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Diabetic ketoacidosis in children: Treatment and

complications
AUTHOR: Nicole Glaser, MD
SECTION EDITORS: Joseph I Wolfsdorf, MB, BCh, Adrienne G Randolph, MD, MSc
DEPUTY EDITOR: Jessica Kremen, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2024.

This topic last updated: Jan 17, 2024.

INTRODUCTION

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type
1 diabetes, with a case fatality rate ranging from 0.15 to 0.31 percent in the United States and
other resource-abundant settings [1-3]. DKA also can occur in children with type 2 diabetes; this
presentation is most common among adolescents of African American descent [4-8]. (See
"Classification of diabetes mellitus and genetic diabetic syndromes".)

The management of DKA in children is summarized in the table ( table 1) and is reviewed in
detail below. Other aspects of DKA are discussed in separate topic reviews:

● (See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)

● (See "Diabetic ketoacidosis in children: Cerebral injury (cerebral edema)".)

● (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical

features, evaluation, and diagnosis".)

DEFINITION

● Diabetic ketoacidosis (DKA) – DKA is defined by the presence of all of the following in a
patient with diabetes, as outlined in a consensus statement from the International Society
for Pediatric and Adolescent Diabetes in 2022 [9]:
 • Hyperglycemia – Blood glucose of >200 mg/dL (11 mmol/L)
• Metabolic acidosis – Venous pH <7.3 or serum/plasma bicarbonate <18 mEq/L (18
mmol/L)
• Ketosis – Determined by the presence of ketones in the blood (beta-hydroxybutyrate
[BOHB] >3 mmol/L [31 mg/dL]) or urine ("moderate" or "large" urine ketones)

(See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)

Disturbances in fluid and electrolyte balance result in volume depletion and mild to
moderate serum hyperosmolality. The clinical manifestations of DKA are related to
hypovolemia, electrolyte imbalances, and acidosis [10]. Some children present with severe
hyperglycemia and may have mixed features of DKA and hyperglycemic hyperosmolar
state, as described below. (See "Diabetic ketoacidosis in children: Clinical features and
diagnosis".)

● Hyperglycemic hyperosmolar state (HHS) – HHS is a hyperglycemic emergency that is

distinguished from DKA by:

• Marked hyperglycemia – Blood glucose >600 mg/dL (>33.3 mmol/L)

• Minimal acidosis – Venous pH >7.25, arterial pH >7.3, or serum bicarbonate >15
mmol/L
• Absent to mild ketosis
• Marked elevation in serum osmolality – Effective osmolality >320 mOsm/kg

Patients with HHS frequently have altered consciousness (in approximately 50 percent)
and moderate lactic acidosis. HHS requires prompt recognition and management that
differ from that of DKA. In particular, dehydration in HHS is typically severe (12 to 15
percent of body weight) and requires greater fluid resuscitation than DKA. In addition,
delayed initiation of insulin treatment and lower insulin doses are recommended for HHS.
HHS is more common among adolescents at the onset of type 2 diabetes compared with
type 1 diabetes [9,11]. A mixed presentation with features of both HHS and DKA
(hyperosmolar DKA) can also occur and often requires greater fluid resuscitation and
electrolyte replacement than are typical for DKA [9]. Further details about how to identify
and treat HHS are discussed in separate topic reviews. (See "Diabetic ketoacidosis in
children: Clinical features and diagnosis", section on 'Hyperglycemic hyperosmolar state'
and "Diabetic ketoacidosis in adults: Treatment".)

INITIAL RAPID ASSESSMENT

All patients with suspected DKA should be rapidly evaluated as follows.

Clinical assessment

● Measure vital signs and assess for signs of shock caused by volume depletion (eg,
decreased blood pressure, reduced peripheral pulses, tachycardia, and significant postural
changes in blood pressure). Of note, hypertension is present in more than 10 percent of
children when they present with DKA (despite hypovolemia) or may develop during
treatment [12]. This finding is associated with more severe DKA, stage 2 to 3 acute kidney
injury (AKI), and alterations in mental status. Such patients require volume replacement
despite the hypertension and should be monitored particularly carefully for signs and
symptoms of impending cerebral injury.

● Measure weight for use in calculating fluid replacement and insulin infusion rates. If
recent measurements of weight are available (within the previous one to two weeks),
these should be compared with the current weight to estimate the fluid deficit.

● Estimate the degree of dehydration. Note that clinical symptoms and signs of dehydration,
such as skin turgor and dryness of mucus membranes, tend to underestimate the degree
of dehydration in a child with DKA, and urine specific gravity is not valid, because of both
glycosuria and ketonuria. Therefore, targets for fluid repletion generally rely on
assumptions of a 5 to 10 percent fluid deficit, rather than on clinical estimates of
dehydration. Children with a new onset of diabetes typically have more severe dehydration
than those with previously diagnosed diabetes. (See 'Dehydration' below.)

● Assess the neurologic state using the Glasgow Coma Scale (GCS) or similar assessment
( table 2). GCS and/or other neurologic assessments should be repeated hourly
throughout treatment or until the patient is clinically recovered from ketoacidosis and
mental status has returned to normal. (See 'Cerebral injury' below.)

Severe neurologic compromise at presentation is concerning because such patients may

have DKA-related cerebral injury or be at increased risk for developing cerebral injury
during therapy. (See "Diabetic ketoacidosis in children: Cerebral injury (cerebral edema)",
section on 'Treatment'.)

Laboratory testing

● Immediate (point-of-care) testing – Measure using a point-of-care meter (if available) to

confirm the diagnosis of DKA:

• Blood glucose – Blood glucose >200 mg/dL (11 mmol/L) confirms hyperglycemia.
 • Blood beta-hydroxybutyrate (BOHB) – Concentrations ≥3 mmol/L (31 mg/dL) are
consistent with DKA [9]. Once the initial degree of ketonemia has been established,
either BOHB or the anion gap may be used to monitor the response to treatment, as
described below. (See 'Monitoring' below.)

• Urine ketones – Measurement of urine ketones confirms ketosis but should not be
used to judge the severity of ketonemia or acidosis, because this test measures
acetoacetate rather than BOHB, which is the predominant ketone body at presentation
of DKA. Urine acetoacetate (ketonuria) may persist for some time after resolution of
DKA and should not be considered an indication of persistent ketoacidosis.

● Additional testing – Send to the laboratory for more accurate measurements and to
further characterize the patient's acid-base status, electrolyte balance, and dehydration:

• Blood glucose
• BOHB
• Electrolytes – Including bicarbonate
• Blood urea nitrogen (BUN), creatinine
• Venous or arterial pH and partial pressure of carbon dioxide (pCO2)
• Complete blood count
• Calcium, phosphorus, magnesium – Severe abnormalities in these measures are
uncommon but can have serious consequences if undetected, particularly in the case
of hypophosphatemia

● Additional evaluation for specific circumstances:

• Blood lactate – In a patient with very severe dehydration or shock, sepsis, or

hyperglycemic hyperosmolar state (HHS). In such patients, the blood lactate level will
help determine the contribution of lactic acid to the metabolic acidosis.

• Cultures of blood, urine, and/or throat or other evaluation for infection – If fever or
localizing signs of infection are present. Note that the white blood cell count is
frequently elevated in children with DKA and should not be considered a sign of
infection in the absence of other findings.

• Electrocardiogram – If laboratory measurement of potassium status is delayed. In this

case, the electrocardiogram will help to assess for evidence of hyperkalemia (indicated
by the finding of a peaked T wave). Prolonged QTc has also been found to occur
frequently in children with DKA and is correlated with DKA severity and anion gap
[13,14]. Patients with prolonged QTc interval (>460 msec) should have continuous
 monitoring of heart rhythm during DKA treatment because of possible increased risk
for arrhythmias.

Assessment of severity — Categorizing the severity of DKA at presentation helps to determine

the appropriate level of care (eg, need for intensive care unit admission).

● Venous pH and serum bicarbonate – The severity of DKA at presentation is categorized

by acid-base status ( table 3) [9]:

• Mild – pH 7.2 to <7.3, bicarbonate 10 to <18 mEq/L

• Moderate – pH 7.1 to <7.2, bicarbonate 5 to 9 mEq/L
• Severe – pH <7.1, bicarbonate <5 mEq/L

Venous pH is a clinically practical and accurate measure of the overall level of acidosis
(with metabolic and, possibly, respiratory contributors). However, measurements of serum
bicarbonate may be used alone, especially in resource-limited settings, and are closely
correlated with venous pH [15].

● Anion gap – The anion gap can be used as an index of the severity of the metabolic
acidosis and is calculated from the following equation:

This formula is too large to be displayed on your mobile device. Try again in landscape or on a larger device.

At presentation, the presence of a large anion gap in the absence of significant ketosis
(BOHB <3 mmol) strongly suggests significant lactic acidosis and the possibility of HHS or
sepsis [9]. (See 'Definition' above.)

