Approach Considerations

In patients with diabetic ketoacidosis, the first principals of resuscitation apply (ie, the ABCs [airway,
breathing, circulation]).[3] Outcomes are best when children are closely monitored and a changing status is
promptly addressed.[39, 2] Give oxygen, although this has no effect on the respiratory drive of acidosis.
Diagnose by clinical history, physical signs, and elevated blood glucose.
Fluid, insulin, and electrolyte (potassium and, in select cases, bicarbonate) replacement is essential in the
treatment of diabetic ketoacidosis.
Early in the treatment of diabetic ketoacidosis, when blood glucose levels are very elevated, the child can
continue to experience massive fluid losses and deteriorate. Strict measurement of fluid balance is
essential for optimal treatment.
Continuous subcutaneous insulin infusion therapy using an insulin pump should be stopped during the
treatment of diabetic ketoacidosis.

Inpatient care
Children with severe acidosis (ie, pH < 7.1) or with altered consciousness should be admitted to a
pediatric intensive care unit.
In cases in which the occurrence of diabetic ketoacidosis signals a new diagnosis of diabetes, the
process of education and support by the diabetes team should begin when the patient recovers.
In cases in which diabetic ketoacidosis occurs in a child with established diabetes, explore the cause of
the episode and take steps to prevent a recurrence.
Following recovery from diabetic ketoacidosis, patients require subcutaneous insulin therapy.

Outpatient care
Organize outpatient care through the pediatric diabetes care team.

Consultations
Consult a neurosurgeon if cerebral edema is suspected.

Diet
Once the child has recovered, he or she can resume a normal diet.

Fluid Replacement
No randomized trials of fluid replacement have been conducted, and over the years, various regimens
have been proposed. Published series suggest that the best outcomes have been achieved by using
isotonic sodium chloride solution or half-strength sodium chloride solution for first resuscitation and
replacement.[2]Slowly correcting the fluid deficit over 48 hours appears to be safer than rapid rehydration
and, thus, forms the basis of the following regimen:

Calculate fluid deficit by weight loss or clinical assessment to a maximum 8% of body weight
In a child with severe acidosis or compromised circulation, an initial resuscitation of 10-20 mL/kg of
isotonic sodium chloride solution (0.9%) can be administered over 30 minutes
Remember to subtract any initial resuscitation fluid boluses given from the total calculated deficit
After resuscitation, slowly correct the fluid deficit over 48 hours by providing normal maintenance fluids
together with the calculated deficit
Administer isotonic sodium chloride solution until blood glucose levels have fallen to 250-300 mg/dL (ie,
12-15 mmol/L), at which time glucose-containing fluids should be introduced (either 5% glucose with
0.9% saline or 5% glucose with 0.45% saline); continue maintenance with dextrose saline until the child
is eating and drinking normally.

If cerebral edema develops, restrict fluid replacement to two thirds of normal maintenance and replace
the deficit over a period of 48 hours or longer
Although strict assessment of fluid balance is important, replacement of ongoing losses is not normally
required
The fluid maintenance rates typically advised for children are probably too generous for use in children
with diabetic ketoacidosis. Table 2, below, can be used to calculate more appropriate infusion rates.
Table 2. Suggested Daily Maintenance Fluid Replacement Rates (Open Table in a new window)
Weight

