DIABETIC

KETOACIDOSIS
IN CHILDREN

Jose RL Batubara
Pediatric Endocrinology
Faculty of Medicine Universitas Indonesia, Jakarta
Introduction
DKA is the a leading cause of morbidity and
mortality in T1DM
Most deaths in DKA occur as a result of
cerebral edema
Incidence :
25-40% in newly diagnose type 1DM
In type 2 DM incidence varied 0-50%
Early diagnosis and adequate treatment are
important
ADA. Diabetes 2012;(6):139-49
Annual Incidence of DMT1 1991 -2013
base on National Registry
DKA from 1997 2013
base on National registry
Definition
DKA consist of biochemical triad
Hyperglycemia
Ketonemia
Acidemia
Biochemical criteria :
Hyperglycemia: BG > 200 mg/dL (>11
mmol/L)
Acidosis: pH <7,3 and/or HCO3- <15
mEq/L
Ketonemia and ketonuria
Salvodelliet al 2010. Diab Metab Syndrome 2010;2:1-9
Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
Etiology

Inadequate insulin
Accidental or intentional omission
Inappropriate intervention when stressed
Newly diagnosed
Infection
Epidemiology
Frequency of DKA at onset : 15-67% in Europe
and North America
Higher in developing country
The risk of DKA : 1-10% per patient per year in
established T1DM
Usher Smith. Diabetologia 2012;55:2878-94
Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
 epidemiology
Risk of DKA increased in:
Poor metabolic control
Previous episode of DKA
Peripubertal and adolescent girls
Children with eating disorders
Low socioeconomic / lack of health insurance
Alvi et al:
Asian children <5 years had an eightfold
increased risk of DKA compared to non
Asian children
Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
Alvi NS, dkk. Arch Dis Child 2001;85: 60-1
Morbidity and Mortality
Mortality:
USA 0,15%
UK 0,31%
Canada 0,18%
Cerebral edema is responsible for 57-87% death
in DKA
Incidence of cerebral edema :
USA 0,87%
UK 0,68%
Canada 0,46%
Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
Classification
HCO3
Severity pH
(mEq/L)
Mild <7.3 <15

Moderate <7.2 <10

Severe <7.1 <5

Severity of dehydration
severity estimation (%)
infant children
Mild 5 3
Moderate 10 6
Severe 15 9
Pathophysiology
Insulin deficiency counter regulatory hormone

Glycogenolysis Lipolysis
Gluconeogenesis Ketogenesis

Hyperglycemia Ketosis

Osmotic diuresis vomiting Acidosis

Dehydration

White NH. Rev in Endocrine & Metabolic Dis 2003;4:343-53

 pathophyisiology
Precipitating factors
Infection (most common)
Newly diagnosed T1DM
Insulin omission/ inadequate insulin treatment
Trauma
Drugs
Psychological problems

Rosenbloom AL Diab Ther 2010;1:103-120

Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
 Clinical Manifestation
Clinical manifestation of KAD varies
Polyuria, polydypsia, weight loss
Vomiting, abdominal pain
Dehydration, Shock
Rapid-deep respiration (Kussmaul)
CNS depression impaired sensorial to coma
acetone smell
Precipitating event

Diagnosis of KAD is often late

Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
Sivanandan. Indian J Pediatr 2011:78;576-88
Management principles

1. Fluid therapy : restore circulation/perfusion

2. Insulin to halt ketone overproduction
3. Replace electrolyte deficits
4. Treat any underlying or precipitating causes
5. Monitor for complications of therapy
Rosenbloom AL Diab Ther 2010;1:103-120
Walsdorf et al. 2011. Pediatr Diab.2011 10s. 118-33
Walsdorf et al 2011 IDF 2011 70-81
 management
ICU
Severe DKA
Children < 2 years old
CNS activity - headache, change in sensory
Always use flow sheet
Easy for reviewing data
Important step in critical analysis of response to therapy
Initial Evaluation
History and PE - SHOCK?
Cerebral edema?)
Severity of disease
Level of dehydration
CNS status
Evidence of infection
Labs - STAT Osmolality
= 2 x (Na + K) + Glucose/18 + BUN/2.8
Electrolytes
Anion Gap: = [Na+] - ([Cl-] + [HCO3-]) >
Blood gas Analysis (DKA>12)
Blood glucose, BUN Infection
Ketone (serum & urine) Pseudohyponatremia?
CBC, urine
Principle of fluid therapy
DO not exceed 4L/m2/day
Use isotonic fluid
Fluid restriction for 48 hrs if :
Signs or symptoms of increased ICP
Initial serum glucose > 1,000 mg/dl
Initial corrected serum sodium > 150 mEq/L
Fluid therapy

Correction for dehydration :

Infant : children :
Mild (5%) = 50cc/KgBW (3%) = 30cc/KgBW
Moderate (10%) = 100cc/KgBW (6%) = 60cc/KgBW
Severe (15%) = 150cc/KgBW (9%) = 90cc/KgBW
Fluid resuscitation for 48 jam.
200cc/KgBW for the first 10 kgBW,
100cc/KgBW for the second 10 kgBW
40cc/KgBW for every kgBW thereafter
Fluid and electrolyte resuscitation
Do not overestimate degree of dehydration
use weight if known
Replace deficit over 48 hours
i.e. 10 % dehydration in 20 kg pt (2000ml over 48hrs)
Fluid for shock (20-30cc/kg given 10cc/kg at a
time) is included in above calculation
DKA = hyperosmolarity resuscitate slowly
 fluid and electrolyte

