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Aug.10.2019

Diabetic ketoacidosis

Synopsis

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 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

  • Initial urgent actions for DKA
    • Rapidly assess patients in whom DKA is suspected with bedside fingerstick glucose test and blood or urine test strip for ketones
    • 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
    • Start treatment of DKA with volume expansion, establishing at least 1 large-bore IV line to deliver 0.9% normal saline
    • Begin an IV infusion of regular insulin only after rehydration has begun and potassium level is documented to be within reference range or high. If potassium level is low, add potassium to infusing IV fluids before administering insulin
    • Perform ECG in all adult patients to assess for myocardial ischemia or infarction as a precipitating stressor causing DKA
    • Suspect infection as the precipitating stressor in febrile patients. Obtain cultures and begin appropriate empiric antibiotics quickly in this group
  • Initial urgent actions for cerebral edema in children r3
    • Adjust fluid administration rate to maintain normal blood pressure while avoiding excessive fluid administration that might increase cerebral edema
    • Give mannitol, 0.5 to 1 g/kg IV, over 10 to 15 minutes
      • Effect should be apparent after 15 minutes and should last 2 hours; if no response, repeat after 30 minutes
    • An alternative or addition to mannitol is hypertonic saline (3%) with suggested dose of 2.5 to 5 mL/kg over 10 to 15 minutes
    • Elevate head of bed to 30° and keep patient's head in midline position
    • Be prepared to intubate if there are any signs of impending respiratory failure

Pitfalls

  • 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 due 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 to 4 hours for basal insulin analogues) r4

Terminology

Clinical Clarification

  • Diabetic ketoacidosis is a crisis that occurs as an acute metabolic complication of diabetes mellitus; it is defined by 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) r5

Classification

  • 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
      • Alert to drowsy mental status
      • 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 7.2 to 7.3 or bicarbonate level less than 15 mEq/L r3
    • Moderate DKA
      • Venous pH 7.1 to 7.2 or bicarbonate level less than 10 mEq/L r3
    • Severe DKA
      • Venous pH less than 7.1 or bicarbonate level less than 5 mEq/L r3
  • 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)

Diagnosis

Clinical Presentation

History

  • Adult patients most often have a history of type 1 diabetes, although DKA can rarely develop in patients with ketosis-prone type 2 diabetes r5c1
  • Children and young adults (younger than 20 years) present with DKA 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 c2
    • Polyuria c3
    • Fatigue c4
    • Blurry vision c5
    • Weight loss c6
  • Other symptoms that are found variably include:
    • Nausea, vomiting, and abdominal pain (40%-75% of cases) r10c7c8c9
      • Abdominal pain attributable solely to DKA is typically diffuse and follows periods of protracted vomiting and worsening acidemia r11c10c11
    • Dyspnea, due to tachypnea c12
    • Headache, due to cerebral edema (children) r12c13
    • New-onset enuresis (children) r12c14
    • Confusion or drowsiness c15c16
  • Other symptoms that can suggest a precipitating event:
    • Chest pain (acute coronary syndrome) c17
    • Fever (many infections), although hypothermia can also occur from peripheral vasodilation c18c19
    • Cough and dyspnea (pneumonia or heart failure) c20c21c22c23
  • 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 DKA:
      • Alcohol
      • Methanol
      • Ethylene glycol
      • Isoniazid

Physical examination

  • Physical examination findings vary, depending on degree of dehydration and any other accompanying conditions
  • Tachycardia and hypotension, due to volume depletion r4c27c28
  • Dry mucous membranes, poor skin turgor, and sunken eyes r4c29c30c31
  • Prolonged capillary refill time (especially useful for predicting dehydration in young children) r3c32c33
  • Kussmaul respiration (tachypnea with deep inspirations) r4c34
  • Fruity breath odor r4c35
  • Altered mental status, ranging from drowsiness to coma with increasing severity of DKA r4c36c37c38
  • Fever, in the setting of infection

