A 76 y/o female patient with a history of type II diabetes mellitus, hypertension, hyperlipidemia, and mild CHF is brought to the ER by her husband with complaints of significant lethargy and confusion. Her vital signs are Temp - 101, HR 94, BP 90/60, Resp - 32. Her labs are : Na - 132, K - 4.5, CL - 99, HCO3 - 5, BUN 97, Cr - 9.5. Her serum pH was 6.9 from an arterial blood gas. Her meds on admission were lisinopril, furosemide, simvastatin, metformin, ibuprofen, and conj estrogens.

What is her likely problem? What is the likely cause? How would you treat this patient?

  ** This was an actual case.**

This patient has a severe metabolic acidosis. In this case, it was due to metformin (lactic acidosis). Let's discuss a few things about the treatment of anion-gap metabolic acidosis.

1) Stop the metformin or other offending agent.
2) An anion gap metabolic acidosis can be caused by several things. There are bunches of pneumonics that can be used to jog your memories. I use "M U D P I E - A C E" but "SLUMPED" or "MUDPILES" or "DR MAPLES" work just as well. MUDPIE-ACE stands for:

M - methanol
U - uremia
D - DKA
P - Paraldehyde (not available anymore)
I - infection, ischemia, or isoniazid OD
E - ethylene glycol (antifreeze)
A - aspirin or salicylates
C - cyanide (Yes, I actually saw a case from CN poisoning as a resident)
E - ethanol

3) Fluids - usually start with 0.9% sodium chloride. These patients are often significantly fluid depleted (anywhere from 3-10 liters or more). Fluid will also help the kidney compensate/fix the acidosis. Esp in DKA
patients, should switch to a dextrose containing IV solution once the serum glucose was lowered to ~ 250 mg/dL.

4) Bicarbonate - Bicarb administration to acidotic patients is controversial but I think most people would give bicarbonate in this patient. Goal is to nudge and NOT to push the pH in the right direction. Again, there's several ways top accomplish this. Either calculate the entire HCO3 deficit and replace half of it OR calculate the amount of bicarb to get the serum HCO3 to ~ 12 OR calculate the deficit using a smaller than usual estimate for total body water. Any will work. The goal is nudge, NOT push! Calculate as follows:

HCO3 deficit = 0.6 L/Kg * Wt (kg) * (target HCO3 - actual HCO3) If using this formula, you'll know the amount for total repletion. ONLY GIVE ½ to 2/3 of this amount. (Nudge, don't push!!)

5) Metformin - this drug is probably the first line agent for treatment of type II diabetes, esp after the UHPDS trial publication. Metformin is CONTRAINDICATED in males with a serum Cr > 1.5 mg/Dl and females with a
serum Cr > 1.4 mg/dL and in patients with CHF requiring drug therapy. It's predecessor (phenformin or DBI-TD ®) was pulled from the market in the late 70'secause of a high incidence of lactic acidosis. Metformin may still cause lactic acidosis but the incidence is much less compared to phenformin.

A comment on this patient's pharmacotherapy: She was on multiple medications that can harm the kidney - an ACE inhibitor, a loop diuretic, and a NSAID. Her age (> 65 y/o) puts her at greater risk also. All summed together was too much for this patient. When the metformin was added, her kidney and other systems couldn't remove the lactate, allowing it to accumulate, eventually causing the acidosis. (FYI - COX2 NSAIDs are NOT renal sparing or renal protective!)