This document provides an overview of diabetic ketoacidosis (DKA) presented by Dr. Sreekanth Reddy. It defines DKA, discusses epidemiology and etiology. It covers pathophysiology, clinical features, differential diagnosis, investigations and monitoring. Management is outlined including fluid resuscitation, correcting acidosis, hypokalemia and hyperglycemia. Complications of DKA like cerebral edema are also reviewed. Clinical case examples are provided to demonstrate features of DKA.

1. PRESENTER: DR. SREEKANTH REDDY
MODERATOR: DR. PENCHALAIAH MD, DCH
PROFESSOR, NMCH

2. OVERVIEW
DEFINITION
EPIDEMIOLOGY
ETIOLOGY
CLASSIFICATION
PATHOPHYSIOLOGY
CLINICAL FEATURES
D/D
INVESTIGATIONS
MONITORING
MANAGEMENT
COMPLICATIONS and its MANAGEMENT

3. • 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. 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

4. DEFINITION
DKA is the end result of the metabolic abnormalities resulting from a severe
deficiency of insulin or insulin effectiveness leading to
● Hyperglycemia – Blood glucose > 200 mg/dL (11.1 mmol/L)
● Ketosis – Blood ketone > 3 mmol/L or
Urine ketone > 2+
● Metabolic acidosis – pH < 7.3,
Serum bicarbonate < 15 mmol/L,
Base excess > -5 mmol/L

5. EPIDEMIOLOGY
30 - 40 % freshly diagnosed children with T1DM present with DKA.
This can vary from 16-67% depending on geographical, racial and socioeconomic factors.
Although large epidemiological data from India is lacking, the figure is substantially higher
than the developed countries.
In children with established T1DM the risk of development of DKA is 13 episodes per
1000 T1DM patient years. This usually occurs due to omission of insulin or inadequate
management during stress or infection.

6. ETIOLOGY
 DKA is seen in both Type 1 DM and Type 2 DM.
 It is seen in Type 1 DM in
1. New onset DIABETIS MELLITUS (20-40 %)
2. Known case of type 1 DM with omitted insulin dose or intercurrent illness.
3. Idiopathic.
 It is seen in Type 2 DM in
1. Serious infections
2. Trauma
3. Cardiovascular or other emergencies

7.  The primary abnormality is Insulin deficiency
 Increase in counter regulatory hormones such as
Glucagon, Catecholamine, Cortisol and Growth
hormone.

9. CLASSIFICATION
 DKA may be arbitrarily classified as MILD, MODERATE and SEVERE.
 The range of symptoms depends on the depth of ketoacidosis.

10. IJPP CLASSIFICATION

12. PATHOPHYSIOLOGY
As Serum Glucose exceeds the renal threshold of 180 mg/dl, an osmotic diuresis occurs,
resulting in the loss of extracellular water and electrolytes.
Osmotic Diuresis Leads to intravascular volume depletion, which decreases Renal Blood flow
and Glomerular Perfusion, Limiting the body ability to excrete glucose and worsening the
hyperglycemia.
Epinephrine also promotes Lipolysis (FFA release through the activation of adipose tissue
Hepatic sensitive lipase) and then Ketogenesis (through the activation of Hepatic Beta oxidation
of FFA to KETONE BODIES).
BETA HYDROXY BUTYRATE & ACETOACETATE.
Accumulation of Ketoacids is the primary cause of the Metabolic acidosis in DKA

15. In the setting of Metabolic acidosis, Potassium ,primarily an intracellular ion, is
transported out of cell into the plasma in exchange for Hydrogen ion and is lost
in the urine
Thus Virtually all patients with DKA develop a “total body deficiency “ of K, regardless of
their serum K level.
Phosphate another intracellular ion is handled similarly.
Deficiency of 2,3 DPG may also contribute to the lactic acidosis ,complicating the
ketoacidosis
As Na and K are Excreted in the urine with lactate and acidosis, Hyperchloremia occurs.