During treatment, administration of large amounts of chloride in intravenous (IV) fluids,

and preferential renal excretion of ketones rather than chloride, often causes
hyperchloremic acidosis. Therefore, the anion gap is a better measure of the effectiveness
of treatment and DKA resolution than is the serum bicarbonate concentration. (See
'Metabolic acidosis' below.)

Other clinical features associated with more severe ketoacidosis include longer duration of
symptoms, depressed level of consciousness, or compromised circulation [16-18].

Disposition — All patients with DKA should be managed in a unit with personnel and facilities
capable of frequent monitoring of clinical symptoms, fluid status, and laboratory results. The
experienced clinician is in the best position to determine the safest place for therapy within a
particular institution. In most tertiary care institutions, patients should be triaged as follows [9]:
 ● A pediatric intensive care unit (PICU) or specialized inpatient diabetes care unit is
appropriate for patients with severe DKA or signs of or risk factors for cerebral injury,
which include:

• Altered consciousness
• Age younger than five years
• Severe acidosis (venous pH <7.1)
• Low pCO2 (≤20 mmHg)
• High BUN
• Significant hyper- or hypokalemia, or other severe electrolyte disturbances.

In some institutions, all patients receiving IV insulin or needing frequent monitoring are
hospitalized in the PICU.

● The regular inpatient care area is appropriate for patients with mild to moderate
uncomplicated DKA, if this unit is capable of providing close monitoring and IV insulin
infusions [19]. Patients who will be managed without continuous cardiac monitoring
should have an initial electrocardiogram to measure the QTc interval. (See 'Clinical
assessment' above.)

● Emergency department care with outpatient follow-up may be appropriate for patients
with established diabetes and very mild DKA. In some cases, initial IV fluid and insulin
therapy in the emergency department can significantly improve the clinical picture and
allow the medical team to discharge the patient to home, provided that the patient has
access to point-of-care testing of both glucose and ketones, the caretakers are proficient
in diabetes sick-day management, and the patient has access to ongoing advice from an
experienced diabetes care team via telephone. (See 'Treatment of mild diabetic
ketoacidosis' below.)

TREATMENT OF MODERATE AND SEVERE DIABETIC KETOACIDOSIS

The general approach and principles of management are the same for all children with DKA,
regardless of the severity. The clinician must individualize the treatment plan based on the
child's physical and laboratory findings, and treatment will need to be adjusted over time for
each child. Protocols for management of fluids and insulin dosing are helpful but should be
used in conjunction with clinical reassessments and judgment. Flow charts can be used to track
hourly vital signs and neurologic symptoms, fluid status (input and output), and insulin dosing,
as well as laboratory results ( table 4). During therapy, the patient should be carefully
monitored for signs of cerebral injury. (See 'Monitoring' below and 'Cerebral injury' below.)

For patients with moderate and severe DKA, the main principles of management are to
administer insulin to resolve ketosis and reduce hyperglycemia, correct dehydration with
intravenous (IV) fluids, and correct electrolyte abnormalities with electrolyte replacement.

Dehydration

Estimated fluid deficit — Average water losses are approximately 7 percent, ie, 70 mL/kg
(range 30 to 100 mL/kg) [20-22]. Volume depletion is caused by urinary losses from osmotic
diuresis, as well as gastrointestinal losses from vomiting and insensible losses from
hyperventilation. In a large cohort study of more than 750 children with DKA in the United
States, the degree of dehydration (calculated as the difference between admission and
discharge weights) was mild (<5 percent fluid loss) in 47 percent, moderate (5 to 10 percent fluid
loss) in 42 percent, and severe (>10 percent fluid loss) in 11 percent [23]. Estimating the degree
of dehydration at presentation with DKA is challenging because clinical signs of dehydration
tend to be inaccurate in this patient population [20].

When a child presents with DKA, the degree of dehydration can be estimated as follows:

● Children with new onset of diabetes, pH <7.1, or blood urea nitrogen (BUN) >20 mg/dL –
Assume 8 percent dehydration

● All other children – Assume 6 percent dehydration

● Children with obesity – Use actual body weight (up to 100 kg), rather than ideal body
weight or other adjustments [24]

The strategy outlined above is based on a large clinical study in which increased BUN and low
pH were the best predictors of dehydration severity [23]. Children with new onset of diabetes
also tend to have more severe dehydration.

Hypovolemic shock is rare in DKA but, if present, should be promptly treated. Patients in shock
should be evaluated for other causes of shock, such as sepsis. (See "Diabetic ketoacidosis in
children: Clinical features and diagnosis", section on 'Signs and symptoms'.)

Initial volume expansion — The goals of initial volume expansion are to restore the effective
circulating volume by acutely replacing some of the sodium and water loss and to improve the
glomerular filtration rate to enhance clearance of ketones and glucose from the blood [9].
Initial volume expansion of 10 to 20 mL/kg should be administered as an IV bolus, using
isotonic saline (0.9% sodium chloride [NaCl]) or Ringer's lactate infused over 20 to 30 minutes
[9,25]. If circulating volume is still compromised after the initial bolus is complete, additional IV
bolus infusions of 10 to 20 mL/kg can be given (see "Diabetic ketoacidosis in children: Clinical
features and diagnosis", section on 'Signs and symptoms'). Patients with mild DKA who may not
require hospital admission also often benefit from an IV fluid bolus and/or fluid infusion during
management in the emergency department to hasten recovery. (See 'Treatment of mild diabetic
ketoacidosis' below.)

Subsequent fluid administration — Once the child is hemodynamically stable, additional IV

fluids should be administered, using IV fluids with 0.45 to 0.9% NaCl. The rate of fluid
administration is calculated to replace the remaining fluid deficit over 24 to 48 hours. Because
the fluid deficit is a percentage of body weight, children with obesity will have relatively high
fluid infusion rates, but this is appropriate, as discussed below.

A range of IV fluid protocols can be safely used to rehydrate children with DKA. This was shown
in a large randomized clinical trial (the Pediatric Emergency Care Applied Research Network
FLUID Study), which found no differences in acute or post-recovery neurologic outcomes of
children with DKA treated with more rapid versus slower rehydration [25]. Similarly, there were
no differences in neurologic outcomes of children treated with 0.9 versus 0.45% NaCl fluids. A
separate analysis of this cohort found that children with overweight or obesity also had similar
outcomes regardless of whether they were treated with more rapid versus slower rehydration
[24]. Thus, the volume deficit can be based on actual body weight (up to 100 kg).

Children presenting with very low Glasgow coma scale (GCS) scores (suggesting cerebral injury
prior to treatment) were not enrolled in this study. Fluid therapy in children with cerebral injury
is discussed separately. (See "Diabetic ketoacidosis in children: Cerebral injury (cerebral
edema)", section on 'Pathophysiology'.)

Clinical findings and laboratory values should be carefully monitored during DKA treatment and
the IV fluid volume and composition adjusted as necessary based on the patient's fluid balance
and hemodynamic state. Administration of IV fluids should not be unnecessarily restricted (due
to concerns about causing cerebral edema), if clinical and laboratory findings suggest the need
for increased fluid volume. Potassium replacement is also a necessary component of IV fluid
therapy. (See 'Serum potassium' below.)

Hyperglycemia — An IV insulin infusion should be initiated approximately one hour after the
patient begins IV fluids. Insulin administration suppresses hepatic glucose output and
ketogenesis and stimulates peripheral glucose uptake and metabolism to lower serum glucose
concentrations and resolve ketosis. In addition, volume expansion will lower the serum glucose
concentration by dilution and via improvements in renal perfusion. (See "Diabetic ketoacidosis
and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis".)

Insulin infusion — Insulin should be administered as an IV infusion at a rate of 0.1

unit/kg/hour [9]. Small studies comparing lower insulin infusion rates (0.05 unit/kg/hour) with
this standard rate found no differences in the rate of blood glucose decline and time to achieve
the blood glucose target of 250 mg/dL [26,27]; however, larger-scale randomized trials are
needed for a more comprehensive comparison of benefits and risks of various insulin infusion
rates. Until more evidence is available, lower rates of insulin infusion should mainly be
considered for children with mild DKA.

Insulin can be mixed in saline (0.45 or 0.9% NaCl) and administered in a syringe infusion pump
to control the rate of administration. The solution should be concentrated as much as possible
and should be flushed through the tubing before starting the infusion to minimize binding of
insulin to the tubing and syringe. As an example, 50 units of regular insulin are added to 50 mL
of 0.45% NaCl, providing 1 unit per mL of infusate. The syringe is then "piggybacked" into the
patient's IV catheter as close as possible to the venous site.

An initial insulin "bolus" or loading dose is unnecessary because the continuous IV insulin
infusion rapidly achieves steady-state serum insulin levels (100 to 200 microU/mL) [28,29].

