DIABETIC KETOACIDOSIS

DANA BARTLETT, RN, BSN, MSN, MA, CSPI

Dana Bartlett is a professional nurse and author. His clinical experience includes 16
years of ICU and ER experience and over 27 years as a poison control center
information specialist. Dana has published numerous CE and journal articles, written
NCLEX material, textbook chapters, and more than 100 online CE articles, and done
editing and reviewing for publishers such as Elsevier, Lippincott, and Thieme. He has
written widely on the subject of toxicology and was a contributing editor, toxicology
section, for Critical Care Nurse journal. He is currently employed at the Connecticut
Poison Control Center. He lives in Wappingers Falls, NY.

ABSTRACT

Diabetic ketoacidosis is an acute complication of diabetes mellitus, which

requires prompt, aggressive, treatment. Complications of diabetic
ketoacidosis throughout the age spectrum and during pregnancy require a
close evaluation of symptoms, testing, treatment and outcomes to treatment.
Anyone with diabetes, regardless of age or gender, can develop ketoacidosis.
Guidelines exist that guide diabetes health teams and clinical care of the
diabetic patient. Appropriate and timely treatment can reduce diabetic
ketoacidosis complications and patients can recover to full health.

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Policy Statement
This activity has been planned and implemented in accordance with the
policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's Commission on
Accreditation for registered nurses.

Continuing Education Credit Designation

This educational activity is credited for 2 hours at completion of the activity.

Statement of Learning Need

Diabetes mellitus is one of the leading chronic diseases in the country and
diabetic ketoacidosis is one of the most serious complications. When patients
in diabetic ketoacidosis crisis receive the right treatment they are able to
recover and to improve health. Health clinicians need to be able to identify
prevalence and treatment of diabetes ketoacidosis in all age groups and for
special conditions, such as pregnancy.

Course Purpose
To help clinicians early identify signs and symptoms of diabetic ketoacidosis
and its recommended treatment.

Target Audience
Advanced Practice Registered Nurses, Registered Nurses, and other
Interdisciplinary Health Team Members.

Disclosures
Dana Bartlett, BSN, MSN, MA, CSPI, William Cook, PhD, Douglas Lawrence,
MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures. There is
no commercial support.

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Self-Assessment of Knowledge Pre-Test:

1. Which of the following is the correct definition of diabetic

ketoacidosis (DKA)?

a. Metabolic disorder with hyperglycemia, metabolic acidosis, elevated

ketones.
b. Metabolic disorder with normal glucose, metabolic alkalosis,
elevated ketones.
c. Endocrine disorder caused by inappropriate insulin secretion.
d. Endocrine disorder caused by abnormal carbohydrate metabolism.

2. The two most common causes of diabetic ketoacidosis (DKA) are:

a. Atypical antipsychotics and gestational diabetes.

b. Infection and poor compliance with medication regimens.
c. CVA and pregnancy.
d. Glucagon-producing tumors, sepsis.

3. The diagnostic criteria of diabetic ketoacidosis (DKA) include:

a. A serum pH > 7.5, a serum glucose > 250 mg/dL.

b. A serum pH < 7.30, a serum glucose < 250 mg/dL.
c. A serum pH > 7.2, a serum glucose < 125 mg/dL.
d. A serum pH < 7.3, a serum glucose > 250 mg/dL.

4. The serum potassium in diabetic ketoacidosis (DKA) is:

a. Typically very low.

b. Deceptively high: there is actually profound hypokalemia.
c. Typically normal.
d. Deceptively low: the total body content is normal.

5. Pregnant women who have diabetic ketoacidosis (DKA):

a. Always have elevated serum glucose.

b. Are rarely acidotic.
c. May be euglycemic.
d. Have a high mortality rate.

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 Introduction

Diabetic ketoacidosis is a very serious complication of diabetes mellitus,

a metabolic disorder that is characterized by hyperglycemia, metabolic
acidosis, and increased ketone body concentrations. The most common causes
of diabetic ketoacidosis (DKA) are infection and poor compliance with
medication regimens. Other causes include undiagnosed diabetes, alcohol use,
stress and a multitude of medical conditions such as cerebrovascular accident
(CVA), complicated pregnancy, myocardial infarction (MI) and pancreatitis.
DKA is a complicated pathology. Early recognition and a good understanding
of the pathological processes of DKA, and aggressive treatment are the keys
to successful treatment. With appropriate care, DKA can be managed and the
patient is able to survive.

Epidemiology

Most cases of DKA are seen in patients with type 1 diabetes,1 but
approximately 20%-30% of all cases of DKA occur in patients with type 2
diabetes.1,2 The incidence of DKA in the United States is increasing,1 and the
incidence of DKA in people who have type 2 diabetes appears to be increasing,
as well.2.3 There is also a variation of type 2 diabetes, ketosis-prone diabetes,
that is common in African Americans and Hispanic Americans and this
subgroup of diabetic patients is particularly likely to develop DKA.4

Between 20% and 67% of children diagnosed with type 1 diabetes

present with diabetic ketoacidosis,5-7 and the yearly risk for DKA in this patient
population is 1%-10%.8 The mortality rate of DKA in adults is approximately
<1% to <2%,1,9 it is higher in the elderly and in patients with serious
comorbidities,10 and DKA is a leading cause of mortality in children and
adolescents who have type 1 diabetes.8,9,11

Glucose, Insulin, and Diabetes: A Brief Review

Glucose is an essential source of energy. For glucose to be used for

energy it must be transported into the cells, but the glucose molecule is too

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large to passively move through the cell membrane. Glucose must be actively
carried into the cell and that is the function of insulin; it is a transport
molecule. This section briefly reviews how the body utilizes glucose to
function.

