Prehospital administration of calcium in trauma

Calcium and haemorrhagic shock

Calcium ions initiate actin-myosin filament binding, resulting in myofibril (muscle-fibre) shortening and muscle contraction. Depletion of calcium ions because of loss during haemorrhage and consumption from clot formation can therefore reduce myocardial contractility and vascular smooth-muscle tone, thereby reducing cardiac output and blood pressure, exacerbating shock (Spahn et al, 2019).

Calcium is also essential for platelet adhesion and factors II, VII, IX and X in the clotting cascade. Hypocalcaemia therefore has the potential to exacerbate coagulopathy, leading to further haemorrhage. Patients who receive transfusions to replace blood loss are at risk of experiencing further depletion of calcium ions from citrate, a chelating (ion-binding) agent that is added to transfusion products to prevent calcium from causing donor blood to coagulate (Spahn et al, 2019). This is a pertinent consideration for prehospital administration of blood products, as well as for paramedics who may not carry or transfuse blood products but expect a patient with shock from traumatic haemorrhage to receive blood transfusions on arrival at hospital.

Many trauma centres now supplement multiple blood transfusions with intravenous calcium within their mass transfusion protocol (MTP) (Spahn et al, 2019; Cornelius et al, 2020). Some prehospital services, including several UK-based helicopter emergency medical services, do this too. In Australia, Ambulance Victoria flight paramedics administer intravenous calcium gluconate when they administer four or more units of packed red blood cells (pRBC) (Ambulance Victoria, 2020).

The purpose of this systematic literature review was to determine whether paramedic administration of intravenous calcium for haemorrhagic shock in trauma has the potential to reduce morbidity and mortality.

Methods

The MEDLINE and CINAHL databases were searched on 20 August 2021 using the strategy shown in Table 1.

One person screened the titles of peer-reviewed articles investigating hypocalcaemia associated with traumatic haemorrhage published from 2016 onwards. Articles before 2016 (older than 5 years) were excluded to ensure relevance to current practice, especially given recent evolutions in prehospital transfusion practice. Studies unrelated to trauma were also excluded.

A manual search of references within the articles that met the inclusion criteria was also conducted to capture all relevant publications.

A total of 52 abstracts were screened from the database search with nine articles meeting the inclusion criteria. A further five studies were found after the references of these articles were manually checked. This yielded 14 articles (Figure 2).

Prehospital studies were keenly sought; five met the inclusion criteria. The remaining nine studies assessed hospital patients within the emergency department (ED) or trauma centre. All hospital and prehospital articles included in this review were relevant to paramedic practice in that they assessed aspects of patient management during or immediately after receiving paramedic care and had findings pertinent to paramedic practice.

Both military and civilian studies were included to assess whether injuries in either setting were associated with similar or differing patterns of hypocalcaemia.

The hierarchy of evidence was considered for all recommendations in this review. The rating system developed by Harbour and Miller (2001) was used to determine the level of evidence for each finding and to grade each recommendation (Table 2). These ratings are expressed alongside each finding and recommendation.

Results

Table 3 summarises the included studies.

Discussion

This is the first systematic literature review investigating prehospital hypocalcaemia management for trauma patients with haemorrhagic shock.

The evidence suggests that hypocalcaemia manifests in at least half of these patients before blood transfusion and three-quarters after transfusion, and is associated with hypotension, coagulopathy, increased transfusion requirements and mortality (Webster et al, 2016; Kyle et al, 2018; Vasudeva et al, 2020; Conner et al, 2021; Hall et al, 2021). Early calcium correction may benefit these patients and paramedicine can potentially play a key role.

Matthay et al (2020) recommend maintaining normal ionised calcium levels during critical bleeding given the association between hypocalcaemia and coagulopathy. It is important to note that prehospital intravenous administration of calcium was shown to halve the incidence of hypocalcaemia in patients who had received blood products (Kyle et al, 2018). Ambulance services therefore should and regularly do give calcium supplementation to trauma patients receiving multiple units of blood products (grade B recommendation).

However, should consideration also be given to empirical administration of calcium when blood transfusion is foreseeable for trauma patients in haemorrhagic shock? Considerations regarding policy for this might include mechanism of injury, injury patterns and signs such as hypotension associated with traumatic haemorrhage.

Logistical considerations might also be important. Longer duration transport or increased time on scene in situations such as entrapment or where lengthy interventions are required for stabilisation might lend to greater patient benefit from calcium replacement. Conversely, if administering calcium delays the arrival of a trauma patient to definitive care or distracts a small prehospital team from performing other critical interventions, it might be detrimental to the patient.

It is worth noting that it is recommended to give 1 g of calcium gluconate over 2–5 minutes intravenously, as it can cause hypotension and bradycardia if administered too rapidly (Ambulance Victoria, 2020).

Treatment methods for hypocalcaemia varied in the literature as did some of the results. Kyle et al (2018) found prehospital administration of 1 g intravenous calcium chloride normalised calcium levels on ED admission for the majority of patients who had received an average of four units of pRBC or fresh frozen plasma (grade B). Giancarelli et al (2016), however, found that twice that amount of calcium chloride was still not enough to normalise calcium levels in patients receiving mass transfusion in the ED (grade B). MacKay et al (2017), on the other hand, found incidences of overcorrection when greater amounts of calcium were given with their MTP, linking hypercalcaemia to increased mortality (lower-quality evidence).

These results underscore the need for clear protocols to guide paramedic administration of calcium during haemorrhagic shock in trauma. Choice of calcium preparation may also be important and paramedic practice may benefit from a standardised approach. It is important to note that calcium chloride contains three times as much calcium per millilitre as calcium gluconate and carries a greater risk of tissue necrosis than calcium gluconate if extravasation occurs (Ambulance Victoria, 2020). They must therefore not be used interchangeably.

Limitations in the data gathered are evident in this review as all studies except two are retrospective. Controls therefore could not be implemented to determine whether hypocalcaemia and calcium replacement have causative or correlative relationships with trauma mortality.

While it appears that empirical calcium administration may reduce hypocalcaemia, the safest and most effective indications, dosage and preparations need to be determined. A double-blinded randomised control trial could determine whether prehospital calcium administration would benefit patients with severe traumatic haemorrhage.

Conclusion

The findings in this systematic literature review link the ramifications of hypocalcaemia to poor yet potentially modifiable outcomes in trauma.

Ambulance services should consider treatment with calcium when patients receive or are expected to receive a blood transfusion for haemorrhagic shock in trauma. The significance of hypocalcaemia has been established, and further research is needed to differentiate whether hypocalcaemia is a cause or a predictor of trauma mortality and to guide prehospital calcium administration protocols.