DKA: pseudohyponatremia need to

calculate natrium corrected

[Na+ corr] + ( 1,6 x [glucose -100 mg/dL] / 100 or

[Na+ corr] + (1,6 x [glucose -5,6 mM] / 5,6
 fluid and electrolyte
Na+corr high:
Sign of hypertonic dehydration
rehydration should be done slowly
Na+corr decreased below normal value:
Rehydration is too fast
Water retention
Potassium
Potassium deficit occurs as a result of
major loss from intracellular pool
Insulin and asidosis correction
potassium return to intracellular
Potassium correction:
40 mEq/L (BB <30 kg) or
80 mEq/L (BB> 30 kg)
Infusion rate should not exceed > 40
mEq/hr or 0,3 mEq/kg/hr
Phosphate
Depletion occurs as a result of osmotic diuresis
It is cause by decreasing 2,3 diphosphoglycerate
(2,3 DPG)
Phosphate replacement does not have significant
benefit
Severe hypophosphatemia should be treated
Administration of phosphate may induce
hypocalcemia
Metabolic Acidosis
Associated with accumulation of ketone
bodies
Lactic asidosis may contribute to the acidosis
in certain cases
Generally corrected with insulin and fluid
replacement
Acidosis can be monitor by
HCO3- level
pH level
anion gap which should be decreasing toward
normal (12 2mEq/l)
Metabolic Acidosis
Bicarbonate correction : controversial
Bicarbonate correction risk for
development of cerebral edema
(RR =4,2; 95%CI 1,5-12,1; p=0,008)
Bicarbonate only be considered if pH<6,9
Bicarbonate should not be given as part of
the fluid resuscitation or to acutely correct
acidosis
Insulin
Regular Insulin
0,1 U/kg/hr IV using syringe pump
Every 1 U insulin diluted in 10 ml NaCl
0,9% every 1 ml sol contain 0,1 U
insulin
Practical: 5 U insulin diluted in 50 ml NaCl
0,9%
Bolus insulin should be consider if there is
a delay in continuous insulin infusion
.
 insulin
Dose can be increased up to 50-100% to
achieved adequate response
Wagner et al:
very low dose insulin (0,5-4U/hr) is save
and effective

Kibachi et al:
low dose insulin (0,1 U/kg/hr) is as save
and useful as high dose insulin
 insulin
Decrease BG by 50-100 mg/dl/hr
If BG < 300: add D5NS ( = 1/2 D10NS +
maintenance bag)
If BG < 200: change to D10NS
May decrease insulin rate
Continue insulin until acidosis corrected
Adjust insulin and fluid BG level
between 150 250 mg/dl during ivfd
No insulin stat needed
 insulin
Change to insulin sc
HCO3 > 15
At breakfast or lunch
Give insulin sc 30 minutes before meal and stop
insulin iv 1 hr later
Ketonemia typically takes longer to clear
than hyperglycemia.
During therapy, -OHB is converted to
acetoacetic acid, which may lead the clinician to
believe that ketosis has worsened.
.
Monitoring
Vital sign every 30 60 minutes
Fluid balance every hour
Neurological status every 30-60 minutes
ECG monitoring (certain indication)
Lab monitoring initially:
electrolyte, blood gas analysis BG every
hour
Clinically better, checked every 4 hr
Monitor the sign of cerebral edema
Complication
Hypoglycemia
Hypokalemia
Secondary Hyperglycemia
Cerebral edema, rare but fatal
Cerebral Edema
Potential devastating complication occurs in the first
day of treatment
Too rapid changes in intracellular and extracellular
osmolality
Should be suspected when there is unexpected
deterioration in neurological status
 cerebral edema
Risk factors for cerebral edema:
serum natrium cons during treatment
Severe asidosis
Low pCO2
serum urea

Durr et al:
cerebral edema often occur before treatment
.
 cerebral edema
Glaser et al (2001):
Bicarbonate is the only treatment that has an
association with the occurrence of cerebral edema

Therapy:
manitol 0,25-1,0 g/kgBW IV in 30 minutes
Prevention
Before diagnosis
Early diagnosis of DM with genetic and
immunological screening of high risk children
Increased public awareness of sign and
symptoms of DM
 prevention
Beyond diagnosis
Better diabetes education to family members and
patients
Availability of 24 hour hotlines to the diabetic
center and multidisciplinary health care teams
Conclusion
DKA is an emergency and life threatening condition
Early detection and prompt treatment is mandatory
Clinical manifestation is vary, sometimes mimicking other
conditions
Diagnosis of DKA base on Hyperglycemia, acidosis and
Ketonemia
Principalof treatment consist of rehydration, insulin,
correction of aciidosis and electrolyte imbalance and
monitoring
Cerebral edema is the most common complication of DKA
Thankyou