Diabetic ketoacidosis

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1st line –

intravenous fluids

Fluid deficit averages 6 L.[90] In all patients, fluid therapy should be started immediately without waiting for results of initial laboratory evaluations. In adults without renal or cardiac compromise, an infusion of isotonic saline (0.9% sodium chloride) or balanced crystalloid solution should be started at a rate of 500-1000 mL/hour for the first 2-4 hours of fluid therapy.

After the initial management, hydration status should be evaluated clinically and continuous fluid therapy started at an appropriate rate to correct the deficit. Correction should be undertaken gradually over 24-48 hours, as overly rapid correction can result in the patient developing cerebral edema.[1]

Severe volume depletion is indicated by the presence of orthostatic hypotension or supine hypotension, dry mucous membranes, and poor skin turgor. Extreme cases may be hemodynamically unstable. The Joint British Diabetes Societies for Inpatient Care advise that a systolic blood pressure (SBP) cutoff of 90 mmHg may be used in assessing the severity of hydration (with patients who have SBP <90 mmHg on admission considered to have severe hypovolemia), caveating that age, sex, presence of heart failure, and concomitant drugs should also be taken into account.[66]

Severe hypovolemia should be treated by infusion of isotonic saline (or other crystalloid) at the rate of 1 L/hour until signs of severe volume depletion have resolved.[1][14][66]

Once SBP is ≥90 mmHg or other methods of clinical assessment indicate resolution of severe hypovolemia, patients should continue to receive fluid therapy as for mild hypovolemia.[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid to avoid hypoglycemia.[1]

Plus – intravenous insulin once serum potassium reaches 3.5 mEq/L (3.5 mmol/L)

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Plus –

potassium therapy

Treatment recommended for ALL patients in selected patient group

Insulin therapy and correction of acidemia and hyperosmolality will drive potassium into cells, which may cause serious hypokalemia. Within 48 hours of hospital admission, potassium levels typically decline by 1-2 mEq/L (1-2 mmol/L).[1] Severe hypokalemia ≤2.5 mEq/L (≤2.5 mmol/L) during treatment of diabetic ketoacidosis (DKA) has been reported to be associated with a threefold increase in mortality.[1] The goal, therefore, is to correct the actual potassium deficits and thereby prevent fatal complications of hypokalemia, including respiratory paralysis and cardiac dysrhythmia. To avoid hypokalemia, serum potassium should be checked 2 hours after starting insulin administration and every 4 hours thereafter until the resolution of DKA.[1]

Low-normal or low potassium levels (<3.5 mEq/L [<3.5 mmol/L]) are present on admission in 5% to 10% of patients with DKA.[1] In such cases, potassium replacement should begin at a rate of 10 mEq/hour (10 mmol/hour) and insulin therapy should be delayed until the potassium level increases to >3.5 mEq/L (>3.5 mmol/L).[1]

Once the potassium level is in the range 3.5 to 5.0 mEq/L (3.5 to 5.0 mmol/L), insulin therapy should be started alongside ongoing potassium replacement to maintain a potassium level of 4-5 mEq/L (4-5 mmol/L). The American Diabetes Association/European Association for the Study of Diabetes guidelines recommend achieving this by adding 10-20 mEq (10-20 mmol) of potassium to each liter of intravenous infusion fluid as needed.[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

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Plus –

intravenous insulin once serum potassium reaches 3.5 mEq/L (3.5 mmol/L)

Treatment recommended for ALL patients in selected patient group

Insulin therapy is the cornerstone of diabetic ketoacidosis management.[1] The goal is the steady but gradual reduction of serum glucose and plasma osmolality by low-dose insulin therapy, in order to reduce the risk of treatment complications including hypoglycemia and hypokalemia.

A continuous fixed-rate intravenous infusion of short-acting regular insulin at 0.1 units/kg/hour should be started after exclusion of hypokalemia (potassium level should be >3.5 mEq/L [3.5 mmol/L] before initiation of insulin therapy). Frequent close monitoring in an ICU setting is required for administration of intravenous insulin infusion. If there is a delay in setting up the infusion (e.g., if a delay in obtaining venous access is anticipated), an intravenous bolus of short-acting regular insulin 0.1 units/kg (or intramuscularly if intravenous administration is not possible) should be given, followed by the intravenous infusion.[1] Once blood glucose falls below 250 mg/dL (13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline (0.9% sodium chloride)/crystalloid infusion and the insulin infusion rate should be reduced to 0.05 units/kg/hour. Thereafter, the insulin infusion should be adjusted to maintain glucose levels between 150 and 200 mg/dL (8.3 and 11.0 mmol/L) and continued until the ketoacidosis is resolved (plasma/capillary ketones <0.6 mmol/L and venous pH ≥7.3 or bicarbonate ≥18 mEq/L [≥18 mmol/L]).[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

