This document defines diabetic ketoacidosis (DKA) and describes its causes, pathophysiology, clinical manifestations, diagnostic criteria, and management. DKA is caused by low insulin levels and high counterregulatory hormones, resulting in hyperglycemia, dehydration, and metabolic acidosis. It is often triggered by missed insulin injections, illness, or stress in patients with type 1 diabetes. Treatment involves fluid resuscitation, insulin therapy, electrolyte replacement, and identifying/treating any precipitating causes to reverse the condition.

3. DKA Definition:
A state of absolute or relative insuline
defeciency resulting in hyperglycemia,
dehydration and accumulation of
ketone bodies in the blood with
subsquent metabolic acidosis.

4. Causes of DKA:Causes of DKA:
A. Initial presentation of type 1 diabetesA. Initial presentation of type 1 diabetes
mellitusmellitus
B. Missed insulin injectionsB. Missed insulin injections
C. Inadequate insulin dosage in a knownC. Inadequate insulin dosage in a known
diabetic patientdiabetic patient
D. Emotional stress/ trauma/surgeryD. Emotional stress/ trauma/surgery
without adequate insulin adjustmentwithout adequate insulin adjustment
E. Intercurrent illness/infection withoutE. Intercurrent illness/infection without
appropriate dose adjustmentappropriate dose adjustment

5. PathophysiologyPathophysiology
The combination of low serum insulin and highThe combination of low serum insulin and high
counterregulatory hormone concentrationscounterregulatory hormone concentrations
results in:results in:
 an accelerated catabolic state with increasedan accelerated catabolic state with increased
glucose production by the liver and kidney (viaglucose production by the liver and kidney (via
glycogenolysis And gluconeogenesis)glycogenolysis And gluconeogenesis)
 impaired peripheral glucose utilizationimpaired peripheral glucose utilization
resulting in hyperglycemia andresulting in hyperglycemia and
hyperosmoLality , and increased lipolysis andhyperosmoLality , and increased lipolysis and
ketogenesis ,causing Ketonemia and metabolicketogenesis ,causing Ketonemia and metabolic
acidosisacidosis

6. .Hyperglycemia that exceeds the renal
threshold [180mg/dL]) and hyperketonemia
cause osmotic diuresis, dehydration, and
obligatory loss of electrolytes, which often is
aggravated by vomiting.
These changes stimulate further stress hormone
production ,which induces more severe insulin
resistance and worsening hyperglycemia and
hyperketonemia.

7. If this cycle is not interrupted with exogenousIf this cycle is not interrupted with exogenous
insulin, fluid and electrolyte therapy , fatalinsulin, fluid and electrolyte therapy , fatal
dehydration and metabolic acidosis will ensue.dehydration and metabolic acidosis will ensue.
Ketoacidosis may by aggravated by lacticKetoacidosis may by aggravated by lactic
acidosis from poor tissue perfusion or sepsis.acidosis from poor tissue perfusion or sepsis.

8. Clinical manifestations of diabeticClinical manifestations of diabetic
ketoacidosisketoacidosis

9. •• DehydrationDehydration
•• Rapid, deep, sighing (Kussmaul respiration)Rapid, deep, sighing (Kussmaul respiration)
••Nausea, vomiting, and abdominal painNausea, vomiting, and abdominal pain
mimicking an acute abdomenmimicking an acute abdomen
••Progressive obtundation and loss ofProgressive obtundation and loss of
consciousnessconsciousness
•• Increased leukocyte count with left shiftIncreased leukocyte count with left shift
•• Non-specific elevation of serum amylaseNon-specific elevation of serum amylase
•• Fever only when infection is presentFever only when infection is present

10. Biochemical criteria for the
diagnosis of DKA

11. • Hyperglycemia (blood glucose > 11mmol/L [≈
200 mg/dL])
• Venous pH <7.3 or bicarbonate <15mmol/L
• Ketonemia and ketonuria

12. The severity of DKA is categorized by the
degree of acidosis :
• Mild: venous pH <7.3 or bicarbonate
<15mmol/L
• Moderate: pH <7.2 , bicarbonate <10mmol/L
• Severe : pH <7.1, bicarbonate <5mmol/L

13. note
?

