Treatment and Complications of Diabetic Ketoacidosis in Children and Adolescents - UpToDate

12/10/2019 Treatment and complications of diabetic ketoacidosis in children and adolescents - UpToDate
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Treatment and complications of diabetic ketoacidosis in

children and adolescents
Author: Nicole Glaser, MD
Section Editors: Joseph I Wolfsdorf, MB, BCh, Adrienne G Randolph, MD, MSc
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2019. | This topic last updated: Jan 18, 2019.
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 percent to 0.31 percent in the United States and
other resource-rich countries [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. The clinical manifestations and diagnosis of DKA in children, and the pathogenesis of DKA are
discussed elsewhere. (See "Clinical features and diagnosis of diabetic ketoacidosis in children and
adolescents" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults:
Epidemiology and pathogenesis".)
DEFINITION
● Diabetic ketoacidosis – Diabetic ketoacidosis (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 (ISPAD) in 2018 [9]:
• Hyperglycemia – Blood glucose of >200 mg/dL (11 mmol/L)

• Metabolic acidosis – Venous pH <7.3 or a plasma bicarbonate <15 mEq/L (15 mmol/L)
• Ketosis – Determined by the presence of ketones in the blood or urine
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Ketosis is ideally determined by measuring serum beta-hydroxybutyrate (BOHB) in the

laboratory or by a point-of-care device. BOHB concentrations ≥3 mmol/L (31 mg/dL) are
consistent with DKA [9]. (See "Clinical features and diagnosis of diabetic ketoacidosis in
children and adolescents".)
Disturbances in fluid and electrolyte balance result in volume depletion and mild to moderate
serum hyperosmolality. The clinical manifestations of DKA are related to volume depletion,
electrolyte imbalances, and acidosis [10]. Some children present with severe hyperglycemia and
may have mixed features of DKA and hyperglycemic hyperosmolar state (HHS), as described
below. (See "Clinical features and diagnosis of diabetic ketoacidosis in children and
adolescents".)
● Hyperglycemic hyperosmolar state – 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/L
Patients with HHS frequently have altered consciousness (in approximately 50 percent) and
moderate lactic acidosis. HHS requires prompt recognition and management that is distinct from
that of DKA. In particular, dehydration in HHS is typically severe and requires greater fluid
resuscitation than DKA. In addition, delayed initiation of insulin treatment is 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 can also occur.
Further details about how to identify and treat HHS are discussed in separate topic reviews. (See
"Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents", 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).
● Measure weight for use in calculating fluid replacement and insulin infusion rates. If recent
measurements of weight are available, 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. (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 "Cerebral injury (cerebral edema) in children with diabetic ketoacidosis", 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 laboratory for more accurate measurements and to further
characterize the patient's acid-base status, electrolyte balance, and dehydration:
• Blood glucose.
• Electrolytes – Including bicarbonate.
• Blood urea nitrogen (BUN), creatinine.
• Venous pH and partial pressure of carbon dioxide (pCO2).
• Complete blood count.
• Calcium, phosphorus, magnesium – Severe abnormalities in these values are uncommon

but can have serious consequences if undetected, particularly in the case of
hypophosphatemia.
● Additional evaluation for specific circumstances:
• Blood lactate – To determine the contribution of lactic acid to the metabolic acidosis. Lactic
acidosis is more likely in a patient with very severe dehydration or shock, sepsis, or
hyperglycemic hyperosmolar state (HHS).
• Cultures of blood, urine, and/or throat, or other evaluation for infection if fever or localizing
signs of infection are present.
• Electrocardiogram to assess for evidence of hyperkalemia (peaked T wave) if laboratory

measurement of potassium status is delayed.
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):
• Mild – pH 7.2 to <7.3; bicarbonate 10 to <15 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 the most accurate measure of acidosis. However, measurements of serum

bicarbonate may be used alone, especially in resource-limited settings, and are closely
correlated with venous pH [12]. For particularly vulnerable patients such as young children or in
resource-limited settings, higher thresholds for bicarbonate may be used for increased sensitivity
(eg, bicarbonate <7 mEq/L for severe DKA and <18 mEq/L for mild DKA).
● 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:

