Diabetic Ketoacidosis

Diabetic ketoacidosis
Straight to the point of care
Last updated: Feb 07, 2020

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Etiology 4
Pathophysiology 5
Classification 6
Prevention 8
Primary prevention 8
Screening 8
Diagnosis 9
Case history 9
Step-by-step diagnostic approach 9
Risk factors 13
History & examination factors 14
Diagnostic tests 16
Differential diagnosis 19
Diagnostic criteria 20
Treatment 22
Step-by-step treatment approach 22
Treatment details overview 27
Treatment options 31
Follow up 70
Recommendations 70
Complications 71
Prognosis 71
Guidelines 72
Diagnostic guidelines 72
Treatment guidelines 72
References 73
Images 81
Disclaimer 85
Summary
◊ Diabetic ketoacidosis is characterized by a biochemical triad of hyperglycemia, ketonemia, and

acidemia, with rapid symptom onset.
◊ Common symptoms and signs include polyuria, polydipsia, polyphagia, weakness, weight loss,
tachycardia, dry mucous membranes, poor skin turgor, hypotension, and, in severe cases, shock.
◊ Successful treatment includes correction of volume depletion, hyperglycemia, electrolyte imbalances,

and comorbid precipitating events, with frequent monitoring.
◊ Complications of treatment include hypoglycemia, hypokalemia, hypoxemia, and rarely pulmonary

edema.
◊ Cerebral edema, a rare but potentially rapidly fatal complication, occurs mainly in children. It may be
prevented by avoiding overly rapid fluid and electrolyte replacement.
Diabetic ketoacidosis Basics
Definition
Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes that is potentially fatal and
requires prompt medical attention for successful treatment. It is characterized by absolute insulin deficiency
BASICS
and is the most common acute hyperglycemic complication of type 1 diabetes mellitus.[1]
Triad of DKA
Adapted with permission from: Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am. 1995;79:9-37
Epidemiology
In the US from 2000-2009, the rate of hospitalizations for DKA decreased overall, from 21.9 to 19.5 in 1000
persons with diabetes, but then increased from 2009-2014 to 30.2 in 1000 persons with diabetes.[7] In 2014,
rates of hospitalization for DKA were highest among people aged <45 years (44.3 in 1000 persons with
diabetes) and decreased with age (5.2 in 1000 persons with diabetes aged 45-64 years; 1.6 in 1000 65-74
years; and 1.4 in 1000 ≥75 years).[7]From 2000-2014, in-hospital mortality rates among people with DKA
consistently decreased, from 1.1% to 0.4%.[7] In 2014 in the US, about 207,000 emergency department
visits for people aged ≥18 years were for hyperglycemic crises (e.g., DKA, hyperglycemic hyperosmolar
state).[8]
Etiology
In DKA, there is a reduction in the net effective concentration of circulating insulin along with an elevation of
counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). These alterations
lead to extreme manifestations of metabolic derangements that can occur in diabetes. The two most common
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precipitating events are inadequate insulin therapy or infection. Underlying medical conditions such as
myocardial infarction or stroke that provoke the release of counter-regulatory hormones are also likely to
result in DKA in patients with diabetes. Drugs that affect carbohydrate metabolism, such as corticosteroids,
thiazides, pentamidine, sympathomimetic agents (e.g., dobutamine and terbutaline), second-generation
BASICS
antipsychotic agents, and immune checkpoint inhibitors may contribute to the development of DKA.[1] [9] [10]
The use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors has also been implicated in the development
of euglycemic DKA in patients with both type 1 and type 2 diabetes.[11] [12] [13] [14]
Pathophysiology
Reduced insulin concentration or action, along with increased insulin counter-regulatory hormones, leads to
the hyperglycemia, volume depletion, and electrolyte imbalance that underlie the pathophysiology of DKA.
Hormonal alterations in DKA lead to increased gluconeogenesis, hepatic and renal glucose production, and
impaired glucose utilization in peripheral tissues, which result in hyperglycemia and hyperosmolarity. Insulin
deficiency leads to release of free fatty acids from adipose tissue (lipolysis), hepatic fatty acid oxidation, and
formation of ketone bodies (beta-hydroxybutyrate and acetoacetate), which result in ketonemia and acidosis.
Studies have demonstrated the elevation of proinflammatory cytokines and inflammatory biomarkers (e.g.,
CRP), markers of oxidative stress, lipid peroxidation, and cardiovascular risk factors with hyperglycemic
crises. All of these parameters return to normal following insulin and hydration therapies within 24 hours of
hyperglycemic crises. Elevation of proinflammatory cytokines, and markers of lipid peroxidation and oxidative
stress, have also been demonstrated in non-diabetic patients with insulin-induced hypoglycemia.[15] The
observed proinflammatory and procoagulant states in hyperglycemic crises and hypoglycemia may be the
result of adaptive responses to acute stress and not hyperglycemia or hypoglycemia per se.[1] [15] [16] It
has also been postulated that ketosis-prone diabetes comprises different syndromes based on autoantibody
status, human leukocyte antigen (HLA) genotype, and beta-cell functional reserve.[17]
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Feb 07, 2020.
5
BASICS Diabetic ketoacidosis Basics
Pathogenesis of DKA and HHS; triggers include stress, infection, and

insufficient insulin. FFA: free fatty acid; HHS: hyperosmolar hyperglycemic state
From: Kitabchi AE, Umpierrez GE, Miles JM, et al. Diabetes Care. 2009,32:1335-43; used with permission
Classification
Clinical DKA classification[1]
Diagnostic criteria and classification:
Mild DKA
• Plasma glucose: >250 mg/dL

• Arterial pH: 7.25 to 7.30
• Serum bicarbonate: 15-18 mEq/L
• Urine ketone: positive
• Serum ketone: positive
• Effective serum osmolality: variable
• Anion gap: >10
• Mental status: alert.
Moderate DKA

• Arterial pH: 7.00 to <7.24
• Serum bicarbonate: 10 to <15 mEq/L
BASICS
• Anion gap: >12
• Mental status: alert and/or drowsy.
Severe DKA

• Arterial pH: <7.00
• Serum bicarbonate: <10 mEq/L
• Anion gap: >12
• Mental status: stupor and/or coma.
7
Diabetic ketoacidosis Prevention
Primary prevention
Patient education about management of their diabetes during periods of mild illness (sick-day management)
is vital for preventing DKA. This should include information on when to contact a healthcare professional,
blood glucose monitoring, use of insulin, and initiation of appropriate nutrition during illness. This information
should be reinforced with patients periodically. Patients should be advised to continue insulin and to seek
professional advice early in the course of the illness. Close follow-up is very important, as it has been shown
that 3-month visits to the endocrine clinic will reduce the number of emergency department admissions for
DKA.[1] [33] [34] Self-monitoring of ketones is also emerging as a potential strategy.[35]
SGLT-2 inhibitor-associated DKA in patients with type 2 diabetes is typically precipitated by insulin omission
or significant dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate
diets, or excessive alcohol intake. DKA prevention strategies should include withholding SGLT-2 inhibitors
when precipitants are present, and avoiding insulin omission or large insulin dose reduction.[36] [37]
Many cases can be prevented by better access to medical care, proper education, and effective
communication with a healthcare provider during an intercurrent illness. Adequate supervision by
family and healthcare provider may decrease the rates of hospitalization and mortality.[1] [38] Hospital
admission with DKA, and recurrent admissions in particular, may be considered a "red flag" for triggering
psychiatric assessment so that mental health problems can be addressed and further admissions with DKA
PREVENTION
prevented.[19]
Screening
If a patient is brought to the emergency department with signs and symptoms of hyperglycemia (polyuria,
polydipsia, and abdominal pain), volume depletion, acetone breath, and changes in mental status (even
without a history of diabetes), then plasma glucose and urine ketones should be checked. In the presence
of high plasma glucose and/or positive urine ketones, full diagnostic laboratory evaluations for DKA and
hyperosmolar hyperglycemic state should be performed.[1]
Diabetic ketoacidosis Diagnosis
Case history
Case history #1
A 20-year-old man is brought to the emergency department with abdominal pain, nausea, and vomiting
with increasing polyuria, polydipsia, and drowsiness since the day before. He was diagnosed with
type 1 diabetes 2 years previously. He mentions that he ran out of insulin 2 days ago. Vital signs at
admission are: BP 106/67 mmHg, heart rate 123 beats per minute, respiratory rate 32 breaths per
minute, temperature 98.8°F (37.1°C). On mental status examination, he is drowsy. Physical examination
reveals Kussmaul breathing (deep and rapid respiration due to ketoacidosis) with acetone odor and mild
generalized abdominal tenderness without guarding and rebound tenderness. Initial laboratory data are:
blood glucose 450 mg/dL, arterial pH 7.24, pCO₂ 25 mmHg, bicarbonate 12 mEq/L, WBC count 18,500/
microliter, sodium 128 mEq/L, potassium 5.2 mEq/L, chloride 97 mEq/L, BUN 32 mg/dL, creatinine 1.7
mg/dL, serum ketones strongly positive.
Other presentations
It is now well recognized that new-onset type 2 diabetes can manifest with DKA. These patients are
obese and have undiagnosed hyperglycemia, impaired insulin secretion, and insulin resistance. However,
after treatment of the acute hyperglycemic episode with insulin, beta-cell function and insulin effects
improve so these patients are able to discontinue insulin therapy and may be treated orally or by diet
alone, with 40% remaining insulin-independent 10 years following the initial episodes of DKA. These
patients do not have the typical autoimmune laboratory findings of type 1 diabetes.[2] This type of
diabetes has been labeled as "type 1 and ½" or "type 1 and a half" diabetes, "Flatbush" diabetes,
or "ketosis-prone" diabetes. Conversely, an extreme hyperosmolar state similar to hyperosmolar
hyperglycemic state (HHS) has been reported in combination with DKA in type 1 diabetes.[3] [4] [5] [6]
Step-by-step diagnostic approach
DIAGNOSIS
The symptoms of DKA usually develop rapidly over 1 day or less. DKA may be the initial presentation in
up to 25% of people with newly diagnosed diabetes. Hyperglycemia is a key diagnostic criterion for DKA;
however, a wide range of plasma glucose levels can be present on admission, and approximately 10% of
DKA patients present with glucose <250 mg/dL (“euglycemic DKA”).[1] Hyperosmolar hyperglycemic state
(HHS) is often discussed as a separate condition. However, DKA and HHS represent two points on the
spectrum of metabolic derangements in diabetes. In contrast to DKA, HHS may evolve insidiously over days
to weeks. Symptoms of hyperglycemia in both DKA and HHS include polyuria, polydipsia, weakness, and
weight loss.
Important factors to consider in the patient's past or current medical history include infection, myocardial
infarction, pancreatitis, stroke, acromegaly, hyperthyroidism, and Cushing syndrome, as these may be
precipitants or risk factors for DKA. In euglycemic DKA, pregnancy, starvation, concomitant alcohol use, and
sodium-glucose cotransporter 2 (SGLT-2) inhibitors have all been implicated in its etiology.[12] [39]
It is essential to take a full medication history, in particular looking for corticosteroids, thiazides, pentamidine,
sympathomimetics, second-generation antipsychotic agents, and immune checkpoint inhibitors, as these
affect carbohydrate metabolism and may participate in the development of hyperglycemic crises.[1] [25] [11]
9
[27] [40] Cocaine abuse may be an independent risk factor associated with recurrent DKA.[28] [10] SGLT-2
inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin), used for glycaemic control of type 2 diabetes, have
been the subject of an FDA warning about a risk for DKA.[29]
Physical exam
Physical signs of volume depletion include dry mucous membranes, poor skin turgor, tachycardia,
hypotension, and, in severe cases, shock. DKA patients may exhibit nausea, vomiting, Kussmaul
respiration, acetone breath, and, occasionally, abdominal pain. Abdominal pain may correlate with the
degree of acidosis in patients with DKA, and it may be confused with an acute abdominal crisis. Mild
hypothermia may be observed in some patients, due to peripheral vasodilation. Hyperthermia is not usual,
even in the presence of infection.[1] Mental status may be altered in DKA, varying from alert in mild DKA
to stupor and/or coma in severe DKA. In HHS, mental obtundation and coma are more frequent. Focal
neurologic signs (hemianopia and hemiparesis) and seizures may also be features in HHS.[1]
Initial laboratory evaluation

