Diabetic ketoacidosis

Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them.


Diabetic Ketoacidosis


Key Points

  • DKA is the condition of ketonemia, anion gap metabolic acidosis, and (usually) hyperglycemia associated with insulin deficiency in people with diabetes (usually in those with type 1 diabetes; occasionally in those with type 2 diabetes)
  • Lack of adherence to insulin administration (eg, missing doses) and/or a precipitating physiologic stressor (eg, infection, myocardial infarction) are the most common causes of DKA
  • Diagnostic criteria for DKA include pH of 7.3 or lower, serum bicarbonate level less than 15 to 18 mEq/L, and ketonemia with hyperglycemia r1
  • Treat intravascular volume depletion rapidly with 0.9% normal saline. Potassium supplementation is needed in most patients; insulin is administered by IV infusion r2
  • Frequent monitoring of glucose and electrolyte levels (with laboratory tests or bedside point-of-care tests) as well as calculation of anion gap, are necessary to adjust insulin dosage, IV fluid composition, and IV fluid infusion rate

Urgent Action

  • For the rare patient with DKA in shock, rapidly restore circulatory volume with isotonic saline (20 mL/kg boluses for pediatric patients) infused as quickly as possible through a large-bore cannula


  • Do not rely on urine ketone analysis to document the presence of ketosis, as it will detect only acetoacetate level and therefore may show falsely low ketone levels. Serum β-hydroxybutyrate is the preferred test for ketonemia
  • Initiate potassium replacement before beginning insulin therapy if the patient is hypokalemic, and proactively if/when potassium level enters reference range owing to total body deficiency of intracellular potassium stores
  • Administration of insulin before correcting potassium deficiencies can lead to hypokalemia and cardiac arrhythmias
  • Acute coronary syndrome with silent myocardial ischemia can precipitate DKA
  • Initial insulin therapy for children with DKA does not include a bolus of insulin
  • Because hyperglycemia resolves faster than ketoacidosis, ongoing insulin therapy is required even after glucose levels have fallen until ketoacidosis resolves
  • Relapse of ketoacidosis can occur if an IV insulin infusion is discontinued without overlap with subcutaneous insulin (2 hours for isophane insulin and 3-4 hours for basal insulin analogues) r3


Clinical Clarification

  • DKA (diabetic ketoacidosis) is a crisis that occurs as an acute metabolic complication of diabetes mellitus; it is defined by presence of ketonemia, anion gap metabolic acidosis, and (usually) hyperglycemia r2
  • Caused by absolute or relative insulin deficiency and an increase in counterregulatory hormone levels (eg, glucagon, catecholamines, cortisol) r4


  • Adults
    • Mild DKA r1
      • Plasma glucose level greater than 250 mg/dL
      • Ketones present in serum or urine
      • Blood gas pH 7.25 to 7.3
      • Serum bicarbonate level of 15 to 18 mEq/L
      • Anion gap greater than 10 mEq/L
      • Alert mental status
    • Moderate DKA r1
      • Plasma glucose level greater than 250 mg/dL
      • Ketones present in serum or urine
      • Blood gas pH 7 to 7.24
      • Serum bicarbonate level of 10 to less than 15 mEq/L
      • Anion gap greater than 12 mEq/L
      • Alert or drowsy mental status
    • Severe DKA r1
      • Plasma glucose level greater than 250 mg/dL
      • Ketones present in serum or urine
      • Blood gas pH less than 7
      • Serum bicarbonate level lower than 10 mEq/L
      • Anion gap greater than 12 mEq/L
      • Stuporous or comatose mental status
  • Children
    • Mild DKA
      • Venous pH less than 7.3 or bicarbonate level less than 18 mEq/L r5
    • Moderate DKA
      • Venous pH less than 7.2 or bicarbonate level less than 10 mEq/L r5
    • Severe DKA
      • Venous pH less than 7.1 or bicarbonate level less than 5 mEq/L r5
  • Euglycemic DKA
    • Ketonemia and anion gap metabolic acidosis are present but glucose level is lower than 200 mg/dL r6
    • Uncommon compared with hyperglycemic DKA r7r8
      • Observed in pregnancy, sepsis, or in patients using sodium-glucose cotransporter 2 inhibitors (gliflozins)


Clinical Presentation


  • Adult patients most often have a history of type 1 diabetes, although diabetic ketoacidosis can rarely develop in patients with ketosis-prone type 2 diabetes r4c1c2
  • Children and young adults (younger than 20 years) present with diabetic ketoacidosis as the initial manifestation of diabetes in 30% of cases r9
  • Most common symptoms, which usually develop over a period of hours to days:
    • Polydipsia c3
    • Polyuria c4
    • Fatigue c5
    • Blurry vision c6
    • Weight loss c7
  • Other symptoms that are found variably include:
    • Nausea, vomiting, and abdominal pain (40%-75% of cases) r10c8c9c10
      • Abdominal pain attributable solely to DKA is typically diffuse and follows periods of protracted vomiting and worsening acidemia r11c11c12c13
    • Dyspnea, due to tachypnea c14
    • Headache, due to cerebral edema (children) r12c15
    • New-onset enuresis (children) r12c16
    • Confusion or drowsiness c17c18
  • Other symptoms that can suggest a precipitating event:
    • Chest pain (acute coronary syndrome) c19
    • Fever (many infections), although hypothermia can also occur from peripheral vasodilation c20c21
    • Cough and dyspnea (pneumonia or heart failure) c22c23
  • Medication and substance history may identify a precipitant or alternative diagnosis
    • Ingestion of agents that may cause or exacerbate hyperglycemia: r11
      • Sympathomimetic amines c24
      • Corticosteroids c25
      • Atypical antipsychotics c26
    • Ingestion of agents that may cause a metabolic acidosis unrelated to diabetic ketoacidosis:
      • Alcohol
      • Methanol
      • Ethylene glycol
      • Isoniazid

Physical examination

  • Physical examination findings vary, depending on degree of dehydration and any other accompanying conditions c27
  • Tachycardia and hypotension, due to volume depletion r3c28c29
  • Dry mucous membranes, poor skin turgor, and sunken eyes r3c30c31c32
  • Prolonged capillary refill time (especially useful for predicting dehydration in young children) r13c33c34
  • Kussmaul respiration (tachypnea with deep inspirations) r3c35
  • Fruity breath odor r3c36
  • Altered mental status, ranging from drowsiness to coma with increasing severity of diabetic ketoacidosis r3c37c38c39
  • Fever, in the setting of infection c40

Causes and Risk Factors


  • Type 1 diabetes plus precipitating factors c41d1
    • Medical or surgical illness (altogether accounts for 60% of cases) r14
      • Infection (eg, sepsis, pneumonia, urinary tract infection, meningitis) c42c43c44c45c46
        • COVID-19 infection may precipitate DKA in patients with preexisting diabetes or not-yet-diagnosed diabetes r15c47
      • Myocardial ischemia c48
      • Cerebrovascular accident c49
      • Gastrointestinal bleeding c50
      • Pancreatitis (common in adults,r11but rare in childrenr16) c51c52
      • Less common: r11
        • Gastrointestinal diseases causing nausea and vomiting c53
        • Trauma c54
        • Surgery c55
        • Alcohol use c56
        • Substance misuse (eg, cocaine) c57c58
        • Pregnancy c59
        • Eating disorders c60
        • Ingestion of drugs that decrease carbohydrate metabolism
          • Sympathomimetics c61
          • Corticosteroids c62
          • Atypical antipsychotics c63
          • Thiazide diuretics c64
        • Off-label use of sodium-glucose cotransporter 2 inhibitors (gliflozins) by patients with type 1 diabetes r17c65
        • Fasting (eg, during Ramadan) r18r19c66
    • Inadequate exogenous insulin (accounts for 40% of cases) r14c67
      • Omission of insulin due to nonadherence or self-administration error c68
      • Unrecognized interruption of insulin delivery by users of insulin pumps (eg, insulin pump malfunction) c69
  • Type 2 diabetes plus precipitating factors c70d2
    • Acute decrease in insulin production owing to pancreatic β-cell dysfunction and temporary insulin resistance r20c71c72
    • Use of sodium-glucose cotransporter 2 inhibitors (gliflozins) r7r21r22r23c73
      • Associated with almost 3-fold increased risk of DKA r24
  • Treatment with immune checkpoint inhibitors may precipitate ketoacidosis secondary to autoimmune diabetes in patients with previously normal glucose tolerance r23r25c74

