3. DR. EMAD AHMED, MD
Ass. Professor of Anesthesia and
Intensive Care
Suez Canal University
4. Diabetic Ketoacidosis (DKA)
It is a life threatening but reversible
complication of
type 1 diabetes due to absolute insulin
deficiency.
Ketoacidosis: High anion gap metabolic acidosis
due to excessive blood concentration of ketone
bodies (Ketoanion).
5. Pathogenesis of DKA
A-The basic underlying mechanisms are:
-Absolute deficiency of circulating insulin.
-↑secretion of insulin counterregulatory hormones;
glucagon, adrenaline, cortisol and growth
hormone.
6. B-This leads to disturbances in the following physiological processes:
-↓glucose utilization (hyperglycemia).
-↑ proteolysis (↑ amino acids, glutamine and alanine).
-↑ lipolysis (↑ glycerol and FFAs).
-↑ glycogenolysis (breakdown of muscle glycogen →↑ lactate).
-↑ gluconeogensis (glutamine & alanine & glycerol & lactate are the
precursors).
7. C-This results in the following metabolic abnormalities:
1-Hyperglycemia.
2-Hyperketonemia: 2 main mechanisms:
a-↑ Production of ketone bodies (ketogenesis):
-Increase FFAs →↑ hepatic uptake → FFAs enter
the mitochondria → oxidation to form acetoacetic
acid.
-Large part of acetoacetic acid → reduced to β
-hydroxy butyric acid (β -HBA).
-Small part of acetoacetic acid is decarboxylated
to acetone.
The 3 ketone bodies are released to the blood in a
ratio between acetoacetic acid to β-HBA of 8 : 1 .
b-↓ Utilization of ketone bodies.
8. D-The consequences of these metabolic abnormalities are:
a-Hyperglycemia:
-Osmotic diuresis.
-Excessive urinary losses of H2O & Na, K.
-Dehydration and hypotension.
b-Hyperketonemia:
-Ketonuria.
- ↑ Blood acidity (acetoacetic acid and β-HBA are strong
acids).
-Obligate losses of sodium and potassium due to ↑ urinary
excretion of ketone bodies (salt) →↓ alkaline reserve.
-Acetone is a CNS anaesthetic.
9. E-Electrolytes and acid base disturbances during DKA:
a-Serum K: Usually high (hyperkalemia) secondary to:
1-Shift of K from intracellular to extracellular compartment
due to:
-Insulin deficiency and hyperglycemia.
-Extracellular hyperosmolarity.
-Acidosis.
-↑ Catabolism and breakdown of cellular protein.
2-Impaired cellular uptake of K.
10. b-Serum sodium: Usually low secondary to:
-Hyperglycemia leads to ↑ osmotic flux of H2O from intracellular
to extracellular space.
-Obligate sodium loss with ketonuria.
c-Metabolic acidosis: Secondary to:
-↑ Production and ↓ utilization of strong acids; acetoacetic acid
and β-HBA.
-↓ Alkaline reserve (sodium and K losses).
11. Clinical features of DKA
A-Symptoms of DKA:
1-Classic symptoms of hyperglycemia: short period of time:
Polyuria, polydipsia, wt loss and thirst.
2-Other symptoms:
- General weakness, malaise and lethargy.
-Nausea, vomiting and abdominal pain.
-↓ Perspiration.
- Disturbed consciousness and confusion.
3-Symptoms of underlying infections or other conditions; fever,
abdominal pain, dysuria, chest pain…etc.
12. B- Physical signs of DKA:
a-General signs: Ill appearance and disturbed consciousness.
b-Signs of dehydration:
-Skin: Dry, hot, flushed, and loss of skin turgor.
-Tongue: Dry (sometimes woody tongue).
-Eyes: Sunken eyes and dark circles under the eyes.
c-Vital signs:
-Tachycardia, hypotension and tachypnea.
d-Specific signs:
-Ketotic breath: A strong, fruity breath odour (similar to nail
polish remover or acetone).
-Acidotic breath (Kussmaul's respiration): deep and rapid.
-Abdominal tenderness.
13. Diagnostic criteria of mild to
moderate DKA:
Blood glucose > 300 mg/dl.
Mild to moderate dehydration.
Ketonuria: mild (+) to moderate (++).
Serum bicarbonate < 15 m Eq/L.
pH is acidic (Metabolic acidosis):
Arterial < 7.3. Or
Venous < 7.25.
