Pediatric emergency medicine trisk 467

TABLE 89.2
PRINCIPLES OF MANAGEMENT OF DIABETIC KETOACIDOSIS
Life-threatening complications
Cerebral edema
Cardiovascular collapse
Profound metabolic acidosis
Hyperkalemia
Hypokalemia
Hypophosphatemia
Areas of management decisions
• Fluids. Treat hypovolemia with crystalloid extracellular fluid expander. Use normal saline
(0.9%) and infuse 10 mL/kg in the first 1–2 hrs. (Avoid hypotonic solutions initially
because they are inefficient volume expanders and may contribute to cerebral edema.)
Continue infusion at this rate until perfusion is improved and urine output is reestablished.
After first 1–2 hrs, start half-normal saline—use greater tonicity, up to normal saline, if the
initial serum sodium is less than 135 mmol/L or if the serum sodium falls with therapy.
Total fluid administration in first 48 hrs should rarely exceed one and one-half to two
times maintenance.
• Alkali. Avoid bicarbonate therapy in DKA. Only consider if arterial pH <6.9 and impaired
cardiac contractility and vascular tone, or if patient has life-threatening hyperkalemia.
• Potassium. Start potassium therapy with administration of insulin. Starting concentration in
fluid should be 40 mEq/L as a combination of potassium acetate and potassium phosphate.
If the patient is hypokalemic (<4 mmol/L), a higher concentration of potassium, 60–80
mEq/L, may be necessary. Administer high concentrations of potassium only with
electrocardiographic monitoring. If hyperkalemic (>6 mmol/L), decrease the concentration
to 0–20 mEq/L.
• Insulin. Should be given as a continuous IV infusion (0.1 Unit/kg/hr).
• Glucose. Add 5% glucose to solutions when plasma glucose is approximately 300 mg/dL.
Continue adding glucose up to 12.5% in a peripheral IV in order to keep plasma glucose
in target range of 200–300 mg/dL.
• Phosphate. Add one-half of potassium in IVF as potassium phosphate up to 20 mEq/L.

Monitoring
• Clinical monitoring. Blood pressure, pulse, respirations, neurologic status, and fluid intake
and output.
• Laboratory monitoring. Obtain initial glucose, electrolytes, blood gases, blood urea
nitrogen, and beta-hydroxybutyrate. Measure blood glucose every hour initially as guide
to insulin dosage. Repeat electrolytes, beta-hydroxybutyrate, and pH measurements every
2 to 4 hrs as necessary, every hour if severe abnormalities.
• Use flow sheet.
DKA, diabetic ketoacidosis; IV, intravenous; IVF, intravenous fluids; ETCO2 , end-tidal CO2 .


TABLE 89.3
RISK FACTORS FOR CEREBRAL EDEMA IN DIABETIC KETOACIDOSIS
Elevated blood urea nitrogen
Low Pco2
Treatment with bicarbonate
Failure of measured serum [Na+ ] to rise steadily with correction of hyperglycemia
Age <3 yrs
New-onset diabetes
Once adequate intravascular volume is established, the fluid deficit should be replaced over
the next 48 hours. Classically, it has been recommended that during the first 4 to 6 hours of
this period, isotonic fluids should be used with appropriate additional electrolyte
supplementation as detailed below. The total body water deficit may be estimated based on a
clinical estimate of dehydration, or intravenous (IV) fluid may be administered at a rate
between one and one-half and two times maintenance fluid requirements (see Chapters 22
Dehydration and 100 Renal and Electrolyte Emergencies ). A 2018 randomized controlled trial
of fluid resuscitation in 1,389 episodes of DKA compared slow versus fast replacement of
isotonic (0.9% NS) versus hypotonic (0.45% NS) fluids and did not find differences in
neurologic outcomes suggesting a range of fluid protocols may be used to rehydrate children
with DKA. However, 98% of patients in this trial had GCS score ≥14, therefore, these

