Case of the Month 12 – Answer

The differential in this patient could be approached from many different perspectives. The history and exam are non-specific, so we will have to start looking at lab results and think more broadly. After reading the comments in the article, there were some good thoughts thrown out about DKA and bowel obstruction. We can expand it more generally to infections, toxins, and endocrinopathy. Let’s look at the labs a little bit more.

Looking at the VBG and CMP, we notice an anion gap (21) metabolic acidosis. Thinking back to MUDPILES and our patient, we can quickly rule out the toxins like methanol, propylene glycol, ethanol, and also salicylates. There is slight bump in BUN:creatinine ratio (25) but with these numbers, we can rule out uremia. We’re left with DKA and lactic acidosis. Ndana had a nice thought with DKA but the ketones were negative and the sugar was only 230, making DKA less likely. We come to a conclusion that his acid-base disturbance is likely due to a lactic acidosis, possibly from dehydration. This can be supported by the history of vomiting, BUN:creatinine ratio of ~25, sodium of 119, and chloride of 80.  Keep reading as the differential will unfold before our eyes.

Is there more to the story than dehydration? Is it compensated? Are we looking at a single, double, or triple acid-base disorder? ABGs can be incredibly interesting and rewarding. Let’s delve into this further.

Since this patient has a metabolic acidosis, the next step is to calculate the respiratory compensation using Winter’s formula:

Expected PCO₂ = [(1.5 x HCO₃^–) + 8] +/- 2.

We do the math and calculate the expected PCO₂ to be 35 +/- 2. Our PCO₂ of 44.2 tells you the patient has higher CO₂ than should be expected and therefore may be exhibiting inadequate respiratory compensation. This would be an additional respiratory acidosis.

Does this person have a triple acid-base disorder? Is there an additional metabolic alkalosis? To assess for this, we need to calculate the delta ratio, also known as the delta-delta gap.

Delta ratio = (change in anion gap from normal)/(change in HCO₃^– level from normal).

—    Or    —

Delta ratio = (actual anion gap – 12)/(24 – actual HCO₃^–)

To understand this ratio, we need to discuss how buffering works in our body. Normally, bicarbonate is our buffer when an acid enters our body. The acid, lets call it “HA”, splits to H⁺ and A^–. The H⁺ and HCO₃^– make CO₂ and H₂O. This A^– therefore replaces the bicarbonate. This change in bicarbonate shouldn’t affect the delta ratio, as the drop in the bicarbonate is counteracted by an increase in anion gap due to A^–. As the anion gap increases by 1, the bicarbonate should decrease by 1. The delta ratio will remain the same because the change (delta) in anion gap and change (delta) in bicarbonate levels are both 1. When there is an inappropriate change in bicarbonate relative to the anion gap – lets call this “Greenstein’s rule of inappropriate buffering” – another metabolic process exists. There are two common situations where this rule would apply. For starters, if the reduction in bicarbonate is MORE than the change in anion gap (ie; from loss in the GI tract), it indicates an additional normal anion gap metabolic acidosis. On the other hand, if the bicarbonate reduction is LESS than the change in anion gap (ie; production of bicarbonate through vomiting), there is an additional metabolic alkalosis.

In our case, the delta ratio is (21-12)/24-18) = 1.5. This ratio indicates that there is a pure elevated anion gap metabolic acidosis.

Here is how to interpret delta ratio:

<0.4: Hyperchloremic normal anion gap acidosis

< 1: Elevated anion gap with normal anion gap acidosis

1-2: Pure elevated anion gap acidosis

>2: Elevated anion gap acidosis with a metabolic alkalosis. Can also occur in pre-existing compensated respiratory acidosis.

Putting it all together, this patient has an elevated anion gap acidosis, likely secondary to the lactic acidosis. In addition, this patient has inadequate respiratory compensation. We must therefore look out for things like hypoventilation, altered mental status, and lung disease. Our patient clearly did not have any of these. An alternative explanation for the elevated PCO₂ could simply be a result of the bicarbonate buffer. As more CO₂ is created, we might simply be seeing gas exchange in front of our eyes that is reflected in the VBG.

A lactate of 3.3 mmol/L is always concerning. In our case, this is likely due to dehydration, and the patient will require serial measurements in order to ensure a proper response to intravenous hydration. Another helpful value in the ABG is the base excess. This can be helpful in a single, undifferentiated ABG, but even more useful in a situation where you are repeating an ABG. The base excess is the amount of acid that must be added to blood to return the pH to 7.4. In some institutions, this is measured. However at KCHC, this is calculated from the Henderson-Hasselbalch Equation. Of note, the base excess will only tell you about a metabolic process and not a respiratory process. The normal range is from -2 to +2. In the case of metabolic acidosis, the blood is already acidemic, and therefore acid needs to be removed to return to a normal pH.  As such, your base excess value will be negative reflecting the removal of acid. In a metabolic alkalosis, base needs to be added, so in this situation, base excess will be positive. In our case, the base excess was -5.8 indicating a metabolic acidosis. For starters, this will help you confirm the metabolic process despite what may be a falsely reassuring, normal pH.

Below is an example to illustrate the point.

ABG 1: pH 7.432, pCO2: 25.4, HCO3: 19.4 BE:-6.9

ABG 2: pH: 7.419, pCO2: 25.1, HCO3: 18.7, BE: -7.7

ABG 3 from floors: pH: 7.347, PCO2: 29.9, HCO3: 17.8, BE: -8.6

ABG 4 from floors: pH 7.211, PCO2: 35.1, HCO3:  14.3 BE: -12.8

On ABG 1, the patient has a primary respiratory alkalosis with a base excess of -6.9. The negative base excess indicates there is an additional metabolic acidosis. Interventions are made and the repeat ABG is drawn. You will notice that the pH normalizes in ABG 2 and ABG 3, while the base excess did not. In fact, the base excess became more negative, indicating worsening acidosis. The concern is that by looking at just the pH and bicarbonate, one might be tempted to call this a compensatory process. However, in this setting of a worsening base excess and despite there being a normal pH, an active metabolic acidosis exists. This acidosis could be the true driving force pulling the pH to normal. The intervention you just made in all actuality might not have helped. Rather, the metabolic component is now the stronger of the acid-base processes, and if unnoticed will eventually manifest as a primary metabolic acidosis (ABG 4). While base excess is calculated and will always move in the same direction as the HCO₃^– (based on the Henderson-Hasselbalch Equation), some might find the base excess beneficial in that it is also easy to trend. This ability to trend can be helpful in exposing an acid-base disturbance that has not yet manifested itself clinically.

Now back to the original question. Does the base excess help you in the setting of an elevated lactate? Yes! While it can’t be correlated exactly with lactate level, if it doesn’t become more positive, in sync with a decreasing lactate level, be suspicious for an alternative, underlying metabolic process that may be more occult.