Diabetic ketoacidosis

Background

This page is for adult patients. For pediatric patients, see: diabetic ketoacidosis (peds)

• Diabetic ketoacidosis (DKA) is a life-threatening hyperglycemic emergency characterized by hyperglycemia (or euglycemia in ~10%), metabolic acidosis, and ketonemia
• Hospital admissions for DKA have increased substantially over the past decade
• Patients in DKA are almost always K⁺ depleted despite initially normal or elevated serum K⁺
  • Extracellular shift of K⁺ occurs due to acidosis, hyperosmolality, and insulin deficiency
  • Insulin infusion drives K⁺ back intracellularly → can unmask severe total body K⁺ depletion

Epidemiology

• Inpatient DKA mortality: approximately 0.2% in type 1 diabetes and 1.0% in type 2 diabetes
• DKA can occur in both type 1 and type 2 diabetes (up to 50% of DKA admissions are T2D in some series)
• ~6-21% of adults with T1D present with DKA as their initial diagnosis
• Recurrent DKA is common and often driven by insulin omission due to cost, mental health, substance use, or social determinants — the ED is an opportunity to screen and connect to resources

Pathophysiology

Defining features include hyperglycemia (glucose >200 mg/dL, or any glucose in a patient with known diabetes), acidosis (pH <7.3 or HCO₃ <18), and ketonemia (BHB ≥3 mmol/L)

Hyperglycemia

• Leads to osmotic diuresis and depletion of electrolytes including sodium, potassium, magnesium, calcium, and phosphorus
• Further dehydration impairs GFR and contributes to acute kidney injury
• Hypokalemia may inhibit insulin release
• Euglycemic DKA (~10% of cases): glucose <200 mg/dL with metabolic acidosis and ketonemia — seen with SGLT-2 inhibitors, pregnancy, low carbohydrate intake, fasting, or recent insulin use

Acidosis

• Due to insulin deficiency → lipolysis → accumulation of ketoacids (represented by increased anion gap)
• Compensatory respiratory alkalosis (tachypnea/hyperpnea — Kussmaul breathing)
• Breakdown of adipose creates first acetoacetate, then conversion to beta-hydroxybutyrate (the predominant ketone in DKA)

Dehydration

• Causes activation of RAAS in addition to osmotic diuresis
• Average fluid deficit: 3-6 liters in adults (100 mL/kg)
• Initial serum values for electrolytes (especially K⁺) may be higher than actual total body stores
• Cation loss (in exchange for chloride) worsens metabolic acidosis

Clinical Features

• May be the initial presentation of unrecognized T1DM (6-21% of adults with T1D present with DKA as first diagnosis)
• OR symptoms/signs of an inciting precipitant (e.g. medication/dietary nonadherence, signs/symptoms of infection, insulin pump malfunction)
• Presenting features may include:

Constitutional

• • Generally ill-appearance
  • Fatigue, weakness, malaise
  • +/- Weight loss (may be significant in new-onset T1D)

Volume Depletion

• • Polydipsia, polyuria (initially) → decreased urine output (as volume depleted)
  • Signs of dehydration: dry mucous membranes, poor skin turgor, sunken eyes, delayed capillary refill
  • Hypotension, tachycardia
  • Most adults are 3-6 liters depleted at presentation

Gastrointestinal

• • Abdominal pain — present in up to 50% of DKA; can mimic an acute abdomen (appendicitis, pancreatitis, mesenteric ischemia)
    • ED Pearl: Abdominal pain that does not improve with correction of acidosis and hydration warrants further workup for intra-abdominal pathology — do not assume it is "just DKA"
    • Abdominal pain correlates with severity of acidosis; more common with pH <7.2
  • Nausea/vomiting (present in >75% of cases)
  • Anorexia
  • Ileus / decreased bowel sounds (from electrolyte derangements and acidosis)
  • Gastroparesis — increases aspiration risk, especially if intubation is being considered

