1. Diabetic Ketoacidosis
Local seminar
Medical Oncology department
By
Salah Mabruok Khalaf
Master internal medicine
MD Medical Oncology
South Egypt Cancer Institute
2013

2. Overview
• Definition
• Epidemiology
• Pathophysiology of DKA
• Etiology
• Clinical manifestation
• Investigations
• Differential Diagnosis
• Prevention
• Treatment
• Pitfalls in DKA
• A guide protocol

3. DKA Definition
DKA = 3 letters= triad of D K A
Diabetic
glucose >250 mg/dL (usually 500-800)
Keto
ketones produced
ketones – both in urine and in serum
acetoacetate, acetone, betahydroxybutyrate
fruity smell, not often encountered in real life)
consider that if these criteria aren’t met, it may not be DKA
Acidosis
Increased anion gap, metabolic acidosis; HCO3- <15, pH<7.30

4. Epidemiology
• Annual incidence in U.S.
– 5-8 per 1000 diabetic subjects
• DKA is reported in 2-5% of known type 1 diabetic
patients in industrialized countries, while it occurs
in 35-40% of such patients in Africa.
• Higher incidence below 5 years
• 2.8% of all diabetic admissions are due to DKA
• Overall mortality rate ranges from 2-10%
– Higher is older patients

5. Pathophysiology
Normal
Counterregulatory hormones
Insulin Glucagon, Epinephrine, Cortisol,
Growth hormone

6. Pathophysiology
DKA
Insulin deficiency
Excess counterregulatory
hormones

7. Insulin Deficiency
Glucose uptake Lipolysis
Proteolysis
Glycerol Free Fatty Acids
Amino Acids
Gluconeogenesis
Hyperglycemia Glycogenolysis Ketogenesis
Osmotic diuresis Acidosis
Dehydration
Excess counterregulatory hormones

8. Etiology
• Insulin deficiency • Excess Counterregulatory
– Insulin missed dose hormones
– Pancreatitis – Infection i.e. Pneumonia
– Heavy meal – MI
– Stroke
– Trauma
– Emotional
– Pregnancy
– Iatrogenic

9. Clinical manifestations
Insulin Deficiency
Glucose uptake Lipolysis
Proteolysis
Glycerol Free Fatty Acids
Amino Acids
Gluconeogenesis
Hyperglycemia Glycogenolysis Ketogenesis
Osmotic diuresis
Polyuria Electrolyte imbalance Acidosis
Polydipsia
Fruity breath (acetone smell)
Kussmaul breathing (acidotic)
Dehydration Mental status changes
Dry tongue Tachycardia Hypotension Abd pain

10. Clinical manifestations
Special notes
• Abdominal pain
It is more common in children than in adults
It is multifactorial
 dehydration of muscle tissue
 Delayed gastric emptying
 Ileus from electrolyte disturbances
 Metabolic acidosis;
It sometimes mimicks acute abdomen
It is classically periumbilical

11. Differential Diagnosis
• DD of acidotic breathing
– Renal failure
– Amonia increase in HCF
– Hysterical
• DD of diabetic coma
– Lactic acidosis
– Hyperosmolar non-ketotic coma
– Hypoglycemia
• DD of coma in general
• DD of acute abdomen

12. DKA vs. HHS
DKA HHS
Age More in children More in elderly
DM type More in type I More in type II
Glucose > 250 > 600
Ketonuria/emia +++++ + or -
pH <7.3 >7.3
HCO3 <15 >15
S osmolarity Variable Hyperosmolarity
Sensitivity to insulin Variable Sensitive to small dose

13. DKA vs. HYPOGLYCEMIA
DKA Hypoglycemia
Etiology Insulin deficiency or increased Insulin overdose or
counter-reg hormones hyperinsulinemia
Onset Gradual Acute
Symptoms and signs S of hyperglycemia -S of Brain glucopenia
S of dehydration - S of sympathetic overactivity
S of acidosis
RBS hyperglycemia hypoglycemia
Ketonuria Yes No
Ketonemia Yes No
IV glucose No effect Rapidly recover if early
Golden rule
Any diabetic patient with DKA versus hypoglycemia, give
glucose even before glucose measuring