For mild DKA treated in the emergency department (see 'Treatment of mild diabetic
ketoacidosis' below) or in unusual circumstances where facilities to administer IV insulin are not
readily available, subcutaneous insulin can be used. A protocol for this approach has been
suggested by the International Society for Pediatric and Adolescent Diabetes [19,30]. However,
when insulin is administered subcutaneously, absorption may be inconsistent, particularly in
the setting of volume depletion and secondary sympathetic activation, which can decrease
peripheral perfusion [9,31-33].

Adding dextrose to intravenous fluids — In most patients, insulin and IV fluid treatment
correct the hyperglycemia before resolving the ketoacidosis. When the serum glucose
concentration decreases to 250 to 300 mg/dL (13.9 to 16.7 mmol/L), dextrose should be added
to the IV fluid infusion. This allows continued administration of insulin, which is necessary to
correct the residual ketoacidosis [9]. If the blood glucose level falls below 150 mg/dL (8.0
mmol/L) before complete resolution of ketoacidosis, the concentration of dextrose in the IV
solution should be increased (eg, to 10 or 12.5%) to permit continued insulin infusion. To avoid
hypoglycemia or hyperglycemia, it is advisable to keep blood glucose concentrations around
100 to 150 mg/dL in older children (5.5 to 8.3 mmol/L), or 150 to 180 mg/dL (8.3 to 11.1 mmol/L)
in younger children, throughout the insulin infusion.

The "two-bag system" is an efficient method to maintain the patient's blood glucose in an
acceptable range [34]. In this technique, two bags of the selected IV fluid solution are infused
concurrently, one containing 10% dextrose and the other containing no dextrose. By adjusting
the relative rates of fluid administration from each bag, the rate of fluid and electrolyte
administration can be kept constant, while variable rates of dextrose infusion can be achieved
to respond to changes in the patient's blood glucose concentrations.

For most patients, the insulin infusion rate should be reduced only after the ketoacidosis is
corrected or nearly corrected. However, if the patient shows marked sensitivity to insulin, as in
some younger or malnourished children, it may be necessary to decrease the insulin infusion
rate to avoid hypoglycemia (eg, to 0.05 units/kg/hour), provided that the ketoacidosis continues
to improve [9]. Rare patients who develop severe hypokalemia or severe hypophosphatemia
during DKA treatment may also require temporary reductions in insulin infusion until potassium
or phosphorus levels improve.

If ketoacidosis does not improve as anticipated with insulin and IV fluid infusion, the patient
should be assessed for causes of persistent acidosis, such as infection/sepsis or incorrect
preparation or administration of the insulin solution.

Electrolyte and acid-base disturbances

Serum sodium — The serum sodium concentration at the time of diagnosis of DKA can vary
widely, but many patients have mild hyponatremia due to osmotic effects of hyperglycemia.
During treatment, the serum sodium concentration should gradually rise because water moves
out of the vasculature as the blood glucose declines. To determine if the hyponatremia is
appropriate for the degree of hyperglycemia, some clinicians calculate a "corrected" sodium
concentration, as described in the related topic review on evaluation. (See "Diabetic ketoacidosis
in children: Clinical features and diagnosis", section on 'Serum sodium'.)

The serum sodium concentration should be measured every two to four hours during
treatment. It is anticipated that the measured sodium concentration will rise approximately 1.6
mEq/L for every 100 mg/dL (5.5 mmol/L) decrease in glucose concentration [35]. In older
retrospective studies, failure of the serum sodium concentration to rise during treatment was
found to be associated with cerebral injury [36,37]. However, a subsequent large prospective
study found no such association, with similar rates of altered mental status and clinical
diagnoses of cerebral injury among patients with and without declines in serum sodium
concentration during treatment [38]. Although changes in sodium concentrations do not
appear to contribute to risk of cerebral injury, declines in intravascular volume should be
avoided, particularly in children with severe dehydration or findings suggesting circulatory
compromise. In these situations, the sodium content of the fluid should be increased if the
measured serum sodium concentration is low and does not rise appropriately as the plasma
glucose concentration falls.

Serum sodium trends have been shown to be mainly driven by the sodium content of IV fluids,
rather than the rate of infusion [38]; however, development of severe hypernatremia during
DKA treatment may indicate insufficient volume replacement. (See "Diabetic ketoacidosis in
children: Cerebral injury (cerebral edema)".)

Serum potassium — Patients with DKA have a total body deficit of potassium, although
potassium levels at presentation may be normal or increased. Potassium levels routinely decline
during DKA treatment due to insulin-stimulated transport to the intracellular space and
exchange for intracellular hydrogen ions with correction of acidosis. Therefore, potassium
replacement is necessary for nearly all DKA patients. (See "Diabetic ketoacidosis in children:
Clinical features and diagnosis".)

Potassium replacement should generally begin after initial volume expansion, concurrent with
initiation of insulin therapy. In rare cases of hyperkalemia or renal failure, potassium
replacement should be delayed. It is uncommon for patients to have hypokalemia before
volume expansion; however, should this be the case, earlier and more aggressive potassium
replacement is indicated [9].

Specific recommendations based on the initial serum potassium concentration are as follows:

● If the patient is hyperkalemic, defer potassium replacement therapy until the serum
potassium falls to normal and urine production/adequate renal function is documented
(to rule out acute renal failure caused by acute tubular necrosis or renal vein thrombosis).

● If the patient is normokalemic and voiding, potassium replacement should be given with
the start of insulin therapy. The usual starting concentration is 40 mEq/L (40 mmol/L) of
potassium added to the IV fluid solution (but not in the initial fluid bolus).

● If the patient is hypokalemic, potassium replacement should be started immediately and

the insulin infusion should be delayed until serum potassium has been restored to a near-
normal concentration. The serum potassium concentrations should be monitored hourly
and the replacement adjusted as needed.
Potassium replacement should be given as a mixture of potassium phosphate and either
potassium chloride or potassium acetate (see 'Phosphate' below). Administration of potassium
chloride alone should be avoided to reduce the risk of hyperchloremic metabolic acidosis.

Potassium replacement therapy should continue throughout IV insulin and fluid therapy. The
serum potassium should typically be monitored every two to four hours and the potassium
concentration in IV fluids adjusted as necessary to maintain normal serum potassium levels.
Electrocardiographic monitoring is recommended for most DKA patients but particularly for
those with either hyperkalemia or hypokalemia.

Metabolic acidosis — Either the calculated anion gap or measured beta-hydroxybutyrate

(BOHB) concentrations can be used to monitor resolution of ketosis. Ketoacidosis can be
considered resolved when the anion gap is normal (12±2 mEq/L or mmol/L), serum BOHB is ≤1
mmol/L (10.4 mg/dL), and venous pH is ≥7.3 [9,39]. Ketonuria (urine acetoacetate) may persist
for some time after resolution of DKA and should not be considered an indication of persistent
ketoacidosis.

Treatment resolves acidosis through several mechanisms: Insulin promotes the metabolism of
ketoacid anions (BOHB and acetoacetic acid), which also generates bicarbonate. Insulin also
halts hepatic production of ketoacids and the release of free fatty acids from fat to fuel
ketogenesis. Meanwhile, rehydration improves renal perfusion and promotes excretion of
ketone bodies. Improved tissue perfusion also corrects lactic acidosis that may contribute to the
metabolic acid load.

Hyperchloremic acidosis often develops during DKA treatment as a result of urinary ketoacid
loss (which reduces bicarbonate generation from ketoacid oxidation) and the high chloride load
administered in IV fluids. For this reason, the anion gap or serum BOHB concentrations are
better indicators of resolution of ketosis than the serum bicarbonate concentration.

Bicarbonate therapy generally should not be used in children with DKA. In addition to lack of
clinical benefit [40,41], there are potential risks from bicarbonate therapy:

● Bicarbonate therapy can decrease the acidemic stimulus for hyperventilation, leading to a
rise in partial pressure of carbon dioxide (pCO2) and causing a paradoxical fall in cerebral
pH as the lipid-soluble CO2 rapidly crosses the blood-brain barrier [42,43].

● The administration of alkali may slow the rate of resolution of ketosis [44].

● Bicarbonate therapy has been associated with the development of cerebral injury [37].
(See 'Cerebral injury' below.)
 ● The rapid correction of acidosis with bicarbonate therapy may result in hypokalemia
[45,46].

In rare situations (severe acidosis resulting in impaired cardiac contractility and hemodynamic
instability, life-threatening hyperkalemia), cautious administration of bicarbonate therapy can
be considered [9].

Phosphate — Cellular phosphate depletion is common in uncontrolled diabetes. Similar to the

serum potassium concentration, the serum phosphate concentration may initially be normal or
elevated due to movement of phosphate out of cells. Serum phosphate concentrations typically
decline during DKA treatment, and hypophosphatemia can occur.

