Document Text Contents
Page 1
PIER logo[Converted] copy.eps
Page 8
© 2010 American College of Physicians ITC1-8 In the Clinic Annals of Internal Medicine 1 January 2010
glucose level is greater than 33.3
mmol/L (600 mg/dL) and often
greater than 55.5 mmol/L (1000
mg/dL) but with minimal ketone
accumulation and only mild reduc-
tion in the arterial pH (Table 3)
(15). As the main metabolite of
ketones, β-hydroxybutyrate levels
are elevated in DKA but are usu-
ally normal in HHS. The in-
creased serum osmolality in HHS
reflects serious dehydration and
often produces mental status
changes, including coma in 25%
to 50% of cases. However, DKA
and HHS can overlap and have
many similarities. Like DKA,
HHS usually results from a
precipitating factor, such as an
infection or poor adherence to
diabetes medications.
What conditions should be
considered in the differential
diagnosis of DKA?
If the blood glucose level is less than
13.9 mmol/L (250 mg/dL), another
cause of the metabolic acidosis needs
to be considered (Table 4). Other
conditions, such as starvation, can
increase ketones, but this elevation is
usually mild. DKA can co-occur
with other causes of metabolic aci-
dosis, including lactic acidosis.
Diagnosis... Patients with DKA may present with a wide variety of nonspecific
symptoms; therefore, it is important to have a high index of suspicion. The physi-
cal examination can yield clues to the diagnosis, such as a fruity-smelling breath
from ketonemia, or to the severity of the episode, such as signs of significant de-
hydration. Laboratory assessment typically shows a blood glucose level greater
than 13.9 mmol/L (250 mg/dL), arterial pH less than 7.3, serum bicarbonate less
than 15 mmol/L, and a moderate degree of ketonemia or ketonuria. Patients with
type 2 diabetes are at greater risk for HHS, in which glucose level is often greater
than 55.5 mmol/L (1000 mg/dL) but the ketones are minimally elevated and the
pH is only mildly depressed. The venous pH may offer an alternative to the arteri-
al pH in the emergency department.
CLINICAL BOTTOM LINE
Table 3. Diabetic Ketoacidosis Versus Hyperosmolar Hyperglycemic State*
Value Mild DKA Moderate DKA Severe DKA HHS
Plasma glucose
mmol/L >13.9 >13.9 >13.9 33.3
mg/dL >250 >250 >250 >600
Arterial pH 7.25 to 7.30 7.00 to <7.24 <7.00 >7.30
Serum bicarbonate, mmol/L 15 to 18 10 to <15 <10 18
Urine ketones Positive Positive Positive Small
Serum ketones (β-hydroxybutyrate) High High High Normal or
elevated
Effective serum osmolality, mOsm/kg† Variable Variable Variable >320
Anion gap‡ >10 >12 >12 Variable
Alteration in sensoria or mental obtundation Alert Alert/drowsy Stupor/coma Stupor/coma
DKA = diabetic ketoacidosis; HHS = hyperosmolar hyperglycemic state.
* Adapted from Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32
1335-43. [PMID: 19564476]
† Effective serum osmolality = 2 × (measured Na [mmol/L]) + (glucose [mg/dL] ÷ 18).
‡ Anion gap = Na
+
− (Cl− + HCO3
− [mmol/L]).
Page 9
© 2010 American College of PhysiciansITC1-9In the ClinicAnnals of Internal Medicine1 January 2010
Do all patients with DKA require
hospitalization?
In some cases, patients with un-
complicated mild-to-moderate
DKA can be treated and dis-
charged from the emergency de-
partment if they are stable, able to
adhere to treatment, and have good
support at home. Rapid-acting
insulin analogs, such as lispro,
glulisine, and aspart, can be used
subcutaneously in these patients.
Although patients may respond to
therapy quickly, they can relapse if
they do not monitor themselves or
use sufficient doses of insulin.
Patients with moderate-to-severe
DKA should be hospitalized, often
in the intensive care unit or in an
intermediate care unit. Following of
practice guidelines, frequent moni-
toring, and continuous insulin infu-
sion are associated with mortality
rates of less than 1%. Patients with
an arterial pH level less than 7.25,
a bicarbonate level less than 15, or
a significant precipitating illness
should be treated in care units that
are experienced with DKA man-
agement and associated diseases.
Some, patients may require special-
ized therapy, such as treatment for
a myocardial infarction at a coro-
nary care unit.
What is the role of hydration in
the management of DKA?
