Diabetes Ketoacidosis in Pediatrics

Sarah Kandil MD
November 14th 2019

Date
Disclosure/COI

• Co-Investigator for Pfizer PHASE 1 study assessing

pharmacokinetics, safety and tolerability of ceftazidime-
avibactam (caz-avi) in children.

• No COI

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Objectives

• Recognize DKA
• Initialize therapy
• Recognize life-threatening complications

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Epidemiology

• Has increased 1.54 per 1000 under age 20

• 40% present in DKA

○ Vague symptoms
○ Delay diagnosis

• DKA -- Most frequent cause of death in children with Type 1

DM (0.15% - 0.3%)
○ ~1 in 350 children by age 18 in US have DM
Pathophysiology

• Insulin deficiency has three main effects:

1. Loss of insulin-dependent glucose transport into peripheral
tissues
2. Increased gluconeogenesis in the liver
3. Increased breakdown of fat, protein, and glycogen

Thus, insulin deficiency results in hyperglycemia (from

increased hepatic glucose production and decreased peripheral
uptake) and acidosis (primarily derived from hepatic fatty acid
oxidation into ketoacids).

Common Cause: New onset, intercurrent illness, insulin pump

malfunction, or purposeful insulin omission

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Diagnosis/Biochemical

• Diabetes  Hyperglycemia (BG>11mmol/L or 200 mg/dL)

• Keto  Ketones in the urine or blood (Ketonuria or

Ketonemia)  βhydroxybutyrate (BOHB); a level ≥3mmol/L is
indicative of DKA

• Acidosis  Venous pH <7.3 or bicarbonate <15 mmol/L

○ Mild: venous pH<7.3 or bicarbonate <15mmol/L
○ Moderate: pH<7.2, bicarbonate <10mmol/L
○ Severe: pH<7.1, bicarbonate <5mmol/L.

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Clinical Signs

• Dehydration (polyuria)
• Tachycardia
• Tachypnea
• Deep, sighing(Kussmaul)
respiration
• Acetone breath
• Nausea, vomiting
• Abdominal pain that may
mimic an acute abdominal
condition
• Confusion, drowsiness,
progressive loss of
consciousness.

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Risk Factors

• Very young children

• Lower social economic
Background
• Prior poor compliance
• Concomitant psychiatric
disease
• Adolescent girls

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Complications of DKA

• Cerebral Edema
• Cardiac Arrhythmias
• Severe Electrolyte abnormalities
• Severe Dehydration
• Thrombosis (CVL related, Stroke)
• Pulmonary edema
• Renal Failure
• Pancreatitis
• Rhabdomyolysis
• Severe Infections/Sepsis
• Death

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Laboratory Investigation

• Glucose, urine dip

• Blood gas (venous or arterial)
• Electrolytes and other labs

Na is typically low. For every 100 mg/dL glucose above 200 mg/dL,
the measure Na should be reduced by 1.6 mEq/L

Nacorrected = Nameasured + 1.6 x [Glucose] - 200

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K+  total body depletion
Ca and phosp typically low
BUN/Cr typically elevated in dehydration
WBC and left shift  typically due to acute stress but also look
for infectious trigger process

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Goals of Therapy

Correction of Dehydration, electrolyte deficits, hyperglycemia, and

acidosis.

A. Cardiovascular collapse
○ From dehydration
○ Treatment involves intravascular fluid expansion with ISOTONIC fluids
B. Overwhelming acidosis
○ From ketoacid production and lactic acid accumulation
○ Volume expansion and tissue reperfusion to correct lactic acidosis
○ Prompt initiation of insulin to stop fatty acid oxidation and ketone
production
○ Consider use of sodium bicarbonate in patients with arterial pH < 6.9 and/or
evidence of myocardial depression/collapse
• C. Hypokalemia
○ Insulin therapy is associated with rapid intracellular movement of potassium
○ Adequate potassium replacement in rehydration fluids and frequent
monitoring with blood tests and EKG’s

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Treatment of DKA
• Hyperglycemia
Dia
gno • Ketoacidosis
se
• Isotonic fluid bolus
Flui • 1.5 to 2 X M (with NS)
ds

Ins
• 0.1 U/kg/hr start after first fluid bolus
ulin

Dex • Add when glucose drops below 300 mg/dL

tros
e

• Add if adequate renal function

K+

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When to add sugar back in?