14. Partially treated children and children whoPartially treated children and children who
have consumed little or no carbohydratehave consumed little or no carbohydrate
may have, on rare occasion, only modestlymay have, on rare occasion, only modestly
increased blood glucose concentrationincreased blood glucose concentration
(‘‘euglycemic ketoacidosis’’)(‘‘euglycemic ketoacidosis’’)

15. managementmanagementA. History (key points)A. History (key points)
1.Classic triad = polydipsia, polyuria, and weight1.Classic triad = polydipsia, polyuria, and weight
loss (polyphagia is unusual in children)loss (polyphagia is unusual in children)
2. Vomiting/abdominal pain2. Vomiting/abdominal pain
3. Increased, difficult, or deep respirations3. Increased, difficult, or deep respirations
4. Symptoms of infection/flu (may be similar to4. Symptoms of infection/flu (may be similar to
those of DKA)those of DKA)
5. Illness in family members or close friends5. Illness in family members or close friends
6. In a known diabetic:6. In a known diabetic:
*when and how much insulin was last taken?*when and how much insulin was last taken?
*missed shots?*missed shots?
*emotional stress as clues to missed shots?*emotional stress as clues to missed shots?

16. B. Physical exam :B. Physical exam :
1. Vital signs1. Vital signs
2 Hydration status / peripheral perfusion /2 Hydration status / peripheral perfusion /
hypovolemic shock?hypovolemic shock?
3. Acetone-fruity breath3. Acetone-fruity breath
4. Kussmaul respirations4. Kussmaul respirations
5. Neurologic status5. Neurologic status
6. Signs of infection6. Signs of infection

17. C. Initial labs-statC. Initial labs-stat
1.For diagnosis: blood glucose and urine ketones.1.For diagnosis: blood glucose and urine ketones.
A simple urine dipstick and/or a meter glucose level inA simple urine dipstick and/or a meter glucose level in
an ED or officean ED or office
2.2. Serum glucose, electrolytes including Na+, K+,Serum glucose, electrolytes including Na+, K+,
HCO3 and BUN, venous pH and PC02.HCO3 and BUN, venous pH and PC02.
[Arterial PC02 less than 20 mmHg may be an important[Arterial PC02 less than 20 mmHg may be an important
predictor of cerebral edema in severe DKA. (pH <7.0)predictor of cerebral edema in severe DKA. (pH <7.0)

18. 3-Calcium ,phosphorus, and magnesium
concentrations (ifpossible), HbA1c, hemoglobin
and hematocrit or complete
Blood count .
Note, however, that an elevated white blood cell count
in response to stress is characteristic of DKA an does
not necessarily indicative of infection

19. 4-4- Perform a urine analysis for ketones.Perform a urine analysis for ketones.
5- Measurement of blood ß-hydroxy butyrate5- Measurement of blood ß-hydroxy butyrate
concentration, if available, is usefull toconcentration, if available, is usefull to
confirm ketoacidosis and may be used toconfirm ketoacidosis and may be used to
monitor the response to treatmentmonitor the response to treatment
6- Obtain appropriate specimens for culture6- Obtain appropriate specimens for culture
(blood, urine , throat), if there is evidence of(blood, urine , throat), if there is evidence of
infection.infection.

20. 7- If laboratory measurement of serum7- If laboratory measurement of serum
potassium is delayed, perform an (ECG) forpotassium is delayed, perform an (ECG) for
baseline evaluation of potassium statusbaseline evaluation of potassium status

21. Additional calculations thatAdditional calculations that
may be informativemay be informative
Anion gapAnion gap = Na − (Cl + HCO3): normal is= Na − (Cl + HCO3): normal is
12 ± 212 ± 2 (m mol/L)(m mol/L)
In DKA the anion gap is typicallyIn DKA the anion gap is typically 20–3020–30
m mol /L;m mol /L;
An anion gapAn anion gap >35>35 m mol/L suggestsm mol/L suggests
concomitant Lactic acidosisconcomitant Lactic acidosis

22. Pseudohyponatremia (hyperglycemia and
hyperlipidemia result in falsely lowered plasma
sodium
(Naactual = Nameasured+ 1.6[(glucose – 100)/100]

23. ••Corrected sodiumCorrected sodium = measured Na + 2= measured Na + 2
([plasma glucose − 5.6] /5.6 ) (mmol/L)([plasma glucose − 5.6] /5.6 ) (mmol/L)
•• Effective osmolalityEffective osmolality = (mOsm /kg) 2x(Na += (mOsm /kg) 2x(Na +
K) + glucose (mmol/L)K) + glucose (mmol/L)

