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DIABETIC KETO-ACIDOSIS

MANAGEMENT
INTRODUCTION


HHS and DKA are not mutually exclusive but rather two
conditions that both result from some degree of insulin
deficiency.



They can and often do occur simultaneously. In fact, one

third of patients admitted for hyperglycemia exhibit
characteristics of both HHS and DKA.
14th edition of Joslin's Diabetes Mellitus
DEFINITION
DKA is defined as the presence of all three of the
following:
(i)

Hyperglycemia (glucose >250 mg/dL)

(ii)

Ketosis,

(iii)

Acidemia (pH <7.3).

14th edition of Joslin's Diabetes Mellitus
Diabetes ketoacidosis
PATHOPHYSIOLOGY
Insulin Deficiency
Glucose uptake

Lipolysis

Proteolysis
Glycerol

Free Fatty Acids

Amino Acids

Hyperglycemia

Osmotic diuresis

Ketogenesis

Gluconeogenesis
Glycogenolysis

Dehydration

Acidosis

14th edition of Joslin's Diabetes Mellitus
ROLE OF INSULIN
 Required




for transport of glucose into:

Muscle
Adipose
Liver

 Inhibits

lipolysis

 Absence

of insulin

Glucose accumulates in the blood.
 Uses amino acids for gluconeogenesis
 Converts fatty acids into ketone bodies :
Acetone, Acetoacetate, β-hydroxybutyrate.

DIABETIC KETOACIDOSIS
PRECIPITATING EVENTS
 Infection(Pneumonia

/ UTI / Gastroenteritis /

Sepsis)
 Inadequate

insulin administration

 Infarction(cerebral,
 Drugs

coronary, mesenteric, peripheral)

(cocaine)

 Pregnancy.

Harrison’s Principle of internal medicine 18th edition p2977
SYMPTOMS

DKA

PHYSICAL FINDINGS

can be the first

Dehydration/hypotension

presentation.

Tachypnea/kussmaul
Nausea/vomiting

Thirst/polyuria
Abdominal

pain

Shortnessof

Tachycardia

breath

respirations/respiratory
distress
Fruity odour in breath.
Abdominal tenderness(may
resemble acute pancreatitis or
surgical abdomen)
Lethargy/obtundation/cerebra
l edema/possibly coma.

Harrison’s Principle of internal medicine 18th edition p 2976
Differential Diagnosis of Ketosis and Anion Gap Acidosis
FEATURES

DIABETIC
ALCOHOL
STARVATION
URAEMIC
KETOACIDOSIS KETOACIDOSIS KETOACIDOSIS ACIDOSIS

LACTIC
ACIDOSIS

PH
PLASMA
GLUCOSE
ANION GAP

SERUM
KETONES
SERUM
OSMOLALITY

14th edition of Joslin's Diabetes Mellitus
DIAGNOSIS


INITIAL EVALUATION

Identify precipitating event leading to elevated glucose

(pregnancy, infection, omission of insulin, myocardial
infarction, central nervous system event)


Assess hemodynamic status



Examine for presence of infection



Assess volume status and degree of dehydration



Assess presence of ketonemia and acid-base disturbance

14th edition of Joslin's Diabetes Mellitus
DIAGNOSIS

LAB INVESTIGATIONS



Complete blood count



Serum ketones/ Urine ketones and sugar



Calculate serum osmolality and anion gap



Urinalysis and urine culture



Consider blood culture



Consider chest radiograph



Acid-base assessment

14th edition of Joslin's Diabetes Mellitus
LABORATORY VALUES IN DKA AND HHS
DKA

HHS

Glucose,mg/dl

250-600

600-1200

Sodium meq/L

125-135

135-145

Potassium

Normal to↑

Normal

Osmolality mosm/kg

300-320

330-380

Plasma ketones

++++

+/-

Serum bicarbonate

<15meq/L

Normal to slightly ↓

Arterial pH

6.8-7.3

>7.3

Arterial pCO2

20-30

Normal

Anion gap

↑

Normal to slightly↑

Harrison’s Principle of internal medicine 18th edition
TYPICAL BODY DEFICIT OF WATER AND
ELECTROLYTES
TREATMENT OF DKA
Initial hospital management
Replace fluid and electrolytes
 IV Insulin therapy
 Watch for complications
 Treat causes





