Diabetic Ketoacidosis…
…when we are too sweet for our own good!
Brenda Morgan RN BScN MSc
Clinical Nurse Specialist, CCTC
London Health Sciences Centre
Pancreas
Endocrine
Alpha cells: glucagon
Beta cells: insulin
Delta: somatostatin
Pancreatic Polypeptide
Exocrine
Pancreatic juices
Physiology
Glucagon
Insulin
Insulin:Glucagon
Insulin
Glucagon
Stimulated by:
Stimulated by:
Increased BS
decreased BS
Exercise
malnutrition
increased AA
SNS
Insulin
Glucagon
Effects:
Effects:
Movement of glucose
and K into cell
Raise blood sugar
Decreased fat
mobilization
Glycogenolysis
Decrease protein
breakdown leaving
protein available for
cell growth
Maintains serum
osmolality
Gluconeogenesis
Fat mobilization
Protein mobilization
Fed State
Insulin > Glucagon (insulin activity
dominates)
Movement of nutrients into cells
Storage of nutrients for later use
Fasting State
Glucagon > Insulin (glucagon activity
dominates)
Use of endogenous fuels to maintain
blood sugar for energy and metabolism
Fasting State
Liver becomes major source for glucose
Stored sugar in liver (glycogen) is
converted to glucose (glycogenolysis)
Decreased insulin causes lipolysis to
increase free fatty acids (used for
muscle fuel)
Fasting State
Free fatty acids converted to ketones
in liver by glucagon (another energy
source for brain and muscle)
– Beta-hydroxybutyrate vs acetoacetate
Glycerol (released by lipolysis) and
alanine (from protein catabolism)
provides additional substrates for
gluconeogenesis in liver
Other Triggers
Cortisol
Catecholamines
Growth hormones
Renal Regulation
Glucose filtered in glomerulus
Filtered glucose reabsorbed in proximal
tubules to maintain serum glucose
Kidney removes excess glucose
Decreased renal perfusion impairs
glucose removal
Diabetic Complications
Effects of Diabetes
chronic complications develop in 75% of patients
magnitude and duration of hyperglycemia correlates to:
microvascular disease:
retinopathy
nephropathy
neuropathy
gastroparesis
diarrhea
impotence
resting tachycardia, bradyarrhythmias
postural hypotension
limb sensation
Diabetic Complications
Macrovascular diseases
coronary artery disease
peripheral vascular disease
cerebrovascular disease
hypertension
Macrovascular and Neuropathy
foot disease
risk increases with smoking, obesity, hyperglycemia,
lipid abnormalities.
increased lipid alterations increases with hyperglycemia
neuroglycopenia
Diabetic Ketoacidosis
Primarily Type I DM risk
Exaggerated expression of fasting
state
Little has changed in mortality
Prevention of deaths through early
detection
Role for urine testing for ketones
DKA
Insufficient Insulin
Lipolysis
Ketosis
Increased serum
osmolality
Osmotic Diuresis
Dehydration
Anion Gap Acidosis
Kushmaul breathing
Glucagon>Insulin
increased hepatic
glucose production
Signs and Symptoms
Key Features of DKA
Hyperglycemia
Anion gap metabolic acidosis
Ketonuria
Dehydration, secondary tachycardia and
hypotension
Polyuria, polydipsia
Increased serum:urine osmolarity
Kussmaul's respiration; fruity acetone breath
Normal to low temperature
Hyperkalemia
Hyponatremia
Diabetic Ketoacidosis
Hyperglycemia
Metabolic acidosis with ketosis
Fluid and electrolyte imbalance
Altered mental state
Only 10% in coma; 20% clear mentated
Hypothermia may be present, but fever
not due to DKA
Look for precipitating event!
Hyperglycemic Hyperosmolar
Non-Ketotic Syndrome (HONK, HHNS)
Similar to DKA except hepatic ketogenesis is
inhibited (insulin presence)
Symptoms similar to DKA without ketosis and
acidosis
Hyperglycemia (and hyperosmolality) often
worse (syndrome usually persists longer before
seeking treatment; +/- renal impairment)
Mortality higher than DKA
Larger volume deficit
Hypo or Hyper?
Coma may occur in either
Cold, clammy and shaky vs volume
depleted, acidotic
When in doubt?
