Ketoacidosis

By Alex Yartsev - 11/07/2015

The mechanisms and management strategies for diabetic ketoacidosis are discussed elsewhere, as one of the scenarios in critical care endocrinology.

Rather than get bogged down in thick endocrinology (thereby duplicating content from the Endocrinology section) I offer this brief summary, aimed at answering the short ABG interpretation questions rather than the long "how'd you manage this ketoacidosis" or "critically evaluate something" questions.

Ketoacidosis-asociated ABG interpretation questions include the following:

Question 7.1 from the second paper of 2013
Question 26.2 from the second paper of 2013
Question 8.3 from the first paper of 2012
Question 7.1 from the first paper of 2009
Question 6.1 from the first paper of 2008

Just like in real life, the ketoacidosis in these questions if often paired with some sort of hyperglycaemic hyperosmolar state. Calculation of corrected sodium is occasionally called for.

A brief summary of different ketoacidosis subvarieties follows:

The Varieties of Ketoacidosis
	Starvation ketoacidosis	Alcoholic ketoacidosis	Diabetic ketoacidosis
Trigger	Prolonged starvation: ~3 days	Starvation following a binge	Inadequate insulin supplementation in the face of increased requirements. eg. sepsis
Mechanism	Diminished intake of carbohydrates leads to decreased insulin levels, and thus ketogenesis Ketogenesis occurs in the absence of adequate hepatic glycogen stores	Diminished intake of carbohydrates leads to decreased insulin levels, and thus ketogenesis Hepatic metabolism of ethanol depletes NAD⁺ and increases NADH levels, favouring conversion of acetoacetate into β-hydroxybutyrate	In the absence of insulin, and the presence of stress hormones and glucagin, hepatic lipid metabolism switches to ketogenesis
Characteristic features	mild acidosis Low ketone levels Anion gap may be normal BSL is frequently low Patient is neither a diabetic nor an alcoholic	moderate acidosis β-hydroxybutyrate is the most prevalent ketone species BSL is frequently low	Severe acidosis May be mixed high and normal anion gap (ketones are excreted along with strong cations; SID decreases as a result) Severe dehydration
Management	Recommencement of nutrition results in a release of insulin Refeeding syndrome may occur	Recommencement of nutrition results in a release of insulin Severe acidosis - usually requires insulin/dextrose infusion Refeeding syndrome may occur	Insulin/dextrose infusion Volume replacement: Water deficit: 100ml/kg Electrolyte replacement: Na⁺: 7-10mmol/kg K⁺ deficit: 3-5mmol/kg Cl^- deficit: 3-5mmol/kg PO₄ deficit: 1-1.5mmol/kg Mg²⁺ deficit: 1-1.5mmol/Kg Ca²⁺ deficit: 1-2mmol/Kg

Points to note:

Starvation ketoacidosis typically is not especially acidotic, and with lowish ketone levels
β-hydroxybutyrate is the prevalent ketone in ketoacidosis; the normal ratio of beta-hydroxybutyrate and acetoacetate is 3:1, and it can rise to 10:1 in diabetic ketoacidosis. Acetone is the least abundant.
In alcoholic ketoacidosis, β-hydroxybutyrate is even more prevalent
Urine dipstick ketone tests rely on the reaction between acetoacetate or acetone and sodium nitroprusside; this means beta-hydroxybutyrate will not be detected.
Conversely, the point-of-care capillary fingerprick ketones test detects only beta-hydroxybutyrate.

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.

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