Once resolved
Convert to home insulin regimen
Prevent recurrence
Diabetes ketoacidosis
Diabetes ketoacidosis
Diabetes ketoacidosis
Diabetes ketoacidosis
Diabetes ketoacidosis
Diabetes ketoacidosis
Diabetes ketoacidosis
FLUID REPLACEMENT


Administer NS as indicated to maintain hemodynamic
status, then follow general guidelines:



NS for first 4 hr.



Consider half NS thereafter.



Change to D5 half NS when blood glucose ≤250 mg/dL.

14th edition of Joslin's Diabetes Mellitus
FLUID REPLACEMENT CONTD…
Hours









1st half-hour to 1 hour
2nd hr
3rd hr
4th hr
5th hr
Total 1st 5 hr
6th–12th hr

Volume
1L
1L
500 mL– 1 L
500 mL– 1 L
500 mL– 1 L
3.5 - 5 L
250– 500 mL/hr

May need to adjust type and rate of fluid administration in the
elderly and in patients with congestive heart failure or renal failure.

14th edition of Joslin's Diabetes Mellitus
INSULIN MANAGEMENT


Regular insulin 10 U i.v. stat (for adults) or 0.15 U/kg i.v. stat.



Start regular insulin infusion 0.1 U/kg per hour or 5 U per hour.



Increase insulin by 1 U per hour every 1–2 hr if less than 10% decrease
in glucose or no improvement in acid-base status.



Decrease insulin by 1–2 U per hour (0.05–0.1 U/kg per hour) when
glucose ≤250 mg/dL and/or progressive improvement in clinical status
with decrease in glucose of >75 mg/dL per hour.



Do not decrease insulin infusion to <1 U per hour.
14th edition of Joslin's Diabetes Mellitus
INSULIN MANAGEMENT

CONTD…



Maintain glucose between 140 and 180 mg/dL.



If blood sugar decreases to <80 mg/dL, stop insulin infusion for no more

than 1 hr and restart infusion.


If glucose drops consistently to <100 mg/dL, change i.v. fluids to D10 to
maintain blood glucose between 140 and 180 mg/dL.



Once patient is able to eat, consider change to s.c. insulin:



Overlap short-acting insulin s.c. and continue i.v. infusion for 1–2 hr.



For patients with previous insulin dose: return to prior dose of insulin.



For patients with newly diagnosed diabetes: full-dose s.c. insulin based
on 0.6 U/kg per day.

14th edition of Joslin's Diabetes Mellitus
TREATMENT OF DKA
FLUIDS AND ELECTROLYTES
•

Sodium replacement
– Calculate effective serum sodium
– Serum sodium + 1.6 ( blood glucose-100)/100
–

isotonic saline (0.9% NaCl) is infused at a rate of 15–20
ml ·/ kg/ body wt /· h or greater during the 1st hour (∼1–
1.5 l in the average adult). Subsequent choice for fluid
replacement depends on the state of hydration, serum
electrolyte levels, and urinary output.

–

In general, 0.45% NaCl infused at 4–14 ml / kg/ h is
appropriate if the corrected serum sodium is normal or
elevated; 0.9% NaCl at a similar rate is appropriate if
corrected serum sodium is low.
Williams textbook of endocrinology 10th edition p 454
POTASSIUM REPLACEMENT


Do not administer potassium if serum potassium >5.5
mEq/L or patient is anuric.



Use KCl but alternate with KPO4 if there is severe
phosphate depletion and patient is unable to take
phosphate by mouth.



Add i.v. potassium to each liter of fluid administered unless
contraindicated.

Williams textbook of endocrinology 10th edition p 454
POTASSIUM REPLACEMENT CONTD…

Serum K (mEq/L)

Additional K required

<3.5 - 4.0

40 mEq/L

-

3.5–4.5

-

20 mEq/L.