16. More severe Dehydration leads to poor peripheral tissue perfusion, with
resultant increase in LACTIC ACIDOSIS
Abdominal pain and vomiting ,which occur as a result of the intestinal ileus
brought on by ketoacids and dehydration ,then prevents pts. from maintaining
Hydration with Oral fluids.
Although Insulin defect is a primary cause ,physiologic stress caused by Acidosis
and progressive dehydration stimulates the release of counter regulatory
hormones such as Glucagon, catecholamine and cortisol

17. Cerebral edema typically occurs with in 1st 12 hrs. after the onset of the
treatment.
Mechanism: Vasodilatation (increase in cerebral capillary endothelial
permeability)
Hypothesis: Ketone Stimulation of the production of Vasoactive peptides and
Reperfusion During Rehydration Therapy of Ischemic Cerebral Tissues
Increased Levels Of Taurine and Myoinositol in DKA.
These Generated by Brain cells in order to maintain adequate cell volume
during the acute onset, and they induce an osmotic edema during Vigorous
Rehydration Therapy.

18. DIABETIC KETOACIDOSIS
DECREASED INSULIN
INCREASED COUNTER
REGULLATORY HORMONES
HYPERGLYCEMIA
OSMOTIC DIURESIS
HYPOVOLEMIA
DEHYDRATION
DECREASED TISSUE
PERFUSION
LACTIC ACIDOSIS
LIPOLYSIS
INCREASED FFA
KETONE PRODUCTION
ACIDOSIS KETOSIS

19. CLINICAL FEATURES
There is a need for high index of suspicion for DKA.
DKA should be considered in the presence of any of the following:
● Acute diabetic presentation – polyuria, polydipsia, weight loss.
● Unexplained encephalopathy
● Acute abdomen (Abdominal pain, tenderness, and guarding).
● Unexplained dehydration with polyuria
● Acidotic breathing

20.  Patients with uncontrolled diabetes present with nonspecific complaints.
 If the disease follows an indolent course over months to years, patients
can manifest profound wasting, cachexia, and prostration.
 Misdiagnosis usually occur in patients with new-onset diabetes.

21. HISTORY
 H/O polyuria, polydipsia, nocturia, enuresis, weight loss and lethargy.
 H/O nausea, vomiting and abdominal pain.
GENERAL EXAMINATION:
 CHILD IS LETHARGIC,
 DEHYDRATION PRESENT(dry mucous membranes, poor skin turgor)
 WASTING / CACHEXIA PRESENT.

22. VITALS :
 PULSE : TACHYCARDIA, WITH MILD – MODERATE VOLUME DEPLETION.
 R.R : TACHYPNEIC WITH DEEP, SLOW BREATHS (KUSSMAUL RESPIRATIONS)
associated with the fruity odor of acetone.
 B.P : NORMOTENSIVE ( most cases ).
 Temp : HYPOTHERMIA (even with underlying infection might not manifest
fever).
 CRT: Delayed capillary refill

23. D/D
 Not all patients with hyperglycemia and an anion gap metabolic acidosis
have DKA.
 Other causes of metabolic acidosis must be considered in these patients,
particularly if the serum or urine ketone measurements are not elevated.
 Following causes of metabolic acidosis need to be considered in the
differential diagnosis of DKA.

24. DKA D/D
1. Lactic acidosis:
1. serum glucose and ketones should be
normal.
2. serum lactate concentration should be
greater than 5 mmol/L.
2. Starvation ketosis:
1. Blood glucose concentration-normal.
2. The urine can have large amounts of
ketones.
3. Hyperglycemic Hyperosmolar Coma :
1. Non ketotic acidosis, severe hyperglycemia,
severe dehydration, depressed sensorium or
frank coma.
2. Condition is uncommon in children.
4. Uremic acidosis :
1. Large elevations in the BUN (often >200
mg/dL) and creatinine (>10 mg/dL) values
with normoglycemia.
2. The pH and anion gap are usually only mildly
abnormal.
5. Toxic ingestions : KLUMPIES
1. Salicylate, Methanol and ethylene glycol.
2. Isopropyl alcohol is metabolized to acetone.