Respiratory

• • Tachypnea — compensatory for metabolic acidosis
  • Kussmaul breathing (deep, labored breathing pattern) — classic finding in moderate-severe DKA; represents maximal respiratory compensation
  • Acetone / fruity smell on breath — from exhaled ketones; may be subtle or absent; not all clinicians can detect it
  • ED Pearl: A DKA patient who is no longer tachypneic despite persistent acidosis is decompensating — respiratory compensation is failing and the patient may need emergent airway management

Neurologic

• • Altered mental status — ranges from drowsiness and lethargy to confusion, stupor, and coma
    • Severity correlates with serum osmolality more than glucose level or pH
    • AMS is present in ~15-25% of DKA patients at presentation
  • Decreased reflexes
  • Headache
  • Seizures (uncommon; more frequent in pediatric DKA)
  • Cerebral edema — significantly increases mortality, especially in children; suspect if neurologic status worsens during treatment (see Cerebral edema in DKA)

Cardiovascular

• • Tachycardia (from dehydration, acidosis, and catecholamine surge)
  • Hypotension / shock (from severe volume depletion)
  • Arrhythmia — from hyperkalemia (at presentation) or hypokalemia (during treatment); obtain ECG early
  • Chest pain — may represent ACS as a precipitant or consequence

Other

• • Hypothermia — DKA patients may be normothermic or hypothermic even in the presence of infection; absence of fever does NOT exclude infection as a precipitant
  • Blurred vision (from osmotic lens swelling)
  • Muscle cramps (from electrolyte derangements)
  • Deep vein thrombosis / pulmonary embolism — DKA is a hypercoagulable state; consider VTE in patients with unexplained tachycardia, hypoxia, or chest pain disproportionate to presentation

Differential Diagnosis

Causes of DKA (Precipitants)

Search for a precipitant in every DKA patient — it changes management

• Infection (most common precipitant worldwide, 14-58% of cases)
• Insulin noncompliance/omission — most common in T1D; ask about cost, access, mental health, pump malfunction
• Cardiac ischemia / MI
• Stroke
• Pancreatitis
• Pulmonary embolism
• SGLT-2 inhibitors (euglycemic DKA)
• Pregnancy (higher risk of euglycemic DKA)
• Steroid use (new or dose escalation)
• Alcohol use
• Toxicologic exposure
• Hyperthyroidism / thyroid storm
• GI Hemorrhage
• Renal Failure
• New-onset diabetes (DKA as initial presentation)
• Insulin pump malfunction (kink, disconnection, site infection, battery failure)
• Substance use (cocaine, methamphetamine)
• Trauma

Hyperglycemia

Diabetic Emergencies

• Diabetic ketoacidosis (DKA)
• Diabetic ketoacidosis (peds)
• Hyperosmolar hyperglycemic state (HHS)
• Nonketotic hyperglycemia
• Euglycemic DKA (SGLT-2 inhibitors, pregnancy, fasting)

Diabetes Mellitus (New or Known)

• Type 1 diabetes mellitus (new-onset or uncontrolled)
• Type 2 diabetes mellitus (new-onset or uncontrolled)
• Medication noncompliance or insulin pump malfunction
• Gestational diabetes
• Latent autoimmune diabetes of adults (LADA)

Medication/Drug-Induced

• Corticosteroids (most common drug-induced cause)
• Thiazide diuretics
• Atypical antipsychotics (olanzapine, clozapine, quetiapine)
• Beta-blockers (especially non-selective)
• Phenytoin
• Tacrolimus, cyclosporine (transplant patients)
• Protease inhibitors (HIV antiretrovirals)
• Catecholamines (epinephrine, norepinephrine infusions)
• SGLT-2 inhibitors (paradoxical DKA with euglycemia)
• Total parenteral nutrition (TPN)
• Dextrose-containing IV fluids (iatrogenic)
• Niacin
• Pentamidine (initially hyperglycemia, then hypoglycemia from beta-cell destruction)