14. Investigations
For diagnosis
Triad for diagnosis
1. RBS  Hyperglycemia > 300 mg/dl
2. Ketonemia and ketonuria
3. Blood gas metabolic acidosis
– pH < 7.35, anion gap (Na + K) – (Cl + Bicarb) > 10, and
Bicarbonate <15 mEq/L

15. Investigations
For diagnosis
• Other findings
– Electrolyte serum level
• Hyperkalemia (rarely Hypokalemia), Hyponatremia (rarely
Hypernatremia )
– Investigation for the cause such as
• Urine Analysis, AMI panel and ECG, Chest x-ray
– Hyperosmolarity
• Normal = 285-295 milli-osmoles per kilogram (mOsmol/kg)
• [Glucose] and [BUN] are measured in mg/dL

16. Investigations
For Monitoring
• RBS
– Every 1 hour till RBS reaches 200 mg/dL or less, then
every 6 hours
• Urine ketones
– Every 8h
• Blood gas after fluid replacement
• Electrolyte serum level every 4 hours till correction

17. Treatment of DKA
• Treatment of predisposing factors
• Initial hospital management
– Care of comatosed patients
– Fluid and electrolytes replacement
– Insulin replacement and glucose administration when needed
– Treatment of complications
• Once resolved
– Convert to home insulin regimen
– Prevent recurrence

18. Fluids and Electrolytes
• Fluid replacement
– Restores perfusion of the tissues
– Average fluid deficit 3-6 liters
• Initial resuscitation with saline
– 1 L of normal saline over the first ½ hour then
– ½ L of normal saline over ½ hour then
– ½ L of normal saline over 1 hour then
– ½ L of normal saline over 2 hours
– Then the rate will depend on clinical judge (BP, CVP,
basal lung crepitation)

19. Fluids and Electrolytes
• K+ level
– If Hyperkalemia (> 5.5 meqlL)
• initially present
• No treatment as it resolves quickly with insulin drip
– If normal level (3.5-5.5 meqlL)
• Add 26 mmol for each Liter of infused fluid
– If Hypokalemia (<3.5 meqlL)
• Add 39 mmol for each Liter of infused fluid

20. Fluids and Electrolytes
• Phosphate deficit
– May want to use potassium phosphate
• Bicarbonate
– Not given unless pH <7 or bicarbonate <5 mmol/L or unresolved
acidosis after fluid replacement
BW x Becar deficit
– Dose (mmol of NaHco3) = -------------------------------------------
6
BW x Becar deficit
– Dose (No of ampoules of NaHco3) = ----------------------------------------
150

21. Fluids and Electrolytes
• Na level:
– Calculate the corrected Sodium (for each 100 mg/dL
glucose above 100, add 1.6 meq/l to Na level)
• If corrected Na is High or Normal  use Half NS (250-1000
ml/hr)
• If corrected Na is Low  use NS, rate depends on severity of
volume depletion

22. Insulin Therapy
• Initial dose
– IV bolus of 0.1-0.2 units/kg (~ 10 units) regular insulin
– Infusion insulin at 0.1 units/kg/hr (max 8 units/hr).
• Maintenance dose (Check BG Q1hour, goal is 50-80
mg/dl/hr)
– If falling too rapidly, decrease the rate
– If falling too slowly increase the rate by 50-100%
• Continue IV insulin until urine is free of ketones and
RBS reaches 250-300 mg/dl

23. Insulin Therapy
• When RBS reaches 250-300 mg/dl
– Decrease the rate of insulin inf to 0.05-0.1 IU/kg/hr (goal
is to keep RBS in this range until the gap closes (normal
gap 7-8 mEq/l) then start home maintenance SC insulin
under umbrella of infused insulin for 2 hours, then
continue on SC insulin only .