Plasma glucose
• Plasma glucose is typically >250 mg/dL with presence of acidosis and ketonemia. However, a
wide range of plasma glucose levels can be present on admission, and approximately 10% of DKA
patients present with glucose <250 mg/dL (euglycemic DKA).[1]
Urinalysis
• Positive for glucose and ketones. Other potential findings include leukocytes and nitrites in the
presence of infection, and myoglobinuria and/or hemoglobinuria in rhabdomyolysis.
Arterial and venous blood gases
• Arterial blood gas (ABG) shows a metabolic acidosis, which is essential for the diagnosis of DKA.
Arterial pH measurement is necessary for diagnosis of DKA, but venous pH is recommended for
monitoring treatment, due to the pain and risk of infection in obtaining frequent arterial samples.
DIAGNOSIS
A venous pH sample is usually 0.03 units lower than arterial pH, and this difference should be
considered.
• The pH varies from 7.00 to 7.30, and the arterial bicarbonate ranges from <10 mEq/L in severe
DKA to >15 mEq/L in mild DKA.
Capillary or serum ketones (beta-hydroxybutyrate)
• There are three main ketones that are produced in DKA that can be measured: acetone,
acetoacetate, and beta-hydroxybutyrate (BOHB).
• In early DKA, the acetoacetate concentration is low, but it is a major substrate for ketone
measurement by many laboratories (nitroprusside reaction method). Therefore, serum ketone
measurement by usual laboratory techniques has a high specificity, but low sensitivity for the
diagnosis of DKA; hence a negative test for serum ketones does not exclude DKA. Acetone is
rarely measured due to its volatile nature.[41] Conversely, BOHB is an early and abundant ketoacid
that can be the first signal of the development of DKA. Point-of-care BOHB testing is widely
available and is highly sensitive and specific for the diagnosis of DKA.[42]
• During the treatment of DKA, BOHB is converted to acetoacetate, which is detected by the
nitroprusside method. Therefore, the increase in acetoacetate during the treatment of DKA may
mistakenly indicate a worsening of ketonemia.
• Another potential source of error in detecting ketone bodies is the patient's medications. Some
drugs, such as the ACE inhibitor captopril, contain sulfhydryl groups that can react with the reagent
in the nitroprusside test and give a false-positive result. Therefore, clinical judgement and other
biochemical tests will be required in patients who are receiving such medications.[1]
BUN
• Typically increased due to volume depletion.

Serum electrolytes[1] [18]
• Sodium: serum sodium is usually low due to osmotic reflux of water from the intracellular to
extracellular space in the presence of hyperglycemia. Total sodium deficit is 7 to 10 mEq/
kg. Hypernatremia in the presence of hyperglycemia indicates profound volume depletion.
Alternately, in the presence of high serum chylomicron concentration, pseudonormoglycemia and
pseudohyponatremia may occur.
• Calculation of the corrected sodium: the corrected serum sodium level should be evaluated as this
is used to guide appropriate fluid replacement. The equation for conventional units is: corrected
sodium (mEq/L) = measured sodium (mEq/L) + 0.016 (glucose [mg/dL] - 100).
• Potassium: total potassium deficit is 3 to 5 mEq/kg. Serum potassium is usually elevated due to
extracellular shift of potassium caused by insulin insufficiency, hypertonicity, and acidemia, but the
total body potassium concentration is low due to increased diuresis. Therefore, low potassium level
on admission indicates severe total-body potassium deficit.
• Chloride: usually low. The total chloride deficit is 3 to 5 mEq/kg.
• Magnesium: usually low. The total body deficit of magnesium is usually 1 to 2 mEq/kg.
• Calcium: usually low. Total body calcium deficit is usually about 1 to 2 mEq/kg.
• Phosphate: despite the total body phosphate deficit averaging 1.0 mmol/kg, serum phosphate is
often normal or increased at presentation, but decreases with insulin therapy.
DIAGNOSIS
Anion gap
• The calculated serum anion gap in mEq/L (serum sodium - [serum chloride + bicarbonate]) gives
an estimate of the unmeasured anions in plasma, which in DKA are ketoacids. The anion gap is
typically more than 10 to 12 mEq/L in DKA.
• Normalization of the anion gap reflects correction of the ketoacidosis as these anions are removed
from the blood.
Creatine phosphokinase
• Rhabdomyolysis is common in cocaine users with concurrent DKA, and creatine phosphokinase
levels should be assessed in known or suspected cocaine users who present with DKA.[28]
• In rhabdomyolysis, pH and serum osmolality are usually mildly elevated and plasma glucose and
ketones are normal. Myoglobinuria and/or hemoglobinuria are detected on urinalysis.
Serum lactate
• Measured to exclude lactic acidosis. Lactate levels are normal in DKA but elevated in lactic
acidosis.
11
Liver function tests (LFTs)
• Usually normal, and are used to screen for an underlying hepatic precipitant. Abnormal LFTs
indicate underlying liver disease such as fatty liver, or other conditions such as congestive heart
failure.
Serum amylase and lipase
• Amylase is elevated in the majority of patients with DKA, but this may be due to nonpancreatic
sources such as parotid glands.
• Serum lipase is usually normal and may be beneficial in differentiating pancreatitis in patients with
elevated amylase level. However, mildly elevated serum lipase level in the absence of pancreatitis
has also been reported in patients with DKA.[1]
Plasma osmolality
• This is variable in DKA.

CBC with differential
• Leukocytosis is present in hyperglycemic crises and correlates with blood ketone levels. However,
leukocytosis >25,000/microliter may indicate infection and requires further evaluations.[1]
Additional tests
ECG
• Used to exclude myocardial infarction (MI) as a precipitant or to look for cardiac effects of
electrolyte disturbances (usually of potassium). Evidence of MI includes Q waves or ST segment
changes. Evidence of hypokalemia (U waves) or hyperkalemia (tall T waves) may be present.
• A high index of suspicion for MI should be maintained as diabetic patients often present with
atypical symptoms.
DIAGNOSIS
Chest x-ray
• Indicated to exclude pneumonia. In pneumonia, may show typical changes of pneumonia including
infiltration, consolidation, effusions, and cavitation.
Blood, urine, or sputum cultures
• Should be obtained if there are signs of infection such as chills, constitutional upset (e.g., fatigue,
confusion, anxiety), or symptoms and signs of specific infections. The most common precipitating
infections are pneumonia and urinary tract infections. Patients are usually normothermic or
hypothermic due to peripheral vasodilation so fever may not be seen.
Cardiac biomarkers
• Usually normal, but are elevated if MI is the precipitant. A high index of suspicion should be
maintained as diabetic patients often present with atypical symptoms.
Typical deficits in mild DKA

