One of my main teaching philosophies includes understanding how to teach basics and when to move to more advanced concepts. Solving yesterday’s problem requires some more advanced concepts.

• The normal anion gap depends on the albumin level (albumin is the major component of the normal anion gap.) Therefore, when the albumin is decreased below 4 we must adjust our normal anion gap. The precise formula is 12 – (2.5 for each gram of albumin below 4.) We use 3 times the albumin as a rough estimate (first suggested by one of our residents.) Therefore, in this case we use 9 as our baseline anion gap.
• When you use 9 rather than 12 as the baseline anion gap, you find that this is a pure anion gap metabolic problem.
• Most students, residents and attendings use the measured bicarbonate for calculating the Winter’s equation. This is actually incorrect. The original article (Albert MS, Dell RB, Winters RW. Quantitative displacement of acid-base equilibrium in metabolic acidosis. Ann Intern Med. 1967 Feb;66(2):312-22. – which is available through most medical libraries as a pdf file) analyzed children with various metabolic acidoses. They calculated the equation using only ABG data. Thus, the pCO2 calculation is based on the ABG estimated bicarbonate.
• Our case is a classic example because the ABG followed the electrolyte panel by several hours. I suspect that the acidosis was worsening during this time, explaining the large discrepancy between the measured and estimate bicarbonate.
• Using the estimated bicarbonate, the respiratory compensation is predicted thus we have a pure anion gap acidosis.
• Now we must consider the differential diagnosis of an anion gap acidosis. My first Medscape case included my standard discussion of anion gap acidosis. A Disoriented, Nauseated Car-Wreck Victim and Solution to “A Disoriented, Nauseated Car Wreck Victim”
• Note that the patient has an elevated osm gap – measured osms = 345 and calculated osms = 320. Thus, we have an increased osm gap.
• The patient did not develop these abnormalities until several days into his hospitalization. The classic causes of an increased anion gap and osm gap (ethylene glycol and methanol) are very unlikely, because he would have no access to these liquids in the ICU.
• As Dr. RW surmised, his sedation medication was lorazepam (Ativan). His dose at this time was 70 mg/hr. Any dose over 7 mg/hr puts patients at risk for the combination of increased anion gap acidosis with increased osm gap and subsequent renal toxicity. The best discussion that I have read on this complication is accessible – Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam
• His measured lactic acid level with 4.5. His ketones were negative. The resident recognized the syndrome from discussions in previous morning reports. He stopped the IV lorazepam and the laboratory abnormalities resolved. He remains in DTs.