Causes and Risk Factors

Causes

  • Type 1 diabetes plus precipitating factors c39d1
    • Medical or surgical illness (altogether accounts for 60% of cases) r13
      • Infection (eg, sepsis, pneumonia, urinary tract infection, meningitis) c40c41c42c43c44
      • Myocardial ischemia c45
      • Cerebrovascular accident c46
      • Gastrointestinal bleeding c47
      • Pancreatitis (common in adults,r11but rare in childrenr14) c48c49
      • Less common: r11
        • Gastrointestinal diseases causing nausea and vomiting c50
        • Trauma c51
        • Surgery c52
        • Alcohol use c53
        • Substance misuse (eg, cocaine) c54c55
        • Pregnancy c56
        • Eating disorders c57
        • Ingestion of drugs that decrease carbohydrate metabolism
          • Sympathomimetics c58
          • Corticosteroids c59
          • Atypical antipsychotics c60
          • Thiazide diuretics c61
        • Off-label use of sodium-glucose cotransporter 2 inhibitors (gliflozins) in patients with type 1 diabetes c62
    • Inadequate exogenous insulin (accounts for 40% of cases) r13c63
      • Omission of insulin due to nonadherence or self-administration error c64
      • Unrecognized interruption of insulin delivery in users of insulin pumps (eg, insulin pump malfunction) c65
    • Type 2 diabetes plus precipitating factors c66d2
      • Acute decrease in insulin production owing to pancreatic β-cell dysfunction and temporary insulin resistance r15
      • Use of sodium-glucose cotransporter 2 inhibitors (gliflozins) r8r16c67

Risk factors and/or associations

Age
  • Incidence and mortality higher in children than in adults c68c69
  • 30% of patients younger than 20 years first receive diabetes diagnosis when they present with DKA r9
Other risk factors/associations
  • Patients with established type 1 diabetes at risk for DKA include those with high hemoglobin A1C, diabetes duration of 5 to 10 years, and migrant status r17c70c71
  • Higher frequency of DKA is observed in patients with lower socioeconomic status r18c72
  • Recurrent DKA is associated with greater fragmentation of health care r19c73c74
  • Insulin pump therapy, compared with insulin injection therapy, is associated with lower risk of DKA in children, adolescents, and young adults r20

Diagnostic Procedures

Primary diagnostic tools

  • History and physical examination findings suggest the disorder, but biochemical criteria define it c75
  • Obtain initial laboratory evaluation in all patients, including determination of plasma glucose level, BUN and creatinine levels, serum or urine ketone level, electrolyte levels (with calculated anion gap), osmolality, urinalysis, venous or arterial pH, and CBC with differential r5
    • A tentative diagnosis can be made with bedside tests of capillary blood glucose level and urinary dipstick ketone level
  • Biochemical diagnostic criteria for DKA in adults r3
    • Hyperglycemia (blood glucose level greater than 250 mg/dL)
    • Arterial or venous pH less than 7.3 or bicarbonate level less than 18 mEq/L
    • Ketonemia (positive acetoacetater21 or β-hydroxybutyrate level greater than 40 mg/dL [3.8 mmol/L] in adultsr21r22)
    • Ketonuria
    • Anion gap greater than 10 mmol/L
  • Biochemical diagnostic criteria for DKA in children r3
    • Hyperglycemia (blood glucose level greater than 200 mg/dL)
    • Arterial or venous pH less than 7.3 or bicarbonate level less than 15 mmol/L
    • Ketonemia (positive acetoacetate or β-hydroxybutyrate level greater than 31 mg/dL [3 mmol/L] in childrenr22r21)
    • Moderate or large ketonuria
  • Diagnostic caveats
    • In euglycemic DKA, the glucose level is below 200 mg/dL, but other criteria apply r6
    • 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 r23
    • Acetoacetate may be negative early in ketoacidosis

Laboratory

  • Initial diagnostic testing
    • Capillary blood glucose level (while chemistry panel results are pending) r5c76
    • Chemistry panel, including levels of glucose, sodium, potassium, phosphate, magnesium, bicarbonate, BUN, and creatinine r5c77c78c79c80c81c82c83c84c85
      • Sodium must be corrected for hyperglycemia r13
        • 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 r13
        • Subtract 0.6 mEq/L from measured laboratory test value for each decrease of 0.1 in blood gas pH r24
    • Calculated anion gap level r25c86
      • 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 c87
      • 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 c88
      • Venous blood gas is comparable to arterial blood gas for measuring pH in DKA r26
      • 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 1 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 r2c89
      • Direct measurement of β-hydroxybutyrate is preferred diagnostic test of ketonemia because it is an early and most abundant ketoacid that may first signal development of DKA r27
        • May be measured either via a laboratory service or by a point of care meter
      • Serum β-hydroxybutyrate level in DKA is greater than 31 mg/dL (3 mmol/L) in children and greater than 40 mg/dL (3.8 mmol/L) in adults r21r22
      • Serum acetoacetate (via nitroprusside reaction) is an acceptable alternative test if testing for β-hydroxybutyrate is not available
    • Urine ketone bodies measurement c90
      • 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%) r28
    • Hemoglobin A1C test c91
      • 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) c92
      • 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 r4
    • Blood and urine cultures if there is fever c93c94
    • Serum lactate level, if sepsis is suspected c95
    • Cardiac biomarkers, such as troponin, if there is chest pain or abnormal ECG result c96c97c98c99
    • Specific toxin level (eg, salicylate, acetaminophen, alcohols) if toxin is suspected c100
    • Amylase and lipase (if abdominal pain is present or pancreatitis is suspected) c101c102c103c104
      • Not specific for pancreatitis in DKA; elevated levels are found in almost one-third of patients with DKA overall r29
      • If levels are elevated, follow up with abdominal CT scan r5c105