Physiologic Stress Response

• Sepsis / critical illness (stress hyperglycemia — very common in the ED)
• Trauma / major surgery / burns
• Acute coronary syndrome / myocardial infarction
• Stroke (especially hemorrhagic)
• Pancreatitis (both a cause and consequence)
• Shock (any etiology)
• Pain (catecholamine surge)
• Seizure (postictal)
• Physiologic stress alone rarely causes glucose >200 mg/dL in non-diabetics; glucose >200 in a "stress response" should prompt evaluation for undiagnosed diabetes or prediabetes

Endocrine

• Cushing syndrome / Cushing disease (cortisol excess)
• Pheochromocytoma (catecholamine excess)
• Hyperthyroidism / thyroid storm
• Acromegaly (growth hormone excess)
• Glucagonoma (rare)
• Somatostatinoma (rare)

Pancreatic

• Pancreatitis (acute or chronic — destruction of islet cells)
• Pancreatic malignancy (adenocarcinoma, neuroendocrine tumors)
• Post-pancreatectomy
• Cystic fibrosis-related diabetes
• Hemochromatosis (iron deposition in pancreas — "bronze diabetes")

Toxic/Overdose

• Iron toxicity (hepatic injury → impaired glucose regulation)
• Salicylate toxicity (can cause both hyper- and hypoglycemia)
• Sympathomimetic toxicity (cocaine, methamphetamine)
• Calcium channel blocker toxicity (impairs insulin secretion)
• Carbon monoxide toxicity (stress response)

Other

• Renal failure (chronic kidney disease, acute kidney injury — impaired insulin clearance AND insulin resistance)
• Cirrhosis / hepatic failure (impaired glycogenolysis regulation)
• Pregnancy (gestational diabetes, steroid administration for fetal lung maturity)
• Parenteral nutrition (TPN, dextrose-containing fluids)
• Post-transplant diabetes (immunosuppressants)

Complications of Diabetes (Not Causes of Hyperglycemia)

These are associated conditions that may be present alongside hyperglycemia but do not themselves cause elevated glucose:

• Diabetic foot infection
• Diabetic peripheral neuropathy
• Cerebral edema in DKA
• Diabetic retinopathy
• Diabetic nephropathy

Evaluation

Workup

Workup to confirm diagnosis, assess severity, and search for precipitating cause (e.g., infection, ACS)

• BMP (glucose, BUN/Cr, Na⁺, K⁺, Cl⁻, HCO₃⁻, anion gap)
• Blood glucose (and bedside point-of-care glucose)
• Beta-hydroxybutyrate (BHB) — preferred ketone marker for diagnosis, severity assessment, and monitoring resolution; ideally point-of-care
• VBG (arterial blood gas is rarely needed)
• Magnesium, phosphorus, calcium
• CBC (leukocytosis is common in DKA even without infection — >25,000 or left shift more suggestive of infection)
• ECG — evaluate for hyperkalemia/hypokalemia, ischemia, arrhythmia
• Urinalysis — ketonuria may be a useful screen but serum BHB is preferred (see below)
• CXR — if infection suspected
• Blood cultures — if concern for sepsis or bacteremia
• Lipase — if concern for pancreatitis
• Lactate — if concern for sepsis or tissue hypoperfusion
• Troponin — if chest pain or concern for ACS (interpret with caution in CKD)
• Pregnancy test — in all women of childbearing age
• HbA1c — helpful in assessing chronic glycemic control and distinguishing new-onset T1D from poorly controlled known diabetes

Diagnosis

Diagnosis is made based on the presence of acidosis AND ketonemia in the setting of diabetes

2024 ADA/EASD Consensus Diagnostic Criteria

Criterion	Diagnostic Threshold
Glucose	>200 mg/dL (11.1 mmol/L) OR known history of diabetes (glucose cutoff removed for known diabetics)
pH	<7.3 (venous)
Bicarbonate	<18 mEq/L
Beta-hydroxybutyrate	≥3.0 mmol/L (preferred), or significant ketonuria if BHB unavailable

