In Hospital Management of Pediatric Diabetic ketoacidosis

1. Pediatric DKA: Concerns
in Management
Dr. Saurav Shishir
Dept Of Endocrinology
Medical College, Kolkata

2. An 18-month-old girl presented -
• depressed consciousness, comatose state, pale skin with peripheral cyanosis
• heart rate - 155/min with thread pulse
• respiratory rate - 60/min with Kussmaul breathing
• dry mucous membranes, sunken eyes, poor capillary return, cold fingers and toes
• Weight- 11 kg
• No adenopathy, with normal findings on lung and heart auscultation
Case Vignette

3. • 3 days before admission- the child was agitated, with rare vomiting, elevated temperature,
anorexic and complaining of abdominal pain.
• Her mother consulted a general practitioner, who put her on cotrimoxazole and
paracetamol
• But the child started to vomit ever more frequently and was drowsy.
• The parents took the child to the hospital again, and the doctors tested her for glycemia,
which was 350 mg/dL

4. Laboratory testing:
• serum glucose - 350 mg/dL
• venous pH 6.9, bicarbonates 4.8 mmol/L
• Na 132 mmol/L, K 3.5 mmol/L
• WBC- 12,000 cu mm
• urea = 96 mg/dL, creatinine – 1.5 mg/dL
• ketonuria +++
• Serum osmolarity - 311 mmol/kg

5. Learning objectives
• Diagnosis
• Emergency assessment
• Supportive management
• Fluid management
• Insulin therapy
• Acidosis , potassium and phosphate correction
• Complications – cerebral edema

6. Concerns in diagnosis
• The younger the child, the more difficult it is to obtain the classical history
• Infants and toddlers in DKA misdiagnosed as having pneumonia, reactive
airways disease (asthma), or bronchiolitis and -treated with glucocorticoids
and/or sympathomimetic agents- exacerbate the metabolic derangements
• duration of symptoms - longer - more severe dehydration and acidosis and
ultimately to obtundation and coma.

7. 15–70% of all newly diagnosed infants and children with diabetes present
with DKA
Risk factors for DKA in newly diagnosed cases -
• younger age (<2 yr)
• delayed diagnosis,
• lower socioeconomic status
• countries with low prevalence of type 1 diabetes mellitus

8. • The risk of DKA in established type 1 diabetes is 1–10% per patient per year
• Risk is increased in -
• Children who omit insulin
• poor metabolic control or previous episodes of DKA.
• Gastroenteritis with persistent vomiting and inability to maintain hydration.
• psychiatric disorders, including those with eating disorders.
• difficult or unstable family circumstances (e.g., parental abuse).
• Peripubertal and adolescent girls.
• Insulin pump therapy (as only rapid- or short-acting insulin is used in pumps,
interruption of insulin delivery for any reason rapidly leads to insulin deficiency)

9. Pathophysiology of Diabetic Ketoacidosis. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents; a consensus
statement from the American Diabetes Association. Diabetes Care 2006: 29: 1150–1159.

10. Clinical signs and symptoms of DKA –
• Dehydration
• Tachycardia
• Tachypnea (which may be mistaken for pneumonia or asthma)
• Deep, sighing (Kussmaul) respiration; breath has the smell of acetone (described as the
odor of nail polish remover or rotten fruit)
• Nausea, vomiting (mistaken for gastroenteritis)
• Abdominal pain - mimic an acute abdominal condition
• Confusion, drowsiness, loss of consciousness

11. Biochemical criteria
• Hyperglycemia [blood glucose (BG) >11 mmol/L(≈200 mg/dL)]
• Venous Ph <7.3 or bicarbonate <15 mmol/L
• Ketonemia and ketonuria
The severity of DKA is categorized by the degree of acidosis :
• Mild: venous pH<7.3 or bicarbonate <15 mmol/L
• Moderate: pH<7.2, bicarbonate <10 mmol/L
• Severe: pH<7.1, bicarbonate <5 mmol/L.

12. Management of DKA

13. Emergency assessment
• Immediately measure BG and blood BOHB (or urine ketone) concentrations with bedside
meters.
- blood BOHB concentration confirm ketoacidosis (≥3 mmol/L in children) and is
used to monitor the response to treatment
• Perform a clinical evaluation to identify a possible infection
• Weigh the patient
• If body surface area is used for fluid therapy calculations, measure height or length to
determine surface area.