Rehydration alone will replace the
fluid deficit, lower the glucose level,
and improve insulin sensitivity and
renal function. It should be started
immediately after the diagnosis of
DKA. Serum sodium should be
corrected for hyperglycemia (for
each 5.55 mmol/L [100 mg/dL] of
glucose more than 5.55 mmol/L
[100 mg/dL], add 1.6 mmol to
sodium value for corrected serum
sodium value). Begin with normal
saline (0.9% sodium chloride), and
reassess fluid-replacement hourly
Table 4. Differential Diagnosis of Diabetic Ketoacidosis
Disease Characteristics Notes
Starvation ketosis Patients may have intercurrent Blood glucose can be normal, low or somewhat
illness and quite ill, usually a clear elevated. Starvation ketosis does not lead to
history of not eating, and possibly acidosis; bicarbonate levels usually >18 mmol/L.
nausea or vomiting.
Alcoholic ketoacidosis History of excessive alcohol intake Blood glucose is key: if normal or low with
in patients with long-term ketonemia and metabolic acidosis, alcoholic
alcohol abuse. ketoacidosis is likely. An osmolar gap occur (differ-
ence between measured and calculated osmolality).
Lactic acidosis Serum lactate is usually about Can co-occur with diabetic ketoacidosis. Measure
5 mmol/L lactate if lactic acidosis suspected or history of
metformin use.
Salicylate intoxication Anion gap metabolic acidosis, Blood glucose level is usually not elevated and may
but often with primary respiratory be low. Measure the salicylate level.
alkalosis.
Methanol intoxication Ketones not significantly elevated, Blood glucose level is normal to elevated. Measure
symptoms include blurry vision methanol level.
and abdominal pain.
Ethylene glycol Ketones not usually increased, but Blood glucose level is variable. Calcium oxalate and
intoxication anion gap and osmolar gap are hippurate crystals can be seen in the urine. Measure
typically high. ethylene glycol.
Chronic renal failure Mild acidosis with slight increase History of increased serum creatinine.
in anion gap, but ketones not
elevated.
Pseudoketosis Paraldehyde or isopropyl Normal pH and normal anion gap.
alcohol ingestion.
Rhabdomyolysis Creatine kinase is usually very pH low, glucose level normal, ketones normal with
high. Causes of rhabdomyolysis, anion gap and myoglobinuria.
such as statins, trauma, or heat
stroke, may be present.
Treatment
PIER logo[Converted] copy.eps
Page 8
© 2010 American College of Physicians ITC1-8 In the Clinic Annals of Internal Medicine 1 January 2010
glucose level is greater than 33.3
mmol/L (600 mg/dL) and often
greater than 55.5 mmol/L (1000
mg/dL) but with minimal ketone
accumulation and only mild reduc-
tion in the arterial pH (Table 3)
(15). As the main metabolite of
ketones, β-hydroxybutyrate levels
are elevated in DKA but are usu-
ally normal in HHS. The in-
creased serum osmolality in HHS
reflects serious dehydration and
often produces mental status
changes, including coma in 25%
to 50% of cases. However, DKA
and HHS can overlap and have
many similarities. Like DKA,
HHS usually results from a
precipitating factor, such as an
infection or poor adherence to
diabetes medications.
What conditions should be
considered in the differential
diagnosis of DKA?
If the blood glucose level is less than
13.9 mmol/L (250 mg/dL), another
cause of the metabolic acidosis needs
to be considered (Table 4). Other
conditions, such as starvation, can
increase ketones, but this elevation is
usually mild. DKA can co-occur
with other causes of metabolic aci-
dosis, including lactic acidosis.
Diagnosis... Patients with DKA may present with a wide variety of nonspecific
symptoms; therefore, it is important to have a high index of suspicion. The physi-
cal examination can yield clues to the diagnosis, such as a fruity-smelling breath
from ketonemia, or to the severity of the episode, such as signs of significant de-
hydration. Laboratory assessment typically shows a blood glucose level greater
than 13.9 mmol/L (250 mg/dL), arterial pH less than 7.3, serum bicarbonate less
than 15 mmol/L, and a moderate degree of ketonemia or ketonuria. Patients with
type 2 diabetes are at greater risk for HHS, in which glucose level is often greater
than 55.5 mmol/L (1000 mg/dL) but the ketones are minimally elevated and the
pH is only mildly depressed. The venous pH may offer an alternative to the arteri-
al pH in the emergency department.