Typical deficits[18]
Mild DKA:
• Total water (L): 6

• Water (mL/kg): 100
• Na+ (mEq/kg): 7 to 10
• Cl- (mEq/kg): 3 to 5
• K+ (mEq/kg): 3 to 5
• PO4 (mmol/kg): 5 to 7
• Mg++ (mEq/kg): 1 to 2
• Ca++ (mEq/kg): 1 to 2.
Notes: Deficits based on per kg of body weight.
Risk factors
Strong
inadequate or inappropriate insulin therapy
• Reduction in the net effective concentration of insulin leads to impaired carbohydrate, lipid, and
ketone metabolism in DKA. Decreased insulin results in increased gluconeogenesis, accelerated
glycogenolysis, and impaired glucose utilization by peripheral tissues.[1]
• Non-compliance with insulin therapy has been found to be the leading precipitating factor in black
people and is present in over 30% of patients with DKA.[18] [9] Psychological and social factors may
impact on glycemic control, and low socio-economic status is correlated with a higher risk for DKA.[19]
[20]
infection
• The most common precipitating factor in DKA is infection. Increased counter-regulatory hormones,
particularly epinephrine, as a systemic response to infection lead to insulin resistance, increased
DIAGNOSIS
lipolysis, ketogenesis, and volume depletion, which may contribute to the development of
hyperglycemic crises in patients with diabetes.[1]
myocardial infarction#
• Underlying cardiovascular events, particularly myocardial infarction, provoke the release of counter-
regulatory hormones that are likely to result in DKA in patients with diabetes.[1] [21]
Weak
pancreatitis
• Medical conditions such as pancreatitis, characterized by increased levels of counter-regulatory
hormones and compromised access to water and insulin, may contribute in the development of
hyperglycemic crises.[1] [22]
stroke
• Acute medical events such as stroke, with increased levels of counter-regulatory hormones and
compromised access to water and insulin, may contribute to the development of hyperglycemic
crises.[1]
13
acromegaly
• Hormonal derangements in some endocrine glands lead to increased counter-regulatory hormones
and development of DKA in patients with concomitant diabetes.[23]
hyperthyroidism
• Hormonal derangements in some endocrine glands lead to increased counter-regulatory hormones
and development of DKA in patients with concomitant diabetes.[24]
drugs (e.g., corticosteroids, thia zides, pentamidine, sympathomimetics,

second-generation antipsychotics, cocaine, immune check point inhibitors,
or SGLT-2 inhibitors)
• Drugs that affect carbohydrate metabolism may precipitate hyperglycemic crises.[25] [11] [26]
[27] Cocaine abuse may be an independent risk factor associated with recurrent DKA.[28] [10]
• Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin),
used for glycemic control of type 2 diabetes, have been the subject of an FDA warning about a risk for
DKA.[29]
• Immune checkpoint inhibitor therapy for cancer (PD-1 and PD-L1 blocking antibodies such as
nivolumab, pembrolizumab, and avelumab) appears to be associated with a risk for DKA and type 1
diabetes mellitus.[30] [31]
Cushing syndrome
• Hypercortisolism leads to insulin resistance and may occasionally precipitate DKA in patients with
concomitant diabetes; it more commonly precipitates hyperosmolar hyperglycemic state.
Hispanic or black ancestry

• Ancestry plays a role in ketosis-prone diabetes, with DKA a presenting manifestation of undiagnosed
type 2 diabetes in young adults. Approximately 80% of obese black patients with DKA have type
2 diabetes, characterized by higher insulin secretion, the absence of autoimmune markers, and a
lack of human leukocyte antigen (HLA) genetic association compared with lean patients with type 1
DIAGNOSIS
diabetes.[3]
bariatric surgery
• DKA has been reported in patients with type 1 diabetes who have had bariatric surgery.[32]
History & examination factors

Other diagnostic factors
polyuria (common)
• Symptom of hyperglycemia.
polyphagia (common)
polydipsia (common)
weight loss (common)
weakness (common)
nausea or vomiting (common)

• Abdominal pain, nausea, and vomiting in DKA correlate with the degree of acidosis and may be
confused with acute abdominal crisis.[1]
abdominal pain (common)

• Abdominal pain, nausea, and vomiting in DKA correlate with the degree of acidosis and may be
confused with acute abdominal crisis.[1]
dry mucous membranes (common)

• Sign of volume depletion.
poor skin turgor (common)

sunken eyes (common)

tachycardia (common)
hypotension (common)
Kussmaul respiration (common)
DIAGNOSIS
• Rapid and deep respiration due to acidosis. Common in DKA.
acetone breath (common)

• Sign of ketosis. Common in DKA.
altered mental status (common)

• Mental status may be altered, and varies from alert in mild DKA to stupor/coma in severe DKA. Studies
have shown that acidosis is independently associated with altered sensorium in DKA patients, but
hyperosmolarity and serum ketone levels are not. Combination of hyperosmolarity and acidosis
predicts altered sensorium with good sensitivity (61%) and specificity (87%) in DKA patients.[43]
hypothermia (uncommon)
• Although concomitant infection is common, patients usually are normothermic or hypothermic due to
peripheral vasodilation. Severe hypothermia is a poor prognostic sign.[44]
15
Diagnostic tests
1st test to order
Test Result
plasma glucose elevated
• A plasma glucose test should be performed as an initial laboratory
evaluation. In DKA, it is usually >250 mg/dL with acidosis and
ketonemia.
• However, 10% of DKA patients present with blood glucose <250 mg/
dL, which is termed euglycemic DKA.[1]
ABG pH varies from 7.00 to
7.30 in DKA; arterial
• Acidosis is essential for the diagnosis of DKA. Arterial pH
bicarbonate ranges from
measurement is necessary for diagnosis of DKA, but venous pH is
<10 mEq/L in severe DKA
recommended for monitoring treatment, due to the pain and risk of
infection in obtaining frequent arterial samples. A venous pH sample to >15 mEq/L in mild DKA
is usually 0.03 units lower than arterial pH, and this difference should
be considered.
• In hyperosmolar hyperglycemic state, the arterial pH is usually >7.30
and the arterial bicarbonate is >15 mEq/L.[1]
capillary or serum ketones beta-hydrox ybutyrate
elevated ≥3.8 mmol/L in
• There are three main ketones that are produced in DKA that can be
measured: acetone, acetoacetate, and beta-hydroxybutyrate (BOHB). adults or ≥3.0 mmol/L in
children
• In early DKA, acetoacetate concentration is low, but it is a
major substrate for ketone measurement by many laboratories
(nitroprusside reaction method). Therefore, serum ketone
measurement by usual laboratory techniques has a high specificity,
but low sensitivity for the diagnosis of DKA; hence a negative test for
serum ketones does not exclude DKA. Acetone is rarely measured
due to its volatile nature.[41] Conversely, BOHB is an early and
abundant ketoacid that can be the first signal of the development of
DKA. Point-of-care BOHB testing is widely available and is highly
DIAGNOSIS
sensitive and specific for the diagnosis of DKA.[42]

• During the treatment of DKA, BOHB is converted to acetoacetate,
which is detected by the nitroprusside method. Therefore, the
increase in acetoacetate during the treatment of DKA may mistakenly
indicate a worsening of ketonemia.
• Another potential source of error in detecting ketone bodies is
the patient's medications. Some drugs, such as the ACE inhibitor
captopril, contain sulfhydryl groups that can react with the reagent
in the nitroprusside test and give a false-positive result. Therefore,
clinical judgement and other biochemical tests will be required in
patients who are receiving such medications.[1]
urinalysis positive for glucose and
ketones; positive for
• Glucose and ketones are typical findings in DKA.[1]
leukocytes and nitrites in
the presence of infection
serum BUN elevated

• Increased due to volume depletion.[1]
serum creatinine elevated
• Increased due to volume depletion.[1]
Test Result
serum sodium usually low
• Serum sodium is usually low due to osmotic reflux of water from the
intracellular to extracellular space in the presence of hyperglycemia.
Total sodium deficit is 7 to 10 mEq/kg. Hypernatremia in the presence
of hyperglycemia in DKA indicates profound volume depletion.
Alternately, in the presence of high serum chylomicron concentration,
pseudonormoglycemia and pseudohyponatremia may occur in DKA.
• The corrected serum sodium level should be evaluated as this is used
to guide appropriate fluid replacement. The equation for conventional
units is: corrected sodium (mEq/L) = measured sodium (mEq/L) +
0.016 (glucose [mg/dL] - 100).[1] [18]
serum potassium usually elevated
• Total potassium deficit is 3 to 5 mEq/kg. Serum potassium is
usually elevated due to extracellular shift of potassium caused
by insulin insufficiency, hypertonicity, and acidemia, but the total
body potassium concentration is low due to increased diuresis.
Therefore, low potassium level on admission indicates severe total-
body potassium deficit.[1] [18]
serum chloride usually low
• Total chloride deficit is 3 to 5 mEq/kg.[1] [18]
serum magnesium usually low
• Total body deficit of magnesium is usually 1 to 2 mEq/kg.[1] [18]
serum calcium usually low
• Total body calcium deficit is usually about 1 to 2 mEq/kg.[1] [18]
serum phosphate normal or elevated
• Despite the total body phosphate deficit averaging 1.0 mmol/kg,
serum phosphate is often normal or increased at presentation, but
decreases with insulin therapy.[1] [18]
anion gap calculation elevated anion gap (>10-12
DIAGNOSIS
• Anion gap is calculated by subtracting the sum of serum chloride and mEq/L)
bicarbonate from measured sodium concentration. [1]
serum creatine phosphokinase elevated in
rhabdomyolysis
• In patients with history of cocaine abuse and DKA, rhabdomyolysis
is common; therefore, checking creatine phosphokinase level can be
initially assessed in patients with DKA if clinically indicated.
• In rhabdomyolysis, pH and serum osmolality are usually mildly
elevated and plasma glucose and ketones are normal. Myoglobinuria
and/or hemoglobinuria are detected in urinalysis.[1] [18]
serum lactate elevated in lactic acidosis
• Plasma glucose and serum ketones are normal in lactic acidosis.
Serum lactate is >5 mmol/L in lactic acidosis.[1]
LFT usually normal
• Used to identify underlying diseases such as fatty liver or congestive
heart failure.[1]
serum amylase usually elevated due to
extrapancreatic sources
• Amylase is elevated in majority of patients with DKA, but this may be
due to nonpancreatic sources such as parotid glands.[1]
17
Test Result
serum lipase usually normal
• Serum lipase may be beneficial in differentiating pancreatitis in
patients with elevated amylase level. However, mildly elevated serum
lipase level in the absence of pancreatitis has also been reported in
patients with DKA.[1]
serum osmolality variable
• The serum osmolality is variable in DKA but is >320 mOsm/kg in
hyperosmolar hyperglycemic state.[1]
CBC elevated white cell count
• Leukocytosis is present in hyperglycemic crises and correlates with
blood ketone levels. However, leukocytosis >25,000/microliter may
indicate infection and requires further evaluations.[1]
Other tests to consider
Test Result
chest x-ray may be compatible with
pneumonia
• The most common infections are pneumonia and urinary tract
infections.[1]
ECG may show evidence of MI
or hyper- or hypokalemia
• If clinically indicated, should be performed for identification of the
precipitating cardiovascular diseases, such as myocardial infarction
(MI) or severe electrolyte abnormalities.[1]
• Evidence of MI includes Q waves or ST segment changes.
• Evidence of hypokalemia (U waves) or hyperkalemia (tall T waves)
may be present.[1]
cardiac biomarkers may be elevated in the
presence of MI
• MI is a common precipitant of DKA in diabetic patients.[1]
DIAGNOSIS
blood, urine, or sputum cultures positive in the presence of