Risk factors and/or associations

  • Increased risk of DKA for patients aged 13 to 25 years r26c75
  • 30% of patients younger than 20 years first receive diabetes diagnosis when they present with DKA r9
  • Incidence and mortality higher in children than in adults c76c77
  • Increased risk of DKA observed among patients with type 1 diabetes in ethnic minority groups r27c80
Other risk factors/associations
  • Patients with established type 1 diabetes at risk for DKA include those with high hemoglobin A1C, diabetes duration of 5 to10 years, and migrant status r28c81c82
  • Higher frequency of DKA is observed among patients with lower socioeconomic status and those with psychiatric disorders r26r29c83c84
  • Recurrent DKA is associated with greater fragmentation of health care r30c85
  • Insulin pump therapy, compared with insulin injection therapy, is associated with lower risk of DKA for children, adolescents, and young adults r31
  • Use of continuous glucose monitoring is associated with lower risk of DKA for children and adolescents with type 1 diabetes r32

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination findings suggest the disorder, but biochemical criteria define it c86
  • Obtain initial laboratory evaluation for all patients, including determination of plasma glucose level, BUN and creatinine levels, serum or urine ketone levels, electrolyte levels (with calculated anion gap), osmolality, urinalysis, venous or arterial pH, and CBC with differential r4
    • A tentative diagnosis can be made with bedside tests of capillary blood glucose level and urinary dipstick ketone level
  • Biochemical diagnostic criteria for diabetic ketoacidosis in adults
    • Hyperglycemia: blood glucose level greater than 250 mg/dL (13.9 mmol/L) or greater than 200 mg/dL (11 mmol/L) in British guidelines r1r33
    • Arterial or venous pH less than 7.3 and/or bicarbonate level less than 15 mEq/L (British guidelines) or less than 15-18 mEq/L (ADA guidelines) r1r33
    • Ketonemia (positive acetoacetater34 or β-hydroxybutyrate level greater than 31 mg/dL [3 mmol/L] r33r34)
    • Ketonuria (2+ or more on standard urine sticks) r33
    • Anion gap greater than 10 mmol/L r1
  • Biochemical diagnostic criteria for DKA in children r5
    • Hyperglycemia: blood glucose level greater than 200 mg/dL (11 mmol/L)
    • Arterial or venous pH less than 7.3 or bicarbonate level less than 18 mmol/L
    • Ketonemia (positive acetoacetate or β-hydroxybutyrate level greater than 31 mg/dL [3 mmol/L] r34r35)
    • Moderate or large ketonuria (2+ or more on standard urine sticks)
  • Diagnostic caveats
    • DKA can occur with normal or only mildly elevated blood glucose levels (referred to as euglycemic DKA) r5
      • May occur in patients who are partially treated or who have consumed little or no carbohydrate; may also be seen with use of sodium-glucose cotransporter 2 inhibitors r5r6
      • Blood glucose level is below 200 mg/dL, but other criteria still apply r6r23
    • Most patients have a low serum bicarbonate level, low pH, and elevated anion gap, but approximately 10% have at least one of these reported as within reference range r36
    • Acetoacetate may be negative early in ketoacidosis


  • Initial diagnostic testing
    • Capillary blood glucose level (while chemistry panel results are pending) r4c87
    • Chemistry panel, including levels of glucose, sodium, potassium, phosphate, magnesium, bicarbonate, BUN, and creatinine r4c88c89c90c91c92c93c94c95c96
      • Sodium must be corrected for hyperglycemia r14
        • Measured sodium (mEq/L) + 0.016 × (glucose [mg/dL] − 100) for glucose level lower than 400 mg/dL
        • Measured sodium (mEq/L) + 0.024 × (glucose [mg/dL] − 100) for glucose level higher than 400 mg/dL
      • Corrected potassium (for acidemia) may be estimated, as acidosis drives potassium from intracellular to extracellular compartments r14
        • Subtract 0.6 mEq/L from measured laboratory test value for each decrease of 0.1 in blood gas pH r37
    • Calculated anion gap level r38c97
      • Sodium (mEq/L) − (chloride [mEq/L] + bicarbonate [mEq/L])
      • Reference range is 6 to 10 mEq/L; a value greater than 10 mEq/L is consistent with DKA
    • Serum osmolality c98
      • Differentiates DKA from hyperglycemic hyperosmolar state in patients with type 2 diabetes r2
        • Reference range is 285 to 295 mOsm/kg; a value greater than 320 mOsm/kg is found in hyperglycemic hyperosmolar state r2
    • Blood gas analysis c99
      • Venous blood gas is comparable to arterial blood gas for measuring pH in DKA r39
      • Arterial blood gas adds information if there is suspected mixed acid-base disorder (ie, vomiting that is confusing the acid-base picture) and helps to clarify the degree of respiratory compensation
      • In the absence of a mixed acid-base disorder, pH is used to differentiate from hyperglycemic hyperosmolar state, and degree of acidosis is one parameter used to classify DKA as mild, moderate, or severe r1
        • pH greater than 7.3: consistent with hyperglycemic hyperosmolar state
        • pH 7.25 to 7.3: consistent with mild DKA
        • pH 7 to 7.24: consistent with moderate DKA
        • pH less than 7: consistent with severe DKA
    • Serum ketone level r2c100
      • Direct measurement of β-hydroxybutyrate is preferred diagnostic test for ketonemia because it is an early and most abundant ketoacid that may first signal development of DKA r40
        • May be measured either via a laboratory service or by a point-of-care meter r41
      • Serum β-hydroxybutyrate level in DKA has been shown to greater than 31 mg/dL (3 mmol/L) in children and greater than 40 mg/dL (3.8 mmol/L) in adults r34r35
      • In practice, a threshold of 31 mg/dL (3 mmol/L) has been adopted for all age groups r33r41
      • Serum acetoacetate (via nitroprusside reaction) is an acceptable alternative test if testing for β-hydroxybutyrate is not available
    • Urine ketone bodies measurement c101
      • Urine ketone tests measure acetoacetate, which may be present in low concentrations initially, even when there is a high level of serum β-hydroxybutyrate
      • Urine ketone body dipstick testing is rapid, convenient, and sensitive (98%) but has poor specificity for DKA (approximately 35%) r42
    • Hemoglobin A1C test c102
      • Not essential for diagnosis or management of DKA but may be useful because it provides information about duration of hyperglycemia
  • Other laboratory testing to aid differential diagnosis or to identify precipitating event, as driven by the clinical presentation: r11
    • CBC (to evaluate for hemorrhage or infection as precipitating causes) c103
      • Leukocytosis with WBC counts in the range of 10,000 to 15,000 cells/µL can be observed in DKA even without infection, owing to stress, dehydration, and demargination of leukocytes r3
    • Blood and urine cultures if there is fever c104c105
    • Serum lactate level, if sepsis is suspected c106
    • Cardiac biomarkers, such as troponin, if there is chest pain or abnormal ECG result c107c108
    • Specific toxin level (eg, salicylate, acetaminophen, alcohols) if toxin is suspected c109
    • Amylase and lipase (if abdominal pain is present or pancreatitis is suspected) c110c111
      • Not specific for pancreatitis in patients with DKA; elevated levels are found in almost one-third of patients with DKA overall r43
      • If levels are elevated, follow up with abdominal CT scan r4c112


