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+4) - (114+10) = 23
    The delta ratio suggests that there is mixed high anion gap and normal anion gap metabolic acidosis here.
    (23 - 12) / (24 - 10) = 0.78
  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

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