Definition: The syndrome of a “wide-gap metabolic acidosis, malnutrition, and binge drinking superimposed on chronic alcohol abuse” (Wrenn 1991)


  • 15.1 million US adults suffer from alcohol use disorder
  • Prevalence of AKA correlates with the prevalence of alcohol use disorder in the community
  • No ethnic or gender differences have been identified as contributing to the likelihood of developing AKA (NIAAA)
  • A 2014 study of 1588 Japanese men with alcohol use disorder found that alcoholic ketosis was significantly associated with slow-metabolizing alcohol dehydrogenase-1B, whiskey and shochu, hypoglycemia, lower BMI, and smoking (Yokoyama 2014)


  • Ketone bodies are generated by the liver in the fasting state, under conditions of low glucose. Hepatocytes beta-oxidize long-chain fatty acids to generate acetyl-CoA, which is then converted to acetoacetic acid, beta-hydroxybutyric acid, and acetone, the three major ketones.
  • Ketones are water-soluble and can be used by organs, particularly the brain, to maintain metabolism when glucose is low. In a healthy, fasting subject, the rate of ketogenesis is matched by ketone use by peripheral tissues and loss in the urine. Buffer systems in the body maintain a normal pH with a base deficit and mild anion gap.
  • In certain disease states that accelerate production or prevent elimination, ketones accumulate, causing a metabolic acidosis with a drop in pH and serum bicarbonate and an increase in the anion gap.
  • Potassium shifts out of cells in exchange for hydrogen ions pumped in. Sodium and potassium are lost in the urine with ketoacid anions.
  • Ethanol is metabolized by hepatocytes to acetic acid, which is converted to acetyl CoA. Acetyl CoA can be further oxidized through the Krebs cycle, used to synthesize fatty acids, or used in ketogenesis.
  • Ketogenesis is favored over the other pathways when there is a low insulin:glucagon ratio, when the body is in the starved state.
  • AKA occurs when a malnourished patient with alcohol use disorder stops drinking, and falling ethanol levels increase catecholamines and cortisol, which amplify the hormonal response to the fasting state, accelerating lipolysis and synthesis of ketones. Oxidation of ethanol to acetaldehyde also produces molecules of NADH, which suppress gluconeogenesis through negative feedback, further exacerbating hypoglycemia and the production of ketones.


  • Presenting symptoms are related to acute effects of alcohol, alcohol withdrawal, and ketoacidosis.
  • A 1991 case series found that the most common symptoms among 74 patients presenting with AKA are nausea (76%), vomiting (73%), and abdominal pain (62%). These symptoms often develop one to two days before ketoacidosis and are due to other effects of alcohol, like gastritis. They may be the reason that patients abruptly stop drinking, triggering ketoacidosis. Though these abdominal complaints are common, they are less commonly accompanied by signs such as abdominal distension, hypoactive bowel sounds, or rebound tenderness. Abdominal tenderness and hepatomegaly are more common (Wrenn 1991).
  • Patients are also often hypovolemic due to vomiting, diarrhea, and urinary losses. Tachycardia and hypertension may result from withdrawal, pancreatitis, or hypovolemia.
  • Symptoms of withdrawal, such as tremulousness, are less common.
  • Altered mental status is less common in AKA than in DKA, as neurological manifestations in DKA are thought to be secondary to a rise in plasma osmolality due to hyperglycemia and consequent water loss.

Differential diagnosis: 

  • Other causes of anion gap metabolic acidosis:
    • Methanol
    • Uremia
    • Propylene glycol, diethylene glycol, ethylene glycol
    • Lactic acidosis
    • Salicylate
  • Other causes of ketoacidosis:
    • Starvation
    • Diabetes mellitus

Laboratory findings: 