  • Imaging is not a required component to make a diagnosis of DKA, but it may be necessary to evaluate for precipitating causes
  • If imaging is obtained, direct it at specific anatomical areas as deemed appropriate according to presenting signs, symptoms, and examination findings; options include chest radiograph or CT scan of brain, abdomen and pelvis, or chest r11c113c114c115c116c117

Functional testing

  • Perform ECG for all adults
    • Acute coronary syndrome and acute myocardial infarction are common precipitants of DKA r11c118
    • Hyperkalemia resulting from DKA may cause characteristic ECG changes, such as prolonged PR interval, peaked T waves, and wide QRS complexes r44
    • Rarely, a pseudoinfarction pattern, with ST-elevation that resolves with correction of biochemical abnormalities may be seen r44



Other diagnostic tools

  • Calculation of water deficit c120
    • For patients with hypernatremia and severe dehydration, an estimate of the water deficit is useful to gauge the amount of fluid necessary to restore a euvolemic state
    • Water deficit: 0.6 × (body weight in kg) × (1 − [corrected sodium / 140]) r45
  • Calculation of anion gap r38c121
    • Standard anion gap: sodium (mEq/L) − (chloride [mEq/L] + bicarbonate [mEq/L]) c122
      • Reference range is 6 to 10 mEq/L; more than 10 mEq/L is consistent with DKA
    • Although the standard anion gap is sufficient in most cases, adjustment for albumin concentration is recommended in cases of hypoalbuminemia c123
      • Albumin-corrected anion gap: anion gap − 2.5 × (4 − serum albumin [g/dL]) r38c124
  • Although the measured serum osmolality is sufficient in most cases, a calculated osmolality is needed to determine the osmolar gap, which is useful to assess for other causes of high anion gap metabolic acidosis c125
    • Calculated formula: (2 × measured sodium [mEq/L]) + (glucose [mg/dL] / 18) + (BUN [mg/dL] / 2.8) r38
    • Osmolal gap c126
      • Difference between measured osmolality and calculated osmolality
      • Can be used as a rapid screen for ethanol, methanol, or ethylene glycol intoxication when there is a high anion gap acidosis
      • High osmolal gap indicates presence of an abnormal solute present in significant amount
      • Osmolal gap greater than 10 can be caused by most toxic alcohols (ethanol, methanol, ethylene glycol) r46

Differential Diagnosis

Most common

  • Hyperglycemic hyperosmolar state c127
    • An acute metabolic complication of diabetes that most often occurs in patients with type 2 diabetes r14
    • Defined by hyperglycemia (usually greater than 600 mg/dL), serum osmolality greater than 320 mOsm/kg, and absence of appreciable metabolic acidosis or ketonemia r14
    • Major overlapping clinical features include hyperglycemia, altered mental status, and dehydration
    • Differentiating factors include the following:
      • Ketonemia and ketonuria, if present, are much less severe in hyperglycemic hyperosmolar state r14
      • Hyperglycemia is elevated in both conditions but more pronounced in hyperglycemic hyperosmolar state, in which glucose concentrations are frequently greater than 600 mg/dL r14
      • Osmolality is usually within reference range or mildly elevated in DKA but is elevated in hyperglycemic hyperosmolar state to more than 320 mOsm/kg r14
      • Typically, there is no metabolic acidosis in hyperglycemic hyperosmolar state (the latter shows bicarbonate level greater than 18 and pH greater than 7.3) r14
      • Severity of dehydration is typically more severe in hyperglycemic hyperosmolar state r14
      • Onset of hyperglycemic hyperosmolar state occurs over several days, whereas DKA can occur within several hours to up to 2 days r2

Other causes of anion gap metabolic acidosis

  • Alcoholic ketoacidosis r36c128
    • Occurs most frequently in people who consume excessive amounts of alcohol and stop drinking abruptly d3
    • Similar to DKA, high anion gap acidosis and serum ketonemia (primarily β-hydroxybutyrate) are present
    • Differentiating factors include the following:
      • Glucose level will usually be within reference range or low in alcoholic ketoacidosis; severe hyperglycemia is uncommon r4
      • Ketonemia is more severe in alcoholic ketoacidosis with a β-hydroxybutyrate to acetoacetate ratio of 7:1 or higher versus a ratio of 3:1 in DKA r4
      • Blood ethanol screen is positive in alcoholic ketoacidosis
      • Osmolal gap greater than 10 mOsm/kg is consistent with alcoholic ketoacidosis
  • Starvation ketosis c129c130
    • Occurs in the setting of prolonged fasting, very-low-carbohydrate diets, or vomiting during pregnancyr47
    • Similar to DKA, laboratory abnormalities show a high anion gap metabolic acidosis; however, the degree of acidosis is typically not as severe
    • Differentiated from DKA by serum bicarbonate level, which is usually at least 18 mEq/L, and absence of hyperglycemia r4
    • Rapid resolution occurs after treatment with IV dextrose
  • Lactic acidosis r48c131
    • As with DKA, laboratory abnormalities show a high anion gap metabolic acidosis
    • Major causes include sepsis, systemic inflammatory response syndrome, cardiogenic or hypovolemic shock, hypoxemia, and severe trauma
    • Metformin, an oral hypoglycemic medication that is sometimes prescribed off-label for patients with insulin-resistant type 1 diabetes, can cause lactic acidosis in the setting of renal failure, so maintain high degree of suspicion if patient is on metformin
    • Factors that favor a diagnosis of lactic acidosis include the following:
      • Elevated blood lactate level (confirm elevated venous lactate level by arterial sampling) confirms a diagnosis of hyperlactatemia
      • Glucose level within reference range
      • Increase in the anion gap closely mirrors the rise in blood lactate level
  • Uremia c132
    • Shared clinical features include symptoms of nausea, vomiting, fatigue, and altered mental status
    • As with DKA, laboratory abnormalities show a high anion gap metabolic acidosis, which develops when GFR falls below 10 mL/1.73 m²/minute r49
    • Differentiated by renal function tests and absence of ketonemia and hyperglycemia r4
  • Toxic ingestion of methanol, ethylene glycol, salicylates, or isoniazid c133c134c135c136d4
    • Shared clinical features include symptoms of altered mental status
    • Similar to DKA, toxic alcohols cause an increase in anion gap levels, but hyperglycemia is not usually present
    • Osmolal gap greater than 10 mOsm/kg is indicative of ingestion of a toxic amount alcohol, and gap greater than 25 mOsm/kg is typical of methanol or ethylene glycol toxicity r36
    • Measurement of serum salicylate, ethanol, and methanol levels is diagnostic r1
    • Ethylene glycol (antifreeze) is suggested by the presence of calcium oxalate and hippurate crystals in the urine r1
    • Methanol toxicity is suggested by visual symptoms
    • Isoniazid toxicity usually produces seizures
    • Salicylate toxicity often has the early triad of hyperventilation, tinnitus, and gastrointestinal upset d5



  • Restore circulatory volume and tissue perfusion
  • Correct hyperglycemia, acidosis, and electrolyte abnormalities as follows r33
    • Reduce blood ketone concentration by 0.5 mmol/L/hour
    • Increase venous bicarbonate by 3.0 mmol/L/hour
    • Reduce capillary blood glucose by 3.0 mmol/L/hour
    • Maintain potassium between 4.0 and 5.5 mmol/L
  • Monitor for and manage any complications of DKA or its treatment
  • Identify and treat the precipitating event


Admission criteria

Most patients with DKA require admission owing to the need for prolonged clinical and laboratory assessment and correction/treatment of the precipitating event, even if fluid resuscitation and correction of acidosis have been accomplished in the emergency department r50

Discharge home from the emergency department or observation unit may be considered for adults if all of the following are present:

  • DKA is mild
  • Precipitating event is easily remedied (eg, missed doses of insulin) and all metabolic abnormalities, including hyperglycemia, acidosis, and electrolyte deficiencies, are corrected and remain stable
  • Patient easily tolerates oral fluids
  • Patient has insulin and glucometer at home, and clinician has confidence that patient is likely to use them correctly

Admit most children with DKA

Criteria for ICU admission
  • Underlying critical illness (eg, myocardial ischemia, sepsis, gastrointestinal hemorrhage)
  • Continued severe acidosis, hypoxia, hypotension, suspected sepsis, altered mental status, or high risk for pulmonary or cerebral edema
  • In children, severe DKA (long symptom duration, hemodynamic compromise, or decreased level of consciousness) or increased risk for cerebral injury r5
    • Conditions that increase risk of cerebral edema in children include the following: r5
      • Age younger than 5 years
      • Low PCO₂ (<21 mm Hg)
      • High BUN level (>20 mg/dL)
      • Severe acidosis (pH < 7.1)

Recommendations for specialist referral

  • Refer to an intensivist when admission to ICU is warranted
  • Refer to an endocrinologist/diabetologist or glucose management team for inpatient management r51
  • For children with DKA, refer to pediatric endocrinologist and/or pediatric intensivist (when possible) for care management
  • Refer all patients with newly diagnosed diabetes or patients who were previously insulin naive to a clinical diabetes educator r3

Treatment Options

Initial treatment often occurs in the emergency department and is continued in the inpatient setting

  • Patients with uncomplicated DKA may sometimes be treated with subcutaneous insulin in the emergency department or step-down unit r51

Major components of treatment include administration of fluids, insulin, and electrolytes

Initial treatment steps:

  • Critical first step is to replenish lost fluids
    • Net fluid losses in DKA average 10% to 15% of body weight in adultsr20 and 5% to 10% in childrenr5
    • Begin aggressive fluid therapy using isotonic saline at a rate of 500 to 1000 mL/hour to increase blood pressure and restore renal perfusion r2r52
    • Goal is to replace total volume loss within 24 to 36 hours, with 50% of resuscitation fluid being administered during the first 12 hours r40
  • Begin insulin therapy after fluids have been started (with supplemental potassium if hypokalemia is presentr53) r2
    • An insulin bolus is often given to adults, but it is not standard practice for children
    • In critically ill and mentally obtunded patients with DKA, continuous IV insulin is the standard of care r51
    • In mild to moderate DKA, subcutaneous injections of rapid-acting insulin analogues are an acceptable alternative to insulin infusion, provided that fluids are replaced adequately, glucose is monitored frequently, and precipitating causes (eg, infection) are treated r51
      • Treatment of mild to moderate DKA with subcutaneous insulin protocols results in significantly lower utilization of hospital resources with no increase in hypoglycemia or mortality r54
      • Subcutaneous injections of rapid-acting insulin analogues are not recommended for patients with hypotension or moderate to severe cases of DKA r3
  • Start electrolyte infusions in the IV fluids to correct imbalances, in accordance with results from laboratory testing r1
    • Initiate IV potassium before insulinr53 when serum concentration is below the upper limit of reference range for the particular laboratory (usually 5-5.2 mEq/L)
      • There is risk of precipitating fulminant hypokalemia in this situation; however, in practice, hypokalemia requiring correction is rare r53
    • Bicarbonate and phosphate replacement is usually unnecessary, but monitor levels closely r55

Drug therapy

  • Insulin c137
    • Adult insulin therapy r2
      • Delay insulin administration until IV fluid is infusing and potassium level is higher than 3.3 mEq/L r2
      • Continuous IV infusion of regular insulin is indicated for patients with moderate to severe DKA or for patients with coexisting critical illness (ie, hypotension, anasarca)
      • Either continuous IV regular insulin infusion or subcutaneous injections of rapid-acting insulin analogues are acceptable in uncomplicated, mild DKA (non-ICU settings) r56
        • Continuous IV insulin infusion has the advantage of rapid half-life and easy titration, but it usually requires greater hospital resources (nursing personnel)
          • Glucose typically falls at a rate of approximately 60 to 120 mg/dL/hour with IV insulin infusion and hydration r2
        • Use of subcutaneous injections of rapid-acting insulin analogues lispror57 or aspartr58 leads to resolution of DKA equally rapidly as IV infusion of regular insulin, but it has been studied only in mild DKA cases
        • Clinical outcomes are similar for treating mild DKA when using IV regular insulin versus subcutaneous rapid-acting analogues, provided that aggressive fluid replacement and blood glucose monitoring are frequent r56
    • Pediatric insulin therapy r5
      • Start insulin administration after starting fluid and potassium (if low initially) replacement
      • IV route is usually preferred for patients with uncomplicated DKA; however, subcutaneous insulin is acceptable in circumstances in which continuous IV administration is not possible and for children with uncomplicated mild to moderate DKA
        • During the COVID-19 pandemic, subcutaneous insulin may be considered for uncomplicated mild to moderate DKA to avoid ICU admission (for IV insulin) when ICU resources are constrained or risk of acquiring COVID-19 infection in this setting is high r59
      • IV route r5
        • Give regular insulin via IV infusion without an initial bolus
          • IV bolus of insulin is not advisable for children with DKA because it may increase risk of cerebral edema, precipitate shock, and exacerbate hypokalemia
        • Continue insulin infusion until DKA resolves (as measured by pH higher than 7.3, bicarbonate level higher than 15 mEq/L, or closure of anion gap); glucose level normalizes earlier than DKA resolves
        • Add 5% dextrose to the IV fluid when the glucose falls to approximately 14 to 17 mmol/L (250-300 mg/dL), or sooner if falling precipitously
      • Subcutaneous route r5
        • Subcutaneous rapid-acting insulin analogue (insulin lispro or insulin aspart) is safe and may be as effective as IV regular insulin infusion for patients with uncomplicated mild to moderate DKA
        • Subcutaneous administration of short-acting (regular) insulin is another alternative for mild DKA when continuous IV infusion or subcutaneous rapid-acting insulin analogues are unavailable
        • Do not use subcutaneous route for patients whose peripheral circulation is impaired
    • Regular insulin c138
      • IV route
        • Insulin Regular (Recombinant) Solution for injection; Infants, Children, and Adolescents: 0.05 to 0.1 unit/kg/hour continuous IV infusion beginning at least 1 hour after starting fluid replacement therapy and continuing until the acidosis is corrected. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.
        • Insulin Regular (Recombinant) Solution for injection; Adults: 0.14 units/kg/hour continuous IV infusion, or alternatively, 0.1 units/kg/dose IV bolus, followed by 0.1 units/kg/hour continuous IV infusion, initially. If serum glucose does not decrease by at least 10% in the first hour, give 0.14 units/kg/dose IV bolus. Adjust dose every 1 to 2 hours based on blood glucose concentration. When the blood glucose concentration decreases to 200 to 250 mg/dL, reduce dose to 0.02 to 0.05 units/kg/hour continuous IV infusion or transition to rapid-acting subcutaneous insulin. Adjust dose to maintain blood glucose of 150 to 200 mg/dL until the acidosis is corrected.
      • Subcutaneous route
        • Insulin Regular (Recombinant) Solution for injection; Infants, Children, and Adolescents: 0.13 to 0.17 units/kg/dose subcutaneously every 4 hours, initially. Adjust dose by 10% to 20% based on blood glucose concentration before the next insulin injection; may increase frequency to every 2 or 3 hours if acidosis is not improving. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.
    • Insulin aspart c139
      • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents: 0.15 units/kg/dose subcutaneously every 2 hours beginning at least 1 hour after the start of fluid replacement therapy. May reduce dose to 0.1 units/kg/dose subcutaneously every 2 hours if blood glucose continues to decrease by more than 90 mg/dL despite the addition of dextrose to intravenous fluids. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.
      • Insulin Aspart (Recombinant) Solution for injection; Adults: 0.2 or 0.3 units/kg/dose subcutaneously as a single bolus dose, then 0.1 units/kg/dose subcutaneously every hour or 0.2 units/kg/dose subcutaneously every 2 hours, initially. Monitor blood glucose concentration every 1 to 2 hours, and when the blood glucose concentration decreases to 200 to 250 mg/dL, reduce dose to 0.1 units/kg/dose subcutaneously every 2 hours to maintain blood glucose of 150 to 200 mg/dL until the acidosis is corrected. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.
    • Insulin lispro c140
      • Insulin Lispro Solution for injection; Children and Adolescents: 0.15 units/kg/dose subcutaneously every 2 hours beginning at least 1 hour after the start of fluid replacement therapy. May reduce dose to 0.1 units/kg/dose subcutaneously every 2 hours if blood glucose continues to decrease by more than 90 mg/dL despite the addition of dextrose to intravenous fluids. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.
      • Insulin Lispro Solution for injection; Adults: 0.2 or 0.3 units/kg/dose subcutaneously as a single bolus dose, then 0.1 units/kg/dose subcutaneously every hour or 0.2 units/kg/dose subcutaneously every 2 hours, initially. Monitor blood glucose concentration every 1 to 2 hours, and when the blood glucose concentration decreases to 200 to 250 mg/dL, reduce dose to 0.1 units/kg/dose subcutaneously every 2 hours to maintain blood glucose of 150 to 200 mg/dL until the acidosis is corrected. Transition to a multi-dose, basal-bolus subcutaneous insulin regimen once the acidosis is corrected and oral intake is tolerated.