25. OTHER D/D
1. HYPERGLYCEMIA HYPEROSMOLAR SYNDROME.
2. ACUTE GASTRO ENTERITIS.
3. SURGICAL ABDOMEN.
4. PNEUMONIA.
5. RENAL TUBULAR ACIDOSIS.

26. INVESTIGATIONS
1) SERUM SODIUM (Na)
■ Status – Deficit (20% of total body sodium, 4-6 mmol/kg)
■ Sodium levels are falsely reduced in hyperglycemia (use corrected
sodium)
■ Implication – Rapid decline is a risk factor for cerebral edema
2) SERUM POTASSIUM (K)
■ Status
Intracellular – Deficit (20% of total body potassium, 3-6 mmol/kg)
18

27. Extracellular – Elevated due to acidosis and insulin deficiency
■ Implication – Treatment of DKA is associated with risk of hypokalemia due to intracellular shift
secondary to reversal of metabolic acidosis and correction of insulin deficiency.
3) PLASMA OSMOLALITY :
■ Status – Elevated (300-350 mOsm/kg)
■ Estimation – Effective plasma osmolality
Effective osmolality- 2 (Na + K) + Glucose (mg/dL) mOsm/kg
18
Implication: Aim is to have gradual fall in osmolality of 2 mOsm/kg/hour.
More rapid fall than this is a risk factor for cerebral edema

28. 4) BLOOD LACTATE :
■ Status – Normal (0.4-1.8 mmol/L)
■ Implication – Lactic acidosis in DKA should prompt evaluation for
cerebral edema, infection or hemodynamic compromise
5) SERUM PHOSPHATE :
■ Status – Deficit (0.5-1 mmol/kg)
■ Implications – Hypophosphatemia may be associated with decreased
responsiveness to insulin and lactic acidosis

29. 6) INFECTION SCREENING
■ Complete blood examination: Transient leukocytosis is common in DKA.
Consider infection only in the presence of persistent leukocytosis and
fever.
■ Urine examination
■ Blood and urine cultures
■ Chest X ray in the presence of persistent tachypnea and chest signs
● Renal function tests – High urea indicative of severe DKA
● Electrocardiography – For evidence of hypo/hyperkalemia

30. FREQUENCY OF INVESTIGATIONS
1. Blood glucose Every Hourly
2. Serum Electrolytes every 6th Hourly
3. Arterial Blood Gases every 6th Hourly
4. Serum Bicarbonate
5. Blood urea every 8-12th hourly
6. Hematocrit every 8-12th hourly
7. Plasma or Urinary Ketones 24th hourly
8. End tidal CO2 measurements
9. Serum Phosphate
10. CBP
11. ECG

31. MONITORING
EVERY HOUR
1. VITALS, PULSE OXIMETRY.
2. FLUID INPUT & OUTPUT .
3. PUPILS & NEUROLOGICAL SIGNS ( GCS,
warning signs of cerebral oedema ).
4. BLOOD SUGAR LEVELS.
EVERY 4-8 HOURLY
1. ABG / Q 2-4 hrly
2. SERUM ELECTROLYTES / Q 2-4 hrly
3. BLOOD UREA, CREATININE / Q 8-12 hrly
4. HEMATOCRIT / Q 8-12 hrly

33. MANAGEMENT
PROTOCOLS FOR MANAGING DKA
1. DEHYDRATION/ SHOCK
2. ACIDOSIS
3. HYPOKALEMIA
4. HYPERGLYCEMIA
5. HYPEROSMOLARITY
6. CEREBRAL OEDEMA
7. PRECIPITATING INFECTIONS

34. 1. DEHYDRATION

35. MILWUAKEE
PROTOCOL
It can be used for children of all ages and with all degrees of DKA
It is designed
to restore most electrolyte deficits,
to reverse the acidosis and
to rehydrate the moderately ill child in about 24 hr.
A standard water deficit (85 mL/kg) is assumed. This amount, when added to maintenance,
yields about 4 L/m2 for children of all sizes

