypocalcemia

Hypocalcemia affects both the peripheral and central nervous systems. When sick, the patient’s neuromuscular excitability increases, showing symptoms such as unsteady walking, uncoordinated gait, general weakness, headache, and other abnormal symptoms; foot, throat, and other spasms, causing epilepsy and accompanying mental disorders; and severe arrhythmia may cause malignant ventricular fibrillation. If low calcium levels persist, especially in patients with hypocalcemia, they must visit the hospital for timely treatment; otherwise, it will be life-threatening.

Why the blood calcium decreased

Reasons for the decrease in blood calcium: (1) Vitamin D can promote the absorption of calcium, and lack of vitamin D can lead to low blood calcium and vitamin D dependence; vitamin D loses the effect of promoting calcium absorption, leading to low blood calcium; (2) Hypoparathyroidism, including congenital hypothyroidism, autoimmune diseases, thyroid surgery, and radiation therapy, damages the parathyroid glands, resulting in parathyroid hormone deficiency and hypocalcemia; (3) Insufficient calcium intake, a long-term low-calcium diet, or malabsorption can lower blood calcium; and (4) Other diseases, such as chronic renal failure, liver disease, uremia, and distal convoluted tubular acidosis, can decrease blood calcium.

Additionally, critically ill patients are prone to hypocalcemia, and critically ill patients with hypocalcemia have a worse prognosis than those with normal blood calcium levels, indicating that hypocalcemia increases disease severity[5]. During the treatment of critically ill patients, timely intervention to reduce the occurrence of hypocalcemic complications is beneficial for reducing mortality and improving the prognosis.

How to prevent hypocalcemia

Finally, patients with hypocalcemia should consume more calcium-containing foods, such as milk, dried shrimp, soy products, and bones; consume more fruits; receive more sunlight; and take vitamin D supplements to promote calcium absorption.

RESULTS

Comparison of the general data between the two groups

The data between the two groups (general and clinical) were compared. A total of 99 patients with multiple injuries were included: 81 with hypocalcemia, 18 with normocalcemia, and no patients with hypercalcemia. The incidence of hypocalcemia was 81.82%, the Sequential Organ Failure Assessment (SOFA) score, the Acute Physiology and Chronic Health Evaluation (APACHE) II score, and the ICU length of stay among the two groups (Table 1).

Table 1 Comparison of general and clinical data between two groups of patients.

Indicators	Low blood calcium group (n = 81)	Normal blood calcium group (n = 18)	χ2/t	P value
Sex (Male/Female), cases (%)	54 (66.67)/27 (33.33)	16 (88.89)/2 (11.11)	3.511	0.061
Age (yr)	58.19 ± 16.24	51.83 ± 19.16	1.452	0.150
Blood calcium (mmol/L)	1.84 ± 0.15	2.18 ± 0.08	-13.922	< 0.001
HCT	0.26 ± 0.06	0.32 ± 0.06	-4.232	< 0.001
APACHE II (points)	17.93 ± 9.55	8.89 ± 4.99	5.702	< 0.001
SOFA (points)	7.84 ± 3.80	4.39 ± 3.22	3.575	0.001
Duration of mechanical ventilation (h)	70.16 (33.38-143.28)	20.63 (0-57.23)	-3.124	0.002
Length of ICU stay (d)	5 (3-9)	4 (2-6.25)	-1.954	0.051

HCT: Hematocrit; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment; ICU: Intensive care unit.

A comparison of the 28 d survival prognosis between the hypocalcemia and normocalcemia groups revealed 20 deaths in 81 cases of hypocalcemia and no deaths in 18 cases of the normocalcemia group; the mortality rate in the hypocalcemia group was higher than that in the normocalcemia group, and the difference was statistically significant (χ² = 4.143, P = 0.042) (Table 2).

Table 2 Comparison of 28 days survival prognosis between hypocalcemia and normocalcemia groups.

Group	Number of cases	28 days survival prognosis
		Deaths	Survival
Hypocalcemia group	81	20	61
Normocalcemic group	18	0	18
χ2 value		4.143
P value		0.042

Correlation analysis of blood calcium values with various clinical indicators in patients with multiple injuries

Blood calcium values in patients with multiple injuries were negatively correlated with APACHE II and SOFA scores (P < 0.05), positively correlated with hematocrit (HCT) (P < 0.001), and did not correlate with the duration of mechanical ventilation (P > 0.05) (Table 3).

Table 3 Correlation of blood calcium values with each index in patients with multiple injuries.

