Acetone breath: causes and examination

Acetone breath is a characteristic "fruity" or "lacquer-acetone" odor of exhaled air, most often associated with the accumulation of ketone bodies in the blood and tissues. This symptom can occur in healthy individuals during physiological ketosis due to fasting or a low-carbohydrate diet, as well as in dangerous conditions, including diabetic ketoacidosis, alcoholic ketoacidosis, fasting ketoacidosis, and euglycemic ketoacidosis due to the use of sodium-glucose cotransporter-2 inhibitors. [1]

The clinical significance of the symptom is determined by the context. In a person on a ketogenic diet, a sweetish odor may be expected and reversible, but its sudden onset in a patient with diabetes, especially along with thirst, polyuria, nausea, abdominal pain, rapid breathing, and weakness, requires urgent evaluation for ketoacidosis. [2]

The mechanism of odor is related to the volatility of acetone, one of three ketone bodies. Acetone concentration in exhaled air correlates with the severity of ketosis and can serve as a noninvasive biomarker of metabolic state. [3]

It is important to remember that the “acetone” smell is not a mandatory sign of ketoacidosis and its absence does not exclude a severe form of metabolic disorder, so the decision is always based on laboratory data and clinical examination. [4]

Epidemiology

Diabetic ketoacidosis is more common in type 1 diabetes and can be the first manifestation of the disease in adolescents and young adults. It also occurs in type 2 diabetes, especially in the presence of triggers such as infection and insulin deficiency. Clinical guidelines emphasize the need for regular glucose and ketone monitoring in children and adolescents at risk. [5]

Alcoholic ketoacidosis is primarily observed in people with chronic alcohol consumption following periods of binge drinking and reduced food intake. It is often associated with thiamine deficiency and electrolyte imbalance. [6]

Hunger ketoacidosis is less common but can occur in individuals with prolonged caloric insufficiency, significant weight loss, breastfeeding women, and during severe stress or intercurrent illnesses. In practice, its recognition is difficult and requires exclusion of other causes of metabolic acidosis. [7]

Euglycemic ketoacidosis has been reported in patients receiving sodium-glucose cotransporter-2 inhibitors, most often in combination with low carbohydrate intake, infection, surgery, or dehydration. Although the absolute risk is low, clinicians are advised to teach "sick day rules" and temporarily discontinue the drug in risky situations. [8]

Reasons

The underlying cause of acetone odor is ketogenesis—the increased formation of ketone bodies from fatty acids due to a lack of effective insulin action. Key conditions include diabetic ketoacidosis, starvation ketoacidosis, alcoholic ketoacidosis, and euglycemic ketoacidosis, in which glucose levels may remain low. [9]

Diabetic ketoacidosis develops with a relative or absolute insulin deficiency and excessive counter-insulin hormone activity. Dehydration, hyperventilation, abdominal pain, nausea, and vomiting are typical, and a fruity breath odor is possible. [10]

Alcoholic ketoacidosis occurs hours to days after cessation of binge drinking with low carbohydrate intake and vomiting; it is characterized by high anion gap metabolic acidosis, hypovolemia, and thiamine deficiency.[11]

Hunger ketoacidosis develops with prolonged calorie restriction, acute illnesses, or severe hyperemesis gravidarum; severe cases with a threat to both mother and fetus have been described in pregnancy. [12]

Risk factors

Risk factors for diabetic ketoacidosis include insulin omissions, infection, acute surgical procedures, trauma, and the onset of diabetes. Pregnant women have an increased risk, with up to 30% of cases being euglycemic. [13]

Alcoholic ketoacidosis is characterized by chronic alcohol consumption, vomiting, and malnutrition, accompanied by thiamine deficiency and impaired carbohydrate metabolism. [14]

Hunger ketoacidosis is caused by prolonged fasting, low-carbohydrate diets without medical supervision, fever, lactation, severe infections and stress, and, in pregnancy, vomiting and poor nutrition. [15]

Triggers associated with the use of sodium-glucose cotransporter type 2 inhibitors include carbohydrate restriction, dehydration, infection, and insulin dose reduction; the drug is temporarily discontinued if there is a risk of ketoacidosis. [16]

Pathogenesis

Insufficient insulin action activates lipolysis, increasing the flow of free fatty acids into the liver and their beta-oxidation. Excess acetyl-coenzyme A condenses into ketone bodies: beta-hydroxybutyrate, acetoacetate, and acetone. The latter is volatile and is responsible for the characteristic odor. [17]

In diabetic ketoacidosis, the accumulation of ketone acids leads to a high anion gap metabolic acidosis, compensated for by deep, rapid Kussmaul breathing. The severity of the condition is determined by volume dehydration, electrolyte shifts, and the trigger. [18]

In alcoholic ketoacidosis, thiamine deficiency impairs oxidative metabolism and carbohydrate deficiency promotes ketogenesis, leading to treatment based on glucose administration along with thiamine and volume replenishment.[19]

