Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) are acute complications of diabetes that result from insufficient insulin levels. DKA is characterized by high blood glucose, low pH and bicarbonate levels, and ketones in the blood or urine. HHS involves extremely high blood glucose without significant ketosis or acidosis. Treatment for DKA involves rehydration, insulin administration, and correcting electrolyte imbalances. Complications can include hypokalemia, hypoglycemia, and in rare cases cerebral edema in children. Proper patient education aims to prevent DKA episodes.

1. DIABETIC
KETOACIDOSIS (DKA)
&
HYPEROSMOLAR HYPERGLYCEMIC
SYNDROME (HHS)
DR. JAYESH VAGHELA

2. KETONE BODIES
SYNTHESIS

3. 2

4. SPECTRUM OF
DKA AND HYPEROSMOLAR COMA
Pure
Ketoacidosis
Ketoacidosis-
Hyperosmolar
Coma
Pure
Hyperosmolar
Coma
Rapid Onset
Marked Insulin
Lack
Intermediate Slow Onset
Mild Insulin Lack

5. DIABETIC
KETOACIDOSIS

6. INTRODUCTION
•Diabetic : Glucose >250 mg/dL
•Keto – :ketones produced
 Blood concentration: 90mg/100ml
 Urinary excretion: 5000mg/24 hr
•Acidosis :
 Anion gap metabolic acidosis;
 HCO3
- : <15mEq/L,
 pH : <7.30
[N: 70-110mg/dL]
[N : < 3mg/100 ml]
[N :  125mg/24 hr]
[N: 5-16 mEq/L]
[N: 22-26 mEq/L]
[N: 7.35-7.45]

7. • DKA - potentially life-threatening complication
• Medical emergency,
• Predominantly in those with type 1 diabetes ,It may be the
first symptom of previously undiagnosed diabetes.
• can occur in patients with type 2 diabetes .

8. HISTORY
• The first full description of DKA : Julius Dreschfeld
• In 1886,described the main ketones, acetoacetate and β-hydroxybutyrate, and
their chemical determination.
• DKA remained almost universally fatal until the discovery of insulin in the
1920s;
• 1930s, mortality had fallen to 29%
• 1950s : less than 10%

9. HISTORY CONTD.
• The entity of “ketosis-prone type 2 diabetes” was first fully described in 1987.
• It was initially thought to be a form of maturity onset diabetes of the young
• Then went through several other names, such as,
• "idiopathic type 1 diabetes",
• "Flatbush diabetes",
• "atypical diabetes“
• "type 1.5 diabetes"

10. CLASSIFICATION
2006, American Diabetes Association (for adults)
Grade Blood pH S. Bicarbonate Status of patient
Mild 7.25 - 7.30
15–18 mEq/L
( N: > 20)
Patient is alert
Moderate 7.00–7.25 10–15 mEq/L
Mild drowsiness may
be present
Severe < 7.00
< 10 mEq/L Stupor or coma may
occur

11. 2004, European Society for Paediatric Endocrinology and the
Lawson Wilkins Pediatric Endocrine Society (for children)
Grade Blood pH S. Bicarbonate
Mild 7.20 - 7.30 10–15 mEq/L
Moderate 7.1 – 7.2 5-10 mEq/L
Severe < 7.1 < 5 mEq/L

12. PRECIPITATING FACTORS
1. Inadequate insulin administration
2. Infections (Pneumonia, UTI, Gastroenteritis, Sepsis)
3. Infarction (Cerebral, myocardial, coronary, mesenteric, etc.)
4. Pregnancy
5. Use of medications: steroids (glucocorticoids), thiazide diuretics, calcium-
channel blockers, propranolol, Cocaine

13. PATHOPHYSIOLOGY

14. ↑ Glycogenolysis
↑ Gluconeogenesis,
↑ Protein catabolism
↑ Hyperglycemia
Glucosuria
Osmotic diuresis
Dehydration
↓
↓
↓
↓
Diabetic ketoacidosis
Insulin deficiency
↑ Lipolysis
↑ Free fatty acids
↓
↓
↑ Ketone bodies
Hyperketonemia
↓
↓
Acidosis

15. CLINICAL
PRESENTATION

16. SYMPTOMS
• Nausea & vomiting
• Polyuria / ↑ Thirst
• Abdominal pain
• Shortness of breath
SIGNS
Dehydration
• Mild: Dry mouth
• Severe: Tachycardia, Low BP ( d/t ↓ circulatory volume)
Abdominal tenderness (may resemble acute
pancreatitis / Acute Appendicitis)
• Tachypnoea, Kussmaul’s respiration, “Fruity” smell of
breath, Respiratory distress
• Lethargy, cerebral edema & coma

