1. Diabetic Ketoacidosis in Children
Jim Tsung, MD
Bellevue Hospital Center

2. DKA
Is the most common cause of hospitalization of children with diabetes
Is the most common cause of death in children with diabetes
Is fatal in <1% (from 1-2% of children in the 1970’s)
Most DKA deaths are attributable to cerebral edema (62-87%), which occurs in 0.4-1% of kids with DKA
Ciordano B, Rosenbloom AL, Heller DR, et al: Regional services for children and youth with diabetes.
Pediatrics. 1977;60:
Rosenbloom AL. Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 1990;13:22-33.
Edge J, Ford-Adams M, Dunger D. Causes of death in children with insulin-dependent diabetes
Arch Dis Child. 1999;81:

3. Background
Though it varies depending on the population, 20-40% of newly diagnosed T1DM patients are in DKA.
Therefore, a major goal of outpatient diabetes management is to prevent DKA
with a high index of suspicion with early DKA symptoms in new or established T1DM patients
with close supervision of established patients
Pinkney J et al. Presentation and progress of childhood diabetes mellitus: a prospective population-based study.
Diabetologia. 1994;37:70-74.
G, Fishbein H, Ellis E. The epidemiology of diabetic acidosis: a population-based study.
Am J Epidemiol. 1983;117:551

4. Etiology of DKA--New Onset DM
Always due to insulin deficiency--absolute or relative
Many previously undiagnosed patients have been seen in pediatric offices or ERs where a detailed history and lab studies could make the diagnosis before DKA ensues
A simple urine dip could be life-saving!
High index of suspicion is especially important in infants and young children

5. Etiology of DKA--Established Patients
***Failure to take insulin, especially in adolescents--most common cause of recurrent DKA
Acute stress--trauma, febrile illness, psychological turmoil with elevated counterregulatory hormones (glucagon, epi, GH, cortisol)

6. Etiology of DKA--Established Patients (continued)
Poor sick day management
not giving insulin because the child is not eating
failing to increase insulin for the illness, as dictated by fingerstick blood sugars
failure to monitor ketones

7. Definition Definitions vary, but in general:
Hyperglycemia > 200 mg/dl
Ketonemia/ketonuria--large serum or urine ketones
Acidosis with venous pH <7.3
Serum bicarb <18
Mild 16-22
Moderate 10-15
Severe <10
*Sometimes DKA can occur with normoglycemia when there is continued insulin therapy, vomiting, and/or reduced intake of carbohydrates

8. Glucagon>Catechols >Cortisol>GH
Acetyl-CoA
Pyruvate
Free Fatty Acids
Glycerol
Β-hydroxybutyrate
Acetoacetate
Acetone

9. Presentation Hyperglycemia
insulin deficiency causes decrease glucose uptake with tissue starvation, glycogenolysis, and gluconeogenesis from protein and lipid breakdown.
Thirst/Dehydration 20 Osmotic Diuresis/Vomiting
dehydration is usually hyperosmolar, so may be underestimated by clinical exam
Acidosis
from breakdown of lipids to ketone bodies to ketoacids
Fruity Odor from Acetone (ketone body, not a ketoacid)
from tissue hypoperfusion/dehydration

10. Presentation (continued)
Kussmaul (rapid deep) respiration
compensatory response to the metabolic acidosis, contributing to dehydration
Coma- due to hyperosmolarity, not acidosis
Calculated osm >320 is associated with coma
Hyperosmolarity- largely due to glucose, calculated as:
2(Na) + Glucose/ BUN/2.8
Other: Na, K, BUN, Cr, WBC

11. Management--General
Resuscitation (ABC’s, O2) if in shock/poor perfusion with NS or albumin cc/kg over min, may repeat as needed, NGT if vomiting and impaired LOC.
The cause of cerebral edema remains unclear.
Too rapid reduction of intravascular osmolality thought to aggravate the process. Recommended to rehydrate children with DKA more slowly than in other causes of dehydration.
However, newer evidence seems to question this.
Start, maintain, and utilize your flowsheet!