Severity Classification

	Mild	Moderate	Severe
pH	7.25-7.30	7.00-7.24	<7.00
Bicarbonate	15-18 mEq/L	10-14.9 mEq/L	<10 mEq/L
BHB	3.0-5.9 mmol/L	6.0-9.9 mmol/L	≥10.0 mmol/L
Mental status	Alert	Alert/drowsy	Stupor/coma

Key Laboratory Pearls

• Blood Gas: VBG is sufficient — pH difference from ABG is ±0.02 units
• Urinary ketones: May give a false negative later in DKA — the urine dipstick detects acetoacetate, not beta-hydroxybutyrate. As DKA worsens, the ratio shifts toward BHB, so urine ketones may paradoxically appear negative in severe DKA
• Bicarb may be normal despite DKA due to compensatory/contraction alkalosis — the elevated anion gap or BHB may be the only clues
• Corrected sodium: Na⁺ decreases by ~1.6 mEq/L for every 100 mg/dL increase in glucose above 100 (some use 2.4 mEq/L per 100 mg/dL for glucose >400). The corrected sodium should rise as glucose falls during treatment — if it is falling, suspect excessive free water administration (risk of cerebral edema)
• ETCO₂: An ETCO₂ ≥35 mmHg is 100% sensitive to rule out DKA; an ETCO₂ ≤21 mmHg is 100% specific for DKA in patients with glucose >550
• Leukocytosis is common in DKA even without infection (stress response); WBC >25,000 or bandemia is more suggestive of true infection

Management

Algorithm for the management of diabetic ketoacidosis

• If the patient has an insulin pump, shut it off and remove the subcutaneous catheter

Volume Repletion

• Administer 15-20 mL/kg/h isotonic crystalloid during the first hour (typically 1-1.5L)
  • Most important step in treatment since osmotic diuresis is the major driving force
  • Most adult patients are 3-6L depleted; aim to correct ~50% of fluid deficit in first 8-12 hours
  • Lactated Ringers is preferred over NS — may resolve DKA faster and causes less hyperchloremic acidosis
  • When blood glucose (BG) <250-300 mg/dL → add a D10 infusion at an equal rate to LR to prevent hypoglycemia while continuing insulin to clear ketones
  • Patients can eat and drink if mental status is intact
• Use caution in patients with CHF, chronic kidney disease, or ESRD — smaller boluses with frequent reassessment

Electrolyte Repletion

Potassium (Most Important!)

• Check K⁺ BEFORE starting insulin. Do not give insulin until K⁺ supplementation is underway if K⁺ <3.5

K⁺ Level	Action
<3.5 mEq/L	Hold insulin. Start aggressive K⁺ repletion: 20-40 mEq KCl/hr IV. Recheck q1-2h. Start insulin only after K⁺ ≥3.5.
3.5-5.5 mEq/L	Start K⁺ repletion: 20-30 mEq KCl per liter of IVF. May start insulin concurrently.
>5.5 mEq/L	Hold K⁺ repletion. Start insulin. Recheck K⁺ in 1-2 hours (it will fall rapidly with insulin + fluids).

Other Electrolytes

• Sodium: Calculate corrected Na⁺ (see above). If truly hyponatremic, use NS. If hypernatremic, consider LR or half-NS.
• Hypophosphatemia: Replete if <1.0 mg/dL (IV K₂PO₄ — has the added benefit of providing K⁺). Severe hypophosphatemia can cause cardiac/respiratory dysfunction and hemolytic anemia.
• Hypomagnesemia: Replete if Mg <2.0 mg/dL (2g MgSO₄ IV over 1 hour)

Insulin Overview

• A bolus dose is NOT recommended — no benefit and may increase hypoglycemic episodes
• Expect BG to fall by 50-100 mg/dL per hour with adequate insulin and fluids
• Refractory hyperglycemia → consider unrecognized infection, inadequate fluid resuscitation, or insulin delivery failure

Intravenous Insulin (Standard for Moderate-Severe DKA)