Anion gap = Sodium – (chloride + bicarbonate); a normal anion gap is 12±2
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, the anion gap tends to normalize before resolution of the acidosis, frequently
resulting in a mild "non-gap" acidosis as treatment progresses. This is usually associated with
hyperchloremic metabolic acidosis, resulting from the large amount of chloride administered
during rehydration. Therefore, the anion gap is a better measure of effective treatment than 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 [13-15].
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 or low pCO2),
high BUN, significant hyper- or hypokalemia, or other severe electrolyte disturbances. In some
institutions, all patients receiving intravenous (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.
● 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 DKA' below.)
TREATMENT OF MODERATE AND SEVERE DKA

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 — Average water losses in children with DKA are approximately 70 mL/Kg (range 30 to
100 mL/Kg) [16-18]. Volume depletion is caused by urinary losses from osmotic diuresis, as well as
gastrointestinal losses from vomiting and insensible losses from hyperventilation.
Clinical signs of dehydration tend to be inaccurate for assessing dehydration severity in DKA [16].
Increased blood urea nitrogen (BUN) concentrations or elevated hematocrit can be helpful markers of
hydration status. Fluid calculations usually should be based upon the assumption of 5 to 7 percent
dehydration for mild to moderate DKA, and 7 to 10 percent for severe DKA. 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 "Clinical features and diagnosis of diabetic ketoacidosis
in children and adolescents", 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 percent sodium chloride [NaCl]) or Ringer's lactate [9,19]. 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 "Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents",
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 DKA' below.)
Subsequent fluid administration — Once the child is hemodynamically stable, additional IV

fluids should be administered, calculated to replace the remaining fluid deficit over 24 to 48 hours,
using IV fluids with 0.45 to 0.9 percent NaCl.

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 [19]. Similarly, there were no differences in
neurologic outcomes of children treated with 0.9 percent NaCl versus 0.45 percent NaCl fluids.
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 cerebral injury is discussed separately.
(See "Cerebral injury (cerebral edema) in children with diabetic ketoacidosis", 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 — Following the initial IV fluid bolus [20], an IV insulin infusion should be
administered. Insulin administration offsets insulin resistance, 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 [21,22]; however, larger scale randomized trials are needed for a more comprehensive
comparison of benefits and risks of various insulin infusion rates.
Insulin can be mixed in saline (0.45 or 0.9 percent 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 percent
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) [23,24].

For mild DKA treated in the emergency department (see 'Treatment of mild DKA' 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 (ISPAD) [25]. 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 [9,26-28].
Adding dextrose to intravenous fluids — In most patients, insulin and intravenous (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 percent) 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 [29]. In this technique, two bags of the selected IV fluid solution are infused concurrently, one
containing 10 percent 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 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].
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 "Clinical features and diagnosis of diabetic
ketoacidosis in children and adolescents", section on 'Serum sodium'.)
The serum sodium concentration should be measured every two to four hours during treatment to
ensure that it is rising as expected, at a rate of approximately 1.6 mEq/L for every 100 mg/dL (5.5
mmol/L) decrease in glucose concentration [30]. Failure of the serum sodium concentration to rise as
the glucose concentration declines has been associated with cerebral injury [31,32]. Therefore, lack
of the expected rise in the serum sodium concentration should prompt careful and frequent
assessment of the patient's neurologic status. (See "Cerebral injury (cerebral edema) in children with
diabetic ketoacidosis".)
Serum potassium — Patients with DKA have a total body deficit of potassium, although
potassium levels at presentation may be normal or even 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 "Clinical features and diagnosis of diabetic ketoacidosis in
children and adolescents".)
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, potassium replacement should not be given initially, but should be
initiated when the serum potassium falls to normal and after verifying urine production/adequate
renal function (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, serum BOHB ≤1 mmol/L (10.4 mg/dL), and venous pH ≥7.3 [9,33].
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 [34,35], 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 carbon dioxide (CO2) rapidly crosses the blood-brain barrier [36,37].
● The administration of alkali may slow the rate of resolution of ketosis [38].
● Bicarbonate therapy has been associated with the development of cerebral injury [32]. (See
'Cerebral injury' below.)
● The rapid correction of acidosis with bicarbonate therapy may result in hypokalemia [39,40].
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In rare situations (severe acidosis resulting in 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 asymptomatic; however, case reports describe rhabdomyolysis,
muscle weakness/paralysis, and hemolytic anemia resulting from severe hypophosphatemia during
DKA treatment [41-43]. In addition, hypophosphatemia could theoretically have adverse effects on
tissue oxygenation because it decreases erythrocyte 2,3-diphosphoglycerate concentrations, which
could shift the oxyhemoglobin dissociation curve, although the clinical relevance of this effect is
debated [44]. (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, urea nitrogen, 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.

