Download diabetic ketoacidosis

DIABETIC KETOACIDOSIS
DANA BARTLETT, RN, BSN, MSN, MA
Dana Bartlett is a professional nurse and author. His clinical experience includes 16
years of ICU and ER experience and over 20 years of as a poison control center
information specialist. Dana has published numerous CE and journal articles, written
NCLEX material, written textbook chapters, and done editing and reviewing for
publishers such as Elsevire, Lippincott, and Thieme. He has written widely on the
subject of toxicology and was recently named a contributing editor, toxicology
section, for Critical Care Nurse journal. He is currently employed at the Connecticut
Poison Control Center and is actively involved in lecturing and mentoring nurses,
emergency medical residents and pharmacy students.
ABSTRACT
Diabetic ketoacidosis (DKA) is an acute complication of diabetes
mellitus, which requires prompt, aggressive, treatment. Complications
of DKA 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 DKA. Guidelines exist that guide diabetes health teams and
nursing care of the diabetic patient. Appropriate and timely treatment
can reduce DKA complications and patients can recover to full health.
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Continuing Nursing Education Course Planners
William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,
Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner
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. It is the policy of
NurseCe4Less.com to ensure objectivity, transparency, and best
practice in clinical education for all continuing nursing education (CNE)
activities.
Continuing Education Credit Designation
This educational activity is credited for 2 hours. Nurses may only claim
credit commensurate with the credit awarded for completion of this
course activity.
Statement of Learning Need
Diabetes mellitus is one of the leading chronic diseases in the country
and DKA is one of the most serious complications. When patients in
DKA crisis receive the right treatment they are able to recover to
improved health. Nurses need to be able to identify prevalence and
treatment of diabetes ketoacidosis (DKA) in all age groups and for
special conditions, such as pregnancy.
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Course Purpose
This course will help nurses identify signs and symptoms of diabetic
ketacidosis and its recommended treatment.
Target Audience
Advanced Practice Registered Nurses and Registered Nurses
(Interdisciplinary Health Team Members, including Vocational Nurses
and Medical Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Dana Bartlett, RN, BSN, MSN, MA, William S. Cook, PhD,
Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC - all
have no disclosures.
Acknowledgement of Commercial Support
There is no commercial support for this course.
Activity Review Information
Reviewed by Susan DePasquale, MSN, FPMHNP-BC
Release Date: 1/1/2016
Termination Date: 3/31/2017
Please take time to complete a self-assessment of knowledge,
on page 4, sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge
learned will be provided at the end of the course.
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1) Which of the following is the correct definition of 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 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 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 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 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 (DKA) 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 DKA are infection and poor compliance with
medication regimens. Other causes include undiagnosed diabetes,
alcohol abuse, stress and a multitude of medical conditions such as
cerebrovascular accident (CVA), complicated pregnancy, myocardial
infarction and pancreatitis.
Diabetic ketoacidosis is a complicated pathology. Early recognition of
DKA, a good understanding of the pathological processes of DKA, and
aggressive treatment are the keys to successful treatment. With good
care, DKA can be managed and the patient will survive.
Epidemiology
Most cases of DKA are seen in patients with type 1 diabetes, but
approximately 10%-30% of all cases of DKA occur in patients with
type 2 diabetes.1 The incidence of DKA in the United States is
increasing,2,3 and the incidence of DKA in people who have type 2
diabetes appears to be increasing, as well.4 There is also a variation of
type 2 diabetes, ketosis-prone diabetes, and this subgroup of diabetics
accounts for 20-50% of all persons with DKA.
5
The incidence of DKA is
approximately two episodes per 100 patient years of diabetes.6
Diabetic ketoacidosis is more common in Caucasians than in other
racial groups, and the incidence of DKA is higher in women than in
men.6 The mortality rate for DKA is approximately ≤ 2%.6
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The danger of DKA also affects children and adolescents, and there is
evidence that these age groups are increasingly at risk for DKA.
Approximately one-third of children and adolescents with type 1
diabetes have DKA at the time of diagnosis,7 and one researcher found
the incidence of DKA in these populations at the time of diagnosis to
be 77.1%.8
In children and adolescents who have type 2 diabetes, approximately
25% will have DKA at the time of diagnosis,9 and children aged 0-4
had an incidence of DKA at the time of diagnosis of 37.3%.10 Diabetic
ketoacidosis is the most common cause for hospitalization in the
pediatric population,9 and DKA is the most common cause of diabetesrelated death in children and adolescents with type I diabetes.11,12
Unlike adults, infection is an infrequent cause of DKA in children.
Glucose, Insulin, And Diabetes: A Short Review
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
we eat (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.
Glucose is an essential source of energy. In order for glucose to be
used for energy it must be transported into the cells, but the glucose
molecule is too 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. The process by which insulin
promotes glucose entry into the cells is called facilitated diffusion. This
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process has not been completely outlined and 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 a glucose transporter, Glut4.
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 (i.e., 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 2 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.
People with type I diabetes essentially do not produce insulin.
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.
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Type 1 and type 2 Diabetes Classification System: Out of Date?
Diabetes mellitus has traditionally been classified as type 1 or type 2;
however, there is growing recognition that not everyone with diabetes
mellitus can be described by one of those two categories. 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. For example, Vacante, et al., (2011)
proposed three classifications of diabetes for older adults and the
elderly: maturity onset diabetes, maturity onset diabetes in the
elderly, and senile diabetes.13 Adolescents and children with diabetes
could be considered to have one of four types of diabetes14, as listed
below:

Autoimmune plus insulin-sensitive (IS)

Autoimmune plus insulin-resistant (IR)

Non-autoimmune plus IS, and

Non-autoimmune plus IR
Also, some people who have type 2 diabetes are much more
susceptible to developing DKA, a sub-group of diabetics that are said
to have ketosis-prone diabetes.4,15-17
Pathophysiology Of DKA
The underlying cause of DKA is insulin deficiency. This 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, the lack of insulin causes hyperglycemia, and
hyperglycemia initiates several pathogenic mechanisms that produce
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the signs, symptoms, and metabolic derangements of DKA. These
mechanisms are outlined below:18-19

Increased hormone release:
Hyperglycemia in DKA stimulates the body to increase
production of the hormones cortisol, epinephrine, glucagon, and
growth hormone in an attempt to produce energy. 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.

Metabolic shift:
The increased release of hormones and the lack of insulin cause
a shift in metabolism. The body now depends on fats for energy
instead of carbohydrates. One of the byproducts of fat
metabolism is ketones, and the ketones (acetone, acetoacetate
and beta-hydroxybutyrate) dissociate to produce hydrogen ions,
thus causing the metabolic acidosis. Acetoacetate and betahydroxybutyrate are the two ketones that are primarily
responsible for this metabolic effect.
Because of the increased hormone production and the shift in
metabolism, the serum glucose is elevated and there is high acid load.
The high serum glucose causes an osmotic diuresis, which leads to
dehydration. The intense production of ketones overwhelms the body’s
buffering mechanisms. This causes a metabolic acidosis which in turn
causes: 1) nausea and vomiting; 2) Kussmaul respirations, and; 3) a
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shift of potassium from the intracellular space to the extracellular
space. These pathologic mechanisms lead to profound dehydration,
hyperkalemia, and loss of electrolytes.
Causes Of DKA
Diabetic ketoacidosis is caused by: 1) new-onset diabetes; 2) poor
compliance with prescribed insulin regimen; 3) increased insulin need
because of infection or stress, or; 4) prescription or illicit drug use.20
The majority of cases of DKA are caused by non-compliance with the
prescribed insulin regimen or by an infection.
Gastroenteritis, pneumonias, sepsis, and urinary tract infections are
common infections that may precipitate DKA.20-22 Acromegaly, CVA,
Cushing disease, glucagon-producing tumors, heat-related illness,
hemochromatosis, hemorrhage, hyperthyroidism, major trauma,
myocardial infarction or ischemia, pancreatitis, pregnancy, pulmonary
embolism, or major surgery can all cause DKA;18,23,24 and, these
stressors, along with infections, account for approximately 40% of all
cases of DKA.2 These medical conditions and pathologies can cause or
contribute to DKA by increasing the production of stress hormones,
elevating the serum glucose, or blunting the normal physiological
warning signs of hyperglycemia and acidosis. Pregnancy can also be a
cause of DKA, and this will be discussed in a separate section of this
learning module.
Drugs that may cause or contribute to DKA, or have been temporally
associated with DKA include cocaine,25,26 corticosteroids or
glucorticoids,27-29 diuretics,30 glucagon,31 interferon,32 and
sympathomimetics.33 The atypical antipsychotics are known to cause
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weight gain, adversely affect glucose regulation, and can cause DKA.34
The topic of DKA and the atypical antipsychotics will also be discussed
in a separate section of this learning module.
Defining DKA
When assessing a patient for DKA, 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, be sure to ask these
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?
There are signs and symptoms that are commonly noted in patients
with DKA, but they are not specific to DKA. Patients suffering from
DKA often have abdominal pain, decreased skin turgor, dehydration,
dry mucous membranes, electrolyte abnormalities, fever, hypotension,
hypothermia, malaise, mental status changes, such as drowsiness, or
in profound cases there may be coma, nausea, polydipsia, polyuria,
tachycardia, tachypnea, and vomiting.2,18,20 These signs and
symptoms are certainly not exclusive to DKA, but if the pathological
processes of DKA are examined, the genesis of the clinical picture of
DKA becomes clear. Several examples are raised below:
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Example #1:
Hypotension in the patient who has DKA is caused by dehydration.
Poor oral intake, nausea and vomiting, polyuria, and the osmotic
diuresis caused by hyperglycemia lead to the complication of
dehydration in individuals with DKA.
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 respirations are caused by metabolic acidosis and are a way
of excreting carbon dioxide (CO2). This breathing pattern can also
contribute to dehydration. Occasionally the patient’s breath will have
an odor that is sweet or fruity because a certain amount of the high
ketone load is excreted through the lungs. Diabetic ketoacidosis can
develop very quickly, for example, over several hours, in patients who
have type 1 diabetes, or it can develop very slowly over a period of
weeks in patients who have type 2 diabetes. The presentation can be
mild with the patient complaining of abdominal pain, fatigue, malaise,
and nausea or the presentation can be profound. In a serious case of
DKA the patient may be comatose and have severe metabolic
abnormalities
Laboratory Tests And DKA
The laboratory abnormalities seen in DKA that are commonly
considered to be the definitive criteria for a diagnosis of DKA are listed
below:2,20
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1. hyperglycemia with a blood glucose > 250 mg/dL;
2. metabolic acidosis with a blood pH < 7.30 and a serum
bicarbonate of < 18 mEq/L;
3. an elevated serum ketone level and ketones in the urine, and;
4. an elevated anion gap.
Other laboratory test results that may be abnormal in a patient who
has DKA are identified and explained below:

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
patient may be profoundly depleted of potassium.

Hyponatremia:
Hyperglycemia causes an osmotic shift of fluid into the vascular
space and hyponatremia. Sodium is also lost renally because of
the 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. 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. Initially the serum phosphate may be normal or even
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high because an insulin deficiency will drive phosphate out of the
cells, but the typical phosphate deficit may be up quite high.

Amylase and lipase:
Serum amylase and lipase levels can be elevated by DKA. It is
important to remember that pancreatitis can be a cause of DKA.

Hepatic transaminases:
The level of hepatic transaminases can be elevated. This can be
from DKA 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.

Serum osmolality:
This may be 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, pre-renal azotemia, or by a
laboratory error caused by interference by ketones.

Troponin levels:
Elevated serum tropinin levels associated with DKA have been
reported.
35,36
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
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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.37 Additionally, several of the diagnostic
criteria of DKA must be interpreted carefully; for example, normal
serum glucose has been reported in pregnant women who have DKA.38
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.2,39
Learning Break:
Euglycemic diabetic ketoacidosis in pregnancy is well described and will be
discussed later in this learning module. However, can someone who is not
pregnant have euglycemic DKA? This phenomenon has been reported
sporadically in the literature. 40-45. It is important to remember that euglycemia
means normal serum glucose. In the cases of euglycemic diabetic ketoacidosis
that have been reported, all of the patients had elevated serum glucoses that
were above the upper limit of normal.
It is true that some patients diagnosed as having euglycemic diabetic
ketoacidosis had serum glucoses that were < 250 mg/dL, some as low as 171
mg/dL; however, serum glucose levels below 180mg/dL in patients with
diabetic ketoacidosis is rare. It is not clear how this phenomenon happens.
Possible causes include a pre-existing fasting state, decreased hepatic stores
of glucose, decreased hepatic glucose production, and greater than normal
urinary losses of glucose.43
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Some authors have divided DKA into three categories, mild, moderate,
and severe, based on the initial laboratory test results.20,30 These
categories are described below.
 Mild DKA:
The anion gap is > 10; the arterial pH is 7.24-7,30; the serum
bicarbonate level is 15-18 mEq/L, and; the patient is awake and
alert.
 Moderate DKA:
The anion gap is > 12; the arterial pH is 7.00-7.24; the serum
bicarbonate level is 10-15 mEq/L, and; the patient is alert or
drowsy.
 Severe DKA:
The anion gap is > 12; the arterial pH is < 7.00; the serum
sodium bicarbonate is < 10 mEq/L, and; the patient is stuporous
or comatose.
Complications Of DKA
Patients who have diabetic ketoacidosis that is promptly recognized
and promptly and correctly treated should survive. The complications
of DKA are complications of treatment and complications associated
with or caused by the DKA itself.
Treatment complications are hypoglycemia, hyperkalemia, and
occasionally pulmonary edema. These can be avoided by careful
insulin therapy, monitoring blood glucose very closely, and by carefully
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managing fluid replacement. The complications of treatment will be
discussed in more detail later on in this learning module.
Complications associated with or caused by DKA itself include:
Cerebral edema, electrolyte disorders, prolonged QT interval, renal
failure, rhabdomyolysis, thrombosis and stroke.20,46-52 Cerebral edema
and electrolyte disorders are the most common of these complications.
Cerebral edema is a very serious consequence of DKA, and it will be
discussed in more detail later in the module.
Pregnancy And DKA
Diabetic ketoacidosis occurring during pregnancy deserves special
consideration, and it is considered to be a serious complication of
pregnancy.53 Diabetic ketoacidosis during pregnancy is quite
uncommon, with an incidence rate of 1-3%.53-55 If DKA in the pregnant
woman is recognized early and treated properly, the outcome for the
mother should be good, and the maternal mortality rates have been
reported to be < 1.0%.
55
However, serious maternal morbidities such
as acute renal failure, adult respiratory distress syndrome, cerebral
edema, and myocardial ischemia are possible, and the fetal mortality