• Fixed rate: 0.1 units/kg/hr (or 0.14 units/kg/hr without bolus; or 0.05 units/kg/hr per some protocols)
  • Fixed rate infusion has improved outcomes over variable rate
• Do NOT stop insulin infusion until DKA has resolved — resolution requires clearance of ketones, not merely correction of glucose
• Resolution criteria (2024 consensus):
  • BHB <0.6 mmol/L (preferred), AND
  • Venous pH >7.3, AND
  • Bicarbonate ≥18 mEq/L
  • If BHB is not available, normalization of anion gap is an acceptable surrogate
• When BG <250-300 mg/dL → add D10 infusion; do NOT decrease insulin below 0.05 units/kg/hr until ketones clear
• Maintain BG between 150-250 mg/dL until resolution of acidosis

Subcutaneous Insulin (Appropriate for Mild DKA Only)

SC regimen requires rapid-acting insulin (e.g., aspart, lispro). Appropriate only for mild DKA (pH 7.25-7.3, alert, tolerating PO, able to void). Poor perfusion may impair absorption.

1-Hour Protocol:

• Initial: 0.3 units/kg SC, then 0.1 units/kg SC every hour
• When BG <250: add D5 0.45% NS; reduce to 0.05 units/kg/hr SC
• Target BG ~150 mg/dL until DKA resolution

2-Hour Protocol:

• Initial: 0.3 units/kg SC, then 0.2 units/kg SC at 1 hour, then 0.2 units/kg SC q2hr
• When BG <250: add D5 0.45% NS; reduce to 0.1 units/kg q2hr SC
• Target BG ~150 mg/dL until DKA resolution

Transition to Basal-Bolus Insulin

• Start basal insulin (glargine) 1-2 hours BEFORE discontinuing IV insulin infusion
• Two approaches:
  • Early basal: Glargine 0.3 U/kg SC ×1 early in DKA course (protects against rebound hyperglycemia, eliminates the 1-2h overlap waiting period)
  • Traditional: Close the anion gap / clear BHB → start basal insulin 1-2h before stopping infusion → verify patient is eating before fully transitioning

Bicarbonate

• No evidence supports the use of sodium bicarb in DKA, with a pH >6.9
• However, no studies have been performed for patients with pH <6.9 and the most recent ADA guidelines recommend it for patients with pH <7.1
• Generally NOT recommended — multiple studies show no benefit in DKA resolution or time to discharge
• Consider only if pH <6.9 (or <7.0 per some protocols) with hemodynamic instability
• Pitfalls of bicarbonate in DKA:
  • Paradoxical CSF acidosis
  • Hypokalemia from H⁺/K⁺ shifts
  • Large sodium bolus
  • Risk of cerebral edema
  • Shifts oxygen-hemoglobin dissociation curve leftward → decreased O₂ delivery

Additional Management Considerations

• VTE prophylaxis: DKA is a hypercoagulable state — consider prophylactic-dose heparin or enoxaparin (adjust for renal function) in immobilized or critically ill patients
• Infection: Treat empirically if suspected; do not wait for culture results to initiate antibiotics
• Continuous telemetry: Hyperkalemia and hypokalemia are both arrhythmogenic; monitor throughout treatment

Intubation

• Avoid intubation in DKA whenever possible — this is a critical ED pearl
• Risks:
  • During sedation/paralysis, loss of compensatory hyperventilation → precipitous pH drop that can cause cardiac arrest
  • Severe gastroparesis in DKA → high aspiration risk
  • Awake DKA patients can generally achieve greater minute ventilation than a mechanical ventilator
• If intubation is unavoidable:
  • Set the ventilator to match the patient's pre-intubation respiratory rate and tidal volume (high RR, high Vt)
  • Avoid paralyzing the patient if possible
  • Pre-oxygenate aggressively
• See Intubation in severe metabolic acidosis for more detail