24. Glucose Administration
• Supplemental glucose
– Hypoglycemia occurs
• Insulin has restored glucose uptake
• Suppressed glucagon
– Prevents rapid decline in plasma osmolality
• Rapid decrease in insulin could lead to cerebral edema
• Glucose decreases before ketone levels decrease
• Start glucose when plasma glucose < 300 mg/dl

25. Insulin-Glucose Infusion for DKA
Blood glucose Insulin Infusion D5W Infusion
<70 0.5 units/hr 150 ml/hr
70-100 1.0 125
101-150 2.0 100
151-200 3.0 100
201-250 4.0 75
251-300 6.0 50
301-350 8.0 0
351-400 10.0 0
401-450 12.0 0
451-500 15.0 0
>500 20.0 0

26. Complications of DKA
• Infection • Pulmonary Edema
– Precipitates DKA – Result of aggressive fluid
– Leukocytosis can be secondary resuscitation
to acidosis
• Cerebral Edema
• Shock – First 24 hours due to aggressive
– If not improving with fluids r/o correction of hypoglycemia or
MI administration of hypotonic
solution
• Vascular thrombosis
– c/p: Mental status changes
– Severe dehydration
– Tx: Mannitol
– Cerebral vessels
– May require intubation with
– Occurs hours to days after DKA
hyperventilation

27. Causes of Cerebral Edema
Mechanism:
• The brain adapts by producing intracellular osmoles
(idiogenic osmoles) which stabilize the brain cells from
shrinking while the DKA was developing.
• When the hyperosmolarity is rapidly corrected, the
extracellular fluids is corrected faster than brain cells
– The brain becomes more hypertonic than the extracellular fluids →
water flows into the cells → cerebral edema

28. Causes of Cerebral Edema
The many factors have been implicated:
 Rapid and/or sharp decline in serum osmolality with
treatment.
 High initial corrected serum Na concentration.
 High initial serum glucose concentration.
 Failure of serum Na to raise as serum glucose falls during
treatment. Osmolality
Na
Glucose

29. Presentations of Cerebral Edema
Cerebral Edema Presentations include:
 Deterioration of level of consciousness.
 Headache and blurring of vision
 Vomiting
 Convulsion.

30. Treatment of Cerebral Edema
• Reduce IV fluids
• Raise foot of Bed
• IV Mannitol
• Elective Ventilation
• Dialysis if associated with fluid overload or renal
failure.
• Use of IV dexamethasone is not recommended.

31. Prevention of DKA
• Never omit insulin
– Cut long acting in half
• Prevent dehydration and hypoglycemia
• Monitor blood sugars frequently
• Monitor for ketosis
• Provide supplemental fast acting insulin
• Treat underlying triggers
• Maintain contact with medical team

32. Pitfalls in DKA
• Plasma glucose is usually high but not always
– DKA can be present with RBS < 300 due to
• Impaired gluconeogenesis
– Liver disease
– Acute alcohol ingestion
– Prolonged fasting
– Insulin-independent glucose is high (pregnancy)
• Chronic poor control but taking insulin
• Ketone in urine may be –ve in DKA, but always +ve
in blood
– Due to measurement of acetoacetic acid in urine not,
betahydroxybuteric acid
– Acetone in blood should be done in this case

33. Pitfalls in DKA
• High WBC may be present without infection
• Infection may be present without fever
• High Creatinine may be present without true renal function: it
may cross react with ketone bodies.
• Blood urea may be elevated with prerenal azotemia
secondary to dehydration.
• Serum amylase is often raised even in the absence of
pancreatitis

34. Email: salahmab76@yahoo.com
Email: salahmab76@yahoo.com
salahmab76@gmail.com
salahmab76@gmail.com
Facebook: Dr salah mabrouk
Facebook: Dr salah mabrouk
YouTube channel: salahmab1
YouTube channel: salahmab1
Mobil: (202) 01004081234
Mobil: (202) 01004081234