Imaging

  • 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 anatomic 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 r11c106c107c108c109c110

Functional testing

  • Perform ECG in all adults, because acute coronary syndrome and acute myocardial infarction are common precipitants of DKA r11c111c112

Other diagnostic tools

  • Calculation of water deficit c113
    • For hypernatremic patients with 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]) r30
  • Calculation of anion gap r25
    • Standard anion gap: sodium (mEq/L) − [chloride (mEq/L) + bicarbonate (mEq/L)]
      • 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 c114
      • Albumin-corrected anion gap: anion gap − 2.5 × [4 − serum albumin (g/dL)] r25
  • 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 c115
    • Calculated formula: [2 × measured sodium (mEq/L)] + [glucose (mg/dL) / 18] + [BUN (mg/dL) / 2.8] r25
    • Osmolal gap
      • 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) r31

Differential Diagnosis

Most common

  • Hyperglycemic hyperosmolar state c116c117
    • An acute metabolic complication of diabetes that most often occurs in patients with type 2 diabetes r13
    • Defined by hyperglycemia (usually greater than 600 mg/dL), serum osmolality greater than 320 mOsm/kg, and absence of appreciable metabolic acidosis or ketonemia r13
    • 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 r13
      • Hyperglycemia is elevated in both conditions but more pronounced in hyperglycemic hyperosmolar state, where glucose concentrations are frequently greater than 600 mg/dL r13
      • Osmolality is usually within reference range or mildly elevated in DKA, but is elevated in hyperglycemic hyperosmolar state to more than 320 mOsm/kg r13
      • Typically, there is no metabolic acidosis in hyperglycemic hyperosmolar state (the latter shows bicarbonate greater than 18 and pH greater than 7.3) r13
      • Severity of dehydration is typically more severe in hyperglycemic hyperosmolar state r13
      • 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 r23c118c119
    • Occurs most frequently in people who abuse 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 r5
      • 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 r5
      • Blood ethanol screen is positive in alcoholic ketoacidosis
      • Osmolal gap greater than 10 mOsm/kg is consistent with alcoholic ketoacidosis
  • Starvation ketosis c120c121c122
    • Occurs in the setting of prolonged fasting, very-low-carbohydrate diets, or vomiting during pregnancyr32
    • 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 r5
    • Rapid resolution occurs after treatment with IV dextrose
  • Lactic acidosis r33c123
    • 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 used off-label in 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 c124
    • 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/minute/1.73 m² r34
    • Differentiated by renal function tests and absence of ketonemia and hyperglycemia r5
  • Toxic ingestion of methanol, ethylene glycol, salicylates, or isoniazid c125c126c127c128
    • Shared clinical features include symptoms of altered mental status
    • Similar to DKA, toxic alcohols cause an increase in anion gap levels, but patient is not usually hyperglycemic
    • Osmolal gap greater than 10 mOsm/kg is indicative of ingestion of a toxic alcohol, and gap greater than 25 mOsm/kg is typical of methanol or ethylene glycol toxicity r23
    • 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 d4

Treatment

Goals

  • Restore circulatory volume and tissue perfusion
  • Correct hyperglycemia, acidosis, and electrolyte abnormalities
  • Monitor for and manage any complications of DKA or its treatment
  • Identify and treat the precipitating event

Disposition

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 has been accomplished in the emergency department r35

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
    • Conditions that increase risk of cerebral edema in children include the following: r3
      • Age younger than 5 years
      • Low PCO₂
      • High BUN level
      • Severe acidosis
    • Generally, admit all children younger than 5 years to ICU because of high risk for cerebral edema r3

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 r36
  • 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 r4

Treatment Options

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

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

Initial treatment steps:

  • Critical first step is to replenish lost fluids
    • Begin aggressive fluid therapy using isotonic saline at a rate of 500 to 1000 mL/hour to increase blood pressure and restore renal perfusion r2
    • Goal is to replace total volume loss within 24 to 36 hours, with 50% of resuscitation fluid being administered during the first 12 hours r27
    • Net fluid losses in DKA average 10% to 15% of body weight in adultsr15 and 5% to 10% in childrenr3
  • Begin insulin therapy after fluids have been started r2
    • An insulin bolus is often given in adults, but it is not standard practice for children
    • Insulin is typical administered via IV infusion in DKA
      • In critically ill and mentally obtunded patients with DKA, continuous IV insulin is the standard of care r36
      • For uncomplicated mild cases only, subcutaneous injections of rapid-acting insulin analogues are an acceptable alternative provided that fluids are replaced adequately and glucose is monitored frequently r36
        • Subcutaneous injections of rapid-acting insulin analogues are not recommended for patients with hypotension or moderate to severe cases of DKA r4
  • Start electrolyte infusions in the IV fluids to correct imbalances, in accordance with results from laboratory testing r1
    • Initiate IV potassium when serum concentration is below the upper limit of reference range for the particular laboratory (usually 5-5.2 mEq/L)
    • Bicarbonate and phosphate replacement is usually unnecessary, but levels should be monitored closely