Coma…look for other causes
Fluid and Electrolyte Impairment
Dry, dry, dry
Overall loss of sodium, potassium,
chloride, phosphate and magnesium but
serum levels often elevated due to
hypovolemia or shifts
Management of DKA
ABC’s with fluid resuscitation
Insulin
Electrolyte replacement
Lab monitoring
Critical Lab Monitoring
•
•
•
•
Glucose
Sodium
Bicarbonate
Anion Gap
– Albumin
– Chloride
Osmolality
Calculated Osmolality
= (2 X Na + urea + Glucose + [EtoH])
Increased
blood
sugar,
ketones
Increased
serum
osmolality
Water
moves from
cells to
plasma
Hyperosmolar
diuresis leads
to dehydration
and dilutional
reduction in
sodium
Sodium
High or low
Mild dilutional hyponatremia common
High sodium in severe dehydration
Net sodium deficit due to urinary loss
(bound to ketones)
Sodium can be falsely low with
hyperglycemia
Recalculate prior to changing IV
infusion
Sodium Correction
Several methods used
Correction of sodium for hyperglycemia to
identify underlying sodium deficit
For every 10 mmol/L rise in blood glucose > 8
mmol/L, upwardly correct Na by 3 mmol/L
Sodium Correction
Glucose-8
10
X
3
+ Na
Sodium Correction
Na =
Glucose =
138
49
What is the corrected sodium?
Sodium Correction
Na =
Glucose =
138
49
Glucose-8
10
X
3
+ Na
Sodium Correction
Na =
Glucose =
49-8
10
138
49
X
3
+ 138
Corrected Sodium
Na = 150
Chloride
Net chloride loss is often less than
sodium (not bound to ketones)
Hyperchloremia commonly develops
following fluid resuscitation with 0.9%
NaCl
Vomiting causes loss of chloride ions
(favouring alkalosis)
Mixed picture
Potassium
May have normal, hyper or hypokalemia
(20%)
Deficit usual present due to diuresis, GI
loss and dehydration induced aldosterone
release
Potassium
Insulin deficit causes shift from cells:
May present with hyperkalemia despite overall
deficit
Renal impairment may be associated with
hypekalemia
Ketones
• In DKA, beta hydroxybutyrate to acetacetate
ratio is 3:1
• Most labs measure acetoacetate (nitroprusside
reagent test strip)
• Ketonuria may be under-detected in early DKA
• Insulin converts beta-hydroxybutyrate to
acetoacetate, increasing ketonuria during
recovery
• Ketonuria detection ~36 hours post stabilization;
poor marker of resolution
Assessment of Metabolic Acidosis
Anion gap is calculated when metabolic acidosis is
diagnosed, to help narrow down the possible
cause.
Anion Gap =
Cations (+ charges) – Anions (- charges)
Measured Anions
Measured Cations
Sodium
135-145
chloride
98-107
Potassium
3.5-5.0
bicarb
22-29
Total Cations:
144 mmol/L
Total Anions:
-
130 mmol/L
Normal = ~7-15 (if K is included)
Normal = ~3-11 (if K excluded)
Measured Charges:
Cations > Anions
Unmeasured Anions (-)
Unmeasured Cations (+)
protein
15 mmol/L
PO4
2 mmol/L
1 mmol/L
SO4
organic acids 5 mmol/L
potassium 4.5 mmol/L
calcium
5.0 mmol/L
magnesium 1.5 mmol/L
Total
23 mmol/L
Total
11 mmol/L
Unmeasured Charges:
Anions > Cations
An increased anion (fewer measured
negatives) usually indicates there are more
unmeasured negatives.
Anion Gap Acidosis
Possible sources for unmeasured anions (causes
for increased anion gap acidosis > 15):
“MUDPILERS”
Methanol
Uremia
Diabetic ketoacidosis
Paraldehyde
Isoniazide/iron
Lactate
Ethylene glycol
Rhabdomyolysis
Salicylates
Is this an anion gap acidosis?
Na
144
K
5.2
Cl
95
HCO3 9
Glucose 45
144
40
104
Is this an anion gap acidosis?
Na
144
K
3.2
Cl
118
HCO3 18
144
8
136
Unmeasured Anions (-)
Unmeasured Cations (+)
protein
15 mmol/L
PO4
2 mmol/L
1 mmol/L
SO4
organic acids 5 mmol/L
potassium 4.5 mmol/L
calcium
5.0 mmol/L
magnesium 1.5 mmol/L
Total
23 mmol/L
Total
11 mmol/L
6.5
What is the effect of a low
albumin?
Is this an anion gap acidosis?