recommendations may not apply to the sickest patients, that is, those with GCS scores below
14. Urine output should be monitored and ongoing urinary losses in excess of 5 mL/kg/hr
(osmotic diuresis) should also be replaced.
The Na+ deficit typically approximates 10 mEq/kg body weight and Na+ maintenance is 3
mEq/100 mL of maintenance fluid. From a practical point of view, half-normal (0.45%) saline
can be started after the initial 4-hour period of isotonic fluids. The measured serum sodium
should rise as therapy progresses, and as blood glucose declines. If the initial serum sodium is
less than 136 mEq/L, or if the serum sodium falls with therapy, the IV fluid should be changed
to a more concentrated sodium solution, and the patient should be watched particularly closely.
Serum sodium failing to rise with therapy has been identified as a risk factor for cerebral
edema. Correcting the serum sodium for the degree of hyperglycemia may be useful in
following the patient’s total body sodium status:
Corrected [Na+ ] = measured [Na+ ] + [(glucose level − 100)
× 0.016].
All children with DKA can be assumed to be total-body potassium depleted (approximately
5 mEq/kg body weight); therefore, potassium replacement is an important part of therapy. If
the initial serum [K+ ] is 3 to 4.5 mEq/L, 40 mEq/L of potassium is added to the infusion after
vascular competency has been established and the child has urinated. If the serum [K+ ] is 4.6
to 5.0 mEq/L, only 20 mEq/L of potassium should be added, and if the [K+ ] is above 5.0
mEq/L, potassium should be withheld in the initial fluids. Generally, K+ is provided as


potassium acetate (or chloride) and potassium phosphate in equal amounts. If the initial serum
[K+ ] is less than 4 mEq/L, potassium replacement should be initiated promptly; if less than 3
mEq/L, IVF concentrations of K+ of 60 mEq/L or greater may be necessary. With the higher
concentrations of potassium, the phosphate component must be adjusted not to exceed the
maximum allowable phosphate infusion rate. If the K+ initial concentration is low, monitoring
via an electrocardiogram (ECG) is indicated.
Phosphate depletion is almost universal in patients with DKA; however, the clinical
significance of this reaction remains uncertain. As noted earlier, half of the K+ replacement is

with potassium phosphate, up to a maximum of 20 mEq potassium phosphate per liter except
in the rare situation of severe hypophosphatemia (serum phosphate less than 2 mEq/L).
Infusion of excess phosphate results in hypocalcemia, which may be complicated by tetanic
seizures.
Bicarbonate Therapy
In retrospective reviews of patients with DKA who developed significant cerebral edema,
bicarbonate administration was identified as a significant risk factor ( Table 89.3 ). This may
be because the sickest patients are the ones most likely to have received bicarbonate therapy;
however, without further clarification of the pathophysiology, bicarbonate therapy is reserved
for patients with both severe acidosis (pH <6.9) and secondary hemodynamic compromise that
is unresponsive to inotropic agents.
A theoretical mechanism for the complications observed with bicarbonate therapy is the
development of a paradoxical acidosis of the central nervous system (CNS) and resultant
cerebral depression. Paradoxical acidosis occurs because administered HCO3 − combines with
excess H+ ions in the bloodstream to form H2 O and CO2 . Because the blood–brain barrier is
relatively more permeable to CO2 than to HCO3 − , CO2 accumulates in the CNS, resulting in
further exacerbation of acidosis in this compartment, while acidosis is being corrected
systemically.
Insulin and Glucose
Regular insulin is used for the treatment of ketoacidosis, but it should not be administered until
the initial isotonic fluids have been administered for 1 hour. Insulin is initially necessary to
stop ongoing ketone body production, the primary cause of the acidosis. Insulin should be
started after 1 hour of initial fluid expansion to steadily correct the acidosis and may be either
infused intravenously or, if necessary, injected intramuscularly at hourly intervals. Intermittent
injections of insulin should be avoided because of the uncertainties of absorption in a
dehydrated patient, although in a resource-limited setting, hourly intramuscular injections may
be a suitable substitution for continuous intravenous dosing. The starting dose of insulin for
continuous infusion is 0.1 Unit/kg/hr, infused by a regulated pump. Small studies comparing
low-dose insulin infusions (0.05 Unit/kg/hr) with this standard infusion rate found no
difference in rate of blood glucose decline or time to achieve blood glucose target in mild