Subsequent Monitoring

• Glucose check Q1hr (bedside POC)
• BMP Q2hr initially (then Q4hr as improving); include anion gap calculation
• BHB Q2-4hr if available (preferred over anion gap for monitoring resolution)
• Check VBG pH PRN based on clinical status
• Assess insulin dose adequacy Q1hr (BG should fall 50-100 mg/dL per hour)
• Monitor corrected sodium trend — should be rising as glucose falls
• K⁺ with every BMP — and whenever insulin rate is changed
• Sliding scale insulin to be started once DKA has fully resolved and patient is eating a full diet

Disposition

• Admit to ICU or step-down: Moderate-severe DKA (pH <7.24), AMS, hemodynamic instability, significant comorbidity, need for IV insulin infusion
• Admit to monitored bed: Mild DKA on SC protocol, but requiring observation for resolution and precipitant evaluation
• Consider ED treatment and discharge (rare): Only for mild DKA in a known, reliable patient with clear precipitant (e.g., insulin pump failure), DKA fully resolved before discharge (BHB <0.6 or anion gap closed, pH >7.3, bicarb ≥18, BG <200, tolerating PO, K⁺ normal), and close follow-up within 24-48 hours
• Discharge education: Sick day rules (never stop basal insulin, check BG and ketones when ill, maintain hydration), when to seek care (persistent vomiting, BG >300, positive ketones), insulin access resources if cost is a barrier
• Schedule outpatient follow-up within 1-2 weeks if medications were changed (or within 1 month)

Complications

• Cerebral Edema in DKA: More common in pediatric DKA; risk factors include excessive free water, rapid glucose correction, failure of corrected sodium to rise, and bicarbonate use
• Hypokalemia: Most dangerous iatrogenic complication — from insulin-driven intracellular K⁺ shift without adequate repletion
• Hypoglycemia: From excessive insulin without adequate dextrose supplementation
• ARDS/pulmonary edema: From aggressive fluid resuscitation, especially in patients with cardiac or renal comorbidities
• Venous thromboembolism: DKA is a prothrombotic state
• Rhabdomyolysis (rare)
• Dialysis disequilibrium-like syndrome (rapid osmolar shifts)

Insulin 0.1 units/kg/hr IV infusion (no bolus); reduce to 0.02-0.05 units/kg/hr when BG <250 IV drip — Do NOT stop until DKA resolved; no bolus recommended Insulin 0.3 units/kg SC initial, then 0.1-0.2 units/kg SC q1-2h SC — Mild DKA only (pH 7.25-7.3, alert, tolerating PO); poor perfusion impairs absorption Sodium bicarbonate 100 mEq in 400 mL sterile water IV over 2 hours IV drip — Generally NOT recommended; consider only if pH <6.9 with hemodynamic instability

See Also

• Diabetes mellitus (main)
• Evidence Review: Sodium Bicarbonate in DKA
• Diabetic ketoacidosis (peds)
• Ketonemia
• Cerebral edema in DKA
• Hyperglycemia
• Hyperosmolar hyperglycemic state
• Alcoholic Ketoacidosis
• Chronic kidney disease

External Links

• ADA 2024 Consensus Report: Hyperglycemic Crises in Adults (Full Text)
• IBCC - DKA Management
• DDxOf: Management of Diabetic Ketoacidosis

References

📊 Corrected Sodium for Hyperglycemia Calculator [show]

Corrected Sodium

Corrected Sodium for Hyperglycemia

Parameter	Value
Measured Sodium (mEq/L)
Serum Glucose (mg/dL)
Results
Corrected Na⁺ (Katz, 1.6 mEq per 100 mg/dL)	mEq/L
Corrected Na⁺ (Hillier, 2.4 mEq per 100 mg/dL)	mEq/L

References

Katz MA. Hyperglycemia-induced hyponatremia — calculation of expected serum sodium depression. N Engl J Med. 1973;289(16):843-844. PMID 4763428. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999;106(4):399-403. PMID 10225241. Classic formula (Katz): Corrected Na = Measured Na + 1.6 × (Glucose − 100) / 100 Revised formula (Hillier): Corrected Na = Measured Na + 2.4 × (Glucose − 100) / 100 (preferred when glucose >400)