Continuing Education Activity

Alcoholic ketoacidosis (AKA) is a condition seen commonly in patients with alcohol use disorder or after a bout of heavy drinking. It is a clinical diagnosis with patients presenting with tachycardia, tachypnea, dehydration, agitation, and abdominal pain. This activity illustrates the evaluation and treatment of alcoholic ketoacidosis and explains the role of the interprofessional team in managing patients with this condition.

Objectives:

• Identify the etiology of alcoholic ketoacidosis.
• Describe the evaluation of alcoholic ketoacidosis.
• Review the fluid and volume resuscitation and correction of electrolyte abnormalities used in the treatment of alcoholic ketoacidosis.
• Summarize the importance of collaboration and communication among the interprofessional team to enhance the delivery of care for patients affected by alcoholic ketoacidosis.

Introduction

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.[1][2][3][4]

Etiology

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 formation of ketones and elevated gap ketoacidosis in the absence of diabetes.[5][6]

Epidemiology

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 in persons aged 20-60 years who are chronic alcohol abusers. Rarely, AKA occurs after a binge in persons who are not chronic drinkers.[7]

Pathophysiology

After about of heavy drinking, patients present in a dehydrated state 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 increased 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 an increased NADH/NAD+ ratio. 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.[8][9]

Toxicokinetics

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.

History and Physical

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.

• Tachycardia is common and due to several factors, including (1) several days of ethanol ingestion, which blocks antidiuretic hormone (ADH) and causes diuresis and increased urinary frequency, (2) nausea and vomiting, which result in decreased oral intake 1 to 3 days prior to presentation, (3) abdominal pain which exacerbates decreased oral intake. Patients develop acidosis, which causes an increase in respiratory rate and fluid loss.
• Dehydration causes an elevated heart rate and dry mucous membranes.  A degree of alcohol withdrawal and agitation are likely to be present, resulting in an increased heart rate as well.
• Patients often become tachypneic due to acidosis, dehydration, alcohol withdrawal, and abdominal pain.
• Abdominal pain is commonly present, although it may be secondary to alcoholic gastritis or pancreatitis. Rebound tenderness is not common, and the pain is commonly epigastric in nature. If rebound tenderness or peritoneal signs are present, another cause should be sought for the pain.  

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.

Evaluation

Laboratory analysis plays a major role in the evaluation of a patient with suspected alcoholic ketoacidosis. 

• Complete blood count (CBC) - The white blood cell count (WBC), hemoglobin, and hematocrit levels may be elevated in a dehydrated patient.  An elevated mean corpuscular volume (MCV) is often seen in patients with chronic alcohol use disorder.
• Metabolic Panel - The basic metabolic panel will likely be abnormal. Potassium levels can be normal or low, as dehydration and decreased oral intake frequently decrease the serum potassium level. Bicarbonate or HCO3 will likely be decreased with the presence of metabolic acidosis. The blood urea nitrogen (BUN) to creatinine ratio may be elevated if the patient is dehydrated. Glucose levels are usually mildly elevated but are not generally above 250 mg/dl. The initial glucose levels are more likely to be in the normal range.
• Beta-Hydroxybutyrate - The serum beta-hydroxybutyrate (B-OH) level will be significantly elevated. The degree of elevation of B-OH will be much greater than the elevation of lactate. If the lactate is greater than 4 mmol/L, another cause of the acidosis should be investigated. Serum alcohol levels are often low or absent.
• Arterial blood gas (ABG) - The blood gas analysis will most likely reveal a pH that is low or normal. There will be a metabolic acidosis present with a decreased HCO3 level. If the patient is capable, a respiratory alkalosis will be mounted by the patient. The presence of a mixed disorder may also be present as significant vomiting can cause metabolic alkalosis.
• Urinalysis - Urinalysis may show an elevated specific gravity as the patient is usually dehydrated. The specific gravity of the urine can be in the normal range if the patient has been drinking recently enough for the effect of antidiuretic hormone (ADH) inhibition to be still present or if the patient has been able to tolerate oral fluids over the last 24 hours, but no significant solid food.  
• Nitroprusside Test - The nitroprusside test can be used to document ketonuria by the detection of acetoacetate. It may be weakly positive despite the presence of significant ketosis as the urine nitroprusside test may vastly underestimate the presence of beta-hydroxybutyrate, which is the major ketoacid present in AKA. Glucosuria will likely be absent.

Other tests:

• Electrocardiogram (EKG) - The EKG will likely show sinus tachycardia, but atrial fibrillation or atrial flutter can be seen in a dehydrated patient with chronic alcohol abuse disorder and alcoholic ketoacidosis.
• The initial chest x-ray is usually negative.

