Ted A. Bonebrake, M.D.
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A 14 y/o female is brought to the emergency
department by her mother after being found
unresponsive at home. She had been ill the
day before with nausea and vomiting, but
was not running a fever. Her parents had kept
her home from school that day.
When her mother came home at lunchtime to
check on her, she was very lethargic and not
responding coherently.
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By the time she arrived at the hospital, she
had to be brought in to the ED on a gurney.
Initial evaluation showed O2 sat 100% on
room air, pulse 126, respirations 30, BP 92/68,
temperature 101.2 F.
She appears pale, mucous membranes are
dry and she only responds to painful stimuli.
Exam shows diffuse abdominal tenderness
with guarding.
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Differential diagnosis?
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What initial treatment would you suggest?
What labs would you order?
Any xrays or additional studies?
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CBC
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WBC 23,500
Hgb 14.2 g/dL
Hct 45%
Platelets 425,000
BMP
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Sodium 126
Potassium 5.2
Chloride 87
CO2 <5
BUN 32
Creatinine 1.5
Glucose 1,376
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Arterial Blood Gases
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pH 7.19
Po2 100 mm Hg
HCO3 7.5 mmo/L
Pco2 20 mm Hg
Sao2 98% (room air)
Urine
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Specific gravity 1.015
Ketones 4+
Leukocytes few
Glucose 4+
Nitrates 0
RBCs many
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Diabetic ketoacidosis (DKA) is an acute metabolic
complication of diabetes characterized by
hyperglycemia, hyperketonemia, and metabolic
acidosis. DKA occurs mostly in type 1 diabetics.
It causes nausea, vomiting, and abdominal pain
and can progress to cerebral edema, coma, and
death.
DKA is diagnosed by detection of hyperketonemia
and anion gap metabolic acidosis in the presence
of hyperglycemia.
Treatment involves volume expansion, insulin
replacement, and prevention of hypokalemia.
 Diagnosis
 Epidemiology
 Pathophysiology
 Treatment
 Initial (emergency) treatment
 Ongoing management and monitoring
 Prognosis
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Symptoms and signs of DKA
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Nausea & vomiting
Abdominal pain--particularly in children
Lethargy and somnolence
Kussmaul respirations
Hypotension
Tachycardia
Fruity breath due to exhaled acetone
Fever +/- if present may signify underlying infection
In the absence of timely treatment, DKA progresses
to coma and death.
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Arterial pH
Serum ketones
Calculation of anion gap
Electrolytes, BUN and creatinine, glucose, ketones,
and osmolarity should be measured
Urine ketones
Patients who appear significantly ill and those with
positive ketones should have ABG measurement.
DKA is diagnosed by an arterial pH < 7.30 with an
anion gap > 12 and serum ketones in the presence of
hyperglycemia.
A presumptive diagnosis can be made when urine
glucose and ketones are strongly positive.
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Calculation Anion Gap
 AG = ([Na+] + [K+]) − ([Cl−] + [HCO3−])
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Or omit potassium
 AG = [Na+] − ([Cl-] + [HCO3−])
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Alcoholic Ketoacidosis
Appendicitis, Acute
Hyperosmolar Coma
Hypophosphatemia
Hypothermia
Lactic Acidosis
Metabolic Acidosis
Myocardial Infarction
Pancreatitis, Acute
Pneumonia, Immunocompromised
Septic Shock
Salicylate Toxicity
Urinary Tract Infection
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DKA accounts for 50% of diabetes-related
admissions in young persons and 1-2% of all
primary diabetes-related admissions.
DKA frequently is observed during the
diagnosis of type 1 diabetes and often
indicates this diagnosis.
While the exact incidence is not known, it is
estimated to be 1 out of 2000.
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DKA occurs primarily in patients with type 1
diabetes.
The incidence is roughly 2 episodes per 100
patient years of diabetes.
About 3% of patients with type 1 diabetes
initially present with DKA.
It can occur in patients with type 2 diabetes
as well; this is less common, however.
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The incidence of DKA is higher in whites
because of the higher incidence of type 1
diabetes in this racial group.
The incidence of diabetic ketoacidosis (DKA)
is slightly greater in females than in males for
reasons that are unclear.
Recurrent DKA frequently is seen in young
women with type 1 diabetes and is caused
mostly by the omission of insulin treatment.
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Among persons with type 1 diabetes, DKA is
much more common in young children and
adolescents than it is in adults.
DKA tends to occur in individuals younger than
19 years, but it may occur in patients with
diabetes at any age.
