I’m writing this blog post after listening to the ever excellent Scott Weingart on the EMCrit podcast in discussion with the authors of this paper, to which I highly recommend you listen. Why bother to write about hypocalcaemia on St Emlyn’s when it’s already in the FOAMed forum I hear you ask. Well, I thought it would be worth considering in the UK context (as well as getting the discussion going as widely as possible). I also wanted to combine this with a critique of this paper, published in the same journal and on the same topic a few months later.
Setting the Scene
You are attending a road traffic collision as part of the pre hospital team and your patient is hypotensive and tachycardic with abdominal tenderness, especially in the left upper quadrant and obvious bleeding from an open fracture of the tibia and fibula. You have reduced the fracture, applied a pelvic binder, and given pain relief and tranexamic acid and have decided to commence a blood transfusion. You wonder if there is any benefit (or harm) in giving a bolus of calcium alongside the other therapies?
Our care of patients with uncontrollable bleeding has advanced hugely in recent years, with many areas now having prehospital teams that can use techniques to both try to stop bleeding, as well as the ability to deliver blood products. However, these patients still represent a large proportion of potentially preventable death.
There are several pathways that are intimately involved in the bodies response to major haemorrhage that are dependant upon calcium: cardiac contractility; platelet function and haemostasis. During bleeding calcium present in the blood itself is lost, calcium haemostasis is disrupted and the citate used to preserve the blood we are then giving chelates calcium reducing it even further.
In other words: we really need calcium when we are bleeding, but when we are bleeding we lose calcium.
Paper 1 – Hypocalcaemia in trauma patients: A systematic review
J Trauma Acute Care Surg Volume 90, Number 2
The authors reviewed studies including trauma patients aged 18 or over, who had an ionized calcium measured before blood transfusion and found three studies for inclusion, with a total of just over 1000 patients. All of these were unblinded cohort studies performed in either the USA or Australia.
Outcomes looked at included mortality, transfusion requirements, coagulopathy. Hypocalcaemia was defined as <1.0mmol/L.
Higher mortality rates were observed in patients with hypocalcaemia in all three studies
Transfusion requirements seemed to parallel the severity of hypocalcaemia.
There was a significant association between hypocalcaemia and coagulopathy and clot strength.
There is likely to be a degree of publication bias, in that papers that do not show a relationship between hypocalcaemia and bleeding may be less likely to be published. Although all three studies met the inclusion criteria, the numbers of patients requiring massive transfusion in some was small.
Paper 2 – A review of transfusion- and trauma-induced hypocalcemia: Is it time to change the lethal triad to the lethal diamond?
J Trauma Acute Care Surg Volume 88, Number 3
In this review, initial studies were identified by searching Ovid for English language articles using the key words: hypocalcaemia in trauma; prehospital blood transfusion; and hypocalcaemia and transfusion. Additional studies were then identified from the reference lists of the most relevant studies. Interestingly they found seventeen articles to review, although several were not directly related to the question of hypocalcaemia in major bleeding.
Again, they conclude that hypocalcaemia leads to increased mortality and worse outcomes.
The lethad triad becomes a lethal diamond?
The authors suggest that we should no longer think about the lethal triad, with which we are so familiar, but also add hypocalcaemia into that making a diamond. As discussed above calcium affects, or is affected by, all three of these and each has a co-dependent relationship, such that if we fail to address all aspects we cannot treat bleeding adequately.
What does this mean for us?
All of this seems to suggest to me that we should be considering giving calcium much earlier, in fact as soon as we identify that a blood transfusion secondary to traumatic injury may be required.
It seems that we can assume that all of our trauma patients will be, or will soon become, hypocalcaemic and this can have devastating effects on the ability to stem bleeding.
The Joint Trauma System in the US military has already added calcium to their Damage Control Resuscitation
“in hemorrhagic shock during or immediately after transfusion of the first unit of blood product and with ongoing resuscitation after every 4 units of blood products.”
Calcium itself is a very familiar drug to us and is already carried by prehospital services, usually as a handy minijet of 10% calcium chloride, as part of the treatment of hyperkalaemia, presumed hypocalcaemia or calcium channel blocker toxicity. It is easy to administer (and in minijet form does not even require drawing up).
Possible harms are few: it can cause nasty necrosis if tissue extravasation occurs, so careful checking of the cannula is important; in the patient taking digoxin it may potentiate the drug’s action if given in large doses (but you could argue that they have bigger worries if they are bleeding to death).
I think the time has come for us to consider giving a bolus of calcium chloride alongside the first unit of blood in the patient with traumatic haemorrhage. This intervention is low cost, easy to administer, already present in the drug packs of prehospital teams, and, although not directly studied yet, the potential benefits far outweigh the potential harm. In fact, I would recommend a minijet of 10% calcium choride (which contains 1g of Calcium Chloride dihydrate) is added to the kit bags containing blood products to make this even easier to remember.
I would love to hear your thoughts on this. Will you be adding the administration of calcium early in the patient’s management when looking after those with major haemorrhage?