Primary options

insulin regular: consult local protocols for dosing guidelines

Plus – supportive care + ICU admission

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Plus –

supportive care + ICU admission

Treatment recommended for ALL patients in selected patient group

Indications for intensive care unit (ICU) admission include hemodynamic instability or cardiogenic shock, altered mental status, respiratory insufficiency, and severe acidosis. The diagnosis of hemodynamic instability should be made by observing for hypotension and clinical signs of poor tissue perfusion, including oliguria, cyanosis, cool extremities, and altered mental state.

Initial management in hemodynamically unstable patients includes fluid resuscitation to correct hypovolemia and hypotension, close monitoring, and vasopressor therapy under specialist supervision.[87] After admission to ICU, intensive monitoring is required.

Oxygenation and airway protection are critical. Intubation may be required, but is generally avoided in patients with DKA as it can lead to worsening acidosis. In DKA, severe metabolic acidosis results in respiratory compensation with hyperventilation, but the apneic period required during the endotracheal intubation procedure worsens the acidosis, and this can lead to rapid decompensation and cardiac arrest. However, endotracheal intubation may not be avoidable when the patient cannot protect their airway, such as in the case of coma, or if they develop respiratory muscle fatigue and failure. In intubated patients, hyperventilation will need to be maintained to prevent worsening acidosis.[88][89]

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Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Routine bicarbonate administration is not recommended in diabetic ketoacidosis (DKA).[1][4] The American Diabetes Association guidelines note that several studies have failed to show any difference in acidosis resolution or time to discharge in people with DKA when bicarbonate was used.[4] At arterial blood pH >7.0, intravenous fluid resuscitation and administration are sufficient to resolve the metabolic acidosis of DKA without the need to add bicarbonate. Moreover, administering bicarbonate therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema.[1] However, because severe metabolic acidosis may lead to adverse vascular effects, bicarbonate therapy should be considered in patients with arterial blood pH <7.0 (i.e., severe acidosis).[1]

The decision to give bicarbonate therapy is individualized. If indicated, an isotonic solution of 100 mEq (100 mmol) sodium bicarbonate in 400 mL sterile water (an 8.4% solution) can be given every 2 hours until the pH is >7.0.[1]

Bicarbonate therapy, as well as insulin therapy, lowers serum potassium; therefore, based on expert opinion, potassium chloride should be added to the isotonic bicarbonate infusion to prevent hypokalemia.

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Consider –

phosphate therapy

Treatment recommended for SOME patients in selected patient group

Despite the fact that total body phosphate deficits in diabetic ketoacidosis (DKA) can be up to 1 mmol/kg of body weight, serum phosphate is often normal or increased at presentation, but decreases with insulin therapy. Studies have failed to show any beneficial effects of phosphate replacement on the clinical outcome of DKA.[1] Furthermore, excessively rapid phosphate replacement may precipitate hypocalcemia.[1] Therefore, routine replacement of phosphate is not recommended.[1]

Phosphate should not be given unless there is muscle weakness, such as respiratory or cardiac compromise, and a phosphate level <3.1 mg/dL (<1 mmol/L).[1]

If replacement is indicated, 20-30 mEq/L (20-30 mmol/L) potassium phosphate should be added to each liter of intravenous fluid.[1]

serum potassium 3.5 to 5.0 mEq/L (3.5 to 5.0 mmol/L)

Plus – intravenous insulin

Back

1st line –

intravenous fluids

Severe volume depletion is indicated by the presence of orthostatic hypotension or supine hypotension, dry mucous membranes, and poor skin turgor. Extreme cases may be hemodynamically unstable. The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) advise that a systolic blood pressure (SBP) cutoff of 90 mmHg may be used in assessing the severity of hydration (with patients who have SBP <90 mmHg on admission considered to have severe hypovolemia), caveating that age, sex, presence of heart failure, and concomitant drugs should also be taken into account.[66]

Severe hypovolemia should be treated by infusion of isotonic saline (or other crystalloid) at the rate of 1 L/hour until signs of severe volume depletion have resolved.[1][14][66] Once SBP is ≥90 mmHg or other methods of clinical assessment indicate resolution of severe hypovolemia, patients should continue to receive fluid therapy as for mild hypovolemia,[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid solution to avoid hypoglycemia.[1]

