eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Alcoholic Ketoacidosis

Chaiya Laoteppitaks, MD, Staff Physician, Department of Emergency Medicine, State University of New York Kings County Hospital Center
Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate, Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Updated: Jul 28, 2009

Introduction

Background

Alcoholic ketoacidosis (AKA) is an acute metabolic acidosis seen in those with a recent history of binge drinking and little or no nutritional intake. It was first described by Dillon et al in 1940. Previously, diabetes mellitus was the most common cause of a severe ketoacidosis. Dillon described 5 patients with ketoacidosis and normal or slightly elevated blood glucose concentrations. Four of the 5 patients were alcoholics with a recent marked increase in their ethanol intake and a decrease in their normal dietary intake. 

Alcoholic ketoacidosis is characterized by high serum ketone levels and an elevated anion gap. A concomitant metabolic alkalosis is also common, resulting from vomiting and volume depletion. Although AKA most commonly occurs in adults with alcoholism, alcoholic ketoacidosis has been reported in less-experienced drinkers of all ages. 

Pathophysiology

Alcoholic ketoacidosis (AKA) is a result of starvation with glycogen depletion and counter-regulatory hormone production, an increased nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD⁺) ratio related to ethanol metabolism, and volume depletion, resulting in ketogenesis. 
 
The body decreases insulin activity in the starvation state and increases the production of counter-regulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone. Hormone-sensitive lipase is inhibited by insulin, and, when insulin levels fall, lipolysis is up-regulated causing the release of free fatty acids from peripheral adipose tissue. Free fatty acids are either oxidized to CO₂ or ketone bodies (acetoacetate, hydroxybutyrate, and acetone), or they are esterified to triacylglycerol and phospholipid. Carnitine acyltransferase (CAT) is responsible for transporting the free fatty acids into the mitochondria and therefore regulates the entry of fatty acids into the oxidative pathway. The decreased insulin-to-glucagon ratio that occurs in starvation indirectly reduces the inhibition on CAT activity, thereby allowing more free fatty acids to undergo oxidation and ketone body formation. 
 
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 decreased ratio of NAD ⁺ to NADH 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 hydroxybutyrate (β-OH) to acetoacetate (AcAc) equilibrium toward β-OH. Unlike diabetic ketoacidosis, the predominant ketone body is -OH. Routine clinical assays for ketonemia test for AcAc and acetone but not for -OH. Clinicians underestimate the degree of ketonemia if they rely solely on the results of laboratory testing.

Frequency

United States

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

Mortality/Morbidity

Mortality is rare; however, alcoholic ketoacidosis (AKA) has been reported as the cause of death in a number of alcoholics. 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

Alcoholic ketoacidosis usually occurs in persons aged 20-60 years who are chronic abusers of alcohol. Alcoholic ketoacidosis occurs only rarely after a binge in persons who are not chronic drinkers. Recently, a case report was published of an 11 year-old boy who presented in AKA after drinking ethanol-based mouthwash.¹

Clinical

History

Example case of alcoholic ketoacidosis: A 35 year-old man who chronically abuses alcohol presents with abdominal pain and intractable emesis for 2 days. After 5 days of heavy drinking, he developed the pain and emesis and has stopped eating and drinking altogether. He complains of epigastric pain that radiates through to his back. He is afebrile, tachycardic, and borderline hypotensive. He is sleepy, but awakens easily to verbal stimuli. 

Typical symptoms of alcoholic ketoacidosis (AKA) and related conditions may include the following:

• Nausea, vomiting, and abdominal pain (each found in 60-75% of patients)
• Dyspnea, tremulousness, and/or dizziness (10-20% each)
• Muscle pain, diarrhea, syncope, and seizure (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 alcoholic ketoacidosis (AKA) are related to poor nutritional status due to long-standing alcohol abuse. AKA is often precipitated by another medical illness such as infection or pancreatitis. The diagnostic evaluation of AKA should search for potential precipitating factors when not clearly identified by history.