24. Hyperosmolality as a result of progressive
hyperglycemia contributes to cerebral obtundation in
DKA
Serum osmolality:

25. Hyperglycemic Hyperosmolar
Syndrome (HHS)

26. DKA vs. HHS

27. Pathophysiology
With progressive
dehydration, acidosis,
hyperosmolality, and
diminished cerebral
oxygen utilization,
consciousness becomes
impaired, and the
patient ultimately
becomes comatose

28. treatmenttreatment
Goals of therapyGoals of therapy
Correct dehydrationCorrect dehydration
Correct acidosis and reverse ketosisCorrect acidosis and reverse ketosis
Restore blood glucose to near normalRestore blood glucose to near normal
Avoid complications of therapyAvoid complications of therapy
Identify and treat any precipitating eventIdentify and treat any precipitating event

29. A. Mistakes and how to avoid them
1) Failure to recognize the problem (e.g., the diagnosis of
new onset diabetes, cerebral edema, hypokalemia, etc.).
2) Failure to react to the situation, whether the problem is
due to the natural course of the disease, or secondary to
therapy.
a. Keep a flow sheet for fluids, insulin, vital signs, lab
values, etc. b. Record all intake and output
meticulously. c. ECG monitor
for K+ changes if severe acidosis or elevated K+.
d. Urinary catheter only if unconscious. If conscious, ask
patient to void every hour. In the young child, weigh
the diapers hourly.
e. Check pupils and sensorium hourly (for cerebral

30. Fluids
1. Initial volume expansion =10 to20cc/kg
(300-600cc/m2) of a physiologic solution
(such as saline or lactated Ringers solution)
over the first one to two hours.
This may need to be repeated if the
patient is severely dehydrated and/or if urine
output is massive. However, the initial bolus
re-expansion should never exceed 40 cc/kg
as a total fluid dose for the first four hours of
treatment.

31. 2. 24 hour fluid therapy
a. Replacement: Use estimates of dehydration based on
physical exam varying from 5 to 10% of body weight for mild to
severe losses.
Deficits should be replaced evenly over 48 hours.
Remember to subtract the quantities given in the first hours of
re-expansion from the 24 hour totals.
Follow urine output to be certain initial estimates are adequate.
Replacement of urine output (“cc” for “cc”) is generally not
required, since excessive urine output should resolve within the
initial 2 to 4 hours of therapy as the hyperglycemia resolves.
Total fluid replacement should not exceed 4 L per square meter
per 24 hours.

32. b. Maintenance
body weight (kg) 24 hour fluid maintenance
up to 10 100 ml/kg
10 to 20 1000 ml + 50 ml/kg over 10 kg
>20 1500 ml + 20 ml/kg over 20 kg
c. Special additional losses
Additional replacement may be required where
there is severe vomiting, etc.

33. Insulin therapy
Although rehydration alone causes some decrease
in blood glucose concentration, insulin therapy is
essential to normalize blood glucose and suppress
lipolysis and ketogenesis.
• Start insulin infusion 1–2hours after starting fluid
Replacement therapy; i.e .after the patient has
Received initial volume expansion

34. Correction of insulin deficiency
Dose: 0.1 unit/kg/hour (for example,one method is
to dilute 50 units regular [soluble] insulin in 50 mL
normal saline, 1unit = 1mL)
Route of administration IV
An IV bolus is unnecessary, may increase the
risk of cerebral edema , and should not be used at
the start of therapy

35. Goal is to slowly decrease serum glucose > 100
mg/dl/hr
The dose of insulin should usually remain at
0.1 unit/kg/hour at least until resolution of
DKA (pH > 7.30 , bicarbonate > 15 mmol/L
and/or closure of the anion gap), which
invariably takes longer than normalization of
blood glucose concentrations

36. To prevent an unduly rapid decrease in plasma
glucose concentration and hypoglycemia , 5%
glucose should be added to the IV fluid (e.g., 5%
glucose in 0.45% saline) when the plasma
glucose falls to approximately 14–17 mmol/L
(250–300 mg/dL), or sooner if the rate of fall is
precipitous.

37. It may be necessary to use 10% or even 12.5%
dextrose to prevent hypoglycemia while
continuing to infuse insulin to correct the
metabolic acidosis.