CLINICAL BOTTOM LINE
Table 3. Diabetic Ketoacidosis Versus Hyperosmolar Hyperglycemic State*
Value Mild DKA Moderate DKA Severe DKA HHS
Plasma glucose
mmol/L >13.9 >13.9 >13.9 33.3
mg/dL >250 >250 >250 >600
Arterial pH 7.25 to 7.30 7.00 to <7.24 <7.00 >7.30
Serum bicarbonate, mmol/L 15 to 18 10 to <15 <10 18
Urine ketones Positive Positive Positive Small
Serum ketones (β-hydroxybutyrate) High High High Normal or
elevated
Effective serum osmolality, mOsm/kg† Variable Variable Variable >320
Anion gap‡ >10 >12 >12 Variable
Alteration in sensoria or mental obtundation Alert Alert/drowsy Stupor/coma Stupor/coma
DKA = diabetic ketoacidosis; HHS = hyperosmolar hyperglycemic state.
* Adapted from Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32
1335-43. [PMID: 19564476]
† Effective serum osmolality = 2 × (measured Na [mmol/L]) + (glucose [mg/dL] ÷ 18).
‡ Anion gap = Na
+
− (Cl− + HCO3
− [mmol/L]).
Page 9
© 2010 American College of PhysiciansITC1-9In the ClinicAnnals of Internal Medicine1 January 2010
Do all patients with DKA require
hospitalization?
In some cases, patients with un-
complicated mild-to-moderate
DKA can be treated and dis-
charged from the emergency de-
partment if they are stable, able to
adhere to treatment, and have good
support at home. Rapid-acting
insulin analogs, such as lispro,
glulisine, and aspart, can be used
subcutaneously in these patients.
Although patients may respond to
therapy quickly, they can relapse if
they do not monitor themselves or
use sufficient doses of insulin.
Patients with moderate-to-severe
DKA should be hospitalized, often
in the intensive care unit or in an
intermediate care unit. Following of
practice guidelines, frequent moni-
toring, and continuous insulin infu-
sion are associated with mortality
rates of less than 1%. Patients with
an arterial pH level less than 7.25,
a bicarbonate level less than 15, or
a significant precipitating illness
should be treated in care units that
are experienced with DKA man-
agement and associated diseases.
Some, patients may require special-
ized therapy, such as treatment for
a myocardial infarction at a coro-
nary care unit.
What is the role of hydration in
the management of DKA?
Rehydration alone will replace the
fluid deficit, lower the glucose level,
and improve insulin sensitivity and
renal function. It should be started
immediately after the diagnosis of
DKA. Serum sodium should be
corrected for hyperglycemia (for
each 5.55 mmol/L [100 mg/dL] of
glucose more than 5.55 mmol/L
[100 mg/dL], add 1.6 mmol to
sodium value for corrected serum
sodium value). Begin with normal
saline (0.9% sodium chloride), and
reassess fluid-replacement hourly
Table 4. Differential Diagnosis of Diabetic Ketoacidosis
Disease Characteristics Notes
Starvation ketosis Patients may have intercurrent Blood glucose can be normal, low or somewhat
illness and quite ill, usually a clear elevated. Starvation ketosis does not lead to
history of not eating, and possibly acidosis; bicarbonate levels usually >18 mmol/L.
nausea or vomiting.
Alcoholic ketoacidosis History of excessive alcohol intake Blood glucose is key: if normal or low with
in patients with long-term ketonemia and metabolic acidosis, alcoholic
alcohol abuse. ketoacidosis is likely. An osmolar gap occur (differ-
ence between measured and calculated osmolality).
Lactic acidosis Serum lactate is usually about Can co-occur with diabetic ketoacidosis. Measure
5 mmol/L lactate if lactic acidosis suspected or history of
metformin use.
Salicylate intoxication Anion gap metabolic acidosis, Blood glucose level is usually not elevated and may
but often with primary respiratory be low. Measure the salicylate level.
alkalosis.
Methanol intoxication Ketones not significantly elevated, Blood glucose level is normal to elevated. Measure
symptoms include blurry vision methanol level.
and abdominal pain.
Ethylene glycol Ketones not usually increased, but Blood glucose level is variable. Calcium oxalate and
intoxication anion gap and osmolar gap are hippurate crystals can be seen in the urine. Measure
typically high. ethylene glycol.
Chronic renal failure Mild acidosis with slight increase History of increased serum creatinine.
in anion gap, but ketones not
elevated.
Pseudoketosis Paraldehyde or isopropyl Normal pH and normal anion gap.
alcohol ingestion.
Rhabdomyolysis Creatine kinase is usually very pH low, glucose level normal, ketones normal with
high. Causes of rhabdomyolysis, anion gap and myoglobinuria.
such as statins, trauma, or heat
stroke, may be present.
Treatment