Differential Diagnoses

Other Problems to Be Considered

Korsakoff psychosis

Workup

Laboratory Studies

• Arterial blood gas determination
  • Arterial blood gas (ABG) measurement may show a low pCO ₂ level, low bicarbonate level, and normal partial pressure of oxygen (pO ₂ ) level in a pattern consistent with a metabolic acidosis with a respiratory compensation. 
  • Serum pH levels may be misleading because the patient with alcoholic ketoacidosis (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. 
  • Venous blood gas measurements correlate very well with arterial measurements. One should consider using venous blood gas measurements in lieu of arterial blood gas measurements.²
• 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. Direct serum measurements of β–OH should be used when available.
  • 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 alcoholic ketoacidosis (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 alcoholic ketoacidosis.
  • 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. Serum magnesium levels are not reliable indicators of total body magnesium stores, however. Due to the linked excretion between potassium and magnesium, the presence of hypokalemia is a strong indicator of hypomagnesemia and can be used as a surrogate test to determine if magnesium replacement is needed.
  • 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 due to chronic liver disease.
• 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. Blood alcohol levels do not typically change the management of AKA and are therefore not often necessary.

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

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 and thiamine.
• 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 (AKA) is established, the mainstay of treatment is hydration with 5% dextrose in normal saline (D5 NS) to address the principal physiologic derangement, a lack of metabolic substrate (glucose).³ Carbohydrate and fluid replacement reverse this process by increasing serum insulin levels and suppressing the release of glucagon and other counter-regulatory hormones and by providing metabolic substrate. 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 upon initiation of dextrose. Patients who can tolerate oral nutrition should be fed.
• 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 diabetic ketoacidosis (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. 
• If the anion gap fails to close as resuscitation continues, it is important to consider other causes of an anion gap acidosis such as methanol or ethylene glycol ingestion (co-ingestion). When considering other co-ingestants, note that alcoholic ketoacidosis can cause a mildly elevated osmolar gap (~20 mmol/kg).
• Evaluate the patient for signs of alcohol withdrawal syndrome, which may include tremors, agitation, diaphoresis, tachycardia, hypertension, 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 alcoholic ketoacidosis (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

A requirement for any medication other than D₅ NS is uncommon. Fluid resuscitation is the mainstay of treatment in alcoholic ketoacidosis (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.

Alkalinizing agents

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

Sodium bicarbonate (Neut)

Bicarbonate therapy should be reserved for patients with severe life-threatening acidosis unresponsive to fluid resuscitation. Severe complications such as volume overload, hypernatremia, hyperosmolality, and paradoxical CSF acidosis can arise from bicarbonate administration. If bicarbonate therapy is initiated, do not attempt to fully correct the serum pH or bicarbonate level. Sodium bicarbonate should rarely be given as rapid bolus; instead, it should be added to the patient's IV fluid. Administration of bicarbonate in the presence of metabolic acidosis is a temporizing measure; place primary emphasis on correction of the underlying cause of the acidosis.

Dosing

Adult

100mL of sodium bicarbonate 8.4% added to 1L of D5/0.45% NS or 150mL of sodium bicarbonate 8.4% added to 1L of D5W (sodium content of these mixtures approximates that of NS); administer IV

Pediatric

Initially, 1 mEq/kg IV, which is 1 mL/kg of 8.4% solution

Interactions

None significant

Contraindications

Alkalosis; hypernatremia; severe pulmonary edema; hypocalcemia; abdominal pain of unknown etiology

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Rapid administration of this drug may result in paradoxical CSF acidosis, impaired oxygen delivery, hypokalemia, hypocalcemia, overshoot alkalosis, hypernatremia, or hyperosmolality

Vitamin supplementation

This is indicated to correct a thiamine deficiency.

Thiamine (Vitamin B-1)

Supplementation ensures adequate cofactor for maintenance of cellular aerobic respiration. CNS depletion of thiamine may result in Wernicke's encephalopathy. Chronic thiamine deficiency may cause heart failure. Thiamine is an important element of the treatment of AKA, but there is little evidence that patients without clinical signs of Wernicke's will have an acute decompensation when treated initially with dextrose alone. Although thiamine should always be administered, dextrose should not be withheld pending thiamine availability in patients without clinical signs of Wernicke's.