  • Diagnosis of AKA requires the detection of ketone bodies in the urine and serum. Urine can be tested with nitroprusside tablets or dipsticks, though this rapid test cannot indicate whether the degree of ketone accumulation can account for the total anion gap. Direct testing for beta-hydroxybutyrate in the serum is replacing nitroprusside tests.
  • NADH from the metabolism of ethanol to acetaldehyde drives the equilibrium between acetoacetic acid and beta-hydroxybutyric acid towards beta-hydroxybutyric acid. Acetoacetic acid is the acid detected by several diagnostic tests for AKA, like the nitroprusside test, so false negatives may result.
  • Blood pH and bicarbonate are both low, while anion gap is elevated. Metabolic acidosis often coexists with other acid-base disorders in AKA (Wrenn 1991). Liver disease is associated with chronic respiratory alkalosis, and the acute stress of withdrawal may cause an acute respiratory alkalosis.
  • AKA typically begins with a low ethanol level, so plasma alcohol level is often low or not detectable.
  • Elevated total bilirubin, AST, ALT, and GGT are common findings. They are not directly related to the pathogenesis of AKA, but higher levels are associated with higher levels of urine ketones (Yokoyama 2014).
  • Potassium lost in vomit, diarrhea, and urine as well as potassium movement into cells in order to buffer hydrogen ions, and malnutrition contributes to hypokalemia.
  • Hypomagnesemia was the most common electrolyte abnormality in alcohol use disorder patients identified in a 1995 study. It was due to a combination of mechanisms, including loss in urine and diarrhea, and malnutrition (Elisaf 1995).


  • All forms of ketoacidosis require treatment of the underlying disease to normalize the rate of ketogenesis and allow for metabolism of accumulated ketones so that bicarbonate can be regenerated. However, loss of sodium and potassium with ketones in the urine as organic acid salts causes a hyperchloremic metabolic acidosis in a later recovery phase as the kidneys excrete ammonium chloride to regenerate bicarbonate.
  • In AKA, correcting hypoglycemia with dextrose infusion increases the insulin:glucagon ratio to slow ketogenesis and fatty acid release for oxidation by the liver.
  • Isotonic saline is given to correct fluid deficits from vomit and sodium and potassium losses in urine. Correction of fluid deficits helps to reduce secretion of catecholamines and glucagon to further slow ketogenesis.
  • Dextrose and saline infusions are titrated to patients’ electrolyte status. In severe hypokalemia, potassium should be repleted prior to dextrose administration to avoid insulin-driven shift of potassium into cells.
  • Patients with alcohol use disorder require 100 mg of thiamine IV or IM prior to glucose to decrease the risk of precipitating Wernicke’s encephalopathy.
  • Potassium, phosphate, and magnesium are often low in patients with AKA and should be repleted along with glucose. The choice of oral vs. IV replacement depends on the severity of the abnormality and the ability of the patient to tolerate PO.


  • A study of 30 cases of sudden death in patients with chronic alcohol use disorder found that beta hydroxybutyrate levels were 10 times higher in patients whose death was unexplained compared to those in whom the cause of death was identified, suggesting that untreated AKA may be responsible for death (Kadis 1999).

Take home points: 

  • AKA is a common syndrome of patients with alcohol use disorder in the ED.
  • Symptoms result not only from an anion gap metabolic acidosis but also from coexisting disorders, like withdrawal from alcohol and the acute effects of binge drinking. Laboratory testing reflects the combination of these disorders.
  • AKA should be treated with thiamine, dextrose, isotonic saline, and repletion of deficient electrolytes, titrating appropriately for each patient’s biochemical status.
  • When managed appropriately, AKA resolves completely with few lasting sequelae. If not recognized or treated, AKA may result in sudden death.



Elisaf M, Merkouropolous M, Tsianos EV, Siamopolous KC. Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. Journal of Trace Elements in Medicine and Biology (1995). 9(4):210-4. PMID 8808192

Kadiš P, Balažic J, Marolt VF. Alcoholic ketoacidiosis: a cause of sudden death of chronic alcoholics. Forensic science international. 1999 Aug 16;103:S53-9.

National Institute of Alcohol Abuse and Alcoholism. “Alcohol Facts and Statistics.” NIAAA, 13 Aug 2019,

Wrenn KD, Slovis CM, Minion GE, Rutkowski R. The syndrome of alcoholic ketoacidosis. Am J Med (1991). 91(2):119-28. PMID 1867237

Yokoyama A, Yokoyama T, Mizukami T, Matsui T, Shiraishi K, Kimura M, Matsushita S, Higuchi S, Maruyama K. Alcoholic ketosis: prevalence, determinants, and ketohepatitis in Japanese alcoholic men. Alcohol Alcohol (2014). 49(6):618-25. PMID 25085997