Drug therapy

  • Insulin
    • 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) r37
        • Continuous IV insulin infusion has the advantage of rapid half-life and easy titration, but it usually requires greater hospital resources (nursing personnel)
        • Use of subcutaneous injections of rapid-acting insulin analogues lispror38 or aspartr39 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 r37
      • IV route
        • Administer regular insulin bolus of 0.1 units/kg r2
        • Continue regular insulin infusion of 0.1 units/kg/hour r2
          • Glucose typically falls at a rate of approximately 60 to 120 mg/dL/hour with insulin and hydration r2
        • Reduce regular insulin rate to 0.05 units/kg/hour (or half of initial rate) once blood glucose level reaches 250 mg/dL r2
        • Thereafter, adjust regular insulin infusion rate (range of 0.02-0.05 units/kg/hour) to maintain glucose level between 150 and 200 mg/dL until resolution of ketoacidosis r1
      • Subcutaneous route
        • Administer rapid-acting insulin analogue bolus of 0.2 units/kg r2
        • Continue rapid-acting insulin analogue with doses of 0.2 units/kg every 2 hours r2
        • Reduce insulin rate to 0.1 units/kg (or half of initial rate) every 2 hours once blood glucose level reaches 250 mg/dL r2
        • Thereafter, adjust insulin dose and frequency to maintain glucose level between 150 and 200 mg/dL until resolution of ketoacidosis r1
    • Pediatric insulin therapy r3
      • 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 where continuous IV administration is not possible r3
      • IV route
        • Give regular insulin via IV infusion without an initial bolus
        • IV bolus of insulin is not advisable in children with DKA because it may increase risk of cerebral edema, precipitate shock, and exacerbate hypokalemia
        • Start infusion at 0.05 to 0.1 units/kg/hour IV
        • Continue insulin infusion at this rate 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
        • Progressively reduce rate (ie, to 0.05 units/kg/hour, then 0.03 units/kg/hour) as glucose level falls
      • Subcutaneous route r3
        • Administer rapid-acting insulin analogue bolus of 0.3 units/kg
        • After 1 hour, administer subcutaneous lispro or aspart at 0.15 to 0.2 units/kg every 2 to 3 hours
        • Once blood glucose level falls to 250 mg/dL, reduce subcutaneous insulin lispro or aspart to 0.05 unit/kg/hour to keep blood glucose level at about 200 mg/dL until resolution of DKA
        • Subcutaneous route should not be used in patients whose peripheral circulation is impaired
    • Regular insulin (preferred) c129
      • Regular insulin is preferred over the rapid-acting insulin analogues for the IV route
      • Insulin Regular (Recombinant) Solution for injection; Infants, Children, and Adolescents: 0.05 to 0.1 unit/kg/hour IV beginning 1 to 2 hours after starting fluid replacement; continue until DKA resolves. If patient is very sensitive to insulin, the infusion rate may be reduced if acidosis continues to resolve. Add 5% dextrose to IV fluid when blood glucose reaches 250 to 300 mg/dL or sooner if blood glucose decline is precipitous. Once DKA has resolved and the patient is tolerating oral intake, transition to subcutaneous insulin. Give first dose of rapid-acting insulin 15 to 30 minutes or regular insulin 1 to 2 hours prior to stopping insulin infusion and providing a meal.
      • Insulin Regular (Recombinant) Solution for injection; Adults: Initially, 0.14 units/kg/hour IV continuous infusion. Alternatively, 0.1 units/kg IV bolus, followed by 0.1 units/kg/hour via continuous IV infusion. If serum glucose does not decrease by at least 10% in the first hour, give 0.14 units/kg as an IV bolus, then continue the previous treatment. Adequate fluid therapy must also be initiated (usually 0.9% NaCl Injection for the first hour, then 0.45% NaCl Injection if indicated); adjust fluid type and requirements as needed. Adjust insulin infusion to achieve a blood glucose reduction rate of about 50 to 75 mg/dL/hour. When the blood glucose reaches 250 mg/dL, reduce the insulin infusion rate to 0.02 to 0.05 units/kg/hour or give rapid-acting insulin at 0.1 units/kg subcutaneously every 2 hours. Once blood glucose is approximately 200 to 250 mg/dL, add 5% dextrose to IV fluid. Adjust insulin and IV fluids to maintain a blood glucose of roughly 150 to 200 mg/dL until the acidosis is resolved.
    • Insulin lispro c130
      • Subcutaneous route
        • Insulin Lispro Solution for injection; Children and Adolescents: 0.3 unit/kg subcutaneously, followed 1 hour later by 0.1 unit/kg/dose subcutaneously every 1 hour or 0.15 to 0.2 units/kg/dose subcutaneously every 2 hours. If BG falls to less than 250 mg/dL before DKA resolves, reduce to 0.05 unit/kg/dose every 1 hour to keep BG approximately 200 mg/dL until DKA resolves. Consider adding glucose to IV fluids if concern for hypoglycemia or precipitous fall in BG.
        • Insulin Lispro Solution for injection; Adults: ADA recommends regular insulin continuous IV, unless DKA is mild. Initially, 0.2 units/kg subcutaneously, then 0.2 unit/kg subcutaneously every 2 hours until blood glucose level is 250 mg/dL or lower, then 0.1 units/kg subcutaneously every 2 hours. Check blood glucose every 1 to 2 hours; concentrations should decrease 80 to 100 mg/dL/hour. Rapid blood glucose decrease is associated with adverse effects. Initiate IV fluids. Monitor serum potassium and replace as indicated.
      • IV route
        • Insulin Lispro Solution for injection; Children and Adolescents: 0.05 to 0.1 unit/kg/hour IV beginning 1 to 2 hours AFTER starting fluid replacement therapy. Do NOT administer an IV bolus at the start of therapy. Generally, maintain the infusion rate between 0.05 to 0.1 unit/kg/hour until resolution of DKA. If the patient is sensitive to insulin, the dosage may be reduced to prevent hypoglycemia if the metabolic acidosis continues to resolve. Add dextrose to IV fluids when plasma glucose falls to approximately 250 to 300 mg/dL or sooner if the rate of glucose decline is precipitous. Monitor vital signs, fluid status, acid-base status, blood glucose, blood beta-hydroxybutyrate [if test is available], serum electrolytes, and neurological status until DKA is fully resolved. Once ketoacidosis has resolved and patient is tolerating oral intake, transition to subcutaneous insulin. Administer rapid-acting insulin 15 to 30 minutes or regular insulin 1 to 2 hours prior to stopping insulin infusion and providing a meal; continue subcutaneous insulin at a dose individualized to patient's response.
        • Insulin Lispro Solution for injection; Adults: Usual dosing of insulin IV for diabetic ketoacidosis: 0.1 to 0.15 units/kg IV bolus followed by 0.1 units/kg/hour via continuous IV infusion. Use adequate fluid therapy as well. Check blood glucose levels hourly and adjust the insulin infusion rate as needed. When the blood glucose falls to 250 mg/dL or less, usually decrease insulin to 0.05 to 0.1 unit/kg/hour IV and change fluid therapy to a 5% dextrose-containing fluid infusion; adjust to maintain a blood glucose of 150 to 250 mg/dL until the acidosis is corrected.
    • Insulin aspart c131
      • Subcutaneous route
        • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents: Studies have used Novolog insulin aspart products. 0.3 unit/kg subcutaneously, followed 1 hour later by 0.1 unit/kg/dose subcutaneously every 1 hour or 0.15 to 0.2 unit/kg/dose subcutaneously every 2 hours. If blood glucose declines to less than 250 mg/dL before DKA resolves, reduce dosage to 0.05 unit/kg/dose every 1 hour to keep blood glucose approximately 200 mg/dL until resolution of DKA. Consider adding glucose to IV fluids if there is concern of hypoglycemia or there is a precipitous fall in blood glucose. Treatment with subcutaneous insulin aspart has been shown to be an effective alternative for mild and moderate DKA; however, patients with severe DKA, hypotension, anasarca, or associated severe critical illness should be managed with intravenous regular insulin in the ICU.
        • Insulin Aspart (Recombinant) Solution for injection; Adults: Studies have used Novolog insulin aspart products. Initially, 0.2 units/kg subcutaneously, then 0.2 unit/kg subcutaneously every 2 hours until blood glucose is 250 mg/dL or less; then, reduce insulin dose to 0.1 units/kg subcutaneously every 2 hours. Check blood glucose every 1 or 2 hours; blood glucose should decline by 80 to 100 mg/dL per hour; more rapid lowering associated with adverse effects. Initiate IV fluids. When the blood glucose is 250 mg/dL or less, change fluids to a 5% dextrose-containing fluid infusion and adjust to maintain blood glucose at roughly 200 to 250 mg/dL until the acidosis is corrected. Monitor serum potassium; replace as indicated. Treatment with subcutaneous insulin aspart has been shown to be an effective alternative for mild and moderate DKA; however, patients with severe DKA, hypotension, anasarca, or associated severe critical illness should be managed with intravenous regular insulin in the ICU.
      • IV route
        • Insulin Aspart (Recombinant) Solution for injection; Children and Adolescents: Studies have used Novolog insulin aspart products. 0.05 to 0.1 unit/kg/hour IV infusion beginning 1 to 2 hours AFTER starting fluid replacement therapy. Do NOT administer an IV bolus at the start of therapy. Generally, maintain the infusion rate between 0.05 to 0.1 unit/kg/hour until resolution of DKA. If the patient is sensitive to insulin, the dosage may be reduced to prevent hypoglycemia if the metabolic acidosis continues to resolve. Add dextrose to IV fluids when plasma glucose falls to approximately 250 to 300 mg/dL or sooner if rate of blood glucose decline is precipitous. Monitor vital signs, fluid status, acid-base status, blood glucose, blood beta-hydroxybutyrate [if test is available], serum electrolytes, and neurological status until DKA is fully resolved. Once ketoacidosis has resolved and patient is tolerating oral intake, transition to subcutaneous insulin. Administer rapid-acting insulin 15 to 30 minutes or regular insulin 1 to 2 hours prior to stopping insulin infusion and providing a meal; continue subcutaneous insulin at a dose individualized to patient's response.
        • Insulin Aspart (Recombinant) Solution for injection; Adults: Studies have used Novolog insulin aspart products. Usual dosing of insulin IV for diabetic ketoacidosis: 0.1 to 0.15 units/kg IV bolus followed by 0.1 units/kg/hour via continuous IV infusion. Use adequate fluid therapy as well. Check blood glucose levels hourly and adjust the insulin infusion rate as needed. When the blood glucose falls to 250 mg/dL or less, usually decrease insulin to 0.05 to 0.1 unit/kg/hour IV and change fluid therapy to a 5% dextrose-containing fluid infusion; adjust to maintain a blood glucose of 150 to 250 mg/dL until the acidosis is corrected. Monitor serum potassium; replace as indicated.