infection
• If indicated clinically, further sepsis workup should be performed.[1]
Differential diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Hyperosmolar • Patients are typically older • Serum glucose is >600 mg/
hyperglycemic state (HHS) than patients with DKA and dL. Serum osmolality is
are usually patients with type usually >320 mOsm/kg.
2 diabetes. Older nursing • Urine ketones are normal or
home residents with poor only mildly positive. Serum
fluid intake are at high risk. ketones are negative.
• Symptoms evolve insidiously • Anion gap is variable but
over days to weeks. typically <12 mEq/L.
• Mental obtundation • Total chloride deficit is 5 to
and coma are more 15 mEq/kg.
frequent. Focal neurologic • ABG: arterial pH is typically
signs (hemianopia and >7.30, whereas in DKA it
hemiparesis) and seizures ranges from 7.00 to 7.30.
are also seen. Seizures may Arterial bicarbonate is >15
be the dominant clinical mEq/L.
features.[1]
Lactic acidosis • The presentation is identical • Serum lactate >5 mmol/L.[1]

to that of DKA. In pure
lactic acidosis, the serum
glucose and ketones should
be normal and the serum
lactate concentration should
be elevated.
Starvation ketosis • Starvation ketosis • The blood glucose is usually

results from inadequate normal. Although the urine
carbohydrate availability can have large amounts of
resulting in physiologically ketones, the blood rarely
appropriate lipolysis and does. Arterial pH is normal
DIAGNOSIS
ketone production to provide and the anion gap is at most
fuel substrates for muscle. mildly elevated.[1]
Alcoholic ketoacidosis • Classically, these are people • In isolated alcoholic

with long-standing alcohol ketoacidosis, the metabolic
use disorder for whom acidosis is usually mild
ethanol has been the main to moderate in severity.
caloric source for days to The anion gap is elevated.
weeks. The ketoacidosis Serum and urine ketones
occurs when for some are always present. Blood
reason alcohol and caloric alcohol may be undetectable
intake decreases. and the patient may be
hypoglycemic.[1]
Salicylate poisoning • Can be differentiated by • The plasma glucose is

history and laboratory normal or low, ketones
investigation. Salicylate are negative, osmolality
intoxication produces an is normal, and salicylates
anion gap metabolic acidosis are positive in blood and/
usually with a respiratory or urine. It should be noted
alkalosis. that salicylates may cause
false-positive or false-
19
Condition Differentiating signs / Differentiating tests

symptoms
negative urinary glucose
determination.[1]
Ethylene glycol/methanol • Methanol and ethylene glycol • Methanol/ethylene glycol

intoxication also produce an anion gap serum levels are elevated.
metabolic acidosis without They can produce an
hyperglycemia or ketones. increase in the measured
serum osmolality.[1]
Uremic acidosis • This is characterized by • Elevated BUN usually

markedly elevated BUN >200 mg/dL and elevated
and creatinine with normal creatinine usually >10 mg/
plasma glucose. The pH and dL.[1]
anion gap are usually mildly
abnormal.
Diagnostic criteria
Hyperglycemic crises in adult patients with diabetes: a consensus
statement from the American Diabetes Association[1]
Plasma glucose (mg/dL)
• >250 in DKA.
Arterial pH
• 7.25 to 7.3 in mild DKA

• 7.00 to <7.24 in moderate DKA
• <7.00 in severe DKA.
DIAGNOSIS
Serum bicarbonate (mEq/L)
• 15-18 in mild DKA

• 10-15 in moderate DKA
• <10 in severe DKA.
Urine and serum ketones (nitroprusside reaction method)
• + in DKA.
Effective serum osmolality (mOsm/kg)
• variable in DKA.
Anion gap (mEq/L)
• >10 in mild DKA

• >12 in moderate and severe DKA.
Mental status
• alert in mild DKA

• alert/drowsy in moderate DKA
• stupor/coma in severe DKA.[1]
The most widely used diagnostic criteria for DKA are plasma glucose >250 mg/dL, arterial pH <7.3, and
presence of ketonemia and/or ketonuria. However, severity of DKA or the required number of criteria for
diagnosis have not been officially stated, and the above-mentioned classification has been based heavily on
prospective studies of DKA.[1]
DIAGNOSIS
21
Diabetic ketoacidosis Treatment
Step-by-step treatment approach

The main goals of treatment are:
• Restoration of volume deficits

• Resolution of hyperglycemia and ketosis/acidosis
• Correction of electrolyte abnormalities (potassium level should be >3.3 mEq/L before initiation of
insulin therapy; use of insulin in a patient with hypokalemia may lead to respiratory paralysis, cardiac
arrhythmias, and death)
• Treatment of the precipitating events and prevention of complications.
It must be emphasized that successful treatment requires frequent monitoring of clinical and laboratory
parameters to achieve resolution criteria. A treatment protocol and a flow sheet for recording the treatment
stages and laboratory data should be maintained.[1] [46] [47] [48]
Initial and supportive treatment

The majority of patients present to the emergency department, where treatment should be initiated. There
are several important steps that should be followed in early management:
• Fluid therapy should be started immediately after initial laboratory evaluations.

• Infusion of isotonic solution of 0.9% sodium chloride at a rate of 1.0 to 1.5 L/hour should be used
for the first hour of fluid therapy.
Indications for admission to the intensive care unit (ICU) are hemodynamic instability or cardiogenic
shock, altered mental status, respiratory insufficiency, severe acidosis, and hyperosmolar state with
coma.
The diagnosis of hemodynamic instability should made by observing for hypotension and clinical signs
of poor tissue perfusion, including oliguria, cyanosis, cool extremities, and altered mental state. After
admission to ICU, central venous and arterial lines are required, with continuous percutaneous oximetry.
Oxygenation and airway protection are critical. Intubation and mechanical ventilation are commonly
required, with constant monitoring of respiratory parameters. Nasogastric suctioning is always performed
because of frequent ileus and danger of aspiration.
Initial management in hemodynamically unstable patients includes fluid resuscitation to correct