14. • 3 most useful individual signs for predicting 5% dehydration in young children aged 1
month to 5 yr are:
• Prolonged capillary refill time (normal capillary refill is ≤1.5–2 s)
• Abnormal skin turgor (‘tenting’ or inelastic skin)
• Abnormal respiratory pattern (hyperpnea)
• Other useful signs –
- dry mucus membranes,
- sunken eyes, absent tears, weak pulses, and cool extremities.
• ≥10% dehydration - weak or impalpable peripheral pulses, hypotension, and oliguria
Severity of dehydration

15. Level of consciousness

16. Laboratory measurement
• Plasma glucose
• Electrolytes (including bicarbonate)
• Blood urea nitrogen, creatinine
• Serum osmolality
• Venous pH, pCO2
• Hemoglobin, hematocrit and complete blood count
• Albumin, calcium, phosphorus, magnesium, urinalysis for ketones.
• Specimens for culture (blood, urine, and throat) if evidence of infection (e.g., fever).
• If laboratory measurement of serum potassium is delayed, perform an electrocardiogram
(ECG) for baseline evaluation of potassium status

17. Calculations:
• Anion gap=Na−(Cl+HCO3): normal is 12 ± 2 mmol/L
• Corrected sodium=measured Na+2 [(plasma glucose−5.6)/5.6] mmol/L
= measured Na+2 [(plasma glucose−100)/100] mg/dL
• Effective osmolality (mOsm/kg)=2×(plasma Na + K)+plasma glucose
mmol/L or (mg/dl / 18)

18. Supportive measures

19. • Secure the airway and empty the stomach by continuous nasogastric suction to prevent
pulmonary aspiration in the unconscious or severely obtunded patient
• Intubation should be avoided if possible; a sudden increase of pCO2 during or following
intubation may cause cerebrospinal fluid (CSF) pH to decrease and contribute to
worsening of cerebral edema
• Oxygen - patients with severe circulatory impairment or shock.
• Cardiac monitor - electrocardiographic monitoring to assess T waves for evidence of
hyper- or hypokalemia

20. • A second peripheral intravenous (IV) catheter should be placed for convenient and
painless repetitive blood sampling.
• An arterial catheter - some critically ill patients managed in an intensive care unit
• Central venous pressure monitoring - guide fluid management in the critically ill,
obtunded, or neurologically compromised patient
- high risk of thrombosis, especially in the very young
- if a central catheter has been inserted, remove it as soon as the patient’s
clinical status permits
• Insulin should preferably not be given through a central line-
- infusion may be interrupted when other fluids are given through the same line.

21. • Antibiotics- febrile patients after obtaining appropriate cultures of body
fluids.
• Catheterization of the bladder - usually not necessary
- done if the child is unconscious or unable to void on demand (e.g.,
infants and very ill young children)

22. Principles of water and salt replacement

23. • Deficit in ECF volume - 5–10% .
• Shock - rare in paediatric DKA.
• Clinical estimates of the volume deficit - subjective and inaccurate; either
under- or overestimate the deficit .
• Dehydration - 5–7% in moderate DKA and 10% in severe DKA.
• Effective osmolality - 300- to 350-mosm/l
• Increased serum urea nitrogen and haematocrit - useful markers of the
severity of ECF contraction
• Serum sodium – inaccurate marker ; dilutional hyponatremia and lipemia
Koves IH, Neutze J, Donath S et al. The accuracy of clinical assessment of dehydration during diabetic ketoacidosis in childhood. Diabetes Care 2004: 27:2485–2487
Sottosanti M, Morrison GC, Singh RN et al. Dehydration in children with diabetic ketoacidosis: a prospective study. Arch Dis Child 2012: 97: 96–100

24. Resuscitation fluids
• DKA in shock-
- isotonic saline in 20 mL/kg boluses infused as quickly as possible through a
large bore cannula with reassessment after each bolus.
• Severely volume depleted but not in shock-
- 0.9% saline to restore the peripheral circulation
- 10–20mL/kg over 1–2 h
- may need to be repeated until tissue perfusion is adequate.
• No data to support the use of colloid in preference to crystalloid