rate associated with maternal DKA can be quite high; the incidence of
fetal death caused by DKA has been reported to be 9-36%.55
Diabetic ketoacidosis occurring during pregnancy tends to happen
more quickly than DKA will 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.56 Diabetic
ketoacidosis in pregnant women who have type 2 diabetes is more
common if glucocorticoids or β2 agonists are used during the
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pregnancy.54 Diabetic ketoacidosis is considered to be a rare
complication of gestational diabetes.57-58
Pregnant women have a higher risk for developing DKA than do
women who have diabetes who are not pregnant. Factors that can
predispose a pregnant woman to developing DKA include those listed
below:53,59
 Starvation
 Dehydration
 Decreased calorie intake
 Decreased buffering capacity (caused by the compensated
respiratory alkalosis of pregnancy)
 Increased production of insulin antagonistic hormones cortisol,
human placental lactogen, and prolactin.
Pregnant women of course are also susceptible to infections that may
cause DKA, and they may be non-compliant with their medication
regimens.
One of the most important issues regarding DKA during pregnancy is
euglycemic DKA. Euglycemic DKA is a well-known phenomenon,
56,59-62
and serum glucose levels as low as 87 mg/dL have been reported in
pregnant woman with DKA.61 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.59
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Other factors that can explain euglycemic DKA during pregnancy are
increased glucose utilization during pregnancy, water retention that
can cause hemodilution, and the high risk for ketosis that accompanies
pregnancy, causing DKA to occur at lower glucose levels.59
Atypical Antipsychotics And DKA
The atypical antipsychotics can cause many metabolic disorders such
as hyperlipidemia, hyperglycemia, hyperprolactinemia, insulin
resistance, intra-abdominal obesity, metabolic syndrome, type 2
diabetes and weight gain.63-64 These drugs have also been noted to
cause DKA. The mechanism or mechanisms by which the atypical
antipsychotics cause DKA are not known. These drugs, as mentioned
previously, can cause weight gain, and that is a risk factor for
developing type 2 diabetes and DKA. However, many patients who
have been taking an atypical antipsychotic who developed DKA had
not gained weight and were not obese.65,66 It may be that it is not
weight gain, but a relative increase in the amount of adipose tissue
that is partly to blame, or glucose dysregulation caused by the binding
of these drugs to certain neuroreceptors that in turn affects insulin
sensitivity.65
Fortunately, DKA caused by the use of atypical antipsychotics appears
to be rare. A 2013 review of the literature indentified only 69 cases
65
and given the widespread popularity of these drugs and their
increasing use, this is a very small number. Routine monitoring of
patient’s weight and BMI (body mass index) is recommended as part
of the treatment plan when FGA’s (1st generation antipsychotics) and
SGA’s (2nd generation antipsychotics) are prescribed that have the risk
to cause weight gain and increase the potential to develop diabetes.
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Adults should have waist circumference measured and, especially,
children and adolescents should have routine height and weight, as
well as BMI, trends on follow up exams. Consistent monitoring of
weight gain and BMI when a patient is prescribed antipsychotic
medication can help to avoid health problems later on.
Children, DKA And Cerebral Edema
Cerebral edema is perhaps the most feared complication of DKA in
children. It is fortunately rare, occurring in < 1% of all pediatric cases
of DKA, but the mortality rate has been estimated to be 20-60%,37,67
and 10-25% of these children will suffer permanent long-lasting or
permanent cognitive or motor deficits and in the worst case, a
permanent vegetative state.68 This complication of DKA affects
children almost exclusively and it is rarely seen in adults over the age
of 20.69,70
Cerebral edema caused by DKA usually occurs in the first 4 to 12
hours of treatment, but the onset can be seen earlier or delayed for
24-48 hours,7,71 and it can occur before therapy has been started.7,21
Children who have DKA and are likely to develop cerebral edema
typically have some of these risk factors:7,37,73
 New onset of diabetes
 Prolonged duration of symptoms
 A PCO2 that is < 20 mm Hg
 Treatment with NaHCO3
 A high BUN
 High volume of fluid resuscitation in the first four hours of
treatment, e.g., > 50 mL/kg
 Serum pH < 7.1
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 Insulin administration in the first hour of treatment
 Young age: Cerebral edema caused by DKA is more common in
children < 5 years.

