Diabetic Ketoacidosis in Children

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Diabetic Ketoacidosis in Children

• Jim Tsung, MD

Bellevue Hospital Center
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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 lt1 (from 1-2 of children in the
  1970s)
• 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. 197760492498.
Rosenbloom AL. Intracerebral crises during
treatment of diabetic ketoacidosis. Diabetes Care
19901322-33. Edge J, Ford-Adams M, Dunger D.
Causes of death in children with
insulin-dependent diabetes 1990-96. Arch Dis
Child. 199981318-323.
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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.
19943770-74. G, Fishbein H, Ellis E. The
epidemiology of diabetic acidosis a
population-based study. Am J Epidemiol.
1983117551
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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

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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)

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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

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Definition

• Definitions vary, but in general
• Hyperglycemia gt 200 mg/dl
• Ketonemia/ketonuria--large serum or urine ketones
• Acidosis with venous pH lt7.3
• Serum bicarb lt18
• Mild 16-22
• Moderate 10-15
• Severe lt10
• Sometimes DKA can occur with normoglycemia when
  there is continued insulin therapy, vomiting,
  and/or reduced intake of carbohydrates

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GlucagongtCatechols gtCortisolgtGH
Acetyl-CoA
Pyruvate
Free Fatty Acids
Glycerol
?-hydroxybutyrate Acetoacetate
Acetone
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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

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Presentation (continued)

• Kussmaul (rapid deep) respiration
• compensatory response to the metabolic acidosis,
  contributing to dehydration
• Coma- due to hyperosmolarity, not acidosis
• Calculated osm gt320 is associated with coma
• Hyperosmolarity- largely due to glucose,
  calculated as
• 2(Na) Glucose/18 BUN/2.8
• Other Na, K, BUN, Cr, WBC

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Management--General

• Resuscitation (ABCs, O2) if in shock/poor
  perfusion with NS or albumin 10-20 cc/kg over
  10-30 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!

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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

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Fluids

• IVF needed
• Maintenance Deficit Ongoing Losses
• Caution Fluids should not exceed 4
  L/m2/day, as this has been associated with
  cerebral edema and poor outcome (?)

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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 gt1000 or serum osm
  gt320) or if corrected Na is gt150 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

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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/Os at least every 4 hrs for
  first 24 hrs

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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)

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Sodium

• Use NS if the corrected sodium is lt140 and/or if
  serum osm gt310
• 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

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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 Ts on ECG or K ? 6
• Hypokalemia on presentation is an ominous sign
  beware of arrhythmias

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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 lt3, hold insulin until K has been
  added to IVFs

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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 lt3, give half of K requirement as Kphos
• If hypocalcemia develops, stop Phos and adjust
  total K as KCl

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Bicarbonate Dont Do It!

• May be given if pH lt6.9 - 7.0 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.
2001344264-269.
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Insulin

• Goal is to decrease blood sugar by 50-100
  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/hr0.5ml/kg/hr)
• Consider starting at 0.05 u/kg/hr if new
  diabetic, age lt 2 yrs, marked hyperglycemia
  (gt1200), or recent large SQ insulin dose in known
  diabetic

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Insulin (continued)

• If poor response on 0.1 u/kg/hr (e.g. insulin
  resistance, ongoing infection), may need to
  increase drip to 0.15-0.2 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 120-200. Do not decrease
  drip below 0.03 u/kg/hr. If pt is becoming
  hypoglycemic at this rate, increase dextrose
  concentration.

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Glucose

• Add D5W to IVF when glucose drops below 200-250
  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.
1999134376-3
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Other

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

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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)
• TFTs

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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.
20018516-22. Glaser N et al. Risk factors for
cerebral edema in children with diabetic
ketoacidosis. N Engl J Med. 2001344264-269 Mahon
ey C, Vlcek B, DelAguila M. Risk factors for
developing brain herniation during diabetic
ketoacidosis. Pediatr Neurol. 199921721-727.
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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

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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

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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. 2003141793-797
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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

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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 240-400mg and urine ketones
  negative - give 10 TDD
• Blood glucose 240-400mg and urine ketones
  positive - give 20 TDD
• Blood glucose gt400mg - 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!

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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). (?)