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1. Project: Ghana Emergency Medicine Collaborative
Document Title: Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic
State (2012)
Author(s): Jennifer N. Thompson, M.D., Project Hope
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2

3. Diabetic
Ketoacidosis
and
Hyperosmolar
Hyperglycemic
State
Jennifer
N.
Thompson,
MD
Project
Hope
3

4. Objectives
DKA:
Diabetic
Ketoacidosis
HHS:
Hyperosmolar
Hyperglycemic
State
(HONKC
–
hyperosmolar
nonketotic
coma)
l What
is
the
difference
between
DKA
and
HHS?
l How
do
I
manage
DKA
and
HHS?
l What
complications
should
I
look
out
for?
l What
does
the
data
say
about
cerebral
edema?
4

5. Diabetic
Ketoacidosis
HHS
-­‐
Hyperosmolar
hyperglycemic
state
Blood
glucose
Glucose
>250
(13.9)
Glucose
>600
(33.3)
Arterial
pH
pH
<7.3
pH
>7.3
Serum
Bicarbonate
<15
>15
Serum
osmolality
varies
>320
mOsm
Urine
ketones
+++
Small
or
none
Anion
gap
>12
Demographics
Mostly
type
I
DM
Children,
young
people
Mostly
type
II
DM
Elderly,
mentally
or
physically
impaired
Insulin
activity
Absolute
functional
insulin
deficiency
Relative
insulin
deficiency
Mortality
in
admitted
patients
1-­‐4%
10%
or
more
Definitions
5

6. Classic
presentation
of
DKA
l Young
people,
Type
I
DM
Age
History
l Polydipsia,
Polyuria,
Fatigue
l Nausea/vomiting,
diffuse
abdominal
pain.
l In
severe
cases
–
lethargy,
confusion
Physical
l Ill
appearance
l Signs
of
dehydration:
Dry
skin,
dry
mucous
membranes,
decreased
skin
turgor
(skin
tenting)
l Signs
of
acidosis:
l Tachypnea

Kussmaul
respirations
l Characteristic
acetone
(ketotic)
breath
odor
6

7. Role
of
Insulin
l Required
for
transport
of
glucose
into
cells
for
use
in
making
ATP
l Muscle
l Adipose
l Liver
l Inhibits
lipolysis
l Type
I
DM
=
inadequate
insulin
7
Source
Undetermined

8. Pathophysiology
in
DKA
Counterregulatory
Insulin
hormones
Glucagon
Epinephrine
Cortisol
Growth
Hormone
Gluconeogenesis
Glycogenolysis
Lipolysis
8
Ketogenesis

9. Counterregulatory
Hormones
-­‐
DKA
Increases
insulin
resistance
Epinephrine
Activates
glycogenolysis
and
gluconeogenesis
Activates
lipolysis
Inhibits insulin
secretion
X
X
X
X
X
X
Glucagon
X
Cortisol
X
Growth
Hormone
X
X
9

10. Insulin
Deficiency
Glucose
uptake
Lipolysis
Proteolysis
Glycerol
Free
Fatty
Acids
Amino
Acids
Hyperglycemia
Gluconeogenesis
Glycogenolysis
Ketogenesis
Osmotic
diuresis
Dehydration
Acidosis
² No
Liploysis
=
No
Ketoacidosis
² Only a small amount of functional insulin required to suppress lipolysis
10

11. Underling
stressors
that
tip
the
balance
Pathophysiology
l Newly
diagnosed
diabetics
Insulin
l Missed
insulin
treatments
Glucagon
Epinephrine
Cortisol
Growth
Hormone
l Dehydration
l Underlying
infection
l Other
physiologic
stressors:
l Ex)
Pulmonary
embolism,
Illicit
drug
use
(sympathomimetics),
Stroke,
Acute
Myocardial
Infarction,
Gluconeogenesis
Glycogenolysis
Lipolysis
Ketogenesis
l Young
type
II
diabetics
with
stressors
11