Euglycemic ketoacidosis is associated with a decrease in the insulin-glucagon ratio in the presence of sodium-glucose cotransporter type 2 inhibitors, which increases lipolysis and ketogenesis even with moderate glycemia. [20]

Symptoms

Key signs of ketoacidosis include thirst, polyuria, weakness, nausea, vomiting, abdominal pain, rapid, deep breathing, and sometimes confusion. Some patients experience a fruity odor from the mouth. The absence of odor does not rule out the diagnosis. [21]

On examination, tachycardia, hypotension, signs of dehydration, and Kussmaul respirations may be present. Some patients experience hypothermia or fever with an infectious trigger. [22]

Alcoholic ketoacidosis is typically characterized by symptoms of alcohol withdrawal, vomiting, abdominal pain, sometimes a decrease in temperature, and laboratory findings of ketosis with normal or low glucose. [23]

Starvation ketoacidosis is characterized by signs of nutritional deficiency, low blood pressure and pulse, weakness; rapid decompensation is possible in pregnancy. [24]

Forms and stages

Based on the causative factor, the following are distinguished: diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis, euglycemic ketoacidosis, including drug-induced ketoacidosis. Rapid primary stratification is important for clinical practice. [25]

Severity is assessed based on the degree of acidosis, blood ketone levels, state of consciousness, severity of dehydration and electrolyte disturbances; formal scales are used in emergency department protocols. [26]

In children and adolescents, pediatric algorithms are used that take into account the risk of cerebral edema and the need for careful rehydration, as well as systematic monitoring of glucose and ketones. [27]

In the euglycemic variant, the clinical picture of acidosis with moderate glycemia is alarming, which requires mandatory measurement of beta-hydroxybutyrate and blood gases. [28]

Complications and consequences

Untreated ketoacidosis can lead to hypovolemic shock, cardiac arrhythmia, cerebral edema, acute renal failure, and high mortality. Early recognition and standardized therapy reduce the risk of complications. [29]

Alcoholic ketoacidosis without correction of thiamine deficiency can be complicated by Wernicke's encephalopathy and cardiomyopathy. Therefore, thiamine is administered before glucose. [30]

In pregnancy, ketoacidosis is associated with a threat to the fetus, including intrauterine death, which requires immediate therapeutic tactics and multidisciplinary monitoring. [31]

Even with a favorable outcome, severe ketoacidosis can lead to prolonged asthenia, electrolyte imbalance, and the need for correction of hypoglycemic therapy. [32]

Diagnostics

The basic volume includes measurement of capillary or venous glucose, blood ketones with priority for beta-hydroxybutyrate, blood gases or venous bicarbonate, electrolytes with calculation of anion gap, creatinine, urea, general urine analysis, and, if necessary, osmolar gap. [33]

Physical examination focuses on Kussmaul's breathing, signs of dehydration, and a "fruity" odor, but the diagnostic decision is always confirmed laboratory testing. In children and adolescents, assessment is conducted according to pediatric society protocols. [34]

If alcoholic ketoacidosis is suspected, glucose levels, ketones, acid-base balance, electrolytes, and, if necessary, markers of alcohol consumption are determined, and thiamine replenishment is necessarily planned. [35]

In patients receiving sodium-glucose cotransporter type 2 inhibitors, the possibility of euglycemia should be considered and ketones should be measured even in moderate glycemia. Diagnostic vigilance is especially important during pregnancy. [36]

Table: Laboratory guidelines for conditions with an "acetone" odor

Parameter	Diabetic ketoacidosis	Euglycemic ketoacidosis	Alcoholic ketoacidosis	Hunger ketoacidosis
Glucose	Usually elevated	Normal or moderately elevated	Normal, low or moderately elevated	Normal or low
Beta-hydroxybutyrate	Increased	Increased	Increased	Increased
Acid-base balance	High anion gap metabolic acidosis	Likewise	Likewise	Often more moderate acidosis
Key signs	Thirst, polyuria, Kussmaul	The same spectrum with moderate glycemia	Vomiting, thiamine deficiency	Nutritional deficiencies, weight loss

Based on contemporary reviews and consensus. [37]

Differential diagnosis

The "acetone" odor associated with ketosis should be distinguished from other types of halitosis: liver "fetor" associated with liver failure, an ammonia-like odor associated with uremia, and a putrid odor associated with oral infections and ENT diseases. Laboratory tests can help clarify the cause. [38]

In cases of unclear metabolic acidosis, toxic causes are considered, including methanol and ethylene glycol, lactic acidosis, salicylate intoxication, and sepsis. The diagnosis is guided by the anion and osmolar gaps, medical history, and toxicology screening results. [39]

In pregnant women, it is necessary to differentiate ketoacidosis from hyperemesis gravidarum, infectious complications and acute surgical conditions; clinical and laboratory assessment determine the tactics. [40]

Finally, one should not forget about functional and dietary factors: physiological ketosis against the background of carbohydrate restriction is accompanied by the smell of acetone without severe acidosis and is stopped by normalizing the diet. [41]

