Description

• Increased production of ketoacids due to:
  • Depleted glycogen stores in the liver after alcohol binge, malnutrition, and decreased food intake
  • Increased stress hormone production in response to starvation and/or alcohol withdrawal leads to amplification of ketone body production
  • Dehydration (nausea/vomiting, ADH inhibition)
  • Increased free fatty acid production
• Elevated NADH/NAD ratio leads to the predominate production of β-hydroxybutyrate (BHB) over acetoacetate (AcAc)

Etiology

• Malnourished, chronic alcohol abusers following a recent episode of heavy alcohol consumption:
  • Develop nausea, vomiting, or abdominal pain
  • Leading to the cessation of alcohol ingestion
  • Leading to the cessation of caloric intake
• Presentation usually occurs within 12–72 hr

Signs and Symptoms

• Nausea, vomiting, and abdominal pain: Most common symptoms
  • Usually diffuse with nonspecific tenderness
  • Epigastric pain is common
  • Uncommon: Rebound tenderness, abdominal distension, hypoactive bowel sounds
    • These findings mandate a search for an alternative, coexistent illness
• Tachycardia (common) due to:
  • Dehydration with associated orthostatic changes
  • Concurrent alcohol withdrawal
• Tachypnea
  • Common
  • Deep Kussmaul respirations may be present with significant acidosis
• Decreased urinary output from hypovolemia
• Fever absent unless there is an underlying infection
• Mental status:
  • Minimally altered as a result of hypovolemia and possibly intoxication
  • Altered mental status mandates a search for other associated conditions such as:
    • Head injury, cerebrovascular accident (CVA), or intracranial hemorrhage
    • Hypoglycemia
    • Alcohol withdrawal
    • Encephalopathy
    • Toxins
• Visual disturbances:
  • Reports of isolated visual disturbances with AKA (more common with severe acidosis)

• Recent binge
• Abrupt cessation

• Findings of dehydration most common
• May have ketotic odor
• Kussmaul respirations
• Palmar erythema (cirrhosis)
• Abdominal tenderness without rebound or guarding

Essential Workup

• Increased anion gap metabolic acidosis secondary to the presence of ketones:
  • Venous blood gas may be utilized in lieu of arterial
• Differentiate from diabetic ketoacidosis (DKA), toxic alcohol ingestion, and other causes of anion gap metabolic acidosis

Diagnostic Tests and Interpretation

• Acid–base disturbance:
  • Increased anion gap metabolic acidosis hallmark
  • Mixed acid–base disturbance common:
    • Respiratory alkalosis
    • Metabolic alkalosis secondary to vomiting and dehydration
    • Hyperchloremic acidosis
  • Mild lactic acidosis common:
    • Due to dehydration and the direct metabolic effects of ethanol
    • Profound lactic acidosis should prompt a search for other disorders such as sepsis, shock, seizures, and hypoxia
  • Positive urine and serum nitroprusside reaction tests for ketoacids:
    • May not reflect the severity of the underlying ketoacidosis, since BHB predominates and is not measured by this test
    • May become misleadingly more positive during treatment as more AcAc is produced
  • β–hydroxybutyrate assay, if available, is more accurate in detecting ketoacids:
    • BHB in ↑↑↑ in AKA, and only ↑ in DKA
• Electrolytes:
  • Decreased serum bicarbonate
  • Hypokalemia due to vomiting
  • Hypocalcemia
  • Hypophosphatemia (may worsen with treatment)
  • Hypomagnesemia:
    • Serum magnesium level may not accurately reflect total-body depletion
  • Initially, can potentially see hyperkalemia and/or hyperphosphatemia (despite total-body depletion):
    • Will correct with treatment of the acidosis
• Glucose:
  • May be reduced, normal, or mildly elevated
  • Should be monitored frequently, as with DKA
• Alcohol level may be negative
• BUN and creatinine mildly elevated due to dehydration, unless underlying renal disease
• Urinalysis:
  • Ketonuria without glucosuria
• Lipase (more specific)/amylase:
  • May be elevated with associated acute pancreatitis
• Osmolal gap:
  • May be elevated
  • Elevation >20 mOsm/kg should prompt evaluation for other ingestions (methanol and ethylene glycol)
  • Correct for ethanol level in osmolal gap by dividing ethanol level by 4.6
• LFTs:
  • May have mildly elevated LFTs
• Hemoglobin A1C: May help differentiate AKA vs. DKA:
  • Hyperglycemia >250 mg/dL less common in AKA:
    • A normal A1C makes AKA more likely
  • Euglycemia with elevated A1C increases likelihood of euglycemic DKA (e.g., due to use of SGLT2 [sodium-glucose cotransporter 2] inhibitor)
• CBC:
  • Mild leukocytosis: neither sensitive nor specific
  • Thrombocytopenia and anemia commonly due to chronic alcoholism

