DIABETIC

KETOACIDOSIS
ANANTHU
FIRST
YEAR POSTGRADUATE
UNIT 5
PROFESSOR
[Link] MD UNIT
 CASE – 1
• 65 year old male k/c/o type 2 diabetes for more than 6
years, dyslipidemia and hypertension on irregular
medications presented in the emergency department with
a history of multiple episode of vomiting , abdominal pain
and weakness
• On examination – he was confused and lethargic ,
hydration poor , vitals stable , CBG -550 mg/dl , urine
acetone positive
• On system examination – paucity of movement of left
upper and lower limb with left side extensor plantar
INVESTIGATIONS
 CASE 2
• 60 year old male k/c/o Type 2 DM for 13 years
uncontrolled, on irregular medication presented in the
emergency department with breathlessness and fever
• On examination _ He was drowsy and lethargic , vitals
stable ,CBG 578, urine acetone positively
• On local examination _ left leg diabetic foot infected
 INTRODUCTION
• Acute, life-threatening complication of DM
• Predominantly in patients with type 1 DM
• There has been an increased number of DKA in patients
with newly diagnosed type 2 DM
• A better understanding of the pathophysiology of DKA and
an aggressive, uniform approach to its diagnosis and
management have reduced mortality to <1% of reported
episodes in experienced centers
 DIABETIC KETOACIDOSIS
• Hyperglycemia ( Serum glucose > 250 mg/dL)
• Metabolic acidosis (pH < 7.3 or S. Bicarbonate < 15mmol/ L)
• Ketosis ( Plasma betahydroxybutyrate >3 mmol/L )
 PATHOPHYSIOLOGY

• DKA is a response to
cellular starvation -
relative insulin
deficiency and
counterregulatory
hormone excess
 KETOACIDOSIS

• Counter regulatory hormones : Glucagon, Catecholamines,

Cortisol, and Growth hormone

• ketone bodies : β-hydroxybutyrate (βHB)

Acetoacetic acid (AcAc)
Acetone
• Renin-angiotensin-aldosterone system activation:
exacerbates renal potassium losses
• Superimposed hyperchloremic acidosis : chloride is
retained in exchange for the ketoanions.
• Prostaglandins I2 and E2 : paradoxical vasodilation
 CLINICAL FEATURES
• Hyperglycemia : diuresis - polyuria and polydipsia
• Volume depletion : tachycardia, orthostatic hypotension, poor skin
turgor, and dry mucous membranes
• Acidosis : kussmaul respirations, peripheral vasodilation
• Prostaglandins I2 and E2 : peripheral vasodilation, nausea, vomiting,
and abdominal pain
• Acetone: fruity odour
• Impaired mental status :multifactorial - metabolic acidosis,
hyperosmolarity, low extracellular fluid volume, and poor hemodynamic
 DIAGNOSIS
• Glucose level >250 mg%
• Anion gap >10 meq/L ,
• HCO3 level <15 meq/L, &
• pH <7.3
• With moderate ketonuria or ketonemia
 Classification of DKA:
Arterial pH HCO3 AG
(mEq/L ) (mEq/L)
Mild 7.2 - 7.3 10 to 15 >10

Moderate 7.1 - 7.2 5 to 10 >12

Severe <7.1 <5 >12
 TREATMENT
• The order of therapeutic priorities:

1. Volume repletion
2. Correction of potassium deficits, and
3. Insulin administration

• Metabolic disturbances - corrected over 24 to 36 hours.

 TREATMENT
• The goals of therapy are:-
1) Volume repletion
2) Reversal of the metabolic consequences of insulin
insufficiency
3) Correction of electrolyte and acid-base imbalances
4) Recognition and treatment of precipitating causes, and
5) Avoidance of complications
 GOALS OF TREATMENT
• The goals of treatment are:-
1. Glucose = 150-200 mg/dL
2. HCO3 ≥18 mEq/L and
3. Venous pH >7.3
 VOLUME REPLETION
• Average adult patients has
- water deficit = 100 mL/ kg (5 to 10 L)
• Fluid helps restore
- intravascular volume and normal tonicity
- improve perfusion
- improve GFR
- lower serum glucose and ketone levels
- improves the response to low-dose insulin therapy
• Initial fluid bolus
- isotonic crystalloid = 15 to 20 mL/kg/h (first hour)
• After the initial bolus,
- Hyponatremic patients , NS = 250 to 500 mL/h
- Normal or Hypernatremic patients , 0.45% NS = 250 to 500
mL/h
• In general, 50% fluid replacement in first 12 hrs
- First 2L/2 hrs
- Next 2L/4hrs
- Additional 2L/6 hrs.
• Remaining 50% fluid deficit = replaced over the
subsequent 12 hrs
• When the blood glucose level falls <250 mg/dL
change to 5% dextrose .Goal is to prevent hypoglycemia. 2 bag
approach .glucose as separate infusion of 50-100 ml/hr.
concurrently reduce insulin infusion to 0.05 units/kg/h