Nondrug and supportive care

IV fluids r2c141c142

  • Immediately begin therapy to replace fluids, preceding insulin therapy c143
  • Adult fluids
    • Administer 0.9% normal saline at 0.5 to 1 L/hour for the first 1 to 2 hours r2
    • Subsequent choice of fluid depends on serum sodium level, state of hydration, and glucose levels
      • After 1 to 2 hours, evaluate corrected serum sodium level
        • If sodium level is low, reduce IV fluid rate to between 250 and 500 mL/hour, depending on state of hydration; change to 0.45% normal saline once sodium level is within reference range r2
        • If sodium level is within reference range or higher, switch to 0.45% normal saline at 250 to 500 mL/hour, with rate reduction depending on state of hydration r2
      • Measure and assess glucose level every hour r2
        • Add 5% dextrose to IV fluids when glucose level is approximately 200 to 250 mg/dL
        • Continue 5% dextrose in IV fluids (typically with 0.45% normal saline by this point) until resolution of ketoacidosis r11
    • Aim to replace the total volume loss within 24 to 36 hours, with 50% of resuscitation fluid being administered during the first 12 hours r40
  • Pediatric fluids r5
    • Initially administer 0.9% normal saline at 10 to 20 mL/kg over 20 to 30 minutes to restore circulatory volume r5
      • Higher-volume fluid infusion rates (20 mL/kg bolus + 1.5 × maintenance rate) for pediatric patients with DKA shorten metabolic normalization time compared with lower-volume rates (10 mL/kg bolus + 1.25 × maintenance rate) r60
      • Rapidity of IV fluid replacement and sodium chloride content (0.45% or 0.9%) does not influence rates of cerebral injury r61
      • Use crystalloid not colloid
      • If patient has hypokalemia, start potassium replacement at this time and before starting insulin therapy
    • Subsequently aim to replace the estimated fluid deficit evenly over 24 to 48 hours (in addition to providing the usual daily maintenance fluid requirement) r5
      • Fluid deficit can be replaced with 0.45% to 0.9% saline or a balanced salt solution (Ringer's lactate, Hartmann's solution or Plasma-Lyte)
      • Add potassium to replacement fluids concurrent with initiation of insulin therapy (required regardless of the serum potassium concentration)
      • Add 5% dextrose to IV fluids when glucose level falls to approximately 250 to 300 mg/dL or sooner if falling precipitously
        • If metabolic acidosis persists, change to 10% or 12.5% dextrose while continuing insulin infusion to prevent hypoglycemia


  • Potassium c144
    • Potassium deficit in both children and adults is approximately 3 to 5 mEq/kg (although initial serum potassium level may be measured as within reference range or frankly elevated, owing to hypertonicity, insulin deficiency, and acidosis) r2
    • Ensure that there is adequate urine output and kidney function before replacing potassium
      • Adults
        • Potassium repletion in IV fluids is required unless initial potassium is higher than the upper limit of reference range for the particular laboratory (usually 5-5.2 mEq/L) or there is no urine output r1
        • Add potassium chloride, at 20 to 30 mEq/hour, to 0.45% normal saline and infuse until serum potassium level is greater than 3.3 mEq/L; continue to add potassium chloride to each liter of IV fluid to maintain potassium level within reference range r1
        • If initial potassium level is low, assume that a large potassium deficit exists and that repletion may require more potassium chloride
      • Children
        • If hypokalemic at presentation, start potassium replacement when initiating volume expansion (before starting an insulin infusion) r5
        • If normokalemic, start potassium replacement after volume expansion (when beginning insulin)
        • If hyperkalemic, defer potassium replacement until urine output is well maintained and potassium level is falling
        • Begin with 40 mEq/L potassium in the infusate; maximum rate of IV potassium replacement is usually 0.5 mmol/kg/hour r5
          • May use potassium chloride, potassium phosphate, or potassium acetate individually or in combination
          • Administration of potassium entirely as potassium chloride increases the risk of hyperchloremic metabolic acidosis, whereas administration entirely as potassium phosphate can result in hypocalcemia
  • Bicarbonate c145
    • Adults
      • Bicarbonate is rarely required in the management of DKA for adults because it has not been found to hasten rate of recovery from ketoacidosis or hyperglycemia and may contribute to hypokalemia and cerebral edema r55r62
      • Correction of acidosis with bicarbonate is recommended only if venous pH is less than 6.9 r1
        • For adults with pH less than 6.9, give 100 mEq sodium bicarbonate in 400 mL of sterile water with 20 mEq potassium chloride administered at a rate of 200 mL/hour for 2 hours until the venous pH is greater than 7 r4
        • If pH is less than 7 after first infusion, repeat every 2 hours until pH is greater than 7 r1
    • Children
      • Bicarbonate replacement is associated with elevated risks of cerebral edema and prolonged hospitalization for pediatric patients r62
      • Bicarbonate is not recommended for children, except for treatment of life-threatening hyperkalemia or unusually severe acidosis (pH less than 6.9) with evidence of compromised cardiac contractility r5
  • Phosphate c146
    • Adults
      • Phosphate is rarely required in management of DKA because replacement has not been found to affect clinical outcomes and because aggressive repletion can precipitate hypocalcemia r63
      • Correction of hypophosphatemia is recommended only under very limited circumstances (ie, cardiogenic shock, respiratory failure, serum phosphorus level less than 1 mg/dL) r64
        • If phosphate level is lower than 1 mg/dL or if phosphate level is low and patient is in cardiac or respiratory failure, add 1 mL potassium phosphate to each liter of fluid, with fluid running at 500 mL/hour r64
          • 1 mL of potassium phosphate = 4.4 mEq potassium + 3 mmol (93 mg) phosphate r64
          • Maximal rate of phosphate replacement considered safe is 4.5 mmol/hour (1.5 mL/hour of K₂HPO₄), or a total of 90 mmol/day r64
        • Monitor serum phosphate, magnesium, and calcium levels in patients receiving phosphate infusion r1
    • Children
      • Prompt correction of hypophosphatemia is recommended when serum phosphate level is lower than 1 mg/dL, irrespective of symptoms r5
        • Insulin infusion may be reduced or withheld until phosphorus levels increase
      • Routine phosphate replacement to prevent hypophosphatemia is advisable when readily available, particularly for patients with severe DKA r5
      • Potassium phosphate may be added to replacement IV fluids alone or in combination with potassium chloride or potassium acetate r5
        • Monitor serum calcium level in patients receiving phosphate infusion