Therefore, phosphate should be replaced during DKA treatment (typically by including

potassium phosphate in IV fluids), guided by intermittent monitoring of serum phosphate
concentrations. Most hypophosphatemia during DKA is mild and asymptomatic; however,
severe hypophosphatemia resulting in rhabdomyolysis, muscle weakness/paralysis, and
hemolytic anemia may also occur [47-49]. (See 'Serum potassium' above.)

Calcium and magnesium — Mild hypocalcemia and hypomagnesemia may occur during DKA
treatment. Severe or symptomatic abnormalities are rare. Periodic monitoring of calcium and
magnesium (approximately every four to six hours during DKA treatment) is recommended.

Monitoring — Treatment of DKA requires close monitoring of the patient's clinical condition,
including changes in vital signs, neurologic status, fluid status, and metabolic state [9].
Flowcharts or electronic spreadsheets are useful for the tracking of trends in clinical and
laboratory measures.

Routine monitoring should generally include the following, as detailed in the table ( table 4):

● Blood glucose concentrations should be monitored hourly while the patient is receiving IV
insulin infusion. Venous measurements may be necessary early in treatment when blood
glucose concentrations are frequently above the detectable range of point-of-care meters.

● Electrolytes (sodium, potassium, chloride, bicarbonate, BUN, and creatinine), venous pH,
and pCO2 should be measured every two to four hours. More frequent measurements
may be necessary for patients with severe electrolyte derangements or rapidly changing
electrolyte levels. Serum phosphate, calcium, and magnesium can generally be measured
less frequently (every four to six hours) unless significant derangements in these
electrolytes are present.
 ● Clinical parameters including heart rate, respiratory rate, blood pressure, and oxygen
saturation should be monitored continuously. Inappropriate declines in heart rate or
development of severe hypertension are concerning findings suggesting possible cerebral
injury. Continuous cardiac monitoring is prudent for children with moderate to severe DKA
and those with prolonged QTc interval on initial electrocardiogram.

● Neurologic examinations (GCS or other similar measures) should be done hourly to detect
possible cerebral injury. More frequent neurologic assessments may be necessary in
patients with altered mental status or severe DKA. (See 'Cerebral injury' below.)

● Fluid intake and output should be accurately measured and recorded to ensure ongoing
positive fluid balance. If the patient is neurologically impaired or it is difficult to ascertain
urine output, a urine catheter should be placed.

The initial evaluation of children with DKA is discussed separately. (See "Diabetic ketoacidosis in
children: Clinical features and diagnosis".)

Discontinuing the insulin infusion — The insulin infusion should continue at 0.05 to 0.1
units/kg/hour until all of the following conditions are met:

● Serum anion gap reduced to normal (12±2 mEq/L) or serum BOHB ≤1 mmol/L (10.4 mg/dL)
● Venous pH >7.3 or serum bicarbonate >18 mEq/L
● Blood glucose <200 mg/dL (11.1 mmol/L)
● Patient is tolerating oral intake

Patients may continue to have mild hyperchloremic acidosis and/or ketonuria for some time
after the above conditions are met. Hyperchloremic acidosis with a normal anion gap is not a
contraindication for switching the patient to subcutaneous insulin.

The most convenient time to transition to subcutaneous insulin is before a meal. For patients
using basal-bolus insulin, the IV insulin infusion should be discontinued 15 to 30 minutes after
the first injection of rapid-acting insulin. Basal insulin can be administered either (A) at the same
time as the first injection of rapid-acting insulin, or (B) earlier (for example, the previous
evening), along with a decrease in the rate of IV insulin infusion [50].

TREATMENT OF MILD DIABETIC KETOACIDOSIS

Older children and adolescents with established diabetes and mild DKA ( table 3) can
frequently be managed in the emergency department. These patients often improve
substantially after intravenous (IV) fluid therapy and subcutaneous insulin administration.
Rapid-acting insulin can be given at an initial dose of 0.1 units/kg every one to two hours, with
close monitoring of blood glucose and adjustment of insulin dose based on the clinical
response [51]. Regular insulin (given every four hours) has also been used in these
circumstances [52].

Subsequent management can be done at home, provided that acidosis has resolved after
emergency department treatment and the patient is tolerating oral fluids. The patient must
have access to point-of-care testing of both blood glucose and urine or blood ketone levels, and
the caretakers must be proficient in diabetes sick-day management (see 'Disposition' above).
Ongoing home management will include administration of rapid-acting insulin subcutaneously
every three hours (with the dose adjusted depending upon the response), rehydration with oral
fluids, and frequent monitoring of both glucose and ketone levels.

COMPLICATIONS AND MORTALITY

Reported mortality rates for DKA are consistent in developed countries, ranging from 0.15 to
0.31 percent in national population studies in Canada, the United Kingdom, and the United
States [1-3,53]. Cerebral injury accounts for the majority of deaths (60 to 90 percent) [37,54].
Mortality is substantially higher in resource-limited settings [55].

Cerebral injury — Cerebral injury occurs in 0.3 to 0.9 percent of children with DKA and has a
high mortality rate of 21 to 24 percent [2,25,37,53,56]. Children who have severe acidosis and/or
severe dehydration are at the greatest risk. A range of intravenous (IV) fluid protocols can be
used for treatment of DKA without apparent effect on risk for cerebral injury [25]. (See
'Subsequent fluid administration' above.)

Cerebral injury generally develops during the first 12 hours of treatment but can also occur
before treatment [37,57]. Throughout the course of treatment for DKA, all children should be
carefully monitored for signs and symptoms that suggest cerebral injury, which include changes
in mental status, urinary incontinence, and new headache or recurrence of vomiting [9]. The
decision to treat should be based on clinical changes in mental status or the neurologic
examination; abnormalities detectable by head computed tomography may not be present at
the time of neurologic deterioration. If DKA-related cerebral injury is suspected, treatment
should be initiated promptly using mannitol (0.5 to 1 gm/kg) and/or hypertonic saline (3%
saline, 2.5 to 5 mL/kg over 30 minutes). An approach to monitoring and intervention is outlined
in the table ( table 5) and discussed in detail separately. (See "Diabetic ketoacidosis in
children: Cerebral injury (cerebral edema)".)
Cognitive impairment — DKA may be associated with subtle neurocognitive dysfunction after
recovery, even in patients who did not have clinical evidence of cerebral injury during DKA
treatment [58-61]. Subtle alterations in memory, attention, and intelligence quotient (IQ) and
changes in cerebral microstructure have been detected in children with a history of DKA,
compared with children with diabetes but no history of DKA [58,60-63].

Venous thrombosis — Children with DKA are at increased risk for deep venous thrombosis,
particularly in association with femoral central venous catheter placement [64,65]. This may in
part be due to a prothrombotic state associated with DKA [66].

Pancreatic enzyme elevations — Mild elevations in serum amylase and lipase are seen in
approximately 40 percent of children with DKA and are also common in adults with DKA [67,68].
In most cases, this does not reflect acute pancreatitis. The diagnosis of acute pancreatitis
should be based on clinical findings and confirmed by a computed tomography scan. (See
"Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features,
evaluation, and diagnosis", section on 'Serum amylase and lipase'.)

Acute kidney injury — Studies have documented a high frequency of acute kidney injury (AKI)
in children with DKA (approximately 50 percent) [69-72]. Many of these children have stage 2 or
3 AKI, suggesting intrinsic tubular injury beyond prerenal dysfunction. Kidney failure can also
occur but is rare. Renal function generally returns to normal after recovery from DKA; however,
episodes of DKA-related AKI have been shown to increase the long-term risk of diabetic kidney
disease [73].

Other complications — Rare complications of pediatric DKA include cardiac arrhythmias

resulting from electrolyte derangements, pulmonary edema, multiple organ dysfunction
syndrome, intestinal necrosis, and acute pancreatitis [13,69,74-82]. Patients with DKA are also
uniquely susceptible to rhinocerebral or pulmonary mucormycosis, a rare and frequently fatal
fungal infection [83,84]. Cases of mucormycosis occur most commonly in patients with chronic
poor glycemic control who likely have ongoing intermittent ketosis. (See "Mucormycosis
(zygomycosis)".)

PREVENTION

Attempts should be made to prevent DKA both before and after the diagnosis of diabetes has
been established. Methods that may promote earlier diagnosis of diabetes include increasing
awareness among health care providers and the general public [85] and identifying high-risk
individuals through family history, genetic, and immunologic screening. (See "Type 1 diabetes
mellitus: Disease prediction and screening" and "Type 1 diabetes mellitus: Prevention and
disease-modifying therapy".)

In children with established diabetes, insulin omission or other diabetes mismanagement is the
most common cause of recurrent DKA (see "Diabetic ketoacidosis in children: Clinical features
and diagnosis", section on 'Precipitating factors'). Diabetes care providers can address frequent
DKA recurrences by increasing the intensity of parental involvement in diabetes care,
reinforcing diabetes self-management education, and intensifying the involvement of the
diabetes care team with the family via frequent phone calls or clinic visits. Psychologic
counseling may also be helpful. (See "Overview of the management of type 1 diabetes mellitus
in children and adolescents", section on 'Other management issues'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Diabetes mellitus in
children" and "Society guideline links: Hyperglycemic emergencies".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword[s] of interest.)