Dosing

Adult

100 mg IV/IM q24h

Pediatric

Not established

Interactions

None for this emergency

Contraindications

None for this emergency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Sensitivity reactions can occur (intradermal test-dose recommended in suspected sensitivity); deaths have resulted from IV use; administer before or together with dextrose-containing fluids in suspected thiamine deficiency

Follow-up

Further Inpatient Care

• Admit patients for continued treatment. Restoration of volume status and correction of the acidosis may be difficult to accomplish in the ED.
• Counseling and/or therapy for alcohol abuse should be part of the patient's treatment regimen and should continue following discharge.

Inpatient & Outpatient Medications

• 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 but not a carboxylic acid, unlike acetoacetate).

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

Medicolegal Pitfalls

• Failure to consider alcoholic ketoacidosis (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
• Failure to identify precipitating medical illness such as infection or pancreatitis

References

1. Manini AF, Hoffman RS, Nelson LS. Alcoholic ketoacidosis in an 11-year-old boy. Pediatr Emerg Care. Mar 2008;24(3):170-1. [Medline].

2. Kelly AM. The case for venous rather than arterial blood gases in diabetic ketoacidosis. Emerg Med Australas. Feb 2006;18(1):64-7. [Medline].

3. Mihai B, Lacatusu C, Graur M. [Alcoholic ketoacidosis]. Rev Med Chir Soc Med Nat Iasi. Apr-Jun 2008;112(2):321-6. [Medline].

4. Adams SL. Alcoholic ketoacidosis. Emerg Med Clin North Am. Nov 1990;8(4):749-60. [Medline].

5. Al-Sanouri I, Dikin M, Soubani AO. Critical care aspects of alcohol abuse. South Med J. Mar 2005;98(3):372-81. [Medline].

6. 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].

7. Fox JC, Whitcomb DC. Alcohol deficiency, stress hormones and bad acidosis: aka AKA. N C Med J. Feb 1991;52(2):69-73. [Medline].

8. Halperin ML, Hammeke M, Josse RG, Jungas RL. Metabolic acidosis in the alcoholic: a pathophysiologic approach. Metabolism. Mar 1983;32(3):308-15. [Medline].

9. Hoffman RS, Goldfrank LR. Ethanol-associated metabolic disorders. Emerg Med Clin North Am. Nov 1989;7(4):943-61. [Medline].

10. Kearns T, Wolfson AB. Metabolic acidosis. Emerg Med Clin North Am. Nov 1989;7(4):823-35. [Medline].

11. Moss M, Burnham EL. Alcohol abuse in the critically ill patient. Lancet. Dec 23 2006;368(9554):2231-42. [Medline].

12. Palmer JP. Alcoholic ketoacidosis: clinical and laboratory presentation, pathophysiology and treatment. Clin Endocrinol Metab. Jul 1983;12(2):381-9. [Medline].

13. Thomsen JL, Simonsen KW, Felby S, Frohlich B. A prospective toxicology analysis in alcoholics. Forensic Sci Int. Nov 10 1997;90(1-2):33-40. [Medline].

14. 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].

15. Williams HE. Alcoholic hypoglycemia and ketoacidosis. Med Clin North Am. Jan 1984;68(1):33-8. [Medline].

16. Wrenn KD, Slovis CM, Minion GE, Rutkowski R. The syndrome of alcoholic ketoacidosis. Am J Med. Aug 1991;91(2):119-28. [Medline].

Keywords

alcoholic ketoacidosis, AKA, alcoholic acidotic coma, alcohol withdrawal, acute metabolic acidosis, metabolic alkalosis, alcohol abuse, glycogen depletion, lipolysis, ketogenesis, ethanol consumption, ketonemia, alcoholism, chronic alcoholism, chronic alcohol abuse, ketones, substance abuse, ketosis, binge drinking, Wernicke encephalopathy, Wernicke's encephalopathy

Contributor Information and Disclosures

Author

Chaiya Laoteppitaks, MD, Staff Physician, Department of Emergency Medicine, State University of New York Kings County Hospital Center
Chaiya Laoteppitaks, MD is a member of the following medical societies: American College of Emergency Physicians and Emergency Medicine Residents Association
Disclosure: Nothing to disclose.

Coauthor(s)

Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate, Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center
Sage W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center
Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Mary Claire O'Brien, MD, and Roy Alson, MD, PhD, to the development and writing of this article.

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