  • COVID-19 r59c148
    • COVID‐19 infection may precipitate severe metabolic complications of diabetes including DKA, which may be the initial presentation of new-onset diabetes r15r65r66
    • During the COVID-19 pandemic, utilize telehealth for sick day management and routine diabetes care
    • An increased prevalence of DKA has been noted during the pandemic, which may be a result of inadequate treatment of patients who delay scheduled clinic visits for fear of contracting COVID-19 as well as a direct effect of the SARS-CoV-2 virus r67
    • Patients admitted with DKA who are COVID-positive have increased mortality secondary to more severe COVID-19 rather than DKA r67

Special populations

  • Adolescents with recurrent DKA
    • Psychological evaluation for concurrent psychiatric disease is recommended r68
      • Depression in this population may lead to more missed insulin doses
        • Children's Depression Inventory is a validated tool to screen for depression r69
      • Higher incidence of recurrent DKA is also seen in adolescents with eating disorders
  • DKA in patients with chronic kidney disease r40
    • Clinical presentation and laboratory values in patients with DKA on dialysis may differ from those not on dialysis
      • Patients on dialysis usually have minimal or no signs of volume depletion
      • Hyperkalemia is typically more severe in patients on dialysis compared with those not on dialysis for the same levels of hyperglycemia
      • Metabolic acidosis is usually present in DKA, but a mixed acid-base disorder can occur owing to concomitant metabolic alkalosis from exposure to high-bicarbonate dialysate
      • High anion gap is always present and serves as a valuable clue, particularly when the anion gap is very high (ie, more than 20 mEq/Lr40)
    • Optimal treatment strategies for DKA in patients with advanced chronic kidney disease on dialysis have not been determined by prospective studies r70
      • IV fluids may not be required; however, consider them if there is evidence or history of extracellular fluid loss such as vomiting, diarrhea, or excessive insensible losses
      • If fluids are needed, give small boluses of normal saline (250 mL)r40 while monitoring respiratory and hemodynamic parameters closely
      • Suggested initial rate of IV insulin administration for patients on dialysis is similar to that of patients not on dialysis, with initial insulin bolus of 0.1 units/kg followed by continuous insulin infusion at 0.05 units/kg/hourr40
      • Insulin is typically the only treatment necessary for hyperkalemia due to DKA in patients on dialysis; give potassium only if the level falls below 3.3 mEq/L r40
      • Emergent hemodialysis for patients with DKA is controversial; the main indications are pulmonary edema and severe hyperkalemia
  • DKA in patients with cardiac disease
    • Administer IV fluids cautiously to avoid volume overload and pulmonary edema r14
  • DKA in pregnant patients
    • Pregnant patients develop DKA at significantly lower blood glucose values, and it progresses more rapidly in this population than in patients who are not pregnant r71
    • After 24 weeks of gestation, continuously monitor fetal status owing to risk for fetal hypoxemia and acidosis r72
    • If cesarean delivery of a term infant is deemed necessary owing to nonreassuring fetal heart rate tracings or fetal distress, delay until maternal metabolic status is stabilized (correction of acidosis, electrolyte replacement, and intravascular volume repletion) r71
    • Preterm labor management must take into account maternal condition, viability of the fetus (gestational age), and fetal heart rate tracings r71
      • Magnesium sulfate is the tocolytic of choice
      • Avoid β-adrenergic tocolytics, which can exacerbate hyperglycemia and nifedipine if patient is dehydrated and hypotensive
  • DKA associated with sodium-glucose cotransporter 2 inhibitor therapy (gliflozins) r35
    • Be aware that low serum bicarbonate level and/or presence of positive urinary ketones may not correctly identify DKA; direct measurement of serum ketones (β-hydroxybutyrate) is more accurate
    • For management, stop the drug immediately and proceed with the traditional diabetic ketoacidosis treatment protocol


  • Clinical monitoring during treatment
    • Hourly vital signs and fluid input/output measurements c149c150
    • Hourly assessment by examination for complications related to fluid replacement
      • Signs of pulmonary edema, through auscultation of lungs c151
      • Neurologic assessment (Glasgow coma scale score or similar assessments for warning signs and symptoms of cerebral injury), particularly in children r5
    • Use cardiac monitoring to detect worsening hypokalemia c152
  • Serial monitoring of metabolic parameters during treatment (at intervals noted, until there is resolution of DKA) r4r20
    • Glucose: measure hourly by fingerstick test until DKA has resolved and transition to subcutaneous insulin has occurred c153
    • Electrolytes: measure every 2 to 4 hours c154
      • Monitor calcium level carefully if phosphate is given r5c155
    • Anion gap: calculate every 1 to 2 hours c156
    • Venous pH: measure every 2 to 4 hours (usually corrects slowly over a period of hours to days) c157
    • Unnecessary (optional) parameters to monitor
      • Ketonemia and ketonuria will persist for 1 or 2 days beyond resolution of hyperglycemia and acidosis; repeated measurement is usually not helpful
  • Transition from IV to subcutaneous insulin
    • For patients treated with IV infusion of insulin, transition to subcutaneous route is appropriate once ketoacidosis has resolved, patient is alert, and oral intake is tolerated r73
    • Inject subcutaneous basal insulin at least 2 hours before stopping the insulin infusion
      • Give subcutaneous basal insulin at least 2 hours before discontinuing the IV insulin infusion; inject earlier if a basal insulin analogue (eg, glargine, detemir, degludec) r3
      • Patients previously treated with insulin can resume their usual home insulin schedule and dose if outpatient glycemic control was acceptable
      • Initiate a multidose insulin regimen for patients who are insulin naive, preferably consisting of a basal-bolus protocol using insulin analogues r1r13d1
        • Multidose insulin regimens with basal insulin and prandial rapid-acting insulin analogues are the preferred insulin regimens for patients with type 1 diabetes r3
          • Basal insulin analogue plus prandial insulin analogue regimens are associated with less hypoglycemia than isophane insulin/regular insulin regimens r74
      • Continue subcutaneous insulin with individualized dose based on response; continue fingerstick glucose monitoring at hourly intervals during this process c158
      • Continue fingerstick glucose monitoring at hourly intervals during the transition process, but frequency may be decreased incrementally thereafter (ie, to every 4 hours) r40
  • Criteria for resolution of DKA
    • Blood glucose level less than 200 mg/dL plus any 2 of the following: r1
      • Serum bicarbonate level 15 mEq/L or higher r1
      • Venous blood pH greater than 7.3 r1
      • Anion gap 12 mEq/L or less r1