● 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. 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 "Clinical features and
diagnosis of diabetic ketoacidosis in children and adolescents".)
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 (HCO3) >15 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 [45].
TREATMENT OF MILD DKA
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 [46]. Regular insulin (given every four
hours) has also been used in these circumstances [47].
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 [1-3,48].
Cerebral injury accounts for the majority of deaths (60 to 90 percent) [32,49]. Mortality is likely
substantially higher in resource-limited settings.
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 [2,19,32,48,50]. 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 [19]. (See 'Subsequent fluid
administration' above.)
Cerebral injury generally develops during the first 12 hours of treatment but can also occur before
treatment [32]. 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 percent saline, 5 to 10 mL/kg over 30 minutes). An approach to monitoring
and intervention is outlined in the table (table 5) and discussed in detail separately. (See "Cerebral
injury (cerebral edema) in children with diabetic ketoacidosis".)
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
[51-53]. 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 [51,53-55].
Venous thrombosis — Children with DKA are at increased risk for deep venous thrombosis,
particularly in association with femoral central venous catheter placement [56,57]. This may in part be
due to a prothrombotic state associated with DKA [58].
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 [59,60]. In
most cases, this does not reflect acute pancreatitis. The diagnosis of acute pancreatitis should be
based on clinical findings and confirmed by CT scan. (See "Diabetic ketoacidosis and hyperosmolar
hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Serum
amylase and lipase'.)
Other complications — Rare complications of pediatric DKA include cardiac arrhythmias resulting
from electrolyte derangements, acute kidney injury or renal failure, pulmonary edema, multiple organ
dysfunction syndrome, intestinal necrosis, and acute pancreatitis [61-70]. Patients with DKA are also
uniquely susceptible to rhinocerebral or pulmonary mucormycosis, a rare and frequently fatal fungal
infection [71,72]. 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 mellitus has
been established. Methods that may promote earlier diagnosis of diabetes include increasing
awareness among health care providers and the general public [73] and identifying high-risk
individuals through family history, genetic, and immunologic screening. (See "Prediction of type 1
diabetes mellitus" and "Prevention of type 1 diabetes mellitus".)
In children with established diabetes, insulin omission or other diabetes mismanagement is the most
common cause of recurrent DKA (see "Clinical features and diagnosis of diabetic ketoacidosis in
children and adolescents", 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 "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: Controlling blood sugar in children with diabetes (The Basics)")
● Beyond the Basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
The following is a summary of the above discussion regarding the treatment of diabetic ketoacidosis
(DKA) and is consistent with guidelines from the International Society for Pediatric and Adolescent
Diabetes (ISPAD) [9]:
● Obtain initial laboratory studies including blood glucose, electrolytes, blood urea nitrogen (BUN)
and creatinine, venous pH and partial pressure of carbon dioxide (pCO2), hematocrit,
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 until ketoacidosis
is resolved. (See 'Laboratory testing' above and 'Monitoring' above.)
● 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, younger than five
years of age, severe acidosis or hypocapnia, or high BUN. Some hospitals require PICU
admission for all children treated with IV insulin infusions. (See 'Disposition' above.)

● 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.)
● Treatment of DKA involves administration of IV fluids and insulin. (See 'Dehydration' above and
'Hyperglycemia' above.)
• Initial volume expansion should be given 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 initial volume expansion, an IV insulin infusion should be administered at a rate of 0.1
unit/kg per hour. An insulin bolus is unnecessary and is not recommended. (See 'Insulin
infusion' above.)
• After the initial fluid bolus(es), replacement of the remaining fluid deficit should be
accomplished over 24 to 48 hours using 0.45 to 0.9 percent 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.)
● The serum anion gap or BOHB level can be used to monitor DKA resolution. (See 'Assessment
of severity' above and 'Metabolic acidosis' above.)
● Bicarbonate should not be administered to treat acidosis except in specific rare circumstances.
(See 'Metabolic acidosis' above.).
ACKNOWLEDGMENTS
The editorial staff at UpToDate would like to acknowledge George S Jeha, MD, and Morey Haymond,
MD, who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.
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22:7.
Topic 5808 Version 35.0