17. DIAGNOSIS
1. History and physical examination:
2. Laboratory investigations:

18. PARAMETER NORMAL VALUE VALUE in DKA
1. B. Glucose 70-110 mg/dL 250 -600 mg/dL
2. S. Bicarbonate 22-26 mEq/ L < 15 mEq/ L
3. Ketone bodies
• Plasma concentration < 3 mg/ 100 ml 90 mg/ 100 ml (++++)
• Urine excretion  125 mg/ 24 hr 5000 mg/ 24 hr(++++)
4. S. Osmolality 275-295 mosm/L 300-320 mosmol/L
5. Art. pH 7.35-7.45 6.8 - 7.3
6. Art. pCo2 35-45 mmHg 20-30 mmHg

19. PARAMETER NORMAL VALUE VALUE in DKA
7. S. Electrolytes
• K + 3.5 – 6.5mEq/ L N to ↑
• Na + 135 – 148 mEq/ L
125-135 mEq /L
(100mg ↑ in glucose asso. with
1.6 mEq reduction in S. Na )
• Mg +2 1.5 -2.5 mg/dL N
• Phosphate 2.2 -4.8 mg/dL ↓
• Chloride 46-112 mEq/ L N
• Anion gap
[ Na – (Cl + Hco3) ]
5-16 mEq/ L ↑

20. TREATMENT
1. Initial evaluation & admission to hospital
2. Dehydration (fluid therapy)
3. Hyperglycemia (insulin)
4. Electrolyte deficits (potassium , sodium,
phosphate therapy)
5. Ketoacidosis ( insulin as well as bicarbonate
therapy)
6. Other measures.

21. 1.
Initial evaluation
&
Admission to
hospital

22. If vomiting Or altered mental status : insert nasogastric tube.
Intensive care is necessary for frequent monitoring, If pH is < 7.0 or pt is unconscious.
 Assess patient:
History & Physical examination
Blood sugar.
 S. Electrolytes
 Acid base status
Renal function
CBC with differential count, ECG

23. TREATMENT Contd…
• Start I.V. Fluids 1 L, 0.9 % Normal saline / Hr (15-20ml/kg/hr)
• Confirm the Diagnosis :
• Blood Glucose : > 250 mg/dl
• Arterial pH : < 7.3
• S. Bicarbonate < 15 mEq/L
• ketonuria & ketonemia

24. 2.
Fluid Therapy
(Dehydration)
THESE IS THE MAINSTAY OF THERAPY…

25. • Deficit : 3-5 L
• 2-3 L → Isotonic Saline ( 0.9 % NaCl) → over 1-3 hrs (Bolus) ( 10-15ml/ kg/ hr)
↓ followed by
• 150 – 300 ml/ hr → Hypotonic Saline ( O.45 % NaCl)
• Only when Haemodynamic stability & adequate Urine output are achieved
↓
• When Blood Glucose comes to 250-300 mg/dL
• 100-200 ml/ hr → ½ NS ( O.45 % NaCl) + 5 % Glucose
• Amount of i. v. fluids to be used: ~ 3L /m2/24 hr

26.  Advantages of early rehydration:
1. Dehydration :Restores circulatory volume
2. Hyperglycemia is treated
3. Hyperkalemia is reversed
 Complications of fluid therapy:
1. Excessive therapy may result in ARDS
2. Cerebral edema
3. Hyperchloremic acidosis

27. 3.
Insulin therapy
(Hyperglycaemia)

28. INSULIN TREATMENT
1. Type of insulin: Plain / Regular insulin
2. Route : Bolus I.V. → CLDII (Continuous low dose i.v. infusion)
3. Dose : 0.1 U /kg → I. V. Bolus immediately
↓
0.1U/kg/hr → CLDII (Conti. low dose i.v. inf.)
Mix to run @ 10ml/hr
(regular insulin equal to wt. in kg x 2.5, mixed in 250ml bag of saline)
Example: weight = 50kg
[50 x 2.5 = 125 units in 250ml = 5u/hr (i.e. 0.1 U/kg/hr)

29. INSULIN TREATMENT CONTD.
↓
Double the dose : if B. Glucose does not fall in 2 hrs
 When decrease in B. Glucose level = 10% /hr : Adequate response
 Hyperglycemia improves at a rate of 75-100 mg/dl/hr

