The document discusses diabetic ketoacidosis, providing an overview of its pathophysiology, classification, diagnosis, and treatment. Diabetic ketoacidosis results from a lack of insulin and leads to hyperglycemia, ketonemia, and metabolic acidosis if not treated. Treatment involves fluid resuscitation, electrolyte replacement, insulin therapy to reduce blood glucose levels and resolve acidosis, and careful monitoring to prevent complications such as cerebral edema.

1. Diabetic Ketoacidosis
Gary David Goulin, MD

2. Goals & Objectives
• Understand the action of insulin on the
metabolism of carbohydrates, protein, and
fat
• Understand the pathophysiology of IDDM
and DKA
• Understand the management approach to
the patient with DKA
• Appreciate the complications that can occur
during treatment of DKA

3. Introduction
• Diabetes mellitus is a syndrome of
disturbed energy homeostasis caused by a
deficiency of insulin or of its action
resulting in abnormal metabolism of
carbohydrate, protein, and fat
• Diabetes mellitus is the most common
endocrine-metabolic disorder of childhood
and adolescence

4. Introduction
• Individuals affected by insulin-dependent
diabetes confront serious burdens that
include an absolute daily requirement for
exogenous insulin, the need to monitor their
own metabolic control, and the need to pay
constant attention to dietary intake

5. Introduction
• Morbidity and mortality stem from
metabolic derangements and from long-
term complications that affect small and
large vessels and result in retinopathy,
nephropathy, neuropathy, ischemic heart
disease, and arterial obstruction with
gangrene of the extremities

6. Classification
• Type I Diabetes (insulin-dependent diabetes
mellitus, IDDM)
– characterized by severe insulinopenia and
dependence on exogenous insulin to prevent
ketosis and to preserve life
– onset occurs predominantly in childhood
– probably has some genetic predisposition and is
likely autoimmune-mediated

7. Classification
• Type II Diabetes (non-insulin-dependent
diabetes mellitus, NIDDM)
– patients are not insulin dependent and rarely develop ketosis
– generally occurs after age 40, and there is a high incidence of
associated obesity
– As the prevalence of childhood obesity increases, more adolescents
are presenting with NIDDM
– insulin secretion is generally adequate; insulin resistance is present
– no associated genetic predisposition

8. Classification
• Secondary Diabetes
– occurs in response to other disease processes:
• exocrine pancreatic disease (cystic fibrosis)
• Cushing syndrome
• poison ingestion (rodenticides)

9. Type I Diabetes Mellitus:
Epidemiology
• Prevalence of IDDM among school-age
children in the US is 1.9 per 1000
• The annual incidence in the US is about 12 -
15 new cases per 100,000
• Male to female ratio is equal
• Among African-Americans, the occurrence
of IDDM is about 20 - 30% of that seen in
Caucasian-Americans

10. Type I Diabetes Mellitus:
Epidemiology
• Peaks of presentation occur at 5 - 7 years of
age and at adolescence
• Newly recognized cases appear with greater
frequency in the autumn and winter
• Definite increased incidence of IDDM in
children with congenital rubella syndrome

11. Type I Diabetes Mellitus:
Etiology and Pathogenesis
• Basic cause of clinical findings is sharply
diminished secretion of insulin
• The mechanisms that lead to failure of
pancreatic -cell function are likely
autoimmune destruction of pancreatic islets
• IDDM is more prevalent in persons with
Addison’s disease, Hashimoto’s thyroiditis,
and pernicious anemia

12. Type I Diabetes Mellitus:
Etiology and Pathogenesis
• 80 - 90% of newly diagnosed patients with
IDDM have anti-islet cell antibodies

13. Type I Diabetes Mellitus:
Pathophysiology
High Plasma Insulin Low Plasma Insulin
(Postprandial State) (Fasted State)
Liver: Glucose uptake Glucose production
Glycogen synthesis Glycogenolysis
Absence of gluconeogenesis Gluconeogenesis
Lipogenesis Absence of lipogenesis
Absence of ketogenesis Ketogenesis
Muscle: Glucose uptake Absence of glucose intake
Glucose oxidation Fatty acid and ketone oxidation
Glycogen synthesis Glycogenolyss
Protein synthesis Proteolysis and amino acid release
Adipose tissue: Glucose uptake Absence of glucose uptake
Lipid synthesis Lipolysis and fatty acid release
Triglyceride uptake Absence of triglyceride uptake

14. Type I Diabetes Mellitus:
Pathophysiology
• Progressive destruction of -cells leads to a
progressive deficiency of insulin
• As IDDM evolves, it becomes a permanent
low-insulin catabolic state which feeding
does not reverse
• Secondary changes involving stress
hormones accelerate the metabolic
decompensation

