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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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