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What about Bicarb?

• No recommended for routine care

• Can lead to paradoxical worsening
• And associated with higher risk of cerebral edema
• Consider use of sodium bicarbonate in patients with arterial
pH < 6.9 and/or evidence of myocardial
depression/collapse

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What about K?

• Potassium deplete
• Therapy (insulin and
correcting acidosis) cause
K to shift back into cells
• Check EKG/monitor
• Replete K if renal function
okay

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Cerebral Edema

• Most common cause of mortality

• Increased over last decade

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Cerebral Edema

• Hypertonic dehydration in DKA is associated with the

production of osmotically active particles in the brain that act
to prevent neuronal cellular dehydration.

• Correction of hyperosmolar state leads to fluid influx into the

brain. Rapid rates of rehydration or correction of
hyperosmolarity may lead to cerebral cellular swelling
and brain herniation.

• It usually occurs 6-18 hours into therapy, just as the patient appears to
be clinically and biochemically improving.
• This is the most common cause of mortality in children with DKA !!!
⎯ Mortality rate of 20% and morbidity rate of 25%

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Cerebral Edema

• Much of the etiology and pathophysiology of cerebral edema is

still unknown, but the risk should be minimized by attention
to the following:

• Slow fluid replacement (over 48 hrs) with isotonic fluids

• Frequent monitoring and slow rise of calculated CORRECTED Na values
• Close neurologic surveillance for early signs of increased ICP
(headache, lethargy, slurred speech, obtundation) and rapid
evaluation & action

• Don’t exceed 4L/m2/24 hours

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Treatment of Cerebral Edema

• Initiate treatment as soon as the condition is suspected.

• Reduce the rate of fluid administration.
• Give mannitol, 0.5–1g/kg IV over 10–15min, and repeat if
there is no initial response in 30min to 2h
• Hypertonic saline(3%),suggested dose 2.5–5mL/kg over 10–
15min, may be used as an alternative to mannitol.
• Elevate the head of the bed to 30◦.
• Intubation may be necessary for the patient with impending
respiratory failure.
• After treatment for cerebral edema has been started, cranial
imaging may be considered.
○ The primary concern is whether the patient has a lesion requiring
emergency neurosurgery (e.g., intracranial hemorrhage) or a lesion
that may necessitate anticoagulation (e.g., cerebrovascular
thrombosis).

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The High-Risk Patient

• Age < 3 years

• Significantly altered or deteriorating mental status
• pH < 7.2
• Glucose > 900 mg/dl
• Na (calculated)>160 or any patient with falling (calculated) Na
• K < 3.5 mEq/L on admission
• Severe hyperosmolality (Sosm > 350 mOsm)
• Other organ system dysfunction that complicates treatment

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Hyperglycemia Hyperosmolar State (HHS)
formerly hyperosmolar nonketotic coma

• Plasma glucose concentration >33.3mmol/L (600mg/dL)

• Arterial pH>7.30; venous pH>7.25
• Serum bicarbonate >15mmol/L
• Small ketonuria, absent to small ketonemia
• Effective serum osmolality >320mOsm/kg
• Obtundation, combativeness, or seizures(in approximately
50%).

• Primarily Type 2 diabetics but can overlap with Type 1

especially in those with severe dehydration or those with high
carbohydrate load before hand
• Volume Resuscitation and insulin (often less)

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YACCESS 888-YNHH-BED (888-964-4233)

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References

• Nichols, David. Rogers’ Textbook of Pediatric Intensive Care. 2008. 1599-1614.

• Wolfsdorf JI, Allgrove J, Craig ME, et al. ISPAD Clinical Practice Consensus Guidelines
2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes.
2014;15(suppl 20):154–179.

• Abulebda, K; Whitfill, T; Montgomery, E; Kirby, M; Ahmed, R; Cooper, D; Nitu, M;

Auerbach, M; Lutfi, R; Abu-Sultaneh, S. Improving Pediatric Diabetic Ketoacidosis
Management in Community Emergency Departments Using a Simulation-Based
Collaborative Improvement Program. Pediatric Emergency Care: March 2019.

• https://www.aboutkidshealth.ca/Article?contentid=1727&language=English

• Google images

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