Back

Plus –

intravenous insulin

Treatment recommended for ALL patients in selected patient group

A continuous fixed-rate intravenous infusion of short-acting regular insulin at 0.1 units/kg/hour should be started after exclusion of hypokalemia (potassium level should be >3.5 mEq/L [>3.5 mmol/L] before initiation of insulin therapy). Frequent close monitoring in an ICU setting is required for administration of intravenous insulin infusion. If there is a delay in setting up the infusion (e.g., if a delay in obtaining venous access is anticipated), an intravenous bolus of short-acting regular insulin 0.1 units/kg (or intramuscularly if intravenous administration is not possible) should be given, followed by the intravenous infusion.[1] Once blood glucose falls below 250 mg/dL (13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline (0.9% sodium chloride)/crystalloid infusion and the insulin infusion rate should be reduced to 0.05 units/kg/hour. Thereafter, the insulin infusion should be adjusted to maintain glucose levels between 150 and 200 mg/dL (8.3 and 11.0 mmol/L) and continued until the ketoacidosis is resolved (plasma/capillary ketones <0.6 mmol/L and venous pH ≥7.3 or bicarbonate ≥18 mEq/L [≥18 mmol/L]).[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

If plasma potassium falls below 3.5 mEq/L (3.5 mmol/L) at any point, insulin should be discontinued and potassium replaced intravenously. Insulin therapy can be restarted when the potassium level returns to 3.5 mEq/L (3.5 mmol/L).

Primary options

insulin regular: consult local protocols for dosing guidelines

Plus – supportive care + ICU admission

Back

Plus –

supportive care + ICU admission

Treatment recommended for ALL patients in selected patient group

Back

Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Routine bicarbonate administration is not recommended in diabetic ketoacidosis (DKA).[1][4] The American Diabetes Association guidelines note that several studies have failed to show any difference in acidosis resolution or time to discharge in people with DKA when bicarbonate was used.[4] At arterial blood pH >7.0, administration of insulin blocks lipolysis and resolves ketoacidosis without the need to add bicarbonate. Administering bicarbonate therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema.[1] However, because severe metabolic acidosis may lead to adverse vascular effects, bicarbonate therapy should be considered in patients with arterial blood pH <7.0 (i.e., severe acidosis).[1]

The decision to give bicarbonate therapy is individualized. If indicated, an isotonic solution of 100 mEq (100 mmol) sodium bicarbonate in 400 mL sterile water (8.4% solution) can be given every 2 hours until the pH is >7.0.[1]

serum potassium >5 mEq/L (>5 mmol/L)

Plus – intravenous insulin

Back

1st line –

intravenous fluids

Severe volume depletion is indicated by the presence of orthostatic hypotension or supine hypotension, dry mucous membranes, and poor skin turgor. Extreme cases may be hemodynamically unstable. The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) advise that a systolic blood pressure (SBP) cutoff of 90 mmHg may be used in assessing the severity of hydration (with patients who have SBP <90 mmHg on admission considered to have severe hypovolemia), caveating that age, sex, presence of heart failure, and concomitant drugs should also be taken into account.[66]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid solution to avoid hypoglycemia.[1]

Back

Plus –

intravenous insulin

Treatment recommended for ALL patients in selected patient group

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

Potassium replacement is not required, but serum potassium should be checked every 2 hours. If levels drop to less than 5 mEq/L (5 mmol/L), intravenous potassium replacement should be commenced.[1]

Primary options

insulin regular: consult local protocols for dosing guidelines

Plus – supportive care + ICU admission

Back

Plus –

supportive care + ICU admission

Treatment recommended for ALL patients in selected patient group

Back

Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Routine bicarbonate administration is not recommended in diabetic ketoacidosis (DKA).[1][4] The American Diabetes Association guidelines note that several studies have failed to show any difference in acidosis resolution or time to discharge in people with DKA when bicarbonate was used.[4] At arterial blood pH >7.0, administration of insulin blocks lipolysis and resolves ketoacidosis without the need to add bicarbonate. Administering bicarbonate therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema.[1] However, because severe metabolic acidosis may lead to adverse vascular effects, bicarbonate therapy should be considered in patients with arterial blood pH <7.0 (i.e., severe acidosis).[1]

mild to moderate volume depletion

serum potassium <3.5 mEq/L (<3.5 mmol/L)