Failure of serum sodium to increase as expected after insulin
therapy and fluid resuscitation.
Learning Break:
There are many reasons why young children are more likely to develop DKArelated cerebral edema: 1) The early signs and symptoms can be non-specific and
attributed to a viral illness; 2) young children cannot communicate how they feel
and this can make diagnosing DKA difficult; 3) 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, and; 4) for several physiological reasons young children are more
vulnerable to cerebral edema. Adolescents are more likely than adults to be noncompliant with their insulin regimen.
The signs and symptoms of cerebral edema caused by DKA include
age-inappropriate incontinence, agitation, bradycardia, central nervous
system (CNS) decorticate or decerebrate posturing, depression,
fluctuations in mental status, headache, hypertension, irregular
respirations, papillary edema, and persistent vomiting. Coma and
seizures may be seen, as well. However, not all children with cerebral
edema will have dramatic or obvious signs of neurological impairment,
and premonitory symptoms may be absent in many children. The
exact incidence is not known, but sub-clinical cerebral edema caused
by DKA appears to be relatively common, and it is likely that all
children with severe DKA have some degree of cerebral edema.
Children with sub-clinical cerebral edema may be asymptomatic or
have only subtle signs of cerebral edema,74,75 and approximately 40%
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of children who have cerebral edema caused by DKA will have a
normal brain imaging scan.37 Whether or not subclinical cerebral
edema is predictive of progression to significant cerebral edema is not
known.
The cause, or causes of DKA-related cerebral edema are not clearly
understood.76 Decreased cerebral perfusion, reperfusion injury,
vasogenic edema that is caused by disruption of the blood-brain
barrier, and excessive fluid resuscitation have all been identified as
possible causes.7,37,77 The close temporal association between
excessive fluid resuscitation and the development of cerebral edema in
children who have DKA has long been a subject of interest. However,
many children with DKA will develop cerebral edema before treatment
begins, and the current literature does not support excessive fluid
resuscitation as a primary cause of cerebral edema.7,12,37,71,77 The
diagnosis of cerebral edema is a clinical diagnosis. The diagnostic
criteria for cerebral edema are:77

Abnormal motor or verbal response to pain

Decoricate or decerebrate posturing

Cranial nerve palsy, especially III, IV, and VI

Neurogenic respiratory patterns, such as apneusis, CheyneStokes respiration, grunting, or tachypnea
In addition, cerebral edema is likely to be present if any of the
following two major criteria or one of the major criteria and two of the
minor criteria is present.77 The major criteria are:
1) altered or fluctuating level of consciousness;
2) a sustained decrease in heart beat of more than 20 beats a
minute, and;
3) age-inappropriate incontinence.
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The minor criteria are:
1) vomiting;
2) headache;
3) lethargy;
4) difficulty rousing from sleep; and,
5) diastolic blood pressure > 90 mm Hg, and 6) age < 5 years.
Treatment For Diabetic Ketoacidosis
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:

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.
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Treatment of DKA is focused on the following five areas:
1) fluid replacement;
2) insulin therapy;
3) monitoring for and correcting electrolyte imbalances;
4) monitoring for and correcting acid-base disturbances; and,
5) monitoring for and treating complications.
Fluid Replacement
Fluid replacement will replace the fluid deficit, help decrease the blood
glucose level, and maintain renal function. Because patients who have
DKA often have very significant fluid losses of 3 to 10 liters, in the
initial treatment of a patient who has DKA fluid replacement is more
important than insulin therapy and should take precedence.2,6,20,21,78
There are several different approaches/formulas available that can
help guide fluid replacement.,6,20,21 These are highlighted below.
Give 1000 mL of 0.9% normal saline solution (NSS) over 30 minutes.
Some authorities recommend this initial bolus for all patients, some
recommend the bolus only if the patient is severely dehydrated.
↓
After the initial bolus, give 15-20 mL/kg/hour of NSS. This should be
continued until the patient is euvolemic.
↓
Once the patient is euvolemic, the rate of fluid infusion should be
decreased to 4-14 mL/kg/hour. Depending on the corrected serum
sodium level, the fluid should be either 0.95 NSS or 0.45% NSS.
↓
When the serum glucose is 200-250 mg/dL, the IV fluid should be
changed to 5% dextrose/0.45% NSS at a rate of 150-250 mL/hour.
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Insulin Therapy
Insulin therapy is a critical part of the treatment of DKA. There is
agreement on the general guidelines of insulin therapy. The two areas
in which there is some disagreement and/or treatment guidelines differ
are: 1) the use of an initial bolus of insulin, and; 2) the use of IV
versus subcutaneous insulin. These issues will be discussed at the end
of this section.
The following are the guidelines for insulin therapy.2,6.20,21 Insulin
therapy should not be started immediately. It should be started one to
two hours after fluid resuscitation has been started. This is highlighted
in the table below.
Give a bolus of regular insulin, 0.1 units/kg. A bolus dose is not
recommended in children and is optional for adults.
↓
After the bolus dose, start a continuous infusion of regular insulin, 0.1
units/kg/hour. The continuous infusion should be delayed if the serum
potassium is < 3.3 mEq/L because of the risk of hypokalemia.
↓
The insulin infusion should be continued until: 1) the serum pH is
greater than 7.3; 2) the bicarbonate is ≥ 18 mEq/L: 3) the ketonemia
has resolved; 4) the anion gap is normal, and; 5) the serum glucose is <
200 mg/dL.
↓
Once the serum glucose is 250mg/dL, the insulin infusion should be
decreased to maintain the serum glucose between 150-200 mg/dL.
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The serum glucose level will usually decrease by 50-70 mg/dL an hour.
If the serum glucose does not decrease as expected it is likely that an
infection is the cause of the DKA. If the serum glucose does not
decrease by 50-70 mg/dl in the first hour, the patient can be given a
bolus of 0.2-0.4 units/kg or the infusion rate can be doubled.21
When the insulin infusion has been stopped the patient should be
transitioned to subcutaneous insulin. There are no universally accepted
protocols for this transition,21 but most sources agree on the following
points:
1) the insulin infusion can be stopped once the patient tolerates
oral fluids, the serum glucose is < 200 mg/dL, and the other
criteria mentioned above have been met;
2) the IV infusion of insulin should be continued for one to two
hours after the subcutaneous insulin regimen has been
started. If this is not done there is a risk for a recurrence of
hyperglycemia and/or ketoacidosis;
3) the patient should be given both a short-acting insulin and
along-acting insulin.
It is prudent to consult with an endocrinologist during the transition,
especially if the patient has new-onset diabetes
The use of an insulin bolus has been recommended, but there is no
evidence that a bolus dose, when compared to simply initiating the
continuous infusion, is helpful.79-81 A bolus of insulin should not be
given to a child who has DKA; it is not needed, and, may increase the
risk of developing hypoglycemia and cerebral edema.37,82-85
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Patients who have what would be considered uncomplicated DKA may
be able to be managed with rapid acting insulin analogs given
subcutaneously rather than a continuous insulin infusion by a pump.
This has been shown to be safe, cost-effective, and equally as effective
as an IV infusion of insulin.21,86-88 Several different regimens have
been recommended; such as, an initial injection of 0.2 unit/kg followed
by 0.1 unit/kg every hour or an initial dose of 0.3 unit/kg followed by
0.2 unit/kg every 2 hours until the serum glucose is < 250 mg/dL.
When that point is reached, decrease the insulin dose by half to 0.05
or 0.1 unit/kg, respectively, and administer it every 1 or 2 hours until
DKA has been resolved.21
Electrolyte Imbalances
The total body loss of potassium caused by DKA can be profound, up
to 5 mEq/kg; however, as mentioned earlier, the measured serum
potassium will often be normal or elevated. When fluids are given and
insulin is administered, serum potassium will drop because of
correction of acidosis, hemodilution, movement into the cells, and
renal excretion - at that point the true level of potassium will be
revealed.
The following guidelines can be used to manage serum potassium in
cases of DKA.21
1. If the initial serum potassium is < 3.3 mEq/L, insulin therapy
