What is the role of calcium in trauma?
Major trauma is still a leading cause of death in children and young people. Severe bleeding can occur following injury, and many of the deaths that occur following an injury are due to bleeding. If bleeding is recognised and treated, this is a potentially survivable cause of death. Reflecting this, managing major trauma patients and bleeding is a consensus-based research priority in Paediatric Emergency Medicine, Emergency Medicine, and Pre-Hospital Emergency Medicine, which has also been agreed upon by patients and the public.
Calcium helps the blood to clot, the heart to beat stronger, and blood vessels to better respond to blood loss. Low levels (hypocalcaemia) can theoretically contribute to cardiovascular decompensation and worsening bleeding (coagulopathy).
What do we know?
For a long time, we have known that free calcium levels (ionised calcium) can be low in trauma patients after they have received a blood transfusion. This is because citrate, which is in blood products to stop them from clotting, can bind with and reduce the body’s free calcium. However, we are now recognising that hypocalcaemia can occur in trauma patients before they receive blood product transfusions, often called trauma-induced hypocalcaemia. The reasons for this are complex and not completely understood. This may be due to the body’s response to the injury (such as calcium loss in the blood or shifts in intracellular levels due to hypoperfusion), some of the treatments we administer in the early stages of injury treatment (such as fluid replacement that dilutes calcium), or a combination of both.
Among adult major trauma patients, trauma-induced hypocalcaemia is relatively common and has been reported to occur in up to 50% of injured patients. This has been associated with increased mortality, coagulopathy, shock, and increased blood transfusion requirements. Evidence on the prevalence of hypocalcaemia among children and its association with adverse findings is limited to a small number of studies, which have used different cut-off levels for hypocalcaemia and yielded varying results regarding its frequency (ranging from 5.3% to 46.5%).
Meta-analyses of these studies have suggested that trauma-induced hypocalcaemia occurs in approximately one in six children and adolescents. Although there does not appear to be significant differences in mortality between children with low and normal calcium levels, there does appear to be an increase in shock and increased treatment requirements, such as blood transfusions or interventional radiology/surgery, in the first 24 hours. Larger prospective studies are needed to explore this further.
What don’t we know?
Although guidelines recommend monitoring calcium levels and maintaining normal levels for major trauma patients, especially during massive transfusions, the guidance does not specify when to measure calcium or how this should be replaced in a protocolised manner.
There is a lack of consensus opinion on what represents a clinically significant hypocalcaemia in children. Anecdotally, there is also significant variation in massive transfusion protocols and how calcium measurement and replacement fit into these. We are also not entirely sure how often free calcium levels are measured amongst paediatric trauma patients or in what situations clinicians would choose to measure and replace hypocalcaemia.
Protocolised replacement of hypocalcaemia is also not quite as simple as it might initially seem, as high calcium levels are also associated with poor outcomes. Moreover, no current paediatric studies have explored the effect of calcium administration on trauma-induced hypocalcaemia.
Our survey aims to explore current practices and opinions regarding the measurement and replacement of calcium in paediatric trauma, and we would be grateful if you could help us further investigate this topic.
References
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DeBot M, Sauaia A, Schaid T, Moore EE. Trauma-induced hypocalcemia. Transfusion. 2022;62 Suppl 1:S274-S280. doi:10.1111/trf.16959
Epstein D, Ben Lulu H, Raz A, Bahouth H. Admission hypocalcemia in pediatric major trauma patients-An uncommon phenomenon associated with an increased need for urgent blood transfusion. Transfusion. 2022;62(7):1341-1346. doi:10.1111/trf.16936
Gimelraikh Y, Berant R, Stein M, Berzon B, Epstein D, Samuel N. Early Hypocalcemia in Pediatric Major Trauma: A Retrospective Cohort Study. Pediatr Emerg Care. 2022;38(10):e1637-e1640. doi:10.1097/PEC.0000000000002719
Helsloot D, Fitzgerald M, Lefering R, et al. Calcium supplementation during trauma resuscitation: a propensity score-matched analysis from the TraumaRegister DGU®. Crit Care. 2024;28(1):222. Published 2024 Jul 5. doi:10.1186/s13054-024-05002-1
Helsloot D, Fitzgerald M, Lefering R, Verelst S, Missant C; TraumaRegister DGU. Trauma-induced disturbances in ionized calcium levels correlate parabolically with coagulopathy, transfusion, and mortality: a multicentre cohort analysis from the TraumaRegister DGU®. Crit Care. 2023;27(1):267. Published 2023 Jul 6. doi:10.1186/s13054-023-04541-3
Hibberd O, Barnard E, Ellington M, Harris T, Thomas SH. Association of Non-Transfusion-Related Admission Hypocalcaemia With Haemodynamic Instability in Paediatric Major Trauma: A Retrospective Single-Centre Pilot Study. Cureus. 2024;16(7):e64983. Published 2024 Jul 20. doi:10.7759/cureus.64983
Hibberd O, Barnard E. In paediatric major trauma patients is admission hypocalcaemia associated with adverse outcomes? Trauma. 2024;26(2):192-194. doi:10.1177/14604086231222340
Hibberd O, Price J, Thomas SH, Harris T, Barnard EBG. The incidence of admission ionised hypocalcaemia in paediatric major trauma-A systematic review and meta-analysis. PLoS One. 2024;19(5):e0303109. Published 2024 May 28. doi:10.1371/journal.pone.0303109
Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80. Published 2023 Mar 1. doi:10.1186/s13054-023-04327-7
Rushton TJ, Tian DH, Baron A, Hess JR, Burns B. Hypocalcaemia upon arrival (HUA) in trauma patients who did and did not receive prehospital blood products: a systematic review and meta-analysis [published correction appears in Eur J Trauma Emerg Surg. 2024 Dec;50(6):3353. doi: 10.1007/s00068-024-02544-5]. Eur J Trauma Emerg Surg. 2024;50(4):1419-1429. doi:10.1007/s00068-024-02454-6
Toner MB, Coffey M, Nurmatov U, Mullen S. Paediatric trauma and hypocalcaemia: a systematic review. Arch Dis Child. Published online December 12, 2024. doi:10.1136/archdischild-2023-326576