Glucose and Energy

The body needs energy to function, and a great deal of this energy is
provided by glucose. Glucose is derived from the breakdown of foods
consumed (particularly carbohydrates) and glucose is converted into
adenosine triphosphate (ATP) by the glycolytic pathway. Adenosine
triphosphate provides energy for basic body functions when the high energy
bonds of the ATP molecule are broken down.

The process by which insulin promotes glucose entry into the cells is
called facilitated diffusion. This process is not completely understood, but it
may be that when insulin binds to an insulin receptor on a cell membrane, it
increases the membrane concentration of Glut4, which is a glucose
transporter.

In the normal person, blood glucose is maintained within a narrow range

of 70-125 mg/dL, and fasting glucose for adults should be 70-99 mg/dL. Close
control of blood glucose is important, as glucose is the only nutrient that can
be used by important organs such as the brain, retina, etc. When blood
glucose rises, such as after a meal, the secretion of insulin rises dramatically,
both in the amount and the speed in which this rise occurs, as glucose enters
the pancreatic β cells and stimulates insulin release.

Diabetes is a disease that affects glucose metabolism. There are

essentially two types of diabetes - Type 1 (also called juvenile–onset diabetes)
and Type 2 (also called adult onset or non-insulin-dependent diabetes). Type
1 diabetes is caused by destruction of the pancreatic β cells that produce
insulin. The destruction of the β cells is thought to be an autoimmune process
that occurs in genetically susceptible people and is triggered by an infection
or an environmental factor.

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 People with type I diabetes essentially do not produce insulin. Whereas,
type 2 diabetes is characterized for the most part by insulin resistance and
inadequate insulin secretion. Due to age, genetics, lifestyle factors, and
possibly environmental triggers, the body is unable to use insulin to transport
glucose into the cells. In both type 1 and type 2 diabetes, medications and
lifestyle modifications are needed so that blood glucose remains within a
specified range.

Type 1 and Type 2 Diabetes Classification System: Out of Date?

Diabetes mellitus has traditionally been classified as type 1 or type 2,

but there is growing recognition that not everyone with diabetes mellitus can
be described by one of those two categories.13 Many researchers now feel that
the age of onset, the presence or absence of auto-antibodies, and the
functioning of the β cells should be considered when classifying diabetes as
these factors may have important clinical considerations. Thomas, et al.,
(2015) noted that the existing classification systems are to some degree
inconsistent and have some overlaps; the classification of diabetes is still
evolving, and it is difficult to classify diabetes “... in the absence of a complete
understanding of the pathogenesis of the major forms.”13 The classification
system used by the American Diabetic Association (ADA) recognizes the
complexity of the disease: “... for clinician and patient, it is less important to
label the particular type of diabetes than it is to understand the pathogenesis
of the hyperglycemia and to treat it effectively.”14

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 There are many causes of diabetes that will be discussed in a later
section. To further illustrate the complexity of the disease, the following sub-
classifications are included.13

● Type 1 diabetes can be classified as type 1a, type 1b, latent autoimmune
diabetes of adults, or as type 1 diabetes associated with the IPEX
syndrome.
● Other specific types of type 1 diabetes include the monogenic forms of the
disease, neonatal monogenic diabetes (permanent or transient and mature
onset diabetes of the young (MODY). Monogenic diabetes is caused by a
mutation of a single disease and it accounts for approximately 1%-5% of
all cases of diabetes in children.
● Gestational Diabetes: Pregnancy can cause diabetes, and gestational
diabetes may be a self-limiting condition or predispose the patient to
developing type 2 diabetes.
● Type 2 diabetes occurs in people who have a low body mass index (BMI).
● Diseases and diabetes: Diabetes can be caused by many diseases,
including (but not limited to) acromegaly, cystic fibrosis, hepatitis C, HIV
infection, and pancreatitis.
● Drugs and diabetes: Diabetes can be caused by drugs, including (but not
limited to) antipsychotics and glucocorticoids.

Pathophysiology of DKA

The two primary pathogenic mechanisms of DKA are insulin deficiency

and elevated levels of counter-regulatory hormones such as catecholamines,
cortisol, and glucagon.1,9 Insulin deficiency can be absolute (when no insulin
is produced or no insulin is administered) or it can be relative (when the
amount of insulin available is not sufficient to the needs). In either case,
insulin deficiency causes hyperglycemia and this hyperglycemia and the
elevated levels of counter regulatory hormones are the cause of signs,
symptoms, and metabolic derangements of DKA. This process is outlined
below.1,9

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 The hyperglycemia of DKA stimulates the body to increase production
of the hormones cortisol, epinephrine, glucagon, and growth hormone to
produce energy; the patient’s blood glucose is very high but insulin deficiency
prevents glucose movement into the cells. These hormones break down fats
to provide the body with energy and stimulate the liver to increase fatty acid
oxidation. They also increase blood glucose by initiating gluconeogenesis and
glycogenolysis, and by decreasing the ability of peripheral tissues to use
glucose. The body now depends on fats for energy instead of carbohydrates
and one of the byproducts of fat metabolism is ketones. The ketones produced
during DKA, acetoacetate and beta-hydroxybutyrate, dissociate to produce
hydrogen ions, thus causing metabolic acidosis.