should not be started and the patient should be given 10-15
mEq/hour until the serum potassium is > 3.3 mEq/L.
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2. If the initial serum potassium is > 3.3 mEq/L but < 5.3 mEq/l,
the initial IV fluid resuscitation should provide 10 mEq of
potassium per hour for at least four hours.
3. If the initial serum potassium is > 5.3 mEq/L, do not give
supplemental potassium, check the level every two hours.
4. The goal is to maintain the serum potassium between 4-5
mEq/L.
The treatment recommendations for DKA may differ from source to
source, and there are certainly other treatment protocols that are used
for monitoring and replacing serum potassium in cases of DKA.20
However, despite differences in recommendations as to when to give
supplemental potassium and how much to give, all of these protocols
have similarities, which are outlined below:
1) if the initial serum potassium is very low, insulin therapy
should be delayed until this has been corrected;
2) if the serum potassium is above the top normal, no
supplementation is needed, and;
2) if the serum potassium is somewhere in between, potassium
supplementation is indicated.
Serum magnesium and serum phosphate should also be closely
monitored in cases of DKA. Replacement of serum phosphate is not
recommended unless the serum level is < 1.0 mg/dL21, and
magnesium supplementation is not recommended unless the serum
level is < 1.2 mg/dL.20 In either case, magnesium and/or phosphate
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supplementation should be considered if the patient has signs of a
deficit of either of these electrolytes.
Acid-Base Disturbances and Bicarbonate
Patients who have DKA can be severely acidotic, and there can be a
temptation to administer bicarbonate. Acidosis can cause decreased
cardiac contractility, peripheral vasodilation, hypotension, shifting of
the oxyhemoglobin dissociation curve to the right, and worsening of
CNS depression. However, the routine use of bicarbonate to treat DKA
is not recommended as there is no proof that it improves clinical
outcomes, and there is evidence that suggests that the use of
bicarbonate can have many harmful effects, such as, severe
hypokalemia, oxyhemoglbin dissociation, cerebral edema, and central
nervous system.6,20,21,89,90
The potential for harmful effects may be especially true for children
who have DKA. Bicarbonate therapy should only be used if the serum
pH is < 6.9 or if the acidosis is causing severe systemic effects, such
as, coma, hypotension, or hyperkalemia that is life threatening.20,21 If
bicarbonate therapy is needed, the American Diabetes Association
(ADA) does recommend, for a severe acidosis with a pH < 6.9, the
patent should receive 100 mEq of NaHCO3 in 400 mL IV fluid along
with 20 mEq of potassium chloride; this should be infused at 200
mL/h. Repeat this every two hours until the pH is ≥ 7.0.1,20
Monitoring For Complications
Common complications of DKA and the treatment of DKA include
hypoglycemia, hypokalemia, hyperkalemia, pulmonary edema, and
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renal failure. These can be prevented by close monitoring of BUN and
creatinine, serum electrolytes, serum glucose, and intake and output.
Treatment Of Cerebral Edema
Treatment of cerebral edema caused by DKA should be focused on
reducing intracranial pressure. Initiate the following therapies before
confirmation from imaging studies.6,12,37,91
1. Elevate the head of the bed.
2. Reduce the IV fluid rate by 30%.
3. Administer mannitol: the dose is 0.25-1.0 grams/kg IV, infused
over 20 minutes. Repeat the dose if there is no response or an
inadequate response. Monitor the patient’s urine output because
mannitol can cause diuresis, hypotension and thus reduced
cerebral blood flow.
4. If the patient needs elective intubation and mechanical
ventilation make sure that the PCO2 does not fall below 22 mm
Hg; this could decrease cerebral blood flow and cause cerebral
ischemia.
Some sources recommend the use of 3% hyper tonic saline 5-10
mL/kg IV, infused over 30 minutes, if the response to mannitol is not
ideal, given along with mannitol, or as an alternative to mannitol.7,12,37
However, the clinical experience with 3% hypertonic saline for this
purpose is limited,67,76,92,93 and there is evidence suggesting that when
compared to mannitol, 3% hypertonic saline was associated with an
increased risk of mortality.67
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Nursing Care, Prevention And Education
When providing care for a patient in the acute phase of DKA, the nurse
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 do
not take their medication or do not take them properly, they fail to
follow their prescribed diet and lifestyle plans, and they do not or
cannot understand the basics of self-care and prevention as related to
diabetes.
If non-compliance was the cause of a particular 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 may not have money for
medications.
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
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 issues:
For many people, diabetes requires lifestyle changes that they
may not be willing to emotionally accept.
Learning Break:
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 noncompliance that happen because the patient has not been properly educated, or
doesn’t have or doesn’t know how to get the resources he/she needs.
When it has been determined that non-compliance was the cause of a
particular case of DKA, the patient should be interviewed to find out
the following:
a) the emotional impact of diabetes on the patient’s life;
b) how much he/she knows about the disease and the
treatments, and;
