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Three Part Question

In [paediatric major trauma patients] is [admission hypocalcaemia] associated with [adverse outcomes]?

Clinical Scenario

A 7-year-old girl has been bought in by ambulance to the emergency department having being involved in a motor vehicle collision. She is tachycardic, has abdominal bruising over her left upper quadrant, and is generally tender and guarding on examination. A venous blood gas on admission demonstrates hypocalcaemia. Since the ionised calcium level on a blood gas measures the physiologically active component of calcium (as opposed to total calcium which includes albumin bound calcium), you wonder whether the ionised hypocalcaemia might be related to adverse outcomes.

Search Strategy

Ovid MEDLINE (R) 1946 (inception) to July 3rd 2023 using the OVID interface, and Medline Epub. Embase 1974 to July 2023 using the OVID interface. The Cochrane Library and Google Scholar databases were also searched.

Ovid MEDLINE (R) 1946 (inception) to July 3rd 2023 using the OVID interface, and Medline Epub
Ahead of Print, In-Process & Other Non-Indexed Citations:

(‘Paediatric hypocalcaemia’/exp OR ‘Pediatric hypocalcaemia’) AND (‘trauma’/exp OR ‘trauma’)

Embase 1974 to July 2023 using the OVID interface:

(‘Paediatric hypocalcaemia’/exp OR ‘Paediatric hypocalcaemia’) AND (‘trauma’/exp OR ‘trauma’)

Search Outcome

22 papers were identified, seven papers were duplicates and a further 11 irrelevant for inclusion following abstract review by a single author. The remaining four papers are summarised in table 1.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ciaraglia et al. 2023. USA.	142 paediatric trauma patients (<18yrs) requiring the highest level of trauma team activation.	Retrospective cohort study. Level III.	Definition of hypocalcaemia was ionised calcium <1.00mmol/L. The primary outcomes were mortality at 4-hours, 24-hours, and overall, in-hospital mortality. Secondary outcomes were total blood product requirements (pre-hospital, 4-hour, 24-hour, and total).	66/132 (46.5%) patients were hypocalcaemic on admission. There was no observed difference in early or in-hospital mortality between hypocalcaemic and normocalcaemic patients. Hypocalcaemic patients had a higher proportion of patients with shock (shock index paediatric adjusted) and higher transfusion volumes at the 4-hour and 24-hour timepoints.	Retrospective. Single-centre. Underpowered to detect a mortality difference. Inclusion criteria by trauma team activation may miss more subtle presentations of major trauma patients (e.g., low-risk mechanism, initially haemodynamically normal). Did not capture whether hypocalcaemic patients had timely calcium supplementation.
Cornelius et al. 2021. USA.	1305 paediatric trauma patients (<19yrs).	Retrospective cohort study. Level III.	Definition of hypocalcaemia was total calcium <2.25mmol/L. The primary outcome was the incidence of hypocalcaemia. Secondary outcomes were the volume of total blood products required, operative intervention, and mortality (all within 24 hours).	625/1305 (47.9%) patients were hypocalcaemic. Hypocalcaemic patients required increased amounts of transfusion and operative intervention when compared to normocalcaemic patients. The average calcium concentration was lower in patients who died. Only a small number 34/625 (5.4%) of hypocalcaemic patients had calcium supplementation.	Retrospective. Single-centre. Undertaken at a Level 2 paediatric trauma centre. Mean Injury Severity Score is less than 15. Included isolated orthopaedic injuries. Used total calcium rather than ionised calcium. Did not perform subgroup analysis for the effect of calcium supplementation in hypocalcaemic patients.
Epstein et al. 2022. Israel.	457 paediatric (<18yrs) major trauma patients (Injury Severity Score >15).	Retrospective cohort study. Level III.	Definition of hypocalcaemia was ionised calcium <1.10mmol/L, and <1.00mmol/L for severe hypocalcaemia. The primary outcome was the incidence of admission hypocalcaemia. The secondary outcome was the need for blood product transfusion in the emergency department.	Hypocalcaemia was observed in 21/457 (4.6%) patients and severe hypocalcaemia in 3/457 (0.7%). Hypocalcaemia was an independent predictor of the need for blood transfusion. No significant mortality difference.	Retrospective. Single-centre. Did not include other adverse outcomes, such as need for operative intervention. Did not capture whether hypocalcaemic patients had this supplemented
Gimelraikh et al. 2022. Israel.	111 paediatric (<18yrs) major trauma patients (Injury Severity Score >15).	Retrospective cohort study. Level III.	Definition of hypocalcaemia was ionised calcium <1.16mmol/L, and <1.00mmol/L for severe hypocalcaemia. The primary outcome was the incidence of admission hypocalcaemia. Secondary outcomes included length of stay, volume of blood product transfusion in the first 48 hours, and in-hospital mortality.	22/111 (19.8%) of patients were hypocalcaemic (iCa <1.16 mmol/L) and 3/111 (2.7%) were severely hypocalcaemic, There were no statistically significant differences in outcomes.	Retrospective. Single-centre. Underpowered. Did not capture whether hypocalcaemic patients had this supplemented.

Comment(s)

Calcium has an essential role in the coagulation cascade and platelet function, and is required for cardiac contractility and vascular tone. Hypocalcaemia forms part of the “diamond of death” in haemorrhage, alongside hypothermia, acidosis, and coagulopathy. Admission hypocalcaemia prior to blood transfusion is prevalent in adult major trauma patients. Amongst paediatric major trauma patients, the four retrospective cohort studies identified in this short-cut review demonstrate heterogenous results with regards to the incidence of hypocalcaemia. Definitions of hypocalcaemia also differed between studies (<1.00 mmol/L to <1.16mmol/L). The majority of these studies observed an association between admission hypocalcaemia and the subsequent transfusion requirements. There is also potentially increased haemodynamic instability and need for operative intervention amongst hypocalcaemic paediatric major trauma patients. The lack of mortality difference likely reflects the low overall mortality observed in paediatric major trauma, and much larger multi-centre studies would be required to identify any mortality difference. None of the studies explored the effect of calcium supplementation in hypocalcaemic paediatric major trauma patients and this remains an area where further research is required.

Clinical Bottom Line

The incidence of admission hypocalcaemia in paediatric major trauma remains poorly defined, and hypocalcaemia may be associated with haemodynamic instability, increased transfusion requirements, and a need for operative intervention. Further studies are required, and the included studies may benefit from formal systematic review.

References

1. Ciaraglia A, Lumbard D, Deschner B, et al. The Effects of Hypocalcemia in Severely Injured Pediatric Trauma Patients. J Trauma Acute Care Surg. 2023;10.1097/TA.0000000000003902.
2. Cornelius BG, Clark D, Williams B, et al. A retrospective analysis of calcium levels in pediatric trauma patients. Int J Burns Trauma. 2021;11(3):267-274.
3. 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.
4. Gimelraikh Y, Berant R, Stein M, et al. Early Hypocalcemia in Pediatric Major Trauma: A Retrospective Cohort Study. Pediatr Emerg Care. 2022;38(10):e1637-e1640.