Infusion rate

0-12.9 kg

80 mL/kg/24 h

13-19.9 kg

65 mL/kg/24 h

20-34.9 kg

55 mL/kg/24 h

35-59.9 kg

45 mL/kg/24 h

Adult (>60 kg) 35 mL/kg/24 h

Insulin Replacement
Continuous, low-dose, intravenous (IV) insulin infusion is generally accepted as the safest and most
effective method of insulin delivery for treating diabetic ketoacidosis. Low-dose IV insulin infusion is
simple, provides more physiologic serum levels of insulin, allows gradual correction of hyperglycemia, and
reduces the likelihood of sudden hypoglycemia and hypokalemia.
The results of a prospective national study of diabetic ketoacidosis in the United Kingdom suggested a
greater risk of cerebral edema in patients who received insulin within the first hour of treatment. [21] In light
of these results, starting insulin therapy an hour after fluid resuscitation has commenced is prudent,
especially in the newly diagnosed child.
The correct dose of insulin to infuse in the treatment of diabetic ketoacidosis is under debate.
Traditionally, 0.1 U/kg/h is given, but a lower dose of 0.05 U/kg/h is enough to prevent gluconeogenesis
and results in a slower reduction of blood glucose levels. One study showed no disadvantage to using the
lower infusion rate of 0.05 U/kg/h.[40] Adolescents with secondary diabetic ketoacidosis and insulin
resistance may need more than 0.1 U/kg/h.
Authorities commonly recommend that blood glucose levels not fall faster than 90 mg% (ie, 5 mmol/L) per
hour. The infusion rate of insulin can be reduced as blood glucose levels fall but should not drop below
0.05 U/kg/h, to prevent any recurrence of ketosis. Do not discontinue infusion until subcutaneous insulin
has been given when the child has recovered. If blood glucose falls below 120 mg% (ie, 7 mmol/L),
increase the concentration of infused glucose to prevent hypoglycemia. Ketosis clears more quickly if
insulin infusions are prolonged for 36 hours or more.
In cases of mild to moderate diabetic ketoacidosis in which the patient is able to tolerate oral fluids, giving
repeated (hourly) subcutaneous injections of regular or fast-acting analogue insulins in a dose of 0.1 U/kg
is possible. This is as effective as IV insulin.[41, 42]

Electrolyte Replacement

Potassium
Patients with diabetic ketoacidosis always have a total-body deficit of potassium. After initial resuscitation
and if serum/plasma levels are below 5 mEq/L or a good renal output has been maintained, add
potassium to all replacement fluids.
Table 3, below, provides examples of infusion concentrations in milliequivalents per liter for differing
degrees of potassium status. Potassium chloride most commonly is administered. This theoretically could
make the acidosis worse, but no evidence indicates that administration of other potassium salts, such as
phosphate or acetate, is more effective.
Table 3. Infusion Rates of Potassium Chloride (Open Table in a new window)
Serum/Plasma K+(mEq/L)

Potassium Chloride (KCL) Dose in Infusion Fluids

< 2.5 mEq/L

Carefully monitored administration of 1 mEq/kg body weight by separate infusion over 1 h

2.5-3.5 mEq/L

40 mEq/L

3.5-5 mEq/L

20 mEq/L

5-6 mEq/L

10 mEq/L (optional)

Over 6 mEq/L

Stop K+ and repeat level in 2 h

Bicarbonate
Although metabolic acidosis may be severe, no evidence supports the administration of IV sodium
bicarbonate to improve outcomes; on the contrary, the evidence indicates that IV bicarbonate may cause
harm and delay recovery.[43, 44]Failure of the acidosis to improve with treatment more likely reflects
inadequate fluid and insulin replacement. The only justification for using IV bicarbonate is acidosis
sufficiently severe to compromise cardiac contractility.

Other electrolytes
Although patients usually have an absolute deficit of phosphate and magnesium, no evidence indicates
that either needs to be replaced in patients with diabetic ketoacidosis.

Diabetes Ther. Dec 2010; 1(2): 103120.

Published online Jan 12, 2011. doi: 10.1007/s13300-010-0008-2
PMCID: PMC3138479

The management of diabetic ketoacidosis in children

Arlan L. Rosenbloom

Management
Children with established diabetes, who are not vomiting or severely ill, and whose caregiver has
been trained in sick day management, can be managed at home or at an outpatient facility, with
appropriate supervision and follow-up.2,2932 Children who are vomiting and not severely ill may
be managed with intravenous (IV) fluids in an emergency department and discharged to home if
able to take fluids orally following rehydration, if venous pH is above 7.25, and telephone
follow-up can be assured. Children requiring IV rehydration over an extended period need to be
admitted to a unit in which neurological status and vital signs can be monitored frequently and
blood glucose levels measured hourly.2 Nursing staff trained in monitoring and management of
DKA should be available and written guidelines should be provided.2,32With severe DKA (long
duration of symptoms, compromised circulation, depressed level of consciousness) or if there are
other factors increasing the risk for cerebral edema (CE; age under 5 years, low partial pressure
of carbon dioxide [pCO2], high serum urea nitrogen), an intensive care unit, preferably pediatric,
or an equivalent facility is appropriate.2
Fluid and Insulin Replacement

Goals of Treatment with Fluid and Insulin

Restore perfusion, which will increase glucose uptake in the periphery, increase glomerular
filtration, and reverse the progressive acidosis.

