Abstract
Background
Hypocalcemia is a common metabolic disturbance in trauma and may contribute to coagulopathy, hemodynamic instability, and adverse outcomes. This study aimed to investigate whether admission ionized calcium (iCa) levels are associated with in-hospital mortality and transfusion requirements in moderate-to-severe trauma patients.
Methods
This retrospective cohort study included adults (≥ 18 years) with moderate-to-severe trauma, defined as an Injury Severity Score (ISS) ≥ 9, admitted to the emergency department of a tertiary university hospital between January 2019 and December 2024. Patients with cardiac arrest, pregnancy, insufficient admission laboratory results, ISS < 9, or pre-hospital transfusion were excluded. Severe hypocalcemia was defined as iCa < 0.9 mmol/L. Baseline characteristics were compared between survivors and non-survivors, and the diagnostic performance of severe hypocalcemia (iCa < 0.9 mmol/L) for predicting mortality and transfusion was analyzed.
Results
A total of 1,071 trauma patients were included; 136 (12.7%) died. Severe hypocalcemia was more common among non-survivors than survivors (23.5% vs. 7.3%; p < 0.001) and among transfused patients than non-transfused patients (16.2% vs. 8.3%; p = 0.003). Severe hypocalcemia showed high specificity but low sensitivity for both mortality and transfusion prediction. In multivariate analysis, age, male gender, prolonged PT, pH < 7.30, elevated lactate, and severe hypocalcemia were independent predictors of mortality.
Conclusion
Severe hypocalcemia is a significant predictor of adverse outcomes in trauma patients, remaining significant after adjustment for demographic and metabolic confounders. Future prospective studies are needed to determine whether early correction of hypocalcemia can improve survival and transfusion outcomes in trauma care.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12873-026-01476-0.
Keywords: Ionized calcium, Hypocalcemia, Trauma, Mortality, Transfusion
Introduction
Trauma causes approximately 4.4 million deaths worldwide each year and accounts for about 8% of all deaths, representing a major public health problem and an important source of preventable mortality in emergency departments [1]. Early identification of patients at high risk for adverse outcomes is therefore crucial for guiding resuscitation, transfusion strategies, and intensive care needs. Although several trauma scores and laboratory markers have been proposed to predict prognosis, many of them are dynamic parameters that change rapidly with resuscitation, which may limit their reproducibility and clinical applicability [2–4].
Calcium is a key electrolyte involved in blood coagulation, myocardial contractility, vascular tone, muscle contraction, and intracellular signaling. Hypocalcemia is frequently observed in trauma patients and has been associated with hypotension, acidosis, and increased mortality risk [4]. In this context, the traditional “lethal triad” of hypothermia, acidosis, and coagulopathy has recently been expanded to the “lethal diamond” by incorporating hypocalcemia [5]. Ionized calcium [iCa], rather than total serum calcium, more accurately reflects the physiologically active fraction and plays a central role in calcium-dependent clotting factors and cardiovascular stability [4, 6–8]. Previous studies have reported that hypocalcemia is common among severely injured patients, particularly in those requiring massive transfusion, and may be associated with worse clinical outcomes [6–12].
Institutional laboratory reference values in our center define hypocalcemia as iCa < 1.12 mmol/L and severe hypocalcemia as iCa < 0.9 mmol/L, which are consistent with recent literature [7, 12]. Based on this background, the present study aimed to investigate whether admission iCa levels are associated with in-hospital mortality and transfusion requirements in patients presenting to the emergency department with moderate-to-severe trauma. We hypothesized that severe hypocalcemia at admission would be independently associated with adverse outcomes in this population.
Methods
Study design and setting
This was a retrospective cohort study conducted in the emergency department of a tertiary university hospital that admits approximately 40,000 trauma patients annually. All data were extracted from the hospital’s electronic medical record system and emergency department registry. Ethical approval was obtained from the Düzce University Non-Interventional Health Research Ethics Committee (Date: January 6, 2025; No: 2025/01).
