KETOACIDOSIS

✓ Medically ReviewedDISEASEID: MDBT0256🚨 TRIAGE: EMERGENCYICD-10: E87.2

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Definition

CLINICAL DEFINITION

Ketoacidosis is a high anion gap metabolic acidosis characterised by elevated serum ketone bodies (acetoacetate and beta-hydroxybutyrate) resulting from accelerated lipolysis and hepatic ketogenesis exceeding peripheral utilisation. It typically arises from absolute or relative insulin deficiency combined with excess counter-regulatory hormones, leading to uncontrolled fatty acid oxidation and acid accumulation. Diagnostic criteria generally include arterial pH < 7.30, bicarbonate < 15 mmol/L, and demonstrable ketonaemia or significant ketonuria.

IN PLAIN ENGLISH

Ketoacidosis is a dangerous condition where the blood becomes too acidic because the body produces high levels of ketones when it cannot use sugar for energy. This happens when there is not enough insulin or carbohydrate intake, forcing the body to break down fat rapidly for fuel.

COMMON MISCONCEPTION / WHAT IT DOES NOT MEAN

Ketoacidosis is NOT synonymous with nutritional ketosis; physiological ketosis maintains normal acid-base balance with lower ketone levels. It is also distinct from lactic acidosis and other causes of high anion gap metabolic acidosis such as toxic alcohol ingestion or uraemia.

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Word Breakdown

keton-

=acetone or ketone (from Greek 'aketon')

-osis

=abnormal condition or disease state

Literal Meaning: Condition of ketones

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Abbreviations

DKA=Diabetic Ketoacidosis — the most common clinical form of ketoacidosis associated with insulin deficiency

AKA=Alcoholic Ketoacidosis — ketoacidosis occurring in chronic alcohol use disorder with malnutrition

SKA=Starvation Ketoacidosis — mild ketoacidosis resulting from prolonged fasting or caloric deprivation

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Synonyms & Variants

Ketotic Acidosis›

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Category-Specific Context

As a Disease category term, ketoacidosis represents a specific pathological metabolic derangement rather than a single aetiology. It encompasses distinct subtypes including diabetic, alcoholic, and starvation ketoacidosis, each with unique triggers and management nuances despite sharing the core pathophysiology of ketone-mediated acidosis.

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Clinical Context & Usage

CLINICAL SETTINGS

Emergency DepartmentIntensive Care UnitHigh Dependency UnitEndocrinology WardPaediatric Emergency Department

USAGE & DOCUMENTATION NOTES

Clinicians often use 'ketoacidosis' interchangeably with DKA in diabetic contexts, but documentation should specify the subtype (diabetic, alcoholic, starvation) as management differs. Severity is frequently stratified by pH and mental status. Ketone measurement is increasingly performed via capillary beta-hydroxybutyrate rather than urine dipstick, as urine tests detect acetoacetate and may underestimate severity during early treatment when beta-hydroxybutyrate predominates.

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Primary Causes & Pathophysiology

PATHOPHYSIOLOGY

Insulin deficiency or resistance, coupled with elevated counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone), drives unrestrained lipolysis in adipose tissue. Free fatty acids are transported to the liver where they undergo beta-oxidation to acetyl-CoA, which exceeds tricarboxylic acid cycle capacity and is shunted into ketogenesis. The resulting ketone bodies, acetoacetate and beta-hydroxybutyrate, are strong organic acids that dissociate at physiological pH, consuming bicarbonate buffers and lowering serum pH. Concurrent renal impairment or volume depletion reduces ketone excretion, exacerbating acid accumulation. In diabetic ketoacidosis, hyperglycaemia induces osmotic diuresis, causing profound dehydration and electrolyte losses that further impair renal acid clearance.

PRIMARY CAUSES

Absolute Insulin Deficiency (Type 1 Diabetes Mellitus)

Autoimmune beta-cell destruction eliminates endogenous insulin production, permitting unchecked lipolysis and ketogenesis even with modest stress or missed doses.

Relative Insulin Deficiency (Type 2 Diabetes Mellitus)

Severe infection, myocardial infarction, or corticosteroid use increases counter-regulatory hormones beyond the compensatory capacity of residual beta-cell function, precipitating ketosis.

Chronic Alcohol Use Disorder with Malnutrition

Ethanol metabolism depletes NAD+ and glycogen stores while inhibiting gluconeogenesis; starvation and vomiting drive lipolysis and ketogenesis disproportionate to glycaemia.

Prolonged Starvation or Fasting

Glycogen depletion after 24–48 hours shifts metabolism to fatty acid oxidation; ketone production rises but is usually moderated by basal insulin secretion, limiting acidosis severity.

SGLT2 Inhibitor Therapy

Glycosuria lowers plasma glucose, reducing insulin secretion and increasing glucagon, promoting euglycaemic ketoacidosis despite near-normal blood glucose levels.

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Drug-Induced Causes

💊 Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, canagliflozin) ↗

Mechanism: Induce glycosuria and lower insulin-to-glucagon ratio, promoting ketogenesis independent of hyperglycaemia.