Treatment / Management

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.[2][10][11]

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. 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 before 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. Antiemetics such as ondansetron or metoclopramide may also be given to control nausea and vomiting.

Differential Diagnosis

The differential diagnosis of alcoholic ketoacidosis includes all causes of high anion gap metabolic acidosis and are as follows:

• Diabetic ketoacidosis (DKA)
• Methanol toxicity
• Ethylene glycol toxicity
• Uremia
• Lactic acidosis
• Salicylate poisoning

Other differential diagnoses and often concomitantly present diseases that precipitate alcohol ketoacidosis in patients include: 

• Pancreatitis
• Peptic ulcer disease
• Acute cholecystitis
• Acute mesenteric ischemia
• Alcohol withdrawal

Prognosis

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.[12] 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. It should be used as an indicator of the severity of the disease.[13] Identifying these high-risk patients can help set the intensity of monitoring required for the patient to ensure optimal patient outcomes are achieved.

Complications

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 and 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 to treat AKA. Adequate and frequent clinical as well as biochemical monitoring is required to identify these potential complications early and prevent the morbidity associated with this condition.

Deterrence and Patient Education

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.

Enhancing Healthcare Team Outcomes

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. However, 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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References

1.

Ghimire P, Dhamoon AS. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 8, 2023. Ketoacidosis. [PubMed: 30521269]

2.

Gerrity RS, Pizon AF, King AM, Katz KD, Menke NB. A Patient With Alcoholic Ketoacidosis and Profound Lactemia. J Emerg Med. 2016 Oct;51(4):447-449. [PubMed: 27697197]

3.

Noor NM, Basavaraju K, Sharpstone D. Alcoholic ketoacidosis: a case report and review of the literature. Oxf Med Case Reports. 2016 Mar;2016(3):31-3. [PMC free article: PMC4776050] [PubMed: 26949539]

4.

Matsuzaki T, Shiraishi W, Iwanaga Y, Yamamoto A. Case of alcoholic ketoacidosis accompanied with severe hypoglycemia. J UOEH. 2015 Mar 01;37(1):43-7. [PubMed: 25787101]

5.

Suzuki K, Tamai Y, Urade S, Ino K, Sugawara Y, Katayama N, Hoshino T. Alcoholic ketoacidosis that developed with a hypoglycemic attack after eating a high-fat meal. Acute Med Surg. 2014 Apr;1(2):109-114. [PMC free article: PMC5997211] [PubMed: 29930832]

6.

Heltø K. [Alcoholic ketoacidosis and lactic acidosis]. Ugeskr Laeger. 2009 Jan 26;171(5):318-9. [PubMed: 19176163]

7.

Yokoyama A, Yokoyama T, Mizukami T, Matsui T, Shiraishi K, Kimura M, Matsushita S, Higuchi S, Maruyama K. Alcoholic Ketosis: Prevalence, Determinants, and Ketohepatitis in Japanese Alcoholic Men. Alcohol Alcohol. 2014 Nov;49(6):618-25. [PubMed: 25085997]

8.

McGuire LC, Cruickshank AM, Munro PT. Alcoholic ketoacidosis. Emerg Med J. 2006 Jun;23(6):417-20. [PMC free article: PMC2564331] [PubMed: 16714496]

9.

Caspar CB, Risti B, Iten PX, Jost R, Russi EW, Speich R. [Alcoholic ketoacidosis]. Schweiz Med Wochenschr. 1993 Oct 16;123(41):1929-34. [PubMed: 8259474]

10.

Allison MG, McCurdy MT. Alcoholic metabolic emergencies. Emerg Med Clin North Am. 2014 May;32(2):293-301. [PubMed: 24766933]

11.

Chandrasekara H, Fernando P, Danjuma M, Jayawarna C. Ketoacidosis is not always due to diabetes. BMJ Case Rep. 2014 Feb 25;2014 [PMC free article: PMC3939410] [PubMed: 24569261]

12.

Jang HN, Park HJ, Cho HS, Bae E, Lee TW, Chang SH, Park DJ. The logistic organ dysfunction system score predicts the prognosis of patients with alcoholic ketoacidosis. Ren Fail. 2018 Nov;40(1):693-699. [PMC free article: PMC7011874] [PubMed: 30741615]

13.

Iten PX, Meier M. Beta-hydroxybutyric acid--an indicator for an alcoholic ketoacidosis as cause of death in deceased alcohol abusers. J Forensic Sci. 2000 May;45(3):624-32. [PubMed: 10855969]

Disclosure: Robert Howard declares no relevant financial relationships with ineligible companies.

Disclosure: Syed Rizwan Bokhari declares no relevant financial relationships with ineligible companies.