hypovolemia and hypotension, close monitoring, and vasopressor therapy. Dopamine is the vasopressor
of choice, given in an intravenous infusion whose rate is adjusted according to blood pressure and other
hemodynamic parameters. If the patient remains hypotensive despite moderate doses of dopamine, a
direct vasoconstrictor (e.g., norepinephrine) should be started and titrated to maintain a mean arterial
pressure of 60 mmHg.[1] [52]
Fluid therapy
Fluid deficit averages 6 liters.[53] After the initial management, continuous fluid therapy should be started.
The goal is the restoration of fluid loss. Correction of fluid deficits should be undertaken gradually over
TREATMENT
12-24 hours, as overly rapid correction can result in the patient developing cerebral edema.[54] [55]
After initial therapy with 1.0 to 1.5 L of isotonic solution (0.9% NaCl) for the first hour of admission in
all patients, hydration status should be evaluated clinically. The presence of orthostatic hypotension or
supine hypotension with dry mucous membranes and poor skin turgor indicates severe volume depletion,
which should be treated by infusion of 0.9% NaCl at the rate of 1.0 L/hour until signs of severe volume
depletion are resolved. These patients then continue to receive fluid therapy as for mild volume depletion,
based on the corrected serum sodium level.
In patients with mild volume depletion (characterized by an absence of hypotension), corrected serum
sodium level should be evaluated (corrected sodium [mEq/L] = measured sodium [mEq/L] + 0.016
[glucose (mg/dL) - 100]).
• In hyponatremic patients: 0.9% NaCl should be started at 250-500 mL/hour and when the plasma
glucose reaches 200 mg/dL, fluid therapy should be changed to 5% dextrose with 0.45% NaCl at
150-250 mL/hour.[1] [52]
• In hypernatremic or eunatremic patients, 0.45% NaCl at 250-500 mL/hour is recommended and
when plasma glucose reaches 200 mg/dL, it should be changed to 5% dextrose with 0.45% NaCl at
150-250 mL/hour.[1] [40] [52] [56]
Insulin therapy
The goal is the steady but gradual reduction of serum glucose and plasma osmolality by low-dose insulin
therapy, in order to reduce the risk of treatment complications including hypoglycemia and hypokalemia.
Patients should receive a continuous intravenous infusion of regular insulin after exclusion of hypokalemia
(i.e., potassium level should be >3.3 mEq/L before initiation of insulin therapy). Two alternative low-dose
regimens are recommended by current guidelines.[1] [45] The first option is a continuous intravenous
infusion of regular insulin at a dose of 0.14 units/kg/hour (approximately 10 units/hour in a 70 kg patient)
with no initial bolus.[1] This is based on studies that show the use of low-dose regular insulin administered
by intravenous infusion is sufficient for the treatment of DKA, provided the dose is above 0.1 units/kg/hour.
The alternative regimen involves an initial intravenous bolus dose of 0.1 units/kg followed by a continuous
infusion at a dose of 0.1 units/kg/hour.[53] These low-dose insulin therapy protocols decrease plasma
glucose concentration at a rate of 50 to 75 mg/dL/hour.[1]
If plasma glucose does not fall by at least 10% or 50 mg/dL in the first hour of insulin infusion, then a dose
of 0.14 units/kg of regular insulin should be administered as an intravenous bolus and the continuous
insulin infusion rate should be continued (either 0.1 units/kg/hour or 0.14 units/kg/hour depending on the
regimen selected).[1] [53] Insulin injection by a sliding scale is no longer recommended. When serum
glucose is <200 mg/dL, the infusion can be reduced to 0.02 to 0.05 units/kg/hour, at which time dextrose
may be added to the intravenous fluids.[1] [53] The rate of insulin infusion (or the dextrose concentration)
should then be adjusted to maintain a plasma glucose level of between 150-200 mg/dL.[1]
Patients with severe DKA (plasma glucose >250 mg/dL, arterial pH <7.00, serum bicarbonate <10 mEq/
L), hypotension, anasarca (severe generalized edema), or associated severe critical illness should be
managed with intravenous regular insulin in the ICU using the regimen described above.[1] [57] [58]
[59] Patients with mild to moderate DKA (plasma glucose >250 mg/dL, arterial pH 7.00 to 7.30, serum
bicarbonate 10-18 mEq/L) that is not complicated by acute myocardial infarction, congestive heart
failure, end-stage renal or hepatic failure, steroid use, or pregnancy, may be given rapid-acting insulin
subcutaneously as an alternative to intravenous regular insulin.[60] [61] [62] This has been demonstrated
TREATMENT
to be safe and effective from studies in adults in one center.[1] A suggested protocol would be an initial
subcutaneous injection of rapid-acting insulin at a dose of 0.3 units/kg, followed 1 hour later by another
subcutaneous injection of 0.2 units/kg. Thereafter, they should receive 0.2 units/kg every 2 hours until
blood glucose becomes <250 mg/dL. At this point, the insulin dose should be decreased by half to 0.1
units/kg every 2 hours until the resolution of DKA.[58] Until the results of these studies are replicated in
23
multicenter trials, the administration of continuous intravenous infusion of regular insulin should remain
the preferred route because of its short half-life and easy titration (compared with the delayed onset of
action and prolonged half-life of subcutaneously administered insulin). However, in places where there are
increased waiting times for ICU admission or with limited medical resources, the use of insulin analogs
for the treatment of mild uncomplicated DKA episodes can be considered in outpatient, general wards, or
emergency departments.
Management of adult DKA. Abbreviations: blood glucose (BG); diabetic

ketoacidosis (DKA); hour (h); intravenous (IV); subcutaneous (SC)
Image created BMJ Knowledge Centre based on Gosmanov AR, Gosmanova
EO, Dillard-Cannon E. Management of adult diabetic ketoacidosis. Diabetes,
Metabolic Syndrome and Obesity: Targets and Therapy. 2014;7:255-64.
Potassium therapy
Insulin therapy and correction of acidemia and hyperosmolality will drive potassium into cells, which may
cause serious hypokalemia. The goal, therefore, is to correct the actual potassium deficits and thereby
prevent fatal complications of hypokalemia, including respiratory paralysis and cardiac dysrhythmia.
Insulin therapy should be withheld until the serum potassium level reaches 3.3 mEq/L. Likewise, if plasma
potassium falls below 3.3 mEq/L at any point during therapy, insulin should be stopped and potassium
TREATMENT
replaced intravenously. In all patients with a serum potassium level <5.3 mEq/L and an adequate urine
output of >50 mL/hour, 20-30 units (mEq) of potassium should be added to each liter of infusion fluid
to prevent hypokalemia caused by insulin therapy. If potassium level is >5.3 mEq/L, replacement is not
needed but potassium level should be checked every 2 hours.[1]
Bicarbonate therapy
Bicarbonate use in DKA remains controversial. At arterial blood pH >7.0, administration of insulin blocks
lipolysis and resolves ketoacidosis without the need to add bicarbonate. Administering bicarbonate
therapy in these patients may result in increased risk of hypokalemia, decreased tissue oxygen uptake,
and cerebral edema.
Bicarbonate therapy may be used in adult patients with an arterial blood pH <7 in DKA, although data
are limited.[63] Based on studies in adult patients with an arterial blood pH of 6.9 to 7.0, 50 mmol sodium
bicarbonate in 200 mL sterile water with 10 mEq potassium chloride (KCl) may be administered over 1
hour until pH is >7.0.
In adult patients with pH <6.9, it is recommended that 100 mmol sodium bicarbonate in 400 mL sterile
water (an isotonic solution) with 20 mEq KCl be administered at a rate of 200 mL/hour for 2 hours until pH
>7.0. For monitoring of treatment, venous pH is sufficient and should be checked at least each hour in this
setting. Treatment should be repeated every 2 hours until pH >7.0.
Bicarbonate therapy as well as insulin therapy lowers serum potassium; therefore, KCl is added to isotonic
bicarbonate infusion.[1] [64]
TREATMENT
25
Algorithm for the management of potassium and bicarbonate

Modified from: Kitabchi AE, Umpierrez GE, Miles JM, et al. Diabetes Care. 2009,32:1335-43
Phosphate therapy
Despite total body phosphate deficits in DKA that average 1.0 mmol/kg of body weight, serum phosphate
is often normal or increased at presentation, but decreases with insulin therapy. Previous studies have
failed to show any beneficial effects of phosphate replacement in DKA patients. Therefore, routine
replacement of phosphate is not recommended.
TREATMENT
However, to avoid cardiac, respiratory, and skeletal muscle dysfunction, careful phosphate therapy may be
indicated in patients with cardiac dysfunction (e.g., with signs of left ventricular dysfunction), symptomatic
anemia, or respiratory depression (e.g., decreased oxygen saturation), and in those with confirmed
hypophosphatemia (serum phosphate concentration <1.0 mg/dL).[1]
Monitoring of therapy
Monitoring of respiratory parameters and hemodynamic status are essential in hemodynamically unstable
patients.
Subsequent to initial laboratory evaluation, serum glucose and electrolytes are measured at least hourly;
calcium, magnesium, and phosphate are checked every 2 hours, and BUN, creatinine, and ketones every
2-6 hours, depending on the patient's clinical condition and response to therapy.
Serial beta hydroxybutyrate (BOHB) measurements may aid monitoring of the response to treatment
in DKA. However, measurement of ketone bodies, in the absence of a meter with capacity to measure
BOHB, is not recommended. BOHB is converted to acetoacetate, which is detected by the nitroprusside
method, during the treatment of DKA. Therefore, the increase in acetoacetate during DKA treatment may
Present evidence suggests monitoring bicarbonate, anion gap, and pH to reflect the response to therapy.
A flow sheet classifying these findings as well as mental status, vital signs, insulin dose, fluid and
electrolytes therapies, and urine output allows easy analysis of response to therapy and resolution of
crises. Metabolic panel measurement during DKA therapy provides dynamic information on the changes
in renal function and sodium level.
Management and monitoring should continue until resolution of DKA. The criteria for resolution are:[1]
• plasma glucose is <200 mg/dL (at this point, insulin can be decreased by 50%)
• serum bicarbonate is >18 mEq/L
• venous pH is >7.3
• anion gap is <10.
Treatment details overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
TREATMENT
27
Acute ( summary )
severe volume depletion
serum potassium <3.3 1st intravenous fluids

mEq/L
plus supportive care + ICU admission
plus potassium therapy
plus intravenous insulin once serum

potassium reaches 3.3 mEq/L
adjunct vasopressors
adjunct bicarbonate therapy
adjunct phosphate therapy
serum potassium 3.3 to 1st intravenous fluids

5.3 mEq/L
plus intravenous insulin
serum potassium >5.3 1st intravenous fluids

mEq/L
mild to moderate volume depletion:

hyponatremic

mEq/L
plus supportive care ± ICU admission

TREATMENT
plus insulin once serum potassium reaches 3.3

mEq/L
Acute ( summary )

5.3 mEq/L
plus insulin

mEq/L
plus insulin

eunatremic or hypernatremic

mEq/L

mEq/L

5.3 mEq/L
plus insulin

TREATMENT

mEq/L
plus insulin
29
Acute ( summary )
Ongoing ( summary )
DKA resolved and patient able to
tolerate oral intake
1st establish regular subcutaneous insulin

regime
TREATMENT
Treatment options
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
TREATMENT
31
Acute
severe volume depletion

mEq/L
» Severe volume depletion is indicated by
the presence of orthostatic hypotension or
supine hypotension, dry mucous membranes,
and poor skin turgor. Extreme cases may be
hemodynamically unstable.
» The goal of initial fluid therapy is to restore

tissue perfusion. The initial choice of fluid is
isotonic saline infused at a rate of 1.0 to 1.5 L
(or 15-20 mL/kg body weight) for the first hour.
In patients with severe volume depletion or
cardiogenic shock, isotonic fluid therapy and
hemodynamic monitoring should continue in
the intensive care unit until the patient becomes
stable.
» Electrolytes should be checked at least hourly