This study received no external funding. Clinical trial registration was not applicable. The study was conducted in accordance with the principles of the Declaration of Helsinki. The manuscript was prepared in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
Participants
Based on a previous study comparing mortality rates in hypocalcemic and normocalcemic trauma patients, with a 95% confidence interval and a margin of error of 0.05, the minimum required sample size was calculated as at least 119 patients in each group (a total of 238 patients) [6].
Patients admitted between January 1, 2019, and December 31, 2024, who met the inclusion criteria, were included in the study. Mortality was defined as death occurring before hospital discharge. Hypocalcemia was defined as iCa < 1.12 mmol/L, and severe hypocalcemia as iCa < 0.9 mmol/L [7, 10]. Transfusion was defined as the administration of packed red blood cells (PRBCs), platelet concentrates, or fresh frozen plasma. Other blood products were excluded as they were not routinely available in the study center. The Injury Severity Score (ISS) was used to classify trauma severity: scores of 9–15 indicated moderate trauma, and scores > 15 indicated severe trauma [13].
As the study center is the sole trauma referral hospital in the region, all trauma cases requiring ambulance transport were referred to this institution. For walk-in admissions, patients who had previously presented to an outside facility were excluded. Only patients whose initial presentation was to the study center were included. Inclusion criteria were: patients aged ≥ 18 years, admission due to trauma (or ICD-10 diagnosis codes S00–T78), trauma patients with ISS ≥ 9 defined as having moderate to severe trauma, and arterial blood gas, complete blood count and biochemistry parameters sampling at admission. Exclusion criteria were: patients younger than 18 years, those brought in with cardiac arrest, pregnant patients, patients without arterial blood gas, complete blood count and biochemistry parameters analysis, those with an ISS < 9, and patients who received pre-hospital transfusion.
In our region, pre-hospital emergency medical services are provided by physician- or paramedic-led teams who can initiate basic resuscitation and trauma care. However, detailed information on pre-hospital interventions other than documented blood product transfusion is not systematically recorded in the hospital electronic database and was therefore not included in the analysis. Patients with documented pre-hospital transfusion were excluded from the study.
Statistical analysis
Descriptive statistics were expressed as frequencies and percentages. Normally distributed numerical variables were expressed as mean ± standard deviation (SD), whereas non-normally distributed numerical variables were expressed as median and interquartile range (IQR). Independent categorical variables were compared using Pearson’s chi-square test, and Fisher’s exact test was applied when the expected frequency was less than five. Bonferroni correction was applied for multiple subgroup comparisons, with a significance threshold of p < 0.016. For continuous variables, Student’s t-test was used when the data were normally distributed, and the Mann–Whitney U test was used for non-normally distributed data. According to the literature-defined cut-off value for severe hypocalcemia (0.9 mmol/L), odds ratios (ORs), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) were calculated. For LR+ (sensitivity / 1-specificity), values between 1 and 5 indicated low, 5–10 moderate, and ≥ 10 strong clinical significance; for LR- (1-sensitivity / specificity), values < 0.1 were considered clinically significant, 0.1–0.2 moderate, 0.2–0.5 of limited importance, and 0.5–1 negligible [14].
Univariate binary logistic regression analysis was performed to identify factors associated with mortality in trauma patients presenting to the emergency department. Independent variables included age, gender, hemoglobin, hematocrit, PT, aPTT, pH < 7.30, lactate level, severe hypocalcemia (iCa < 0.9 mmol/L), mild hypocalcemia (iCa < 1.12 mmol/L), and blood transfusion status [6, 7, 10]. Variables with a p-value < 0.20 in the univariate analysis were entered into the multivariate logistic regression model to determine independent predictors of mortality. Continuous variables were included in the model as linear terms. Polynomial terms were not used to maintain clinical interpretability and model simplicity. The multivariate model was refined using a backward stepwise elimination method with a removal criterion of p > 0.10. Potential two-way interactions between relevant predictors (e.g., pH × hypocalcemia, PT × hemoglobin) were explored. However, none reached statistical significance (p > 0.10); therefore, only main effects were retained in the final model to ensure model stability and interpretability The final model identified male gender, prolonged PT, low hemoglobin level, pH < 7.30, and severe hypocalcemia as independent predictors of mortality. Multicollinearity among independent variables was assessed using variance inflation factors (VIF < 2.5). Missing data were handled using complete case analysis. Patients with missing values for the primary variables of interest (ionized calcium, blood gas parameters) were excluded from the study as per the exclusion criteria. No imputation techniques were applied. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). A p-value < 0.05 was considered statistically significant.
