A 44-year-old female, who is a type II diabetic, has been fasting for elective morning surgery. She is currently on oral anti-diabetic drugs.

On admission to the day surgery unit, she describes feeling nauseous with diffuse abdominal pain. The following results are obtained:

Parameter

Patient Value

Adult Normal Range

FiO2

0.21

pH

7.28*

7.35 – 7.45

pO2

102 mmHg (13.6 kPa)

pCO2

40.0 mmHg (5.3 kPa)

35.0 – 45.0 (4.6 – 6.0)

SpO2

97%

Bicarbonate

18.0 mmol/L*

22.0 – 26.0

Base Excess

-8.0 mmol/L*

-2.0 – +2.0

Sodium

141 mmol/L

135 – 145

Potassium

3.6 mmol/L

3.5 – 5.0

Chloride

103 mmol/L

95 – 105

Glucose

6.0 mmol/L

3.5 – 6.0

Ketones

5 mg/L*

< 1

  1. Comment on the acid base status. (10% marks)
  1. List three potential causes of the elevated ketone level in this patient. (20% marks

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College answer

a)    Comment on the acid base status.    (10% Mark)
High AG metabolic acidosis
Secondary respiratory acidosis

b)    List three potential causes of the elevated ketone level in this patient? (20% mark)
1.    SGLT2 Inhibitor
2.    Starvation
3.    Alcohol
 

(Note to examiners – diabetic ketoacidosis not accepted unless described as adverse effect of the SGLT2 inhibitor.)

Examiners Comments:

Some candidates paid insufficient attention to the clinical information in the stem, leading to generic responses and inappropriate prioritisation of information. Some failed to list potential causes of hypotension consistent with the ABG and lost potentially easy marks as a result of not slowing down and reading the question.
 

Discussion

"Comment on the acid base status" they asked. The college's "GLOSSARY OF TERMS" from the beginning of the paper does not contain a specific description of the term "comment". The common language definition, "to express an opinion about something", may not be appropriate, as one's opinion of the acid base status may be "it's fucked".  

Anyway, let's assume they wanted us to intrpret the ABG result:

  • The A-a gradient is close to zero. 
  • There is a mild acidaemia
  • There is a mild metabolic acidosis (SBE = -8)
  • The CO2 is higher than it should be: the expected value is 32 mmHg (using the SBE method) or 35 mmH (using Winter's formula). Thus, there is a coexisting (mild) respiratory acidosis.
  • The anion gap is (141 + 3.6) - (103  + 18) = 23.6, or 20 when calculated sans potassium.
  • The delta ratio is (23.6-12)/(24-18) = 1.93, or 1.3 if older values are used (where the standard anion gap value is 12, and the gap is calculated without potassium). Regardless of which formula you subscribe to, the ratio suggests that this is a pure HAGMA. 

List three potential causes of the elevated ketone level in this patient:

The combiation of ketoacidosis, normal glucose and the history of being a Type 2 diabetic on "oral anti-diabetic drugs" is stronly suggestive of SGLT2 inhibitor effects. This sort of ketoacidosis is classically euglycaemic (Rosenstock et al, 2015). Other causes of ketoacidosis can be suggested to explain these findings on the basis of an excellent article by Davids et al 92004), which, though highly informative, is unfortunately written using an imaginary ward round  as a narrative device.

Anyway, the causes:

  • Diabetic ketoacidosis following the commencement of insulin therapy
  • Alcoholic ketoacidosis 
  • Starvation ketoacidosis due to fasting for eletive surgery
  • Inhibition of of insulin release  (α-adrenergic agents and diazoxide) 
  • Acetate excess (eg. unregulated nonglucose carbohydrate excess)
  • Inhibition of acetyl-CoA carboxylase (eg. by firsocostat)

References

References

Rosenstock, Julio, and Ele Ferrannini. "Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors." Diabetes care 38.9 (2015): 1638-1642.

Davids, M. R., et al. "An unusual cause for ketoacidosis.Qjm97.6 (2004): 365-376.