12. Workup
Most
important
labs
to
diagnose
DKA:
l Basic
metabolic
panel
(glucose,
anion
gap,
potassium)
l Arterial
or
venous
blood
gas
to
follow
pH
l Urine
dipstick
for
glucose
and
ketones
(high
sensitivity,
high
negative
predictive
value)
l
l
l
l
Additional
tests:
Serum
ketones
Magnesium,
phosphorus
EKG
–
if
you
suspect
hyperkalemia,
hypokalemia,
arrhythmias
**Determine
the
underlying
cause!
12

13. Management
l Fluids
l Insulin
l Electrolyte
repletion
l Find
and
treat
any
underlying
cause!
13

14. Fluids
l Increases
intravascular
volume
l Reverses
dehydration
l Restores
perfusion
to
kidneys


GFR

urinate
out
excess
glucose
l Restores
perfusion
to
periphery


uptake
and
use
of
glucose
(when
insulin
present)
Take
home
message:
Fluids
hydrate
patient
AND
reverse
hyperglycemia
14

15. Fluids
Pediatrics
l Hypotension:
treat
with
20cc/kg
NS
boluses
l If
no
hypotension:
l 10-­‐20cc/kg
NS
bolus
then
1.5
–
2x
maintenance
OR
l Assume
10%
dehydration
and
calculate
fluid
deficit
plus
maintenance
l Replete
deficit
(plus
maintenance)
over
48-­‐72hrs.
15

16. Insulin
l Allows
glucose
to
enter
and
be
used
by
cells
l Stops
proteolysis
and
lipolysis
Ø Stops
Ketogenesis

Stops
Acidosis
l Allows
potassium
to
enter
cells
Insulin
goal:
Treat
the
anion
gap
acidosis
(not
the
hyperglycemia)
l Never
stop
the
insulin
before
the
anion
gap
is
closed.
16

17. Insulin
l Dosing:
0.05
units/kg
bolus
then
.05
units/kg/hr
insulin
drip.
(Previously
0.1
units/kg/hr)
l Goal:
Decrease
glucose
by
<100
(5.5)
per
hour
l Avoids
sudden
fluid
shifts
that
may
lead
to
cerebral
edema
l Reason
for
IV
insulin
l Not
affected
by
decreased
peripheral
circulation
as
with
subcutaneous
insulin
l Smooth
decline
of
glucose
l Short
half-­‐life
allows
for
more
precise
control
of
serum
insulin
concentration
17

18. Insulin
l If
pt
has
an
anion
gap
and
your
glucose
is
<250
(14),
do
you
stop
the
insulin
drip?
l NO!
l Add
D5
when
glucose
<250
(14).
If
glucose
<150
(8.3),
consider
D10.
TAKE
HOME
POINT:
l Do
not
stop
insulin
until
anion
gap
is
closed.
l Main
goal
of
insulin
therapy
is
to
fix
the
acidosis.
18

19. Transitioning
to
Subcutaneous
Insulin
l
ONLY
after
the
Anion
Gap
is
closed!
l OVERLAP
IV
and
subcutaneous
insulin
administration
l Give
long-­‐acting
insulin
dose
(ex.
lantus)
at
least
30
to
60
minutes
prior
to
stopping
insulin
drip.
l
Feed
patient
19

20. Managing
electrolytes
l Potassium
l Sodium
l Phosphorus
l Glucose
20

21. Electrolyte
management
Potassium
Total
Body
Potassium
depletion
l Acidosis

K+
exits
cells
as
H+
enters
to
buffer
l Dehydration
and
volume
depletion
l Osmotic
diuresis
+

aldosterone

loss
of
K+
 Although
serum
K+
is
usually
normal
or
high,
total
body
K+
is
low.
21

22. Electrolyte
Management
Potassium
l With
insulin
therapy
l K+
moves
into
cells
l To
avoid
hypokalemia
l Give
oral
and/or
IV
potassium
to
avoid
hypokalemia
when
K
<
4.5
l Monitor
K+
levels
and
EKG
l Low
K
–
Biphasic
T,
U-­‐wave
l High
K
-­‐
tall
peaked
T,
flat
P
waves,
wide
QRS
l Cardiac
dysrhythmia
22