36. These calculations will usually cover ongoing losses which in most cases do not need additional
replacement but
EXCESSIVE CONTINUING FLUID LOSSES IN URINE AND /OR VOMITING MIGHT NEED REPLACING
IF THE SEVERITY OF DEHYDRATION IS NOT IMPROVING

37. FLUID DEFICITS
 Calculation of fluid deficits using clinical signs is difficult in children with DKA because
intravascular volume is better maintained in the hypertonic state.
 For any degree of tachycardia, delayed capillary refill, decreased skin temperature, or
orthostatic blood pressure change, the child with DKA will be more dehydrated than
the child with a normotonic fluid deficit.
 The initial intravenous bolus (20 mL/kg of glucose-free isotonic sodium salt solution
such as Ringer lactate or 0.9% sodium chloride) for all patients ensures a quick volume
expansion and may be repeated if clinical improvement is not quickly seen

38.  This bolus is given as isotonic saline because the patient is inevitably
hypertonic, keeping most of the initial infusion in the intravascular space.
 Subsequent fluid is hypotonic to repair the free water deficit, to allow
intracellular rehydration, and to allow a more appropriate replacement of
ongoing hypotonic urine losses.
 The sodium should steadily increase with therapy.
 Declining sodium may indicate excessive free water accumulation and the risk
of cerebral edema.

39. 2. ACIDOSIS
DKA has a wide anion gap metabolic acidosis.
Fluid Therapy and Insulin Therapy Will correct Acidosis.
Hco3 therapy is seldom necessary even in severe DKA but Trials have failed to
show use of HCO3 therapy.

40. BICARBONATE THERAPY
 Conversely HCO3 therapy may cause
1. Severe paradoxical CNS acidosis,
2. Hypokalemia,
3. Accumulate sodium load with consequent risk of Cerebral Edema
 INDICATIONS include –
1. Severe acidosis i.e. pH <6.9,
2. Refractory Shock,
3. Life threatening Hyperkalemia
 In such extreme cases,HCO3 required can be calculated by
0.3 wt. (kgs) base deficit

41. 3. HYPOKALEMIA
 Acidosis + Diuresis ->>> HYPOKALEMIA.
 INSULIN + HYDRATION ----- worsens HYPOKALEMIA.
 serum K+  normal / increased.
 Total body K+  decreased.
 SO, Serum K + is poor indicator of total body potassium.
 Patient with low serum K+  indicates severe pot deletion.

42. WHEN TO GIVE POTASSIUM
 Give 1st – IVF bolus.
2nd – Kcl supplementation.
3rd – insulin infusion.
 DOSAGE : 5 mEq/ Kg / day or 30 - 40 mEq/ L of IVF
 C/I : oliguria , renal failure, serum K+ > 5.5 mEq/ L.
 Assess serum K+ Q hourly until it become normal
Q 2 hourly for next 6 hours
Q 4 hourly thereafter.
INFUSION:
Central line - 0.3 -0.5 mEq/Kg/hr
No central line – 80 mEq /L for 2-3 hrs.

43.  Insulin must be given at the beginning of therapy to
1. Accelerate movement of glucose into cells
2. Subdue hepatic glucose production and
3. Halt the movement of fatty acids from the periphery to the liver .
 An initial insulin bolus does not speed up the recovery and may increase the risk of Hypokalemia
and Hypoglycemia.
 Add 40 units regular insulin to 40ml NS so that 1 ml = 1 unit Insulin
 Insulin infusion is started with a bolus @ 0.1 U/kg/hr.
 Rehydration also lowers glucose levels by improving renal perfusion and enhancing renal
excretion.
4. HYPERGLYCEMIA

44.  Once glucose goes below 180 mg/dL (10 mmol/L), the osmotic diuresis stops
and rehydration accelerates without further increase in the infusion rate.
 When the serum glucose has decreased to about 250 mg/dL, insulin infusion
can also be lowered
To continue the insulin infusion without causing hypoglycemia, glucose must
be added to the infusion.

