Before I begin, I would like to thank Dr. Frank Luo and Dr. Amit Gohil for coming to today’s report and sharing with us their wisdom from years of clinical experience. I also would like to thank Dr. Jacobson for his continuous attendance and invaluable guidance at our reports. As Osler said, “the work of an institution in which there is no teaching is rarely first class” and we owe a debt of gratitude to all of our teachers for their service to us.

To proceed…esteemed colleagues: every once a while you get a case that pushes every aspect of your medical knowledge, diagnostic skills, and clinical reasoning — this was that case. Megan and Trevor presented a case of acute encephalopathy and hypothermia in a patient who ultimately was found to have the following:

1. Lactic Acidosis
2. Ketoacidosis
3. Renal Failure
4. Respiratory Acidosis
5. Elevated Osmolar Gap

…among many many other derangements.

We first went through a focused differential of acute encephalopathy and hypothermia

1. Sepsis
2. Cardiogenic Shock
3. Ingestions
4. Adrenal Crisis
5. Myxedemic Crisis
6. Severe Hypoglycemia
7. Neurologic Crises – brain mass, stroke
8. Severe Trauma

We then learned that the patient was on Metformin and an SGLT-2 inhibitor and postulated the following sequence of events:

• Empagliflozin is an SGLT-2 inhibitor known to cause euglycemic DKA, which may have been the etiology of his ketoacidosis. (on an unrelated note — remember that SGLT-2 inhibitors are known to increase the risk of genitourinary infections, particularly fungal infections)
• The time course of renal failure is difficult to be certain of – but perhaps it was volume depletion from his SGLT-2 inhibitor (via an osmotic diuresis) that led to a pre-renal AKI
• Metformin is known to cause a Type B lactic acidosis, which may have occurred in the setting of his AKI from above
• Additionally, his HCO3 may have been so low, that he developed shock as a result of severe acidemia and subsequent type A lactic acidosis as well
• His acidemia was so profound, that he could not fully compensate, leading to a respiratory acidosis
• The combination of lactic acidosis, ketoacidosis and renal failure all could have contributed to his osmolar gap

Which leads us to a discussion of the osmolal gap. Checking the serum osms is useful in cases of ingestions, particularly when we suspect it could be a glycol or methanol. We calculate the osmolality based on readily available formulas, then compare it to the measured osmolality. If the measured is greater than the calculated by more than 10, you expect there are added extra osmoles in the blood. UpToDate has a fantastic way of approaching this:

• With AGMA
  • Major causes of of a large osmolal gap
    • ethylene glycol
    • propylene glycol
    • methanol 
  • Causes of a smaller osmolal gap
    • ketoacidosis
    • lactic acidosis
    • severe CKD without regular dialysis
    • paraldehyde ingestion or injection
• Without AGMA
  • ethanol
  • isopropanol
  • diethyl ether
  • infusion of mannitol, sorbitol or glycine
  • pseudohyponatremia (severe hyperlipidemia or hyperproteinemia)

Courtesy of UpToDate