15. Type I Diabetes Mellitus:
Pathophysiology
• With progressive insulin deficiency, excessive
glucose production and impairment of utilization
result in hyperglycemia, with glucosuria
developing when the renal threshold of ~ 180
mg/dL is exceeded
• The resultant osmotic diuresis produces polyuria,
urinary losses of electrolytes, dehydration, and
compensatory polydipsia

16. Type I Diabetes Mellitus:
Pathophysiology
• Hyperosmolality as a result of progressive
hyperglycemia contributes to cerebral
obtundation in DKA
• Serum osmolality:
– {Serum Na+ + K+} x 2 + glucose + BUN
18 3

17. Type I Diabetes Mellitus:
Pathophysiology
• DKA results in altered lipid metabolism
– increased concentrations of total lipids,
cholesterol, triglycerides, and free fatty acids
– free fatty acids are shunted into ketone body
formation due to lack of insulin; the rate of
formation exceeds the capacity for their
peripheral utilization and renal excretion
leading to accumulation of ketoacids, and
therefore metabolic acidosis

18. Type I Diabetes Mellitus:
Pathophysiology
• With progressive dehydration, acidosis,
hyperosmolality, and diminished cerebral
oxygen utilization, consciousness becomes
impaired, and the patient ultimately
becomes comatose

19. Type I Diabetes Mellitus:
Clinical Manifestations
• Classic presentation of diabetes in children
is a history of polyuria, polydipsia,
polyphagia, and weight loss, usually for up
to one month
• Laboratory findings include glucosuria,
ketonuria, hyperglycemia, ketonemia, and
metabolic acidosis. Serum amylase may be
elevated. Leukocytosis is common

20. Type I Diabetes Mellitus:
Clinical Manifestations
• Keotacidosis is responsible for the initial
presentation of IDDM in up to 25% of
children
– early manifestations are mild and include vomiting,
polyuria, and dehydration
– More severe cases include Kussmaul respirations, odor
of acetone on the breath
– abdominal pain or rigidity may be present and mimic
acute appendicitis or pancreatitis
– cerebral obtundation and coma ultimately ensue

21. Type I Diabetes Mellitus:
Diagnosis
• Diagnosis of IDDM is dependent on the
demonstration of hyperglycemia in
association with glucosuria with or without
ketonuria
• DKA must be differentiated from acidosis
and coma due to other causes:
– hypoglycemia, uremia, gastroenteritis with
metabolic acidosis, lactic acidosis, salicylate
intoxication, encephalitis

22. Type I Diabetes Mellitus:
Diagnosis
• DKA exists when there is hyperglycemia (>
300 mg/dL), ketonemia, acidosis,
glucosuria, and ketonuria

23. Type I Diabetes Mellitus:
Treatment
• Treatment is divided into 3 phases
– treatment of ketoacidosis
– transition period
– continuing phase and guidance

24. Type I Diabetes Mellitus:
Treatment
• Goals of treatment of DKA
– intravascular volume expansion
– correction of deficits in fluids, electrolytes, and
acid-base status
– initiation of insulin therapy to correct
catabolism, acidosis

25. Type I Diabetes Mellitus:
Treatment
• Intravascular volume expansion
– dehydration is most commonly in the order of 10%
– initial hydrating fluid should be isotonic saline
• this alone will often slightly lower the blood glucose
• rarely is more than 20 cc/kg fluid required to restore
hemodynamics
• Treatment of electrolyte abnormalities
– serum K+ is often elevated, though total body K+ is depleted
– K+ is started early as resolution of acidosis and the administration
of insulin will cause a decrease in serum K+

26. Type I Diabetes Mellitus:
Treatment
• Phosphate is depleted as well. Phosphate may be added as
KPO4 especially if serum chloride becomes elevated
• “Pseudohyponatremia” is often present
– Expect that the Na+ level will rise during treatment
– Corrected Na+ = Measured Na+ + 0.016(measured
glucose - 100)
– If Na+ does not rise, true hyponatremia may be present
(possibly increasing cerebral edema risk) and should be
treated

27. Type I Diabetes Mellitus:
Treatment
• BICARBONATE IS ALMOST NEVER
ADMINISTERED
– bicarbonate administration leads to increased
cerebral acidosis
• HCO3
- combines with H+ and dissociated to CO2
and H2O. Whereas bicarbonate passes the blood-
brain barrier slowly, CO2 diffuses freely, thereby
exacerbating cerebral acidosis and cerebral
depression

28. Type I Diabetes Mellitus:
Treatment
• Indications for bicarbonate administration
include severe acidosis leading to
cardiorespiratory compromise
• Increasing evidence suggests that
subclinical cerebral edema occurs in the
majority of patients treated with fluids and
insulin for DKA

