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Association Between Admission Ionized Calcium Level and Neurological Outcome of Patients with Isolated Severe Traumatic Brain Injury: A Retrospective Cohort Study

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Abstract

Background

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Pathophysiological processes following initial insult are complex and not fully understood. Ionized calcium (Ca++) is an essential cofactor in the coagulation cascade and platelet aggregation, and hypocalcemia may contribute to the progression of intracranial bleeding. On the other hand, Ca++ is an important mediator of cell damage after TBI and cellular hypocalcemia may have a neuroprotective effect after brain injury. We hypothesized that early hypocalcemia might have an adverse effect on the neurological outcome of patients suffering from isolated severe TBI. In this study, we aimed to evaluate the relationship between admission Ca++ level and the neurological outcome of these patients.

Methods

This was a retrospective, single-center, cohort study of all patients admitted between January 2014 and December 2020 due to isolated severe TBI, which was defined as head abbreviated injury score ≥ 4 and an absence of severe (abbreviated injury score > 2) extracranial injuries. The primary outcome was a favorable neurological status at discharge, defined by a modified Rankin Scale of 0–2. Multivariable logistic regression was performed to determine whether admission hypocalcemia (Ca++  < 1.16 mmol L−1) is an independent predictor of neurological status at discharge.

Results

The final analysis included 201 patients. Hypocalcemia was common among patients with isolated severe TBI (73.1%). Most of the patients had mild hypocalcemia (1 < Ca++  < 1.16 mmol L−1), and only 13 (6.5%) patients had Ca++  ≤ 1.00 mmol L−1. In the entire cohort, hypocalcemia was independently associated with higher rates of good neurological status at discharge (adjusted odds ratio of 3.03, 95% confidence interval 1.11–8.33, p = 0.03). In the subgroup of 81 patients with an admission Glasgow Coma Scale > 8, 52 (64.2%) had hypocalcemia. Good neurological status at discharge was recorded in 28 (53.8%) of hypocalcemic patients compared with 14 (17.2%) of those with normal Ca++ (p = 0.002). In multivariate analyses, hypocalcemia was independently associated with good neurological status at discharge (adjusted odds ratio of 6.67, 95% confidence interval 1.39–33.33, p = 0.02).

Conclusions

Our study demonstrates that among patients with isolated severe TBI, mild admission hypocalcemia is associated with better neurological status at hospital discharge. The prognostic value of Ca++ may be greater among patients with admission Glasgow Coma Scale > 8. Trials are needed to investigate the role of hypocalcemia in brain injury.

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Author notes

  1. Michael Roimi and Danny Epstein contributed equally as last authors.

Authors and Affiliations

  1. Critical Care Division, Rambam Health Care Campus, Haifa, Israel

    Karawan Badarni, Elias Andrawus, Yaron Bar-Lavie, Michael Roimi & Danny Epstein

  2. Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Noi Harush, Hany Bahouth, Yaron Bar-Lavie & Aeyal Raz

  3. Trauma and Emergency Surgery, Rambam Health Care Campus, Haifa, Israel

    Hany Bahouth

  4. Department of Anesthesiology, Rambam Health Care Campus, Haifa, Israel

    Aeyal Raz

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  1. Karawan Badarni
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Contributions

KB has contributed to the design of the research, the acquisition of data and drafting the article. NH has contributed to acquisition of data, EA has contributed to the design of the research and the acquisition of data, HB has contributed to the conception of research and acquisition of data. YB and AR has revised the data. MR has contributed to the design of the research, analysis and interpretation of data and drafting the article. DE has contributed to the conception, analysis, and interpretation of data and drafting the article. The final manuscript was approved by all authors.

Corresponding author

Correspondence to Karawan Badarni.

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Conflict of interest

Aeyal Raz reports receiving consultant fees Medtronic and Neuroindex and speaker’s fee from MSD (none related to this work). All the authors declare that they have no conflicts of interest.

Ethical approval/informed consent

The study was performed in concordance with the Helsinki declaration and was approved by the Institutional Review Board at Rambam Health Care Campus (Approval Number 0184-22-RMB-D). The need for written informed consent was waived because of the retrospective study design.

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Badarni, K., Harush, N., Andrawus, E. et al. Association Between Admission Ionized Calcium Level and Neurological Outcome of Patients with Isolated Severe Traumatic Brain Injury: A Retrospective Cohort Study. Neurocrit Care 39, 386–398 (2023). https://doi.org/10.1007/s12028-023-01687-4

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