14. Diagnostic criteria of severe DKA:
Blood glucose > 300 mg/dl.
Heavy ketonuria +++
Severe dehydration.
pH is acidic:
Arterial < 7. Or
Venous < 6.95.
Serum bicarbonate < 10 mEq/l.
↑ Anion gap > 12 mEq/l (normal gap 7-8 mEq/l)
AG = (Na+
) – (Cl-
+ HCO3)
15. Urine testing during DKA
1- Urine glucose conc. Is poorly correlated with BG levels.
2- Renal threshold for glucose and ketones are increased in DKA
& HHS.
3- Most of the available laboratory urine tests (nitroprusside test)
detect only acetoacetate & acetone but not beta–HB.
4- Beta-HB is the predominant ketones in severe untreated DKA
cannot be measured or recognized by the standard
nitroprussid test .
16. 5- When the clinical condition improves with treatment , the
urine test results become positive due to the returning
predominance of acetoacetate .
6- So, during follow up of patients with DKA urine test for ketones
is better avoided.
7- Now blood ketone measurements are available and detect
beta-HB.
17. Complications of DKA
1-Complications of associated illnesses e.g. sepsis or MI.
2-Adult respiratory distress syndrome.
3-Thromboembolism (elderly).
4-Complications of treatment:
a-Hypokalemia: Which may lead to:
-Cardiac arrhythmias.
-Cardiac arrest.
-Respiratory muscle weakness.
18. b-Hypoglycemia.
c-Overhydration and acute pulmonary edema: particularly in:
-Treating children with DKA.
-Adults with compromised renal or cardiac function.
-Elderly with incipient CHF.
19. d-Neurological complications: Cerebral Edema.
-It occurs only in children with DKA.
-Very dangerous and increases mortality.
-The risk is related to the severity, duration and
rapid correction of DKA.
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 brain becomes hypertonic
towards the extracellular fluids → water flows into
the cells → cerebral edema
20. Management of DKA
The main lines of management include:
A-Primary assessment:
-Volume status and degree of dehydration.
-Blood pressure and cardiac condition.
-Degree of consciousness.
-Degree of acidosis.
-Precipitating disease
21. B-Ongoing monitoring:
-Blood glucose (using glucometers) every hour.
-Electrolytes and pH every 4 hours.
-Urine for glucose and ketones every 4 hours
22. C-Initiation of treatment:
1-General measures:
-Airway and O2 inhalation if needed.
-IV line.
-Urinary Foley's catheter (if in shock).
-NGT (Nasogastric Tube): to avoid gastric
dilatation and protection from aspiration .
-Thrombosis prophylaxis: 5000 units of heparin
SC/12 hours.
-Empiric use of 3rd
generation cephalosporin
antibiotics.
23. 2-Specific measures:
Successful therapy of hyperglycemic crises requires the
administration of:
a-Fluids:
1- Correct volume deficit and hypotension.
2- Improve tissue perfusion.
3-Improve insulin sensitivity (↓insulin counterregulatory hormones).
4-Improve glomerular filtration rate:
i-↑ excretion of large amount of glucose in urine.
ii-Clears hyperketonemia.
5- Correct metabolic acidosis.
24. b-Insulin: Reversal of metabolic abnormalities :
i-Corrects hyperglycemia.
ii-Inhibits ketogenesis.
c-Potassium: Prevents complications associated with hypokalemia.
25. Fluid Therapy
The expected volume deficits calculated as:
5-10% of body wt in DKA (3-6 liters).
15 % of body wt in NKHH (9 liters).
Replacement therapy should be given within 24
hours after admission:
50% of the deficit in the first 4 hours.
50% of the deficit in the next time for up to 24 hours,
guided by ongoing clinical evaluation.
For children and adolescents (less than 20 years):
Fluids are given as 10-20 ml/kg/hour in the first four
hours.
Then given guided by clinical evaluation
26. Type of fluid
1-Normal saline (0.9% sodium chloride).
Advantages:
-Available all the time.
-Rapid expansion of extracellular compartment.
-Slow decline of extracellular osmolarity.
-Slow rate of cerebral edema evolution.
Disadvantages: May accentuate hypernatrimia if
present.
Indications:
-All cases of DKA.
-Initial (1st
2 liters) in NKHH state.
27. 2-Half strength saline (0.45% sodium chloride):
Used only if serum corrected sodium is high >145
mEq/L.