Pathophysiology, Signs and Symptoms of DKA

Conditions associated with diabetic ketoacidosis are highlighted in this

section.
● Diuresis: High serum glucose causes an osmotic diuresis.
● Electrolyte disturbances: Osmotic diuresis, nausea, and vomiting cause
loss of calcium, magnesium, phosphate, and potassium. Metabolic acidosis
causes potassium to move from the intracellular space to the extracellular
space.
● Increased metabolic rate: The increased metabolic rate of DKA is caused
by increased/excessive glycogenolysis and gluconeogenesis, increased
respiratory rate, dehydration, elevated levels of circulating
catecholamines, and other physiologic demands of DKA.
● Increased respiratory rate: Compensation for metabolic acidosis.
● Metabolic acidosis: Breakdown of ketone bodies.
● Nausea and vomiting: Caused by metabolic acidosis, worsens dehydration.

Precipitating Causes of DKA

Diabetic ketoacidosis is driven by insulin deficiency and elevated levels

of counter-regulatory hormones, but there must also be a precipitating cause,
a triggering event. The most common precipitating causes of DKA are 1)

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infection, 2) new diagnosis of diabetes mellitus, 3) poor adherence to
treatments, and 4) other causes.1

Other precipitating causes of DKA are conditions or illnesses including

(but not limited to) acromegaly, alcohol use, cerebrovascular accident,
myocardial infarction, pancreatitis, pregnancy, trauma, and drugs, including
(but not limited to) antipsychotics, cocaine, glucocorticoids, interferon,
sympathomimetics, thiazide diuretics, and sodium-glucose co-transporter-2
inhibitors.1,9,10,15-18 These pathologies, conditions, and drugs can initiate DKA
by increasing the production of stress hormones, elevating the serum glucose,
or blunting the normal physiological warning signs of hyperglycemia and
acidosis. Acute gastroenteritis, cellulitis, respiratory tract infections, urinary
tract infections, and mixed infections are common precipitating factors of
DKA.19,20 DKA initiated by gestational diabetes and DKA initiated by
antipsychotics are discussed later on.

Clinical Signs and Symptoms of DKA

Diabetic ketoacidosis develops quickly, typically over a period of hours

to one day.1,10 The presentation of DKA will depend on many factors and it
can be mild to severe. The patient may be awake and alert but complain of
abdominal pain, fatigue, malaise, and nausea or he/she may be comatose,
hypotensive, profoundly acidotic, and have significant metabolic
derangements.

Symptoms of DKA include abdominal pain, drowsiness, fatigue, nausea,

polydipsia, and polyuria.1,10 Signs of DKA often include an acetone odor of the
breath (often described a fruity smell), a notably altered sensorium (coma in
severe cases), diaphoresis, pallor, hypotension, hypothermia, tachycardia,
and tachypnea. These signs and symptoms are non-specific and certainly not
exclusive to DKA, but if the pathological processes of DKA are examined the
genesis of these signs and symptoms and of the common presentation of DKA
becomes clear. Several clinical examples are provided below.

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Example #1

Hypotension in the patient who has DKA is caused by dehydration, and

dehydration in DKA is caused by poor oral intake, Kussmaul’s respirations,
nausea and vomiting, polyuria, and the osmotic diuresis caused by
hyperglycemia.

Example #2

Abdominal pain, nausea and vomiting are very common in patients who have
DKA. Acidosis, elevated serum potassium, and high serum ketone levels cause
these gastrointestinal complaints.

Example #3

Kussmaul’s respiration is defined as deep, labored, and rapid breathing, it is

caused by metabolic acidosis, and it is an adaptive response to the high blood
levels of carbon dioxide (CO2). This breathing pattern can also contribute to
dehydration. Occasionally the patient’s breath will have what can be described
as a fruity odor; this is caused by excess production of ketones.

Diagnosis of DKA

The signs and symptoms of DKA can in hindsight be easily attributed to

DKA if the clinician is aware that the patient has diabetes or has a risk factor
for DKA. However, the clinical presentation of DKA is non-specific and
laboratory testing is needed for definitive proof that a patient has DKA.

Laboratory Tests

The laboratory abnormalities that are the diagnostic criteria for DKA are
1) hyperglycemia, 2) ketonemia, and 3) metabolic acidosis.1,9 Diabetic
ketoacidosis is often classified using those three laboratory tests, and several
others, as being mild, moderate, or severe. 1,9

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 MILD DKA
Glucose: > 250 mg/dL
Ketones: Positive
Arterial pH: 7.25-7.30
Bicarbonate: 15-18 mEq/L
Anion gap: >10
Elevated serum osmolality

MODERATE DKA
Glucose: > 250 mg/dL
Ketones: Positive
Arterial pH: 7.00-7.24
Bicarbonate: 10 - < 15 mEq/L
Anion gap: >12
Elevated serum osmolality

SEVERE DKA
Glucose: > 250 mg/dL
Ketones: Positive
Arterial pH: < 7.00
Bicarbonate: < 10
Anion gap: >12
Elevated serum osmolality

These categories are to some degree imprecise, but they provide a

useful framework for characterizing the severity of DKA. It is not unusual for
the serum glucose of a patient who has DKA to be much higher than 250
mg/dL, and levels of 500 mg/dL are not uncommon. Serum and urine ketones
are positive in DKA, and in DKA there are three ketone bodies that are
produced, acetone, acetoacetate, and β-hydroxybutyrate. The primary ketone
produced in DKA is β-hydroxybutyrate, but commonly used urine dipsticks
that are used to check urine for ketones have a poor specificity for β-
hydroxybutyrate so there is the possibility of false negatives. Direct
measurement of β-hydroxybutyrate is preferred;1,10 a level > 3 mg/dL is
considered abnormal. Other laboratory test abnormalities that occur in DKA
are discussed below.