DKA (pH ≥7.2), however, larger randomized trials are needed for full understanding of
benefits and risks of these different insulin infusion rates. Failure of the glucose to decrease in
response to insulin suggests improper insulin preparation, inadequate hydration, or serious
underlying disease (e.g., appendicitis or fasciitis with resultant significant increases in


counterregulatory hormones). It is unnecessary and possibly detrimental to give an initial bolus
of insulin. The dose for the hourly intramuscular (IM) injection, used if IV access cannot be
obtained, is 0.1 Unit/kg/hr.
Once the blood glucose approaches 300 mg/dL, dextrose should be added to the IV fluids.
As long as the child remains acidotic, insulin infusion should be not be stopped; instead, the
amount of dextrose in the IV infusion should be increased in stepwise fashion up to a
concentration of 12.5 g/dL to maintain the blood glucose between 200 and 300 mg/dL. If the
blood glucose continues to drop, the rate of IV fluid administration should be increased to
twice maintenance. If the blood glucose still cannot be maintained, the insulin infusion should
be decreased by increments of 0.025 Unit/kg/hr. One efficient system to maintain an
acceptable range of blood glucose is the “two bag system” in which two bags of the selected
IV fluid solution are infused concurrently, one with 10% to 12.5% dextrose and the other
without dextrose, both with electrolytes including sodium, chloride, potassium, acetate, and
phosphate. The rates of fluid infused from each bag can be adjusted to allow varying rates of
dextrose infusion without change in electrolyte concentration or overall rate of fluid
administration.
When the child is able to eat and the anion gap has closed (normal = 10 to 12), IV infusion
of insulin can be discontinued. If hourly IM injections are used, they should be continued until
the blood glucose is less than 300 mg/dL and acidosis is correcting. Because IV insulin is
metabolized rapidly, subcutaneous insulin must be given 30 minutes prior to the
discontinuation of the infusion. The initial dose of subcutaneous insulin should be calculated,
with consultation by a pediatric endocrinologist, based on a daily dose of 0.75 Unit/kg/day in
the prepubertal child up to 1.0 Unit/kg/day in the pubertal child and beyond. The total daily
dose must be divided into long-acting and short-acting insulins.

Cerebral Edema
Despite several investigations of the causes and risk factors for clinically significant cerebral
edema in patients with DKA, and subsequent modifications in therapy, the incidence of the
complication has not changed significantly during the past 20 years and remains at
approximately 0.5% to 1%. Table 89.3 lists the leading risk factors published in more recent
years. Clinical signs and symptoms of significant cerebral edema include abnormal motor or
verbal response to pain, decorticate or decerebrate posturing, new cranial nerve palsy, and
abnormal respiratory pattern. Other concerning signs are decrease or fluctuation in level of
consciousness (e.g., Glasgow Coma Scale), age-inappropriate incontinence, vomiting,
headache, and heart rate deceleration.
If these signs are noted by the physician at the bedside, a clinical diagnosis of cerebral
edema must be made and treatment initiated without any diagnostic imaging. The patient
should receive mannitol 1 g/kg IV over 10 minutes. There is some evidence that mannitol is
the preferred first-line agent, but that hypertonic saline (3%) may be an appropriate secondline agent; however, only a large retrospective study and case series data are currently
available.
Endotracheal intubation should be considered rarely: primarily if the patient’s mental status
does not assure a safe airway, and secondarily if the patient is not able to maintain a
respiratory alkalosis to partially compensate for the metabolic acidosis. Noninvasive