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Objectives
ƒ Discuss the signs and symptoms commonly associated
with DKA in the pediatric patient
ƒ Discuss bedside evaluation for DKA associated cerebral
edema
Pediatric Diabetic Ketoacidosis (DKA)
Management in the Emergency Room
and Ensuring Stable Transition to ICU
ƒ Discuss diagnostic studies and management of DKA in the
ER
ƒ Discuss guidelines for consultation and transfer to the ICU
Andrea Hoogerland, MD
April 5, 2013
ƒ Discuss telehealth and recommendations for when it
should be activated
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Definition
DKA – the problem
ƒ DKA is caused by decreased circulating insulin and is defined
by: 1. hyperglycemia (blood glucose >200) 2. acidosis
(venous ph <7.3 and/or HCO3 < 15) 3. elevated ketones
(betahydroxybutyrate and acetoacetate)
ƒ Insulin allows the body to uptake glucose into cells
ƒ Decreased circulating insulin can be seen with an absolute
deficiency (pancreatic destruction) or a relative deficiency
(unable to increase insulin appropriately in stress, illness, etc.)
ƒ An absolute insulin deficiency usually not seen until pancreas
has <10% Beta cell mass (pancreatic destruction-?autoimmune)
ƒ DKA severity graded according to degree of acidosis:
ƒ 1. mild: ph 7.2-7.3
ƒ 2. moderate: ph 7.1-7.2
ƒ 3. severe: ph < 7.1
ƒ Accounts for between 8-29% of hospital admissions for
diabetes
ƒ Almost 70% of DKA patients have a new diagnosis of
diabetes at hospital admission
ƒ Can occur with both type I and type II diabetes, but is much
more commonly seen with type I
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New Diagnosis DKA
New Diagnosis DKA – cont.
ƒ Many parents report a history of polydipsia, polyuria, and
weight loss prior to admission
ƒ Infection can trigger DKA--approximately 25% of new
diagnoses linked to infection
ƒ The classic triad of nausea, vomiting, and abdominal pain
may be the presenting symptoms
ƒ Younger children (<6 years old) and lower socio-economic
status have been shown to increase the risk for DKA as the
initial presenting sign of diabetes
ƒ The abdominal pain can be severe and mimic appendicitis
ƒ In a review of 139 new diagnoses presenting with DKA,
children < 5 years old had a relative risk of 2.7 for DKA;
those children with Medicaid or no insurance made up 62%
of the new diagnosis admissions
ƒ In addition, some parents note “funny breathing” (Kussmaul
respirations)
ƒ Neurologic symptoms (drowsiness, lethargy, coma) are found
usually in the most severe cases
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Established diagnosis type I DM with DKA
Type II DM with DKA
ƒ Children at risk for DKA after diagnosis made include those
with higher Hgb A1C levels and higher insulin requirements
(in other words, poor control)
ƒ Female adolescents (highest risk in patients over 13)
ƒ Uninsured children over 13
ƒ Children with coexistent psychiatric issues who are over 13
ƒ Children who have had DM diagnosis for longer
ƒ In fact, some estimates are that almost 60% of DKA
episodes occur in only 5% of children
ƒ Also an increased risk if on insulin pump (due to pump
malfunction)
ƒ DKA can occur in children with established Type II DM
ƒ A study done at UCSF in 2005 showed that 13% of their
DKA admissions between the ages of 9-13 had type II DM
ƒ This number is likely to increase with our increasing obesity
epidemic
ƒ Obese African American children were particularly at risk,
but non-Caucasian ancestry seems to confer higher an
overall increased risk (Hispanic, Native American,
Canadian aboriginal)
ƒ The obvious question would be whether this is an inherent
risk or is in fact related to socioeconomics with diet choices
and prevalence of obesity
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Cactus Scientists Recommend Drinking 8
Cups Of Water Per Year
Pathophysiology
ƒ Pancreatic destruction leads to deficiency of circulating insulin
ƒ This increases counter-regulatory hormones (glucagon,
catecholamines, cortisol and growth hormone)
ƒ High cortisol levels lead to proteolysis (used for
gluconeogenesis)
ƒ This leads to increased glucose production by the liver &
kidney (think of stress response) with impaired glucose
utilization and uptake
ƒ Abnormal insulin vs. counter-regulatory hormone balance also
activates hormone-sensitive lipase
ƒ Lipase breaks down FFA which are taken up by the liver and
used to make ketones as an alternate energy source
ƒ Essentially, the body goes into “starvation” mode despite
having stores of glucose
News in Brief • Science & Technology • Issue 48•44 • Oct 25, 2012
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ƒ acidosis is caused by ketone body generation
ƒ Acetoacetate, beta-hydroxybutyrate, and acetone collectively are called
ketone bodies. The first two are synthesized from acetyl-CoA, in the
mitochondria of liver cells...Ketogenesis in liver is effectively irreversible
because the enzyme that catalyzes the conversion of acetoacetate to
acetoacetyl-CoA is not present in liver cells. Ketone bodies, unlike fatty
acids and triglycerides, are water-soluble. They are exported from the
liver, and are taken up by other tissues, notably brain and skeletal and
cardiac muscle. Extrahepatic tissues utilize ketone bodies by converting
the beta-hydroxybutyrate successively to acetoacetate, acetoacetatylCoA, finally to acetyl-CoA which is oxidized via the TCA cycle to yield
energy. In a normal person, this pathway of ketone body synthesis and
utilization is most active during extended periods of fasting. Under these
conditions, mobilization and breakdown of stored fatty acids generates
abundant acetyl-CoA acetyl-CoA in liver cells for synthesis of ketone
bodies, and their utilization in other tissues minimizes the demand of
these tissues for glucose.