4.5–5.5

-

10 mEq/L

>5.5

-

Stop K infusion

14th edition of Joslin's Diabetes Mellitus
PHOSPHATE
 Hypophasphatemia may develop during increased
glucose usage

 If serum level <1mg/dl then phosphate supplementation
considered and monitor for hypocalcemia and
hypomagnesemia
 No benefit demonstrated in RCT .
Williams textbook of endocrinology 10th edition p456
BICARBONATE



Clinical trials donot support the rouine use of bicarbonate
replacement



HCO3 replacement and rapid reversal of acidosis can
impair cardiac function, reduce tissue oxygenation and
promote hypokalemia and hypocalcemia.

Williams textbook of endocrinology 10th edition p456
BICARBONATE

CONTD…

 However in presence of sevare acidosis ph<6.9,in

hemodynamic instability with ph<7.1 and hyperkaemia
with ecg finding bicarbonate therapy considered .
 In the presence of severe acidosis (arterial pH <6.9), the
ADA advises bicarbonate [50 mmol/L (meq/L) of sodium

bicarbonate in 200 mL of sterile water with 10 meq/L KCl
per hour for 2 h until the pH is >7.0].

Williams textbook of endocrinology 10th edition
TREATMENT OF DKA
GLUCOSE ADMINISTRATION


Plasma glucose reaches 250 mg/dl in DKA or 300 mg/dl
in HHS,



Decrease the insulin infusion rate to 0.05–0.1 unit/kg/h
(3–6 units/h),





Add dextrose (5–10%) to the intravenous fluids.

Maintain the above glucose values until acidosis in DKA or
mental obtundation and hyperosmolarity in HHS are
resolved

Williams textbook of endocrinology 10th edition p 455
MONITORING


Flow sheet mantained tabulating mental status,
vital signs,insulin dose,fluid and electrolyte
administered and urine output



Capillary glucose 1-2hrly,electrolytes especially
K+,bicarbonate and phosphate) and anion gap
every 4 hrly for first 24 hr



Monitor BP,pulse respiration fluid intake and output
every 1-4 h

Williams textbook of endocrinology 10th edition p 456
ONCE DKA RESOLVED…
•

Most patients require 0.5-0.6 units/kg/day

•

highly insulin resistant patients
–

•

0.8-1.0 units/kg/day

Give subcutaneous insulin at least 2 hours prior to
weaning insulin infusion.

Williams textbook of endocrinology 10th edition p455
COMPLICATIONS OF DKA
Shock



If not improving with fluids
MI

r/o

Cerebral




Vascular





thrombosis
Severe dehydration
Cerebral vessels
Occurs hours to days after DKA



Edema
First 24 hours
Mental status changes
May require intubation
with hyperventilation

Pulmonary



Edema
Result of aggressive fluid
resuscitation

14th edition of Joslin's Diabetes Mellitus
Diabetes ketoacidosis
CLINICAL ERRORS
Fluid shift and shock
 Giving insulin without sufficient fluids
 Using hypertonic glucose solutions
 Hyperkalemia
 Premature potassium administration before insulin has begun
to act
 Hypokalemia
 Failure to administer potassium once levels falling
 Recurrent ketoacidosis
 Premature discontinuation of insulin and fluid when ketones
still present
 Hypoglycemia
 Insufficient glucose administration.

THANK YOU
DKA is defined as the presence of all three of the
following EXCEPT
1.

Hyperglycemia (glucose >250 mg/dL

2.

Ketosis,

3.

Acidemia (pH <7.3).

4.

Pain in abdomen


Which of the following is not seen in cases of DKA
Increased amino acid levels
 Decreased glycerol levels
 Incresed ketone bodies
 Decresed glucose uptake



WHICH OF THE FOLLOWING IS NOT A KETONE
BODY
2.

Acetoacetate,
β-hydroxybutyrate.

1.

ACETIC ACID

1.

Acetone,

1.