(to monitor potassium levels) and BUN, venous
pH, creatinine, and glucose should be checked
every 2-4 hours until the resolution of DKA.
» When plasma glucose reaches 200 mg/dL,

fluid therapy should be changed to 5% dextrose
with 0.45% NaCl at 150-250 mL/hour in order to
avoid hypoglycemia.[1]
Treatment recommended for ALL patients in
selected patient group
» Indications for intensive care unit (ICU)
admission include hemodynamic instability
or cardiogenic shock, altered mental status,
respiratory insufficiency, and severe acidosis.
» After admission to ICU, central venous and

arterial lines are required as well as Swan-Ganz
catheterization and continuous percutaneous
oximetry.
» Intubation and mechanical ventilation are

commonly required, with constant monitoring of
respiratory parameters.
» Nasogastric suctioning is always performed

because of frequent ileus and danger of
aspiration.[1]
TREATMENT

Primary options
Acute
» potassium phosphate: 20-30 mEq added to
each liter of infusion fluid initially, adjust dose
according to serum potassium level
If potassium is <3.3 mEq/L at any point of
therapy, insulin should be discontinued.
OR
» potassium chloride: 20-30 mEq added to

therapy, insulin should be discontinued.
» Insulin therapy and correction of

hyperosmolarity and acidemia decrease plasma
concentration of potassium. For this reason,
insulin therapy should be withheld until the
serum potassium level reaches 3.3 mEq/L.
» Likewise, if plasma potassium falls <3.3 mEq/

L at any point of therapy, insulin should be
discontinued.
» The dose of potassium replacement is 20-30

mEq added to each liter of infusion fluid.[1]
» Choices are potassium phosphate or

potassium chloride. One third of the potassium
replacement should be administered as
potassium phosphate to avoid excessive chloride
administration.
» The serum potassium level should be

monitored at least hourly and replacement
adjusted accordingly.
plus intravenous insulin once serum potassium
reaches 3.3 mEq/L
Primary options
» insulin regular: consult local protocols for

dosing guidelines
» Insulin therapy should not be commenced until

serum potassium reaches 3.3 mEq/L.
» Patients should receive a continuous

intravenous infusion of regular insulin after
TREATMENT
exclusion of hypokalemia (i.e., potassium level

should be >3.3 mEq/L before initiation of insulin
therapy). Two alternative low-dose regimens are
recommended by current guidelines.[1] [45] The
first option is a continuous intravenous infusion
of regular insulin at a dose of 0.14 units/kg/hour
33
Acute
(approximately 10 units/hour in a 70 kg patient)
with no initial bolus.[1] This is based on studies
that show the use of low-dose regular insulin
administered by intravenous infusion is sufficient
for the treatment of DKA, provided the dose
is >0.1 units/kg/hour. The alternative regimen
involves an initial intravenous bolus dose of
0.1 units/kg followed by a continuous infusion
at a dose of 0.1 units/kg/hour.[53] These low-
dose insulin therapy protocols decrease plasma
glucose concentration at a rate of 50-75 mg/dL/
hour.[1]
» If plasma glucose does not fall by at least

10% or 50 mg/dL in the first hour of insulin
infusion, then a dose of 0.14 units/kg of regular
insulin should be administered as an intravenous
bolus and the continuous insulin infusion rate
should be continued (either 0.1 units/kg/hour or
0.14 units/kg/hour depending on the regimen
selected).[1] [53] Insulin injection by a sliding
scale is no longer recommended. When serum
glucose reaches 200 mg/dL, the infusion can be
reduced to 0.02 to 0.05 units/kg/hour, at which
time dextrose may be added to the intravenous
fluids.[1] [53] The rate of insulin infusion (or the
dextrose concentration) should then be adjusted
to maintain a plasma glucose level of between
150-200 mg/dL.[1]
» This regimen should be followed until all

remaining criteria for resolution are met: serum
bicarbonate >18 mEq/L, venous pH >7.3, and
anion gap <10.[1]
Treatment recommended for SOME patients in
Primary options
» dopamine: 5-10 micrograms/kg/min

intravenously initially, adjust rate according
to blood pressure and other hemodynamic
parameters
Secondary options
» norepinephrine: 0.5 micrograms/kg/min

intravenously initially, titrate to maintain a
mean arterial pressure of 60 mmHg
TREATMENT
» In hemodynamically unstable patients,

vasopressor therapy (dopamine therapy)
may also be required. Often these patients
require high doses of dopamine, in the order
of 20 micrograms/kg/minute. If the patient
remains hypotensive despite moderate doses
Acute
of dopamine, a direct vasoconstrictor (e.g.,
norepinephrine) should be started.[1] [52]
Primary options
» sodium bicarbonate: serum pH 6.9 to 7.0:

50 mmol intravenous infusion over 1 hour
until pH >7.0; serum pH <6.9: 100 mmol
intravenous infusion at a rate of 200 mL/hour
for 2 hours or until pH >7.0
» Bicarbonate therapy may be used in adult

patients with pH <7 or a bicarbonate level <5
mEq/L, although data are limited.[1] [63]
» In adults with pH 6.9 to 7.0, 50 mmol sodium

bicarbonate (1 ampule) in 200 mL sterile water
with 10 mEq KCl may be administered over 1
» In adults with pH <6.9, we recommend that

100 mmol sodium bicarbonate in 400 mL sterile
water with 20 mEq KCl be administered at a
rate of 200 mL/hour for 2 hours or until pH >7.0.
Treatment should be repeated every 2 hours
until pH >7.0. Bicarbonate therapy, like insulin
therapy, lowers serum potassium; therefore, KCl
is added to isotonic bicarbonate.[1] [64]
Primary options

each liter of infusion fluid
» Routine replacement of phosphate is not

recommended.
» However, to avoid cardiac, respiratory, and

skeletal muscle dysfunction, careful phosphate
therapy may be indicated in patients with cardiac
dysfunction (e.g., with signs of left ventricular
dysfunction), symptomatic anemia, or respiratory
depression (e.g., decreased oxygen saturation),
and in those with confirmed hypophosphatemia
(serum phosphate concentration <1.0 mg/dL).[1]
TREATMENT
» The dose is 20-30 mEq/L potassium

phosphate added to replacement fluids.
35
Acute
» Phosphate therapy above the recommended
dose may result in severe hypocalcemia.[1] [75]
[76]
serum potassium 3.3 to 5.3 1st intravenous fluids
mEq/L

In patients with severe volume depletion (i.e.,
orthostatic or supine hypotension, dry mucous
membranes, and poor skin turgor) or cardiogenic
shock, isotonic fluid therapy and hemodynamic
monitoring should continue in the intensive care
unit until the patient becomes stable.

(to monitor potassium levels) and BUN, venous


oximetry.


TREATMENT
aspiration.
Acute
Primary options

dosing guidelines

for the treatment of DKA, provided the dose is
above 0.1 units/kg/hour. The alternative regimen
glucose concentration at a rate of 50 to 75 mg/
dL/hour.[1]

glucose reaches 200 mg/dL, the infusion can
be reduced to 0.05 units/kg/hour, at which time
dextrose may be added to the intravenous
150-200 mg/dL.[1]

anion gap <10.[1]
» If plasma potassium falls below 3.3 mEq/L

at any point, insulin should be discontinued
and potassium replaced intravenously. Insulin
TREATMENT
therapy can be restarted when the potassium

level returns to 3.3 mEq/L.
37
Acute
Primary options

therapy, insulin should be discontinued and
potassium replaced intravenously.
OR


hyperosmolarity and acidemia decrease the
plasma concentration of potassium. Concurrent
potassium replacement is recommended if
the serum potassium is in the range 3.3 to 5.3
mEq/L, to prevent cardiac arrhythmias due to
hypokalemia. The dose is 20-30 mEq added
to each liter of infusion fluid. If potassium is
<3.3 mEq/L at any point of therapy, insulin
should be discontinued and potassium replaced
intravenously.[1]

administration.

Primary options

parameters
TREATMENT
Secondary options

Acute
Primary options




is added to isotonic bicarbonate.[64]
Primary options


recommended.

TREATMENT

39
Acute

[76]
mEq/L

In patients with severe volume depletion (i.e.,
orthostatic or supine hypotension, dry mucous
membranes, and poor skin turgor) or cardiogenic
shock, isotonic fluid therapy and hemodynamic
monitoring should continue in the intensive care
unit until the patient becomes stable.

(to monitor potassium levels), and BUN, venous


oximetry.

TREATMENT

aspiration.
Acute
Primary options

dosing guidelines

hour.[1]

150-200 mg/dL.[1]

anion gap <10.[1]
» Potassium replacement is not required, but

TREATMENT
potassium levels should be checked every 2

hours.
41
Acute
Primary options

parameters
Secondary options


Primary options

intravenous infusion over 2 hours or until pH
>7.0



TREATMENT

Primary options
Acute

recommended.



[76]
hyponatremic

mEq/L
» Mild to moderate volume depletion is indicated
by the absence of orthostatic hypotension or
and poor skin turgor. The goal is to gradually
replace half of the fluid deficit over 12-24 hours,
to prevent complications such as cerebral
edema.
» The initial choice of fluid is isotonic saline

infused at a rate of 1.0 to 1.5 L (or 15-20 mL/kg
body weight) for the first hour.
» Following the initial fluid replacement,

corrected serum sodium level should
be evaluated (corrected sodium [mEq/
L] = measured sodium [mEq/L] + 0.016
[glucose (mg/dL) - 100]). In patients found to be
hyponatremic, 0.9% NaCl should be started at
250-500 mL/hour.

