Tasty Morsels of Critical Care 011 | Tumour Lysis Syndrome

10 Dec

Welcome back to the tasty morsels of critical care podcast.

Thanks to the wonders of preemptive rasburicase (which i have a tendency to associate with Rasputin at this point) I don’t think this as common as it used to be. But that is wild speculation on my part as someone who’s only ever looked after cases in the single digits.

The basic premise here goes something like this.

Chemotherapy does exactly what it’s meant to do and kills tumour cells. These cells break down releasing amongst other things the purines that make up various components of the cells. Our bodies have a well established pathway for dealing with an influx of purines and metabolises them to uric acid. Uric acid is weakly soluble and excreted at a certain rate by the kidneys. The problem comes in that the metabolic processes for converting purines to uric acid is much more efficient than the process to remove uric acid from the body. Phenomena like this are widespread in the body and put to good use with the long history of happy hours and shots as a means to bring about inebriation before the pesky liver can catch up.

Interestingly primates are unique in not being able to convert uric acid to the harmless compound allantoin. It’s hard to see what evolutionary advantage our ancient ancestors gained in dropping the enzyme needed but then I can’t imagine beer and steaks were big on the diet of the average primate at that stage.

So in TLS we have production of uric acid far in excess of our ability to excrete. The uric acid then tends to precipitate out of solution into crystals at this stage that have a tendency to crystallise out in the a) joints and b) renal tubules.

We now have a combination of failing kidneys, oliguria, hyperkalaemia from the worsening acidosis and the K release from dying cells.

Enough of the pathophys, what context do we see this in

  • Large tumour mass or bone marrow involvement
    • burkitt’s
    • ALL/AML
  • Small cell lung cancer also appears commonly on lists.

There is something called the Cairo definition that can be used to diagnose it. I’ll spare the details but nice to know it exists.

Obviously it’s common in the days post chemo but it can actually happen spontaneously.

I mentioned rasburicase earlier because this has changed things significantly.  When we give rasburicase we’re providing that enzyme that all the other mammals have that we dropped. This metabolises uric acid to the fairly harmless allantoin, eliminating our dependance on the glacial process of excretion. This drug can be given prophylactically in the right context so we never see the TLS develop.

The other drug you may remember about uric acid from med school days is allopurinol. This blocks production of uric acid (surely a good thing I hear you cry) but merely diverts it into the production of xanthine, a somewhat problematic compound that we’re also not particularly well adapted to get rid of.

Rasburicase is  a recombinant product that seems fungal in origin (so you can make antibodies against it) and also is a reported cause of MetHb. It’s pricy but so is €2000/day in ICU on CRRT.

Of note CRRT will fix all the electrolyte and metabolic issues that are seen in TLS and is a good option for treatment.

References and rationalisations:

Deranged Physiology

IBCC

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