12. Management--Fluids
Initial fluid bolus with NS will depend on assessment of severity of dehydration
most kids in DKA are  10% dehydrated, unless there is hypotension, poor peripheral perfusion, etc.
e.g If 10% dehydrated, should get 10 cc/kg NS over 1 hour

13. Fluids
IVF needed =
Maintenance + Deficit + Ongoing Losses
Caution: Fluids should not exceed L/m2/day, as this has been associated with cerebral edema and poor outcome (?)

14. Fluids Maintenance-as per usual, amount based on weight (4/2/1 rule)
Deficit replacement usually over 48 hours
5% dehydration = 0.05 L/kg
10% dehydration = 0.1 L/kg
Consider deficit replacement over 72 hours if marked hyperosmolality (Gluc >1000 or serum osm >320) or if corrected Na is >150 mEq/L
e.g. 30 kg kid with 10% dehydration has a fluid deficit of (30)(0.1)=3 Liters, 300 cc of which have already been replaced with the 10 cc/kg NS bolus, leaving a 2700 cc fluid deficit

15. Fluids Ongoing losses-usually do not need to replaced
If very polyuric or vomiting excessively, can replace urine/vomitus output 0.5 cc/cc
Reassessment of I/O’s at least every 4 hrs for first 24 hrs

16. Sodium Maintenance = 3-5 mEq/kg/day Deficit = 6 mEq/kg
Serum Na may be high, normal, or low depending on fluid status
Many find calculation cumbersome, so can usually use 1/2 NS as replacement fluid and NS as deficit fluid (running piggyback)

17. Sodium
Use NS if the corrected sodium is <140 and/or if serum osm >310
*To correct Na: Add 1.6 mEq/L to the measured Na for every 100 mg/dl of glucose over 100 mg/dl
Monitor electrolytes every 2 hours at first, and then every 4 hours when trend is normalizing

18. Potassium
DKA is associated with total body K depletion, while correction of acidosis causes hypokalemia due to an intracellular K shift, so add K sooner rather than later
Add K once the patient has documented urine output and no peaked T’s on ECG or K  6
Hypokalemia on presentation is an ominous sign; beware of arrhythmias

19. Potassium Usually add 20 mEq KCl and 20 mEq of KPhos per liter to IVFs
Some centers prefer Kacetate instead of Kphos for theoretical improvement of acidosis
If even mildly hypokalemic, add 40 mEq KCl and 20 mEq of Kphos per liter. Consider K run(s) if hypokalemic.
If serum K <3, hold insulin until K has been added to IVFs

20. Phosphate Body Phosphate is depleted in DKA
Need for replacement is controversial
Phosphate should be given if there has been prolonged illness or if a prolonged period without food is anticipate
Can give half of K requirement as KPhos
If Phos <3, give half of K requirement as Kphos
If hypocalcemia develops, stop Phos and adjust total K as KCl

21. Bicarbonate: Don’t Do It!
May be given if pH < considering that severe acidosis can be life-threatening, but…
Sudden correction of serum pH can paradoxically lower CSF pH, it should be given by slow IV infusion over several hours
Endogenous production of HCO3 occurs as ketones are metabolized
The usual calculations for correction of acidosis greatly overestimate bicarbonate needed in DKA
May increase the risk of hypokalemia
Bicarb use has been associated with increased risk of cerebral edema*
*Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med. 2001;344:

22. Insulin
Goal is to decrease blood sugar by mg/dl/hr, after initial drop from rehydration, avoiding rapid drops
Usual starting dose is 0.1 u/kg/hr (100 units in 500 cc NS, 0.1 u/kg/hr=0.5ml/kg/hr)
Consider starting at 0.05 u/kg/hr if new diabetic, age < 2 yrs, marked hyperglycemia (>1200), or recent large SQ insulin dose in known diabetic

23. Insulin (continued)
If poor response on 0.1 u/kg/hr (e.g. insulin resistance, ongoing infection), may need to increase drip to u/kg/hr, but first make sure IV is infusing properly.
Continue insulin infusion until ketonemia is cleared/clearing. Adjust rate of drip to maintain blood glucose Do not decrease drip below 0.03 u/kg/hr. If pt is becoming hypoglycemic at this rate, increase dextrose concentration.