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Hyperkalemia

Acidosis, release of potassium from the cells caused by glycogenolysis,

insulin deficiency, and several other mechanisms all cause potassium to shift
from the intracellular space to the extracellular space and serum hyperkalemia
is common. However, the osmotic diuresis and vomiting that are commonly
part of DKA cause potassium to be excreted in the urine and lost in the vomit.
The serum potassium level may be high, but the patients are often very
depleted of potassium.9,10

Hyponatremia

Hyperglycemia causes an osmotic shift of fluid into the vascular space

and a subsequent hyponatremia. Sodium is also lost renally because of
osmotic diuresis. Some sources report that each 100 mg/dL of glucose above
the top normal will lower the serum sodium by 1.6-2.4 mEq/L.10 So if the
patient’s serum glucose is 420 mg/dL and the serum sodium is 118 mEq/L,
the corrected serum sodium would be 123-125 mEq/L.

Other Electrolytes

Serum calcium, magnesium, and phosphate are lost through diuresis.9

Initially the serum phosphate may be normal or even high because insulin
deficiency and acidosis will move phosphate out of the cells, but the
developing acidosis along with poor intake and diuresis will eventually result
is significant phosphate losses.10

Amylase and Lipase

Elevated serum amylase and lipase are commonly seen in patients who
have DKA.9,10 Pancreatitis is a well-known cause of DKA and can explain these
laboratory abnormalities, but elevated serum amylase and lipase often
accompany DKA when pancreatitis is absent.

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Hepatic Transaminases

The hepatic transaminases can be elevated in DKA. This can be from

DKA alone or a combination of DKA and fatty liver disease.

Leukocytosis

An elevated white blood cell count is common and is caused by

hemoconcentration and by stress.9 Diabetic ketoacidosis is often precipitated
by an infection however, and a very high white blood cell count should prompt
the clinician to look for an infection.

Serum Osmolality

Serum osmolality is often elevated.

Renal Function Studies

The blood urea nitrogen (BUN) and serum creatinine are often elevated
in patients who have DKA. These results can be explained by volume
depletion, prerenal azotemia, or by a laboratory error caused by interference
by ketones.10 The last of these is unlikely with testing methods that are
currently used.

Troponin Levels

An elevated cardiac troponin level in the absence of myocardial damage

may be seen in patients who have DKA.21,22 This may be caused by acidosis
or reflect what is called silent ischemia.22 It is important to remember that
laboratory values in a patient who has DKA can be misleading as the length
and severity of the DKA, the clinical signs and symptoms, and the stage of
treatment affect these values. For example, serum sodium, phosphate, and
potassium may be low, normal, or high, but the measurements must always
be interpreted with caution and with the knowledge that they often may not
reflect the true levels. Additionally, several of the diagnostic criteria of DKA

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must be interpreted carefully; for example, normal serum glucose has been
reported in pregnant women who have DKA.

Serum and urine ketones are positive in DKA, but in DKA there are three
ketone bodies, acetone, acetoacetate, and β-hydroxybutyrate. The primary
ketone produced in DKA is β-hydroxybutyrate, but commonly used urine
dipsticks that are used to check urine for ketones have a poor specificity for
β-hydroxybutyrate so there is the possibility of false negatives.

Euglycemic DKA

Euglycemic DKA in pregnancy is well described and discussed in more

detail later on. It is described as a rare phenomenon in patients who are not
pregnant.23 Causes of euglycemic DKA include a pre-existing fasting state,
decreased hepatic stores of glucose, decreased hepatic glucose production,
and greater than normal urinary losses of glucose. Some drugs, notably the
sodium-glucose co-transporter 2 inhibitors, can cause euglycemic DKA,18 and
it can happen if an insulin-dependent diabetic is not eating sufficient
carbohydrates but is still taking insulin.24

It is important to remember that euglycemia means normal serum

glucose. In the typical case of euglycemic diabetic ketoacidosis a patient’s
serum glucose is low when compared to the level of hyperglycemia that is
typically seen in DKA, but the level is usually (but not always) abnormally
elevated.

Gestational Diabetes and DKA

Diabetic ketoacidosis caused by gestational diabetes is a serious

complication of pregnancy.25 The incidence of gestational diabetes is
approximately 9%,26 and fortunately DKA is uncommon, occurring in about
0.5%-10% of this patient population.25

Gestational diabetes occurs to women who do not have a prior history

of diabetes and the basic cause is increased insulin resistance caused by

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pregnancy.26 The precipitating factors of DKA in gestational diabetes are
essentially the same as for DKA in men and in women who are not pregnant,
and some of the more common ones are listed below.25,27,28 Diabetic
ketoacidosis occurring during pregnancy tends to happen more quickly than
DKA does in women who are not pregnant; it affects women with type 1
diabetes and women with type 2 diabetes, and; it usually develops in the
second or third trimester.25 The clinical presentation of DKA in gestational
diabetes is no different than that of DKA in men and non-pregnant women,
but it should be remembered that euglycemic DKA with a serum glucose level
as low as 96 mg/dL have been reported.29 Increased glucose uptake by the
fetus and the placenta could in part explain euglycemic DKA. In addition,
glomerular filtration rate and renal blood flow are increased during pregnancy,
but tubular reabsorption of glucose is not increased so excess glucose of DKA
may be lost in the urine.