23. Electrolyte
Management
Sodium
Pseudohyponatremia:
l For
each
100mg/dl
increase
of
glucose
above
100,
Na+
decreases
by
1.6
mEq/L
l Corrected
Na+
=
measured
Na
+
1.6
meq/L
x
(glucose-­‐100)/100))
l Example:
Na+
=
125
meq/L
and
Glucose
=
500
mg/dl
500
–
100
=
400
400/100
=
4
4
x
1.6
=
6.4
meq/L
Corrected
Na+
=
125
+
6.4
=
131.4
meq/L
23

24. **Electrolyte
Management
Phosphorus
Hypophosphatemia
l Occurs
after
aggressive
hydration/treatment
l Monitor
phosphorus
and
replete
as
needed
to
keep
>
1
l Total
body
phosphorus
depleted
l Mostly
a
theoretical
problem
l Potential
complications:
muscle
weakness,
myocardial
dysfunction,
CNS
depression
24

25. Management
review
l Rehydrate
patient
with
IV
fluids
l Continue
insulin
drip
until
anion
gap
is
closed
l Until
insulin
drip
is
off:
l Check
glucose
every
hour.
Avoid
hypoglycemia.
l Check
electrolytes
every
1-­‐2hrs.
Avoid
hypokalemia.
l Replete
potassium
when
K
<
4.5
and
patient
making
urine
25

26. ICU
Monitoring
Careful
nursing
monitoring
of
the
following:
l I/Os
(input
and
urine
output.)
l Urine
dipstick
with
every
void
l resolution
of
ketonuria
may
lag
behind
clinical
improvement
l Monitor
for
any
signs
of
cerebral
edema:
l Change
in
mental
status,
severe
headache
l Sudden
drop
in
heart
rate
l Neurologic
deficits
26

27. DKA
Complications
l
l
l
l
l
l
l
l
l
Dehydration,
shock,
hypotension
Hypokalemia/
hyperkalemia
Hypoglycemia
Aspiration
pneumonia
Sepsis
Acute
tubular
necrosis
Myocardial
infarction
Stroke
Cerebral
edema
*
Death
rate
in
U.S
when
managed
in
hospital
setting
=
1-­‐4%
27

28. DKA
Complications
Cerebral
edema
l Clinical
manifestations:
l Altered
mental
status
l Headache
l Persistent
vomiting
l Sudden
and
persistent
drop
in
heart
rate
l Seizure
l Unequal
or
fixed,
dilated
pupils
l Mostly
children
l High
mortality
rate
l 1%
of
DKA
pts,
>
25%
mortality
rate
l High
morbidity
rate
l High
rate
of
neurologic
complications
28

29. DKA
Complications
Cerebral
edema
l Risk
Factors
l Age
<
5
years
l More
often
seen
in
your
sickest
patients
l (high
BUN,
low
bicarb
<15)
l Fall
in
serum
Na
or
lack
of
increase
during
treatment
l Rapid
correction
of
hyperglycemia
l Goal:
decrease
glucose
<100
mg/dl
(5.5)
per
hour
l Sodium
bicarbonate
administration
l Excessive
fluids
29

30. DKA
Complications
Cerebral
Edema
-­‐
treatment
l Mannitol
1mg/kg
IV
l Reduce
IV
fluid
rate
(ex.
70%
maintenance)
l Consider
intubation
l set
the
ventilator
close
to
rate
that
patient
was
breathing
beforehand
l be
cautious
of
over
hyperventilation
l Temporary
measure
l Keep
pCO2
>
22mmHg
l May
consider
3%
hypertonic
saline
l but
not
enough
data
to
truly
recommend
30

31. Diabetic
HHS
Definitions
-­‐
Hyperosmolar
Ketoacidosis
hyperglycemic
state)
(AKA
HONKC
=
hyperosmolar
nonketotic
coma)
Blood
glucose
Glucose
>250
(13.9)
Glucose
>600
(33.3)
Arterial
pH
pH
<7.3
pH
>7.3
Serum
Bicarbonate
<15
>15
Serum
osmolality
varies
>320
mOsm
Urine
ketones
+++
small
Anion
gap
>12
Demographics
Mostly
type
I
DM
Children,
young
people
Mostly
type
II
DM
Elderly
Insulin
activity
Absolute
functional
insulin
deficiency
Relative
insulin
deficiency
Mortality
in
admitted
patients
1-­‐4%
10%
or
more
31