Treatment

Basic principles

Treatment is aimed at correcting circulating blood volume, electrolytes, and acid-base balance, eliminating the trigger, and, if necessary, administering insulin or carbohydrates. Therapy depends on the type of ketoacidosis and its severity. [42]

Diabetic ketoacidosis. Stepwise rehydration with isotonic solutions, intravenous insulin administration according to a protocol with titration based on glycemia and ketones, correction of potassium and other electrolytes, and identification and treatment of the trigger are performed. In adolescents, pediatric protocols are followed and caution is exercised due to the risk of cerebral edema. [43]

Alcoholic ketoacidosis. The key is to administer thiamine before glucose, then administer glucose solutions and correct volume and electrolytes; insulin is usually not required. Monitoring for alcohol withdrawal syndrome and concomitant infections is essential. [44]

Starvation ketoacidosis. Treatment is based on carbohydrate-rich nutrition, gradual replenishment of calories and fluids, while monitoring electrolytes and the risk of refeeding syndrome. In some cases, intensive therapy is required during pregnancy and lactation. [45]

Euglycemic ketoacidosis. Immediately discontinue the sodium-glucose cotransporter-2 inhibitor, begin rehydration, provide carbohydrates and insulin if necessary, and educate the patient on "sick day rules" for the future. [46]

New and supportive approaches

Rapid measurement of beta-hydroxybutyrate in the blood is preferable to urine ketone assessment, as it more accurately reflects the current status and treatment dynamics. In emergency departments, this speeds decision-making. [47]

Noninvasive methods for monitoring ketosis using exhaled breath acetone are being developed, which are potentially useful for outpatient monitoring of patients on a ketogenic diet or with diabetes. However, such methods complement, rather than replace, laboratory diagnostics. [48]

During pregnancy, management protocols are adapted to the fetus, monitoring is performed, acidosis and glycemia are corrected, and triggers are eliminated. A multidisciplinary team improves outcomes. [49]

Early standardization of the patient's pathway for suspected ketoacidosis reduces the time to treatment and the incidence of complications. In outpatient practice, clear instructions for self-monitoring of ketones during illness and loss of appetite are important. [50]

Table: Therapeutic strategies for ketoacidosis variants

Option	First line	What you must take into account
Diabetic	Rehydration, insulin, potassium correction, trigger treatment	Pediatric protocols in children, risk of cerebral edema
Alcoholic	Thiamine to glucose, glucose solutions, volume and electrolyte correction	Prevention of Wernicke's encephalopathy, withdrawal control
Hungry	Carbohydrate nutrition, rehydration, electrolyte monitoring	Risk of refeeding syndrome, slow increase in calories
Euglycemic	Discontinuation of sodium-glucose cotransporter type 2 inhibitor, fluids, carbohydrates, insulin if necessary	Teaching sick day rules and preventing relapse

Summary of current recommendations and reviews. [51]

Prevention

Patients with diabetes mellitus must adhere to their insulin therapy regimen, regularly monitor glucose and ketone levels during illness, vomiting, or significant loss of appetite, and develop an action plan for sick days. They should promptly seek medical attention if symptoms worsen. [52]

People on low-carb diets should monitor their well-being and fluid intake. If weakness, nausea, vomiting, or deterioration in consciousness occur, discontinue extreme restrictions, return to a balanced diet, and consult a doctor if necessary. When taking sodium-glucose cotransporter-2 inhibitors, it is important to know when to temporarily discontinue the medication. [53]

Forecast

With timely diagnosis and treatment, the prognosis for ketoacidosis is favorable, and most patients recover without lasting consequences. The risk of relapse is reduced by patient education and correction of precipitating factors. [54]

Delaying treatment increases the risk of complications and mortality, especially in vulnerable groups: pregnant women, adolescents, the elderly, and patients with alcoholism. Protocol-based management and a multidisciplinary approach improve outcomes. [55]

FAQ

• Does the smell of acetone from the mouth always mean diabetic ketoacidosis?

No. It occurs in alcoholic, fasting, and euglycemic ketoacidosis, as well as in physiological ketosis due to diet. The context and tests determine the diagnosis. [56]

• What to do at home if you experience a fruity odor and weakness?

Measure your glucose and ketones and start drinking small amounts of fluids. If you experience vomiting, abdominal pain, drowsiness, or deep, rapid breathing, call an ambulance. If you have diabetes, don't skip insulin doses and follow the "sick days" plan. [57]

• Why is thiamine given first and then glucose for alcoholic ketoacidosis?

Thiamine is essential for oxidative metabolism. Administration of glucose without thiamine may worsen the deficiency and trigger Wernicke encephalopathy.[58]

• Is it possible to rely solely on smell?

No. The smell is subjective and may be absent in severe cases. The decision is made based on clinical and laboratory data: blood ketones, acid-base balance, and electrolytes. [59]