24. Glucose
Add D5W to IVF when glucose drops below mg/dl. If necessary, may further increase dextrose concentration to D7.5 - D10.
Consider “2 Bag System” *: One bag NS/0.45NS & 2nd bag D10 NS/0.45NS given simultaneously to vary dextrose concentration while maintaining constant fluid and electrolyte adminstration.
More cost-effective than single bag system
Monitor glucose hourly either by fingerstick (if within range of the meter) or by grey top glucose.
*Grimberg A, Cerri R, Satin-Smith M, et al. The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management. J Pediatr. 1999;134:376-3

25. Other
If patient is not improving, reevaluate IVF calculation, insulin delivery system and dose, change insulin bag, consider sepsis and antibiotics.

26. Initial Labs Fingerstick blood sugar Grey top glucose
Urine and/or serum ketones
VBG
Chem 20
HgA1c
Insulin level, C-peptide
Antibodies: anti-insulin, anti-islet cell, and anti-GAD (glutamic acid decarboxylase)
TFT’s

27. Risks Factors for Cerebral Edema
New Onset DKA (OR-2.9) and Younger
Higher blood urea nitrogen concentrations
Presenting with greater hypocapnia (↓PCO2)
A lesser rise in the measured serum sodium concentration during treatment (as the serum glucose concentration falls)
Bicarbonate administration
No association found for rate of infusion, volume, rate of change of glucose or sodium concentrations
Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child. 2001;85:16-22.
Glaser N et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med. 2001;344:
Mahoney C, Vlcek B, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999;21:

28. Signs & Symptoms of Cerebral Edema during DKA Treatment
Most commonly occurs in the first 24 hrs (5-15 hrs) after starting rehydration therapy when the child may seem to be improving
Does occur prior to treatment in 5% of cerebral edema
Headache-most often sudden, severe
Altered Mental Status--agitation, combativeness, disorientation, increased drowsiness, incontinence
Focal Neurologic Signs-cranial nerve palsies, opthalmoplegia, posturing
Papilledema, seizures, resp arrest are late signs with a very poor prognosis

29. Signs & Symptoms of Cerebral Edema during DKA Treatment
pupillary changes (asymmetry, sluggish to fixed)
change in VS: hypertension or hypotension, tachycardia, bradycardia, or arrhythmia, apnea, gasping, decr 02 sat
falling corrected Na
must exclude hypoglycemia as a cause of the symptoms before instituting therapy

31. Cerebral Edema Treatment
Mannitol should be immediately available during DKA treatment
Exclude hypoglycemia
Mannitol 1 g/kg IV over 20 minutes
Cut IVF rate in half until situation improves
NGT in vomiting child with impaired LOC
Elevate head
Consider intubation/hyperventilation
But, has been associated with poorer outcome*
Consider continuous mannitol infusion
Head imaging (CT/Eyeball US) after stabilized as hemorrhage, thrombus, or infarct may also occur
*Marcin J, Glaser N, Barnett P, et al. Clinical and therapeutic factors associated with adverse outcomes in children with DKA-related cerebral edema. J Pediatr. 2003;141:

32. Other Complications to Watch For:
Pulmonary Edema
CNS hemorrhage or thrombosis
Other large vessel thrombosis (femoral catheter)
Pancreatitis (salivary amylase elevated; check lipase)
Renal Failure
Intestinal necrosis
Rhinocerebral Mucormycosis

33. Transport Issues
On call for Established T1 Diabetic may consider Sliding Scale:
Calculate the present total daily dose (TDD) of insulin (fast plus slow acting).
Blood glucose mg% and urine ketones negative - give 10% TDD
Blood glucose mg% and urine ketones positive - give 20% TDD
Blood glucose >400mg% - give 20% TDD
Avoid use of sedatives or anti-emetics during transport to avoid masking symptoms associated with cerebral edema
Make sure the transport glucometer is working!

34. Primum Non Nocere Do not give bolus insulin
Do not give boluses of sodium bicarbonate
Do not start insulin until a fluid bolus has been given and maintenance fluids begun. This may wait until admission to the hospital if this occurs within 2 hours of admission to the ED.
Do not give more than 20cc/kg as a single fluid bolus. (?)
Do not give more than a total of 30cc/kg of bolus fluids unless the patient is in shock. (?)
Do not give more than 3750cc of maintenance fluids in 24 hours (2500cc/m2/24hrs). (?)