38. Potassium
K+ is a special problem because high urinary
losses occur in association with normal serum
levels caused by the intracellular exodus of K+ in
the presence of acidosis.
Vomiting may also contribute to hypokalemia.
and as a consequence of osmotic diuresis.
Volume depletion causes secondary
hyperaldosteronism,which promotes urinary
potassium excretion

39. Thus, total body depletion of potassium occurs, but
at presentation serum potassium levels may be normal,
increased or decreased. renal dysfunction, by
enhancing hyperglycemia and reducing potassium
excretion, contributes to hyperkalemia.
Total body potassium is usually depleted, but serum
levels may be normal or high.
As acidosis is corrected, K+ is driven back into the
cells and there is usually a fall in serum K+ in spite of
large K+ replacements.

40. Low or high serum potassium levels can be a
cause of cardiac arrhythmias, which can be fatal.
a. Potassium must never be given until the serum
potassium level is known.
b. Once the serum potassium is known to be normal
or low, and after voiding is observed, generally
after the first hour of fluid resuscitation, all IV
fluids should include 20-40 mEq/L of potassium. If
the serum potassium is high, it is best to wait to add
K+
to the IV until the K+ begins to decrease.

41. The potassium may be in the form of KCl, KAc,
K2H PO4 or a combination of thes supplements.
Do not give K+ as a rapid IV bolus or cardiac
arrest may result.
Severe hypokalemia may lead to respiratory
arrest due to muscle dysfunction.
ECG strips (Lead II) may give the best
indication of total body K+ deficit or change.

42. Potassium (give as Kphos, Kacetate, or KCl)
If K > 6 = No K initially
If K 5 – 6 = consider adding K+
If K < 5 = at least 40 mEq/L
Don’t forget “hyperkalemia associated with acidosis”
and role of insulin

43. Acidosis
Severe acidosis is reversible by fluid and insulin
replacement; insulin stops further ketoacid
production and allows ketoacids to be metabolized,
which generates bicarbonate.
Treatment of hypovolemia improves tissue perfusion
and renal function, thereby increasing the excretion
of organic acids.

44. BICARBONATE IS ALMOST NEVER ADMINISTERED
bicarbonate administration can lead to paradoxical
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
ischemia

45. Rapid correction of acidosis with bicarbonate
causes hypokalemia and failure to account for the
sodium being administered and appropriately reducing
the NaCl concentration of the fluids can result in
increasing osmolality

46. Nevertheless, there may be selected patients who
may benefit from cautious alkali therapy. These
include:
Patients with severe acidemia (arterial pH <6.9) in
whom decreased cardiac contractility and
peripheral vasodilatation can further impair tissue
perfusion, and patients with life-threatening
hyperkalemia

47. Complications of therapy
• Inadequate rehydration
• Hypoglycemia
• Hypokalemia
• Hyperchloremicacidosis
• Cerebraledema

48. Case Scenario
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 1.5 maintenance.
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?

49. Treatment pitfalls
Cerebral edema is the major life-threatening
complication seen in the treatment of children with
DKA
usually develops several hours after the institution of
therapy
Most commonly presents in children between 5 –14
years

50. Treatment pitfalls
Cerebral edema is the major life-threatening
complication seen in the treatment of children with
DKA
usually develops several hours after the institution of
therapy
Most commonly presents in children between 5 –14
years

51. Treatment pitfalls
Clinically evident cerebral
edema – about 1%.
However, increasing
evidence suggests that
subclinical cerebral edema
occurs in the majority of
patients treated with fluids
and insulin for DKA
Glaser N J Pediatr. 2004

52. Treatment pitfalls
Cerebral edema
manifestations include
headache, alteration in
level of consciousness,
bradycardia, emesis,
diminished
responsiveness to
painful stimuli, and
unequal or fixed, dilated
pupils

53. Treatment pitfalls
Therapy of cerebral
edema includes
treatment aimed at
lowering increased
intracranial pressure
(mannitol, hypertonic
saline, hyperventilation,
etc..)

54. Treatment pitfalls
Traditional risk factors thought to be excessive use of
fluids, use of bicarbonate, and large doses of insulin
(or just sicker patients?)

55. Treatment pitfalls
More recently identified
risk factors
Increased BUN at
presentation (reflective of
greater dehydration)
Profound neurologic
depression at diagnosis of
cerebral edema
Endotracheal intubation
with hyperventilation (Marcin
J Pediatr 2002)
But ….

