Alcoholic Ketoacidosis

Basics

Description

  • Metabolic acidosis with ketosis in chronic alcohol use
  • 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 predominant production of β-hydroxybutyrate (BHB) over acetoacetate (AcAc)
  • Antidiuretic hormone inhibited by alcohol, leading to reduced water reabsorption and reduced ketoacid urinary excretion

Etiology

  • Malnourished, chronic alcohol abusers following a recent episode of heavy alcohol consumption:
    • Followed by nausea, vomiting, or abdominal pain
    • Resulting in sudden cessation of alcohol ingestion and caloric intake
  • Presentation usually occurs within 12–72 hr

Diagnosis

Signs And Symptoms

  • Nausea, vomiting, and abdominal pain: Most common symptoms:
    • Common: Epigastric pain
    • Uncommon: Rebound tenderness, abdominal distension, hypoactive bowel sounds
  • Volume depletion due to poor oral intake and vomiting and reduced renal reabsorption of water (ADH inhibited)
  • Tachycardia (common) due to:
    • Dehydration, orthostasis
    • Concurrent alcohol withdrawal
  • Tachypnea (common):
    • Kussmaul respirations with significant acidosis
  • Hypotension
  • Hypothermia
  • Decreased urinary output from hypovolemia
  • Altered mental status, ataxia, and oculomotor dysfunction – signs of Wernicke encephalopathy
  • Mental status:
    • Minimally altered as a result of hypovolemia and possibly intoxication
    • If altered mental status consider other associated conditions such as:
      • Head injury, cerebrovascular accident (CVA), or intracranial hemorrhage
      • Hypoglycemia
      • Alcohol withdrawal
      • Encephalopathy
      • Toxins
  • Visual disturbances:
    • Case reports of isolated visual disturbances with AKA (more common with severe acidosis)
    • Consider evaluation for toxic alcohol ingestion

History

Chronic alcohol use:

  • Recent alcohol binge, minimal other oral intake
  • Nausea, vomiting, and abdominal pain with subsequent sudden cessation of alcohol intake

Physical Exam

  • Findings of dehydration most common: Tachycardia, tachypnea, hypotension
  • Abdominal tenderness without rebound or guarding
  • May have ketotic odor
  • Tachypnea, Kussmaul respirations
  • Findings of liver disease: Ascites, jaundice, palmar erythema, spider angioma

Essential Workup

  • Increased anion gap metabolic acidosis:
    • Venous blood gas may be utilized in lieu of arterial
    • Differentiate from other causes of anion gap metabolic acidosis

Diagnostic Tests And Interpretation

Lab

  • Acid–base disturbance:
    • Increased anion gap metabolic acidosis
    • Mixed acid–base disturbance more common (seen in 76%):
      • 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 consideration of other disorders such as sepsis, shock, seizures, and hypoxia
  • Electrolytes:
    • Decreased serum bicarbonate
    • Hypokalemia (GI and renal losses)
    • Hyponatremia (vomiting and volume loss)
    • Hypocalcemia
    • Hypophosphatemia
    • Hypomagnesemia (level may not accurately reflect total-body depletion)
    • Initially, can potentially see hyperkalemia and/or hyperphosphatemia:
      • Will correct with treatment of the acidosis
  • Glucose:
    • May be reduced, normal, or mildly elevated
    • Typically, less than 275 mg/dL
    • 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
    • Urine ketones can be falsely negative
    • Nitroprusside reaction test of urine detects AcAc, but not β-hydroxybutyrate which predominates in AKA:
      • May become misleadingly more positive during treatment as more AcAc is produced
    • Serum β-hydroxybutyrate assay, if available, is more accurate in detecting ketoacids
      • BHB is ↑↑↑ in AKA, and only ↑ in DKA
  • Lipase (more specific)/amylase:
    • May be elevated due to acute pancreatitis
  • Osmolar gap:
    • May be elevated
    • Elevation >20 mOsm/kg should prompt consideration of other ingestions (methanol and ethylene glycol)
  • Mildly elevated LFTs
  • Hemoglobin A1C: Help differentiate AKA vs DKA:
    • Hyperglycemia less common in AKA:
      • A normal A1C makes AKA more likely
    • Euglycemia with elevated A1C increases likelihood of euglycemic DKA
  • CBC:
    • Mild leukocytosis: Neither sensitive nor specific
    • Thrombocytopenia and anemia may be commonly seen due to chronic alcohol abuse:
      • Consider GI bleed

Ecg

  • Prolonged QTc, U waves, flattened T waves
  • 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 (electrolytes or underlying cardiac condition)

Imaging

  • CXR if suspected 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 (large volume, liver failure)
    • Antiretrovirals (NRTI)
    • Toluene
    • Methanol, metformin
    • Uremia
    • Diabetic ketoacidosis
    • Paraldehyde, phenformin, propylene glycol
    • Iron, INH
    • Lactic acidosis
    • Ethylene glycol
    • Salicylate (aspirin), starvation ketosis
  • Hypovolemia (GI bleed, sepsis)
  • Abdominal pain, nausea, vomiting:
    • Pancreatitis
    • GI bleeding
    • Gastritis/esophagitis
    • Hepatitis
    • Perforated ulcer
    • Alcohol withdrawal
    • DKA
    • Obstruction/Ileus
    • Spontaneous bacterial peritonitis
    • Viral illness