Multiple factors (eg, ethnic minority, lack of
health insurance, lower body mass index,
preceding infection, delayed treatment) affect
the risk of developing DKA among children and
young adults
Diabetic ketoacidosis (DKA) is a complex
disordered metabolic state characterized by
hyperglycemia, ketoacidosis, and ketonuria.
 DKA occurs as a consequence of absolute or
relative insulin deficiency that is accompanied
by an increase in counter-regulatory hormones
(ie, glucagon, cortisol, growth hormone,
epinephrine).
 The hormonal imbalance enhances hepatic
gluconeogenesis, glycogenolysis, and lipolysis.
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Hepatic gluconeogenesis, glycogenolysis
secondary to insulin deficiency, and counterregulatory hormone excess result in severe
hyperglycemia
 Lipolysis increases serum free fatty acids.
 Hepatic metabolism of free fatty acids as an
alternative energy source (ketogenesis) results
in accumulation of acidic intermediate and end
metabolites (ketones).
 Ketones include acetone, beta-hydroxybutyrate,
and acetoacetate.
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Increased concentration of ketones initially
leads to a state of ketonemia.
Extracellular and intracellular body buffers
can limit ketonemia in its early stages, as
reflected by a normal arterial pH associated
with a base deficit and a mild anion gap.
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When the accumulated ketones exceed the
body's capacity to extract them, ketonuria
results.
If the situation is not treated promptly, this
leads to clinical metabolic acidosis
(ketoacidosis)
Respiratory compensation for the acidosis
results in rapid shallow breathing (Kussmaul
respirations)
Ketones induce nausea and vomiting that
aggravate fluid and electrolyte loss already
existing in DKA.
 Acetone produces the fruity breath odor that is
characteristic of ketotic patients.
 Hyperglycemia, osmotic diuresis, serum
hyperosmolarity, and metabolic acidosis result
in severe electrolyte disturbances.
 The most characteristic disturbance is total body
potassium loss
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Potassium loss is caused by a shift of potassium
from the intracellular to the extracellular space
in an exchange with hydrogen ions that
accumulate extracellularly in acidosis.
Potassium is lost in urine because of osmotic
diuresis.
Patients with initial hypokalemia are considered
to have severe total body potassium depletion.
High serum osmolarity drives water from
intracellular to extracellular space causing
dilutional hyponatremia.
Sodium also is lost in the urine.
In the absence of insulintissues such as muscle,
fat, and liver do not take up glucose.
 Counterregulatory hormones, such as glucagon,
growth hormone, and catecholamines, enhance
triglyceride breakdown into free fatty acids and
gluconeogenesis.
 This causes the elevation in serum glucose level
in DKA.
 Beta-oxidation of these free fatty acids leads to
increased formation of ketone bodies.
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Metabolism in DKA shifts from the normal fed
state characterized by carbohydrate metabolism
to a fasting state characterized by fat
metabolism.
This results in metabolic acidosis as the ketone
bodies produced by beta-oxidation of free fatty
acids deplete extracellular and cellular acid
buffers.
Osmotic diuresis depletes sodium, potassium,
phosphates, and water, as well as ketones and
glucose.
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Typical free water loss in DKA is
approximately 6 liters or nearly 100 mL/kg of
body weight.
Half of this amount is derived from
intracellular fluid and precedes signs of
dehydration.
The other half is from extracellular fluid and is
responsible for signs of dehydration.
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Typical overall electrolyte loss:
 200-500 mEq/L of potassium
 300-700 mEq/L of sodium
 350-500 mEq/L of chloride.
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The combination of serum hyperosmolarity,
dehydration, and acidosis result in increased
osmolarity in brain cells that clinically
manifests as an alteration in the level of
consciousness.
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The most common causes for diabetic
ketoacidosis (DKA) are:
Underlying or concomitant infection (40%)
Missed insulin treatments (25%)
Newly diagnosed, previously unknown
diabetes (15%)
Other causes make up roughly 20% in the
various scenarios.
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Initial presentation of type 1 diabetes (25% of
patients)
Poor compliance with insulin
 Omission of insulin injections
 Lack of patient/guardian education
 Result of psychological stress, particularly in
adolescents
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Bacterial infection and intercurrent illness
Brittle diabetes
Insulin infusion catheter blockage
Mechanical failure of the insulin infusion pump
Idiopathic
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Intercurrent illness
 Myocardial infarction
 Pneumonia
 Prostatitis
 UTI
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Medications
 Corticosteroids
 Pentamidine, clozapine
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DKA also occurs in pregnant women, either
with preexisting diabetes or with diabetes
diagnosed during pregnancy.