Arrest ketogenesis with insulin administration, which reverses proteolysis and lipolysis while
stimulating glucose uptake and processing, thereby normalizing blood glucose concentration.

Replace electrolyte losses.

Intervene rapidly when complications, especially CE, occur.

Fluid Therapy

Dehydration can be assumed to be 5%10% (50100 mL/kg). As noted above, the degree of
dehydration is usually overestimated. The severity of extracellular fluid (ECF) contraction may be
indicated by serum urea and hematocrit concentrations.11 Serum Na concentration is not

reliable for determining ECF deficit because of the osmotic effect of hyperglycemia-induced
dilutional hyponatremia33,34 and the low Na content of the elevated lipid fraction of the serum in
DKA. Corrected Na, ie for normal glucose levels, can be estimated by adding 1.6 mEq to the
measured value for each 100 mg/dL blood glucose above normal.33
During the first 12 hours, 1020mL/kg 0.9% sodium chloride (NaCl) should be provided to
restore peripheral perfusion.
Maintenance can be calculated as 1000 mL for the first 10 kg body weight + 500 mL for the next
10 kg + 20 mL/kg over 20 kg or 1500 mL/m2 body surface area.
The remainder of replacement after the loading dose, based on 5%10% dehydration, and
maintenance, can be distributed over the subsequent 2223 hours. While many guidelines call
for calculating replacement over 48 hours, there is no evidence basis for this being safer or more
efficacious. Fluids that have recently been administered orally at home (if not vomited) and
parenteral fluids provided in the emergency room or referring institution need to be
incorporated into the calculation.
Except for severely ill and very young individuals, oral intake should begin before 24 hours.
While urinary output should be carefully documented, urinary losses should not be added to
fluid requirements, except in the presence of HHS.2,17,20
After initial 0.9% NaCl bolus, rehydration/maintenance should be continued with 0.45% NaCl.
The measured Na can increase to the level of the corrected Na during rehydration as glycemia
declines and then decline to normal levels if the corrected level was elevated.
Continued use of 0.9% saline after the initial resuscitation may result in hyperchloremic
metabolic acidosis.35,36
To prevent unduly rapid decline in plasma glucose concentration and hypoglycemia, 5% glucose
should be added to the IV fluid when the plasma glucose falls to 300 mg/dL (17 mmol/L). An
efficient method of providing glucose as needed without long delays entailed by the changing of
IV solutions is to have two IV fluid bags connected, one containing 10% dextrose and the
appropriate Na and K concentrations and the other with the same salt concentrations but no
dextrose, the so-called two bag system.37
K (40 mEq/L or up to 80 mEq/L as needed) can be provided as half potassium chloride (KCl), half
potassium phosphate (KPO4; to replenish low phosphate levels and to decrease the risk of
hyperchloremia) or as half KPO4 and half K acetate (which, like lactate, is converted to
bicarbonate to help correct acidosis) after serum K is <6 mmol/L or urine flow is established.
Serum K concentration increases by approximately 0.6 mEq/L for every 0.1 decrease in pH, so
that the serum K level does not reflect the large deficit from diuresis and vomiting, 5 mEq/kg
body weight. Both K and phosphate shift markedly from intracellular to extracellular

compartments with acidosis and re-enter cells rapidly with insulin-induced glucose uptake and
rehydration.26,38
Bicarbonate administration is not indicated in pediatric DKA. There is no evidence that
bicarbonate facilitates metabolic recovery. Restoring circulatory volume will improve tissue

perfusion and renal function, increasing organic acid excretion and reversing lactic acidosis. The
administration of insulin stops further synthesis of ketoacids and reactivates the Krebs cycle,
permitting metabolism of ketoacids, and regeneration of bicarbonate. Bicarbonate therapy may
cause paradoxical central nervous system (CNS) acidosis, rapid correction of acidosis can cause
hypokalemia, the additional Na can add to hyperosmolality, and alkali therapy can increase
hepatic ketone production, potentially slowing recovery.2
Insulin

Insulin should be started after initial fluid expansion. This provides a more realistic starting

glucose level.
0.1 U/kg/hour is given as a continuous infusion, using a pump. Fifty units of regular insulin are

diluted in 50 mL normal saline to provide 1 unit/mL.