If DKA in the pregnant woman is recognized early and treated properly,

the outcome for the mother should be good; the maternal mortality rates of
DKA have been reported to be < 1.0%,28 and the rate of fetal death is not
high.25 However, if the condition is not recognized early in its development
and/or the appropriate treatments are not given soon enough, serious
maternal complications such as acute renal failure, adult respiratory distress
syndrome, cerebral edema, euglycemic DKA, preterm delivery, and
myocardial ischemia are possible.28 In addition, an elevated level of ketoacids
during pregnancy has been associated with deficits in psychomotor and
neurological development of the child.25,28

Atypical Antipsychotics and DKA

The atypical antipsychotics can cause metabolic disorders as well as

DKA, such as hyperglycemia, insulin resistance, metabolic syndrome, and type
2 diabetes.30-3-35 The mechanisms by which this occurs are not known and/or
incompletely understood; it may be related to weight gain (a very common
side effect of these drugs) and insulin resistance, or it may be from previously
undiagnosed type 2 diabetes or latent autoimmune diabetes.34,35

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 Fortunately, DKA caused by the atypical antipsychotics is rare, as the
mortality rate associated with this phenomenon has been reported to be
26.5%.35 Routine monitoring of patient’s weight and BMI (body mass index)
is recommended as part of the treatment plan when typical antipsychotics
(first generation) and atypical antipsychotics (second generation) are
prescribed, and blood glucose and other metabolic markers of diabetes and
DKA should be monitored, as well.34,35

Complications of DKA

Patients who have DKA that is promptly recognized and correctly treated
should survive, but both the treatment and DKA can cause serious
complications.1,9 The primary complications of DKA treatment are
hypoglycemia, hyperkalemia, and fluid overload.1,9 These can be prevented
with conscientious monitoring of serum glucose, serum potassium, and the
patient’s fluid status.

Complications of DKA (aside from those previously discussed) include,

but are not limited to cerebral edema, renal failure, rhabdomyolysis, QTc
prolongation, and stroke.1,9,10,36-43 Many of these are more common in children
than adults, i.e., cerebral edema.1 Cerebral edema is a particularly serious
complication of DKA.

Children, DKA and Cerebral Edema

Cerebral edema is a very dangerous consequence of DKA in children.

Fortunately, cerebral edema is rare, occurring in 0.5%-1% of all pediatric
cases of DKA,1,9,44 but the mortality rate associated with this complication has
been reported to be as high as 90%44 and many children who have DKA-
associated cerebral edema suffer permanent neurological sequelae.9,44
Cerebral edema in children who have DKA will usually develop within the first
seven hours of treatment, but a delay in presentation up to 24 hours is
possible.9,44

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 Obvious and alarming signs and symptoms may be present or the child
may be asymptomatic or have a relatively mild clinical presentation.44 It is
important to remember that DKA-associated cerebral edema is a clinical
diagnosis, and neuroimaging studies are likely to be normal in 40% of all
children who have this complication.44 Diagnostic criteria are listed below.
There are many reasons why young children are more likely to develop DKA-
related cerebral edema. The early signs and symptoms can be non-specific
and attributed to a viral illness. Young children cannot communicate how they
feel, which can make diagnosing DKA difficult. Also, young children have a
higher basal metabolic rate and surface area relative to body weight,
therefore, during treatment for DKA they are more likely to suffer from fluid
and electrolytes disorders. Finally, for several physiological reasons young
children are more vulnerable to cerebral edema. Adolescents are more likely
than adults to be non-compliant with their insulin regimen.

Treatment for Diabetic Ketoacidosis

When assessing a patient for DKA, the clinician should perform a health
history, check for the presence or absence of the typical signs and symptoms
of DKA, and look for the characteristic laboratory abnormalities that are
caused by DKA. In performing the health history, the clinician should be sure
to ask the following questions.

● Does the patient have diabetes and if so, what type?

● Has the patient been eating properly and drinking sufficient amounts? If
the patient uses oral hypoglycemic agents or insulin, has the patient been
taking the medications?
● Has the patient recently had a new medication added to his/her medication
regimen?
● Has the patient recently lost weight or had a fever or infection?

Treatment of a patient who has or is suspected of having DKA begins

with an assessment and a physical exam. The diagnostic and laboratory tests
that should be done are listed below:

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● A1c level
● Serum glucose
● Serum ketones
● Urine ketones
● Arterial or venous blood gas
● Serum electrolytes
● Bun and creatinine
● Serum lactate level
● Serum osmolality
● Serum calcium, magnesium, and phosphate
● 12-lead ECG
● CT scan of the head

Depending on the patient’s clinical presentation, serum amylase and

lipase, hepatic transaminases, and troponin should be measured. If an
infection is suspected, the appropriate diagnostic tests should be done.
Treatment of DKA should be focused on 1) fluid replacement, 2) insulin
therapy, 3) monitoring for and correcting acid-base disturbances, electrolyte
imbalances, and complications, and 4) the assessment for, and treatment of
comorbid conditions and precipitating factors.1,9,46

Fluid Replacement

Treatment of DKA should begin with fluid replacement. Fluid

replacement will restore intravascular volume, help perfuse the kidneys,
stabilize cardiovascular status, and it increases responsiveness to insulin.1,9,45
Patients who have DKA often have a profound fluid deficit of 6 liters or more.9

Recommendations for the initial infusion rate differ but not to a

significant degree. For example, the clinician can infuse fluids at 15-20
mL/kg/hour of isotonic 0.9% saline for several hours45 or infuse 500-1000
mL/hour of isotonic 0.9% saline solution for the first 2-4 hours.1 Regardless
of the specific infusion rate that is used, fluid resuscitation is a primary goal
in the first few hours of treatment for DKA. The infusion rate recommendations
assume the patient is an average sized adult, not in shock, does not have a

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high risk for cardiac decompensation, and 0.9% isotonic saline solution is the
correct fluid to use.1,9,45,46

After initial fluid resuscitation, the clinician should continue infusing

0.9% isotonic saline if the corrected serum sodium is < 135 mEq/L or the
patient is still dehydrated.1,46 If the corrected serum sodium is normal and
fluid losses have been replaced, 0.45% saline should be started. Again, there
are different recommendations for the infusion rate, i.e., 4-14 mL/kg/hour or
250-500 mL/hour.1,46 If the serum glucose level is 200 mg/dL or below, the
IV fluids should contain 5%-10% dextrose;1,46 this will ensure that insulin
therapy can be safely continued.

