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Diabetic Ketoacidosis
in the Pediatric ICU
James P. Orlowski, MD, FAAP, FCCP, FCCM*,
Cheryl L. Cramer, RN, MSN, ARNP,
Mariano R. Fiallos, MD
Pediatric Intensive Care Unit, University Community Hospital, 3100 East Fletcher Avenue,
Tampa, FL 33613, USA
* Corresponding author.
E-mail address: jorlowski@mail.uch.org (J.P. Orlowski).
0031-3955/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.pcl.2008.02.015 pediatric.theclinics.com
578 ORLOWSKI et al
the hepatic oxidation of fatty acids in a state of insulin lack and excess glu-
cagon stimulation provide an important energy source for the brain during
DKA [6–8].
The most important perturbations seen in DKA are metabolic acidosis,
hyperosmolality, dehydration, and electrolyte disturbances. An important
hallmark of DKA is the metabolic acidosis caused by elevated plasma con-
centrations of the ketoacids acetoacetate and beta-hydroxybutyrate. Lack of
insulin permits lipolysis to accelerate in adipose tissue, releasing long-chain
fatty acids. In the liver, these fatty acids are shunted toward beta-oxidation
and ketone production because of increased glucagon levels. Ketones nor-
mally stimulate insulin release and thereby inhibit lipolysis, but in the
absence of this feedback loop extreme lipemia and ketonemia occur. Non-
enzymatic decarboxylation of acetoacetate produces elevated acetone
concentrations in plasma. Typically in DKA the ratio of beta-hydroxybuty-
rate to acetoacetate is about 3:1, but it may range up to 15:1 in severe DKA
[9,10]. Acetone may represent 1.5 to 4 times the molar concentration of ace-
toacetate [11]. Acetone fills an important role as a buffer by continuous non-
enzymatic conversion of acetoacetate to acetone and carbon dioxide.
Acetone then is excreted in breath and urine in a ratio of 5:1, and the carbon
dioxide is excreted in breathing. This mechanism removes about one fourth
of the hydrogen ions generated by hepatic ketogenesis. Lactic acidosis sec-
ondary to hypoxia and/or poor tissue perfusion, shifts acetoacetate toward
beta-hydroxybutyrate, reducing the body’s ability to eliminate ketoacids by
the acetone route. Lactic acidosis occurs in large part from anaerobic glycol-
ysis in hypoperfused tissues secondary to hypovolemia from osmotic diure-
sis. Measuring lactate and acetoacetate gives a crude indication of the
relative proportions of these metabolic acids. Hyperchloremic metabolic
acidosis also can be seen in DKA, most commonly as a result of aggressive
intravenous fluid resuscitation with solutions containing large amounts of
chloride [12]. The metabolic acidosis of DKA should not be treated with
bicarbonate administration, because the hyperosmolar solution and the re-
sultant paradoxical cerebral acidosis may contribute to the development of
cerebral edema [13].
The hyperosmolar state induced by insulin deficiency is responsible for at
least as much of the physiologic derangements seen in DKA as the ketoaci-
dosis. The osmolality is estimated from the formula:
where sodium and potassium concentrations are expressed in mEq/L and glu-
cose and serum urea nitrogen (BUN) concentrations are expressed in mg/dL.
In the typical child who has DKA, glucose is elevated about 400 mg/dL
above normal, and the BUN is elevated by about 15 mg/dL. These eleva-
tions result in an additional osmolar load of about 22 and 5 mOsm/L,
respectively.
580 ORLOWSKI et al
The primary fluid loss is secondary to the osmotic diuresis induced by hy-
perglycemia and glycosuria. The typical child who has DKA is about 10%
dehydrated. Estimation of the degree of dehydration is best made by known
body weights. Unfortunately, this determination is not always possible, and
so estimates are made based on physical findings, which are based on extra-
cellular fluid volume. The extracellular fluid volume in DKA is maintained
by plasma hyperosmolality, however, so the deficit in total body water is
easily underestimated. Loss of water through osmotic diuresis is perhaps
the most dangerous process brought about by DKA. When fluid loss is se-
vere enough to begin to impair renal function (glomerular filtration rate),
the excretion of excess glucose is impaired, and hyperglycemia accelerates.
The combination of rapidly rising glucose and BUN levels results in extreme
hyperosmolality. Hyperosmolality has been shown to correlate better than
other laboratory measurements in DKA with levels of obtundation and
with electroencephalographic slowing [14]; hyperosmolality and its too rapid
correction may set the stage for the rare occurrence of cerebral edema dur-
ing recovery from DKA. Cardiorespiratory function can remain adequate to
sustain life even at the extremes of pH and osmolality seen in DKA, but
shock invariably occurs when dehydration is severe enough, and hypovole-
mic shock can be fatal if not reversed appropriately by volume replacement.
Hyponatremia usually is reported by the laboratory when sera from
DKA patients are analyzed, and quite commonly the reported low value
is an artifact. Extreme lipemia can decrease the measured sodium value sim-
ply by decreasing the aqueous phase of blood in which sodium predomi-
nantly resides. The true serum sodium can be calculated from the formula:
Cerebral edema
Symptomatic cerebral edema occurs in 0.5% to 1% of pediatric DKA
episodes and has a high mortality rate (21%–24%) with a substantial pro-
portion of survivors (15%–26%) left with permanent neurologic sequelae
[2]. It is one of the most dreaded complications of DKA. Its pathophysiol-
ogy and etiology are poorly understood, but it is believed that various
aspects of DKA treatment may cause or exacerbate the development of
cerebral edema [22].
The signs and symptoms of cerebral edema in DKA are:
Headache
New-onset vomiting
Cushing’s signs of slowing of heart rate and hypertension
Changes in respiratory pattern: hyperpnea, apnea, bradypnea
Change in neurologic status: restlessness, irritability, stupor
Development of pathologic neurologic signs: cranial nerve palsies, abnor-
mal pupillary reflexes, posturing
584 ORLOWSKI et al
One then can measure the unmeasured ion effect and the chloride effect
from the following equations:
and
and
Summary
DKA is a common, life-threatening complication of DM in children.
Central nervous system changes seen in DKA include the altered sensorium
seen commonly in DKA and loosely characterized as diabetic coma and the
uncommon but worrisome progressively deepening coma caused by cerebral
edema, which has both a high morbidity and mortality.
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