AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Alcoholic ketoacidosis (AKA) is an acute metabolic acidosis that typically occurs in people who chronically abuse alcohol and have a recent history of binge drinking, little or no food intake, and persistent vomiting. AKA is characterized by elevated serum ketone levels and a high anion gap. A concomitant metabolic alkalosis is common, secondary to vomiting and volume depletion. Although AKA most commonly occurs in adults with alcoholism, AKA has been reported in less-experienced drinkers of all ages.

Pathophysiology

AKA is a result of starvation with glycogen depletion and counter-regulatory hormone production, a raised nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD⁺) ratio related to the metabolism of ethanol, and volume depletion, resulting in ketogenesis.

When the dietary intake of carbohydrates is insufficient to supply glucose for the body's needs and hepatic glycogen stores are depleted by fasting, ketones are produced in the liver as an alternative source of energy. Two steps are required for ketogenesis: (1) enhanced lipolysis with an increased delivery of free fatty acids to the liver and (2) an alteration in hepatic metabolism by which these free fatty acids are converted preferentially into ketones instead of into triglycerides. Decreased insulin activity, increased counter-regulatory hormone levels (primarily glucagon, but also cortisol, catecholamines, and growth hormone), and volume depletion all play a role in ketogenesis.

The body's response to starvation is a decrease in insulin activity and an increase in the production of counter-regulatory hormones. These counter-regulatory hormones cause the release of free fatty acids from peripheral adipose tissue. However, excess fatty acids alone are insufficient to cause ketoacidosis since, normally, the liver metabolizes free fatty acids into triglycerides. The key difference in the starvation state is in mitochondrial enzyme activity; specifically, the rate at which carnitine acyltransferase (CAT) transports free fatty acids into the mitochondria for oxidation. CAT activity is low in the fed state and accelerated in the fasting state. Glucagon excess is believed to have the major role in this hepatic response.

Prolonged vomiting leads to dehydration, which decreases renal perfusion, thereby limiting urinary excretion of ketoacids. Moreover, volume depletion increases the concentration of counter-regulatory hormones, further stimulating lipolysis and ketogenesis.

Ethanol is oxidized to acetaldehyde, which is itself oxidized to acetate. Both steps require the reduction of nicotinamide adenine dinucleotide (NAD⁺) to reduced nicotinamide adenine dinucleotide (NADH). The increased ratio of NADH to NAD⁺ has several implications: (1) impaired conversion of lactate to pyruvate with an increase in serum lactic acid levels, (2) impaired gluconeogenesis because pyruvate is not available as a substrate for glucose production, and (3) a shift in the beta-hydroxybutyrate (β-OH) to acetyl acetate (AcAc) equilibrium toward β-OH. β-OH is the predominate ketone in AKA. Understanding this is essential because routine clinical assays for ketonemia test for AcAc and acetone but not for β-OH. Clinicians underestimate the degree of ketonemia if they rely solely on the results of laboratory testing.

Frequency

United States

The prevalence of AKA in the United States correlates with the incidence and distribution of alcohol abuse within a given community.

Mortality/Morbidity

Mortality is rare. Morbidity more often results from associated complications, such as liver dysfunction, acute pancreatitis, seizures, rhabdomyolysis, hypoglycemia, lactic acidosis, heart failure, or systemic infection.

Race

No specific distribution of this disorder has been identified based on race or ethnicity.

Sex

Males and females are affected equally.

Age

AKA usually occurs in persons aged 20-60 years who are chronic abusers of alcohol. AKA occurs only rarely after a binge in persons who are not chronic drinkers.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Example case of alcoholic ketoacidosis: A man who chronically drinks alcohol and has poor baseline nutritional status engages in a drinking binge. He develops nausea and vomiting and so he stops drinking and eating altogether. He presents to the emergency department 24-48 hours later. The typical symptoms may include the following:

• Nausea, vomiting, abdominal pain, and/or hematemesis (each found in 60-75% of patients
• Dyspnea, tremulousness, and/or dizziness (10-20% each)
• Muscle pain, fever, diarrhea, syncope, seizure, and/or melena (1-8% each) 

Physical

Generally, the physical findings relate to volume depletion and chronic alcohol abuse. The fruity odor of ketones may be present on the patient's breath. The patient's mental status may be impaired. Physical findings may include the following:

• Tachycardia, tachypnea, and/or abdominal tenderness (30-40% each)
• Hypotension, hypothermia, fever, abdominal distention, rebound tenderness, hepatomegaly, ascites, and/or heme-positive stools (These are less common, with each found in 1-15% of patients.)