→ Discontinue SGLT2 inhibitor immediately. Administer intravenous fluids and insulin infusion with dextrose once glucose < 14 mmol/L to suppress ketogenesis while avoiding hypoglycaemia.

💊 Corticosteroids (prednisolone, dexamethasone, hydrocortisone) ↗

Mechanism: Increase insulin resistance and hepatic gluconeogenesis, raising counter-regulatory drive and potentially precipitating DKA in susceptible individuals.

→ Adjust insulin regimen proactively during steroid therapy. Monitor ketones if glucose > 13.9 mmol/L or if symptoms develop. Taper steroids when clinically feasible.

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Epidemiology

Prevalence:In the United States, DKA accounts for approximately 140,000 hospitalisations annually with a case-fatality rate < 1% in adults but higher in children and low-resource settings. Alcoholic ketoacidosis prevalence is less well quantified but represents 10–20% of ketoacidosis presentations in urban emergency departments serving populations with high rates of alcohol use disorder.

Age Group:Children and young adults (peak incidence of new-onset type 1 diabetes); older adults with type 2 diabetes during acute illness; middle-aged adults with chronic alcohol use disorder for AKA.

Sex Predilection:Equal

Geographic Distribution:Higher DKA incidence at presentation in regions with limited access to primary care or insulin. Mortality is significantly higher in low- and middle-income countries due to delayed presentation and resource constraints. No intrinsic geographic variation in pathophysiology.

Red Flags & Triage ★

TRIAGE LEVEL

🚨 EMERGENCY

DO NOT MISS — LIFE-THREATENING PRESENTATIONS

Euglycaemic ketoacidosis in patients taking SGLT2 inhibitors — blood glucose may be < 14 mmol/L despite severe acidosis; check ketones in any unwell patient on these agents regardless of glycaemia
Cerebral oedema in paediatric DKA — subtle early signs (headache, irritability, slowing heart rate) precede herniation; initiate osmotherapy immediately upon suspicion rather than awaiting imaging confirmation

URGENT EVALUATION TRIGGERS

Capillary ketones ≥ 3.0 mmol/L with blood glucose > 11 mmol/L in known diabetes
Unexplained nausea, vomiting, or abdominal pain with tachypnoea or fruity breath odour
Altered mental status or Kussmaul respirations in context of suspected insulin omission or intercurrent illness
SGLT2 inhibitor use with any systemic illness, reduced oral intake, or unexplained acidosis

Contraindications & Precautions

CONTRAINDICATIONS

Bicarbonate therapy is contraindicated in mild-to-moderate DKA (pH ≥ 6.9) due to lack of benefit and potential harm including paradoxical CNS acidosis and hypokalaemia
Rapid bolus fluid administration in paediatric DKA is contraindicated due to association with cerebral oedema; controlled rehydration over 48 hours is standard

SPECIAL PRECAUTIONS

Initiate insulin only after confirming serum potassium ≥ 3.3 mmol/L to prevent life-threatening hypokalaemia-induced arrhythmias
Add dextrose to intravenous fluids once blood glucose falls below 14 mmol/L (250 mg/dL) to permit continued insulin infusion for ketone clearance without inducing hypoglycaemia
Monitor neurological status hourly in paediatric patients for signs of cerebral oedema (headache
bradycardia
hypertension
altered consciousness); prepare mannitol or hypertonic saline at bedside
Avoid routine bicarbonate administration unless pH < 6.9 with haemodynamic compromise
and then only with cautious dosing and intensive monitoring

Complications

DOWNSTREAM CLINICAL COMPLICATIONS

Cerebral Oedema — primarily in children and adolescents
associated with rapid osmolar shifts during resuscitation; carries high mortality and neurological morbidity
Hypokalaemia — total body potassium depletion masked by extracellular shift; insulin therapy drives potassium intracellularly
risking fatal arrhythmias if not repleted
Acute Kidney Injury — prerenal azotaemia from volume depletion compounded by rhabdomyolysis or sepsis in severe cases
Venous Thromboembolism — dehydration
immobility
and inflammatory state increase thrombotic risk during acute episode

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Reference Ranges

CRITICAL (PANIC) VALUEArterial pH < 7.0 or beta-hydroxybutyrate > 6.0 mmol/L indicates severe ketoacidosis requiring intensive care admission and continuous monitoring for haemodynamic instability and cerebral oedema risk.

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Confused With (LASA & DDx) ★

LEXICAL (LASA) — SIMILAR NAMES

Ketosis

Phonetically similar; ketosis refers to elevated ketones without acidosis (e.g., nutritional ketosis, fasting). Ketoacidosis implies pathological acid-base disturbance requiring intervention.

Lactic Acidosis

Both cause high anion gap metabolic acidosis; distinguished by lactate vs. ketone elevation. Misattribution delays correct treatment.