Physiologic changes unique to pregnancy
provide a background for the development of
DKA.
DKA in pregnancy is a medical emergency, as
mother and fetus are at risk for morbidity and
mortality.
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Many of the underlying pathophysiologic
disturbances in DKA are directly measurable
and need to be monitored throughout the
course of treatment.
Close attention to clinical laboratory data
allows for management of the underlying
acidosis and hyperglycemia
This can prevent common, potentially lethal
complications such as hypoglycemia,
hyponatremia, and hypokalemia.
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Diabetic ketoacidosis
 Blood glucose over 300 mg/dL
 Bicarbonate level less than 15 mEq/L
 pH less than 7.30
 ketonemia and ketonuria
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Severe DKA
 pH less than 7.1
 Bicarbonate less than 5 mEq/L.
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Serial laboratory tests are critical, including
potassium, glucose, electrolytes, and, if
necessary, phosphorus.
Initial workup should include aggressive
volume, glucose, and electrolyte
management.
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Considerations
 High serum glucose levels may lead to dilutional
hyponatremia.
 High triglyceride levels may lead to factitious low
glucose levels.
 High levels of ketone bodies may lead to factitious
elevation of creatinine levels.
 Extracellular shift of potassium leads to normal or
elevated serum potassium, despite severely
depleted total body potassium.
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ICU or monitored bed
IVF NS TRA 1000cc/hr for total 20cc/kg
Insulin Drip at 0.1 cc/kg/hr
Blood tests for glucose every 1-2 h until
patient is stable, then every 6 h
Serum electrolyte determinations every 1-2 h
until patient is stable, then every 4-6 h
Initial arterial blood gas (ABG)
measurements, followed with bicarbonate as
necessary
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Blood beta-hydroxybutyrate levels measured by
a reagent strip and serum ketone levels assessed
by the nitroprusside reaction are equally
effective in diagnosing DKA in uncomplicated
cases.
 The Acetest and Ketostix products measure blood and
urine acetone and acetoacetic acid.
 They do not measure the more common ketone body,
beta-hydroxybutyrate
 The patient may have paradoxical worsening as the
latter is converted into the former during treatment.
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Specific testing for beta-hydroxybutyrate can
be performed by many laboratories.
Diagnosis of ketonuria requires adequate
renal function.
Ketonuria may last longer than the
underlying tissue acidosis.
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One study suggests that routine urine testing
for ketones is no longer necessary to
diagnose DKA.
Using capillary beta hydroxybutyrate offers a
distinct advantage of avoiding unnecessary
work-up.
Beta-hydroxybutyrate levels greater than 0.5
mmol/L are considered abnormal, and levels
of 3 mmol/L correlate with the need for
treatment for DKA.
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According to the 2011 Joint British Diabetes
Societies (JBDS) guideline for the management
of diabetic ketoacidosis:
 Capillary blood ketones should be measured in order
to monitor the response to DKA treatment.
 The method of choice is bedside measurement of
blood ketones using a ketone meter.
 In the absence of blood ketone measurement, venous
pH and bicarbonate should be used together with
bedside blood glucose monitoring to evaluate
treatment response
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In patients with DKA, arterial blood gases (ABGs)
frequently show typical manifestations of metabolic
acidosis, low bicarbonate, and low pH (< 7.2).
Venous pH may be used for repeat pH measurements.
Brandenburg and Dire found that pH on venous blood
gas in patients with DKA was 0.03 lower than pH on
ABG.
Because this difference is relatively reliable and not of
clinical significance, there is almost no reason to
perform the more painful ABG.
End tidal CO2 has been reported as a way to assess
acidosis as well.
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Serum potassium levels initially are high or within the reference range in
patients with DKA.
 This is due to the extracellular shift of potassium in spite of severely depleted
total body potassium.
 This needs to be checked frequently, as values drop very rapidly with
treatment.
 An ECG may be used to assess the cardiac effects of extremes in potassium
levels.
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The serum sodium level usually is low in affected patients.
 The osmotic effect of hyperglycemia moves extravascular water to the
intravascular space.
 For each 100 mg/dL of glucose over 100 mg/dL, the serum sodium level is
lowered by approximately 1.6 mEq/L.
 When glucose levels fall, the serum sodium level rises by a corresponding
amount.