29. Type I Diabetes Mellitus:
Treatment
• Cerebral edema is the major life-threatening
complication seen in the treatment of
children with DKA
– clinically apparent cerebral edema occurs in
~1% of episodes of DKA
– mortality is 40 - 90%
– cerebral edema is responsible for 50 - 60% of
diabetes deaths in children

30. Type I Diabetes Mellitus:
Treatment
– Cerebral edema usually develops several hours
after the institution of therapy
– manifestations include headache, alteration in
level of consciousness, bradycardia, emesis,
diminished responsiveness to painful stimuli,
and unequal or fixed, dilated pupils

31. Type I Diabetes Mellitus:
Treatment
• Excessive use of fluids, large doses of insulin, and
especially the use of bicarbonate have been linked to the
increased formation of cerebral edema
– fluids are generally limited to ~ 3 L/m2/24 hours
• Children who present with elevated BUN, PaCO2 < 15 torr,
or who demonstrate a lack of an increase in serum Na+
during therapy have an increased probability of cerebral
edema
• Therapy of cerebral edema may include treatment with
mannitol, hypertonic saline and hyperventilation

32. Type I Diabetes Mellitus:
Treatment
• Insulin Therapy
– continuous infusion of low-dose insulin IV (~
0.1 U/kg/hr) is effective, simple, and
physiologically sound
– goal is to slowly decrease serum glucose (< 100
mg/dL/hr
– frequent laboratory and blood gas analyses are
obtained to ensure ongoing resolution of
metabolic acidosis

33. Type I Diabetes Mellitus:
Treatment
• “Maintenance” IV fluid at a rate of 2000 -
2400 cc/m2/day consists of 2/3 NS (0.66%)
or NS
– 5% Dextrose is added to IVF when blood
glucose is ~ 300 mg/dL
– 10% Dextrose is added when blood glucose is ~
200 mg/dL

34. Type I Diabetes Mellitus:
Treatment
• Insulin is used to treat acidosis, not hyperglycemia
– insulin should never be stopped if ongoing acidosis
persists
• When the acidosis is corrected, the continuous insulin
infusion may be discontinued and subcutaneous insulin
initiated
• With this regimen, DKA usually is usually fully corrected
in 36 to 48 hours

35. Type I Diabetes Mellitus:
Treatment
• Hypoglycemic Reactions (Insulin Shock)
– symptoms and signs include pallor, sweating,
apprehension, trembling, tachycardia, hunger,
drowsiness, mental confusion, seizures and coma
– management includes administration (if conscious) of
carbohydrate-containing snack or drink
– glucagon 0.5 mg is administered to an unconscious or
vomiting child

36. Suggested Reading
• Glaser N, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis.
NEJM 355;4:264-269.
• Menon RK, Sperling MA. Diabetic Ketoacidosis. In: Fuhrman BP, Zimmerman JJ, ed.
Pediatric Critical Care. Second Edition. St. Louis: Mosby-Year Book, Inc., 1998:844-
52.
• Kohane DS, Tobin JR, Kohane IS. Endocrine, Mineral, and Metabolic Disease in
Pediatric Intensive Care. In: Rogers, ed. Textbook of Pediatric Intensive Care. Third
Edition. Baltimore: Williams & Wilkins, 1996:1261-72.
• Magee MF, Bhatt BA. Management of Decompensated Diabetes: Diabetic
Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome. In: Zaloga GP, Marik P, ed.
Critical Care Clinics: Endocrine and Metabolic Dysfunction Syndromes in the
Critically Ill. Volume 17:1. Philadelphia: W.B. Saunders Company, 2001: 75-106.

37. Case Scenario #1
• A 10 y/o male (~30 kg) presents to the ED with a
one-day history of emesis and lethargy.
• Vitals show T 37C, HR 110, RR 25 BP 99/65.
Patient is lethargic, but oriented x 3. Exam reveals
the odor of acetone on the breath, dry lips, but
otherwise unremarkable
• Labs: pH 7.05 PaCO2 20, PaO2 100, BE -20, Na+
133, K + 5.2, Cl 96 CO2 8. Urine shows 4+
glucose and large ketones

38. Case Scenario #1
• How much fluid would you administer as a
bolus?
• Would you administer bicarbonate?
• What is the “true” serum sodium?
• How much insulin would you administer?
• What IVF would you start? At what rate?

39. Case Scenario #2
• A 4 y/o female in the PICU is undergoing
treatment for new onset IDDM and DKA. She is
on an insulin infusion at 0.1 u/kg/hr, and fluids are
running at 2400 cc/m2/day.
• Over the last hour, she has been complaining
about increasing headache. She is now found to
be unresponsive with bilateral fixed and dilated
pupils, HR is 50 with BP 150/100.
• What is your next step in management?