Alcoholic ketoacidosis (AKA) is a clinical syndrome seen mostly in patients with chronic alcohol use disorder and frequently seen in patients who binge drink. Typical patients are usually chronic drinkers who are unable to tolerate oral nutrition for a 1 to 3 day period. Patients often have a recent bout of heavy drinking before the period of relative starvation, with persistent vomiting and abdominal pain contributing to their inability to tolerate PO intake.
The etiology of Alcoholic ketoacidosis stems from the patient's inability to ingest, absorb and utilize glucose from their diet. The vomiting and nausea prevent adequate solute intake from the gastrointestinal tract. The alcohol further depresses gluconeogenesis in the body and keeps blood sugar levels low. An anxiety state and alcohol withdrawal further exacerbate the patient's ability to eat. The lack of nutrients other than alcohol causes the creation of ketones and elevated gap ketoacidosis in the absence of diabetes.
The prevalence correlates with the incidence of alcohol abuse in a community. No racial or sexual differences in incidence are noted. AKA can occur in adults of any age; it more often occurs persons aged 20-60 years who are chronic alcohol abusers. Rarely, AKA occurs after a binge in persons who are not chronic drinkers.
Patients present in a dehydrated state after a bout of heavy drinking and then an ongoing lack of oral intake. This period of poor PO intake lasts from 1 to 3 days. The pathophysiology of AKA starts with low glycogen stores and a lack of oral food intake, which shifts the metabolism from Carbohydrates to fats and lipids. Decreased oral intake causes decreased insulin levels and an increase in counter-regulatory hormones such as cortisol, glucagon, and epinephrine. The lack of insulin also allows an increase in the activity of hormone-sensitive lipase. These changes are further enhanced as ethanol is metabolized to acetaldehyde and acetyl-CoA leading to the NADH/NAD+ ratio to increase. The resultant increased NADH/NAD+ ratio increases lipid metabolism. All of these changes increase the breakdown of lipids to ketoacids. The elevated NADH/NAD+ ratio further encourages the conversion of acetoacetate to beta-hydroxybutyrate. Beta-hydroxybutyrate is the predominant ketoacid in AKA. Ketoacids further accumulate as dehydration and decreased renal perfusion limit the removal of ketoacids. The differential diagnosis includes other causes of an increased anion gap metabolic acidosis. In a patient with diabetes, there must also be a consideration of diabetic ketoacidosis (DKA). A hemoglobin A1C may help in that consideration as well.
The toxicokinetics that are pertinent to the diagnosis of AKA include the rate of alcohol oxidation in the body. Ethyl alcohol oxidizes at a rate of 20 to 25 mg/dL per hour in most individuals. The accompanying lack of alcohol in the patient's body and the fact that for some time the only source of calories that a patient has is ethanol both contribute to the clinical syndrome that we see.
The diagnosis of AKA is made on a clinical basis. Patients are usually tachycardic, dehydrated, tachypneic, present with abdominal pain and are often agitated. Most patients will often have a ketone odor on their breath.
Neurologically, patients are often agitated, but may occasionally present lethargic on examination. Alcohol withdrawal, in combination with nausea and vomiting, makes most patients agitated. However, if an AKA patient is lethargic or comatose, an alternative cause should be sought.
Laboratory analysis plays a major role in the evaluation of a patient with suspected alcoholic ketoacidosis.
AKA should be diagnosed clinically. The patients need fluid resuscitation, close monitoring of electrolytes and treatment to prevent alcohol withdrawal. They also need to have a complete history and physical for a complete differential diagnosis. 
The diagnosis of AKA is the first step in treatment. The patient should have blood glucose checked on the initial presentation. The next important step in the management of AKA is to give isotonic fluid resuscitation. The usual choice of fluid is normal saline with dextrose. The dextrose is required to break the cycle of ketogenesis and increase insulin secretion. The dextrose will also increase glycogen stores and diminish counterregulatory hormone levels. It is essential to administer thiamine prior to any glucose administration to avoid Wernicke's encephalopathy preci[itation. If severe hypokalemia is present dextrose containing fluids can be held until potassium levels are normalized. Other electrolyte abnormalities concomitantly present with alcohol abuse and poor oral intake include hypomagnesemia and hypophosphatemia. Magnesium and phosphate levels should be measured and repleted if the serum levels are found low.
Intravenous benzodiazepines can be administered based on the risk of seizures from impending alcohol withdrawal. Antiemetic such as ondansetron or metoclopramide may also be given to control nausea and vomiting.
The differential diagnosis of alcoholic ketoacidosis includes all causes of high anion gap metabolic acidosis and are as follows:
Other differential diagnoses and often concomitantly present diseases that precipitate alcohol ketoacidosis in patients include:
In general, the prognosis for a patient presenting with AKA is good as long as the condition is identified and treated early. Delayed presentation or diagnosis may result in end-organ damage such as acute renal failure with tubular necrosis. The long-term prognosis of patients diagnosed with AKA depends on the severity of their underlying alcohol abuse disorder rather than AKA itself. The major cause of morbidity and mortality in patients diagnosed with AKA is under-recognition of concomitant diseases (that may have precipitated the AKA, to begin with). These include acute pancreatitis, gastrointestinal bleeding, and alcohol withdrawal. Mortality specifically due to AKA has been linked to the severity of serum beta-hydroxybutyric acid in some studies and should be used as an indicator of the severity of the disease. Identifying these high-risk patients can help set the intensity of monitoring required for the patient to ensure optimal patient outcomes are achieved.
Complications associated with AKA can occur with delayed diagnosis or under-resuscitation and failure to end ketogenesis. These include hypovolemic shock and cardiac arrest. It is essential to manage other electrolyte disturbances as well as alcohol withdrawal to prevent seizures, and the dreaded delirium tremens. Often patients with chronic alcohol abuse disorder will have non-ischemic cardiomyopathy, which may become evident as pulmonary edema on fluid resuscitation for the treatment of AKA. Adequate and frequent clinical as well as biochemical monitoring is required to identify these potential complications early and prevent the morbidity associated with it.
After the treatment of AKA, it is important to counsel the patients on alcohol abuse disorder and to refer them to alcohol abuse rehabilitation programs. Due to the limited community resources, often patients find themselves without adequate rehabilitation options as well. It is important for inpatient providers to communicate the diagnosis of AKA and associated alcohol abuse disorder with outpatient primary care providers for the patient to ensure the patient is linked with all available resources to help him/her with their alcohol abuse disorder.
Alcoholic ketoacidosis can affect many organ systems and is best managed by an interprofessional team of healthcare workers including a nurse and clinician. The key is to differentiate alcoholic ketoacidosis from starvation and diabetic-ketoacidosis (DKA). Starvation ketosis is more common than AKA, but starvation ketosis is not often complicated by acidosis. Diabetic ketoacidosis can be confused with AKA. The glucose levels in AKA are rarely above 250 mg/dL. In a hyperglycemic patient, hemoglobin A1C should also be ordered to assess for the presence of uncontrolled blood glucose levels. Also, in AKA, the beta-hydroxybutyrate to acetoacetate ratio will be much higher with ratios of up to 8:1, whereas in DKA beta-hydroxybutyrate to acetoacetate ratios are about 3:1.
Efficient and timely management can lead to enhanced patient outcomes in patients with AKA. After adequate treatment, it is equally essential to refer the patient to alcohol abuse rehabilitation programs to prevent recurrence and long-term irreversible damage from alcohol abuse.
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