A 64-year-old man with a background of heavy alcohol consumption has been admitted to your ICU for several days with a sensitive staphylococcus aureus (MSSA) epidural abscess which has been surgically drained.

The following results were obtained.

Parameter

Value

Normal Range

Sodium

143 mmol/L

134 – 146

Potassium

4.0 mmol/L

3.4 – 5.0

Chloride

114 mmol/L*

100 – 110

Urea

10.1 mmol/L*

3.0 – 8.0

Creatinine

104 mmol/L

50 – 120

Glucose

6.9 mmol/L

3.0 – 7.0

Urinary ketones

Negative

Measured osmolality

300 mOsm/Kg

280 – 300

On 30% oxygen arterial blood gas analysis as follows:

Parameter

Value

Normal Range

pH

7.22*

7.35

– 7.45

PO2

84 mmHg (11kPa)

PCO2

25 mmHg (3.2 kPa)*

35

–

45 (4.6 – 6.0)

Bicarbonate

10 mmol/L*

22

–

27

Lactate

1.8 mmol/L*

<2.0

What is the likely cause of the acid base disturbance?

How would you investigate and manage it?

 

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College Answer

High anion gap metabolic acidosis secondary to pyroglutamic acidaemia.

Can be detected by requesting an organic acid screen, or by plasma or urine pyroglutamate levels.

Management – cessation of precipitating drugs likely paracetamol and flucloxacillin in this case.

N-Acetyl cysteine infusion has been advocated.


Discussion

Let us dissect these results systematically.

  1. The A-a gradient is high:
    PAO2 = (0.3 × 713) - (25 × 1.25) = 182.55
    Thus, A-a = ( 182.55 - 84) = 98.55mmHg.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is not offered but the bicarbonate is 10, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate - the expected PaCO2(10 × 1.5) + 8 = 23mmHg (withn +/- 2mmHg of the reported value)
  6. The anion gap is raised:
     (143) - (114 + 10) = 19, or 23 when calculated with potassium
    The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (19 - 12) / (24 - 10) = 0.5
    This suggests that there is mixed high anion gap and normal anion gap metabolic acidosis here.
  7. Urinary pH and electrolytes are not offered (but would be interesting)

So, what is making this drunk so acidotic? The lactate is not raised; so the differentials for the high anion gap here would include the following:

  • Methanol and the toxic alcohols in general
  • Ethylene glycol
  • Diabetic, alcoholic and starvation ketoacidosis
  • Pyroglutamic acidosis
  • Salicylate overdose
  • Iron overdose

Of course, the MSSA story suggests the college want us to consider pyroglutamic acidosis as a cause.
Investigations for these differentials would include the following:

  • 5-oxoproline level in urine
  • Urinary oxalate
  • Methanol levels
  • Ketone levels
  • Iron studies
  • Salicylate levels

One would want to stop feeding this man the paracetamol and flucloxacillin.

References

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

Duewall, Jennifer L., et al. "5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use." Proceedings (Baylor University. Medical Center) 23.1 (2010): 19.

Akhilesh Kumar and Anand K. Bachhawat Pyroglutamic acid: throwing light on a lightly studied metabolite ,SPECIAL SECTION: CHEMISTRY AND BIOLOGY. CURRENT SCIENCE, VOL. 102, NO. 2, 25 JANUARY 2012. 288