Author:
Nicholas M.V.Schulack
KetanPatel
Ross P.Berkeley
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 mand ate 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 mand ates 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)
History
Chronic alcohol use:
- Recent binge
- Abrupt cessation
Physical Exam
- 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 & Interpretation
Lab
- 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:
- 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
ECG
- 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
Imaging
- 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:
- Abdominal pain, nausea, vomiting:
- Pancreatitis
- GI bleeding
- Gastritis/esophagitis
- Pneumonia
- Hepatitis
- Perforated ulcer
- Alcohol withdrawal
- DKA
- Obstruction/Ileus
- Spontaneous bacterial peritonitis
- Viral illness
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 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
Admission Criteria
- 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
Discharge Criteria
- 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
- AllisonMG, McCurdyMT. Alcoholic metabolic emergencies . Emerg Med Clin North Am. 2014;32(2):293-301.
- FlanneryAH, AdkinsDA, CookAM. 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.
- SchabelmanE, KuoD. Glucose before thiamine for Wernicke encephalopathy: a literature review . J Emerg Med. 2012;42(4):488-494.
- SorkinT, SheppardMN. 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.
See Also (Topic, Algorithm, Electronic Media Element)