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July 1, 2011

Massive Attack (of Calcium)

Some sort of cell.
Do you remember that table from the back of First Aid for Step One? The one with about 10 pages of word associations? When I say "Auer rods" you say "AML"; when I say "negative birefringence" you say "gout." What an unbelievably stupid way to learn, and shame on the NBME for encouraging this style.

Yet much of clinical practice is based on just such things, little free associations. These associations are often passed on as teaching points on shift and I understand why - they are digestible and quick. This kind of stuff, however, reinforces the very worst kind of medical knowledge acquisition - isolated facts devoid of clinical relevance and sometimes incorrect.

Although the statue is made of stone, his heart is made of chocolate.
Hannibal, Sebastien Slodtz (marble) 1655: Louvre, Paris
When I say "digoxin toxicity," you say "stone heart." It's a classic free association; but is it true?

Many of us have probably heard some rumblings that this might not be all that big of a deal. I just came off Toxicology at Toxikon in Chicago. One of the other residents on with me, David Schrift from the UIC EM/IM combined program, gave a great 30 minute talk on this topic. David went through all the literature and I was not surprised to find that it was incredibly weak. Some of the research actually required him to go to the library and get photocopies!
Disclaimer: this is not original MDA work; David produced all of this stuff and graciously agreed to let me reproduce it.
The initial incident that started this nonsense about Calcium + Dig being dangerous was a paper from The JAMA in 1936. There were 2 case reports and then a weird little experiment.
Case #1: 32F s/p cholecystectomy for acute cholecystitis hypotensive and tachy on POD #2, given digalen for PVCs, medicine consult recommended IV calcium for “toxic irritation of the accelerator mechanism through sympathetic involvement." She got some calcium, seized and died. 
Case #2: 55M with hypercalcemia (MM? hyperparathyroid?) presented with bilateral femur fractures. To OR for hemithyroidectomy where he got digalen, developed post-op tetany, got a 1g CaCl bolus, and died.
As David pointed out, in neither case were the electrolytes, acid base status, dig level, or infusion rate of calcium noted. In both cases there were clear other reasons for death. Plus, what the heck is "toxic irritation of the accelerator mechanism" and why would it be treated with IV calcium? This was followed up be a small experiment where dogs were given dig+calcium and some died. Again, many details were omitted. So a body of literature developed over the following decades, but it wasn't good literature.

David did a really cool thing and took all the studies (many of which were animal) and converted the Calcium infusion rates to the equivalent of grams of calcium gluconate given to a 70 kg adult. The results will surprise you. I have modified his table slightly:

Giving Calcium to dig toxic patients is almost certainly ok. The body of literature that says it isn't is not relevant to our practice. In the Archives of Internal Medicine paper, the dogs were getting up to 496g CaGlu equivalents at 15-147 g/min. Even Seth doesn't do that.*

In the American Heart Journal paper, the dogs were loaded with 2.4-5 g/min of calcium and then given digitalis until the went into VTach. Again, we don't do that.

The 2004 Journal of Toxicology study took 12 pigs and loaded then with digoxin; all were noted to have hyperkalemic ECG changes. They got 2g CaClu or saline. There was no change in time of death. This was a small study to be sure, but seems more relevant than bombing some poor dog with IV calcium.

That said, calcium will not be life saving in true dig toxicity. As the tox fellow pointed out during David's talk, if a patient is truly dig toxic, they need DigiBind. This information is only helpful for the ill patient who presents with a wide complex ECG, renal failure, and hyperkalemia** who is on dig but for whom the dig level is not yet known.

Give the calcium, but don't do it at 147 g/min.


from seth:
Debunking pseudoaxioms is fun.
*I routinely give my patients 496g at 147g/min and anyone who doesn't is committing malpractice**,***
**This is not medical advice.
***This is not legal advice, nor is it my practice.

For anyone who didn't get the Massive Attack reference.

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