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

diabetic ketoacidosis (DKA) in children and adolescents
Clinical suspicion
DKA is the first presentation of diabetes in approximately one-third of children. Presenting symptoms:
Initial – Polyuria, polydipsia, fatigue, weight loss, nocturia, enuresis (due to hyperglycemia).
Subsequent – Nausea/vomiting, abdominal pain, fruity breath, 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 <15 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, creatinine, urea nitrogen
Venous pH and pCO 2
Calcium, phosphorus, magnesium
Hemoglobin A1c ¶
Urinalysis
Severity of DKA:
Mild – pH 7.2 to 7.3; bicarbonate 10 to 15 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:
Mild DKA – Assume 5 to 7% fluid deficit.
Moderate to severe DKA – Assume 7 to 10% fluid deficit.
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:
Mild DKA – 10 mL/kg bolus.
Moderate or severe DKA – 20 mL/kg bolus.
Additional boluses may be given if necessary, based on cardiovascular status. Larger fluid volumes may be needed
for patients presenting with mixed features of DKA and HHS, regardless of the level of acidosis.
Hypovolemic shock is a rare occurrence in DKA, and 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. Failure of the
serum sodium to rise appropriately may be an early sign that the patient is at risk for cerebral injury.
Potassium: The timing of potassium replacement depends on the initial serum potassium concentration: Δ
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 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.
Provide potassium as potassium phosphate plus either potassium chloride or potassium acetate.
Insulin: After the initial fluid bolus, 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
Record vital signs and check neurologic status hourly, as well as fluid intake (IV and oral) and losses.
Measure blood glucose hourly. Measure electrolytes, venous pH and pCO 2 every two to four hours. Measure calcium,
phosphorus, and magnesium every four to six hours. More frequent monitoring may be necessary for patients with
severe electrolyte derangements or rapid changes in these laboratory test results.
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, 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.
DKA: diabetic ketoacidosis; HHS: hyperglycemic hyperosmolar state; BOHB: beta-hydroxybutyrate; pCO 2 : partial pressure
of carbon dioxide; NaCl: sodium chloride; IV: intravenous.
* 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.
¶ A1c is only useful in patients with known diabetes, to evaluate the degree of metabolic control.
Δ 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 "two bag system" is a method to maintain the patient's blood glucose in an acceptable range. 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
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 10.0

Glasgow Coma Scale and Pediatric Glasgow Coma Scale
Glasgow Coma
Sign Pediatric Glasgow Coma Scale [2] Score
Scale [1]
Eye Spontaneous Spontaneous 4

opening
To command To sound 3
To pain To pain 2
None None 1
Verbal Oriented Age-appropriate vocalization, smile, or orientation to sound, interacts 5

response (coos, babbles), follows objects
Confused, disoriented Cries, irritable 4
Inappropriate words Cries to pain 3
Incomprehensible Moans to pain 2

sounds
None None 1
Motor Obeys commands Spontaneous movements (obeys verbal command) 6

response
Localizes pain Withdraws to touch (localizes pain) 5
Withdraws Withdraws to pain 4
Abnormal flexion to Abnormal flexion to pain (decorticate posture) 3

pain
Abnormal extension to Abnormal extension to pain (decerebrate posture) 2

pain
None None 1
Best total score 15
The Glasgow Coma Scale (GCS) is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of
three 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. A score of 13 or higher
correlates with mild brain injury, a score of 9 to 12 correlates with moderate injury, and a score of 8 or less represents
severe brain injury. The pediatric Glasgow coma scale (PGCS) was validated in children two 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.

Assessment of severity of diabetic ketoacidosis in children
Defining features Severe Moderate Mild
Venous pH <7.1 7.1 to <7.2 7.2 to <7.3
Serum bicarbonate (mEq/L) <5* 5 to 9 10 to <15*
Venous pH is the most accurate measure of acidosis in patients with diabetic ketoacidosis (DKA). However,
measurements of serum bicarbonate may be used alone especially in resource-limited settings and are closely
correlated with venous pH.
* For particularly vulnerable patients such as young children or in resource-limited settings, higher thresholds for bicarbonate
may be used for increased sensitivity, eg, bicarbonate <7 mEq/L for severe DKA and <18 mEq/L for mild DKA.
Data from: 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.

Monitoring of children during treatment for diabetic ketoacidosis
Parameter Frequency Comments
Vital signs Hourly Decreased resting heart rate or increased blood pressure
suggest possible cerebral injury.
Fluid intake and output Hourly
Neurological status At least hourly Use GCS or similar assessment (refer to UpToDate content
on cerebral injury in children with diabetic ketoacidosis).
Blood glucose Hourly Use a point-of-care meter but cross-check with laboratory
tests to ensure correlation.
Blood beta-hydroxybutyrate Every two to four hours, if Perform if test is available.

available. Resolution of DKA is indicated by beta-hydroxybutyrate ≤1
mmol/L (10.4 mg/dL) on two successive occasions.
Electrolytes, BUN, Every two to four hours Timing of initiating potassium replacement depends on
creatinine, venous blood initial serum potassium level (refer to UpToDate topic
gas text).
Calculate the anion gap:
Anion gap = sodium – (chloride + bicarbonate)
Normal anion gap = 12±2; 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 four to six hours More frequent measurements may be required for patients
phosphorus 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; BUN: blood urea nitrogen; ECG: electrocardiogram.