30. DURATION OF INSULIN THERAPY
Until acidosis recovers
&
Metabolism is normal
↓
Dose: 0.05-0.1U/Kg/hr
Intermediate or Long acting
Insulin
+
Short acting s.c. insulin
↓
As patient resumes eating
It is crucial to continue
Insulin infusion
Until adequate insulin levels
Are achieved by s.c. injection
↓
Even brief episode of
Insulin lack
↓
DKA relapse
With insulin regimen, patient recovers within 36 – 48 hours
Initial S. K+ : < 3mEq/L, Don’t administer insulin until it is corrected to > 3mEq/L

31. • Role of insulin
 Hyperglycemia: Insulin mediated glucose disposal
↓ Hepatic glucose release
 Ketoacidosis: ↓ lipolysis
↓ hepatic Ketone Body formation
↑ Peripheral Ketone Body use
 Hyperkalemia: Transport of K+ In to cell

32. 4.
Electrolyte deficit
(Na+, K+, PO4-)

33.  POTASSIUM TREATMENT :
 Deficit : 3-5 mEq / kg
 During treatment with insulin & I.V. fluids, dangerous hypokalemia can occur
 So K+ repletion is commenced as soon as,
• Adequate Urine output : >1ml /min
• Normal Serum Creatinine
• Normal ECG
• Normal Serum K+ level is achieved

34. B. SODIUM TREATMENT :
 Initial s. sodium may be ‘low’ :
 Depletion secondary to urinary losses / vomiting
 “Pseudohyponatremia” is often present
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

35. C. PHOSPHATE TREATMENT :
 Any patient with phosphate concentration
< 1mg/ dL → should receive phosphate Therapy.
↓
5-10 mmol / hr Na+ Or K+ phosphate .

36. 5.
Bicarbonate
therapy
(Acidosis)

37. Bicarbonate therapy:
 When SEVERE acidosis ( pH < 7 after initial hydration) : l/t cardio-
respiratory compromise
 pH : 6.9-7.0 → 50 mEq /L NaHCo3 in 200 ml sterile water with 10 mEq/L
KCl over 1 hr.
 pH : < 6.9 → 100mEq /L NaHCo3 in 400 ml sterile water with 20 mEq/L
KCl over 2 hr
Until pH > 7.0.

38. OTHER MEASURES
 Assess patient for Precipitating factors:
• Non compliance, Infection, Trauma, Infarction, Drugs history
• Initiate appropriate workup for that event like history, Culture, ECG etc
• Based on that treat the patient with antibiotics & supportive measures.
• Appropriate treatment ↓es the mortality of DKA to < 5%, That is mainly related
to precipitating factors

39.  Measurements:
• Capillary B. Glucose → every 1-2 hrly
• S. Electrolytes → every 4 hrly for first 24 hrs
• Monitor BP /Pulse / Respi./Mental status /Fluid intake & output → every 1-
4 hrly
• Nursing care of patient about skin, mouth, position & bladder.

40. Remember, The Ideal Treatment For DKA Is
Prevention
 Educate the patient about,
• Symptoms of DKA,
• Its precipitating factors
• Management of diabetes during concurrent illness
• Frequent measurement of blood glucose.
• Measure Urinary Ketones when S. Glucose > 300mg/dl
• Drink fluids
• Continuous/Increase insulin
• Seek medical attention, If persistent Vomiting, uncontrolled hyperglycemia &
dehydration

41. COMPLICATIONS
OF
DKA TREATMENT

42. 1) Dehydration / shock
2) Hypokalemia (Cardiac arrhythmia) / hyperkalemia (Cardiac arrest)
3) Hypoglycemia
4) Aspiration pneumonia
5) Sepsis
6) ATN/ MI/ stroke
7) Insulin resistance (unremitting acidosis after 4-6hrs of treatment)
8) Cerebral edema

43. CEREBRAL OEDEMA
• Almost exclusively a condition of childhood.
• The pathophysiology is not completely understood
• Usually occurs between 4-12 hours from the start of treatment,
• but may be present at onset of DKA and can occur up to 24 hours later.
• Responsible for 50-60% of all diabetes-related deaths in children

44.  Causes:
 Excessive use of fluids
 Large doses of insulin
 Use of bicarbonate
 Manifestations:
 Headache - Alteration in level of consciousness
 Bradycardia - Emesis
 Diminished responsiveness to painful stimuli
 Unequal or fixed, dilated pupils