25. Replacement fluids
• Isotonic solution (0.9% saline or Ringer’s lactate) for at least 4–6 h
• Deficit replacement after 4–6 h - solution that has a tonicity ≥0.45% saline (0.675%
saline/ 3/4th NS) with added potassium chloride, potassium phosphate or potassium
acetate
• Rate of IV fluid - calculated to rehydrate evenly over at least 48 h
• Infuse fluid each day at a rate - 1.5–2 times the usual daily maintenance requirement
based on age, weight, or body surface area
• Except for severely ill individuals, oral intake typically begins within 24 h

26. Holliday-Segar formula
• 30 kg = 1500 mL + 20 mL* 10 = 1700 mL/ 24 hr (Maintenance fluid requirement )
• Maintenance electrolyte requirements - per 100mL of maintenance IV fluid

27. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents; a consensus statement from the American Diabetes Association.
Diabetes Care 2006: 29: 1150–1159.

28. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents; a consensus statement from the American Diabetes Association.
Diabetes Care 2006: 29: 1150–1159.

29. • Clinical assessment of hydration status and calculated effective osmolality - guides to fluid
and electrolyte therapy.
• Aim - gradually to reduce serum effective osmolality to normal
- sodium should rise by 0.5 mmol/L for each 1 mmol/L decrease in glucose
concentration)
• Failure of measured serum sodium levels to rise or a further decline in serum sodium levels
with therapy - potentially ominous sign of impending cerebral edema
• Sodium content of the fluid should be increased - if measured serum sodium concentration is
low and does not rise appropriately as the plasma glucose concentration falls

30. • Large amounts of chloride-rich fluids (combined with preferential renal excretion of
ketones over chloride) - may be associated with hyperchloremic metabolic acidosis
• Chloride load -
- reduced by not giving potassium as potassium chloride
- using fluids such as Ringer’s lactate or Plasmalyte in which a portion of the
chloride is replaced by lactate or acetate, respectively

31. Insulin therapy

32. • Rehydration alone frequently causes a marked decrease in BG concentration
• Insulin - normalizes blood glucose and suppreses lipolysis and ketogenesis
• Start insulin infusion 1–2 h after starting fluid replacement therapy; i.e., after the
patient has received initial volume expansion
• Dose: 0.05–0.1 unit/kg/h [e.g., dilute 50 units regular (soluble) insulin in 50mL
normal saline, 1 unit=1mL]
• Route of administration - IV
• An IV bolus should not be used at the start of therapy- may increase the risk of
cerebral edema , can exacerbate hypokalemia and can precipitate shock by
rapidly decreasing osmotic pressure

33. • Dose of insulin -
- 0.05–0.1 unit/kg/h at least until resolution of DKA (pH>7.30, bicarbonate >15
mmol/L, BOHB <1 mmol/L, or closure of the anion gap)
• If the patient shows marked sensitivity to insulin (e.g., some young children with
DKA, patients with HHS, and some older children with established diabetes)-
dose may be decreased provided that metabolic acidosis continues to resolve.
• Insulin has an aldosterone-like effect leading to increased urinary potassium
excretion.
- Time on IV insulin infusion and dose of insulin should be minimized to avoid
severe hypokalemia

34. • During initial volume expansion, the plasma glucose concentration may fall
steeply Thereafter, the plasma glucose concentration typically decreases at a rate
of (54–90 mg/dl/h)
• To prevent an unduly rapid decrease in plasma glucose concentration and
hypoglycemia, 5% glucose should be added to the intravenous fluid when the
plasma glucose falls to 250- 300 mg/dl
• It may be necessary to use 10% or even 12.5% dextrose to prevent
hypoglycaemia while continuing to infuse insulin to correct the metabolic
acidosis

35. Acidosis
• Severe acidosis is reversible by fluid and insulin replacement
• Treatment of hypovolemia improves tissue perfusion and renal function- increasing the
excretion of organic acids
• Insulin stops further ketoacid production and allows ketoacids to be metabolized, which
generates bicarbonate
• Bicarbonate administration may be beneficial in the rare patient with life-threatening
hyperkalemia- 1–2 mmol/kg over 60 min
- may cause paradoxical CNS acidosis and rapid correction of acidosis with
bicarbonate causes hypokalemia

36. Potassium replacement
Deficits of 3–6 mmol/kg ; Causes of deficiency -
• Transcellular shifts of this ion caused by hypertonicity (increased plasma osmolality causes
solvent drag in which water and potassium are drawn out of cells)
• Glycogenolysis and proteolysis secondary to insulin deficiency - potassium efflux from cells
• vomiting
• osmotic diuresis
• Volume depletion causes secondary hyperaldosteronism, which promotes urinary potassium
excretion.