Results
During the study period, a total of 220,567 trauma-related emergency department visits were screened. After applying the exclusion, 1071 patients with moderate-to-severe trauma and available ionized calcium measurements at admission were included in the final analysis (Fig. 1).
Fig. 1.
Patient selection flow chart
Among the 1,071 patients included in the study, 136 (12.7%) died and 935 (87.3%) survived. Baseline demographic, clinical and laboratory characteristics according to survival status are summarized in Table 1. Compared with survivors, non-survivors were older and more frequently male, and showed lower hemoglobin and hematocrit levels, more pronounced coagulation abnormalities, and lower total and ionized calcium levels. Severe hypocalcemia was more common among non-survivors, whereas normocalcemia was more frequent in survivors, while the frequency of mild hypocalcemia was similar between groups.
Table 1.
Descriptive data of patients and comparison with mortality
| Variables | Mortality | p a | ||
|---|---|---|---|---|
| Non-survivors n(%) = 136 |
Survivors n(%) = 935 |
Total n(%) = 1071 |
||
|
Age, years Median (IQR) |
70.5 (65.0–78.0) | 67.0 (54.0–76.0) | 68.0 (55–77) | < 0.001b |
| Gender, Male | 91 (66.9) | 493 (52.7) | 584 (54.5) | 0.002 |
| Hemoglobin (g/dL) | < 0.001 b | |||
| Median (IQR) | 9.7 (8.4–11.6) | 11.7 (9.9–13.4) | 11.4 (9.6–13.3) | |
| Hematocrit (%) | < 0.001 b | |||
| Median (IQR) | 29.1 (24.9–34.0) | 34.2 (29.3–39.0) | 33.6 (28.7–38.8) | |
| PT, INR | < 0.001 b | |||
| Median (IQR) | 1.3 (1.1–1.6) | 1.1 (1.0-1.2) | 1.1 (1.01–1.26) | |
| aPTT, sec | 0.001 b | |||
| Median (IQR) | 33 (28.6–37.4) | 29.9 (26.4–33.3) | 30.1 (26.7–33.6) | |
| Serum Calcium (mg/dL) | 0.001 b | |||
| Median (IQR) | 8.4 (7.7–9.1) | 9 (8.4–9.4) | 8.9 (8.3–9.3) | |
| Blood Gas | ||||
| pH | 0.001 b | |||
| Median (IQR) | 7.36 (7.25–7.43) | 7.39 (7.35–7.43) | 7.39 (7.35–7.43) | |
| Lactate (mg/dL) | 0.001 b | |||
| Median (IQR) | 2.2 (1.3–4.17) | 1.5 (1.1–2.1) | 1.5 (1.1–2.3) | |
| Ionized Calcium (mmol/L) | 0.001 b | |||
| Median (IQR) | 1.04 (0.90–1.12) | 1.11 (1.03–1.17) | 1.1 (1.02–1.17) | |
| Severe hypocalcemia (iCa < 0.9 mmol/L) | 32 (23.5) | 68 (7.3) | 100 (9.3) | < 0.001 |
|
Mild hypocalcemia (iCa < 1.12 mmol/L) |
66 (48.6) | 427 (45.6) | 493 (46) | 0.532 |
|
Normocalcemia (iCa ≥ 1.12 mmol/L) |
38 (27.9) | 440 (47.1) | 478 (44.7) | < 0.001 |
|
ISS 9–15 (Moderate) > 15 (Severe) |
66 (48.5) 70 (51.5) |
855 (91.4) 80 (8.6) |
921 (86) 150 (14) |
< 0.001 |
| Blood Transfusion, Yes | 36 (26.5) | 100 (10.7) | 136 (12.7) | < 0.001 |
IQR: Interquantile Range, PT: Prothrombin Time, aPTT: Activated Partial Thromboplastin Time, a: Pearson Chi Square test, b: Mann-Whitney U test
Transfusion characteristics are presented in Table 2. Patients who received blood transfusion were older, more often male, and had lower hemoglobin, hematocrit and calcium levels, together with prolonged coagulation times, compared with those who did not receive transfusion. Severe hypocalcemia was more frequent and normocalcemia less frequent in the transfusion group, whereas trauma severity categories (ISS 9–15 vs. > 15) did not differ significantly between transfused and non-transfused patients.