Which of the following is not seen in cases of DKA
Glucose 250-600
 Sod. Bicarbonate >15 meq
 SERUM Potassium -Normal to↑
 Osmolality -300-320



During management of DKA which of the electrolyte
is to be strictly monitored
Sodium
 Potassium
 Magnesium
 Calcium

Approximate amount of water deficit in DKA
 100ml/kg
 200ml/kg
 300ml/kg
 400ml/kg

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Diabetes ketoacidosis

  • 2. INTRODUCTION  HHS and DKA are not mutually exclusive but rather two conditions that both result from some degree of insulin deficiency.  They can and often do occur simultaneously. In fact, one third of patients admitted for hyperglycemia exhibit characteristics of both HHS and DKA. 14th edition of Joslin's Diabetes Mellitus
  • 3. DEFINITION DKA is defined as the presence of all three of the following: (i) Hyperglycemia (glucose >250 mg/dL) (ii) Ketosis, (iii) Acidemia (pH <7.3). 14th edition of Joslin's Diabetes Mellitus
  • 5. PATHOPHYSIOLOGY Insulin Deficiency Glucose uptake Lipolysis Proteolysis Glycerol Free Fatty Acids Amino Acids Hyperglycemia Osmotic diuresis Ketogenesis Gluconeogenesis Glycogenolysis Dehydration Acidosis 14th edition of Joslin's Diabetes Mellitus
  • 6. ROLE OF INSULIN  Required    for transport of glucose into: Muscle Adipose Liver  Inhibits lipolysis  Absence of insulin Glucose accumulates in the blood.  Uses amino acids for gluconeogenesis  Converts fatty acids into ketone bodies : Acetone, Acetoacetate, β-hydroxybutyrate. 
  • 7. DIABETIC KETOACIDOSIS PRECIPITATING EVENTS  Infection(Pneumonia / UTI / Gastroenteritis / Sepsis)  Inadequate insulin administration  Infarction(cerebral,  Drugs coronary, mesenteric, peripheral) (cocaine)  Pregnancy. Harrison’s Principle of internal medicine 18th edition p2977
  • 8. SYMPTOMS DKA PHYSICAL FINDINGS can be the first Dehydration/hypotension presentation. Tachypnea/kussmaul Nausea/vomiting Thirst/polyuria Abdominal pain Shortnessof Tachycardia breath respirations/respiratory distress Fruity odour in breath. Abdominal tenderness(may resemble acute pancreatitis or surgical abdomen) Lethargy/obtundation/cerebra l edema/possibly coma. Harrison’s Principle of internal medicine 18th edition p 2976
  • 9. Differential Diagnosis of Ketosis and Anion Gap Acidosis FEATURES DIABETIC ALCOHOL STARVATION URAEMIC KETOACIDOSIS KETOACIDOSIS KETOACIDOSIS ACIDOSIS LACTIC ACIDOSIS PH PLASMA GLUCOSE ANION GAP SERUM KETONES SERUM OSMOLALITY 14th edition of Joslin's Diabetes Mellitus
  • 10. DIAGNOSIS  INITIAL EVALUATION Identify precipitating event leading to elevated glucose (pregnancy, infection, omission of insulin, myocardial infarction, central nervous system event)  Assess hemodynamic status  Examine for presence of infection  Assess volume status and degree of dehydration  Assess presence of ketonemia and acid-base disturbance 14th edition of Joslin's Diabetes Mellitus
  • 11. DIAGNOSIS LAB INVESTIGATIONS  Complete blood count  Serum ketones/ Urine ketones and sugar  Calculate serum osmolality and anion gap  Urinalysis and urine culture  Consider blood culture  Consider chest radiograph  Acid-base assessment 14th edition of Joslin's Diabetes Mellitus
  • 12. LABORATORY VALUES IN DKA AND HHS DKA HHS Glucose,mg/dl 250-600 600-1200 Sodium meq/L 125-135 135-145 Potassium Normal to↑ Normal Osmolality mosm/kg 300-320 330-380 Plasma ketones ++++ +/- Serum bicarbonate <15meq/L Normal to slightly ↓ Arterial pH 6.8-7.3 >7.3 Arterial pCO2 20-30 Normal Anion gap ↑ Normal to slightly↑ Harrison’s Principle of internal medicine 18th edition