Electrolyte Imbalances

There is little mention in the literature about specific therapies for low
serum calcium, magnesium, and phosphate. Phosphate replacement may be
needed if the serum level is < 1.0 mg/dL or the patient has anemia, cardiac
dysfunction, or respiratory dysfunction.1,9

Hyponatremia is treated with infusion of IV saline solutions. A patient

who has DKA often has a significant total body deficit of potassium, and the
aggressive insulin therapy that is used to treat DKA can further lower serum
potassium. Profound hypokalemia can have dire consequences and it should
be treated aggressively.

Insulin Therapy

Patients who have moderate to severe DKA should be treated with IV

insulin; patients who have mild DKA can be treated with subcutaneous insulin
injections.46 The standard recommendation for IV insulin is to give a bolus
dose of regular insulin, 0.1 units/kg, followed by a continuous IV infusion of
regular insulin at 0.1 units/kg/hour.1,46 The clinician should bear in mind that
if the patient’s serum potassium is < 3.3 mEq/L then insulin therapy should
be delayed until the serum potassium is > 3.3 mEq/L.46

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 When the serum glucose is at or close to 200 mg/dL, the rate of the
insulin infusion should be decreased, but the IV insulin should be continued
until the ketoacidosis has resolved, the serum glucose is < 200 mg/dL, and
administration of subcutaneous insulin has been started.46 Ketoacidosis is
considered to have been resolved when the anion gap and the beta-
hydroxybutyrate levels are normal and the patient can eat.

Subcutaneous insulin can be started using the patient’s previous insulin

protocol. If the patient is insulin naïve, the clinician should administer 0.5-0.8
units/kg a day along with bolus doses and basal insulin until the blood glucose
is controlled.46 The IV insulin infusion should be continued for several hours
after the first subcutaneous dose of insulin has been given.46 The serum
glucose level will usually decrease by 50-70 mg/dL an hour and if it does not,
the clinician should double the infusion rate and closely monitor the serum
glucose.46

INSULIN THERAPY FOR DKA

Serum Potassium: Do not treat with insulin until serum potassium is > 3.3 mEq.

Mild DKA: Treat with subcutaneous insulin.

Moderate-Severe DKA: Bolus of 0.1 units/kg regular insulin then a continuous

infusion of regular insulin at 0.1 units/kg/hour.

Serum glucose ~ 200 mg/dL: Decrease rate of insulin infusion until serum
glucose is < 200 mg/dL, ketoacidosis has resolved, and subcutaneous insulin
has been started.

Subcutaneous insulin: Use the patient’s previous insulin protocol. Insulin naïve
patients, give 0.5-0.8 units/kg a day with bolus doses and basal insulin until
blood glucose is controlled. Continue IV insulin infusion for several hours after
the first dose of subcutaneous insulin.

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Acid-Base Disturbances and Bicarbonate Therapy

The acidosis caused by DKA can be severe, and acidosis interferes with
the effectiveness of therapy and it has many deleterious effects like
arrhythmias, cardiac dysfunction, coma, peripheral vasodilation, and shifting
the oxyhemoglobin dissociation curve to the left. Given this, correcting the
acidosis with IV bicarbonate makes intuitive sense. However, bicarbonate
therapy is not recommended as treatment for DKA; there is no proof that it is
effective if the patient’s pH is ≥ 6.9,1,9,46 and there is evidence that bicarbonate
therapy can be harmful by slowing the rate of recovery, increasing the risk for
cerebral edema and hypokalemia and depressing ventilatory drive.1,9,46 The
potential for deleterious effects may be especially true for children who have
DKA.

Bicarbonate therapy should only be used if the serum pH is < 6.9, the
patient has severe hyperkalemia, or if the acidosis is causing severe systemic
effects.1,46 If bicarbonate therapy is needed, the clinician should administer
100 mEq of sodium bicarbonate with 20 mEq of potassium chloride, diluted in
400 mL of sterile water, and infused over two hours.46

Continuing Care and Monitoring for Complications

Arterial or venous pH, serum glucose, potassium, and sodium, serum

osmolality, and beta-hydroxybutyrate should be periodically measured; the
timing between measurements will depend on previous values, the patient’s
clinical condition, and the specific therapies being used.

Common complications of DKA and the treatment of DKA include

hypoglycemia, hypokalemia, hyperkalemia, pulmonary edema, and renal
failure. These can be prevented by close monitoring of the BUN and creatinine,
serum electrolytes, serum glucose, and the patient’s intake and output
measurements.

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 Treatment of Cerebral Edema

Specific recommendations for treating cerebral edema primarily address

the issue of cerebral edema in children and adolescents. General guidelines
for treating elevated intracranial pressure include the following
interventions. 47

● Antiepileptic therapy (done prophylactically if needed).

● Blood pressure control.
● Fever: If the patient is febrile, aggressive temperature control is a priority.
● Position: The patient’s head should be elevated.
● Sedation.