● Basics topics (see "Patient education: Diabetic ketoacidosis (The Basics)" and "Patient
education: Managing blood sugar in children with diabetes (The Basics)")

● Beyond the Basics topic (see "Patient education: Type 1 diabetes: Overview (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS

● Laboratory monitoring – Obtain initial laboratory studies including blood glucose,

electrolytes, blood urea nitrogen (BUN) and creatinine, venous or arterial pH and partial
pressure of carbon dioxide (pCO2), phosphorus, calcium, magnesium, and a urine analysis
(and blood beta-hydroxybutyrate [BOHB], if available) ( table 4). Monitor blood glucose
hourly while receiving intravenous (IV) insulin treatment. Measure electrolytes, venous pH,
and pCO2 every two to four hours and phosphorus, calcium, and magnesium every four to
six hours, until ketoacidosis is resolved. (See 'Laboratory testing' above and 'Monitoring'
above.)

● Care setting – Admission to a pediatric intensive care unit (PICU) for management of DKA
is appropriate for children with increased risk for cerebral injury, including altered
consciousness, age younger than five years, severe acidosis or hypocapnia, or high BUN.
Some hospitals require PICU admission for all children treated with IV insulin infusions.
(See 'Disposition' above.)

● Monitoring for cerebral injury – All children with DKA should have serial monitoring for
signs and symptoms of cerebral injury until the DKA has resolved. Signs and symptoms
that suggest cerebral injury include changes in mental status, urinary incontinence, and
new headache or recurrence of vomiting ( table 5). (See 'Cerebral injury' above.)

● Fluid and insulin therapy – Treatment of DKA involves administration of IV fluids and
insulin. (See 'Dehydration' above and 'Hyperglycemia' above.)

• Estimate the total fluid deficit. For most children, assume a fluid deficit of 6 percent of
the child's body weight (ie, 6 percent dehydration). For children with new onset of
diabetes, pH <7.1, or BUN >20 mg/dL, assume a fluid deficit of 8 percent of the child's
body weight. (See 'Dehydration' above.)

• The first step is volume expansion, using isotonic crystalloid solution (eg, normal
saline) administered as an IV bolus of 10 to 20 mL/kg. This initial volume expansion can
be repeated if there is continued hemodynamic instability or circulatory compromise.
(See 'Initial volume expansion' above.)

• After the initial volume expansion is complete, begin an IV insulin infusion at a rate of
0.1 unit/kg/hour. An insulin bolus is unnecessary and is not recommended. (See 'Insulin
infusion' above.)
 • After the initial volume expansion, replace the remaining fluid deficit over 24 to 48
hours using 0.45 to 0.9% sodium chloride (NaCl). (See 'Subsequent fluid administration'
above.)

• Dextrose should be added to the IV fluids when the blood glucose concentration
decreases to 250 to 300 mg/dL (13.9 to 16.7 mmol/L). Use of a "two-bag system" can
facilitate adjustments of dextrose infusion while maintaining a constant rate of fluid
administration. (See 'Adding dextrose to intravenous fluids' above.)

• All patients with DKA require potassium replacement, and serum potassium should be
carefully monitored during therapy. The timing of initiating potassium replacement
should be based on the serum potassium level at presentation. (See 'Serum potassium'
above.)

• Bicarbonate should not be administered to treat acidosis, except in specific rare

circumstances. (See 'Metabolic acidosis' above.)

● Endpoint of therapy – The insulin infusion should be continued until the anion gap is
normal or BOHB ≤1 mmol/L (10.4 mg/dL), acidosis and hyperglycemia have resolved, and
the patient is tolerating oral intake. (See 'Metabolic acidosis' above and 'Discontinuing the
insulin infusion' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges George S Jeha, MD, and Morey Haymond, MD, who
contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Levitsky L. Death from diabetes (DM) in hospitalized children (1970-1988). Pediatr Res 1991;
29:A195.

2. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent
diabetes 1990-96. Arch Dis Child 1999; 81:318.
3. Curtis JR, To T, Muirhead S, et al. Recent trends in hospitalization for diabetic ketoacidosis in
ontario children. Diabetes Care 2002; 25:1591.
 4. Pinhas-Hamiel O, Dolan LM, Zeitler PS. Diabetic ketoacidosis among obese African-
American adolescents with NIDDM. Diabetes Care 1997; 20:484.
5. Scott CR, Smith JM, Cradock MM, Pihoker C. Characteristics of youth-onset noninsulin-
dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis.
Pediatrics 1997; 100:84.
6. Banerji MA. Impaired beta-cell and alpha-cell function in African-American children with
type 2 diabetes mellitus--"Flatbush diabetes". J Pediatr Endocrinol Metab 2002; 15 Suppl
1:493.
7. Sellers EA, Dean HJ. Diabetic ketoacidosis: a complication of type 2 diabetes in Canadian
aboriginal youth. Diabetes Care 2000; 23:1202.
8. Neufeld ND, Raffel LJ, Landon C, et al. Early presentation of type 2 diabetes in Mexican-
American youth. Diabetes Care 1998; 21:80.
9. Glaser N, Fritsch M, Priyambada L, et al. ISPAD clinical practice consensus guidelines 2022:
Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2022;
23:835.
10. Edge JA, Roy Y, Bergomi A, et al. Conscious level in children with diabetic ketoacidosis is
related to severity of acidosis and not to blood glucose concentration. Pediatr Diabetes
2006; 7:11.
11. Zeitler P, Haqq A, Rosenbloom A, et al. Hyperglycemic hyperosmolar syndrome in children:
pathophysiological considerations and suggested guidelines for treatment. J Pediatr 2011;
158:9.
12. DePiero A, Kuppermann N, Brown KM, et al. Hypertension during Diabetic Ketoacidosis in
Children. J Pediatr 2020; 223:156.
13. Perez MM, Medar S, Quigley L, Clark BC. QTc Prolongation in Pediatric Patients with
Diabetic Ketoacidosis. J Pediatr 2021; 228:235.
14. Kuppermann N, Park J, Glatter K, et al. Prolonged QT interval corrected for heart rate
during diabetic ketoacidosis in children. Arch Pediatr Adolesc Med 2008; 162:544.
15. von Oettingen J, Wolfsdorf J, Feldman HA, Rhodes ET. Use of Serum Bicarbonate to
Substitute for Venous pH in New-Onset Diabetes. Pediatrics 2015; 136:e371.

16. Dunger DB, Sperling MA, Acerini CL, et al. ESPE/LWPES consensus statement on diabetic
ketoacidosis in children and adolescents. Arch Dis Child 2004; 89:188.
17. Dunger DB, Sperling MA, Acerini CL, et al. European Society for Paediatric
Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on
diabetic ketoacidosis in children and adolescents. Pediatrics 2004; 113:e133.
18. Wolfsdorf J, Glaser N, Sperling MA, American Diabetes Association. Diabetic ketoacidosis in
infants, children, and adolescents: A consensus statement from the American Diabetes
Association. Diabetes Care 2006; 29:1150.

19. Priyambada L, Wolfsdorf JI, Brink SJ, 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 2020; 21:1394.

20. Koves IH, Neutze J, Donath S, et al. The accuracy of clinical assessment of dehydration
during diabetic ketoacidosis in childhood. Diabetes Care 2004; 27:2485.
21. Sottosanti M, Morrison GC, Singh RN, et al. Dehydration in children with diabetic
ketoacidosis: a prospective study. Arch Dis Child 2012; 97:96.
22. Ugale J, Mata A, Meert KL, Sarnaik AP. Measured degree of dehydration in children and
adolescents with type 1 diabetic ketoacidosis. Pediatr Crit Care Med 2012; 13:e103.
23. Trainor JL, Glaser NS, Tzimenatos L, et al. Clinical and Laboratory Predictors of Dehydration
Severity in Children With Diabetic Ketoacidosis. Ann Emerg Med 2023; 82:167.
24. Brown KM, Glaser NS, McManemy JK, et al. Rehydration Rates and Outcomes in Overweight
Children With Diabetic Ketoacidosis. Pediatrics 2023; 152.

25. Kuppermann N, Ghetti S, Schunk JE, et al. Clinical Trial of Fluid Infusion Rates for Pediatric
Diabetic Ketoacidosis. N Engl J Med 2018; 378:2275.
26. Nallasamy K, Jayashree M, Singhi S, Bansal A. Low-dose vs standard-dose insulin in
pediatric diabetic ketoacidosis: a randomized clinical trial. JAMA Pediatr 2014; 168:999.