TREATMENT

43
Acute
admission include altered mental status,

oximetry. Intubation and mechanical ventilation
are commonly required, with constant monitoring
of respiratory parameters. Nasogastric
suctioning is always performed because of
frequent ileus and danger of aspiration.
» Mild cases of DKA may be managed without

ICU admission.[1]
Primary options

OR



discontinued.
» The dose is 20-30 mEq added to each liter of

TREATMENT
infusion fluid.[1]
» Choices for potassium therapy are potassium

phosphate or potassium chloride. One third
of the potassium replacement should be
Acute
administered as potassium phosphate to avoid
excessive chloride administration.
mEq/L
Primary options

dosing guidelines
Secondary options
» insulin aspart: consult local protocols for

dosing guidelines
OR
» insulin lispro: consult local protocols for

dosing guidelines


hour.[1]

TREATMENT

45
Acute
to maintain a plasma glucose level of 150-200
mg/dL.[1]
» Patients with mild to moderate DKA (plasma

glucose >250 mg/dL, arterial pH 7.00-7.30,
serum bicarbonate 10-18 mEq/L) that is not
complicated by acute MI, congestive heart
failure, end-stage renal or hepatic failure,
steroid use, or pregnancy, may be given
rapid-acting insulin subcutaneously as an
alternative to intravenous regular insulin.[60]
[61] [62] This has been demonstrated to be
safe and effective from studies in adults in one
center.[1] A suggested protocol would be an
initial subcutaneous injection of rapid-acting
insulin at a dose of 0.3 units/kg, followed 1
hour later by another subcutaneous injection
of 0.2 units/kg. Thereafter, they should receive
0.2 units/kg every 2 hours until blood glucose
becomes <250 mg/dL. At this point, the insulin
dose should be decreased by half to 0.1 units/
kg every 2 hours until the resolution of DKA.[58]
Until the results of these studies are replicated
in multicenter trials, the administration of
continuous intravenous infusion of regular insulin
should remain the preferred route because
of its short half-life and easy titration. This is
compared with the delayed onset of action
and prolonged half-life of subcutaneously
administered insulin. However, in places where
there are increased waiting times for intensive
care unit (ICU) admission or with limited medical
resources, the use of insulin analogs for the
treatment of mild uncomplicated DKA episodes
can be considered in outpatient, general wards,
or emergency departments. Patients with severe
DKA (plasma glucose >250 mg/dL, arterial
pH <7.00, serum bicarbonate <10 mEq/L),
hypotension, anasarca (severe generalized
edema), or associated severe critical illness
should be managed with intravenous regular
insulin in the ICU using the regimen described
above.[1] [58] [57] [59]

anion gap <10.[1]
TREATMENT

Primary options
Acute



Primary options


recommended.



[76]
TREATMENT
mEq/L
47
Acute
edema.


250-500 mL/hour.




ICU admission.[1]
plus insulin
Primary options

dosing guidelines
TREATMENT
Secondary options

dosing guidelines
Acute
OR

dosing guidelines

hour.[1]

mg/dL.[1]

glucose >250 mg/dL, arterial pH 7.00 to 7.30,
TREATMENT

49
Acute
above.[1] [58] [57] [59]
» The intravenous or subcutaneous regimens

should be followed until all remaining criteria for
resolution are met: serum bicarbonate >18 mEq/
L, venous pH >7.3, and anion gap <10.[1]
Primary options

OR

TREATMENT


Acute
hypokalemia. The dose is 20-30 mEq added to
each liter of infusion fluid. If potassium is <3.3
mEq/L at any point of therapy, insulin should be
discontinued.[1]

administration.

Primary options




Primary options
TREATMENT


recommended.
51
Acute


[76]
mEq/L
edema.


250-500 mL/hour.

hours.
» Electrolytes, BUN, venous pH, creatinine, and

glucose should be checked every 2-4 hours until
the resolution of DKA.

TREATMENT

Acute
» Mild cases of diabetic ketoacidosis may be

managed without ICU admission.[1]
plus insulin
Primary options

dosing guidelines
Secondary options

dosing guidelines
OR

dosing guidelines

hour.[1]
TREATMENT

53
Acute
150 and 200 mg/dL.[1]

above.[1] [58] [57] [59]
TREATMENT

Acute
Primary options




Primary options


recommended.


TREATMENT

[76]
55
Acute
eunatremic or hypernatremic

mEq/L
edema.


hypernatremic or eunatremic, 0.45% NaCl at 250
to 500 mL/hour is recommended.



ICU admission.[1]
TREATMENT

Primary options
Acute
OR



discontinued.
» The dose is 20-30 mEq added to each liter of

infusion fluid.[1]
» Choices for potassium therapy are potassium

phosphate or potassium chloride. One third
of the potassium replacement should be
administered as potassium phosphate to avoid
excessive chloride administration.

mEq/L
Primary options

dosing guidelines
Secondary options

TREATMENT
dosing guidelines
OR

dosing guidelines
57
Acute

for the treatment of DKA, provided the dose
is >0.1 units/kg/hour. The alternative regimen
glucose concentration at a rate of 50 to 75 mg/
dL/hour.[1]

150-200 mg/dL.[1]

TREATMENT

Acute
above.[1] [58] [57] [59]

anion gap <10.[1]
Primary options




TREATMENT

59
Acute
Primary options


recommended.



[76]
mEq/L
replace half of the fluid deficit over 12 to 24
hours, to prevent complications such as cerebral
edema.


hypernatremic or eunatremic, 0.45% NaCl at
250-500 mL/hour is recommended.
TREATMENT

Acute


ICU admission.[1]
plus insulin
Primary options

dosing guidelines
Secondary options

dosing guidelines
OR

dosing guidelines

TREATMENT

hour.[1]
61
Acute
150-200 mg/dL.[1]

TREATMENT

above.[1] [58] [57] [59]
Acute
Primary options

OR


hypokalemia. The dose is 20-30 mEq added to
each liter of infusion fluid. If potassium is <3.3
mEq/L at any point of therapy, insulin should be
discontinued.[1]

administration.

TREATMENT
Primary options

63
Acute



is added to isotonic bicarbonate.[64]
Primary options


recommended.



[76]
mEq/L
TREATMENT

edema.
Acute

hypernatremic or eunatremic, 0.45% NaCl at 250
to 500 mL/hour is recommended.

hours.
» Electrolytes, BUN, venous pH, creatinine, and

glucose should be checked every 2-4 hours until
the resolution of DKA.


ICU admission.[1]
plus insulin
Primary options

dosing guidelines
Secondary options

dosing guidelines
TREATMENT
OR

dosing guidelines
65
Acute
hour.[1]

mg/dL.[1]

TREATMENT

Acute
above.[1] [58] [57] [59]


hours.
Primary options



TREATMENT

67
Acute
is added to isotonic bicarbonate.[1] [64] [75]
Primary options


recommended.



TREATMENT
Ongoing
DKA resolved and patient able to
tolerate oral intake
1st establish regular subcutaneous insulin

regime
» When DKA has resolved and the patient

is able to tolerate oral intake, transition to
subcutaneous insulin needs to be initiated.
Patient should be given subcutaneous insulin
1-2 hours before the termination of insulin
infusion to allow sufficient time for subcutaneous
insulin to start work at this time. Intermediate or
long-acting insulin is recommended for basal
requirements and short-acting insulin for prandial
glycemic control.
» If a patient used insulin as their diabetes

treatment prior to DKA, the same dose can
be started; otherwise, the following regimen
is recommended: total daily insulin dose of
0.5 to 0.8 units/kg/day, with 30% to 50% of
the total daily dose given as basal long-acting
insulin, usually at night as a single dose, and the
remainder of the total daily dose given as divided
doses of fast-acting insulin before each meal.[1]
[58] [59]
TREATMENT
69
Diabetic ketoacidosis Follow up
Recommendations
Monitoring
FOLLOW UP
It is possible to manage mild DKA without admission to the intensive care unit (ICU); however, many
cases will require ICU care.
After admission to ICU, central venous and arterial lines are usually required. Swan-Ganz catheterization
and continuous percutaneous oximetry are needed in patients with hemodynamic instability. Monitoring of
respiratory parameters is also required to ensure adequate oxygenation and airway protection.
Initially, serum glucose, electrolytes, BUN, creatinine, calcium, magnesium, phosphate, ketones,
lactate, creatine phosphokinase, LFTs, urinalysis, ECG, upright chest radiograph, CBC, and ABGs are
obtained. Subsequently, glucose and electrolytes are measured at least hourly; calcium, magnesium, and
phosphate are checked every 2 hours and BUN, creatinine, and ketones every 2 to 6 hours, depending on
the patient's clinical condition and response to therapy.
Serial beta hydroxybutyrate (BOHB) measurements may aid monitoring of the response to treatment
in DKA. However, measurement of ketone bodies, in the absence of a meter with capacity to measure
BOHB, is not recommended. BOHB is converted to acetoacetate, which is detected by the nitroprusside
method, during the treatment of DKA. Therefore, the increase in acetoacetate during DKA treatment may
Monitoring bicarbonate, anion gap, and pH has also been shown to reflect the response to therapy. A flow
sheet classifying these findings as well as mental status, vital signs, insulin dose, fluid and electrolytes
therapies, and urine output allows easy analysis of response to therapy and resolution of crises.[1] [38]
[83] [84]
Patient instructions
Management should be reviewed periodically with all patients. This should include:
• When to contact the healthcare provider