Na
144
K
3.2
Cl
118
144
8
136
HCO3 18
Albumin 11
Corrected:
8 + 2.5 (3) = 15.5
Decreased or Falsely Normal
Anion Gap Acidosis
Decreased measured cations (e.g.,
sodium)
Low serum protein
Causes decrease in number of
unmeasured protein anions
If anion gap is normal, other unmeasured
anions must be present
In ketoacidosis:
• Insulin decreases ketosis
• Ketones excreted with hydrogen or
ammonium reduce ketosis and acidosis
• Ketones also excreted with sodium or
potassium (causing loss of bicarb
precursors); acidosis persists despite
reduction in anion gap
In ketoacidosis:
Hyperchloremia (0.9% NaCl administration) a
common cause of non-anion gap acidosis
Non-anion gap acidosis very common for day or
two post resolution of DKA (due to potential
bicarb loss and chloride administration)
• Anion gap increases by 1 for every decrease in
bicarbonate with ketoacidosis
• An anion gap increase > fall in bicarb suggests
additional organic acids present (e.g., lactate)
Is this an anion gap acidosis?
Na
144
K
4.6
Cl
144
22
114
HCO3 8
Albumin 38
122
AG = bicarb deficit
Normal bicarb (24) – Actual bicarb (10) = 14
Measured gap (22) – Normal gap (8) = 14
Is this anion gap due to ketoacidosis?
Na
149
K
5.2
Cl
108
HCO3 6
Glucose 35
149
35
114
AG > bicarb deficit
Albumin 38
Normal bicarb (24) – Actual bicarb (6) = 18
Measured gap (35) – Normal gap (8) = 27
Is this an anion gap acidosis?
Na
142
K
4.0
Cl
119
HCO3 17
Glucose 12
142
6
136
Bicarb deficit > AG
Normal bicarb (24) – Actual bicarb (17) = 7
Measured gap (6) – Normal gap (8) = 0
Treatment Principles
ABCs with fluid resuscitation
Rehydration reduces hepatic glucose
production, promotes insulin action and
renal glucose clearance.
Insulin (stop ketogenesis, liploysis and
gluconeogenesis)
Assess potassium or add to IV empirically if
producing urine
Treatment Principles
Fluid and electrolye replacement
Correct blood pH
Monitor glucose q 1 h and lytes q2h for
patient in shock
Monitor bicarbonate, anion gap and
calculated osmolality
Osmolality:
2(Na) + urea + glucose
Rapid reduction
in osmolality
(rapid reduction
of Na or
glucose)
Decreased
osmolality
Water
moves from
plasma to
interstitium
and cells
Cerebral edema
can occur
Glucose Correction
Insulin 0.1 unit/kg IV bolus plus
Insulin 0.1 unit/kg/h infusion
Higher doses exceed insulin saturation
capacity
Q 1 H blood sugar checks (lab)
Double infusion if glucose has not
dropped after first hour
Double again once if glucose has not
dropped in second hour
Glucose Correction
SC regimen with insulin Lispo for nonshock patients
Requires hourly blood sugar
measurement
0.3 u/kg SC bolus, then 0.1 u/kg q 1h
until glucose 13-15 mmol/L
Glucose Correction
Goal: 3-5 mmol/L/hr reduction
If glucose falls > 5 mmol/L, reduce
infusion (do not stop)
Add 5% dextrose to saline once glucose
~15-16 mmol/l
Glucose Correction
Correct to 10-12 mmol/L; avoid lower
levels in first 24 hours
DO NOT use Intensive Insulin protocol
for DKA
When glucose <13-15 mmol/L, anion gap
is < 12, bicarb > 18 and patient eating,
return to usual insulin Rx
Continue infusion 1-2 hours after initial
sliding scale dose
Fluid Replacement
5-8 L average loss; aggressive
replacement to maintain MBP >70 and
adequate urine output
Start with 0.9% NaCl (correct Na
deficit, protects against rapid reduction
in osmolality)
Hypernatremia usually volume deficit
4-15 mL/kg/hr; usually 1 L/hour for
average adult
Fluid Replacement
Conversion to 0.9% NaCl after volume
deficit replaced
Additional of 40 mmol KCl/L IV
increases osmolality of solution and will
delay correction of hyperosmolality
0.45 % NaCl with 40 mmol KCl/L or
Ringers following hemodynamic
stabilization and correction of defict
Saline
0.9%
154 mmol sodium and chloride/L, 300
mosmol
0.45%
77 mmol sodium and chloride/L
0.25%
39 mmol sodium and chloride/L
Saline
Lactated Ringers
130 mmol sodium and 109 mmol chloride/L
28 mmol lactate, 4 mmol potassium