Table 2.
Descriptive data of patients and comparison with blood transfusion
| Variables | Blood Transfusion | p a | ||
|---|---|---|---|---|
| Yes n(%) = 136 |
No n(%) = 935 |
Total n(%) = 1071 |
||
|
Age, years Median (IQR) |
69 (61–78) | 66 (52.5–76) | 68.0 (55–77) | < 0.009 b |
| Gender, Male | 85 (62.5) | 499 (53.4) | 584 (54.5) | 0.046 |
| Hemoglobin (g/dL) | < 0.001 c | |||
| Mean ± SD | 8.94 ± 1.58 | 11.91 ± 2.20 | 11.50 ± 2.35 | |
| Hematocrit (%) | < 0.001 c | |||
| Mean ± SD | 26.26 ± 4.45 | 34.90 ± 6.05 | 33.81 ± 6.67 | |
| PT, INR | < 0.001 b | |||
| Median (IQR) | 1.2 (1.1–1.4) | 1.1 (1-1.2) | 1.1 (1-1.3) | |
| aPTT, sec | 0.041 b | |||
| Median (IQR) | 31.1 (27.8–34.9) | 29.9 (26.3–33.6) | 30.1 (26.7–33.6) | |
| Serum Calcium (mg/dL) | < 0.001 b | |||
| Median (IQR) | 8.2 (7.6–8.8) | 9 (8.5–9.4) | 8.9 (8.3–9.3) | |
| Blood Gas | ||||
| pH | 0.774b | |||
| Median (IQR) | 7.40 (7.35–7.44) | 7.38 (7.35–7.43) | 7.39 (7.35–7.43) | |
| Lactate (mg/dL) | 0.295b | |||
| Median (IQR) | 1.8 (1.2–2.7) | 1.6 (1.1–2.4) | 1.5 (1.1–2.3) | |
| Ionized Calcium (mmol/L) | < 0.001 b | |||
| Median (IQR) | 1.01 (0.94–1.10) | 1.12 (1.04–1.19) | 1.1 (1.02–1.17) | |
|
Severe hypocalcemia (iCa < 0.9 mmol/L) |
22 (16.2) | 78 (8.3) | 100 (9.3) | 0.003 |
|
Mild hypocalcemia (iCa < 1.12 mmol/L) |
88 (64.7) | 405 (43.3) | 493 (46) | < 0.001 |
|
Normocalcemia (iCa ≥ 1.12 mmol/L) |
26 (19.1) | 452 (48.3) | 478 (44.7) | < 0.001 |
|
ISS 9–15 (Moderate) > 15 (Severe) |
117 (86) 19 (14) |
804 (86) 131 (14) |
921 (86) 150 (14) |
0.557 |
IQR: Interquantile Range, SD: Standard Deviation, PT: Prothrombin Time, aPTT: Activated Partial Thromboplastin Time
a: Pearson Chi Square test
b: Mann-Whitney U test
c: Student-t test
The distribution of calcium status according to trauma severity is shown in Table 3. Severe hypocalcemia was more frequent in patients with severe trauma (ISS > 15), whereas normocalcemia predominated in moderate trauma (ISS 9–15). Early (24-hour) mortality rates did not differ significantly between moderate and severe trauma groups (Table 3).
