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UTHSCSA Pediatric Resident Curriculum for the PICU
Hyperglycemia syndromes
Diabetic Ketoacidosis
Ketoacidosis-Hypersomolar Coma
Spectrum of DKA and
Hyperosmolar Coma
Pure Ketoacidosis
Rapid Onset
Marked Insulin
Lack
KetoacidosisHyperosmolar
Coma
Intermediate
Pure
Hyperosmolar
Coma
Slow Onset
Mild Insulin
Lack
Diabetic Ketoacidosis

Hyperglycemia

Ketonemia

Metabolic Acidosis
Pathophysiology

Insulin Deficiency is the primary defect in
patients with DKA
Muscle
Adipose
Hepatocyte
Glucose
Glycogen
Glucose-P
Amino
Acids
Glucose
Pyruvate, CO2
Ketoacids
Free
fatty
acids
Normal Insulin Activity
Insulin Deficiency


Breakdown of storage forms of energy to
meet energy needs. (Catabolism)
– Glycogenolysis
– Lipolysis
– Gluconeogenesis (from amino acids,
lipids)
Glucagon unopposed by Insulin
stimulates this catabolic reaction
Pathophysiology



Skeletal and cardiac tissues are able to
use free fatty acids and ketone bodies
as an energy source.
Glucose can not be used by these
tissues in the absence of insulin.
The brain is an insulin-independent
tissue and continues to use available
glucose.
Persistent Catabolism



Hyperglycemia is worsened by further
intake of glucose.
Excess Ketone bodies from Lipolysis
– Acetone
– -hydroxybutyrate (BHB)
– Acetoacetate (AA)
Ratio of BHB/AA normally 3:1 is driven to
15:1 in severe DKA
– Ketone test measures only acetoacetate
Hyperosmolar State
• Hyperglycemia acts as an osmotic
•
•
diuretic with obligatory loss of water
and electrolytes.
Osmolality = 2(Na) + Glucose/18 +
BUN/2.8 (normal  293 )
Ketosis/hyperglycemia stimulate
vomiting with aggravation of
dehydration
Hyperosmolar State

Hypovolemia secondary to dehydration
can promote decreased tissue
perfusion with anaerobic metabolism
and elevated lactate production

Total fluid deficit in severe DKA usually
averages around 10% of the total body
weight
Electrolyte Loss
K
I
D
N
E
Y
K+
Intracellular exchange
of potassium with
hydrogen ions
H+
Ketoacids draw out intravascular cations
of Sodium and Potassium
Glucose
Ketoacids
Phosphorous is also depleted in the osmotic diuresis
Fluid Balance in Diabetic
Hyperosmolarity
ECF = 14 L
ICF = 28 L
ECF
ICF
H2O
ECF hyperosmolar from ICF autotransfusion
Osmotic Diuresis
H2O
Osmotic Diuresis
ECF and ICF both hyperosmolar
Clinical Findings in DKA






Polyuria, Polydipsia, Polyphagia
Dehydration + orthostasis
Vomiting (50-80%)
Küssmaul respiration if pH < 7.2
Temperature usually normal or low, if
elevated think infection!
Abdominal pain present in at least
30%.
Clinical Findings of
Hyperosmolarity




Lethargy, delirium
Hyperosmolar coma is the first sign of
diabetes in 50-60 % of adult patients.
Hyperglycemia usually > 700-800mg/dl
Osmolarity above 340 mOsm/L is
required for coma to be present.
Precipitating Factors for
Hyperosmolarity





Too little insulin
Infection, even minor.
Severe stress.
Hypokalemia (Required by insulin).
Inadequate fluid intake
– Infancy (can not ask for fluids)
– Incapacitation (can not get to fluids/ask)
Laboratory Findings in DKAHyperosmolarity


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
Glucose > 700mg/dl
Total body sodium low, level high,
normal or low.
Potassium high, normal or low.
Large urine ketones
Bicarbonate < 15 mEq/L, pH < 7.2
Leukocytosis 15,000-40,000 even
without infection. High temp = infection.
Calculation of Osmolarity
Effective Osmolarity(mOsm/L)
2(Na = K) + Glucose (mg/dl)/20 = 280 - 295 mOsm/L
A calculated osmolarity less than 340 mOsm/L is
unlikely to cause coma. Other processes must be
considered (stroke, infection, toxin).
DKA does not cause coma in the absence of
hyperosmolarity.
Effective Osmolarity


The effective osmolarity calculation
uses only those biologically effective
molecules which are able to draw water
out of the cell.
Urea and other molecules measured in
the lab (alcohol) move freely between
the intra and extravascular spaces and
don’t draw water out of the cell.
Approach to Therapy


Correcting the hyperosmolar state and
dehydration is the initial aim of therapy.
Insulin therapy should be undertaken
only after the patient is stable
hemodynamically.
Glucose and H2O
H2O lost in urine
Loss of ECF, vascular collapse and death
Rehydration