56. Other pitfalls
Thrombosis associated with femoral venous
catheterization in children with DKA (Gutierrez JA. Critical
Care Medicine 2001)
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

57. Cerebral edemaCerebral edema
incidence is 0.5–0.9% and the mortality rate isincidence is 0.5–0.9% and the mortality rate is
21–24%.21–24%.
Pathogenesis is unclear and incompletely understoodPathogenesis is unclear and incompletely understood
Demographic risk factors include:Demographic risk factors include:
•• Younger ageYounger age
•• New onset diabetesNew onset diabetes
•• Longer duration of symptomsLonger duration of symptoms

58. Risk factors at diagnosis or during treatment Of
DKA :
• Greater hypocapnia at presentation after adjusting
For degree of acidosis.
• Increased serum urea nitrogen at presentation.
• More severe acidosis at presentation.
• Bicarbonate treatment for correction of acidosis.
• An attenuated rise in measured serum sodium
Concentrations during therapy.
• Greater volumes of fluid given in the first 4 hours.

59. Warning signs and symptoms of cerebral
edema
• Headache & slowing of heart rate
• Change in neurological status (restlessness,
Irritability ,increased drowsiness,incontinence)
• Specific neurological signs (e.g.,cranial nerve
palsies)
• Rising blood pressure
• Decreased O2 saturation

60. Diagnostic criteria
• Abnormal motor or verbal response to pain
• Decorticate or decerebrate posture
• Cranial nerve palsy (especially III ,IV , and VI)
• Abnormal neurogenic respiratory pattern (e.g.,
Grunting , tachypnea, Cheyne-Stokesrespiration,
apneusis)

61. Major criteria
• Altered mentation/fluctuating level of consciousness
• Sustained heart rate deceleration (decrease more
than 20 beats per minute) not attributable to improved
Intravascular volume or sleep state
• Age-inappropriate incontinence

62. Minor criteria
• Vomiting
• Headache
• Lethargy or not easily arousable
• Diastolic blood pressure >90 mmHg
• Age <5 years

63. One diagnostic criterion ,two major criteria, or
one major and two minor criteria have a
sensitivity of 92% and a false positive rate of
only 4%.

64. Treatment of cerebral edema
• Initiate treatment as soon as the condition is
suspected.
• Reduce the rate of fluid administration by one-third.
• Give mannitol 0.5–1 g /kg IV over 20 minutes and
Repeat if there is no initial response in 30 minutes to
2 hours .

65. • Hypertonic saline (3%), 5–10 mL/kg over30 Minutes ,may
be an alternative to mannitol or a Second line of therapy if
there is no initial response to mannitol .
O Mannitol or hypertonic saline should be available
at the bedside

66. Elevate the head of the bed
Intubation may be necessary for the patient with
impending respiratory failure, but aggressive
hyperventilation (to a pCO2 <2.9kPa [22mmHg]) has
been associated with poor outcome and is not
recommended

67. After treatment for cerebral edema has been
started, a cranial CT scan should be obtained
to rule out other possible intracerebral causes
of neurologic deterioration ( ≈10%ofcases),
especially thrombosis or hemorrhage, which
may benefit from specific therapy.

68. Recommendations/ key points
• DKA is caused by either relative or absolute insulin
deficiency.
• Children and adolescents with DKA should be
managed in centers experienced in its treatment and
where vital signs, neurological status and laboratory
results can be monitored frequently
• Begin with fluid replacement before starting insulin
therapy.
• Volume expansion (resuscitation) is required only if
needed to restore peripheral circulation.

69. Subsequent fluid administration (including oral fluids)
should rehydrate evenly over 48 hours at a rate rarely
in excess of 1.5–2 times the usual daily
Maintenance requirement.
Begin with 0.1U/kg/h. 1–2 hours AFTER starting
fluid replacement therapy.

70. If the blood glucose concentration decreases too
Quickly or too low before DKA has resolved,
Increase the amount of glucose administered. Do
NOT decrease the insulin infusion
Even with normal or high levels of serum potassium
At presentation, there is always a tota lbody deficit of
potassium.
Begin with 40 mmol potassium/L in the infusate or
20 mmol potassium/L in the patient receiving fluid At a rate
>10 mL/kg/h.

71. • There is no evidence that bicarbonate is either
Necessary or safe in DKA.
• Have mannitol or hypertonic saline at the bedside
And the dose to be given calculated before hand.
• In case of profound neurological symptoms, mannitol
should be given immediately.
• All cases of recurrent DKA are preventable