37. • At presentation - serum potassium levels may be normal, increased, or decreased
• Renal dysfunction, by enhancing hyperglycemia and reducing potassium excretion,
contributes to hyperkalemia
• Administration of insulin and the correction of acidosis drives potassium back into the
cells, decreasing serum level
• Potassium replacement therapy is required regardless of the serum potassium
concentration

38. • Hypokalemia- start potassium replacement at the time of initial volume expansion and
before starting insulin therapy
• Otherwise, start replacing potassium after initial volume expansion and concurrent with
starting insulin therapy.
• Hyperkalemia- defer potassium replacement therapy until urine output is documented
• If immediate serum potassium measurements are unavailable- ECG may help to
determine whether the child has hyper- or hypokalemia
• Starting potassium concentration in the infusate - 40 mmol/L
• Continue throughout IV fluid therapy.
• Maximum recommended rate - 0.5 mmol/kg/h.

39. • Potassium phosphate may be used together with potassium chloride or acetate;
e.g.
- 20 mmol/L potassium chloride and 20 mmol/L potassium phosphate
- 20 mmol/L potassium phosphate and 20 mmol/L potassium acetate
• If hypokalemia persists despite a maximum rate of potassium replacement, then
the rate of insulin infusion can be reduced

40. Phosphate
• Deficiency –
- depletion of intracellular phosphate
- osmotic diuresis
- insulin promotes entry of phosphate into cells
- food intake prolonged beyond 24 h
• Prospective studies have not shown clinical benefit from phosphate replacement
• severe hypophosphatemia (1 mg/dl), which may manifest as muscle weakness,
should be treated even in the absence of symptoms

41. • May induce hypocalcemia
- if hypocalcemia develops, administration of phosphate should be stopped
• Potassium phosphate salts may be safely used as an alternative to or combined
with potassium chloride or acetate, provided that careful monitoring of serum
calcium is performed to avoid hypocalcemia

42. Clinical and biochemical monitoring
• flow chart of hour-by-hour clinical observations, IV and oral medications,
fluids, and laboratory results
• Hourly vital signs (heart rate, respiratory rate, blood pressure).
• Hourly neurological observations for warning signs and symptoms of
cerebral edema
• Amount of administered insulin
• Hourly accurate fluid input (including all oral fluid) and output

43. • Capillary blood glucose concentration should be measured hourly
• Laboratory tests: serum electrolytes, glucose, blood urea nitrogen, calcium,
magnesium, phosphorus, hematocrit, and blood gases should be repeated 2–4 h,
or more frequently, as clinically indicated, in more severe cases
• Blood BOHB concentrations every 2 h if available
• Lipids and triglycerides can be grossly elevated causing the blood sample to
show a visible rim of lipids

44. Introduction of oral fluids and transition to SC
Insulin Injections
• Oral fluids - only when substantial clinical improvement has occurred (mild
acidosis/ketosis may still be present)
• IV fluid should be reduced accordingly so that the sum of IV and oral fluids does
not exceed the calculated IV rate (i.e., not in excess of 1.5–2 times maintenance
fluid rate)
• When ketoacidosis has resolved, oral intake is tolerated - change to SC insulin is
planned - the most convenient time to change to SC insulin is just before a
mealtime

45. • To prevent rebound hyperglycemia –
- first SC injection given 15–30 min (with rapid acting insulin)
- or 1–2 h (with regular insulin) before stopping the insulin infusion to allow
sufficient time for the insulin to be absorbed.
• Intermediate / long-acting insulin - overlap should be longer and the rate of IV insulin
infusion gradually lowered.
• Ex - Patients on a basal-bolus insulin regimen, the first dose of basal insulin may be
administered in the evening and the insulin infusion is stopped the next morning.

46. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents; a consensus statement from the American Diabetes Association.
Diabetes Care 2006: 29: 1150–1159.