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Additionally, serum chloride levels and phosphorus levels always are low
in these patients.
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If the potassium level is greater than 6 mEq/L,
do not administer potassium supplement.
If the potassium level is 4.5-6 mEq/L,
administer 10 mEq/h of potassium chloride.
If the potassium level is 3-4.5 mEq/L,
administer 20 mEq/h of potassium chloride.
Monitor serum potassium levels hourly, and
the infusion must be stopped if the potassium
level is greater than 5 mEq/L.
The monitoring of serum potassium must continue
even after potassium infusion is stopped in the case of
(expected) recurrence of hypokalemia.
 In severe hypokalemia, not starting insulin therapy is
advisable unless potassium replacement is under way;
this is to avert potentially serious cardiac dysrhythmia
that may result from hypokalemia.
 Potassium replacement should be started with initial
fluid replacement if potassium levels are normal or
low. Add 20-40 mEq/L of potassium chloride to each
liter of fluid once the potassium level is less than 5.5
mEq/L. Potassium can be given as follows: two thirds
as KCl, one third as KPO4.
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Even in the absence of infection, the CBC
count shows an increased white blood cell
(WBC) count in patients with diabetic
ketoacidosis. High WBC counts (>15 X 109/L)
or marked left shift may suggest underlying
infection.
BUN frequently is increased in patients with
diabetic ketoacidosis.
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Plasma osmolarity usually is increased (>290
mOsm/L) in patients with diabetic ketoacidosis.
 If plasma osmolarity cannot be measured directly, it
may be calculated with the following formula: plasma
osmolarity = 2 (Na + K) + BUN/3 + glucose/18.
 Urine osmolarity also is increased in affected patients.
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Patients with diabetic ketoacidosis who are in a
coma typically have osmolalities greater than
330 mOsm/kg H2 O.
If the osmolality is less than this in a patient who
is comatose, search for another cause.
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Urine and blood culture findings help to
identify any possible infecting organisms in
patients with diabetic ketoacidosis.
Elevated amylase may be seen in patients
with diabetic ketoacidosis, even in the
absence of pancreatitis.
If the patient is at risk for hypophosphatemia
(eg, poor nutritional status, chronic
alcoholism), then the serum phosphorous
level should be determined.
Chest radiography should be used to rule out
pulmonary infection such as pneumonia.
 An MRI is helpful in detecting early cerebral edema; it
should be ordered only if altered consciousness is
present.[
 The threshold should be low for obtaining a head CT
scan in children with diabetic ketoacidosis who have
altered mental status, as this may be caused by
cerebral edema.
 Many of the changes may be seen late on head
imaging and should not delay administration of
hypertonic saline or mannitol in those pediatric cases
where cerebral edema is suspected.
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DKA may be precipitated by a cardiac event, and the
physiological disturbances of DKA may cause cardiac
complications.
 An ECG should be performed every 6 hours during the first
day, unless the patient is monitored. An ECG may reveal
signs of acute myocardial infarction that could be painless
in patients with diabetes, particularly in those with
autonomic neuropathy.
 An ECG is also a rapid way to assess significant
hypokalemia or hyperkalemia. T-wave changes may
produce the first warning sign of disturbed serum
potassium levels. Low T wave and apparent U wave always
signify hypokalemia, while peaked T wave is observed in
hyperkalemia.
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Cerebral edema is a serious, major complication that
may evolve at any time during treatment of DKA and
primarily affects children. It is the leading cause of
DKA mortality in children.
Deterioration of the level of consciousness in spite of
improved metabolic state usually indicates the
occurrence of cerebral edema.
MRI usually is used to confirm the diagnosis.
Cerebral edema that occurs at initiation of therapy
tends to worsen during the course of treatment.
Mannitol or hypertonic saline should be available if
cerebral edema is suspected.
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0.5-1 g/kg intravenous mannitol may be given over the
course of 20 minutes and repeated if no response is seen
in 30-120 minutes.
If no response to mannitol occurs, hypertonic saline (3%)
may be given at 5-10 mg/kg over the course of 30 minutes.
Clinical cerebral edema is rare and carries the highest
mortality rate.
Although mannitol and dexamethasone (2-4 mg q6-12h)
frequently are used in this situation, no specific
medication has proven useful in such instances.
Recent research by Glaser et al indicated that cerebral
edema occurs in 1% of children with DKA, with a mortality
rate of 21% and neurologic sequelae in another 21% of
patients.
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Cardiac dysrhythmia may occur secondary to
severe hypokalemia and/or acidosis either
initially or as a result of therapy in patients
with DKA.
