Transcript Diabetic Ketoacidosis

‫بسم هللا الرحمن‬
‫الرحيم‬
Dr. Fathi El Sewi
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).
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.
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).
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  -hydroxy
butyric acid ( -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 -HBA of 8 : 1 .
b- Utilization of ketone bodies.
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 -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.
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.
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 -HBA.
- Alkaline reserve (sodium and K losses).
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.
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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.
Diagnostic criteria of mild to
moderate DKA:
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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.
Diagnostic criteria of severe DKA:
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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)
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 .
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.
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.
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.
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
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
B-Ongoing monitoring:
-Blood glucose (using glucometers) every
hour.
-Electrolytes and pH every 4 hours.
-Urine for glucose and ketones every 4 hours
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.
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.
b-Insulin: Reversal of metabolic abnormalities :
i-Corrects hyperglycemia.
ii-Inhibits ketogenesis.
c-Potassium: Prevents complications associated with
hypokalemia.
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
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.
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.
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.
• 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.
Potassium Therapy
• Initially: Mild to moderate hyperkalemia occur in
patients with DKA.
• Later on: After initiation of:
Insulin therapy
Correction of acidosis
Volume expansion & hydration
lead to hypokalemia.
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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).
A Guide Protocol
1-Establish the diagnosis.
2-Establish the precipitating disease.
3-Assess the degree of dehydration: (BP, urine output, skin turgor)
4-Calculate total fluid deficit:
• For DKA: about 3-6 liters.
• For NKHH state: about 9 liters.
5-Determine the type of fluid as replacement:
– Use normal isotonic saline 0.9% in:
a-All cases of DKA.
b-Initial (1st 2 liters) in NKHH state.
– Use half strength saline 0.45% if measured sodium > 145 mEq/L.
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.
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
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.
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.
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.
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.
Thank you