• May demonstrate changes in QT interval and/or QRS duration secondary to electrolyte abnormalities and acid–base disturbances
• Dysrhythmias may be seen, including atrial fibrillation and possible ventricular tachycardia, depending on electrolytes and underlying cardiac condition

• CXR if suspect associated pneumonia or aspiration
• Abdominal x-rays to rapidly assess for free air if an acute abdomen is present, followed by CT imaging
• CT head if associated trauma or unexplained altered mental status

Differential Diagnosis

• Elevated anion gap metabolic acidosis: ACAAT MUDPILES:
  • Alcoholic ketoacidosis
  • Cyanide, CO, H₂S, others
  • Acetaminophen:
    • Rare in acute ingestion
    • Rare in chronic ingestion
    • Fulminant hepatic failure
  • Antiretrovirals (NRTI)
  • Toluene
  • Methanol, metformin
  • Uremia
  • DKA:
    • Consider euglycemic DKA with use of an SGLT2 inhibitor
  • Paraldehyde, phenformin, propylene glycol
  • Iron, INH
  • Lactic acidosis
  • Ethylene glycol
  • Salicylate (aspirin), starvation ketosis
• Hypovolemia:
  • GI bleeding
  • Sepsis
• Abdominal pain, nausea, vomiting:
  • Pancreatitis
  • GI bleeding
  • Gastritis/esophagitis
  • Pneumonia
  • Hepatitis
  • Perforated ulcer
  • Alcohol withdrawal
  • DKA
  • Obstruction/Ileus
  • Spontaneous bacterial peritonitis
  • Viral illness

Pre Hospital

• Supportive measures including IV access with 0.9 NS, oxygen (if hypoxic), and cardiac monitoring
• Search for historical clues that may suggest other etiologies such as toxic ingestions or diabetic history, consider scene search
• Attend to other possible coexistent illnesses such as GI bleeding

Initial Stabilization/Therapy

• Cardiac monitor
• Supplemental oxygen (if hypoxic)
• Thiamine and dextrose if altered mental status
• Consider naloxone if altered mental status
• Initiate 0.9 NS IV fluids:
  • 1-L bolus
  • Fluid resuscitation as necessary
  • Promotes renal excretion of ketone bodies

Ed Treatment/Procedures

• Antiemetic for vomiting: ondansetron, prochlorperazine, or promethazine
• Benzodiazepines for symptoms of alcohol withdrawal
• Start dextrose-containing solutions (D₅NS):
  • More rapid resolution of the metabolic abnormalities than with saline alone
  • Rate higher than maintenance, as tolerated, until acidosis resolves
  • Avoid with significant hyperglycemia
  • Helps replete glycogen stores
  • Decreases production of ketone bodies by stimulating the production of endogenous insulin
• Thiamine repletion (IV) prior to, or shortly after, glucose administration to avoid precipitating Wernicke encephalopathy—do not delay glucose administration
• Sodium bicarbonate is not generally indicated:
  • No peer-reviewed evidence to support use
  • Consider in cases of severe acidemia (pH <7.0) with associated cardiovascular dysfunction or irritability
  • Must consider alternative/concomitant etiologies of severe acidemia
• Electrolyte replacement:
  • Hypokalemia occurs with treatment and should be anticipated
  • Magnesium replacement as indicated for both hypokalemia and hypomagnesemia
  • Hypophosphatemia may occur with treatment:
    • May not require repletion unless critically low
• Insulin is not indicated and may precipitate hypoglycemia, even in markedly hyperglycemic patients

Medication

• D₅₀W: 1 amp of 50% dextrose (25 g) IVP
• Lorazepam (benzodiazepine): 2 mg IV, with additional doses titrated to effect
• Ondansetron: 4–8 mg IVP
• Prochlorperazine: 5–10 mg IVP slowly (not >5 mg/min)
• Promethazine: 12.5–25 mg IM
• Thiamine: 100 mg IVP

Disposition

• Persistent metabolic acidosis
• Persistent signs of hypovolemia
• Persistent nausea and vomiting
• Abdominal pain of uncertain etiology
• Comorbid illness requiring admission for treatment
• Need for monitored bed due to electrolyte abnormalities requiring continued treatment

• Most patients will require observation:
  • May consider management in observation unit over 12–24 hr
• Tolerating oral fluids well
• Resolution of metabolic abnormalities
• No other associated illnesses requiring additional therapy

Follow-Up Recommendations

Counseling and referral for alcohol cessation resources

See Also

• Acidosis
• Diabetic Ketoacidosis