  • 13. TYPICAL BODY DEFICIT OF WATER AND ELECTROLYTES
  • 14. TREATMENT OF DKA Initial hospital management Replace fluid and electrolytes  IV Insulin therapy  Watch for complications  Treat causes    Once resolved Convert to home insulin regimen Prevent recurrence
  • 22. FLUID REPLACEMENT  Administer NS as indicated to maintain hemodynamic status, then follow general guidelines:  NS for first 4 hr.  Consider half NS thereafter.  Change to D5 half NS when blood glucose ≤250 mg/dL. 14th edition of Joslin's Diabetes Mellitus
  • 23. FLUID REPLACEMENT CONTD… Hours        1st half-hour to 1 hour 2nd hr 3rd hr 4th hr 5th hr Total 1st 5 hr 6th–12th hr Volume 1L 1L 500 mL– 1 L 500 mL– 1 L 500 mL– 1 L 3.5 - 5 L 250– 500 mL/hr May need to adjust type and rate of fluid administration in the elderly and in patients with congestive heart failure or renal failure. 14th edition of Joslin's Diabetes Mellitus
  • 24. INSULIN MANAGEMENT  Regular insulin 10 U i.v. stat (for adults) or 0.15 U/kg i.v. stat.  Start regular insulin infusion 0.1 U/kg per hour or 5 U per hour.  Increase insulin by 1 U per hour every 1–2 hr if less than 10% decrease in glucose or no improvement in acid-base status.  Decrease insulin by 1–2 U per hour (0.05–0.1 U/kg per hour) when glucose ≤250 mg/dL and/or progressive improvement in clinical status with decrease in glucose of >75 mg/dL per hour.  Do not decrease insulin infusion to <1 U per hour. 14th edition of Joslin's Diabetes Mellitus
  • 25. INSULIN MANAGEMENT CONTD…  Maintain glucose between 140 and 180 mg/dL.  If blood sugar decreases to <80 mg/dL, stop insulin infusion for no more than 1 hr and restart infusion.  If glucose drops consistently to <100 mg/dL, change i.v. fluids to D10 to maintain blood glucose between 140 and 180 mg/dL.  Once patient is able to eat, consider change to s.c. insulin:  Overlap short-acting insulin s.c. and continue i.v. infusion for 1–2 hr.  For patients with previous insulin dose: return to prior dose of insulin.  For patients with newly diagnosed diabetes: full-dose s.c. insulin based on 0.6 U/kg per day. 14th edition of Joslin's Diabetes Mellitus
  • 26. TREATMENT OF DKA FLUIDS AND ELECTROLYTES • Sodium replacement – Calculate effective serum sodium – Serum sodium + 1.6 ( blood glucose-100)/100 – isotonic saline (0.9% NaCl) is infused at a rate of 15–20 ml ·/ kg/ body wt /· h or greater during the 1st hour (∼1– 1.5 l in the average adult). Subsequent choice for fluid replacement depends on the state of hydration, serum electrolyte levels, and urinary output. – In general, 0.45% NaCl infused at 4–14 ml / kg/ h is appropriate if the corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate is appropriate if corrected serum sodium is low. Williams textbook of endocrinology 10th edition p 454
  • 27. POTASSIUM REPLACEMENT  Do not administer potassium if serum potassium >5.5 mEq/L or patient is anuric.  Use KCl but alternate with KPO4 if there is severe phosphate depletion and patient is unable to take phosphate by mouth.  Add i.v. potassium to each liter of fluid administered unless contraindicated. Williams textbook of endocrinology 10th edition p 454
  • 28. POTASSIUM REPLACEMENT CONTD… Serum K (mEq/L) Additional K required <3.5 - 4.0 40 mEq/L - 3.5–4.5 - 20 mEq/L. 4.5–5.5 - 10 mEq/L >5.5 - Stop K infusion 14th edition of Joslin's Diabetes Mellitus
