Question 11.1

A 50-year-old female is admitted to ICU following an elective anterior communicating artery aneurysm clipping procedure. The patient was extubated post-procedure. Her background medical conditions include hypertension, Type 2 diabetes mellitus (T2DM) and dyslipidaemia. Her medications include perindopril, metformin, pioglitazone, empagliflozin, and atorvastatin. The following arterial blood gas analysis was taken on day 2 post-operative.

Parameter Patient Value Adult Normal Range
FiO2 0.21  
pH 6.81* 7.35 – 7.45
pO2 138 mmHg (18.4 kPa)  
pCO2 11.0 mmHg (1.5 kPa)*      35.0 – 45.0 (4.6 – 6.0)
SpO2 98%  
Bicarbonate 2.0 mmol/L* 22.0 – 26.0
Base Excess       -31.3 mmol/L* -2.0 – +2.0
Lactate 3.2 mmol/L* 0.5 – 1.6
Sodium 142 mmol/L 135 – 145
Potassium 4.3 mmol/L 3.5 – 5.0
Chloride 116 mmol/L* 95 – 105
Glucose 10.5 mmol/L* 3.5 – 6.0
Osmolal gap 8 < 10

a)    List the abnormalities on the blood gas analysis.    (20% marks)

b)    Explain the most likely diagnosis and outline how you would investigate this further.
(20% marks)
 

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College answer

Not available.

Discussion

Empagliflozin? They are basically throwing this at you.

No, wait, wait. Let us dissect these results systematically.

  1. It does not take a spark of genius to recognise that there is nothing wrong with the patient's oxygenation, but let's look at it anyway for the exercise. The A-a gradient is not raised:
    PAO2 = (0.21 × 713) - (11 × 1.25) = 136
    Thus, A-a = (138 - 136 = 2mmHg.
  2. There is severe acidaemia
  3. The PaCO2 is appropriately depressed
  4. The SBE is -31.3, suggesting a profound metabolic acidosis.
  5. The respiratory compensation is probably as good as one could wish for. The expected CO2 is 8.7 (40-31.3) by one method, or (1.5 × 2 ) + 8 = 11 by another method.
  6. The anion gap is elevated:
    (142) - (116 + 2) = 24;
    and this is not explained by the paltry lactate of 3.2 
  7. The osmolal gap is already given to us, and it is normal, which narrows the list of MUDPILES down to the causes of HAGMA which are not associated with excess osmoles.

So, this high anion gap metabolic acidosis in a euglycaemic diabetic. What could this possibly be? 

Euglycaemic ketoacidosis comes to mind. It is the natural conclusion in this situation, where the stem clearly gives a history of an SGLT2 inhibitor. It is possible that the college would have wanted more detail, as they asked to "explain" rather than "list" or "give" the most likely diagnosis. In that case, one could go into the mechanism, where:

  • Glycosuria by the SGLT2 inhibitor leads to lower blood glucose
  • Lower blood glucose leads to decreased insulin secretion
  • Lower insulin levels lead to a lower insulin/glucagon ratio
  • The dehydration also produces the release of cortisol and catecholamines
  • Glucagon, cortisol and catecholamines drive lipolysis and ketogenesis

Or at least that's the shortest version of a mechanism described by Bui & Nawathe (2018). Now, to "outline how you would investigate this further". The diagnosis of EDKA rests on the finding of a high anion gap acidosis with raised ketones, where the BSL is below 200 mg/dL, which is 11.1 mmol/L in local terms (Barski et al, 2019). So... a blood ketone level is "how you would investigate this further". However, the college have attributed 20% of the marks to this question, which suggests they might have expected something more than just a one-liner. If one felt compelled to write more, one could hold forth as follows:

  • Primarily a diagnosis of exclusion
  • Other causes of HAGMA would have to be excluded
  • Thus:
    • Blood or urine ketones (to confirm the ketosis)
    • Drug levels (to exclude toxicological cause of  acidosis, eg. salicylate toxicity)
    • Urinary oxalate level (late presentation of ethylene glycol ingestion)
    • Urea and creatinine (renal failure/uraemia)
    • 5-oxoproline level (pyroglutamic acidosis)


 

References

Kalra, Sanjay, and Yashdeep Gupta. "The insulin: glucagon ratio and the choice of glucose-lowering drugs." Diabetes Therapy 7.1 (2016): 1-9.

Wahid, Maryam, Abdul Khaliq Naveed, and Imad Hussain. "Insulin and glucagon ratio in the patho-physiology of diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic diabetes." Journal of the College of Physicians and Surgeons--pakistan: JCPSP 16.1 (2006): 11-14.

Bui, Patrick, and Amar C. Nawathe. "Euglycemic Diabetic Ketoacidosis: Challenge is in the Diagnosis." Proceedings of UCLA Healthcare 22 (2018).

Barski, Leonid, et al. "Euglycemic diabetic ketoacidosis." European journal of internal medicine 63 (2019): 9-14.