Indicators	Blood calcium		Indicators	Blood calcium
	r value	P value		r value	P value
APACHE II	-0.361	< 0.001	HCT	0.403	< 0.001
SOFA	-0.336	0.010	Duration of mechanical ventilation	-0.188	0.650

HCT: Hematocrit; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment.

The prediction of multiple injuries, the receiver operating characteristic curve analysis, and prognosis. The basic parameters were blood calcium values. The result was 0.66. The results are shown in Figure 1.

Figure 1  Receiver operating characteristic curve of blood calcium values to predict the prognosis of patients with multiple injuries.

DISCUSSION

Trauma is one of the main causes of global deaths and an important cause for disability of individuals worldwide. Trauma causes 10% of the total number of global deaths and 16% of disabilities. In individuals aged below 40 years, the main cause of death is trauma. In addition, it is the main factor causing deaths in children aged more than 1 year. Multiple injuries caused by trauma are the most common cause of death among adolescents worldwide. Hypocalcemia is prevalent in critically ill patients, especially those with trauma, and is correlated with patient condition and prognosis[6]. Hypocalcemia is associated with severe musculoskeletal traumas, traumatic brain injuries, the development of complications, and a poor prognosis, and it has been increasingly recognized as a complication associated with critical illnesses, including multiple injuries.

The main evaluation index was neurological dysfunction at the time of discharge (referring to the modified mRS score ≥ 3 points), and the secondary evaluation index was the complications of early hydrocephalus and symptomatic vasospasm within 72 h of admission. The diagnostic criteria for the brain were mean flow velocity ≥ 120 cm/s, anterior circulation Lindegaard ratio ≥ 3 or posterior circulation ≥ 2, or characteristic features of computed tomographic arteriography or digital subtraction angiography. Symptomatic cerebral vasospasm refers to neurological deterioration caused by vasospasm after excluding other causes, such as hydrocephalus, cerebral edema, seizures, electrolyte abnormalities, and infection, by computed tomography or magnetic resonance imaging. Finally, we performed a multivariate logistic regression prognostic analysis to determine whether serum calcium level was an independent predictor of poor prognosis in patients with subarachnoid hemorrhage.

Studies have reported that patients with multiple injuries are at a higher risk of developing hypocalcemia. However, hypocalcemia is often overlooked and has a powerful impact on patients with multiple injuries. Calcium plays a critical role in bone structure, neurotransmission, and endocrine physiology; additionally, intra- and extracellular calcium levels influence cardiac contractile function and vascular contraction and dilation; calcium is highly significant in hemostasis and coagulation[7]. Calcium is involved in the coagulation cascade. Coagulation dysfunction is associated with hypocalcemia; studies have reported that hypocalcemia aggravates acidosis in critically ill patients, indicating that calcium affects serum pH, with hypothermia, acidosis, and coagulation abnormalities comprising the lethal triad of patients with trauma[8].

In this study, there were 81 cases of hypocalcemia among the 99 patients included, all of whom had multiple injuries. The incidence of hypocalcemia was 81.82%, suggesting a high incidence of hypocalcemia in patients with multiple injuries, similar to the incidence of 74% and 75.5% in a study by foreign scholars. However, these results were significantly higher than the 21% in another study, probably because it chose the blood calcium values several days after the occurrence of multiple injuries, and the blood calcium values improved after several days. The causes of hypocalcemia in multiple injuries are ambiguous; however, the possible causes are as follows: (1) Massive transfusion of blood products containing citric acid in patients with multiple injuries, hypoperfusion, and hypothermia owing to shock can lead to a decrease in the rate of citric acid removal by the liver and an increase in the accumulation of citric acid and binding of calcium in the body, leading to the development of hypocalcemia[9]; (2) The loss of calcium during blood loss causes hypocalcemia; (3) Blood loss and pro-inflammatory factors leading to hypocalcemia owing to hypoparathyroidism, the resistance of effector organs to parathyroid hormone, impaired metabolism and action of vitamin D, and redistribution of calcium ions inside and outside cells; (4) Elevated calcitonin levels and increased urinary calcium elimination[10]; (5) Fluid resuscitation can lead to hemodilution and cause hypocalcemia; (6) Lactate can bind large amounts of calcium, and lactic acidosis leads to hypocalcemia[11]; and (7) A few conventional drug treatment, may trigger hypocalcemia, and hypocalcemia in patients with multiple injuries may be caused by a combination of factors[12].