Table 3.
The relationship between calcium levels and moderate-to-severe trauma
| Variables | ISS | p a | ||
|---|---|---|---|---|
| 9–15 Moderate n(%) = 921 |
> 15 Severe n(%) = 150 |
Total n(%) = 1071 |
||
|
Severe hypocalcemia (iCa < 0.9 mmol/L) |
68 (7.4) | 32 (21.3) | 100 (9.3) | < 0.001 |
|
Mild hypocalcemia (iCa < 1.12 mmol/L) |
427 (46.4) | 66 (44) | 493 (46) | 0.590 |
|
Normocalcemia (iCa ≥ 1.12 mmol/L) |
426 (46.3) | 52 (34.7) | 478 (44.6) | 0.010 |
| 24 h Mortality, Yes | 18 (2) | 6 (4) | 24 (2.2) | 0.132b |
a: Pearson Chi Square test, b: Fisher-Exact test
The diagnostic performance of severe hypocalcemia (iCa < 0.9 mmol/L) for predicting in-hospital mortality and blood transfusion requirement is presented in Table 4. Severe hypocalcemia was associated with a higher odds of mortality and transfusion, with low sensitivity but high specificity and negative predictive value for both outcomes (Table 4).
Table 4.
Severe hypocalcemia diagnostic value for mortality and blood transfusion
| Outcome | OR (%95 CI) |
Sensitivity (%) | Specificity (%) | LR+ | LR- | PPV (%) | NPV (%) | p value |
|---|---|---|---|---|---|---|---|---|
| Mortality |
3.92 (2.46–6.28) |
23.53 | 92.73 | 3.24 | 0.82 | 32 | 89.29 | < 0.001 |
| Blood Transfusion |
2.12 (1.27–3.53) |
16.18 | 91.66 | 1.94 | 0.91 | 22 | 88.26 | 0.004 |
OR: Odds Ratio, LR: Likelihood Ratio, PPV: Positive Predictive Value, NPV: Negative Predictive Value
Results of the univariate and multivariate logistic regression analyses for in-hospital mortality are shown in Table 5. In univariate analysis, age, male gender, prothrombin time, pH < 7.30, lactate level and severe hypocalcemia were significantly associated with mortality. In the multivariate model, age, male gender, prothrombin time, pH < 7.30, lactate level and severe hypocalcemia remained independently associated with increased mortality risk. The final model showed acceptable calibration (Hosmer–Lemeshow test, p = 0.253) and moderate explanatory power (Cox & Snell R² = 0.126; Nagelkerke R² = 0.245) (Table 5).
Table 5.
Regression analysis of parameters that may be associated with mortality
| Parameters | Univariate Regression Analysis | Multivariate Regression Analysis* | ||||
|---|---|---|---|---|---|---|
| B | p | OR (%95 CI) | B | p | OR (%95 CI) | |
| Age, years | 0.025 | < 0.001 | 1.03 (1.01–1.04) | - | - | - |
| Gender, Male | 0.595 | 0.002 | 1.81 (1.24–2.65) | 0.645 | 0.010 | 1.91 (1.17–3.11) |
| Hemoglobin (g/dL) | -0.298 | < 0.001 | 0.74 (0.68–0.81) | -0.927 | < 0.001 | 0.40 (0.24–0.66) |
| Hematocrit (%) | -0.088 | < 0.001 | 0.92 (0.89–0.94) | - | - | - |
| PT, INR | 0.983 | < 0.001 | 2.67 (1.87–3.82) | 0.669 | 0.001 | 1.95 (1.34–2.85) |
| aPTT, sec | 0.052 | < 0.001 | 1.05 (1.03–1.08) | - | - | - |
| pH < 7.30 | 2.200 | < 0.001 | 9.03 (5.54–14.72) | 1.391 | < 0.001 | 4.02 (2.18–7.42) |
| Lactate (mg/dL) | 0.240 | < 0.001 | 1.27 (1.18–1.37) | - | - | - |
|
Severe Hypocalcemia (iCa < 0.9 mmol/L) |
1.367 | < 0.001 | 3.92 (2.46–6.28) | 0.665 | 0.047 | 1.95 (0.96–3.96) |
|
Mild hypocalcemia† (iCa < 1.12 mmol/L) |
0.115 | 0.532 | 1.12 (0.78–1.61) | - | - | - |
| Blood Transfusion, Yes | 1.101 | < 0.001 | 3.01 (1.95–4.64) | - | - | - |
Dependent Variable: Mortality; Hosmer and Lemeshow p = 0.253; Cox&Snell R2 = 0.126, Nagelkerke R2 = 0,245
*Backward stepwise logistic regression with p>0.10 removal criteria. Variables with p<0.20 in univariate analysis were included in the initial model
†Not included in multivariate model due to non-significance in univariate analysis (p>0.20)
OR: Odds Ratio, CI: Confidence Interval, PT: Protrombin Time, aPTT: Activated Partial Thromboplastin Time, iCa: Ionized Calcium
