Pathophysiology

• The mechanism of increased ketone production is similar to starvation ketosis. Two factors may account for this:
  1. decreased intake of food secondary to binge drinking, underlying abdominal pathology (gastritis, peptic ulcer disease, pancreatitis), or concurrent infection;
  2. depleted liver glycogen stores secondary to chronic alcoholism. The end result is the mobilization of free fatty acids for ketone production.
• In AKA the predominant ketone is ß-hydroxybutyrate (B-Hb). Alcohol causes an elevation of intracellular NAD/NADH which leads to preferential production of B-Hb. The ratio of B-Hb to acetoacetate in AKA is ˜ 12:1. In contrast, the ratio is ˜ 3:1 in DKA.

Diagnosis and Evaluation

• AKA is probably under diagnosed. Nausea, vomiting, abdominal pain and dehydration are all common and nonspecific presentations of chronic alcohol abuse, making the diagnoses of AKA difficult.
• Furthermore, the term AKA is often a misnomer. AKA frequently involves neither A (alcohol), nor K (ketones), nor A (acidosis). Serum alcohol is usually low or absent, as the patient has stopped drinking 12 to 72 h previously. Ketones are often absent on initial tests for ketonemia or ketonuria, as B-Hb is nonreactive with the ketone assay. However, post-hydration ketones will be present, as B-Hb is converted to the reactive acetoacetate. Alkalemia may be more common than acidemia. Ketoalkalosis is a common finding in AKA secondary to vomiting and dehydration which lead to metabolic and contraction alkalosis respectively.

Signs and Symptoms

• Nausea and vomiting, often severe, is present in almost all cases.
• Abdominal pain is common and usually diffuse and nonspecific. As in DKA, the abdominal pain is often benign, of unclear etiology, and usually resolves as the ketosis clears. However, it is imperative to rule out other more serious pathology common in alcoholics such as gastritis, PUD, pancreatitis, alcoholic hepatitis, and sub acute bacterial peritonitis. Surgical illness, such as appendicitis and acute cholecystitis, acute adrenal insufficiency, must also be considered.
• Manifestations of dehydration are often present including dry mucous membranes, dry skin with decreased turgor, increased thirst, tachycardia, decreased urine output, and in late stages hypotension.
• Tachypnea +/- Kussmaul respirations may be present in the setting of significant metabolic acidosis.
• Generalized weakness and drowsiness is a common finding. True alterations in mental status mandate a thorough search for other conditions. Common coexistent etiologies of altered mental status in the alcoholic population include hypoglycemia, alcohol withdrawal or delirium tremens, and occult head injury with a subdural hematoma.

Laboratory/Studies

• Mixed acid-base disturbances are common. Anion gap metabolic acidosis (ketoacidosis), metabolic alkalosis (vomiting), contraction alkalosis (dehydration), and respiratory alkalosis (compensatory) may all be present concurrently. Acidemia or alkalemia may predominate the clinical the picture.
• Hypoglycemia or hyperglycemia may be present. Hypoglycemia may be present secondary to poor dietary intake and low glycogen stores in the liver. However, a mildly elevated glucose is more common in AKA.
• Hypokalemia can reach life-threatening levels secondary to severe vomiting combined with poor dietary intake.
• Hypomagnesaemia is commonly present in alcoholics.
• Serum and urine ketones initially may be negative becoming positive post-hydration. In contrast to DKA, the urinalysis shows ketonuria without glucosuria.
• Elevated BUN/Cr ratio secondary to dehydration (prerenal azotemia) may be present.
• Mild leukocytosis from stress demargination can occur, making leukocytosis a nonspecific marker for infection.
• Anemia and thrombocytopenia, typical of chronic alcohol abuse, is often found concurrently.
• Liver function tests and pancreatic enzymes (amylase, lipase) should be sent in search of coexistent alcoholic hepatitis or pancreatitis.
• Stool for occult blood should be performed to rule out a GI bleed in any alcoholic with nausea, vomiting, and abdominal pain.
• EKG should be considered in middle age/elderly population with nonspecific abdominal pain to rule out ischemia/infarction. It may also provide an early clue to electrolyte abnormalities.
• Head CT is an important study in the alcoholic patient to rule out other etiologies of altered mental status.

ED Management

There are four basic components in the treatment of AKA:

1. fluid replacement,
2. glucose administration,
3. electrolyte replacement, and
4. treatment of a precipitant or coexisting illness.

• Fluid replacement: If hemodynamically unstable secondary to volume depletion, administer 0.9% NS as a bolus and repeat as necessary. Once stability is restored, begin maintenance fluid with D5 0.45% NS.
• Glucose administration: Glucose-containing IV solutions should be started early in the course of treatment, even in the euglycemic patient. The early use of glucose containing solutions decreases production of ketoacids and replenishes glycogen stores leading to a more rapid resolution of metabolic abnormalities than saline alone. Thiamine repletion is usually needed along with glucose administration for patients with AKA. Theoretically, thiamine should be given before or with glucose to avoid precipitation of Wernicke’s encephalopathy.
• Electrolyte replacement: Hypokalemia should be anticipated and treated early. Administration of fluids alone will initially increase urinary losses of potassium. Replacement of magnesium is usually needed in the chronic alcoholic and will aide in the treatment of hypokalemia.
• Other interventions for AKA include antiemetic as needed and benzodiazepines for withdrawal symptoms.
• Admission criteria include persistent nausea and vomiting, persistent abdominal pain and abdominal pain of unclear etiology, significant electrolyte abnormalities, or significant co morbid illness.