ED Management of DKA
In Infants and Children
DKA?1
No
Yes
Obtain on all patients:
rapid blood glucose, ABG, UA
serum glucose/lytes/Ca/Mg/PO4/BUN/creatinine
Hgb A1C, 12 lead ECG
Initiate fluid therapy3
Initiate insulin therapy4
Monitor closely for & treat cerebral edema5
Monitor dextrose hourly6
Pediatrics/Pediatric Endocrinology Consult
Admit
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Guideline for ED Management of DKA in Children
Management
considerations2
Notes:
1 DKA=blood glucose > 250 mg/dL + academia (pH < 7.30 or serum TCO2
< 15 mEq/L) + ketonuria
2 For pH > 7.3 & TCO2 > 15 mEq/L:
a. hydrate (consider NS 20 mL/kg IV)
a. give regular insulin (consider correction factor of 1 unit regular for every
25-50 mg/dL over 150 mg/dL)
c. send home if: alert; able to drink & retain oral fluids; constant supervision is
available; home blood glucose monitoring can be performed; all necessary
supplies are available at home; suitable physician follow-up has been
arranged; not new-onset
d. suggested home management:
(1) calculate 1 U/kg as total daily dose (TDD) of insulin
(2) give 35-55% of TDD as Lantus qHS
(3) obtain rapid blood glucose qAC
(4) give 1 U regular insulin for every 10-15 carbs per meal/snack
(5) give 1 U regular insulin for every 25-50 mg/dL over 150 mg/dL per
meal/snack
3 Fluid therapy:
a. HOUR 1: give NS 10 mL/kg IV bolus; additional fluid should be given only
after careful patient assessment for evidence of dehydration; DO NOT GIVE
> 20 mL/kg NS
b. HOUR 2: give D10W ½ NS with 20 mEq KCl/L and 20 mM KPhos/L (IVF
#1) + ½ NS with 20 mEq KCl/L and 20 mM Kphos/L (IVF #2) at total rate
(cc/hr) calculated as 1-1 ½ maintenance (maintenance=4 cc/hr for 1st 10 kg +
2 cc/hr for 2nd 10 kg + 1 cc/hr for each additional kg)
4 Insulin: start IV infusion 0.1 U/kg/hr
5 For signs of cerebral edema (deterioration in mental status, change in neuro
exam, signs of increased ICP i.e. increased MAP/bradycardia/change in
respiratory pattern): obtain emergent head CT; initiate mannitol 1 g/kg IV;
RSI; ventilate to maintain pCO2 30-35 mm Hg
6 Start D5W when BG approaches 250 mg/dL
References:
Krane EJ, Rockoff MA, Wallman JK, et al. Subclinical brain swelling in children
during treatment of diabetic ketoacidosis. N Engl J Med 1985;312:1147-51
[Subclinical brain swelling may be a common occurrence during treatment of DKA in
children.]
Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of
diabetic ketoacidosis. J Pediatr 1988;113:10-4
[Excessive secretion of vasopressin may exacerbate brain edema in children with DKA,
and limitation of the rate of fluid administration may be prudent.]
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Guideline for ED Management of DKA in Children
Harris GD, Fiordalasi I, Harris WL, et al. Minimizing the risk of brain herniation
during treatment of diabetic ketoacidemia: a retrospective and prospective study. J
Pediatr 1990;117:22–31
[Failure of the serum sodium concentration to rise as glucose concentration declines is a
marker for excessive administration of free water. An expanded repair period, with repair
fluid containing an average of 125 mmol/L Na+ early in therapy, will usually protect
against a downward trend in the concentration of sodium in serum and therefore against a
rapid decline in effective serum osmolality. This regimen may be protective against neardeath episodes and brain herniation during treatment.]
Rosenbloom AL. Intracerebral crises during treatment of diabetic ketoacidosis.
Diabetes Care 1990;13:22-33
Bello FA, Sotos JF. Cerebral edema in diabetic ketoacidosis in children. Lancet
1990;336:64
Kaufman FR, Halvorson M. The treatment and prevention of diabetic ketoacidosis
in children and adolescents with Type I Diabetes Mellitus. Pediatric Annals 1999;
28:576-82
[Review of DKA management.]
