Alcoholic Ketoacidosis 

Alcoholic Ketoacidosis – 6 Interesting Facts

1. Suspect alcoholic ketoacidosis in patients who have been on an alcohol binge without eating with nausea and vomiting
2. Evaluate with venous blood gas
3. Fluid resuscitate with isotonic balanced solutions and provide dextrose supplementation
4. Consider insulin in your hyperglycemic patients concomitantly with the dextrose infusion
5. Replenish electrolytes, especially potassium and magnesium
6. Delaying dextrose-containing fluids that may lead to hypoglycemia and worsen the metabolic acidosis

Introduction

• AKA (alcoholic ketoacidosis) is a metabolic disorder characterized by alcohol use along with the presence of ketoacidosis
• AKA is a common cause of ketoacidosis in nondiabetic patients and is very likely underdiagnosed

• This underdiagnosis is most likely due to the rapid improvement with resolution of vomiting with antiemetics and subsequent nourishment with food
  • Emergency clinicians likely do not obtain laboratories and make this diagnosis
  • Thus, the true incidence of AKA is unknown
• Mortality for AKA is likely also underreported due to the assumption that patients with chronic alcohol use have likely died of the more common etiologies such as alcoholism or another alcohol-related disease (ie, cirrhosis, trauma)

Etiology and Risk Factors

Pathophysiology

• The development of AKA depends on several conditions to be present. There needs to be¹
  • Malnutrition
  • Increased nicotinamide adenine dinucleotide hydrogen
  • Hypovolemia
• When the body enters a starvation state (eg, malnutrition) glucagon is produced and released to provide the body with some nourishment, primarily glucose from gluconeogenesis and glycogenolysis
• As the production of glucose takes time, the body also begins lipolysis
  • Lipolysis leads to an increased synthesis of beta-hydroxybutyrate and other serum ketone bodies resulting in metabolic acidosis and subsequent symptomology
• During a period of decreased alcohol consumption, caloric intake falls, and lipolysis increases
• This creates a cycle of increasing cortisol, norepinephrine, and glucagon levels
• As a result, an increased number of fatty acids are released from peripheral triglycerides and undergo beta-oxidation to generate acetyl-CoA
• The capacity of the Krebs cycle is exceeded, and oxidation must be achieved through ketogenesis²³⁴
• In the presence of alcohol, pyruvate is preferentially converted to lactic acid leading to increased acidosis
• The increased nicotinamide adenine dinucleotide hydrogen does not allow gluconeogenesis to occur due to decreased pyruvate which contributes to the euglycemia or hypoglycemia seen in AKA⁵
• Alcohol also induces volume depletion
  • Alcohol is an antagonist to free water reabsorption by inhibiting antidiuretic hormone as well as the increased risk for vomiting
  • Because of the reduced volume intravascularly, there is decreased clearance of ketones in the urine leading to increase ketone bodies in the serum and subsequent ketoacidosis⁶

Risk Factors

• Lower BMI⁷
• Whiskey drinkers
• Smokers
• Baseline hypoglycemia

Diagnosis

Approach to Diagnosis

• Prompt recognition and treatment of AKA decreases mortality
• Familiarity with typical presentation may aid in diagnosis
• Laboratory studies such as venous blood gas, basic metabolic panel, lactic acid, urine and serum ketones can help differentiate AKA from other disorders
• EKG may identify concomitant diagnoses

Diagnostic Criteria

• The diagnostic criteria for alcoholic ketoacidosis can be found in Table 1

Table 1. Diagnostic criteria for alcoholic ketoacidosis.

History of alcoholic use disorder or alcohol dependence Euglycemia or hypoglycemia Anion gap metabolic acidosis Presence of urine or serum ketones (beta-hydroxybutyrate is the predominant ketone present) Mildly elevated (approximately 20 mm/kg) osmolal gap

Workup

History

• The typical patient with AKA usually has alcohol use disorder, poor nutrition, and presents in a varying degree of alcohol withdrawal after cessation
• Owing to their chronic malnourishment, they have a significant decrease in caloric intake and commonly exhibit symptoms of nausea, vomiting, abdominal pain, and dehydration⁸⁹¹⁰
• The presentation may include complications such as pancreatitis, gastritis, or esophagitis with or without gastrointestinal bleed, which may be caused by the AKA or may precipitate the AKA¹¹

Physical Examination

• Because of the degree of acidosis present, they will commonly present with tachypnea due to the body’s respiratory compensation for the metabolic acidosis
• Other vital sign abnormalities include tachycardia and hypotension, but they may present with normal or elevated blood pressures due to alcohol withdrawal
• Because plasma osmolality remains grossly normal, they do not have marked altered mental status until their acidosis is profound⁸¹⁰
• Although abdominal tenderness in AKA is common, it should not be peritoneal, so the presence of any signs of a surgical abdomen should warrant prompt evaluation for any other concomitant disease process¹

