Diabetic ketoacidosis in children: Treatment and

complications
Author: Nicole Glaser, MD
Section Editors: Joseph I Wolfsdorf, MD, BCh, Adrienne G Randolph, MD, MSc
Deputy Editor: Alison G Hoppin, MD

Contributor Disclosures

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

Literature review current through: Jan 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 and hyperosmolar hyperglycemic
state 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.
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