2. DKA
Diabetic ketoacidosis (DKA) is an acute, major,
lifethreatening complication of diabetes.
DKA mainly occurs in patients with type 1 diabetes,
but it is not uncommon in some patients with type 2
diabetes.
DKA is clinically defined as an acute state of severe
uncontrolled diabetes that requires emergency
treatment with insulin and intravenous fluids.
3. DKA :definition
A state of absolute or
relative insulin
deficiency resulting in
hyperglycemia and an
accumulation of
ketoacids in the blood
with subsequent
metabolic acidosis
Hyperglycemia
– Blood glucose >250mg
/dL
Acidosis
– pH < 7.30
– Bicarb < 20 mmol/L
Ketosis
– Elevated serum or
urine ketones
– Serum ketones
>5mEq/L
4. physiology
To develop DKA there must be both
a relative lack of insulin and
a relative overactivity of counter-regulatory hormones
Insulin (anabolic)
– Glucose used for
energy substrate or
stored as glycogen
– Protein formation
– Fats stored as
triglycerides
Counter-regulatory
hormones (catabolic)
– Glycogenolysis
– Proteolysis -
gluconeogenesis
– Lipolysis-FFA &
ketone bodies
Glucose and lipid metabolism are regulated by the pancreatic hormone
Insulin,
and its Counter-regulatory hormones:
– Glucagon - Growth hormone – Catecholamines – Cortisol
5. Physiology of DKA
Diabetic ketoacidosis is a super fasted state in which
the body’s tissues are robbed of their normal energy
substrate Glucose,
And the body resorts to catabolism of glycogen,
protein and fat for energy.
6. Pathophysiology of DKA
Severe insulinopenia or lack of effective
insulin action results in a physiological
cascade of events in 3 PATHWAYS
1. Excessive glucose production
+ Reduced glucose utilization
Increased serum glucose
Osmotic diuresis, with loss of fluids, electrolytes
Dehydration
Activation of Renin-Angiotensin-Aldosterone axis
Accelerated Potassium loss
7. 2. Increased Catabolic processes
Cellular losses of sodium, potassium, phosphate
3. Increased release of free fatty acids from
peripheral fat stores
Substrate for hepatic ketoacid production
Ketoacids accumulate
Buffer systems are depleted
METABOLIC ACIDOSIS occurs
8. Progressive rise of blood concentration of these acidic organic
substances initially leads to a state of ketonemia.
Natural body buffers can buffer ketonemia in its early stages.
When the accumulated ketones exceed the body's capacity of
buffering them, they overflow into urine (ie, ketonuria).
If the situation is not treated promptly, more accumulation of
organic acids leads to frank clinical metabolic acidosis (ie,
ketoacidosis), with a drop in pH and bicarbonate serum levels.
Respiratory compensation of this acidotic condition results in
rapid shallow breathing (Kussmaul respirations).
9. Acetone produces the characteristic fruity breath
odour of ketotic patients.
Ketones, in particular beta hydroxybutyrate, induce
nausea and vomiting that consequently aggravate fluid
and electrolyte loss already existing in DKA.
Hyperglycemia usually exceeds the renal threshold of
glucose absorption Significant glycosuria Osmotic
diuresis Water is lost in urine resulting in Severe
dehydration, thirst, tissue hypo perfusion, and, possibly,
lactic acidosis
10. Potassium
The most characteristic disturbance is total body potassium loss.
Both lack of insulin (catabolic predominance) and
acidosis cause a shift of K+ extracellularly.
High urinary losses of K+ occur due to this
compartmental shift ,due to osmotic diuresis & due to
kaliuretic effect of hyperaldosteronism.
Serum K+ levels are usually normal, even when total
body K+ is depleted, because:
– The compartmental shift of K+ inside to outside the cell
– Only extracellular K+ is measured
11. Sodium
Initial serum sodium may be ‘low’ for several reasons:
– Depletion secondary to urinary losses / vomiting
– Hyperlipidemia displaces sodium in the most
frequently used laboratory assay, factitiously lowering
sodium values.