ƒ this is especially true in the brain where glucose is the substrate of choice
for energy production (other tissues can use FA as energy)
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Physiologic effects of acidosis and
hyperglycemia
ƒ Beta-hydroxybutyrate and acetoacetate are strong anions
meaning that they fully dissociate at physiologic ph and
creates H+ ions which combine with HCO3-
ƒ Once the glucose level exceeds the renal threshhold
(approximately 180), osmotic diuresis begins
ƒ With diuresis, large losses of electrolytes occur (sodium,
chloride, and potassium)
ƒ Sodium may be factitiously low however since water is shifted
from the intracellular to the extracellular space which dilutes
the sodium concentration
ƒ The potassium level may remain normal despite low total body
amounts since potassium is also moved to the extracellular
space in exchange for H+ ions
ƒ Phosphate, magnesium, and calcium are also lost in smaller
amounts
ƒ Acidosis also stimulates the respiratory center causing
tachypnea and Kussmaul respirations
ƒ Therefore your bicarb levels drop causing acidosis
ƒ The anion gap increases because beta-hydroxybutyrate
and acetoacetate are taking the place of HCO3
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Clinical presentation
Laboratory findings
ƒ All of the metabolic derangements directly lead to the most
common clinical signs and symptoms of DKA
ƒ Hyperglycemia
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ƒ Acidosis
ƒ Dehydration due to diuresis
ƒ Abdominal pain due to acidosis and/or mesenteric ischemia
ƒ Hyponatremia: sodium falls by 1.6-2.5 mEq/L for every
100 increase in glucose
ƒ Tachypnea due to metabolic acidosis (respiratory
compromise)
ƒ Increased anion gap
ƒ Low pCO2 on blood gas
ƒ Unusual fruity odor to breath due to ketones
ƒ High osmolality (2 (Na + K)+ (glucose/18) + (BUN/2.8))
ƒ Weight loss due to inability to utilize glucose appropriately
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Study: dolphins not so intelligent on land
Treatment – fluid
ƒ Initial treatment is volume expansion which will help with
the fluid and electrolyte depletion and restore circulating
volume to help increase GFR (will enhance ketone and
glucose clearance)
ƒ Start with 10 mL/kg isotonic fluid given over 1 h
ƒ May repeat with another 10 mL/kg if still requires volume
expansion
ƒ Rehydration alone will decrease blood glucose
concentrations (dilutional)
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Treatment – fluid (cont.)
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Treatment – fluid (cont.)
ƒ IVF at 1-1.5x M are then started--should be isotonic
(either LR or NS) to which 40 mEq/L potassium salts are
added (usually KPhos and KAcetate)
ƒ The double bag system of IVF is popular--have both IVF
with and without dextrose and titrate to maintain the
appropriate decrease in serum glucose
ƒ If there is a concern about renal function, may wait to add
potassium to IVF until K < 5
ƒ D10 is used most commonly for the dextrose-containing
fluid
ƒ Once glucose has dropped to approximately 250, add
dextrose to IVF
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Treatment – insulin
Initial laboratory evaluation
ƒ bolus dose not recommended
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Chem 7
Hgb A1C
Venous blood gas
Free T4 and TSH
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Serum phosphate level
Serum magnesium level
Serum calcium level
Beta-hydroxybutyrate level
ƒ can start infusion between 0.05 u/kg/hr and 0.1 u/kg/hr
ƒ No danger in going slow, but danger in dropping glucose
too quickly
> 20-30% of children have associated autoimmune thyroiditis
ƒ one study suggests that cerebral edema risk is
DECREASED by delaying insulin administration for >1hr
after starting IVF (Diabetologia 2006; 49: 2002)
ƒ goal is to lower serum glucose by 50-100 mg/dL/hr
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Labs to consider
Monitoring during treatment
ƒ Amylase, lipase if epigastric pain --although these are
elevated in about 40% of pediatric patients so diagnosis of
pancreatitis should be confirmed by imaging
ƒ Glucose levels should be checked hourly while on an
insulin drip-this will insure the correct rate of decline (50100 mg/dL/hr)
ƒ Celiac disease serologic screening (anti-gliadin IgG and
IgM and anti-endomysial transglutaminase)--rate of celiac
disease is approximately 5x higher in patients with type I
DM and can be relatively asymptomatic
ƒ Venous pH q1h-q2h
ƒ CBC – but can have a left shift and white count elevation
due to stress
ƒ Serum osmolality q4h
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ƒ Renal panel, phospherous, magnesium, calcium q1h-q2h
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Just to review: osmolality
Just to review: osmolality (cont.)
