Question 7.1

A 65-year-old male has been brought into the Emergency Department after being found unconscious at home. He has a heart rate of 87 beats/min, a blood pressure of 96/59 mmHg, and temperature of 31.2°C.
Below is his biochemical profile and arterial blood gas analysis on a Hudson mask delivering 6 L/min oxygen:

Arterial Blood Gas:

Parameter	Patient Value	Normal Adult Range
pH	7.07*	7.35 – 7.45
PaO2	59 mmHg (7.8 kPa)*
PaCO2	25 mmHg (3.3 kPa)*	35 – 45 (4.6 – 6.0)
Bicarbonate	7 mmol/L*	22 – 26
Base Excess	-22 mmol/L*	-2 – +2
Lactate	0.8 mmol/L	< 2.0
Venous Biochemistry:
Parameter	Patient Value	Normal Adult Range
Sodium	133 mmol/L*	135 – 150 mmol/L
Potassium	6.2 mmol/L*	3.4 – 5.0
Chloride	94 mmol/L*	100 – 110
Urea	25.9 mmol/L*	3.0 – 8.0
Creatinine	271 mmol/L*	50 – 120
Total Bilirubin	13 mmol/L	< 20
Albumin	42 G/L	35 – 50
Alanine Aminotransferase	360 U/L*	< 35
Aspartate Aminotransferase	612 U/L*	< 40
g-Glutamyl Transferase	52 U/L*	< 40
Alkaline Phosphatase	123 U/L	35 – 135
Creatine Kinase	335 U/L*	30 – 140
Calcium (corrected)	2.65 mmol/L*	2.15 – 2.60
Magnesium	1.52 mmol/L*	0.7 – 1.10
Phosphate	3.91 mmol/L*	0.8 – 1.50
Glucose	10.5 mmol/L*	3.0 – 5.4
Ketones	6.6 mmol/L*	< 0.5

a) Describe the acid-base abnormalities seen in the arterial blood gas analysis.
b) List three possible causes of the ketosis.
c) What is the most likely cause? Give your reasoning.

[Click here to toggle visibility of the answers]

College Answer

a) High anion gap metabolic acidosis (ketones and other unmeasured anion). Respiratory acidosis / inadequate respiratory compensation.

b) Alcoholic ketosis. Diabetic (euglycaemic) ketoacidosis. Starvation ketosis.

c) Alcoholic ketosis. Combination of severe AG acidosis with high level of ketones (too high for starvation ketosis) and abnormal liver enzymes (less likely with DKA).

Discussion

Let us dissect these results systematically.

The A-a gradient is high; 194 or 337.6mmHg depending on what FiO₂ you think the Hudson mask is delivering.
PAO₂ = (0.4 or 0.6 × 713) - (25 × 1.25) = 253 or 396.6
Thus, A-a = ( 253 or 396.6 - 59) = 194 or 337.6mmHg.
There is acidaemia
The PaCO₂ is compensatory
The SBE is -22, suggesting a severe metabolic acidosis
The respiratory compensation is inadequate - the expected PaCO₂(7 × 1.5) + 8 = 18.5mmHg, and thus there is also a respiratory acidosis
The anion gap is raised:
(133) - (94 + 7) = 32, or 38.2 when calculated with potassium
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (32 - 12) / (24 - 7) = 1.17
This suggests that there is a pure high anion gap metabolic acidosis here.

The lactate cannot account for this, and the renal failure - though severe - is insufficiently severe to serve as an explanation for such a raised anion gap. Ketones remain as the only explanation.

The college asks for three differentials for ketosis, which is helpful (because there only three major types):

Alcoholic ketoacidosis
Starvation ketoacidosis
Diabetic ketoacidosis

Ketoacidosis mechanisms and management strategies for DKA are discussed elsewhere.

This patient is probably a veteran drinker. As the college points out, starvation ketoacidosis does not tend to have such a high ketone level, and DKA patients are unlikely to have such abnormal LFTs.

References

UpToDate has a nice summary of this topic for the paying customer.

Oh's Intensive Care manual: Chapter 58 (pp. 629) Diabetic emergencies by Richard Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Alberti, K. G. M. M., et al. "Role of glucagon and other hormones in development of diabetic ketoacidosis." The Lancet 305.7920 (1975): 1307-1311.

Kitabchi, Abbas E., et al. "Management of hyperglycemic crises in patients with diabetes." Diabetes care 24.1 (2001): 131-153.

Foster, Jennifer Ruth, Gavin Morrison, and Douglas D. Fraser. "Diabetic ketoacidosis-associated stroke in children and youth." Stroke research and treatment 2011 (2011).

Edge, J. A., et al. "The risk and outcome of cerebral oedema developing during diabetic ketoacidosis." Archives of disease in childhood 85.1 (2001): 16-22.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "Acute renal failure in patients with type 1 diabetes mellitus." Postgraduate medical journal 70.821 (1994): 192-194.

Bonfanti, R., et al. "Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child." Acta diabetologica 31.3 (1994): 173-174.

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

Stowe, Michele L. "Plasma-Lyte vs. Normal Saline: Preventing Hyperchloremic Acidosis in Fluid Resuscitation for Diabetic Ketoacidosis." (2012).

Jivan, Daksha. "A comparison of the use of normal saline versus Ringers lactate in the fluid resuscitation of diabetic ketoacidosis." (2013).

Basnet, Sangita, et al. "Effect of Normal Saline and Half Normal Saline on Serum Electrolytes During Recovery Phase of Diabetic Ketoacidosis." Journal of intensive care medicine 29.1 (2014): 38-42.

Hillman, K. "Fluid resuscitation in diabetic emergencies—a reappraisal."Intensive care medicine 13.1 (1987): 4-8.

Wagner, Arnd, et al. "Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application." Diabetes care 22.5 (1999): 674-677.

Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.

[Submit a comment or correction]