CLINICAL DIFFERENTIAL DIAGNOSES (DDx)

Lactic Acidosis

Key Distinguishing Feature: Elevated serum lactate (> 4 mmol/L) with normal or mildly elevated ketones; history of shock, sepsis, metformin toxicity, or mitochondrial dysfunction.

Toxic Alcohol Ingestion (Methanol, Ethylene Glycol)

Key Distinguishing Feature: High osmolar gap, visual disturbances (methanol), calcium oxalate crystalluria (ethylene glycol); ketones typically absent or mild.

Salicylate Toxicity

Key Distinguishing Feature: Mixed respiratory alkalosis and high anion gap metabolic acidosis; tinnitus, hyperthermia, and elevated serum salicylate level.

Uraemic Acidosis

Key Distinguishing Feature: Markedly elevated creatinine and urea; ketones normal; history of advanced chronic kidney disease or acute renal failure.

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Clinical Pearls

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Beta-hydroxybutyrate is the predominant ketone in severe DKA; urine dipsticks detect only acetoacetate and may falsely suggest improvement during early treatment as beta-hydroxybutyrate converts to acetoacetate. Capillary beta-hydroxybutyrate monitoring guides therapy more accurately.

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Total body potassium is depleted in DKA despite normal or elevated initial serum levels due to transcellular shift. Insulin therapy will unmask this deficit rapidly; never start insulin without confirming adequate potassium replacement capability.

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Euglycaemic DKA is a recognised complication of SGLT2 inhibitors, particularly during acute illness, fasting, or perioperative periods. Maintain vigilance even when glucose is normal; discontinue the drug and treat as standard DKA with dextrose-containing fluids.

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Bicarbonate therapy has no proven benefit in DKA with pH ≥ 6.9 and may worsen outcomes through paradoxical CNS acidosis, hypokalaemia, and delayed ketone clearance. Reserve for extreme acidosis with cardiovascular compromise.

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In alcoholic ketoacidosis, administer thiamine before dextrose to prevent Wernicke's encephalopathy. Insulin is rarely needed; volume repletion and carbohydrate provision suppress ketogenesis effectively.

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Example Usage & SOAP

CLINICAL SENTENCE

"The 24-year-old patient with type 1 diabetes presented with DKA precipitated by gastroenteritis, characterised by pH 7.12, beta-hydroxybutyrate 5.8 mmol/L, and blood glucose 28 mmol/L."

IN A SOAP NOTE

S: 19-year-old female with T1DM reports 2 days of vomiting, abdominal pain, and missed insulin doses due to nausea. O: HR 120 bpm, BP 100/60 mmHg, RR 28/min, GCS 15. Dry mucous membranes, fruity breath. Capillary glucose 26 mmol/L, capillary ketones 5.2 mmol/L. VBG: pH 7.15, pCO2 2.8 kPa, HCO3 8 mmol/L, BE -18. Na 131, K 4.8, Cl 98, urea 12, Cr 85. Anion gap 25. A: Severe diabetic ketoacidosis secondary to insulin omission and intercurrent viral illness. No signs of cerebral oedema currently. P: Commence fixed-rate IV insulin infusion 0.1 units/kg/hr. Start 0.9% NaCl at 1 L/hr for first hour, then reassess. Add KCl 40 mmol/L to fluids once urine output confirmed and K < 5.5. Transition to dextrose-containing fluids when glucose < 14 mmol/L. Hourly neuro obs. Target resolution of ketosis within 24 hrs.

DIFFERENTIAL DIAGNOSIS CONTEXT

Differential for high anion gap metabolic acidosis with ketonaemia: (1) Diabetic ketoacidosis — hyperglycaemia, history of diabetes or insulin omission; (2) Alcoholic ketoacidosis — normo/hypoglycaemia, chronic alcohol use, recent binge with poor intake; (3) Starvation ketoacidosis — mild acidosis, prolonged fasting, no alcohol or diabetes history; (4) SGLT2 inhibitor-associated euglycaemic DKA — medication history, near-normal glucose; (5) Salicylate toxicity — mixed acid-base disorder, tinnitus, drug exposure.

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Prognosis

SHORT-TERM OUTCOME

With appropriate protocol-driven management, DKA resolves within 24–48 hours in most adults. Mortality in high-income settings is < 1% for adults but 0.15–0.3% in children, largely attributable to cerebral oedema. AKA typically resolves faster (12–24 hours) with thiamine, fluids, and dextrose.

LONG-TERM PROGNOSIS

Recurrent DKA episodes predict higher long-term mortality and microvascular complications in type 1 diabetes. Single episodes do not confer permanent organ damage if uncomplicated. Survival after AKA depends on addressing underlying alcohol use disorder and nutritional rehabilitation.

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References & Coding

ICD-10 DIAGNOSTIC CODE

E87.2

LITERATURE CITATIONS & GUIDELINES

[1]Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. doi:10.2337/dc09-9032

[2]Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;19(Suppl 27):155-177. doi:10.1111/pedi.12701

[3]National Institute for Health and Care Excellence (NICE). Type 1 diabetes in adults: diagnosis and management. NG17. 2015 (updated 2022).

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