Discussion
This retrospective cohort study suggests that severe hypocalcemia is independently associated with increased mortality and transfusion requirements in trauma patients. Although admission ionized calcium levels were linked to adverse outcomes, their diagnostic performance indicates that iCa is better interpreted as a marker of overall disease severity rather than as an exclusion parameter in triage.
In the mortality group, hemoglobin and hematocrit levels were lower, whereas PT and aPTT values were higher than in survivors. These findings are consistent with previous reports and support the contribution of trauma-related coagulopathy to poor outcomes [15, 16]. Likewise, calcium levels were lower in both the mortality and transfusion groups, in line with the proposed pathophysiologic link between hypocalcemia, bleeding tendency and hemodynamic instability. The parallel increase in mortality and in the prevalence of severe hypocalcemia with higher trauma severity further supports an association between calcium imbalance and the extent of tissue injury.
Acidosis is a well-established component of the classical “lethal triad” in trauma. With the addition of hypocalcemia, this concept has evolved into the “lethal diamond,” underlining the importance of calcium homeostasis in trauma physiology [5, 8]. Although previous studies have questioned the role of hypocalcemia in early (24-hour) mortality [17], our findings suggest that severe hypocalcemia is significantly associated with overall in-hospital mortality, underlining its relevance for long-term prognosis rather than immediate outcomes.
In this study, the median pH in the mortality group remained within the normal range, but was slightly yet significantly lower than in survivors, and lactate levels were higher, in agreement with earlier studies linking acid–base disturbances and hyperlactatemia with adverse prognosis [18–20]. Taken together, these results reinforce the view that hypocalcemia should be interpreted within the broader context of shock, coagulopathy and metabolic derangement rather than as an isolated abnormality.
Admission iCa levels were lower in both the mortality and transfusion groups, consistent with several previous investigations [4, 6, 10, 21, 22]. Reported mortality rates [7, 10, 12, 16] among hypocalcemic trauma patients in the literature range between 15 and 26%, which is comparable to the rate observed in our cohort (16.5%). The higher prevalence of hypocalcemia among transfused patients compared with non-transfused patients further supports the close association between calcium imbalance and bleeding or the need for aggressive resuscitation, and is in line with current massive transfusion protocols.
Although severe hypocalcemia showed a significant association with both mortality and transfusion, the diagnostic performance indices (LR+, LR–, PPV, and NPV) indicate limited utility for triage or exclusion purposes. Therefore, iCa measurement should be viewed primarily as a prognostic rather than diagnostic tool in trauma care.
Based on prior studies [10, 12, 15, 22, 23], parameters including age, gender, hemoglobin, hematocrit, PT, aPTT, pH < 7.30, lactate level, severe hypocalcemia, mild hypocalcemia, blood transfusion were assessed individually using univariate logistic regression and subsequently incorporated into a multivariate logistic regression model. Male gender, each one-second prolongation of PT approximately and severe hypocalcemia doubled the mortality risk. Overall, the model explained 24.5% of the variance in mortality (Nagelkerke R² = 0.245).