45.  TREATMENT:
• Mannitol 0.5-1 gm/kg IV over 15 minutes
• Reduce IV fluid rate to 70% maintenance
• Hypertonic saline ( 3% N.S.)
• Elevate Head end to 45o
• Consider intubation
• hyperventilation
• keep pCO2 > 22mmHg

46. HYPOGLYCEMIC REACTIONS
(INSULIN SHOCK)
• Is a life threatening complication: blood Glucose < 50 mg/dl
Symptoms and signs : pallor, sweating, apprehension, trembling, tachycardia,
hunger, drowsiness, mental confusion, seizures and coma
Management :
• If conscious: - Carbohydrate - containing snack or drink
• If patient is unconscious: - Glucagon 0.5 mg (S.C. or I.M.) or
Glucose solution 20-50 ml I.V. infusion

47. HYPEROSMOLAR
HYPERGLYCEMIC
SYNDROME
(HHS)

48.  Synonym:
• Hyperosmolar hyperglycemic non-ketotic coma (HHNKC)
• Mainly seen in elder individuals with Type 2 DM.
• Is characterized by profound hyperglycemia & dehydration.
• Mortality
• Variable 10-50%
• Most often due to the precipitating illness

49. Difference Between DKA & HHS
Parameters DKA HHS
Type of DM Mc in Type 1 DM Mc in Type 2 DM
Precipitating
factor
Mc : Inadequate or omitted insulin
MC :Serious concurrent illness +
debilitating condition that
compromises water intake
Symptoms Abdominal pain, Kussmaul’s respi. Absent
Signs
Dry mouth,
hypotension, tachycardia
Abdominal tenderness,
Fruity smell of breath
Profound dehydration
↓
Tachycardia, hypotension &
altered mental status
Dehydration
(loss of water)
3 - 5 L 8 - 10 L

50. Parameters Normal value DKA HHS
Blood Glucose 70-110 mg/dL 250 - 600 mg/dL 600 - 1200 mg/dL
S. Bicarbonate 22-26 mEq/ L < 15 mEq/ L
N to slight ↓
Mild or no acidosis
Ketone bodies
ABSENT / Mild
ketosis
• Plasma conc. < 3 mg/ 100 ml 90 mg/ 100 ml (++++)
• Urine
excretion
 125 mg/ 24 hr
5000 mg/ 24 hr
(++++)
S. Osmolality 275-295 mosmol/L 300-320 mosmol/L 330– 380 mosmol/L
Arterial pH 7.35-7.45 < 7.3 > 7.3
Arterial pCo2 35-45 mmHg 20-30 mmHg N
BUN 2.8 -7.9mmol/L 11.4 (mean) 21.8 (mean)

51. Parameter Normal Value Value In DKA HHS
K + 3.5 – 6.5 mEq/ L N to ↑ (4.5) N (3.9)
Na + 135 – 148 mEq/ L
125-135 mEq /L
(100mg ↑ in glucose asso.
with 1.6 mEq ↓ in S. Na+ )
135-145
mEq /L
Mg +2 1.5 -2.5 mg/dL N N
Phosphate 2.2 -4.8 mg/dL ↓ N
Chloride 46-112 mEq/ L N N
Anion gap 5-16 mEq/ L ↑ N to ↑

52. TREATMENT
Initial Evaluation: ABCs; Exam; Labs; Causes
Close Monitoring
Fluid Replacement : vigorous
Insulin Therapy
Electrolyte Replacement
 Patients are prone to develop thrombosis : prophylactic heparin

53. REFERENCES
• Standaert DG & Roberson E. Endocrine Pancreas and Pharmacotherapy of Diabetes
Mellitus and Hypoglycemia.In : Bruton LL, editor. Goodman & Gilman’s – The
Pharmacological basis of therapeutics. 12th edition. New York : Mc Graw Hill
Publication; 2011. p. 609- 28.
• Tripathi KD. Essentials of Medical Pharmacology. 6th ed. Jaypee brothers medical
publishers; New Delhi 2009. p. 425-34.
• Sharma HL & Sharma KK. Principles of Pharmacology. 2nd ed. Paras publication;
New Delhi 2012. p. 532-42.
• Olanow CW, Schapira AH. Diabetes Mellitus. In: LongoDL, editor :Harrisons’s
principles of internal medicine.18th edition. New york:Mc Grew hill;2012. P.3317-35.