27. Puttha R, Cooke D, Subbarayan A, et al. Low dose (0.05 units/kg/h) is comparable with
standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of
diabetic ketoacidosis in children with type 1 diabetes-an observational study. Pediatr
Diabetes 2010; 11:12.
28. Luzi L, Barrett EJ, Groop LC, et al. Metabolic effects of low-dose insulin therapy on glucose
metabolism in diabetic ketoacidosis. Diabetes 1988; 37:1470.
29. Schade DS, Eaton RP. Dose response to insulin in man: differential effects on glucose and
ketone body regulation. J Clin Endocrinol Metab 1977; 44:1038.

30. International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice
Consensus Guidelines 2014. Limited Care Guidance Appendix. Pediatr Diabetes 2014; 15
Suppl 20:281.

31. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by
various routes. N Engl J Med 1977; 297:238.
32. Della Manna T, Steinmetz L, Campos PR, et al. Subcutaneous use of a fast-acting insulin
analog: an alternative treatment for pediatric patients with diabetic ketoacidosis. Diabetes
Care 2005; 28:1856.
33. Soler NG, FitzGerald MG, Wright AD, Malins JM. Comparative study of different insulin
regimens in management of diabetic ketoacidosis. Lancet 1975; 2:1221.

34. Grimberg A, Cerri RW, Satin-Smith M, Cohen P. The "two bag system" for variable
intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis
management. J Pediatr 1999; 134:376.
35. Oh G, Anderson S, Tancredi D, et al. Hyponatremia in pediatric diabetic ketoacidosis:
reevaluating the correction factor for hyperglycemia. Arch Pediatr Adolesc Med 2009;
163:771.

36. Harris GD, Fiordalisi I, Harris WL, et al. Minimizing the risk of brain herniation during
treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr 1990;
117:22.

37. Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with
diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research
Committee of the American Academy of Pediatrics. N Engl J Med 2001; 344:264.

38. Glaser NS, Stoner MJ, Garro A, et al. Serum Sodium Concentration and Mental Status in
Children With Diabetic Ketoacidosis. Pediatrics 2021; 148.
39. Tremblay ES, Millington K, Wu Y, et al. Utility of plasma beta-hydroxybutyrate to define
resolution of diabetic ketoacidosis. Pediatr Diabetes 2022; 23:1621.
40. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis.
Ann Intern Med 1986; 105:836.

41. Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabetic
ketoacidosis. Br Med J (Clin Res Ed) 1984; 289:1035.
42. Assal JP, Aoki TT, Manzano FM, Kozak GP. Metabolic effects of sodium bicarbonate in
management of diabetic ketoacidosis. Diabetes 1974; 23:405.
43. Bureau MA, Bégin R, Berthiaume Y, et al. Cerebral hypoxia from bicarbonate infusion in
diabetic acidosis. J Pediatr 1980; 96:968.
44. Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate in
diabetic ketoacidosis. J Clin Endocrinol Metab 1996; 81:314.
45. Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med
1983; 75:263.
46. Soler NG, Bennett MA, Dixon K, et al. Potassium balance during treatment of diabetic
ketoacidosis with special reference to the use of bicarbonate. Lancet 1972; 2:665.
47. Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion during
treatment of diabetic ketoacidosis and hyperosmolar coma. Diabetes 1980; 29:87.

48. Shilo S, Werner D, Hershko C. Acute hemolytic anemia caused by severe

hypophosphatemia in diabetic ketoacidosis. Acta Haematol 1985; 73:55.
49. Lord GM, Scott J, Pusey CD, et al. Diabetes and rhabdomyolysis. A rare complication of a
common disease. BMJ 1993; 307:1126.
50. Harrison VS, Rustico S, Palladino AA, et al. Glargine co-administration with intravenous
insulin in pediatric diabetic ketoacidosis is safe and facilitates transition to a subcutaneous
regimen. Pediatr Diabetes 2017; 18:742.
51. Mul D, Molendijk E. Question 1: Treatment of mild to moderate ketoacidosis in children and
adolescents with subcutaneous insulin. Arch Dis Child 2015; 100:106.
52. Cohen M, Leibovitz N, Shilo S, et al. Subcutaneous regular insulin for the treatment of
diabetic ketoacidosis in children. Pediatr Diabetes 2017; 18:290.

53. Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence
and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005;
146:688.
54. Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema
developing during diabetic ketoacidosis. Arch Dis Child 2001; 85:16.

55. Poovazhagi V. Risk factors for mortality in children with diabetic keto acidosis from
developing countries. World J Diabetes 2014; 5:932.
56. Scibilia J, Finegold D, Dorman J, et al. Why do children with diabetes die? Acta Endocrinol
Suppl (Copenh) 1986; 279:326.

57. Glaser NS, Quayle KS, McManemy JK, et al. Clinical Characteristics of Children with Cerebral
Injury preceding Treatment of Diabetic Ketoacidosis. J Pediatr 2022; 250:100.
58. Ghetti S, Lee JK, Sims CE, et al. Diabetic ketoacidosis and memory dysfunction in children
with type 1 diabetes. J Pediatr 2010; 156:109.
59. Wootton-Gorges SL, Buonocore MH, Caltagirone RA, et al. Progressive decrease in N-
acetylaspartate/Creatine ratio in a teenager with type 1 diabetes and repeated episodes of
ketoacidosis without clinically apparent cerebral edema: Evidence for permanent brain
injury. AJNR Am J Neuroradiol 2010; 31:780.

60. Cameron FJ, Scratch SE, Nadebaum C, et al. Neurological consequences of diabetic
ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of
 children. Diabetes Care 2014; 37:1554.
61. Ghetti S, Kuppermann N, Rewers A, et al. Cognitive Function Following Diabetic
Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.
Diabetes Care 2020; 43:2768.
62. Antenor-Dorsey JA, Meyer E, Rutlin J, et al. White matter microstructural integrity in youth
with type 1 diabetes. Diabetes 2013; 62:581.
63. Cato MA, Mauras N, Mazaika P, et al. Longitudinal Evaluation of Cognitive Functioning in
Young Children with Type 1 Diabetes over 18 Months. J Int Neuropsychol Soc 2016; 22:293.
64. Worly JM, Fortenberry JD, Hansen I, et al. Deep venous thrombosis in children with diabetic
ketoacidosis and femoral central venous catheters. Pediatrics 2004; 113:e57.
65. Gutierrez JA, Bagatell R, Samson MP, et al. Femoral central venous catheter-associated deep
venous thrombosis in children with diabetic ketoacidosis. Crit Care Med 2003; 31:80.
66. Carl GF, Hoffman WH, Passmore GG, et al. Diabetic ketoacidosis promotes a prothrombotic
state. Endocr Res 2003; 29:73.
67. Haddad NG, Croffie JM, Eugster EA. Pancreatic enzyme elevations in children with diabetic
ketoacidosis. J Pediatr 2004; 145:122.
68. Quiros JA, Marcin JP, Kuppermann N, et al. Elevated serum amylase and lipase in pediatric
diabetic ketoacidosis. Pediatr Crit Care Med 2008; 9:418.
69. Hursh BE, Ronsley R, Islam N, et al. Acute Kidney Injury in Children With Type 1 Diabetes
Hospitalized for Diabetic Ketoacidosis. JAMA Pediatr 2017; 171:e170020.

70. Myers SR, Glaser NS, Trainor JL, et al. Frequency and Risk Factors of Acute Kidney Injury
During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes.
JAMA Netw Open 2020; 3:e2025481.
71. Meena J, Yadav J, Kumar J, et al. Incidence, predictors, and short-term outcomes of acute
kidney injury in children with diabetic ketoacidosis: a systematic review. Pediatr Nephrol
2023; 38:2023.
72. Al Khalifah R, Al-Eyadhy A, Musibeeh N, et al. Risk factors, outcomes, and predictors of
resolution of acute kidney injury in children with diabetic ketoacidosis. Pediatr Nephrol
2023; 38:573.
73. Huang JX, Casper TC, Pitts C, et al. Association of Acute Kidney Injury During Diabetic
Ketoacidosis With Risk of Microalbuminuria in Children With Type 1 Diabetes. JAMA Pediatr
2022; 176:169.