Limitations
This study has several limitations. First, it was conducted as a retrospective, single-center study, which may limit generalizability; thus, multicenter prospective studies are warranted. Second, different threshold values for moderate and severe hypocalcemia have been proposed across centers, making standardization challenging. In this study, we adopted the current reference ranges used in our institution and supported them with recent literature. Third, the sample size may not have been sufficient for external validation, and larger-scale validation studies are needed. Fourth, since only patients with ISS ≥ 9 were included, comorbidities and mechanisms of injury were not analyzed, which may introduce bias. Fifth, parameters such as cause of death, presence of traumatic brain injury and corresponding GCS, vital signs, and body temperature at admission were not included in the study. These parameters were not included primarily due to the inconsistent documentation characteristic of retrospective registry data. We acknowledge that the absence of these established confounding factors is a limitation; however, we attempted to control for overall injury severity using the ISS and physiological compromise using metabolic markers (pH, lactate). However, this limitation may restrict the generalizability of the results. Sixth,, coagulopathy associated with traumatic brain injury is a well-known factor for poor clinical outcomes. However, since our study groups were classified based on the ISS, this condition was not specifically analyzed. Seventh, only packed red blood cells, platelet suspensions, and fresh frozen plasma were available at our center; other blood products and calcium replacement therapy were not included in the analysis. Nevertheless, as laboratory values were obtained prior to any replacement therapy, the reliability of the results was strengthened.
Finally, several methodological biases inherent to the study design warrant specific consideration. Selection bias remains a potential concern due to the use of complete case analysis, where the exclusion of patients with missing laboratory data might have altered the clinical profile of the cohort. Regression dilution bias may have affected our results; relying on a single admission measurement of ionized calcium and other physiological parameters does not account for rapid temporal fluctuations during resuscitation, potentially underestimating the true strength of the associations. Misclassification bias cannot be ruled out, particularly regarding the retrospective chart review and Reliance on ICD codes for trauma diagnoses. Furthermore, although we tested for primary statistical interactions, unmeasured complex biological interactions between coagulopathy, metabolic acidosis, and hypocalcemia may still influence outcomes in ways that a standard logistic model cannot fully capture. Future prospective studies are required to evaluate the effects of calcium replacement on mortality and transfusion requirements.
In conclusion, this study demonstrates that severe hypocalcemia is significantly associated with increased mortality and transfusion requirements in trauma patients, retaining its prognostic value even after adjusting for age, gender, coagulopathy, and metabolic acidosis. Although ionized calcium levels correlate with adverse outcomes, their diagnostic accuracy remains limited, suggesting that iCa should primarily be interpreted as a marker of disease severity rather than a diagnostic criterion. The observed relationship between trauma severity and calcium imbalance further supports the role of calcium homeostasis in trauma physiology. Future multicenter prospective studies are warranted to validate these findings and to determine whether early recognition and correction of hypocalcemia could improve survival and transfusion outcomes in trauma care.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
None.
Author contributions
Concept – KS, MCD, EŞ; Supervision – KS, MCD, EŞ; Materials – KS, MCD, EŞ; Data Collection and Processing – KS, MCD; Analysis and Interpretation –KS, MCD; Writing – KS, MCD, EŞ.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethical approval
This study was initiated in the emergency department of a university hospital following the ethics committee approval. (Duzce University Non-Invasive Health Research Ethics Committee’s approval with decision number Date: 06.01.2025; No:2025/01.
Informed consent
After obtaining ethical approval, the data were collected retrospectively by examining the Hospital Data Processing System and Archive records. The need for signed informed consent was waived due to the retrospective design of the study. The manuscript was prepared in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
Human rights
The study was conducted in accordance with the principles of the Declaration of Helsinki.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.