Nondrug and supportive care

IV fluids r2c132

  • Immediately begin therapy to replace fluids, preceding insulin therapy
  • 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 250 to 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 high, 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 r27
  • Pediatric fluids
    • Administer 0.9% normal saline at 10 to 20 mL/kg over the first 30 to 60 minutes r3
      • Higher-volume fluid infusion rates (20 mL/kg bolus + 1.5 × maintenance rate) for pediatric DKA patients shorten metabolic normalization time, compared with lower volume rates (10 mL/kg bolus + 1.25 × maintenance rate) r40
      • Rapidity of IV fluid replacement and sodium chloride content (0.45% or 0.9%) does not influence rates of cerebral injury r41
    • Subsequent choice of fluid depends on serum sodium level, state of hydration, and glucose levels
      • After 1 to 2 hours, replace fluid deficit with an isotonic solution (0.9% saline or lactated Ringer solution) for at least 4 to 6 hours r3
      • Thereafter, replace fluid deficit with an isotonic solution or 0.45% saline solution, with added potassium r3
      • Aim to replace the estimated fluid deficit evenly over 24 to 48 hours r3
      • Measure and assess glucose level every hour
        • Add 5% dextrose to IV fluids when glucose level falls to approximately 250 to 300 mg/dL r3
          • If blood glucose level falls very rapidly after fluid expansion, consider adding glucose before glucose level decreases to 300 mg/dL r3
        • If metabolic acidosis persists, change to 10% or 12.5% dextrose, while continuing insulin infusion, to prevent hypoglycemia r3