Complications and Prognosis


  • Treatment-related complications
    • Hypokalemia will usually occur if potassium is not replaced, especially if bicarbonate is administered r4c159d6
    • Hypoglycemia can develop with overzealous treatment with insulin c160
      • Risk factors for treatment-related hypoglycemia include inadequate monitoring (insufficient frequency of glucose measurements), failure to reduce insulin infusion rates appropriately, and/or failure to add dextrose to IV fluidsr3 once glucose levels fall to less than 250 mg/dL
    • Pulmonary edema c161
      • Occurs most commonly in patients with known cardiac disease
      • For these patients, administer fluids cautiously with frequent pulmonary auscultation and monitor oxygen saturation with pulse oximetry
    • Acute respiratory distress syndrome r75c162d7
      • Perform frequent pulmonary auscultation and monitor oxygen saturation with pulse oximetry
      • Administer fluids cautiously if there are any signs of pulmonary edema
      • Condition usually requires mechanical ventilation
  • Non–treatment-related complications
    • Cerebral edema c163
      • May or may not be a treatment-related complication, as evidence associates it with various factors such as disease severity and reduced cerebral blood flow with possible reperfusion injury r61
      • Usually develops within 12 hours of commencing treatment r5
      • Occurs most commonly in young people with DKA (ie, younger than 20 years, especially children younger than 5 years) r5r20
      • Risk factors include pH lower than 7, PCO₂ lower than 20 mm Hg, and more than 50 mL/kg fluids administered in first 4 hours r20
      • Symptoms and signs r5
        • Change in neurologic status (eg, confusion, fluctuating level of consciousness, abnormal motor or verbal response to pain)
        • Specific neurologic signs (eg, cranial nerve palsies, decorticate or decerebrate posture)
        • Age-inappropriate incontinence
        • Heart rate slowing by more than 20 beats per minute (unrelated to sleep or intravascular volume repletion) and/or blood pressure > 90 mm Hg diastolic
        • Abnormal respiratory pattern (eg, grunting, tachypnea, Cheyne-Stokes respiration, apneusis)
        • Vomiting, headache, lethargy; development of headache or substantial worsening of headache after commencing treatment is especially concerning
      • Neuroimaging is not required for diagnosis, and treatment of symptomatic patient should not be delayed in order to obtain imaging
      • Immediate treatment measures r5r11r20
        • Impose head-up position
        • Adjust IV fluid administration rate to avoid excess fluid while maintaining normal blood pressure
        • Administer mannitol if necessary
        • Hypertonic saline can be given as an alternative to mannitol or in addition to mannitol
    • Acute kidney injury r52r76c164
    • Disseminated intravascular coagulation (rare) c165


  • Most patients who are treated rapidly and appropriately recover within 48 hours without sequelae r40r77
    • Average time to resolution is between 10 and 18 hours r3
  • Overall mortality in the United States is less than 1%, but it is much higher in developing countries (approximately 11%-30%) r4
  • Higher rates are reported in patients older than 60 yearsr78 and in those with severe concomitant illnessesr2
  • Mortality rate in children is 0.15% to 0.30%; cerebral edema is responsible for 60% to 90% of these deaths r11
  • Mortality rate in adults is usually related to the underlying precipitating event r11