Causes

Most cases of AKA are related to poor nutritional status due to long-standing alcohol abuse.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Korsakoff psychosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Arterial blood gas determination
  
  
  • Arterial blood gas (ABG) measurement may show a low pCO₂ level, low bicarbonate level, and normal partial pressure of oxygen (pO₂) level.
  • Serum pH levels may be misleading because the patient with AKA often has a mixed acid-base disorder. In addition to metabolic acidosis due to ketone formation, a metabolic alkalosis may be present due to vomiting and volume depletion. A respiratory alkalosis may be present secondary to hyperventilation. The possibility of a double or triple acid-base disorder means serum pH levels may be near normal despite a severe acid-base disturbance.
• Serum ketones
  
  
  • The nitroprusside reaction (Acetest) may be negative or only weakly positive for serum ketones because nitroprusside reacts with acetone and AcAc, but not with β-OH
  • In AKA, the β-OH/AcAc formation ratio is 5:1. Therefore, ketosis may be more severe than would be inferred from a nitroprusside reaction alone. With initial therapy, ketone formation shifts toward the production of AcAc so that measured ketone levels rise, although β-OH levels decrease.
• Glucose and electrolyte levels
  
  
  • Serum glucose level may be low, normal, or slightly elevated, which should help the clinician distinguish AKA from diabetic ketoacidosis (DKA). Usually, serum glucose levels are markedly elevated in cases of DKA.
  • Anion gap is elevated.
  • Lactate levels may be elevated.
  • Hyponatremia and hypokalemia have been reported in patients with AKA.
  • Ethanol-enhanced urinary excretion, emesis, and antacid use may contribute to hypophosphatemia in people who have chronic alcoholism.
  • Hypomagnesemia may be caused by poor nutrition, decreased renal absorption of magnesium, or nasogastric suctioning.
  • BUN and creatinine levels are typically elevated.
• Complete blood count
  
  
  • Anemia may be present secondary to nutritional deficiencies, alcoholic bone marrow suppression, or GI bleeding.
  • Hematocrit (Hct) may be falsely elevated from hemoconcentration in the presence of intravascular volume depletion
  • Thrombocytopenia may be present.
• Liver and pancreatic function test results, including hepatic enzymes (eg, serum glutamic-oxaloacetic transaminase [SGOT], lactate dehydrogenase [LDH], alkaline phosphatase), total bilirubin, and pancreatic amylase and lipase levels, may be elevated because of associated illnesses (eg, alcohol-induced hepatitis, pancreatitis).
• Alcohol levels
  
  
  • Alcohol level may be absent or low due to anorexia and decreased drinking in the preceding 1-3 days.
  • Methanol and ethylene glycol may also produce an elevated anion-gap acidosis. Additionally, these agents produce an osmolar gap.

Imaging Studies

• Chest radiography: Consider obtaining a chest radiograph because aspiration pneumonia is common in persons with alcoholism. Esophageal rupture may occur with prolonged retching, resulting in pneumomediastinum or subdiaphragmatic air.
• Urgent abdominal series: Consider obtaining an urgent abdominal series in patients with significant vomiting and abdominal pain because these symptoms may indicate obstruction and/or perforation of a viscus.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Assess the patient's airway and manage as clinically indicated. Administer oxygen as indicated. 
• Obtain intravenous access and administer fluid resuscitation for volume depletion and/or hypotension. Consider and treat hypoglycemia.
• If the patient's mental status is diminished, consider administration of naloxone.
• Note information about the patient's social situation and the presence of intoxicating agents besides alcohol.

Emergency Department Care

• Once the diagnosis of alcoholic ketoacidosis is established, the mainstay of treatment is hydration with 5% dextrose in normal saline (D₅NS.) Carbohydrate and fluid replacement reverse the pathophysiologic derangements that lead to AKA by increasing serum insulin levels and suppressing the release of glucagon and other counter-regulatory hormones. Dextrose stimulates the oxidation of NADH and aids in normalizing the NADH/NAD⁺ ratio. Fluids alone do not correct AKA as quickly as fluids and carbohydrates together. Thiamine supplementation should also be given as a prophylaxis against Wernicke encephalopathy. 
• In general, exogenous insulin is contraindicated in the treatment of AKA because it may cause life-threatening hypoglycemia in patients with depleted glycogen stores. In most cases, the patient's endogenous insulin levels rise appropriately with adequate carbohydrate and volume replacement. Insulin may be required in patients with diabetes who have AKA. If the patient's blood glucose level is significantly elevated, AKA may be indistinguishable from DKA. The disorders also may coexist. 
• As rehydration progresses and adequate renal function is established, consider electrolyte replacement, giving particular attention to potassium and magnesium. 
• Evaluate the patient for signs of alcohol withdrawal syndrome, which may include tremors, agitation, diaphoresis, tachycardia, hypertension, tremors, agitation, seizures, or delirium. Exclude other causes of autonomic hyperactivity and altered mental status. If the diagnosis of alcohol withdrawal syndrome is established, consider the judicious use of benzodiazepines, which should be titrated to clinical response. 
• Bicarbonate therapy should only be considered in the face of severe life-threatening acidosis (ie, pH <7.1) that is unresponsive to fluid therapy. 
• Associated disease states: Patients with AKA may have various coexisting illnesses, especially those commonly associated with chronic alcohol abuse. A thorough history and physical examination must be obtained. Associated conditions include pancreatitis, hepatitis, cirrhosis, coagulopathy, gastritis, GI bleeding, pneumonia, cardiomyopathy, alcohol withdrawal, infection, anemia, seizures, cerebrovascular accident (CVA), myopathy, rhabdomyolysis, neuropathy, arrhythmias, and intoxication with alcohol or other substances. These associated illnesses and conditions may be a significant source of morbidity and mortality if not properly addressed. 