Usually, correction of the cause is sufficient to
treat cardiac dysrhythmia, but if it persists,
consultation with a cardiologist is mandatory.
Performing cardiac monitoring on patients
with DKA during correction of electrolytes
always is advisable.
Pulmonary edema may occur for the same
reasons as cerebral edema in patients with
diabetic ketoacidosis.
 Be cautious of possible overcorrection of fluid
loss, though it occurs only rarely.
 Although initial aggressive fluid replacement is
necessary in all patients, particular care must be
taken in those with comorbidities such as renal
failure or congestive heart failure.
 Diuretics and oxygen therapy often suffice for
the management of pulmonary edema.
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Nonspecific myocardial injury may occur in severe
DKA, which is associated with minute elevations of
myocardial biomarkers (troponin T and CK-MB) and
initial ECG changes compatible with myocardial
infarction (MI).
Acidosis and very high levels of free fatty acids could
cause membrane instability and biomarker leakage.
Coronary arteriography usually is normal, and
patients tend to recover fully without further evidence
of ischemic heart disease.
The presence of minute biomarker elevations and
ECG changes do not necessarily signify MI in DKA.
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Hypoglycemia
 In patients with diabetic ketoacidosis, hypoglycemia
may result from inadequate monitoring of glucose
levels during insulin therapy.
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Hypokalemia
 Hypokalemia is a complication that is precipitated by
failing to rapidly address the total body potassium
deficit brought out by rehydration and insulin
treatment, which not only reduces acidosis but
directly facilitates potassium reentry into the cell.
Managing DKA in the ICU during the first 24-48 hours
always is advisable.
 When treating patients with DKA, the following points
must be considered and closely monitored:
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 Correction of fluid loss with intravenous fluids
 Correction of hyperglycemia with insulin
 Correction of electrolyte disturbances, particularly potassium
loss
 Correction of acid-base balance
 Treatment of concurrent infection, if present
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It is essential to maintain extreme vigilance for any
concomitant process, such as infection, cerebrovascular
accident, myocardial infarction, sepsis, or deep venous
thrombosis.
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When the blood glucose falls below 14 mmol/l
(250 mg/dl), 10% glucose should be added to
allow the fixed-rate insulin to be continued.
If already taking, long-acting insulin
analogues such as insulin glargine (Lantus)
should be continued in usual doses.
The diabetes specialist team should be
involved as soon as possible
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Once the patient is stable, transfer to regular
hospital bed.
If new onset DM, calculate daily insulin dose
 0.3 units/kg/day for patients who are lean, on
hemodialysis, frail and elderly, insulin-sensitive, or
at risk for hypoglycemia
 0.4 units/kg/day for a patient at normal weight
 0.5 units/kg/day for overweight patients
 0.6 units/kg/day or more for patients who are
obese, on high-dose steroids or insulin-resistant
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Between 40% and 50% of that total dose
should be administered as basal, using
Lantus or other long-acting insulin.
The remainder is divided to be given as shortacting insulin (Humalog) prior to each meal.
Check sugars in the AM fasting and 2 hours
after each meal to evaluate the regimen.
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The overall mortality rate for DKA is 2% or less.
The presence of deep coma at the time of diagnosis,
hypothermia, and oliguria are signs of poor prognosis.
The prognosis of properly treated patients with
diabetic ketoacidosis is excellent, especially in
younger patients if intercurrent infections are absent.
The worst prognosis usually is observed in older
patients with severe intercurrent illnesses (eg,
myocardial infarction, sepsis, or pneumonia),
especially when these patients are treated outside an
intensive care unit.
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When DKA is treated properly, it rarely
produces residual effects.
With modern fluid management, the
mortality rate of DKA is about 2% per
episode.
Before the discovery of insulin in 1922, the
mortality rate was 100%.
In the last 20 years, mortality rates from DKA
have markedly decreased, from 7.96% to
0.67%.[10]
DKA accounts for 14% of all hospital admissions of
patients with diabetes and 16% of all diabetes-related
fatalities.
 A fetal mortality rate as high as 30% is associated with
DKA.
 The rate is as high as 60% in diabetic ketoacidosis
with coma.
 Fetal death typically occurs in women with overt
diabetes, but it may occur with gestational diabetes.
 In children younger than 10 years, diabetic
ketoacidosis causes 70% of diabetes-related fatalities.
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 Regular follow up
 Management of risk factors
 Patient/parent education