ƒ Osmolality is an expression of solute osmotic
concentration per mass, whereas osmolarity is per
volume of solvent (thus the conversion by multiplying
with the mass density)
ƒ “When derived by an osmometer in clinical laboratories
that use a method such as freezing point depression of
water (or less commonly, the vapor pressure technique),
the concentration is expressed in terms of solvent and is
appropriately referred to as osmolality.[3, 4] Bedside
calculations of osmotic activity by clinicians (using the
patient's laboratory data), however, are usually
expressed in terms of solution, and hence the term
osmolarity is appropriate.”
ƒ Molarity and osmolarity are not commonly used in
osmometry because they are temperature dependent.
This is because water changes its volume with
temperature.
Osmolality and Osmolarity: Narrowing the Terminology Gap Brian L. Erstad, Pharm.D., Pharmacotherapy. 2003;23(9)
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Calculated serum Osm
ƒ (2x Na)+ (BUN/2.8) + (glucose/18)=most commonly used
ƒ Osmolarity should not decrease by more than 3 mEq/Kg/hr
ƒ But many equations exist to calculate osmolarity
ƒ It is thought that increases faster than this may cause
cerebral edema
ƒ “There seems to be general agreement that less
complicated equations [e.g., serum osmolarity = (2 x serum
sodium [mEq/L]) + (BUN [mg/dl]/2.8) + (glucose
[mg/dl]/18)] will suffice for use at the bedside. In this case,
the calculated osmolarity is considered roughly equivalent
to osmolality (i.e., 1 L ~ 1 kg) since human serum is a
dilute aqueous solution with a specific gravity of 1.01.”
ƒ It is clear from the equation that sodium must increase as
glucose and BUN decrease from therapy in order to
minimize osmolar shifts
Osmolality and Osmolarity: Narrowing the Terminology Gap Brian L. Erstad, Pharm.D., Pharmacotherapy. 2003;23(9)
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Refeeding syndrome
Electrolyte replacement
ƒ Syndrome discovered when POWs were released during
WWII from Japanese internment camps
ƒ Hypophosphatemia may develop-IVF usually have
phosphate in them
ƒ Low phosphate, potassium, magnesium
ƒ Prospective randomized studies have failed to show any
beneficial effect of phosphate replacement on the clinical
outcome in DKA and may cause hypocalcemia
ƒ Analogous to electrolyte disturbances found in DKA once
insulin is started
ƒ Concern that low phosphate can cause effects on tissue
oxygenation via 2,3 DPG--however has not been shown to
be the case in adults
ƒ Consider phosphate replacement if phos <1.0
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Bicarbonate
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Bicarbonate
ƒ Clinical trials have not shown any benefit to exogenous
bicarbonate
ƒ There was no evidence of improved glycemic control or
clinical efficacy. There was retrospective evidence of
increased risk for cerebral edema and prolonged
hospitalization in children who received bicarbonate, and
weak evidence of transient paradoxical worsening of ketosis,
and increased need for potassium supplementation
ƒ Use in pediatrics has been associated with development of
cerebral edema
ƒ Giving bicarb increases CNS acidosis due increased
permeability of CO2 into CSF
ƒ Also decreased ventilatory drive since serum ph increased
ƒ The sudden increase in pCO2 resulting from decreased
peripheral stimulation to ventilate creates an acidic CNS
environment that perpetuates hyperventilation and may result
in cerebral edema
(Nephrology Rounds Jan 2005; vol 3, issue 1)
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Ann Intensive Care. 2011; 1: 23.Bicarbonate in diabetic ketoacidosis - a systematic review
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Fencl Stewart
Acidosis
ƒ Multifactorial in nature--ketones + lactate+ chloride
ƒ Lactate should be metabolized as circulating volume is
restored
ƒ Insulin promotes metabolism of serum ketones which
generates bicarbonate
ƒ However, many ketones will have been spilled in the urine
leaving behind H+
ƒ Anion gap will resolve as ketosis resolves, but patient will
still be acidotic from “left-over” H+
ƒ Also a relative hyperchloremia will exist given IVF and
using up bicarb
(Fencl Stewart)
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Study finds working at work improves
productivity
Morals of the acid/base story
ƒ Don’t let a little acidosis scare you (especially into giving
bicarb)