32. HHS
(Hyperosmolar
Hyperglycemic
State)
l Elderly
and
mentally
or
physically
impaired
patients
l Usually
associated
with
underlying
physiologic
stressors
l Ex.
Infection,
myocardial
infarction,
stroke.
l Slower
onset
(ex.
1
week
vs.
1-­‐2
days
in
DKA)
l Higher
Mortality
rate
than
DKA
(>10%)
l Older
patients,
more
comorbidities
Presentation:
l Altered
mental
status
(confusion,
neurologic
deficits)
l Signs
of
severe
dehydration
(tachycardia,
hypotension,
dry
mucous
membranes,
skin
tenting)
32

33. Insulin
Deficiency
Glucose
uptake
Lipolysis
Proteolysis
Glycerol
Free
Fatty
Acids
Amino
Acids
Hyperglycemia
Gluconeogenesis
Glycogenolysis
Ketogenesis
Osmotic
diuresis
Dehydration
Acidosis
² No
Liploysis
=
No
Ketoacidosis
² Only a small amount of functional insulin required to suppress lipolysis
² Low
catecholamine
levels
in
elderly
patients
à
less
insulin
resistance
33

34. HHS
-­‐
State
of
severe
dehydration
Therapy:
l Fluid
repletion
l Total
fluid
deficit
≈
10
liters
in
adults
l Normal
saline
2-­‐3
liters
rapidly
l Replete
½
in
first
6
hours
l Insulin
drip
0.05
units/kg/hr
l Decrease
glucose
by
approximately
50
mEQ/hr
l Check
electrolytes
q1-­‐2hrs.
Check
glucose
q1hr
l Monitor
potassium
for
hypokalemia/hyperkalemia
• Treat
underlying
precipitating
illness
• Potential
complications
are
the
same
as
DKA
34

35. Summary
l Pathophysiologic
difference
between
DKA
and
HHS
l DKA
is
a
state
of
absolute
functional
insulin
deficiency
l Only
in
DKA
:
Lipolysis
ketogenesis
acidosis
l You
are
never
specifically
treating
the
glucose
l In
DKA
–
you
are
treating
the
underlying
acidosis/
ketogenesis
(reflected
by
the
anion
gap)
l In
HHS
–
you
are
treating
the
underlying
shock
caused
by
poor
tissue
perfusion/severe
dehydration
35

36. Summary
(continued)
l Being
too
aggressive
in
management
may
cause
more
harm
than
good
l If
you
don’t
pay
attention
to
details,
you
will
cause
an
iatrogenic
death
l Monitor
electrolytes
(especially
potassium)
l Beware
cerebral
edema.
l Therapy
for
DKA
and
HHS
is
similar.
36

37. Thank
you
diabetees.spreadshirt.com
37

38. Pathophysiology of diabetic ketoacidosis
Source
Undetermined
38

39. Islets
of
Langerhans
Stress
β-­‐cell
destruction
Polyuria
Volume
Depletion
Ketonuria
Decreased
Glucose
Utilization
&
Increased
Production
isol
Epi,Cort
GH
Amino
Acids
Increased
Lipolysis
Insulin
Deficiency
Muscle
Increased
Protein
Catabolism
FattyAcids
Threshold
180
mg/dl
39
Glucagon
Liver
Increased
Ketogenesis,
Gluconeogenesis,
Glycogenolysis
Hyperglycemia
Ketoacidosis
HyperTG

40. Additional
Information
Attributions
for
Slide
39:
Islets
of
Langerhans:
Afferent
(WikimediaCommons)
Adipocytes:
DBCLS
(WikimediaCommons)
Muscle:
Jeremy
Kemp
(WikimediaCommons)
Liver:
Mikael
Haggstrom
(WikimediaCommons)
Kidney:
Holly
Fischer
(WikimediaCommons)
40