Treatment

Prehospital

  • 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

Initial Stabilization/Therapy

  • Cardiac monitor
  • Supplemental oxygen (if hypoxic)
  • Thiamine followed by dextrose
  • Consider naloxone if altered mental status
  • Crystalloid:
    • Initiate 0.9 NS IV 1 L bolus
    • Continue IV fluid resuscitation as necessary
    • Promotes renal excretion of ketone bodies

Ed Treatment/Procedures

  • Antiemetic for vomiting: Ondansetron, prochlorperazine, or droperidol
  • Benzodiazepines for symptoms of alcohol withdrawal
  • Start infusion of dextrose-containing solution (D5NS):
    • Repletes glucose, increases endogenous insulin secretion, decreased glucagon secretion resulting in reduction of ketone synthesis causing AKA
    • Promotes more rapid resolution of metabolic abnormalities than with saline alone
    • Rate higher than maintenance
    • Switch to D5 1/2NS once electrolyte derangements managed and fluid resuscitated
    • Stop when serum bicarb 18–20 mEq/L with improved oral intake
  • Thiamine repletion (100–200 mg IV) prior to, or shortly after, glucose administration to avoid precipitating Wernicke encephalopathy – do not delay dextrose administration
  • Thiamine 500 mg IV Q8H for Wernicke’s
  • Sodium bicarbonate is generally not indicated:
    • No peer-reviewed evidence to support use
    • May consider in cases of severe acidemia (pH <7.0) with associated cardiovascular dysfunction
    • Severe acidemia should prompt consideration of alternative/concomitant etiologies
  • Electrolyte replacement:
    • Hypokalemia precipitated by endogenous insulin release (once dextrose started)
    • Magnesium replacement as indicated
    • Hypophosphatemia may occur with treatment
    • Expect rapid decline in 1st 24 hr as acidosis resolves
  • Insulin is generally not indicated and may precipitate hypoglycemia

Medication

  • Dextrose (for hypoglycemia): 25 g IV:
    • D50W: 1 ampule (50 mL) of 50% dextrose IVP
    • D10W: 250 mL of 10% dextrose IV wide open
  • Thiamine: 100 mg IVP prophylaxis, 500 mg IVP for Wernicke encephalopathy
  • Lorazepam (benzodiazepine): 2 mg IV, with additional doses titrated to effect
  • Ondansetron: 4–8 mg IVP
  • Prochlorperazine: 5–10 mg IVP slowly
  • Droperidol: 0.625–2.5 mg IVP slowly
  • Naloxone: 0.4–2 mg IVP if suspected opioid toxicity, titrated to respiratory rate

Follow-Up

Disposition

Admission Criteria

  • Persistent metabolic acidosis
  • Persistent signs of hypovolemia
  • Persistent nausea and vomiting
  • Abdominal pain of uncertain etiology
  • Comorbid illness requiring admission for treatment
  • Significant electrolyte abnormalities requiring continued cardiac monitoring and treatment

Discharge Criteria

  • Most require observation for 12–24 hr
  • Tolerating oral fluids well
  • Resolution of metabolic abnormalities
  • No other associated illnesses needing treatment

Follow-Up Recommendations

  • Counseling and referral for alcohol cessation resources

Complications

  • Dysrhythmias and heart failure
  • Decompensation due to untreated hypothermia, rhabdomyolysis, pancreatitis, infection, seizure, and delirium tremens

Pearls And Pitfalls

  • Initial volume resuscitation with NS as necessary then switch to balanced fluids
  • Continue aggressive volume repletion with dextrose-containing fluid
  • Easily missed diagnosis, can be confused with DKA (euglycemic DKA/hyperglycemic AKA)
  • Thiamine repletion before dextrose to prevent Wernicke–Korsakoff precipitation
  • Monitor electrolytes before and after treatment
  • Unrecognized increased osmolar gap
  • Avoid insulin and sodium bicarbonate
  • Inadequate monitoring of glucose levels
  • Failure to recognize initial electrolyte abnormalities and electrolyte shifts caused by treatment
  • Place on cardiac monitor (alcoholic cardiomyopathy, dysrhythmias, electrolytes):
    • Cases of sudden death in AKA

Additional Readings

  1. Allison MG, McCurdy MT. Alcoholic metabolic emergencies. Emerg Med Clin North Am. 2014;32(2):293–301.  [PMID:24766933]
  2. Cartwright MM, Hajja W, Al-Khatib S, et al. Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes. Crit Care Clin. 2012;28(4):601–631.  [PMID:22998993]
  3. Flannery AH, Adkins DA, Cook AM. Unpeeling the evidence for the banana bag: Evidence-based recommendations for the management of alcohol-associated vitamin and electrolyte deficiencies in the ICU. Crit Care Med. 2016;44(8):1545–1552.  [PMID:27002274]
  4. Long B, Lentz S, Gottlieb M. Alcoholic ketoacidosis: Etiologies, evaluation, and management. J Emerg Med. 2021;61(6):658–665.  [PMID:34711442]
  5. Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: A literature review. J Emerg Med. 2012;42(4):488–494.  [PMID:22104258]
  6. Sorkin T, Sheppard MN. Sudden unexplained death in alcohol misuse (SUDAM) patients have different characteristics to those who died from sudden arrhythmic death syndrome (SADS). Forensic Sci Med Pathol. 2017;13(3):278–283.  [PMID:28668989]

See Also (Topic, Algorithm, Electronic Media Element)

Authors

Rebeka Stephen

Ketan Patel

Ross P. Berkeley