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1st line –

intravenous fluids

Mild to moderate volume depletion is indicated by the absence of orthostatic hypotension or supine hypotension, dry mucous membranes, and poor skin turgor. An intravenous solution of isotonic saline or other crystalloid should be given at a clinically appropriate rate, with the aim of replacing 50% of the estimated fluid deficit in the first 8-12 hours.[1]

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid solution to avoid hypoglycemia.[1]

Caution should be exercised in the following groups: young people ages 18-25 years; elderly people; pregnant people; people with heart or kidney failure; and people with other serious comorbidities.[66] In these situations, admission to an intermediate care unit should be considered. Fluids should be replaced cautiously with close hemodynamic monitoring.[1][66]

Plus – insulin once serum potassium reaches 3.5 mEq/L (3.5 mmol/L)

Back

Plus –

potassium therapy

Treatment recommended for ALL patients in selected patient group

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

If potassium is <3.5 mEq/L (<3.5 mmol/L) at any point of therapy, insulin should be discontinued and potassium replaced intravenously.

Back

Plus –

insulin once serum potassium reaches 3.5 mEq/L (3.5 mmol/L)

Treatment recommended for ALL patients in selected patient group

Insulin therapy should not be commenced until serum potassium reaches 3.5 mEq/L (3.5 mmol/L).

Insulin therapy is the cornerstone of diabetic ketoacidosis (DKA) management.[1] The goal is the steady but gradual reduction of serum glucose and plasma osmolality by low-dose insulin therapy, in order to reduce the risk of treatment complications including hypoglycemia and hypokalemia.

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

Patients with mild to moderate DKA (plasma glucose ≥200 mg/dL [≥11.1 mmol/L], arterial pH 7.00 to 7.29, serum bicarbonate 10-18 mEq/L [10-18 mmol/L], serum beta-hydroxybutyrate 3-6 mmol/L, alert/drowsy) that is not complicated by acute myocardial infarction, congestive heart failure, end-stage renal or hepatic failure, corticosteroid use, or pregnancy, may be given rapid-acting insulin subcutaneously as an alternative to intravenous regular insulin, with studies showing no significant difference in outcomes when using either approach alongside aggressive fluid management for mild or moderate DKA.[1][4][91][92][93][94] [ ] Patients treated with subcutaneous insulin should receive adequate fluid replacement, frequent bedside blood glucose testing, and appropriate treatment of underlying causes to avoid recurrent DKA.[4]

The American Diabetes Association advises, however, that continuous intravenous infusion of short-acting regular insulin should remain the preferred route in all patients with DKA because of intravenous insulin's short half-life and easy titration (compared with the delayed onset of action and prolonged half-life of subcutaneously administered insulin).[4] However, if there are prolonged waiting times for intensive care unit (ICU) admission or limited medical resources, the use of rapid-acting insulin analogs for the treatment of mild or moderate uncomplicated DKA episodes can be considered for outpatients, in general floors, or in emergency departments.[1][94] The use of rapid-acting subcutaneous insulin analogs is not recommended for the treatment of severe and complicated DKA.[1]

Primary options

insulin regular: consult local protocols for dosing guidelines

Secondary options

insulin aspart: consult local protocols for dosing guidelines

insulin lispro: consult local protocols for dosing guidelines

Plus – supportive care ± ICU admission

Back

Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Back

Consider –

phosphate therapy

Treatment recommended for SOME patients in selected patient group

Phosphate should not be given unless there is muscle weakness, such as respiratory or cardiac compromise, and a phosphate level <3.1 mg/dL (<1 mmol/L).[1]

If replacement is indicated, 20-30 mEq/L (20-30 mmol/L) potassium phosphate should be added to each liter of intravenous fluid.[1]

serum potassium 3.5 to 5.0 mEq/L (3.5 to 5.0 mmol/L)

Back

1st line –

intravenous fluids

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid solution to avoid hypoglycemia.[1]

Plus – insulin

Back

Plus –

insulin

Treatment recommended for ALL patients in selected patient group

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

The American Diabetes Association advises, however, that continuous intravenous infusion of short-acting regular insulin should remain the preferred route in all patients with DKA because of intravenous insulin's short half-life and easy titration (compared with the delayed onset of action and prolonged half-life of subcutaneously administered insulin).[4] However, if there are prolonged waiting times for intensive care unit (ICU) admission or limited medical resources, the use of rapid-acting insulin analogs for the treatment of mild or moderate uncomplicated DKA episodes can be considered for outpatients, in general floors, or in emergency departments.[1][94] The use of rapid-acting subcutaneous insulin analog is not recommended for the treatment of severe and complicated DKA.[1]