ƒ Acidosis will take longer to resolve than hyperglycemia--but
patient still needs insulin
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Complications of DKA
Cerebral Edema
ƒ Symptomatic cerebral edema occurs in about 1% of DKA
ƒ Most common complication is cerebral edema
ƒ Studies have shown, however, that most children with DKA
have subclinical swelling
ƒ Some evidence that DKA is associated with subsequent
cognitive impairment--unknown if this is associative or
causative
ƒ 50-80% of diabetic deaths in children are caused by
cerebral edema
ƒ DVTs are more common in DKA – especially with femoral
line placement
ƒ Several mechanisms thought to play a role
ƒ Cardiac arrhythmias can happen, although are very rare
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Cerebral Edema
Risk factors
ƒ Osmotic--Na/H transport in acidosis causes intracellular
sodium to rise, ketones, idiogenic osmoles (myoinstol and
taurine) are made in hypertonic environments and take 1224h to dissipate--classical teaching, but some children
have CE prior to treatment
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ƒ Ischemia /cytotoxic + vasogenic (increased cerebral blood
flow despite hypocapnia)= ischemia/reperfusion injury?
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Younger children (<5 year old)
New diagnosis
Failure of serum sodium to rise
Severe acidosis at presentation
Increased BUN at presentation
Use of bicarbonate
Lower pCO2 at presentation (is this a risk factor or a
manifestation of developing edema?)
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Diagnosis
Treatment
ƒ Neuro checks should be done on a q1h basis
ƒ 0.25-1 g/kg mannitol should be available at the bedside
ƒ Elevated BP, low hr, and abnormal respiratory pattern are
clinical signs
ƒ 3% saline (5-10 mL/kg) is another possibility, but hasn’t
been studied
ƒ Any change in mental status or decreased level of
consciousness should be acted upon
ƒ Intubate with RSI if cerebral edema suspected
ƒ Treat first, then get CT
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Hyperglycemic Hyperosmolar State
Hyperglycemic Hyperosmolar State – cont.
ƒ HHS has many of the same hallmarks as DKA with low
insulin levels and hyperglycemia, but the ketosis is absent
ƒ It is associated with type II DM
ƒ It is assumed that the presence of circulating insulin in type
II DM prevents lipolysis while at the same time not being
adequate to prevent hyperglycemia
ƒ Dehydration is more profound (approximately 20%)polyuria and polydipsia usually go unnoticed for longer and
symptoms relating to ketosis are absent
ƒ Can have lactic acidosis due to low circulating volume
ƒ Increasing incidence due to increase in type II DM and
obesity
ƒ Lab markers include serum glucose >600, serum Osm
>320, with only mild acidosis and/or ketosis
ƒ Can have both DKA and HHS
ƒ Mortality is 10-35%
ƒ Lower rates of cerebral edema (despite high osmolar load)
ƒ Increased risk of thrombosis-? heparin with CVL
ƒ Also risk of hyperthermia and rhabdomyolysis
ƒ Mortality usually related to multi-system organ failure
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Treatment
Treatment – cont.
ƒ Requires more vigorous volume resuscitation since
pathology more related to hypoperfusion than acidosis
(and acidosis is secondary to hypoperfusion)
ƒ Insulin should not be started until glucose has stopped
decreasing with volume alone
ƒ Should start at 0.25-0.5 u/kg/hr and aim for decrease in
glucose of 50-75 mg/dL/hr
ƒ With IVF, serum osmolality decreases and fluid shifts
intracellularly-exacerbating hypovolemia
ƒ May need to supplement both potassium and phosphate
ƒ Due to fluid requirements, urine replacements with 0.45 NS
are recommended
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ƒ A rise in CK with increased temperature should be treated
with dantrolene since a malignant hyperthermia-like
syndrome has been observed
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Study: Most Children Strongly Opposed To
Children's Healthcare
A study by the National Center for Policy Analysis found that
children are overwhelmingly against health services like
vaccinations and doctors visits. When asked if they wanted to
go to the doctor 68% screamed "NOOOO!" This is obviously
a political and moral issue for them as they see universal care
as un-American.
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Thank you!
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