Specific therapies that are/may be recommended for children,

adolescents, and adults include:1,46-48

● Mannitol: 0.5-1.0 grams/kg, give IV over 20 minutes. The dose may be

repeated in 1-2 hours if there is no response.
● Hypertonic saline: A 3% saline solution, 5-10 mL/kg, give IV over 30
minutes. This is considered a secondary measure, used only if mannitol is
not effective.

Clinical Care, Prevention and Education

When providing care for a patient in the acute phase of DKA, the health
clinician should focus on hydration status and fluid replacement, monitoring
of acid-base status, serum glucose, and serum electrolytes, close observation
of the patient’s neurological status, and vital signs. Once a case of DKA has
resolved it is important to know why it happened. Infections, medical
conditions, and drugs are common causes of DKA. However, one of the most
important causes of DKA is patient non-compliance with diabetic treatment
regimens.

Patients who do not take their medication or do not take them properly,
fail to follow a prescribed diet and lifestyle plans, and who do not or cannot
understand the basics of self-care and prevention as related to diabetes

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present challenges to diabetes management. If noncompliance was the cause
of a case of DKA, it is very important to determine why the non-compliance
occurred, and there are many possible reasons. Some of the more common
reasons are listed below.

Poor Access to Medical Care

The patient may not have access to health care information, may not
have easy access to a physician, clinic, etc., and may not have or not know
how to use community or public access health care resources. The patient also
may not have money for medications.

Lack of Information

The patient may have a poor understanding of diabetes, and the patient
may not understand the treatment regimens that have been prescribed. Lack
of information can be damaging in many ways. If the patient doesn’t
understand the disease of diabetes, he/she might be less willing to comply
with lifestyle and diet restrictions and less willing to take medications. The
patient would not recognize possible warning signals of DKA.

Emotional Acceptance and Non-compliance

For many people, diabetes requires lifestyle changes that they may not
be willing to emotionally accept. Although it may be said that non-compliance
happens when the patient fails to provide good self-care, the word fail typically
has a negative connotation. Also, when many people hear the term non-
compliance, they think of a person willfully failing to do what he/she knows is
best. However, there are many cases of non-compliance that happen because
the patient has not been properly educated, or doesn’t have or doesn’t know
how to get the resources needed.

When it has been determined that non-compliance was the cause of

DKA, the patient should be interviewed to find 1) the emotional impact of
diabetes on the patient’s life, 2) how much is known about the disease and

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treatments, and 3) what financial, medical, personal, and social resources the
patient has available for self-treatment. Social workers, psychologists, or the
patient’s medical clinician must address some of these issues. However,
nursing clinicians have a primary role to support and educate patients who
have had an incident of DKA related to non-compliance.

Nurses will often be the first person to find out that the patient did not
seek medical attention for an infection because of financial concerns, or due
to inability to reach a physician, or because of a lack of understanding of the
implications of infection in diabetes. All clinicians in primary care settings must
discuss the appropriate patient referrals and establish a teaching plan. Some
of the clinical diagnoses that might apply in these situations would be
imbalanced nutrition, noncompliance, knowledge deficit, and risk for injury.

Summary

Diabetic ketoacidosis is a metabolic disorder characterized by

hyperglycemia, metabolic acidosis, and elevated ketone concentrations. The
basic cause of DKA is insulin deficiency, absolute or relative. The insulin
deficiency most often occurs because of infection or non-compliance with
diabetic treatment regimens. However, there are multiple medical conditions
that can cause DKA and many medications that can do so as well. Excess
hormone concentration and a metabolic shift are the pathogenic mechanisms
that cause the signs and symptoms of DKA.

The common signs and symptoms of DKA, such as abdominal pain,

decreased skin turgor, dehydration, dry mucous membranes, and electrolyte
abnormalities, among others have been discussed. Also, the complications in
adults and children of DKA have been noted. Cerebral edema is a rare
complication of DKA in adults and children, but the mortality and morbidity
rates of this complication in children are high.

The fetal and maternal death is an uncommon complication of DKA. If

DKA if promptly recognized, properly and aggressively treated, and treatment
outcomes appropriately evaluated and followed, patients should survive. The

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treatment for diabetic ketoacidosis should focus on fluid replacement, insulin
therapy, correcting electrolyte abnormalities and acid-base disturbances, and
monitoring for complications.

For many people, diabetes requires lifestyle changes that they may not
be willing to emotionally accept. Many cases of non-compliance happen
because the patient has not been properly educated, or doesn’t have or
doesn’t know how to get the resources needed. While all members of the
health team have a role to support and educate patients with diabetes and
history of DKA, nurses are often the first person to learn why a patient may
not seek medical attention or lacks an understanding of diabetes and
associated risks, such as unbalanced nutrition, infection and noncompliance
to medication to treat diabetes and to prevent diabetic ketoacidosis.

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Self-Assessment of Knowledge Post-Test:

Please take time to help NurseCe4Less.com course planners evaluate

the nursing knowledge needs met by completing the self-assessment
of Knowledge Questions after reading the article, and providing
feedback in the online course evaluation. Completing the study
questions is optional and is NOT a course requirement.

1. Which of the following is the correct definition of diabetic

ketoacidosis (DKA)?

a. Metabolic disorder with hyperglycemia, metabolic acidosis, elevated

ketones.
b. Metabolic disorder with normal glucose, metabolic alkalosis,
elevated ketones.
c. Endocrine disorder caused by inappropriate insulin secretion.
d. Endocrine disorder caused by abnormal carbohydrate metabolism.

2. The two most common causes of diabetic ketoacidosis (DKA) are:

a. Atypical antipsychotics and gestational diabetes.

b. Infection and poor compliance with medication regimens.
c. CVA and pregnancy.
d. Glucagon-producing tumors, sepsis.