The intravenous or subcutaneous regimens should be followed until all criteria for DKA resolution are met, i.e., plasma/capillary ketones <0.6 mmol/L AND serum bicarbonate ≥18 mEq/L (≥18 mmol/L) or venous pH ≥7.3.[1]

Primary options

insulin regular: consult local protocols for dosing guidelines

Secondary options

insulin aspart: consult local protocols for dosing guidelines

insulin lispro: consult local protocols for dosing guidelines

Plus – supportive care ± ICU admission

Back

Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Routine bicarbonate administration is not recommended in diabetic ketoacidosis (DKA).[1][4] The American Diabetes Association guidelines note that several studies have failed to show any difference in acidosis resolution or time to discharge in people with DKA when bicarbonate was used.[4] At arterial blood pH >7.0, administration of insulin blocks lipolysis and resolves ketoacidosis without the need to add bicarbonate. Administering bicarbonate therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema.[1] However, because severe metabolic acidosis may lead to adverse vascular effects, bicarbonate therapy should be considered in patients with arterial blood pH <7.0 (i.e., severe acidosis).[1]

serum potassium >5 mEq/L (>5 mmol)

Plus – supportive care ± ICU admission

Back

1st line –

intravenous fluids

Electrolytes, renal function, venous pH, osmolality, and glucose should be checked every 2-4 hours until stable.[1]

When glucose reaches <250 mg/dL (<13.9 mmol/L), 5% or 10% dextrose should be added to the isotonic saline or crystalloid solution to avoid hypoglycemia.[1]

Plus – insulin

Back

Plus –

insulin

Treatment recommended for ALL patients in selected patient group

Patients with mild to moderate DKA (plasma glucose ≥200 mg/dL [≥11.1 mmol/L], arterial pH 7.00 to 7.29, serum bicarbonate 10-18 mEq/L [10-18 mmol/L], serum beta-hydroxybutyrate 3-6 mmol/L, alert/drowsy) that is not complicated by acute myocardial infarction, congestive heart failure, end-stage renal or hepatic failure, corticosteroid use, or pregnancy, may be given rapid-acting insulin subcutaneously as an alternative to intravenous regular insulin, with studies showing no significant difference in outcomes when using either approach alongside aggressive fluid management for mild or moderate DKA).[1][4][91][92][93][94] [ ] Patients treated with subcutaneous insulin should receive adequate fluid replacement, frequent bedside blood glucose testing, and appropriate treatment of underlying causes to avoid recurrent DKA.[4]

The American Diabetes Association advises, however, that continuous intravenous infusion of short-acting regular insulin should remain the preferred route in all patients with DKA because of intravenous insulin's short half-life and easy titration (compared with the delayed onset of action and prolonged half-life of subcutaneously administered insulin).[4] However, if there are prolonged waiting times for ICU admission or limited medical resources, the use of rapid-acting insulin analogs for the treatment of mild or moderate uncomplicated DKA episodes can be considered for outpatients, in general floors, or in emergency departments.[1][94] The use of rapid-acting subcutaneous insulin analogs is not recommended for the treatment of severe and complicated DKA.[1]

The intravenous or subcutaneous regimens should be followed until all criteria for resolution are met, i.e., plasma/capillary ketones <0.6 mmol/L AND serum bicarbonate ≥18 mEq/L (≥18 mmol/L) or venous pH ≥7.3.[1]

Primary options

insulin regular: consult local protocols for dosing guidelines

Secondary options

insulin aspart: consult local protocols for dosing guidelines

insulin lispro: consult local protocols for dosing guidelines

Back

Consider –

bicarbonate therapy

Treatment recommended for SOME patients in selected patient group

Routine bicarbonate administration is not recommended in diabetic ketoacidosis (DKA).[1][4] The American Diabetes Association guidelines note that several studies have failed to show any difference in acidosis resolution or time to discharge in people with DKA when bicarbonate was used.[4] At arterial blood pH >7.0, administration of insulin blocks lipolysis and resolves ketoacidosis without the need to add bicarbonate. Administering bicarbonate therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake, and cerebral edema.[1] However, because severe metabolic acidosis may lead to adverse vascular effects, bicarbonate therapy should be considered in patients with arterial blood pH <7.0 (i.e., severe acidosis).[1]