Electrolytes

  • Potassium c133
    • 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 20 to 30 mEq/hour of potassium chloride 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 (20 mEq/L) when initiating volume expansion (before starting an insulin infusion) r3
        • 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, or 20 mEq/L potassium in a patient receiving fluid at a rate greater than 10 mL/kg/hour r3
          • 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 c134
    • Adults
      • Bicarbonate is rarely required in the management of DKA in adults, because it has not been found to hasten rate of recovery from ketoacidosis or hyperglycemia and may contribute to hypokalemia and cerebral edema r42
      • 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 r5
        • If pH is less than 7 after first infusion, repeat every 2 hours until pH reaches greater than 7 r1
    • Children
      • Bicarbonate replacement is associated with elevated risks of cerebral edema and prolonged hospitalization in pediatric patients r42
      • Bicarbonate is not recommended in children, except for treatment of life-threatening hyperkalemia or unusually severe acidosis (pH less than 6.9) with evidence of compromised cardiac contractility r3
  • Phosphate c135
    • 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 r43
      • Correction of hypophosphatemia is recommended only under very limited circumstances (ie, cardiogenic shock, respiratory failure, serum phosphorus level less than 1 mg/dL) r44
        • 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 r44
          • 1 mL of potassium phosphate = 4.4 mEq potassium + 3 mmol (93 mg) phosphate r44
          • 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 r44
        • Monitor serum phosphate, magnesium, and calcium levels in patients receiving phosphate infusion r1
    • Children
      • Phosphate is rarely required in management of DKA in children, because replacement has not shown clinical benefit r45
      • Correction of hypophosphatemia is recommended only when serum phosphate level is lower than 1 mg/dL and the patient is symptomatic (eg, encephalopathy, respiratory failure, myopathy) r3
        • Potassium phosphate may be added to replacement IV fluids alone or in combination with potassium chloride or potassium acetate r3
        • Monitor serum calcium level in patients receiving phosphate infusion r3
Procedures
c136

Comorbidities c137

Special populations

  • Adolescents with recurrent DKA
    • Psychologic evaluation for concurrent psychiatric disease is recommended r46
      • Incidence of depression in this population, leading to more missed insulin doses
        • Children's Depression Inventory is a validated tool to screen for depression r47
      • Higher incidence of recurrent DKA is also seen in adolescents with eating disorders
  • DKA in patients with chronic kidney disease r27
    • 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/Lr27)
    • Optimal treatment strategies for DKA in patients with advance chronic kidney disease and dialysis have not been determined by prospective studies r48
      • IV fluids may not be required; they should be considered 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)r27 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/hourr27
      • 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 r27
      • 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 r13
  • DKA in pregnant women
    • Pregnant women develop DKA at significantly lower blood glucose values, and DKA progresses more rapidly in this population than in women who are not pregnant r49
    • After 24 weeks of gestation, continuously monitor fetal status owing to fetal hypoxemia and acidosis r50
    • If Cesarean delivery of a term infant is deemed necessary because of nonreassuring fetal heart rate tracings or fetal distress, delay until maternal metabolic status is stabilized (correction of acidosis, electrolyte replacement, and intravascular volume repletion) r49
    • Preterm labor management must take into account maternal condition, viability of the fetus (gestational age), and fetal heart rate tracings r49
      • 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) r22
    • 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 DKA treatment protocol