3. The diagnostic criteria of diabetic ketoacidosis (DKA) include:

a. A serum pH > 7.5, a serum glucose > 250 mg/dL.

b. A serum pH < 7.30, a serum glucose < 250 mg/dL.
c. A serum pH > 7.2, a serum glucose < 125 mg/dL.
d. A serum pH < 7.3, a serum glucose > 250 mg/dL.

4. The serum potassium in diabetic ketoacidosis (DKA) is:

a. Typically very low.

b. Deceptively high: there is actually profound hypokalemia.
c. Typically normal.
d. Deceptively low: the total body content is normal.

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5. Pregnant women who have diabetic ketoacidosis (DKA):

a. Always have elevated serum glucose.

b. Are rarely acidotic.
c. May be euglycemic.
d. Have a high mortality rate.

6. Young children are more likely to be vulnerable to which of the

following diabetic ketoacidosis (DKA) complications?

a. Cerebral edema.
b. Hypokalemia.
c. Renal failure.
d. Cardiac arrhythmias.

7. The first step in treating diabetic ketoacidosis (DKA) is:

a. Administration of insulin.
b. Fluid resuscitation.
c. Administration of bicarbonate.
d. Potassium supplementation.

8. Patients with moderate to severe diabetic ketoacidosis (DKA)

should be treated by using

a. IV insulin or subcutaneous insulin.

b. subcutaneous insulin.
c. IV insulin.
d. IM insulin.

9. The use of bicarbonate when treating diabetic ketoacidosis (DKA)

a. Is reserved for children who have DKA.

b. Is only indicated if the serum pH is < 7.30.
c. Is reserved for pregnant women who have DKA.
d. Is only indicated if the serum pH is < 6.9.

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10. When switching from continuous IV to subcutaneous insulin

a. the IV infusion should be continued for several hours after starting

subcutaneous insulin.
b. The IV infusion should be stopped 1-2 hours before starting
subcutaneous insulin.
c. The IV infusion should be increased for 1-2 hours before starting
subcutaneous insulin.
d. The IV insulin should be continued for 10-12 hours after starting
subcutaneous insulin.

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CORRECT ANSWERS:

1. Which of the following is the correct definition of diabetic

ketoacidosis (DKA)?

a. Metabolic disorder with hyperglycemia, metabolic acidosis, elevated

ketones.

“Diabetic ketoacidosis is a very serious complication of diabetes mellitus, a

metabolic disorder that is characterized by hyperglycemia, metabolic
acidosis, and increased ketone body concentrations.”

2. The two most common causes of diabetic ketoacidosis (DKA) are:

b. Infection and poor compliance with medication regimens.

“The most common causes of diabetic ketoacidosis (DKA) are infection and
poor compliance with medication regimens.”

3. The diagnostic criteria of diabetic ketoacidosis (DKA) include:

d. A serum pH < 7.3, a serum glucose > 250 mg/dL.

“MILD DKA - Glucose: > 250 mg/dL ... Arterial pH: 7.25-7.30
MODERATE DKA - Glucose: > 250 mg/dL ... Arterial pH: 7.00-7.24
SEVERE DKA - Glucose: > 250 mg/dL ... Arterial pH: < 7.00.”

4. The serum potassium in diabetic ketoacidosis (DKA) is:

b. Deceptively high: there is actually profound hypokalemia.

“The serum potassium level may be high, but the patients are often very
depleted of potassium.... Hyponatremia is treated with infusion of IV saline
solutions. A patient who has DKA often has a significant total body deficit of
potassium, and the aggressive insulin therapy that is used to treat DKA can
further lower serum potassium. Profound hypokalemia can have dire
consequences and it should be treated aggressively.”

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5. Pregnant women who have diabetic ketoacidosis (DKA):

c. May be euglycemic.

“If DKA in the pregnant woman is recognized early and treated properly, the
outcome for the mother should be good; ... if the condition is not recognized
early in its development and/or the appropriate treatments are not given
soon enough, serious maternal complications such as acute renal failure,
adult respiratory distress syndrome, cerebral edema, euglycemic DKA,
preterm delivery, and myocardial ischemia are possible.”

6. Young children are more likely to be vulnerable to which of the

following diabetic ketoacidosis (DKA) complications?

a. Cerebral edema.

“Finally, for several physiological reasons young children are more

vulnerable to cerebral edema. Adolescents are more likely than adults to be
non-compliant with their insulin regimen.”

7. The first step in treating diabetic ketoacidosis (DKA) is:

b. Fluid resuscitation.

“Treatment of DKA should begin with fluid replacement.”

8. Patients with moderate to severe diabetic ketoacidosis (DKA)

should be treated by using

c. IV insulin.

“Patients who have moderate to severe DKA should be treated with IV

insulin; patients who have mild DKA can be treated with subcutaneous
insulin injections.”

9. The use of bicarbonate when treating diabetic ketoacidosis (DKA)

d. Is only indicated if the serum pH is < 6.9.

“Bicarbonate therapy should only be used if the serum pH is < 6.9, the
patient has severe hyperkalemia, or if the acidosis is causing severe
systemic effects.”

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10. When switching from continuous IV to subcutaneous insulin

a. the IV infusion should be continued for several hours after starting

subcutaneous insulin.

“Subcutaneous insulin can be started using the patient’s previous insulin

protocol. If the patient is insulin naïve, the clinician should administer
0.5-0.8 units/kg a day along with bolus doses and basal insulin until the
blood glucose is controlled. The IV insulin infusion should be continued for
several hours after the first subcutaneous dose of insulin has been.”

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