A bolus dose of insulin is not indicated and may increase the risk of CE.39
In some settings it may be necessary to administer insulin subcutaneously. Studies in adults
have indicated no significant difference in recovery time whether insulin was administered
intravenously, intramuscularly, or subcutaneously after the first couple of hours of
treatment.40,43 A study of subcutaneous insulin in children with DKA using a rapid-acting insulin
analog (lispro) provided a dose of 0.15 units/kg every 2 hours; there were no significant
differences from children randomized to receive 0.1 unit/kg per hour intravenously.44 The
administration of 0.1 unit/kg subcutaneously every hour may be preferable and can be adjusted
to maintain blood glucose concentrations at 180200 mg/dL (1011 mmol/L).
Fluid expansion alone will have a dilutional effect, lowering high blood glucose levels by as much
as 180270 mg/dL (1015 mmol/L). With insulin infusion the rate of glucose decline should be
50150 mg/dL (2.88.3 mmol/L/hour), but not >200 mg/dL (11 mmol/L/hour). If serum glucose
values are not dropping adequately, the insulin dose should be increased; this is rarely

necessary.
If the blood glucose concentration falls below 150 mg/dL (8.3 mmol/L) 10% dextrose solution
should be given and the insulin dose reduced to 0.05 U/kg/hour if glucose concentration is not
sustained by the 10% dextrose solution.

Insulin should not be stopped; a continuous supply of insulin is needed to prevent ketosis and
permit continued anabolism. If the patient demonstrates marked sensitivity to insulin, the dose
may be decreased to 0.05 units/kg/hour, or less, provided that metabolic acidosis continues to
resolve.

Persistent acidosis, defined as bicarbonate value <10 mmol/L after 810 hours of treatment, is
usually caused by inadequate insulin effect. Insulin dilution and rate of administration should be
checked, and a fresh preparation made. Too dilute a solution may enhance insulin adherence to
the tubing. If insulin is being given by subcutaneous injection, inadequate absorption may be
occurring. Rare causes of persistent acidosis include lactic acidosis due to an episode of

hypotension or apnea or inadequate renal handling of hydrogen ion as a result of an episode of

renal hypoperfusion.28
Monitoring

Successful management and early intervention for complications requires close monitoring. A
flow chart should be maintained to document all relevant incidents regarding the patients
condition.28 Minimal monitoring frequency recommendations include vital signs and neurologic
checks hourly; blood glucose hourly; venous blood gases every 2 hours for 6 hours, then every 4
hours; Na, K, and ionized calcium every 2 hours for 6 hours, then every 4 hours; magnesium and
phosphorus every 4 hours; basic metabolic profile at admission and then every morning. These
minimum requirements should be adapted to the situation; for example, more frequent (hourly) K
measurements may be indicated, along with electrocardiogram (ECG) monitoring depending on
the initial K value,24,25 or more frequent neurologic and vital sign checks (2030 minutes) if there
is a concern about the patients mental status.28
Ketonuria should not be used as a measure of improvement. The dip sticks used to measure
ketones react with acetoacetate. Concentrations of beta-hydroxybutyrate are much higher than
those of acetoacetate and will be converted to acetoacetate during successful treatment of the
DKA, resulting in sustenance or increase of urinary ketone concentration. Laboratory
measurement or the use of a bedside fingerstick sample monitor for beta-hydroxybutyrate will
avoid this problem.
Transition

IV fluids can be stopped 12 hours after substantial consumption of oral fluids without vomiting.
Subcutaneous insulin injection can be started when IV fluids are no longer needed. Presupper or
prebreakfast time is most convenient for starting or restarting intermediate- or long-acting
insulin. Before then, rapid-acting or regular insulin 0.25 U/kg subcutaneously can be given every
6 hours, and the insulin infusion stopped 60120 minutes after the first subcutaneous dose of
regular insulin or 60 minutes after a rapid-acting insulin analog.
Patients should not be kept in the hospital simply to adjust insulin dosage because food, activity,
and psychosocial environment are not normal in the hospital setting. Therefore, insulin
requirements will not be particularly informative for home management.
Established patients with DKA can resume their usual home dose of insulin.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138479/