Consider most patients with DKA to be
approximately 10% dehydrated.
The difference between the patient’s
weight at baseline and presentation is
an accurate measure of volume loss.
Normal Saline is the replacement fluid
of choice to restore hemodynamics.
Rehydration



Bolus fluids until correction of
circulatory failure.
Correct deficit over 36 to 48 hours.
– Provide maintenance fluids
(1600cc/m2/d) at the same time.
– Subtract resuscitation fluids from
deficit.
Avoid fluid administration > 4L/m2/d
Electrolytes



Sodium content varies between 75 to
154 mEq/L. Reduce as sodium levels
approach normal.
Total body potassium is reduced. When
K levels reach “normal” add 20-40
mEq/L as both KCL and Kphos.
Maximum K infusion rate 0.5 mEq/kg/hr.
Insulin Replacement



Insulin is essential for lowering glucose
to normal and correcting acidosis.
Following initial fluid replacement, then
administer 0.1U/kg IV and initiate an
infusion at 0.1U/kg/hr. (Regular Insulin).
Check serum glucose hourly and avoid
dropping glucose > 100mg/dl/h.
Insulin Replacement


When serum glucose falls below 300
mg/dl, add 5% Dextrose to maintain
stable glucose levels.
Falling glucose should be managed
with increased glucose concentration.
Do not decrease insulin infusion until
the metabolic acidosis is corrected.
Bicarbonate



Should only be used to treat
symptomatic hyperkalemia.
May be used for pH less than 7.0 to
provide some relief of Küssmaul
respiration (1mEg/kg over 1-2 hours).
Inappropriate use may result in
hypokalemia and paradoxical CNS
acidosis.
Intubation


Most patients requiring intubation
have hypovolemia.
– Avoid drugs which lower blood
pressure.
– Consider a small volume load first.
For patients with cerebral edema,
avoid medication which raise ICP
(Ketamine, Succinylcholine).
– Consider Thiopental and Lidocaine.
– Have Mannitol available for sudden
ICP.
Cerebral Edema


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May be sub-clinical at start of therapy.
CSF pressure is usually normal
initially.
Usually occurs unpredictably within
the first 24 hours of therapy.
Classically, patient’s labs are
improving.
No way to determine who will get this
complication.
Pathophysiology

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
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Brain conserves water by producing
osmoprotective molecules (taurine).
Osmolarity becomes
disproportionately higher in the brain
than other tissues.
Sudden fall in serum osmolarity
moves fluid across the blood-brain
barrier.
Brain becomes relatively
hypervolemic.
Cerebral Edema-Clinical Signs

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
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Initial complaint of headache.
Progresses to decreasing level of
consciousness, hypertension,
papilledema and bradycardia.
Coma and death soon follow.
Cerebral edema is a complication of
therapy, not a progression of DKA.
Cerebral Edema - Therapy



The best therapy is to prevent it with
careful rehydration.
Diagnosis available with CT scan.
Therapy for acute episode:
– Intubation and hyperventilation
– IV Mannitol 0.5 - 1.0 Gram/Kg as
bolus.
– IV sedation.
– Slow the rate of osmolar correction.
Evaluation of Therapy

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
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Controlled reduction in serum glucose.
Correction of acidosis “closing the gap”.
Clearing of serum ketones.
Clinical improvement
– fall in respiratory rate
– improved perfusion
– improving mental status.
Complications
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Infection esp. urinary tract infection.
Pancreatitis
Disseminated intravascular coagulation.
Arterial and venous thrombosis.
Hypoglycemia with seizure.
Hypokalemia with dysrhythmias.
Thromboembolism in Diabetes

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In several studies, thromboembolism
accounted for 20 to 50% of mortality.
Virchow’s triad: stasis, endothelial
damage and hypercoagulopathy.
Hypercoagulopathy:
– Hyperreactivity of platelets
– Hyperfibrinogenemia (Especially
Type 2)
– Elevated plasminogen activator (Type
2).
Thromboembolism

Endothelial Damage
– Elevated levels of von Willebrand
factor associated with endothelial
damage
• Seen in decompensated diabetes
esp. those with microvascular
disease
– Catheter placement
• Promotes venous stasis
• Potential endothelial damage
DKA in Type 2 Diabetics


Recent study: Arch of Internal Medicine
– 39% of patients had Type 2 diabetes.
– Majority of patients with Type 2
diabetes were Hispanic.
– 51% of patients were obese
Type 2 diabetics more likely to have
slow onset of ketoacidosis and
progression to hyperosmolar coma.
DKA in Type 2 Diabetes

Hyperosmolarity, obesity, lethargy, and a
relative hypercoagulopathy increase the
propensity for EMBOLISM and
THROMBOSIS in Type 2 diabetics.