74. Breidbart S, Singer L, St Louis Y, Saenger P. Adult respiratory distress syndrome in an

adolescent with diabetic ketoacidosis. J Pediatr 1987; 111:736.
 75. Chan-Cua S, Jones KL, Lynch FP, Freidenberg GR. Necrosis of the ileum in a diabetic
adolescent. J Pediatr Surg 1992; 27:1236.
76. Malone JI, Brodsky SJ. The value of electrocardiogram monitoring in diabetic ketoacidosis.
Diabetes Care 1980; 3:543.
77. Murdoch IA, Pryor D, Haycock GB, Cameron SJ. Acute renal failure complicating diabetic
ketoacidosis. Acta Paediatr 1993; 82:498.
78. Slyper AH, Wyatt DT, Brown CW. Clinical and/or biochemical pancreatitis in diabetic
ketoacidosis. J Pediatr Endocrinol 1994; 7:261.
79. Young MC. Simultaneous acute cerebral and pulmonary edema complicating diabetic
ketoacidosis. Diabetes Care 1995; 18:1288.
80. Bialo SR, Agrawal S, Boney CM, Quintos JB. Rare complications of pediatric diabetic
ketoacidosis. World J Diabetes 2015; 6:167.
81. Todani T, Sato Y, Watanabe Y, et al. Ischemic jejunal stricture developing after diabetic
coma in a girl: a case report. Eur J Pediatr Surg 1993; 3:115.
82. Weissbach A, Zur N, Kaplan E, et al. Acute Kidney Injury in Critically Ill Children Admitted to
the PICU for Diabetic Ketoacidosis. A Retrospective Study. Pediatr Crit Care Med 2019;
20:e10.
83. Dökmetaş HS, Canbay E, Yilmaz S, et al. Diabetic ketoacidosis and rhino-orbital
mucormycosis. Diabetes Res Clin Pract 2002; 57:139.

84. Khanna SK, Soumekh B, Bradley JS, et al. A case of fatal rhinocerebral mucormycosis with
new onset diabetic keto-acidosis. J Diabetes Complications 1998; 12:224.
85. Vanelli M, Chiari G, Ghizzoni L, et al. Effectiveness of a prevention program for diabetic
ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care
1999; 22:7.
Topic 5808 Version 54.0
GRAPHICS

Rapid overview of the initial evaluation and treatment of moderate to severe

diabetic ketoacidosis in children and adolescents

Clinical suspicion
DKA is the first presentation of diabetes in approximately one-third of children. Presenting symptoms:
Initial – Polyuria, polydipsia, weight loss, nocturia, enuresis (due to hyperglycemia), fatigue.
Subsequent – Nausea/vomiting, abdominal pain, fruity breath odor, Kussmaul breathing,
sometimes altered consciousness.

Definition of DKA
DKA is defined by the presence of all of the following in a patient with diabetes:
Hyperglycemia – Blood glucose ≥200 mg/dL (11 mmol/L).
Metabolic acidosis – Venous pH <7.30 and/or serum bicarbonate <18 mEq/L.
Ketosis – Elevated levels of ketones in urine or blood*.

Note: Patients with marked hyperglycemia but with mild or minimal ketosis and acidosis may have
HHS ¶ , which is a metabolic emergency (refer to UpToDate content on HHS).

Laboratory assessment
Immediate (point-of-care) testing:
Blood glucose.
Urine ketones and/or blood BOHB* (if available).

Laboratory tests:
Serum glucose.
Serum electrolytes, bicarbonate, creatinine, urea nitrogen.
Venous (or arterial) pH and pCO2.
Calcium, phosphorus, magnesium.
Hemoglobin A1c Δ .
Blood BOHB*.
Urinalysis.

Severity of DKA:
Mild – pH 7.2 to 7.3, bicarbonate 10 to 18 mEq/L.
Moderate – pH 7.1 to 7.2, bicarbonate 5 to 10 mEq/L.
Severe – pH <7.1, bicarbonate <5 mEq/L.

Degree of dehydration: Patients with DKA are usually more dehydrated than suggested by the clinical
examination. Initial fluid management should be based on:
If pH <7.1 (suggesting severe DKA), BUN >20 mg/dL, or new onset of diabetes – Assume
approximately 8% dehydration.
 All others – Assume approximately 6% dehydration.

Neurologic status: Patients with abnormal mental status may have cerebral injury (refer to
complications below). Monitor mental status closely, and treat promptly if it fails to improve or worsens
during initial treatment.

Management
Fluids:

Give 10 to 20 mL/kg of 0.9% NaCl (normal saline), or other isotonic solution, administered as an IV
bolus over 20 to 30 minutes:
Mild DKA – 10 mL/kg bolus.
Moderate or severe DKA – 20 mL/kg bolus.
Give additional boluses if necessary, based on cardiovascular status. Larger fluid volumes are usually
needed for patients presenting with mixed features of DKA and HHS (hyperosmolar DKA), regardless
of the level of acidosis.

Hypovolemic shock is a rare occurrence in DKA; continued shock after initial fluid resuscitation
should prompt evaluation for other causes, such as sepsis.

Following initial fluid resuscitation, replace the estimated fluid deficit over 24 to 48 hours, in addition
to maintenance fluids. IV fluids with sodium content between 0.45 and 0.9% NaCl should be used as
the replacement fluid.

Electrolytes:

Sodium: Serum sodium levels are generally low (due to dilutional effect of hyperglycemia) but may
be normal or even high (due to water loss). If serum sodium is low, it should rise as hyperglycemia is
corrected.

Potassium: The timing of potassium replacement depends on the initial serum potassium
concentration ◊ :
Low potassium (<3.5 mEq/L) – Add 40 mEq/L of potassium to IV fluids as soon as possible, and
delay insulin therapy until serum potassium is in the normal range.
Normal potassium (3.5 to 4.5 mEq/L) – Add 40 mEq/L of potassium to IV fluids when insulin
therapy is started.
High potassium (>4.5 mEq/L) – Monitor every hour and begin potassium replacement when
serum potassium decreases to the normal range and when urine production or adequate
kidney function is documented.
Provide potassium as a 1:1 mixture of potassium phosphate plus either potassium chloride or
potassium acetate.

Insulin: After the initial fluid bolus is complete, begin a continuous insulin infusion at 0.1 units/kg per
hour § . Mix 50 units of regular insulin in 50 mL of saline (0.45 or 0.9% NaCl), such that 1 mL of the
infusion provides 1 unit of insulin.

Glucose: Add dextrose to the IV fluids when the blood glucose falls below approximately 300 mg/dL (17
mmol/L) to prevent hypoglycemia during treatment ¥ .

Monitoring
 Monitor and record hourly:
Vital signs.
Neurologic status.
Fluid intake (IV and oral) and losses.

Laboratory monitoring:
Blood glucose hourly.
Electrolytes, venous pH and pCO2 every 2 to 4 hours.
Calcium, phosphorous, and magnesium every 4 to 6 hours.

More frequent monitoring may be necessary for patients with severe electrolyte derangements or rapid
changes in these laboratory values.

Complications
Cerebral injury:
Risk factors – Greater degrees of acidosis, hypocapnia, dehydration, and younger age.
Symptoms and signs – Monitor neurologic status carefully during the first 12 to 24 hours of DKA
treatment. Suspicious symptoms include changes in mental status, new or worsening headache,
recurrence of vomiting, and age-inappropriate incontinence ‡ .
Initiate treatment promptly with 0.5 to 1 g/kg of mannitol if cerebral injury is suspected based on
signs and symptoms. Do not rely on cerebral imaging to make or exclude the diagnosis.

Venous thrombosis: Avoid central venous catheters, if possible, because of increased risk for venous
thrombosis in these patients.

Mild pancreatic enzyme elevations are common in patients with DKA; no specific therapy is needed
other than correction of DKA unless other symptoms of pancreatitis are present.

This table outlines a typical protocol for management of DKA in an urgent care setting. Somewhat
different approaches to fluid volumes and composition may be used, according to patient
characteristics and clinician preference.

BOHB: beta-hydroxybutyrate; BUN: blood urea nitrogen; DKA: diabetic ketoacidosis; HHS: hyperglycemic
hyperosmolar state; IV: intravenous; NaCl: sodium chloride; pCO2: partial pressure of carbon dioxide.

* Ketosis is ideally determined by measuring serum BOHB in the laboratory or by a point-of-care device.
BOHB concentrations ≥3 mmol/L (31 mg/dL) are consistent with DKA.

¶ HHS is defined by plasma glucose concentration >33.3 mmol/L (600 mg/dL), venous pH >7.25 (arterial
pH >7.30), serum bicarbonate >15 mmol/L, minimal ketosis, and effective serum osmolality >320
mOsm/kg.

Δ Hemoglobin A1c is useful in patients with known diabetes to evaluate the degree of metabolic control
or in rare cases in which the diagnosis of diabetes/DKA is uncertain.

◊ Regardless of the initial measured serum potassium concentration, patients with DKA have a total body
potassium deficit and therapy with insulin and fluids will lower serum potassium concentration. Use of a
mixture of potassium salts (potassium phosphate plus either potassium chloride or potassium acetate) is
recommended to decrease chloride administration and replace phosphorus losses.
§ For mild DKA treated in the emergency department or in unusual circumstances where facilities to
administer IV insulin are not readily available, subcutaneous insulin can be used.

¥ A "2-bag system" is a method to maintain the patient's blood glucose in an acceptable range. In this
technique, 2 bags of the selected IV fluid solution are infused concurrently, one containing 10% dextrose
and the other containing no dextrose. By adjusting the relative rates of fluid administration from each
bag, the rate of fluid and electrolyte administration can be maintained constant, while varying the rate of
dextrose infusion to respond to changes in the patient's blood glucose concentrations.