Rosenbloom AL, Hanas R. Diabetic ketoacidosis (DKA): treatment guidelines. Clin
Pediatr 1996;35:261–6
Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation
during diabetic ketoacidosis. Pediatr Neurol 1999;21:721-7
[In a retrospective review of children admitted in DKA, severity of acidosis and
hypercapnea were the most reliable risk factors for brain herniation (none of the children
who maintained a blood pH > 7.1 and a PCO2 > 20 mm Hg were affected). Rate of initial
fluid administration in severe DKA was also a risk factor. Hydrating at a rate > 50
mL/kg during the first 4 hours was associated with an increased risk of brain herniation.]
Muir A. Cerebral edema in diabetic ketoacidosis: a look beyond rehydration. J
Clin Endocrinol Metab 2000;85:509-13
[The case is argued for a multifactorial cause of cerebral edema in DKA which cannot be
reliably prevented by cautious rehydration protocols. Healthcare providers can reduce
M&M by vigilantly watching for and responding to sentinel often subtle neurological
signs and symptoms of cerebral edema, which precede often by hours the dramatic
collapse typically described in these patients. Subclinical pathology causing increased
ICP likely precedes initiation of therapy in almost all cases of DKA. Pathogenic
mechanism for cerebral edema is unknown, but potential pathogenic contributors are
hypoxia, vascular occlusion, cytotoxic effects of neuroexcitatory amino acids, and
insulin-induced alterations of metabolism. Whatever the mechanism is, it must account
for: occurrence with rare exceptions after onset of therapy; preponderance of children
being affected; profound neurological dysfunction in the presence of minimal or no
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Guideline for ED Management of DKA in Children
radiologically visible cerebral edema; and initial pathological changes in the basal
regions of the brain. The earliest clinical benefits of mannitol in the treatment of cerebral
edema are not induced by a shift of fluid to the extravascular space, but rather a reduction
of blood viscosity, thereby improving intracerebral blood flow.]
Muir A. Do doctors cause or prevent cerebral edema in children with diabetic
ketoacidosis? Pediatr Diabetes 2000;1:209-16
Felner EI, White PC. Improving management of diabetic ketoacidosis in children.
Pediatrics 2001; 108:735-40
[A revised DKA protocol is offered which necessitates less fluid delivery and fewer
calculations and is associated with more rapid correction of acidosis.]
Dunger DB, Edge JA. Predicting cerebral edema during diabetic ketoacidosis. N
Engl J Med 2001;344:302-3
Edge J, Hawkins MM, Winter DL, et al. The risk and outcome of cerebral edema
developing during diabetic ketoacidosis. Arch Dis Child 2001;85:16–22
[A total of 34 cases of cerebral edema and 2940 episodes of DKA were identified,
yielding a calculated risk of developing cerebral edema of 6.8/1000 episodes of DKA.
This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000)
diabetes. There was no sex or age difference. Cerebral edema was associated with a
significant mortality (24%) and morbidity (35% of survivors).]
Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children
and adolescents with diabetic ketoacidosis. N Engl J Med 2001;344:264–9
[Risk factors for cerebral edema in children with DKA are low PCO2, high serum BUN,
& treatment with bicarbonate.]
Dunger DB, Edge JA. Predicting cerebral edema during diabetic ketoacidosis. N
Engl J Med 2001;344:302-3
[Caution must be used in interpreting the data of Glaser et al. (N Engl J Med 2001;344:
264-9) for the following reasons: (1) corrections were made in blood pH values, pCO2,
and bicarbonate concentrations to account for collection of both arterial & venous blood
samples; (2) bicarbonate may be a confounder (possible association with exposure, i.e.
acidosis, and with outcome, i.e. cerebral edema). Based on this study, it would be
difficult to justify the prohibition of bicarbonate, irrespective of severity of DKA. The
data of Glaser et al. cannot be interpreted as revealing anything more than an association
between severity and duration of DKA and risk of cerebral edema. The increased risk in
new-onset diabetics and the occurrence of cerebral edema before treatment support the
importance of other antecedent factors, such as accumulation of idiogenic, osmotically
active substances that regulate cell volume, and individual biologic responses.]
Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in
children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002;141:793-7
[After adjusting for potential confounding variables and the degree of neurologic
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Guideline for ED Management of DKA in Children
compromise at the initiation of therapy, intubation with hyperventilation is associated
with adverse outcomes of DKA-related cerebral edema. Greater neurologic depression at
the time of diagnosis of cerebral edema and a higher initial serum urea nitrogen
concentration are also associated with poor outcome.]
Chiasson JL, Aris-Jilwan N, Bélanger R, et al. Diagnosis and treatment of diabetic
ketoacidosis and the hyperglycemic hyperosmolar state. CMAJ 2003;168:859–66
[Diabetic ketoacidosis and the hyperglycemic hyperosmolar state are the most serious
complications of diabetic decompensation and remain associated with excess mortality.
Insulin deficiency is the main underlying abnormality. Associated with elevated levels of
counterregulatory hormones, insulin deficiency can trigger hepatic glucose production
and reduced glucose uptake, resulting in hyperglycemia, and can also stimulate lipolysis
and ketogenesis, resulting in ketoacidosis. Both hyperglycemia and hyperketonemia will
induce osmotic diuresis, which leads to dehydration. Clinical diagnosis is based on the
finding of dehydration along with high capillary glucose levels with or without ketones in
the urine or plasma. The diagnosis is confirmed by the blood pH, serum bicarbonate level
and serum osmolality. Treatment consists of adequate correction of the dehydration,
hyperglycemia, ketoacidosis and electrolyte deficits.]
Carlotti APCP, Bohn D, Halperin ML. Importance of timing of risk factors for
cerebral oedema during therapy for diabetic ketoacidosis. Arch Dis Child 2003;88:
170–3
[Cerebral edema is the most common cause of mortality and morbidity during the first
day of conventional treatment for DKA in children. It is possible that therapy contributes
to its development. Risk factors that predispose to cerebral edema should lead to an
expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain
because water normally accounts for close to 80% of brain weight. With respect to the
intracellular fluid compartment, the driving force to cause cell swelling is a gain of
effective osmoles in brain cells and/or a significant decline in the effective osmolality of
the extracellular fluid compartment. Factors leading to an expansion of the intracerebral
extracellular fluid volume can be predicted from Starling forces acting at the blood-brain
barrier. Some of these risk factors have an early impact, while others have their major
effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis,
suggestions to modify current therapy for DKA in children are provided.]
Lawrence S, Pacaud D, Dean H, et al. Pediatric diabetic ketoacidosis. CMAJ 2003;
169:278-9
[The recommendation for fluid replacement in children with DKA is 5-10 mL/kg in the
first hour, with higher rates used only in patients with significant hemodynamic
compromise. Fluid replacement should be calculated over a 48-hour period. Use of
bicarbonate is not routine for all pediatric patients with pH < 7.0. Intravenous bolus of
insulin at the initiation of insulin therapy is not recommended.]
Kamat P, Vats A, Gross M, et al. Use of hypertonic saline for the treatment of
altered mental status associated with diabetic ketoacidosis. Pediatr Crit Care Med
2003;4:239-42
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Guideline for ED Management of DKA in Children
[HS 3% was used to control apparent intracranial hypertension with good clinical
outcome and without apparent side effects in a small series of pediatric patients with
DKA. Use of HS 3% has been shown to reduce raised ICP while augmenting
intravascular volume and increasing MAP. The traditional therapy for cerebral edema in
DKA has been the use of 20% mannitol. However, the brisk diuresis caused by this drug
may lead to intravascular dehydration, hypokalemia, hypotension, prerenal azotemia, and
even decreased cerebral blood flow. A small amount may also be converted to glycogen
in the liver, thus further disturbing the glucose homeostasis.]
White NH. Management of diabetic ketoacidosis. Rev Endocr Metab Disord 2003;4:
343-53
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Guideline for ED Management of DKA in Children