The results of this study showed that blood calcium levels in patients with multiple injuries were negatively correlated with APACHE II and SOFA scores and positively correlated with HCT, whereas there was no correlation with the duration of mechanical ventilation, suggesting that the higher the APACHE II and SOFA scores and the lower the HCT value, the lower the blood calcium value. Additional results showed that blood calcium values have a predictive value for prognosis in patients with multiple injuries, with a sensitivity of 39.2% and a specificity of 95% for predicting prognosis when blood calcium values were < 1.98 mmol/L. Hypocalcemia has been suggested to be more severe and can increase mortality in patients with multiple injuries[13].

Approximately half of the serum calcium is bound to albumin in the blood, and the other half is free calcium, which plays a physiological role. However, since the free calcium in serum cannot be accurately measured clinically. The clinically measured serum calcium of patients with hypoalbuminemia must decrease, the corrected calcium concentration is calculated to compare whether the patient has low calcium[14]. However, most clinicians consider serum calcium < 2.20 mmol/L as the clinical reference value for hypocalcemia. Non-massive blood transfusions did not cause changes in blood calcium levels. Recently, a foreign study reported that hypocalcemia was an independent risk factor affecting the average hospital stay of patients after total knee arthroplasty.

Compared to other abnormal laboratory tests, most patients with hypocalcemia have no clinical symptoms; therefore, such a high attack rate has not received widespread attention in the academic community, and the reason for its high incidence has not been investigated[15]. The current mainstream view is that the main cause of hypocalcemia after joint replacement surgery is excessive blood loss during surgery, resulting in the loss of albumin and calcium ions, and simultaneously, a large amount of fluid replacement will dilute the blood concentration; the secondary cause may be the effect of surgery on the body[16]. Trauma caused by gastrointestinal disturbances reduces the intake and absorption of albumin and calcium ions. Hypoxia in the body during anesthesia has an inhibitory effect on parathyroid gland function, thereby reducing blood calcium ions, which directly damages the cell membrane and increases the permeability of calcium ions. Hypoxia decreases the activity of calcium pumps, which in turn increases the influx of calcium ions. During the stress state of surgery, parathyroid cells secrete large amounts of calcitonin, which increases plasma calcium.

Under stress, the permeability of systemic capillaries increases, and combined calcium and albumin leak out of the blood vessels. The routine application of proton pump inhibitors to prevent postoperative gastric bleeding can lead to a reduction of gastric acid, resulting in poor absorption of magnesium, which affects blood calcium. Sodium citrate in clinical blood products will complex the free calcium ions in blood products, further aggravating the loss of blood calcium. The R2 (adjusted) of Equation 1 obtained in this trial was 0.459 based on controlling for other secondary variables; that is, it can be statistically considered that there is a 45.9% correlation between changes in serum calcium and theoretical blood loss.

The results of this single-center retrospective study showed that hypocalcemia in patients with patients with traumatic hypocalcaemia treated with endovascular therapy was closely related to the occurrence of early acute hydrocephalus and poor neurological prognosis at discharge, which can be regarded as a better condition on admission. Prognostic indicators in patients with Hunt-Hess grades I–III Potential mechanisms include calcium-induced hypercoagulability and hypertension. The authors believe that further randomized controlled trials are needed to verify the prognostic value of hypocalcemia and explore whether hypocalcemia can be a therapeutic target for SSAH.

The serum calcium level for the clinical symptoms of severe hypocalcemia, such as muscle twitching and arrhythmia, is 1.65 mmol/L. In this study, the minimum postoperative serum calcium level was 1.88 mmol/L. The patients had obvious symptoms of hypocalcemia, and a few patients reported muscle spasms in the lower limbs on the affected side; however, their blood calcium values did not drop below the threshold. Besides, Consider limitations such as retrospective design and small sample size. Future larger prospective studies are needed to confirm these results and to explore potential therapeutic interventions for the treatment of hypocalcemia in polytrauma patients.

CONCLUSION

Hypocalcemia has a high probability of occurrence in patients with multiple injuries, and blood calcium values are closely related to the prognosis. Prognosis is directly associated with blood calcium levels, which can be used as an indicator to judge the prognosis of patients with multiple injuries. Thus, this study provides a novel perspective. Hypocalcemia has many adverse effects on patients, and these affect their families and society. Therefore, this study is highly meaningful. However, this study had certain limitations, such as the selection of the sample size, as the sample size was minimal. Another limitation is that this study used cases selected for the retrospective study, not the latest cases. This may have affected the results.