Alcoholic Ketoacidosis

Alcoholic ketoacidosis is a high anion gap metabolic acidosis caused by ketone accumulation, mainly beta hydroxybutyrate, in a person with heavy alcohol use and poor oral intake. Glucose is usually normal, low or mildly raised.

Epidemiology. It is common in chronic alcohol use disorder, usually after a binge followed by vomiting and several days without food. It is frequently missed and often mixed with other disorders.

Causes and associations. Binge drinking followed by vomiting, abdominal pain or pancreatitis, starvation and dehydration. Common co-existing problems are hypokalaemia, hypomagnesaemia, hypophosphataemia, hypoglycaemia, thiamine deficiency, alcohol withdrawal, liver disease, gastritis and infection.

Pathophysiology. Low insulin from reduced intake, with high glucagon, cortisol and catecholamines, drives lipolysis. Ethanol metabolism raises the NADH to NAD ratio, which shifts acetoacetate to beta hydroxybutyrate. Volume depletion reduces renal ketone excretion. Because most ketone is beta hydroxybutyrate, urine nitroprusside tests may be weak or negative.

Presentation is nausea, vomiting, abdominal pain, deep breathing, dehydration and tachycardia, usually 1 to 3 days after the last drink. Mental state may be normal or altered. Signs of chronic liver disease, withdrawal or pancreatitis may be present.

Red flags.

• Severe acidosis (pH under 7.1) or shock.
• Altered consciousness, which may reflect Wernicke encephalopathy, hypoglycaemia or withdrawal.
• Hypokalaemia, hypomagnesaemia or hypophosphataemia.
• Seizures, hallucinations or fever, and suspected toxic alcohol ingestion.

Measure beta hydroxybutyrate, venous gas, bicarbonate, anion gap, lactate, glucose, electrolytes including magnesium and phosphate, urea, creatinine, liver tests, lipase, osmolality (osmolar gap), ethanol level, salicylate and paracetamol levels and ECG. Send cultures when infection is suspected.

Differential diagnosis.

• Diabetic ketoacidosis (glucose usually over 14 mmol/L) and euglycaemic ketoacidosis from SGLT2 inhibitors.
• Toxic alcohols (methanol, ethylene glycol), with an osmolar gap.
• Lactic acidosis, salicylate toxicity and starvation ketosis.
• Pancreatitis and gastrointestinal bleeding.

Thiamine first. Thiamine 200 to 500 mg IV every 8 hours for 3 days when Wernicke encephalopathy is possible, otherwise 100 mg IV daily. Give it before or with the first dextrose.

Fluids and glucose. 0.9% sodium chloride 1 L IV over 1 hour, then 1 L over 2 to 4 hours, repeated as needed, with 5 to 10% dextrose added early. Dextrose is the main treatment because it raises insulin and suppresses ketogenesis. Correct hypoglycaemia with dextrose 25 g IV (50 mL of 50%).

Insulin. Not usually needed. Reserve it for glucose over 14 mmol/L with features of diabetic ketoacidosis, using 0.05 to 0.1 units/kg/h only after potassium is over 3.3 mmol/L and with dextrose running.

Electrolytes.

• Potassium chloride 20 to 40 mmol in each litre of fluid, with a maximum of 20 mmol/h peripherally. Delay insulin if potassium is under 3.3 mmol/L.
• Magnesium sulphate 2 g (8 mmol) IV over 2 hours when magnesium is low, repeated as needed.
• Phosphate replacement when under 0.3 mmol/L or with muscle weakness or respiratory failure, given slowly with monitoring and at a reduced dose in renal impairment.
• Sodium bicarbonate only if pH is under 6.9.

Withdrawal.

• Diazepam 10 to 20 mg orally or IV every 1 to 2 hours until settled, then symptom directed, or chlordiazepoxide 20 to 30 mg orally four times daily reducing over 5 to 7 days.
• Lorazepam 1 to 2 mg orally or IV every 4 to 6 hours is preferred in liver impairment and older adults.
• Monitor sedation and respiration.

Antiemetic and gastric protection. Ondansetron 4 to 8 mg IV every 8 hours (maximum 16 mg a dose, and 8 mg daily in severe liver impairment) with QT monitoring, and a proton pump inhibitor if bleeding or gastritis is likely.

Monitoring. Glucose hourly at first, venous gas and electrolytes every 2 to 4 hours, beta hydroxybutyrate, urine output, mental state and withdrawal scores. Acidosis should resolve within 12 to 24 hours, and failure to improve suggests another cause.

Referral and escalation. High dependency for pH under 7.1, shock, seizures, severe withdrawal or altered consciousness. Alcohol support service before discharge.

Special groups. In liver disease use lorazepam and avoid long acting benzodiazepines. In renal impairment reduce phosphate and potassium doses.