Laboratory Tests

• Venous blood gas
• Basic metabolic panel
  • Almost universally, the anion gap will be elevated in AKA
  • The presence of an elevated anion gap without acidosis should alert the clinician that there may be a mixed acid–base disorder present
    • If there is a mixed acid-base disorder present, the serum bicarbonate and/or the pH on a venous blood gas may be close to normal
• Liver function tests
• Magnesium
• Prothrombin time
• Partial thromboplastin time
• Lactic acid level
  • Commonly elevated but not severely (greater than 4 mmol/L)
  • If the lactic acid level is severely elevated, another concomitant condition may be present and should be investigated for such as sepsis, liver dysfunction, or seizures⁶
• Lipase
• Beta-hydroxybutyrate
  • If available, it should be used
  • Alternatively, serum ketones and urine ketones
    • Rely on nitroprusside testing which detects the presence of acetoacetate and does not detect beta-hydroxybutyrate
    • Do not rely on negative serum or urine ketone testing

Diagnostic Tools

• EKG
  • Quickly evaluate for signs of acute coronary syndrome
  • Evaluate for any concomitant hyperkalemia that may develop due to acidemia
    • Despite an elevated serum potassium measurement, total body potassium levels are low and are falsely elevated due to the acidemia
    • If concomitant hyperkalemia is present with EKG changes, prompt treatment with calcium is warranted; however, further treatment with potassium elimination is usually not recommended

Differential Diagnosis

• The differential diagnosis for a patient presenting with AKA is expansive. The most common are presented in Table 2

Table 2. Differential Diagnosis: Alcoholic ketoacidosis.

Condition	Description	Differentiated by
Gastritis, esophagitis, peptic ulcer disease	Abdominal pain, nausea, and vomiting	Symptoms improve with proton pump inhibitor or histamine receptor antagonist12
Pancreatitis	Abdominal pain, nausea, and vomiting	Elevated amylase and lipase12
Diabetic ketoacidosis	Elevated anion gap acidosis with nausea and vomiting	Elevated serum glucose greater than 250 Normal osmolal gap6
Toxic alcohol intoxication	Elevated anion gap acidosis with nausea and vomiting	Absence of ketones

Treatment

Approach to Treatment

• Prompt treatment of AKA decreases mortality
• The mainstay of treatment for AKA consists of IV fluid resuscitation and glucose and electrolyte replenishment
• The goal of treatment is to replenish volume that has been lost through vomiting and diuresis as well as to slow the rate of ketogenesis and allow the metabolization and urinary clearance of ketone bodies⁸¹¹¹³
• For patients with impaired gluconeogenesis, a dextrose (D5/D10) drip is recommended^168101314
• Electrolytes, particularly potassium, should be replenished intravenously as dictated by the patient’s laboratory analysis^1614151617

Nondrug and Supportive Care

• Balanced electrolyte solutions are the preferred choice for the initial stages of IV resuscitation, as normal saline solution may worsen a hyperchloremic nonanion gap metabolic acidosis

Drug Therapy

• Dextrose infusion running concomitantly with the isotonic fluid will increase insulin secretion and decrease glucagon secretion which will slow down ketogenesis and increase the body’s metabolization of present ketone bodies by providing a better energy substrate for the brain
  • Dextrose 5% as a mixture with the isotonic fluid bag or running concomitantly is usually sufficient in euglycemic patients in AKA
  • Hypoglycemic patients should be treated aggressively with higher concentrations of dextrose such as D10 or D50
• Patients who are subsequently found to have elevated blood glucose may require an insulin infusion with a dextrose infusion running concomitantly
• Hypokalemia should be corrected before administration of dextrose or insulin, as they are likely to shift the potassium into the cells and subsequently lower serum potassium levels
  • Potassium chloride either orally, if tolerant, or IV is recommended
• Often, alcoholic patients are magnesium-depleted with concomitant hypokalemia
  • Magnesium repletion in patients who are hypomagnesemic is required to help replenish potassium
• 500 mg of IV thiamine should be administered in patients at risk of WE (Wernicke’s encephalopathy)¹⁸¹⁹

Admission Criteria

• Most patients with AKA can be safely discharged home if they
  • Are able to tolerate orally
  • Have resolution of their ketoacidosis
  • Have repleted electrolytes
• All others should be admitted for further management

Follow-Up

Complications

• Clinicians should evaluate for alcohol withdrawal, WE, and other common complications associated with chronic alcohol use
• WE is the acute presentation of thiamine deficiency and is reversible if treated promptly
  • Classically presents with the triad of altered mental status, oculomotor dysfunction, and/or gait ataxia

References

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