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

A requirement for any medication other than D₅NS is uncommon. Fluid resuscitation is the mainstay of treatment in AKA.

The need to correct pH actively depends on the severity of the pH imbalance, the compensatory capabilities of the patient, the patient's overall clinical condition, and the potential harm caused by alkali administration. Sodium bicarbonate and other comparable solutions are usually unnecessary with adequate carbohydrate and fluid replacement.

Drug Category: Alkalinizing agents

These agents are sometimes used for the management of severe metabolic acidosis.

Drug Category: Vitamin supplementation

This is indicated to correct a thiamine deficiency.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit patients for continued treatment. Restoration of volume status and correction of the acidosis are rarely accomplished in the ED.


• Counseling and/or therapy for alcohol abuse should be part of the patient's treatment regimen and should continue following discharge.

In/Out Patient Meds

• Daily thiamine
• Daily multivitamin

Complications

• The differential diagnosis for alcoholic ketoacidosis includes isopropyl alcohol ingestion. Isopropyl alcohol ingestion differs from AKA because it leads to ketosis without acidosis. This occurs because isopropyl alcohol is metabolized to acetone (a ketone body with a high measure of acid strength [pKa]).

Prognosis

• With timely and aggressive intervention, the prognosis for a patient with AKA is good. The long-term prognosis for the patient is influenced more strongly by recovery from alcoholism.

Patient Education

• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center. Also, see eMedicine's patient education articles Alcoholism and Alcohol Intoxication.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider AKA as a cause of vomiting and dehydration in a person with alcoholism
• Failure to consider ingestion or co-ingestion of alcohols other than ethanol

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Adams SL. Alcoholic ketoacidosis. Emerg Med Clin North Am. Nov 1990;8(4):749-60. [Medline].
• Al-Sanouri I, Dikin M, Soubani AO. Critical care aspects of alcohol abuse. South Med J. Mar 2005;98(3):372-81. [Medline].
• Diltoer MW, Troubleyn J, Lauwers R, et al. Ketosis and cardiac failure: common signs of a single condition. Eur J Emerg Med. Jun 2004;11(3):172-5. [Medline].
• Fox JC, Whitcomb DC. Alcohol deficiency, stress hormones and bad acidosis: aka AKA. N C Med J. Feb 1991;52(2):69-73. [Medline].
• Halperin ML, Hammeke M, Josse RG, Jungas RL. Metabolic acidosis in the alcoholic: a pathophysiologic approach. Metabolism. Mar 1983;32(3):308-15. [Medline].
• Hoffman RS, Goldfrank LR. Ethanol-associated metabolic disorders. Emerg Med Clin North Am. Nov 1989;7(4):943-61. [Medline].
• Kearns T, Wolfson AB. Metabolic acidosis. Emerg Med Clin North Am. Nov 1989;7(4):823-35. [Medline].
• Moss M, Burnham EL. Alcohol abuse in the critically ill patient. Lancet. Dec 23 2006;368(9554):2231-42. [Medline].
• Palmer JP. Alcoholic ketoacidosis: clinical and laboratory presentation, pathophysiology and treatment. Clin Endocrinol Metab. Jul 1983;12(2):381-9. [Medline].
• Umpierrez GE, DiGirolamo M, Tuvlin JA. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care. Jun 2000;15(2):52-9. [Medline].
• Williams HE. Alcoholic hypoglycemia and ketoacidosis. Med Clin North Am. Jan 1984;68(1):33-8. [Medline].
• Wrenn KD, Slovis CM, Minion GE, Rutkowski R. The syndrome of alcoholic ketoacidosis. Am J Med. Aug 1991;91(2):119-28. [Medline].

Article Last Updated: Jul 2, 2007