Goals
Slow downward correction in sodium if
hypernatremic
If sodium rising or not improving after
rehydration, consider Ringers or 0.45%
NaCl
Recheck corrected sodium before
downscaling sodium
Potassium
Insulin and rehydration will lower
potassium
Add 20 mmol/L if K < 5.5 and patient
producing urine with initial
resuscitation; bolus prn
Safer to add K if potassium value
unknown
Phosphate
May be low, treatment controversal
except
If low at presentation should be treated
(insulin will drop it further)
Monitor phosphate and magnesium and
treat according to usual protocol
Acidosis
Corrects slowly, hours post glucose
normalization
Ketosis corrects faster than
hyperchloremic acidosis
Acidosis may persist after anion gap is
corrected
Anion gap is best method of determining
that ketosis is corrected
Acidosis
Avoid bicarb, not usually given unless pH
<7.00 or patient has life-threatening
hyperkalemia
Bicarb administration increase CO2
production with drop in cerebral pH as
CO2 crosses blood brain barrier
Alkali administration may slow resolution
of ketosis and/or cause alkalosis
Acidosis
Insulin administration key
Continue insulin infusion until anion gap
corrected; give additional glucose if
needed to maintain blood glucose
Monitor pH (venous pH acceptable) and
anion gap for resolution
Cerebral Edema
Highest risk in children
Rapid reduction of osmolality poses risk,
bicarb administration associated with
more cerebral edema
Monitor for headache, lethargy, altered
LOC
Cerebral Edema
Consider 0.25-1 g/kg mannitol or 5-10
ml/kg 3% saline
70% mortality; 7-14% good neurological
recovery
Case 1
•
•
•
•
25 year old woman, 26 weeks gestation
Flu like symptoms, vomiting and diarrhea
Felt too unwell to eat, withheld insulin
Resumed eating and insulin on following
day
• Still feeling week
Case 1
In ED:
• Glucose 16.8
• Lytes: Na 145 K 4.9 Cl 109 Bicarb 15
• 3+ ketones
• “Resolving DKA, resume diabetic
management”
Corrected Na: ~148
Anion Gap: 21
Case 1
•
•
•
•
Labs following day:
Na 148 K 4.9 Cl 111 Bicarb 12
Glucose 22
Sleepy
Corrected Na: ~153
Anion Gap: 25
Case 1
Treated as DKA with IV insulin, 0.9%
Nacl with potassium replacement
The following day:
Na 143 K 3.9 Cl 118 Bicarb 18
Concern regarding persistent acidosis
Anion Gap: 7
Bicarb Gap: 6
Case 2
•
•
•
•
28 year old woman, DMI since childhood
“poor control”
Admitted in coma with DKA
Lab on admission:
Glucose: 42
Lytes: Na 144 K 5.1 Cl 108 Bicarb 8
• Ketones: 1+
Anion Gap: 28
Corrected Sodium: 152
Case 2
• Blood glucose drops to 3.5 after 12
hours
• Insulin infusion stopped and D50
administered
• Over next 12 hours, glucose < 8 mmol/L
• Bicarb dropping; anion gap widening
Case 3
•
•
•
•
•
•
81 year old woman, DMI since 27
Admitted in coma
Blood glucose 36
Na 148 K 5.5 Cl 110 Bicarb 4
What is her anion gap?
Is this DKA alone?
Anion Gap: 34
Corrected Sodium: 156
Bicarb Gap: 20
Case 4
18 year old woman, DMI since age 12
Well controlled
Celebration
Admitted with DKA
Transferred to Level 3 on Day 2
CT shows no differentiation between
grey and white
Summary
Rehydration to restore and maintain
MBP
Initial resuscitation with 0.9% NaCl
Maintain renal perfusion
Insulin bolus 0.1 unit/kg and continuous
infusion 0.1 unit/kg/hr with potassium
to IV
Add potassium to IV unless
hyperkalemic; monitor lytes q 1h
Summary
Avoid glucose reduction > 5 mmol/L/hr
Add dextrose to IV once glucose < 16
mmol/L
Treat with insulin until glucose < 13-15;
AG < 12, bicarb > 18 and eating
Continue IV insulin 1-2 hours after
initial SC
Summary
DO NOT STOP INSULIN
DO NOT USE INSULIN PROTOCOL
DURING ACUTE PHASE
References
Kitabchi (2006). Hyperglycemic crisis in
adult patients with diabetes: a
consensus statement from the American
Diabetes Association. Diabetes Care.
29:2739.
Kitabchi (2009). Treatment of diabetic
ketoacidosis and hyperosmolar
hyperglycemic state in adults. Uptodate
on-line. Last update: May 1, 2009.