48. Algorithm for the management of diabetic ketoacidosis .Adapted from Pinhas-Hamiel and Sperling

49. Complications

50. • Inadequate rehydration
• Hypoglycemia
• Hypokalemia
• Hyperchloremic acidosis
• Cerebral edema

51. Morbidity and mortality
• Population studies - mortality rate from DKA in children is 0.15–0.30%
• Cerebral injury - major cause of mortality and morbidity
• Cerebral edema - 60–90% of all DKA deaths
• 10–25% of survivors of cerebral edema have significant residual morbidity
• Children without overt neurological symptoms during DKA treatment may have subtle
evidence of brain injury, particularly memory deficits, after recovery from DKA

52. Other causes of morbidity and mortality :
• Hypokalemia, hypocalcemia, hypomagnesemia, severe hypophosphatemia
• Hypoglycemia
• CNS complications - dural sinus thrombosis, basilar artery thrombosis,
intracranial hemorrhage, and cerebral infarction
• Venous thrombosis , pulmonary embolism
• Sepsis
• Rhinocerebral or pulmonary mucormycosis
• Aspiration pneumonia
• Pulmonary edema
• Rhabdomyolysis
• Ischemic bowel necrosis
• Acute renal failure
• Acute pancreatitis

53. Cerebral edema
• Incidence of clinically overt cerebral edema - 0.5–0.9%
• Mortality rate - 21–24%
• Mental status abnormalities (GCS scores <14)- 15% of children treated for DKA
• Usually develops - within the first 12 h after treatment has started
- but can occur before treatment has begun or, rarely, may
develop as late as 24–48 h after the start of treatment

54. Risk factors
• Increased serum urea nitrogen at presentation
• More severe acidosis at presentation
• Bicarbonate treatment for correction of acidosis
• Early decrease in serum effective osmolality
• An attenuated rise in serum sodium concentration or an early fall in glucose-corrected
sodium during therapy
• Greater volumes of fluid given in the first 4 h
• Younger age and longer duration of symptoms

55. Pathophysiology
• Fluid influx into the brain caused by rapid declines in serum osmolality and/or overly
vigorous fluid resuscitation
• Recent data suggest that vasogenic, rather than cytotoxic, cerebral edema may be the
predominant finding in DKA
• Activation of ion transporters in the blood-brain barrier may be responsible for fluid
influx into the brain
- result from cerebral hypoperfusion and/or from direct effects of ketosis or
inflammatory cytokines on blood-brain barrier endothelial cells

56. Signs and symptoms
• Headache and slowing of heart rate
• Recurrence of vomiting
• Change in neurological status (restlessness, irritability, increased drowsiness, and
incontinence)
• Specific neurological signs (e.g., cranial nerve palsies, papilledema)
• Rising blood pressure
• Decreased O2 saturation

57. Treatment
• Initiate treatment as soon as the condition is suspected.
• Reduce the rate of fluid administration by one-third.
• Mannitol - 0.5–1 g/kg IV over 10–15 min - repeat if there is no initial response in 30 min
to 2 h
• Hypertonic saline (3%) - 2.5–5 mL/kg over 10–15 min, may be used as an alternative to
mannitol, especially if there is no initial response to mannitol
• Elevate the head of the bed to 30◦.
• Intubation may be necessary for the patient with impending respiratory failure
• Cranial imaging may be considered as with any critically ill patient with encephalopathy
or acute focal neurologic deficit – rule out haemorrhage / thrombosis

58. Prevention of recurrent DKA
• Insulin omission - prevented by comprehensive programs that provide education,
psychosocial evaluation, and treatment combined with adult supervision of the entire
process of insulin administration
• Parents and patients should learn how to recognize and treat ketosis and impending DKA
with additional rapid- or short-acting insulin and oral fluids
• Families should have access to a 24-h telephone helpline for emergency advice and
treatment

59. • Psychosocial reasons for insulin omission :
◦ An attempt to lose weight in an adolescent girl with an eating disorder.
◦ A means of escaping an intolerable or abusive home situation.
◦ Depression or other reason for inability of the patient to manage the diabetes
unassisted
• A psychiatric social worker or clinical psychologist should be consulted to identify the
psychosocial reason(s) contributing to development of DKA

60. Thank you
“A child is not a miniature adult”
- Jean Piaget