46. INFUSION TO SUB-CUTANEOUS
 Anion gap should be resolved.
 Total CO2 >15 mEq/L.
 pH >7.30.
 Sodium stable between 135 and 145 mEq/L
 Child should accept orally and No emesis.
Stop both the IV fluid and insulin infusion simultaneously 30 minutes after the first subcutaneous
injection is given and child has had a meal.
• DAILY DOSE OF SUBCUTANEOUS INSULIN SHOULD BE HALF OF THAT OF TOTAL DOSE OF INSULIN INFUSION
• RESIDUAL SECRETION OF INSULIN MAY NECESSITATE A REDUCTION IN THE INITIAL TOTAL SUBCUTANEOUS INSULIN DOSE
USED IN THE 1ST FEW DAYS OF THERAPY.

47. Give the calculated dose of subcutaneous insulin.
If newly diagnosed:
Weight < 30kg - 0.2 u/kg/dose Insulatard am, 0.1 u/kg/dose Insulatard pm
Weight > 30kg – 0.4 u/kg/dose Mixtard am, 0.2 u/kg/dose Mixtard pm subcutaneously and
LET THE CHILD HAVE A MEAL
wait for
30 min
then stop the IV insulin and IV fluids simultaneously.

49. 5. HYPEROSMOLARITY
 The effective serum osmolality is an accurate index of tonicity of the body fluids, reflecting
intracellular and extracellular hydration better than measured plasma osmolality. It is calculated
with sodium and glucose.
 The initial serum sodium is usually normal or low because of the osmolar dilution of
hyperglycemia.
 If the corrected value is greater than 150 mmol/L, severe hypernatremic dehydration may
be present and may require slower fluid replacement.
 The sodium should steadily increase with therapy.
 Declining sodium may indicate excessive free water accumulation and the risk of cerebral
edema.
(E osm =2 ×[Na uncorrected] +[glucose] mmol/L)

50. 6. CEREBRAL EDEMA
◊ During treatment, serum osmolality may decrease more rapidly than CNS osmolality,
resulting in fluid shifts into the CNS. This may cause life threatening cerebral edema.
◊ Approximately 0.4-1% of children with DKA develop cerebral edema with a high
mortality/morbidity.
◊ Cerebral edema most commonly occurs in the first 24 hours, often secondary to
vigorous rehydration.
◊ It is advisable to avoid more than 30 ml/kg fluid bolus.
◊ In many cases warning signs/symptoms occur which should prompt the emergency
administration of Mannitol.
◊ More dramatic changes such as convulsions, papilledema, respiratory arrest are late
signs associated with extremely poor prognosis.

51. 6. CEREBRAL EDEMA
 Risk factors:
1. Declining sodium may indicate excessive free water accumulation and the risk of cerebral edema.
2. Early administration of insulin
3. High volumes of fluid
 Monitor for Raised signs of ICP : head ache, vomiting, depressed level of consciousness, 6th
cranial nerve palsies, hypertension with or without HR, papilledema.
 Monitor Serum Na Levels
 Monitor GCS every Hourly

52. WARNING SIGNS/SYMPTOMS OF CEREBRAL EDEMA
Clinically the patient may complain of headaches or have a change in mental status hours after
therapy for DKA has begun.
In some there is a premonitory period when development of cerebral edema could be
suspected if there is a
• Change in arousal or behavior,
• Severe headache,
• Incontinence,
• Pupillary changes,
• Seizures
• Change in neurological status
• Decreased O2 saturation.
• Bradycardia,
• Rising BP
• Disturbed temperature regulation.
• Restlessness,
• Irritability,
• Increased drowsiness
• specific neurological signs
(e.g.. cranial nerve palsies)