Monitoring

  • Clinical monitoring during treatment
    • Hourly vital signs and fluid input/output measurements c138c139
    • Hourly assessment by examination for complications related to fluid replacement
      • Signs of pulmonary edema, through auscultation of lungs c140
      • Signs indicative of cerebral edema, particularly in children r3
        • Headache
        • Change in mental status (eg, restlessness, irritability, increased drowsiness, incontinence) c141c142
        • Decreasing heart rate, rising blood pressure, decreasing oxygen saturation c143c144c145c146c147c148
        • Change in neurologic status (restlessness, irritability, increased drowsiness, confusion, incontinence) or specific neurologic signs (eg, cranial nerve palsies, abnormal pupillary responses)
        • Rapidly increasing serum sodium level c149c150
    • Use cardiac monitoring to detect worsening hypokalemia c151
  • Serial monitoring of metabolic parameters during treatment (at intervals noted, until there is resolution of DKA) r5r15
    • Glucose: measure hourly by fingerstick test, until DKA has resolved and transition to subcutaneous insulin has occurred c152
    • Electrolytes: measure every 2 to 4 hours c153
      • Monitor calcium level carefully if phosphate is given r3
    • Anion gap: calculate every 1 to 2 hours c154
    • Venous pH: measure every 2 to 4 hours (usually corrects slowly over a period of hours to days) c155
    • Unnecessary (optional) parameters to monitor
      • Ketonemia and ketonuria will persist 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 r51
    • 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) r4
      • 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 in patients who are insulin-naive, preferably consisting of a basal-bolus protocol using insulin analogues, beginning at a total daily dose of 0.5 to 0.6 units/kg/day r1r3d1
        • Multidose insulin regimens with basal insulin and prandial rapid-acting insulin analogues are the preferred insulin regimen for patients with type 1 diabetes r4
          • Basal insulin analogue plus prandial insulin analogue regimens are associated with less hypoglycemia than isophane insulin/regular insulin regimens r52
      • Continue subcutaneous insulin with individualized dose based on response; continue fingerstick glucose monitoring at hourly intervals during this process c156
      • Continue fingerstick glucose monitoring at hourly intervals during the transition process, but frequency may be decreased incrementally thereafter (ie, to every 4 hours) r27
  • 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

Complications

  • Treatment-related complications
    • Hypokalemia will usually occur if potassium is not replaced, especially if bicarbonate is administered r5d5
    • Hypoglycemia can develop with overzealous treatment with insulin
      • 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 fluidsr4 once glucose levels fall to less than 250 mg/dL
    • Pulmonary edema
      • Occurs most commonly in patients with known cardiac disease
      • In these patients, administer fluids cautiously with frequent pulmonary auscultation and monitor oxygen saturation with pulse oximetry
    • Acute respiratory distress syndrome r53d6
      • 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 c157
      • 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 r41
      • Occurs most commonly in young people with DKA (ie, younger than 20 years) r15
      • 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 r15
      • Warning signs r3
        • Onset of headache after treatment begins or progressively worsening severe headache
        • Heart rate slowing (unrelated to sleep or intravascular volume repletion) and/or rising blood pressure
        • Change in neurologic status (eg, restlessness, irritability, increased drowsiness, confusion, incontinence)
        • Specific neurologic signs (eg, cranial nerve palsies)
        • Decreased oxygen saturation
      • Immediate treatment measures r11r15
        • Impose head-up position
        • Halt current IV fluids
        • Administer mannitol at 0.5 to 1 g/kg over 20 minutes (repeat if needed in 30-120 minutes)
        • Infuse hypertonic saline (5-10 mL/kg over 30 minutes)
    • Disseminated intravascular coagulation (rare) c158

Prognosis

  • Most patients who are treated rapidly and appropriately recover within 48 hours without sequelae r27r54
    • Average time to resolution is between 10 and 18 hours r4
  • Overall mortality in the United States is less than 1%, but it is much higher in developing countries (approximately 11%-30%) r5
  • Higher rates are reported in patients older than 60 yearsr55 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 c159

Prevention

  • Strategies that effectively prevent DKA in new-onset type 1 diabetes have not been conclusively identified
    • Studies are underway to determine if expanding physician and public awareness of the condition may reduce DKA at first diagnosis r56
  • Prevention of recurrent DKA in established type 1 diabetes involves 2 main issues: r57
    • Better access to medical care c160
    • Improved management of individual patients, including education about sick day managementr59r58c161c162
  • Encourage patient to use sick day measures for acute illnesses, as follows: r59
    • Increase fluid intake
    • 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
    • Check ketone level (eg, blood test strip, urine test strip) if glucose level is high or abdominal pain, nausea, or vomiting are present
  • Participation in initiatives to educate patients in self-management can be effective for preventing DKA r57r60
    • Adherence to prescribed insulin regimen c163
    • Adherence to self-monitoring of blood glucose c164
    • Education about sick day management r61c165
      • 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 r27c166c167
  • Prevention of DKA in individuals using sodium-glucose cotransporter 2 inhibitors (gliflozins)
    • 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 starvation r2r22c168c169c170c171c172c173c174
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