‡ Altered mental status in DKA can be caused by a variety of factors other than cerebral injury, including
acidosis, other metabolic derangements, and sleep deprivation. Nonetheless, clinicians should maintain
a high level of suspicion for evidence of cerebral injury and intervene promptly if the diagnosis is
suspected. Refer to UpToDate content on signs and symptoms cerebral injury in DKA.

Graphic 76460 Version 13.0

Glasgow Coma Scale and Pediatric Glasgow Coma Scale

Glasgow Coma
Sign Pediatric Glasgow Coma Scale [2] Score
Scale [1]

Eye opening Spontaneous Spontaneous 4

To command To sound 3

To pain To pain 2

None None 1

Verbal response Oriented Age-appropriate vocalization, smile, or orientation 5

to sound; interacts (coos, babbles); follows objects

Confused, Cries, irritable 4

disoriented

Inappropriate Cries to pain 3

words

Incomprehensible Moans to pain 2

sounds

None None 1

Motor response Obeys commands Spontaneous movements (obeys verbal command) 6

Localizes pain Withdraws to touch (localizes pain) 5

Withdraws Withdraws to pain 4

Abnormal flexion Abnormal flexion to pain (decorticate posture) 3

to pain

Abnormal Abnormal extension to pain (decerebrate posture) 2

extension to pain

None None 1

Best total score 15

The Glasgow Coma Scale (GCS) is scored between 3 and 15, with 3 being the worst and 15 the best. It is
composed of 3 parameters: best eye response (E), best verbal response (V), and best motor response (M).
The components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS of 9.
Traditionally, the GCS defines the severity of traumatic brain injury (TBI) as follows: ≤8: severe brain injury,
9 to 12: moderate injury, and a score ≥13 or higher: mild injury. However, a significant minority of
patients with TBI and a GCS score of 13 have potentially life-threatening intracranial lesions. While a
revised classification has not been widely adopted, a GCS score of 9 through 13 likely best represents the
TBI population at moderate risk for death or long-term disability (ie, "potentially severe").

The Pediatric Glasgow Coma Scale (PGCS) was validated in children 2 years of age or younger.
Data from:
1. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2:81.
2. Holmes JF, Palchak MJ, MacFarlane T, Kuppermann N. Performance of the pediatric Glasgow coma scale in children with
blunt head trauma. Acad Emerg Med 2005; 12:814.

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Assessment of severity of diabetic ketoacidosis in children [1,2]

Defining features Severe Moderate Mild

Venous pH <7.1 7.1 to <7.2 7.2 to <7.3

Serum bicarbonate <5 5 to 9 10 to <18

(mEq/L)

Venous pH is the most accurate measure of acidosis in patients with diabetic ketoacidosis. However,
measurements of serum bicarbonate may be used alone, especially in resource-limited settings, and are
closely correlated with venous pH.

References:
1. von Oettingen J, Wolfsdorf J, Feldman HA, Rhodes ET. Use of serum bicarbonate to substitute for venous pH in new-onset
diabetes. Pediatrics 2015; 136:e371.
2. Glaser N, Fritsch M, Priyambada L, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Diabetic Ketoacidosis and
Hyperglycemic Hyperosmolar State. Pediatr Diabetes 2022.

Graphic 72608 Version 7.0

Monitoring of children during treatment for diabetic ketoacidosis

Parameter Frequency Comments

Vital signs Hourly Decrease in heart rate (not related to sleep or

rehydration) or severe hypertension suggest
possible cerebral injury.

Fluid intake and output Hourly Ensure ongoing positive fluid balance.

Neurologic status At least hourly Use GCS or similar assessment (refer to UpToDate
content on cerebral injury in children with DKA).

Blood glucose Hourly Use a point-of-care meter, but cross-check with

laboratory tests to ensure correlation.

Blood BOHB Every 2 to 4 hours, if Perform if test is available.

available
Resolution of DKA is indicated by BOHB ≤1 mmol/L
(10.4 mg/dL).

Electrolytes, BUN, Every 2 to 4 hours Timing of initiating potassium replacement

creatinine, venous blood depends on initial serum potassium level (refer to
gas UpToDate topic text).

Calculate the anion gap:

Anion gap = sodium − (chloride + bicarbonate)
Normal anion gap = 12±2 (in mEq/L or
mmol/L); indicates resolution of DKA*

Calculate the corrected sodium concentration:

Corrected sodium = measured sodium + 1.6
(glucose − 100 mg/dL)/100

NOTE – For glucose measured in mmol, use:

(glucose − 5.56)/5.56

Calcium, magnesium, Every 4 to 6 hours More frequent measurements may be required for
phosphorus patients with significant derangements in these
laboratory values.

ECG monitoring Continuous, if available Required for patients with severe DKA or significant
electrolyte abnormalities (particularly potassium),
but recommended for all patients.

GCS: Glasgow Coma Scale; DKA: diabetic ketoacidosis; BOHB: beta-hydroxybutyrate; BUN: blood urea
nitrogen; ECG: electrocardiogram.

* Ketoacidosis can be considered resolved when the anion gap is normal (12±2 mEq/L or mmol/L), serum
BOHB is ≤1 mmol/L (10.4 mg/dL), and venous pH is ≥7.3.

Graphic 97153 Version 8.0

Cerebral injury (cerebral edema) in children with diabetic ketoacidosis: Rapid
overview

Risk factors

Severe acidosis at presentation

Substantially elevated BUN at presentation

Severe hypocapnia

Young child (<5 years) and/or new onset of diabetes – These are not independent risk factors but are
markers for more severe DKA because they are associated with delayed diagnosis of DKA

Diagnosis of cerebral injury*

Minor criteria (moderately suspicious findings)

Headache – Although headache is frequently present at diagnosis, worsening or recurrence of

headache during treatment is suspicious for cerebral injury

Vomiting – Vomiting is suspicious if it develops or recurs during treatment

Irritability, lethargy, or not easily aroused from sleep – These features are suspicious particularly if
they occur or worsen after initiation of therapy

Elevated BP (eg, diastolic BP >90 mmHg).

Major criteria (very suspicious findings)

Abnormal or deteriorating mental status after initiation of therapy, agitated behavior, or fluctuating
level of consciousness

Incontinence inappropriate for age

Inappropriate slowing of heart rate – eg, decline more than 20 beats per minute that is not
attributable to improved intravascular volume or sleep state

Diagnostic criteria (signs of significant brain injury, increased intracranial pressure, or brain
herniation)

Abnormal motor or verbal response to pain

Decorticate or decerebrate posture

Abnormal pupillary response or other CN palsy ¶

Abnormal neurogenic respiratory pattern – eg, grunting, tachypnea, Cheyne-Stokes respiration,

apnea

Treatment

Indications*

Child with DKA and:

1 diagnostic criterion, or
 2 major criteria, or
1 major and 2 minor criteria, or
1 major and 1 minor criterion (if child under 5 years of age)
The decision to treat should be based on signs and symptoms; do not rely on neuroimaging to make
or exclude the diagnosis

Interventions

Give mannitol, 0.5 to 1 g/kg intravenously over 15 minutes; the mannitol dose may be repeated in 30
minutes, if there is no initial response Δ

Adjust fluid administration as indicated to maintain normal BP and optimize cerebral perfusion

Avoid hypotension that might compromise cerebral perfusion pressure

Neurosurgery consultation regarding further management, including possible invasive monitoring

of intracranial pressure in selected cases

BUN: blood urea nitrogen; DKA: diabetic ketoacidosis; BP: blood pressure; CN: cranial nerve.

* These clinical criteria and indications are based upon an evidence-based protocol, as outlined in the
source below.

¶ Key steps are to evaluate extraocular movements (CN III, IV, and VI) and pupillary dilation and reactivity
(CN II and III).

Δ Hypertonic (3%) saline (2.5 to 5 ml/Kg over 10 to 15 minutes) can be used as an alternative to mannitol
or if initial treatment with mannitol does not result in improved mental status.

Adapted from: Muir AB, Quisling RG, Yang MCK, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis. Diabetes Care
2004; 27:1541.

Graphic 53017 Version 11.0

Contributor Disclosures
Nicole Glaser, MD No relevant financial relationship(s) with ineligible companies to disclose. Joseph I
Wolfsdorf, MB, BCh Consultant/Advisory Boards: Ultragenyx [Gene therapy trial in type 1A glycogen
storage disease]. All of the relevant financial relationships listed have been mitigated. Adrienne G
Randolph, MD, MSc Grant/Research/Clinical Trial Support: Illumina Inc. [Multisystem inflammatory
syndrome]. Consultant/Advisory Boards: Brahms GmbH [Sepsis]; Inotrem, Inc. [Sepsis]; ThermoFisher
Scientific [Sepsis]; Volition, Inc. [Sepsis]. All of the relevant financial relationships listed have been
mitigated. Jessica Kremen, MD No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

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