Corrected sodium level = measured sodium +
corrected value.
Corrected value: For every 100 mg/dl BG above
the normal baseline of BG 100 mg/dl, Add 1.6
mEq/l Na to the measured serum sodium.
Example: Measured Na = 134 mEq/L, BG=
400mg/dl.
Corrected Na value: 3 x 1.6 mEq/L=4.8
mEq/L.
The serum corrected Na is: 134+4.8 = 138.8
mEq/L.
28. Insulin Therapy
Standard low dose insulin regimen: This regimen is the
only effective therapy in DKA & NKHH state:
1-Inhibits ketogenesis and gluconeogenesis.
2- Presence of insulin resistance state
secondary to:
a- ↑ Stress insulin counterregulatory
hormones.
b- Ketone bodies & FFAs.
c- Hemoconcentration and electrolytes
imbalance. d- Hyperosmolarity.
e- Infection.
29. Type of insulin : Regular : Rapid or short acting insulin U-40 & U-100.
Regimen:
Initial bolus: 0.1 U/kg body wt given IV.
Maintenance: 0.1 U/kg/body wt /hour:
a- IV Infusion set: Add 100 units of regular insulin +500 ml saline i.e.
every 5 cc fluid contains 1 unit of insulin
b-IV infusion set is not available: IM route.
30. Potassium Therapy
Initially: Mild to moderate hyperkalemia occur in patients with DKA.
Later on: After initiation of:
Insulin therapy
Correction of acidosis lead to hypokalemia.
Volume expansion & hydration
31. Rational of potassium therapy
In the 1st
2 liters of fluid → add no potassium.
If urine output confirmed → add KCl from 3rd
liter on.
If serum potassium:
< 3 mEq/L → add 20 – 40 mEq KCl/liter to IV saline.
3-5 mEq/L → add 10 – 20 mEq KCl/liter to IV saline.
> 5 mEq/L → add no potassium.
Patient with oliguria or renal insufficiency: K levels
must be frequently monitored with continuous ECG
evaluation.
The infusion continues until the patient can tolerate
oral potassium supplement (15 CC potassium syrup/ 8
hours).
33. 6-Order the rehydration program as follow (normal saline):
First 4 hours : 50% of the calculated total fluid deficit.
Next time for up to 24h: 50% of the calculated total fluid deficit.
34. 7-Order and start insulin regimen:
Type of insulin: Rapid or short acting insulin.
Initial bolus = 0.1 unit X BW in Kg / direct IV.
Maintenance = 0.1 unit X BW in Kg / hour.
Infusion set available:
Order: Add 100 units of regular insulin to 500 cc
saline i.e. every 5 cc contains one unit of insulin,
calculate the dose and give by IV drip.
Infusion set is not available → IM route
NB: For IM route: it is important to use a needle that is
long enough to insure that the insulin is not given
SC
35. 8-Order potassium replacement regimen:
Type of fluid: potassium chloride ( amp=10 mEq).
Aim: K level should be in the range 4-5 mEq/L.
If serum potassium:
< 3 mEq/L → add 20 – 40 mEq KCl/liter to IV saline.
3-5 mEq/L → add 10 – 20 mEq KCl/liter to IV saline.
> 5 mEq/L → add no potassium.
36. 9-Monitoring:
Blood glucose by glucometer every hour.
Urine analysis for glucose and ketones every 4 hours.
10-Order IV glucose 5% (second line) once blood glucose reaches:
< 250 mg/ dl in DKA.
< 300 mg/ dl in NKHH state.
11-Re-evaluate parameters of rehydration establishment:
Stable blood pressure.
Normal urine output.
Clinical signs of rehydration.
37. 12-Evaluate the criteria for stopping hourly insulin regimen (resolving
DKA):
Acidosis corrected clinically and by pH.
Negative ketonuria.
Eating.
Patient looks good and feels good.
38. 13-Initiate SC insulin therapy:
Give 10 units NPH/SC one hour before stopping
hourly insulin regimen
a-Patients with newly diagnosed diabetes:
Initial dosage is 0.5 - 0.8 U/Kg BW/day:
calculate the dose and give (2/3) before
breakfast and (1/3) before dinner in a ratio (2/3)
NPH and (1/3) regular insulin.
b-Patients with known diabetes:
Initial dosage is the same as the dosage they
were receiving before onset of DKA.
Monitor blood glucose before and after each
meal and at bed time, and upgrade the insulin
doses accordingly.