– Hyperglycemia High serum osmolarilty
Water driven from Intra to Extracellular space
Dilutional hyponatremia
Glucose Sodium
12. For each 100mg increase of serum glucose above 100mg/dl,
there is an expected decrease of about 1.6mEq/L in measured
sodium.
The ‘true’ serum sodium level can be calculated as:
[Na] + Glucose-100 x 1.6
100
The sodium should increase by about 1.6 mmol/L for each
100mg/dl decline in glucose.
If the corrected value is >150 mmol/L, severe
hypernatremic dehydration may be present and may
require slower fluid replacement.
Declining sodium may indicate excessive water
accumulation & risk of cerebral edema.
13. With prolonged illness & severe DKA, total body losses can approach:
- 10-13 mEq/kg of Sodium
- 5-6 mEq/kg of Potassium
- 4-5 mEq/kg of Phosphate
These losses continue for several hours during therapy until catabolic
state is reversed & diuresis is controlled.
Even though Sodium deficit may be repaired within 24 hours,
intracellular Potassium & Phosphate may not be completely restored
for several days.
The combined effects of Serum hyperosmolarity, Dehydration, and
Acidosis
Result in increased osmolarity in brain cells
Clinically manifests as an altered consciousness.
14. CLINICAL FEATURES
Precipitated by intercurrent illness, trauma, infections.
Symptoms:
-Nausea / Vomiting
-Polydipsia / Polyuria / Nocturia
-Abdominal pain
-Shortness of breath
-Weakness
Signs:
- Dehydration
- Hypotension
- Tachycardia
- Tachypnea / Kussmaul respirations
- Acetone odour of breath
- Abdominal tenderness
- Lethargy / altered level of consciousness / possibly coma
15. Lab Abnormalities and Diagnosis
Serum glucose is elevated >250mg/dl
Serum bicarbonate <20 mmol/L
Arterial pH <7.3, depending on the severity of the
acidosis.
Anion gap [(Na+K) – (Cl+HCO3)] >12-16 mEq/L
Urine analysis: Glucosuria + Ketones
16. Laboratory Abnormalities and Diagnosis
Serum amylase - may be due to pancreatitis. (but if
S.lipase is not ,this is likely to be nonspecific/ salivary)
Serum Creatinine may be falsely elevated due to
interference by ketones in the autoanalyzer
methodology.
Blood Urea Nitrogen (BUN) may be elevated.
Complete Blood Counts: may reveal possible infectious
etiology.
CSF study, CXR to rule out other causes for the clinical
condition.
17. Despite a total-body potassium deficit, the serum
potassium at presentation may be mildly elevated,
secondary to the acidosis.
Total-body stores of sodium, chloride, phosphorous,
and magnesium are also reduced in DKA but are not
accurately reflected by their levels in the serum
because of dehydration and hyperglycemia.
Elevated blood urea nitrogen (BUN) and serum
creatinine levels reflect intravascular volume
depletion.
18. MANAGEMENT OF DKA
Aims of management
Restore normal hemodynamic status.
Restore normal acid-base balance.
Correct blood glucose level
Restore perfusion by giving fluids, which will increase glucose
use in the periphery, restore GFR, and reverse the progressive
acidosis.
Stop ketogenesis by giving insulin, which will reverse
proteolysis and lipolysis, and stimulate glucose uptake and
processing, normalize blood glucose, and reverse acidosis.
Correct electrolyte losses by electrolyte supplementation.
Avoid the complications of treatment, including intracerebral
complications, hypoglycemia, and hypokalemia.