Cerebral injury (cerebral edema) in children with DKA: 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 blood pressure (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 cranial nerve palsy. ¶
Abnormal neurogenic respiratory pattern – eg, grunting, tachypnea, Cheyne-Stokes respiration, apnea.
Treatment
Indications:*
Child with DKA and

One diagnostic criterion, or
Two major criteria, or
One major and two minor criteria, or
One major and one 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 blood pressure 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.
DKA: diabetic ketoacidosis; BP: blood pressure; mmHg: millimeters of mercury; CN: cranial nerves.
* 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.

Contributor Disclosures
Nicole Glaser, MD Nothing to disclose Joseph I Wolfsdorf, MB, BCh Consultant/Advisory Boards: Ultragenyx
DSMB [Glycogen storage disease type 1a (AAV gene therapy)]; Xeris DSMB [Hyperinsulinemic hypoglycemia
(Glucagon)]. Adrienne G Randolph, MD, MSc Grant/Research/Clinical Trial Support: Genentech [lipid
biomarkers in influenza critical illness]. Consultant/Advisory Boards: La Jolla Pharmaceuticals [Angiotensin 2 in
pediatric refractory shock]. Equity Ownership/Stock Options: Abbvie. Alison G Hoppin, MD Nothing 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.
Conflict of interest policy

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12/10/2019 Treatment and complications of diabetic ketoacidosis in children and adolescents - UpToDate

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Treatment and complications of diabetic ketoacidosis in

• Hyperglycemia – Blood glucose of >200 mg/dL (11 mmol/L)

Ketosis is ideally determined by measuring serum beta-hydroxybutyrate (BOHB) in the

● Hyperglycemic hyperosmolar state – HHS is a hyperglycemic emergency that is distinguished

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

INITIAL RAPID ASSESSMENT

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

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

• Blood beta-hydroxybutyrate (BOHB) – Concentrations ≥3 mmol/L (31 mg/dL) are consistent

• Electrolytes – Including bicarbonate.

• Blood urea nitrogen (BUN), creatinine.

• Venous pH and partial pressure of carbon dioxide (pCO2).

• Complete blood count.

• Calcium, phosphorus, magnesium – Severe abnormalities in these values are uncommon

● Additional evaluation for specific circumstances:

• Electrocardiogram to assess for evidence of hyperkalemia (peaked T wave) if laboratory

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

• Mild – pH 7.2 to <7.3; bicarbonate 10 to <15 mEq/L

Venous pH is the most accurate measure of acidosis. However, measurements of serum

https://www.uptodate.com/contents/treatment-and-complications-of-diabetic-ketoacidosis-in-children-and-adolescents/print?search=cetoacidosis diab… 4/31

Anion gap = Sodium – (chloride + bicarbonate); a normal anion gap is 12±2

TREATMENT OF MODERATE AND SEVERE DKA

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Initial volume expansion of 10 to 20 mL/kg should be administered as an IV bolus, using isotonic

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

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Insulin infusion — Insulin should be administered as an IV infusion at a rate of 0.1 unit/kg/hour

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Electrolyte and acid-base disturbances

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degree of hyperglycemia, some clinicians calculate a "corrected" sodium concentration, as described

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In rare situations (severe acidosis resulting in hemodynamic instability, life-threatening hyperkalemia),

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

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TREATMENT OF MILD DKA

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COMPLICATIONS AND MORTALITY

SOCIETY GUIDELINE LINKS

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INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

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Use of UpToDate is subject to the Subscription and License Agreement.

11. Zeitler P, Haqq A, Rosenbloom A, et al. Hyperglycemic hyperosmolar syndrome in children:

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21. Nallasamy K, Jayashree M, Singhi S, Bansal A. Low-dose vs standard-dose insulin in pediatric

30. Oh G, Anderson S, Tancredi D, et al. Hyponatremia in pediatric diabetic ketoacidosis:

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41. Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion during treatment of

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

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Topic 5808 Version 35.0

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

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