53.  Slow rehydration of the hyperosmolar (hypernatremic) patient.
 Immediate IV Mannitol 1 g/kg over 20 minutes (i.e.. 5ml / kg 20% solution)
 2-4 ml/kg of Hypertonic (3%) Sodium Chloride to maintain serum Na > 150 mmol/l
 Exclude hypoglycemia
 Half rehydration infusion rate until situation is improved but it is important to maintain insulin
infusion to switch off ketotic process
 Child’s head should be elevated.
 Avoid intubation unless absolutely necessary. Decision for intubation and advice on optimal
pCO2 levels if intubated should be discussed with CICU consultant.
pCO2 should be kept >3.5kPa – very poor outcome associated when pCO2 falls <2.9kPa

54. TREATMENT RELATED COMPLICATIONS

57. DIET
 The dietitian will advise on this according to the child’s usual food
intake.
In the recovery period the child’s appetite is likely to be enormous.
 Do not restrict this.
 The child must however receive starchy carbohydrate food every
2-3 hours with emphasis even to bedtime snack to avoid nocturnal
hypoglycemia.

58. TRIALS
 In genetically high risk population before initiation of autoimmunity, elimination
of auto antigen or induction of tolerance to auto antigen like cow’s milk is
eliminated from the diet of newly born 1st degree relative of patients with T1DM.
 In PREDIABETIC period of autoimmune patients, NICOTINAMIDE and INSULIN,
this was effective in mouse model.
 EXOGENOUS INSULIN can modify the immune response against beta cells.
 IMMUNOSUPRESSIVE AGENTS such as prednisolone, azathioprine and
cyclosporine in recently diagnosed T1DM patients.

59. TERMINOLOGY
DAWN PHENOMENON:
o Blood glucose levels increase in the early morning hours before breakfast.
o Seen in many children using NPH or Lente as the basal insulin at supper or
bedtime.
o Overnight growth hormone secretion and increased insulin clearance
o It is a normal physiologic process seen in most non-diabetic adolescents
(compensated)
o A child with T1DM cannot compensate and may actually have declining insulin
levels if using evening NPH or Lente.

60. SOMOGYI PHENOMENON:
o Theoretical rebound from late night or early morning hypoglycemia, thought to be due to
an exaggerated counter regulatory response

61. BRITTLE DIABETES:
o An adolescent female, with unexplained wide fluctuations in blood glucose, often with
recurrent DKA, who is taking large doses of insulin

62. TAKE HOME MESSAGE
● Diabetic ketoacidosis (DKA) is a life-threatening condition requiring
early diagnosis and appropriate treatment.
● Laboratory tests should be interpreted with caution due to known
fallacies.
● Children younger than 2 years and those with severe DKA should be
managed in an ICU.
● Hydration is the mainstay of management of DKA. Rapid and excessive
fluid administration should however be avoided due to the risk of
cerebral edema.

63. ● Continuous intravenous infusion of insulin is the standard of care for
pediatric DKA. In resource-poor settings intermittent intramuscular
insulin may be used. Intravenous bolus of insulin should be avoided.
● Potassium replacement is required in children with DKA even if the
initial potassium levels are normal.
● Bicarbonate should be used only in children with pH less than 6.9 and
cardiac compromise.
● Resolution of acidosis is the primary criteria for reduction of insulin
infusion rate.

64. ● Mannitol and dextrose should be available at bedside of all patients with DKA
for emergent treatment of cerebral edema and hypoglycemia.
● Cerebral edema should be considered in all patients with sudden
deterioration of neurological and clinical status.
● Insulin infusion should be discontinued 30 minutes after the
administration of subcutaneous insulin.
● Appropriate management during sick days and invasive procedures is
essential for prevention of DKA.

65. REFERRENCE
1. NELSON TEXTBOOK OF PEDIATRICS- 19TH EDITION
2. MANUAL OF PEDIATRIC EMERGENCIES AND CRITICAL CARE BY SUCHITHRA RANJITH - 2ND
EDITION.
3. WILLIAM’S ENDOCRINOLOGY- 12TH EDITION
4. DKA PROTOCOL IJPP – OCT –DEC 2012
5. ROGER'S TEXTBOOK OF PEDIATRIC INTENSIVE CARE, 4TH EDITION

66. CASE 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 ml/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 bpm with BP 150/100.
• What is your next step in management?

68. THANK YOU