Screening and Prevention

Screening c166


  • Strategies that effectively prevent DKA for patients with new-onset type 1 diabetes have not been conclusively identified
    • Studies are underway to determine whether expanding physician and public awareness of the condition may reduce DKA at first diagnosis r79
  • Prevention of recurrent DKA in patients with established type 1 diabetes involves 2 main issues: r80
    • Better access to medical care c167
    • Improved management of individual patients, including education about sick day managementr82r81c168c169
  • Encourage patient to use sick day measures for acute illnesses, as follows: r82
    • Increase fluid intake c170
    • Administer additional immediate-acting insulin boluses to correct for hyperglycemia and ketonemia, even if oral intake is decreased
    • Monitor blood glucose level every 2 to 3 hours c171
    • Check ketone level (eg, blood test strip, urine test strip) if glucose level is high or if abdominal pain, nausea, or vomiting is present
  • Participation in initiatives to educate patients in self-management can be effective for preventing DKA r80r83
    • Adherence to prescribed insulin regimen c172
    • Adherence to self-monitoring of blood glucose c173
    • Education about sick day management r84c174
      • Contact physician early in the process
      • Emphasize the importance of insulin during an illness and stress never to discontinue insulin without contacting a member of the health care team
      • Measure and record logs of body temperature, blood glucose level, blood or urine ketone test results, insulin doses, oral intake, and weight
    • Use of home blood ketone monitoring, which detects β-hydroxybutyrate levels, can allow early recognition of impending ketoacidosis and aid in management of ketosis r40c175c176
  • Prevention of DKA in individuals using sodium-glucose cotransporter 2 inhibitors (gliflozins) r85
    • Potential strategies include advising discontinuation of this drug class during severe illness and 24 hours before planned surgical procedures, avoiding excess alcohol, refraining from very-low-carbohydrate diets, and monitoring serum ketones during illness or periods of fasting r2r35c177c178c179c180
    • Use is not recommended for patients with type 1 diabetes or patients with type 2 diabetes who have risk factors for DKA (eg, pancreatic insufficiency, drug or alcohol use disorder) r24
Kitabchi AE et al: Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 32(7):1335-43, 200919564476Umpierrez G et al: Diabetic emergencies--ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol. 12(4):222-32, 201626893262Fayfman M et al: Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 101(3):587-606, 201728372715Nyenwe EA et al: The evolution of diabetic ketoacidosis: an update of its etiology, pathogenesis and management. Metabolism. 65(4):507-21, 201626975543Glaser N et al: ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 23(7):835-856, 202236250645Modi A et al: Euglycemic diabetic ketoacidosis. Curr Diabetes Rev. 13(3):315-21, 201727097605Rosenstock J et al: Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 38(9):1638-42, 201526294774Lucero P et al: Euglycemic diabetic ketoacidosis in the ICU: 3 case reports and review of literature. Case Rep Crit Care. 2018:1747850, 201830364093Dabelea D et al: Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 133(4):e938-45, 201424685959Umpierrez G et al: Abdominal pain in patients with hyperglycemic crises. J Crit Care. 17(1):63-7, 200212040551Van Ness-Otunnu R et al: Hyperglycemic crisis. J Emerg Med. 45(5):797-805, 201323786780Olivieri L et al: Diabetic ketoacidosis in the pediatric emergency department. Emerg Med Clin North Am. 31(3):755-73, 201323915602Wolfsdorf JI et al: ISPAD clinical practice consensus guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 19(suppl 27):155-77, 201829900641Maletkovic J et al: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 42(4):677-95, 201324286946Reddy PK et al: Diabetic ketoacidosis precipitated by COVID-19: a report of two cases and review of literature. Diabetes Metab Syndr. 14(5):1459-62, 202032771918Quiros JA et al: Elevated serum amylase and lipase in pediatric diabetic ketoacidosis. Pediatr Crit Care Med. 9(4):418-22, 200818496406Goldenberg RM et al: Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: the STOP DKA protocol. Diabetes Obes Metab. 21(10):2192-202, 201931183975Ibrahim M et al: Recommendations for management of diabetes during Ramadan: update 2020, applying the principles of the ADA/EASD consensus. BMJ Open Diabetes Res Care. 8(1), 202032366501Deeb A et al: ISPAD clinical practice consensus guidelines: fasting during Ramadan by young people with diabetes. Pediatr Diabetes. 21(1):5-17, 202031659852Corwell B et al: Current diagnosis and treatment of hyperglycemic emergencies. Emerg Med Clin North Am. 32(2):437-52, 201424766942Horii T et al: On-label use of sodium-glucose cotransporter 2 inhibitors may increase the risk of diabetic ketoacidosis in patients with type 1 diabetes. J Diabetes Investig. ePub, 202133448127Peters AL et al: Diabetic ketoacidosis with canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 1 diabetes. Diabetes Care. 39(4):532-8, 201626989182Morton A: Review article: ketoacidosis in the emergency department. Emerg Med Australas. ePub, 202032266781Douros A et al: Sodium-glucose cotransporter-2 inhibitors and the risk for diabetic ketoacidosis: a multicenter cohort study. Ann Intern Med. 173(6):417-25, 202032716707Hong AR et al: Immune checkpoint inhibitor-induced diabetic ketoacidosis: a report of four cases and literature review. Front Endocrinol (Lausanne). 11:14, 202032047478Ehrmann D et al: Risk factors and prevention strategies for diabetic ketoacidosis in people with established type 1 diabetes. Lancet Diabetes Endocrinol. 8(5):436-46, 202032333879Ebekozien O et al: Full inequities in diabetic ketoacidosis among patients with type 1 diabetes and COVID-19: data from 52 US clinical centers. J Clin Endocrinol Metab. ePub, 202133410917Kalscheuer H et al: Event rates and risk factors for the development of diabetic ketoacidosis in adult patients with type 1 diabetes: analysis from the DPV registry based on 46,966 patients. Diabetes Care. 42(3):e34-6, 201930655381Weinstock RS et al: Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 98(8):3411-9, 201323760624Mays JA et al: An evaluation of recurrent diabetic ketoacidosis, fragmentation of care, and mortality across Chicago. Diabetes Care. 39(10):1671-6, 201627422579Karges B et al: Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes. JAMA. 318(14):1358-66, 201729049584Tauschmann M et al: Reduction in diabetic ketoacidosis and severe hypoglycemia in pediatric type 1 diabetes during the first year of continuous glucose monitoring: a multicenter analysis of 3,553 subjects from the DPV registry. Diabetes Care. 43(3):e40-2, 202031969340Joint British Diabetes Societies for Inpatient Care: The Management of Diabetic Ketoacidosis in Adults. Association of British Clinical Diabetologists website. Revised March 2023. Accessed May 23, 2023.https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_02_DKA_Guideline_with_QR_code_March_2023.pdfhttps://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_02_DKA_Guideline_with_QR_code_March_2023.pdfSheikh-Ali M et al: Can serum beta-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care. 31(4):643-7, 200818184896Handelsman Y et al: American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 22(6):753-62, 201627082665Graber MN: Diabetes and hyperglycemia. In: Adams JG et al, eds: Emergency Medicine. 2nd ed. Saunders; 2013:1369-78Adrogué HJ et al: Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 71(3):456-67, 19817025622Kamel KS et al: Acid-base problems in diabetic ketoacidosis. N Engl J Med. 372(6):546-54, 201525651248Brandenburg MA et al: Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis. Ann Emerg Med. 31(4):459-65, 19989546014Gosmanov AR et al: Management of adult diabetic ketoacidosis. Diabetes Metab Syndr Obes. 7:255-64, 201425061324Kilpatrick ES et al: Controversies around the measurement of blood ketones to diagnose and manage diabetic ketoacidosis. Diabetes Care. 45(2):267-72, 202235050366Arora S et al: Diagnostic accuracy of point-of-care testing for diabetic ketoacidosis at emergency-department triage: {beta}-hydroxybutyrate versus the urine dipstick. Diabetes Care. 34(4):852-4, 201121307381Nair S et al: Association of diabetic ketoacidosis and acute pancreatitis: observations in 100 consecutive episodes of DKA. Am J Gastroenterol. 95(10):2795-800, 200011051350Wray J et al: ST-segment elevation in the setting of diabetic ketoacidosis: is it acute coronary syndrome? Cureus. 12(3):e7409, 202032337133Cheuvront SN et al: Water-deficit equation: systematic analysis and improvement. Am J Clin Nutr. 97(1):79-85, 201323235197Kraut JA et al: Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis. 58(3):480-4, 201121794966Freeman TF et al: Acute intractable vomiting and severe ketoacidosis secondary to the Dukan Diet. J Emerg Med. 47(4):e109-12, 201425154557Kraut JA et al: Lactic acidosis. N Engl J Med. 371(24):2309-19, 201425494270Kraut JA et al: Metabolic acidosis of CKD: an update. Am J Kidney Dis. 67(2):307-17, 201626477665American Diabetes Association: Hospital admission guidelines for diabetes. Diabetes Care. 27(suppl 1):S103, 200414693939ElSayed NA et al: 16. Diabetes Care in the Hospital: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S267-S278, 202336507644Jayashree M et al: Fluid therapy for pediatric patients with diabetic ketoacidosis: current perspectives. Diabetes Metab Syndr Obes. 12:2355-61, 201931814748Jang TB et al: Hypokalemia in diabetic ketoacidosis is less common than previously reported. Intern Emerg Med. 10(2):177-80, 201525403843Rao P et al: Evaluation of outcomes following hospital-wide implementation of a subcutaneous insulin protocol for diabetic ketoacidosis. JAMA Netw Open. 5(4):e226417, 202235389497Forțofoiu M et al: New strategies of diagnostic and therapeutic approach to emergencies in the evolution of patients with diabetes mellitus (Review). Exp Ther Med. 23(2):178, 202235069859Andrade-Castellanos CA et al: Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. Cochrane Database Syst Rev. 1:CD011281, 201626798030Umpierrez GE et al: Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 117(5):291-6, 200415336577Umpierrez GE et al: Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care. 27(8):1873-8, 200415277410Priyambada L et al: ISPAD clinical practice consensus guideline: diabetic ketoacidosis in the time of COVID-19 and resource-limited settings-role of subcutaneous insulin. Pediatr Diabetes. 21(8):1394-402, 202032935435Bakes K et al: Effect of volume of fluid resuscitation on metabolic normalization in children presenting in diabetic ketoacidosis: a randomized controlled trial. J Emerg Med. 50(4):551-9, 201626823137Kuppermann N et al: Clinical trial of fluid infusion rates for pediatric diabetic ketoacidosis. N Engl J Med. 378(24):2275-87, 201829897851Chua HR et al: Bicarbonate in diabetic ketoacidosis--a systematic review. Ann Intensive Care. 1(1):23, 201121906367Fisher JN et al: A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab. 57(1):177-80, 19836406531Miller DW et al: Hypophosphatemia in the emergency department therapeutics. Am J Emerg Med. 18(4):457-61, 200010919539Boddu SK et al: New onset diabetes, type 1 diabetes and COVID-19. Diabetes Metab Syndr. 14(6):2211-7, 202033395782Gorthi RS et al: COVID-19 presenting with diabetic ketoacidosis: a case series. AACE Clin Case Rep. ePub, 202033521253Khan F et al: The impact of COVID-19 on diabetic ketoacidosis patients. Diabetes Metab Syndr. 16(1):102389, 202235016042ElSayed NA et al: 14. Children and Adolescents: Standards of Care in Diabetes-2023. Diabetes Care. 46(Suppl 1):S230-S253, 202336507640Corathers SD et al: Improving depression screening for adolescents with type 1 diabetes. Pediatrics. 132(5):e1395-402, 201324127480Varma R et al: Lesson of the month 1: diabetic ketoacidosis in established renal failure. Clin Med (Lond). 16(4):392-3, 201627481389de Veciana M: Diabetes ketoacidosis in pregnancy. Semin Perinatol. 37(4):267-73, 201323916025Sibai BM et al: Diabetic ketoacidosis in pregnancy. Obstet Gynecol. 123(1):167-78, 201424463678Karajgikar ND et al: Addressing pitfalls in management of diabetic ketoacidosis (DKA) with a standardized protocol. Endocr Pract. ePub, 201930657360Umpierrez GE et al: Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care. 32(7):1164-9, 200919366972Konstantinov NK et al: Respiratory failure in diabetic ketoacidosis. World J Diabetes. 6(8):1009-23, 201526240698Weissbach A et al: Acute kidney injury in critically ill children admitted to the PICU for diabetic ketoacidosis. A retrospective study. Pediatr Crit Care Med. 20(1):e10-4, 201930358661American Diabetes Association: Hyperglycemic crises in diabetes. Diabetes Care. 27(suppl 1):S94-102, 200314693938Malone ML et al: Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc. 40(11):1100-4, 19921401693Baldelli L et al: A survey of youth with new onset type 1 diabetes: opportunities to reduce diabetic ketoacidosis. Pediatr Diabetes. 18(7):547-52, 201727726268Jefferies CA et al: Preventing diabetic ketoacidosis. Pediatr Clin North Am. 62(4):857-71, 201526210621Chiang JL et al: Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 41(9):2026-44, 201830093549Dayton KA et al: What the primary care provider needs to know to diagnose and care for adolescents with type 1 diabetes. J Pediatr. 179:249-55, 201627663214Laffel LM et al: Changing the process of diabetes care improves metabolic outcomes and reduces hospitalizations. Qual Manag Health Care. 6(4):53-62, 199810339045Nyenwe EA et al: Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract. 94(3):340-51, 201121978840Danne T et al: International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors. Diabetes Care. ePub, 201930728224