• Blood glucose goals and the use of supplemental short- or rapid-acting insulin during illness
• Means to suppress fever and treat infection
• Initiation of an easily digestible fluid diet containing electrolytes and glucose during illness.
Patients should be advised to always continue insulin during illness and to seek professional advice early.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitor-associated DKA in patients with type 2 diabetes is

typically precipitated by insulin omission or significant dose reduction, severe acute illness, dehydration,
extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. DKA prevention
strategies should include withholding SGLT-2 inhibitors when precipitants are present, and avoiding
insulin omission or large insulin dose reduction.[36] [37]
The patient (or family member or carer) must be able to accurately measure and record blood glucose,
insulin administration, temperature, respiratory rate, and pulse. Blood ketone (BOHB) should be checked
when blood glucose is >300 mg/dL and, if it is high, the patient should present to the hospital for further
evaluation. The frequency of blood glucose monitoring depends on the patient's clinical condition: in
uncontrolled diabetes (HbA1c >7.0%), it is recommended to check blood glucose before each meal, plus
at bedtime.[1] [85]
Diabetic ketoacidosis Follow up
Complications
Complications Timeframe Likelihood
FOLLOW UP
hypoglycemia short term high
This iatrogenic complication can occur with excessive high-dose insulin therapy. It can be prevented by
following current treatment protocols with frequent monitoring of plasma glucose and use of glucose-
containing intravenous fluids.[1]
hypokalemia short term high
This iatrogenic complication can occur with excessive high-dose insulin therapy and bicarbonate therapy. It
can be prevented by following current treatment protocols with frequent monitoring of potassium levels and
appropriate replacement.[1] [52] [64]
arterial or venous thromboembolic events short term medium
Standard prophylactic low-dose heparin is certainly reasonable in these patients.[1] [38] [82] Applying
prophylactic treatment is based on clinical evaluation by the physician of risk factors for thromboembolic
events. Currently no evidence exists for full anticoagulation.
nonanion gap hyperchloremic acidosis short term low
This occurs due to urinary loss of ketoanions that are needed for bicarbonate regeneration, and also
increased reabsorption of chloride secondary to intensive administration of chloride-containing fluids. This
acidosis usually resolves and should not affect the treatment. It is more likely in pregnant women.[1] [64]
cerebral edema/brain injury short term low
This occurs in 0.7% to 10% of children with DKA and is rare in adults with DKA. Children at ages under
5 years are at increased risk.[77] It is manifested by headache, lethargy, papillary changes, and seizure.
Mortality is high. Mannitol infusion and mechanical ventilation should be used to treat this condition.
Prevention may be achieved by avoidance of overzealous hydration and by maintaining the glucose
level at 150-200 mg/dL in DKA..[1] [18] [78] [79] Results of the first prospective randomised study to
evaluate fluid regimens in children with DKA found that neither the sodium chloride content nor the speed
of delivery of intravenous fluids affected the short- and long-term neurologic outcomes.[80]
acute respiratory distress syndrome (ARDS) short term low
Treatment-related reduction in colloid osmotic pressure may lead to accumulation of water in the lungs,
decreased lung compliance and possibly hypoxemia in DKA. Management includes the monitoring
of blood oxygen levels with pulse oximetry and lowering the fluid intake with addition of colloid
replacement.[18] [81]
Prognosis
The mortality rate is 5% in experienced centers. Death is rarely caused by the metabolic complications of
hyperglycemia or ketoacidosis but rather relates to the underlying illness. The prognosis is substantially
worsened at the extremes of age and in the presence of coma and hypotension.[1]
71
Diabetic ketoacidosis Guidelines
Diagnostic guidelines
International
Standards of medical care in diabetes - 2020 (ht tps://

professional.diabetes.org/content-page/standards-medical-care-diabetes)
[45]
Published by: American Diabetes Association Last published: 2020
Hyperglycemic crises in adult patients with diabetes (ht tps://

care.diabetesjournals.org/content/32/7.toc) [1]
Treatment guidelines
GUIDELINES
International
Standards of medical care in diabetes - 2020 (ht tps://

professional.diabetes.org/content-page/standards-medical-care-diabetes)
[45]
Hyperglycemic crises in adult patients with diabetes: a consensus statement

from the American Diabetes Association (ht tps://care.diabetesjournals.org/
content/32/7.toc) [1]
Diabetic ketoacidosis References
Key articles
• Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with
REFERENCES
diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2009
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Jan;42(suppl 1):S1-S193. Full text (https://care.diabetesjournals.org/content/42/Supplement_1)
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Diabetic ketoacidosis Images
Images
IMAGES
Figure 1: Triad of DKA
Adapted with permission from: Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am.
1995;79:9-37
81
IMAGES Diabetic ketoacidosis Images
Figure 2: Pathogenesis of DKA and HHS; triggers include stress, infection, and insufficient insulin. FFA: free
fatty acid; HHS: hyperosmolar hyperglycemic state
From: Kitabchi AE, Umpierrez GE, Miles JM, et al. Diabetes Care. 2009,32:1335-43; used with permission
Diabetic ketoacidosis Images
IMAGES
Figure 3: Management of adult DKA. Abbreviations: blood glucose (BG); diabetic ketoacidosis (DKA); hour
(h); intravenous (IV); subcutaneous (SC)
Image created BMJ Knowledge Centre based on Gosmanov AR, Gosmanova EO, Dillard-Cannon E.
Management of adult diabetic ketoacidosis. Diabetes, Metabolic Syndrome and Obesity: Targets and
Therapy. 2014;7:255-64.
83
IMAGES Diabetic ketoacidosis Images
Figure 4: Algorithm for the management of potassium and bicarbonate

Modified from: Kitabchi AE, Umpierrez GE, Miles JM, et al. Diabetes Care. 2009,32:1335-43
Diabetic ketoacidosis Disclaimer
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Contributors:
// Authors:
Aidar R. Gosmanov, MD, PhD, FACE

Associate Professor of Medicine
Division of Endocrinology, Albany Medical College , Chief, Endocrinology Section, Albany VAMC, Albany,
NY
DISCLOSURES: ARG declares that he has no competing interests.
Laleh Ra zavi Nematollahi, MD

Assistant Professor of Medicine
Case Western Reserve University, Cleveland, OH
DISCLOSURES: LRN declares that she has no competing interests.
// Acknowledgements:
Dr Aidar Gosmanov and Dr Laleh Razavi Nematollahi would like to gratefully acknowledge Professor Abbas
E. Kitabchi, the previous contributor to this topic.
DISCLOSURES: AEK is an author of a number of references in this topic.
// Peer Reviewers:
David Jenkins, DM, FRCP

Consultant Physician
Worcestershire Royal Hospital, Worcester, UK
DISCLOSURES: DJ declares that he has no competing interests.
Udaya M. Kabadi, MD, FRCP(C), FACP, FACE

Professor of Medicine
University of Iowa, Iowa City, IA
DISCLOSURES: UMK declares that she has no competing interests.

Diabetic Ketoacidosis

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Diabetic ketoacidosis

Straight to the point of care

Last updated: Feb 07, 2020

◊ Diabetic ketoacidosis is characterized by a biochemical triad of hyperglycemia, ketonemia, and

◊ Successful treatment includes correction of volume depletion, hyperglycemia, electrolyte imbalances,

◊ Complications of treatment include hypoglycemia, hypokalemia, hypoxemia, and rarely pulmonary

Pathogenesis of DKA and HHS; triggers include stress, infection, and

• Plasma glucose: >250 mg/dL

• Plasma glucose: >250 mg/dL

• Plasma glucose: >250 mg/dL

Step-by-step diagnostic approach

Initial laboratory evaluation

• Typically increased due to volume depletion.

• This is variable in DKA.

Typical deficits in mild DKA

• Total water (L): 6

drugs (e.g., corticosteroids, thia zides, pentamidine, sympathomimetics,

Hispanic or black ancestry

History & examination factors

nausea or vomiting (common)

abdominal pain (common)

dry mucous membranes (common)

poor skin turgor (common)

sunken eyes (common)

Kussmaul respiration (common)

acetone breath (common)

altered mental status (common)

sensitive and specific for the diagnosis of DKA.[42]

serum BUN elevated

Other tests to consider

blood, urine, or sputum cultures positive in the presence of

Condition Differentiating signs / Differentiating tests

Lactic acidosis • The presentation is identical • Serum lactate >5 mmol/L.[1]

Starvation ketosis • Starvation ketosis • The blood glucose is usually

Alcoholic ketoacidosis • Classically, these are people • In isolated alcoholic

Salicylate poisoning • Can be differentiated by • The plasma glucose is

Condition Differentiating signs / Differentiating tests

Ethylene glycol/methanol • Methanol and ethylene glycol • Methanol/ethylene glycol

Uremic acidosis • This is characterized by • Elevated BUN usually

• 7.25 to 7.3 in mild DKA

Serum bicarbonate (mEq/L)

• 15-18 in mild DKA

Urine and serum ketones (nitroprusside reaction method)

Effective serum osmolality (mOsm/kg)

Anion gap (mEq/L)

• >10 in mild DKA

• alert in mild DKA

Step-by-step treatment approach

• Restoration of volume deficits

Initial and supportive treatment

• Fluid therapy should be started immediately after initial laboratory evaluations.

Initial management in hemodynamically unstable patients includes fluid resuscitation to correct

Management of adult DKA. Abbreviations: blood glucose (BG); diabetic

Algorithm for the management of potassium and bicarbonate

Treatment details overview

serum potassium <3.3 1st intravenous fluids

plus supportive care + ICU admission

plus potassium therapy

plus intravenous insulin once serum

adjunct bicarbonate therapy

adjunct phosphate therapy

serum potassium 3.3 to 1st intravenous fluids

plus supportive care + ICU admission