19. TREATMENT OF DKA
(Milwaukee DKA PROTOCOL)
CommentsTherapyTime
NPO
Can be repeated
10-20 ml/kg IV bolus NS or RL
insulin drip at 0.05-0.1
U/kg/hr
1st hour
If K<3mEq/L, give 0.5-
1mEq/Kg as oral K soln or
increase IV K to 80 mEq/L
0.45% NS + continue insulin
drip.
20 mEq/L Kphos & 20 mEq/L
Kac.
5% glucose if bl.sugar
<250mg/dl *
2nd hour until
DKA
resolution
No emesis. Normal
CO2 >16mEq/L. pH>7.30
Oral intake + S/C insulinVariable
electrolytes
* IV rate = 85ml/kg + maintenance – bolus
23 hr
20. This protocol corrects a deficit of 85ml/kg (8.5%
dehydration) for all patients in the first 24 hours.
Children with mild DKA rehydrate earlier & can be
switched to oral intake, whereas those with severe DKA and
a greater volume deficit require 30-36 hours with this
protocol.
The initial BOLUS given is a sugar free ISOTONIC
solution. The patient is invariably hypertonic, keeping
most of the initial infusion in the intravascular space.
This ensures quick volume expansion.
Subsequent fluid is HYPOTONIC to repair the free water
deficit, to allow intracellular rehydration and to allow a
more appropriate replacement of on-going hypotonic urine
losses.
21. Insulin should be given at the beginning to
-accelerate the movement of glucose into cells
-to subdue hepatic glucose production
-to halt movement of fatty acids from periphery to liver
However, an initial insulin BOLUS does NOT speed recovery,
and may increase the risk of hypoglycemia and hypokalemia.
Therefore, insulin INFUSION is started (WITHOUT A BOLUS)
at the rate of 0,1 U/kg/hour.
Rehydration also lowers glucose levels by
-improving renal perfusion enhancing renal excretion
Once glucose level goes below 180 mg/dl, osmotic diuresis stops
and therefore rehydration becomes faster without further
increase in fluid infusion rate.
22. Hyperglycemia is corrected well before the correction of acidosis.
Therefore, even after normal glucose levels are reached, insulin
is still required to control fatty acid release.
Thus insulin infusion can be lowered but NOT STOPPED once
hyperglycemia has resolved.
However ,to continue insulin infusion without causing
hypoglycemia, GLUCOSE should be added to the solution
usually as a 5% solution.
This glucose is added when serum glucose has decreased to 250
mg/dl, so that there is sufficient time to infusion before serum
glucose falls further.
23. Cautious rehydration:
Important to approach any child with hyperosmotic state
with cautious rehydration.
Effective Serum Osmolality =
{ 2 x [Na uncorrected] + [Glucose] }
(This is an accurate index of tonicity of body fluids reflecting the
intracellular & extracellular hydration better than measured plasma
osmolality.)
This value is usually elevated in the beginning, and should gradually
normalize.
A rapid decline or a slow decline to a sub-normal range may indicate
an excess of free water entering the vascular space, and therefore
an increasing risk of developing CEREBRAL EDEMA.
25. Cerebral edema
Clinically apparent cerebral edema occurs in approximately 1% of childhood
DKA and is associated with high mortality and neurological morbidity.
The pathogenesis of the cerebral edema is not understood; Some studies
have attributed it to cellular swelling as a result of rapid osmolar changes
occurring during intravenous infusions.
Several studies, however, have shown no relationship to the volume or
sodium content of the infusion nor any association with the rate of change
in serum glucose concentration. This suggests that other factors may be
important in the pathophysiology of DKA-related cerebral edema.
Clinical signs are variable
– Gradual deterioration and worsening of conscious level, or
– More commonly a gradual general improvement followed by sudden
neurological deterioration
Requires a high index of suspicion.
27. Cerebral edema –Treatment :
Urgent recognition and treatment are essential.
Mannitol
Reduce IV fluid rate to 70% maintenance
Elevate head end of bed to 45o
Consider intubation & Controlled hyperventilation
(vasoconstrictor effect of hypocarbia)
