Volume resuscitation is clearly paramount when treating rhabdo, but whether bicarbonate or mannitol is beneficial is controversial. The figure below from a recent NEJM review gives a nice overview of the state of the literature.
Hypocalcemia – Bicarbonate containing solutions have some attractive features based on animal data suggesting that they reduce:
1) Tubular precipitation of Tamm–Horsfall protein–myoglobin complexes
2) Generation of injurious oxidation products
3) Afferent arteriole vasoconstriction induced by metmyoglobin.
Unfortunately, in addition to these theoretical benefits, alkalinization of the blood pH can lead to increased calcium complexing with albumin thus decreasing physiologically active ionized calcium. This complication can be particularly problematic (eg tetany) early in rhabdo when serum calcium is dropping due to movement into damaged muscle and precipitation from serum as calcium phosphate.
Non-Gap Acidosis – Normal saline is used as an intravascular volume expander to replace fluid as it moves into damaged muscle.
Large volumes of NS are sometimes required in rhabdo and can lead to “dilutional acidosis.” There are several proposed mechanisms behind this that are nicely discussed in one of Nate’s prior posts. If clinically significant, lowering of the serum pH and subsequently urine pH could potentiate all of the mechanisms bicarbonate therapy experimentally mitigates.
Osmotic Nephrosis – The use of diuretics is again, controversial (must mean something when that word keeps popping up!) but in volume replete patients mannitol has several sited benefits.
Its main effect is as an osmotic diuretic leading to increased urinary flow and the flushing of nephrotoxic agents through the tubules. It also acts as a free-radical scavenger and an intravascular osmotic agent reclaiming fluid from injured muscles. Unfortunately, when large quantities of mannitol (greater than 200g/day or accumulated doses of greater than 800g) are used they can lead to renal vasoconstriction and direct tubular toxicity. This brand of AKI is termed osmotic nephrosis and histologically appears as tubular cytoplasmic vacuolization.
Pseudohyponatremia – Mannitol has the additional potential complication of hypertonic hyponatremia.
As an effective serum osmole, mannitol raises serum osmolality and pulls free water into the intravascular space diluting the serum sodium concentration. The effect on serum osms can lead to significant serum hypertonicity resulting in seizures as the brain shrinks.
Graham Abra, MD