  • 29. PHOSPHATE  Hypophasphatemia may develop during increased glucose usage  If serum level <1mg/dl then phosphate supplementation considered and monitor for hypocalcemia and hypomagnesemia  No benefit demonstrated in RCT . Williams textbook of endocrinology 10th edition p456
  • 30. BICARBONATE  Clinical trials donot support the rouine use of bicarbonate replacement  HCO3 replacement and rapid reversal of acidosis can impair cardiac function, reduce tissue oxygenation and promote hypokalemia and hypocalcemia. Williams textbook of endocrinology 10th edition p456
  • 31. BICARBONATE CONTD…  However in presence of sevare acidosis ph<6.9,in hemodynamic instability with ph<7.1 and hyperkaemia with ecg finding bicarbonate therapy considered .  In the presence of severe acidosis (arterial pH <6.9), the ADA advises bicarbonate [50 mmol/L (meq/L) of sodium bicarbonate in 200 mL of sterile water with 10 meq/L KCl per hour for 2 h until the pH is >7.0]. Williams textbook of endocrinology 10th edition
  • 32. TREATMENT OF DKA GLUCOSE ADMINISTRATION  Plasma glucose reaches 250 mg/dl in DKA or 300 mg/dl in HHS,  Decrease the insulin infusion rate to 0.05–0.1 unit/kg/h (3–6 units/h),   Add dextrose (5–10%) to the intravenous fluids. Maintain the above glucose values until acidosis in DKA or mental obtundation and hyperosmolarity in HHS are resolved Williams textbook of endocrinology 10th edition p 455
  • 33. MONITORING  Flow sheet mantained tabulating mental status, vital signs,insulin dose,fluid and electrolyte administered and urine output  Capillary glucose 1-2hrly,electrolytes especially K+,bicarbonate and phosphate) and anion gap every 4 hrly for first 24 hr  Monitor BP,pulse respiration fluid intake and output every 1-4 h Williams textbook of endocrinology 10th edition p 456
  • 34. ONCE DKA RESOLVED… • Most patients require 0.5-0.6 units/kg/day • highly insulin resistant patients – • 0.8-1.0 units/kg/day Give subcutaneous insulin at least 2 hours prior to weaning insulin infusion. Williams textbook of endocrinology 10th edition p455
  • 35. COMPLICATIONS OF DKA Shock  If not improving with fluids MI r/o Cerebral   Vascular    thrombosis Severe dehydration Cerebral vessels Occurs hours to days after DKA  Edema First 24 hours Mental status changes May require intubation with hyperventilation Pulmonary  Edema Result of aggressive fluid resuscitation 14th edition of Joslin's Diabetes Mellitus
  • 37. CLINICAL ERRORS Fluid shift and shock  Giving insulin without sufficient fluids  Using hypertonic glucose solutions  Hyperkalemia  Premature potassium administration before insulin has begun to act  Hypokalemia  Failure to administer potassium once levels falling  Recurrent ketoacidosis  Premature discontinuation of insulin and fluid when ketones still present  Hypoglycemia  Insufficient glucose administration. 
  • 39. DKA is defined as the presence of all three of the following EXCEPT 1. Hyperglycemia (glucose >250 mg/dL 2. Ketosis, 3. Acidemia (pH <7.3). 4. Pain in abdomen
  • 40.  Which of the following is not seen in cases of DKA Increased amino acid levels  Decreased glycerol levels  Incresed ketone bodies  Decresed glucose uptake 
  • 41.  WHICH OF THE FOLLOWING IS NOT A KETONE BODY 2. Acetoacetate, β-hydroxybutyrate. 1. ACETIC ACID 1. Acetone, 1.
  • 42.  Which of the following is not seen in cases of DKA Glucose 250-600  Sod. Bicarbonate >15 meq  SERUM Potassium -Normal to↑  Osmolality -300-320 
  • 43.  During management of DKA which of the electrolyte is to be strictly monitored Sodium  Potassium  Magnesium  Calcium 
  • 44. Approximate amount of water deficit in DKA  100ml/kg  200ml/kg  300ml/kg  400ml/kg