c) what financial, medical, personal, and social resources the
patient has available for self-treatment.
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Social workers, psychologists, or the patient’s provider must address
some of the issues listed above. However, nurses have a primary role
in supporting and educating patients who have had an incident of DKA
related to non-compliance. The nurse 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. The nurse must then discuss making the appropriate
referrals and then set up a teaching plan. Some of the nursing
diagnoses that might apply in these situations would be imbalanced
nutrition, noncompliance, knowledge deficient, and risk for injury.
Summary
Diabetic ketoacidosis is a metabolic disorder characterized by
hyperglycemia, metabolic acidosis, and elevated body 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 hormone concentrations cause hyperglycemia, and the metabolic
shift causes acidosis and elevated serum ketones and ketones in the
urine. The basic diagnostic criteria for DKA are a blood glucose > 250
mg/dL, a serum pH < 7.3, a serum bicarbonate < 18 mEq/L, an
elevated serum ketone level and ketones in the urine, and an elevated
anion gap. Hyperkalemia and hyponatremia are common in DKA.
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Hypophosphatemia can be seen. However, the total body load of
potassium and phosphate is often low.
Common signs and symptoms of DKA include abdominal pain,
decreased skin turgor, dehydration, dry mucous membranes,
electrolyte abnormalities, fever, hypotension, hypothermia, malaise,
mental status changes such drowsiness or in profound cases coma,
nausea, polydipsia, polyuria, tachycardia, tachypnea, and vomiting.
Complications of DKA include cerebral edema, electrolyte disorders,
prolonged QT interval, renal failure, rhabdomyolysis, thrombosis and
stroke. Cerebral edema a rare complication of DKA in children, but the
mortality and morbidity rates of this complication are high. Cerebral
edema caused by DKA is rare in adults. Euglycemic DKA is possible in
pregnant women. Fetal mortality is a common complication of DKA,
but maternal death is unusual.
Treatment for DKA should focus on fluid replacement, insulin therapy,
and correcting electrolyte abnormalities, correcting acid-base
disturbances, and monitoring for complications. The complications of
treatment of DKA include hypoglycemia, hyperkalemia, and pulmonary
edema. However, if DKA if promptly recognized, properly and
aggressively treated, and treatment outcomes appropriately evaluated
and followed, patients should survive.
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1) Which of the following is the correct definition of 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 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 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 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 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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6) DKA complications almost exclusively affecting children are:
a. Cerebral edema.
b. Hypokalemia.
c. Renal failure.
d. Cardiac arrhythmias.
7) The first step in treating DKA is:
a. Administration of insulin.
b. Fluid resuscitation.
c. Administration of bicarbonate.
d. Potassium supplementation.
8) DKA can be treated by using:
a. IV insulin.
b. Subcutaneous insulin.
c. IV or subcutaneous insulin.
d. IM insulin.
9) The use of bicarbonate when treating 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.
10) When switching from continuous IV to SUBQ Insulin:
a. The IV infusion should be continued for 1-2 hours after
starting SC insulin.
b. The IV infusion should be stopped 1-2 hours before starting
SC insulin.
c. The IV infusion should be increased for 1-2 hours before
starting SC insulin.
d. The IV insulin should be continued for 10-12 hours after
starting SC insulin.
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Correct Answers:
1) Which of the following is the correct definition of DKA?
a. Metabolic disorder with hyperglycemia, metabolic
acidosis, elevated ketones.
2) The two most common causes of DKA are:
b. Infection and poor compliance with medication regimens.
3) The diagnostic criteria of DKA include:
d. A serum pH < 7.3, a serum glucose > 250 mg/dL.
4) The serum potassium in DKA is:
b. Deceptively high: there is actually profound hypokalemia.
5) Pregnant women who have DKA:
c. May be euglycemic.
6) DKA complications almost exclusively affecting children are:
a. Cerebral edema.
7) The first step in treating DKA is:
b. Fluid resuscitation.
8) DKA can be treated by using
c. IV or subcutaneous insulin.
9) The use of bicarbonate when treating DKA
d. Is only indicated if the serum pH is < 6.9.
10) When switching from continuous IV to SUBQ Insulin:
a. The IV infusion should be continued for 1-2 hours after
starting SC insulin.
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References Section
The reference section of in-text citations include published works
intended as helpful material for further reading. Unpublished works
and personal communications are not included in this section, although
may appear within the study text.
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18. Kitabachi AE. Epidemiology and pathogenesis of diabetic
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23. Trachtenburg DE. Diabetic ketoacidosis. American Family
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24. Anthony LB, Sharp SC, May ME. A case report: diabetic
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25. Isidro ML, Jorge S. Recreational drug use in patients hospitalized
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