Patients without extreme volume depletion = 250 to 500 mL/h

for 4 hrs
Monitor volume status in - Elderly
- Heart or renal disease
Excess fluid may cause - Adult Respiratory Distress Syndrome
- Cerebral edema
 POTASSIUM REPLACEMENT
• S.K value Initially obtained, repeated every 2 hours
• Initial S.K is usually normal or high because of
- intracellular exchange of K for H+ ion due to acidosis
- total-body fluid deficit, and
- diminished renal function
• For each 0.1 change in pH, inverse S.K change of 0.5
mEq/L.
• Rapid hypokalemia - most life-threatening condition
• During initial therapy, the S.K may fall rapidly, due to:-
- action of insulin promoting re-entry of K into cells
- dilution of ECF
- correction of acidosis, and
- increased urinary loss of K
• Rapid hypokalemia will cause - Fatal cardiac arrhythmias
- Respiratory paralysis, paralytic
ileus, and
- Rhabdomyolysis
• General guideline, if:-
 S.K <3.5mEq/L
- Give KCL 40 to 80 mEq/h, until S.K is ≥3.5 mEq/L
- Followed by Insulin therapy
 S.K = 3.5–5.2mEq/L
- Give KCl 20 to 30 mEq/L for 4 hrs
- To keep S.K More than 3.5 mEq/L
 S.K >5.2 mEq/L
- Reflects profound acidemia, volume depletion or renal
insufficiency.
- Fluid and insulin therapy alone
- Salbutamol nebulization
• In DKA, initial potassium replacement is usually IV
• Generally, rate of KCl administration = 10 mEq/h via peripheral
IV
= 20 mEq/h via central line

Goal is to maintain [Link] more than 3.5 mEq/L

• Hyperkalemia
- ECG –look for signs of hyperkalemia once DKA is suspected.
- Giving potassium to a patient in a hyperkalemic potentiating state
(e.g., acidemia, insulin deficiency, volume contraction, renal
insufficiency) will precipitate fatal dysrhythmias
 INSULIN
• Low-dose regular insulin administration by an infusion pump is
- simple and safe
- ensures steady blood concentration of insulin
- allows flexibility in adjusting the insulin dose, and
- promotes a gradual decrease in serum glucose and
ketone body
• The half-life of IV regular insulin = 4 to 5 minutes,
with effective biologic half-life = 20 to 30 minutes
INSULIN REGIMEN:
• 1 to 2 hours after fluids are initiated, Insulin bolus 0.1
Units/kg

• Insulin infusion 0.1 units/kg

• Blood glucose should decrease by 50 to 70 mg/dL/hr

• If there is no response by 2-4 hours then increase the

infusion two to three folds .

• Check blood glucose hourly and charting of CBG has to be

done.

• Blood glucose level < 200mg/dL — insulin infusion rate 0.05

to 0.1 units/kg/hr and dextrose should be added to iv fluids
to maintain blood glucose level between 150-250 mg/dL
 IV INSULIN
• IV bolus dose = 0.1 U/kg, f/b Insulin infusion = 0.1 U/kg/hr
OR
Insulin infusion = 0.14 U/kg/hr, without bolus
• Alternative regimen, IM bolus = 0.1 U/kg, f/b infusion= 0.1
U/kg/h
• Glucose reduced = 50 to 75 mg%/h
 If glucose fails to drop by 10% in 1st hour after initial therapy,
- give = 0.14 unit/kg IV bolus & resume infusion,
- Or, increase the infusion rate by 1 U/h
• Once the serum glucose = 250 milligrams/dL,
- add dextrose to the IV fluids
- reduce the insulin infusion = 0.1to 0.05 unit/kg/h
• Maintain the serum glucose = 150-200 mg/dL

• Continue insulin infusion until DKA is resloved—

1. Glucose <200mg% &
2. Two of the following - HCO3 >15 mEq/L,
- venous pH >7.3, or
- Normal AG
CHANGE TO SUBCUTANEOUS INSULIN
When the patient can take orally and on resolution of DKA, stop IV
fluids.

• Insulin naive patients 0.5 - 0.8 U/kg , split into 50% regular and 50%
basal

• Out of 50% basal — 2/3 in morning and 1/3 in evening

• 50% regular is divided as per number of meals

• Titration of insulin is done according to CBG

• This is overlapped with insulin infusion. Subcutaneous dose must be

given two hours prior to stopping insulin infusion.

• Established DM patients: resume home insulin regimen if previously

controlled or adjust insulin if previously uncontrolled
 S/C Insulin
• Uncomplicated mild-moderate DKA
• S/C Lispro , initial dose = 0.3 unit/kg, f/b 0.1 unit/kg every hour,
or, initial dose = 0.3 unit/kg, f/b 0.2 unit/kg every 2 hours
• Until blood glucose is <250mg/dL
Then, dose is decreased by half and administered every 1 or 2
hrs until resolution of DKA.
• Advantage - Avoid ICU admissions
- Lower hospital costs
 BICARBONATE
• Not routinely recommended
• NaHCO3 correction if the initial pH is <6.9
but do not give if the pH is ≥6.9
• Severe metabolic acidosis - cardiovascular & neurologic
complications
• NaHCO3 Dose =50 - 100 mEq in 1 L 0.45% saline over 30-
60 minutes with 10 -20 mEq KCl at 200 mL/h for 2 hours
until the venous pH >6.9
 INDICATIONS OF
BICARBONATE
• Shock /coma
• PH less than 6.9
• Bicarbonate less than 5 mEq/l
• Cardiac or respiratory dysfunction
• Severe hyperkalemia
• Advantages – Improve myocardial contractility
- Increase ventricular fibrillation threshold
- Improve catecholamine tissue response, and
- Decrease work of breathing
• Disadvantages - Worsening hypokalemia
- Paradoxical CNS acidosis
- Worsening intracellular acidosis
- Impaired (shift to left) oxyhemoglobin
dissociation
- Hypertonicity and sodium overload
- Delayed recovery from ketosis
- Elevation of lactate levels, and
- Possible precipitation of cerebral edema
CRITERIA FOR
RESOLUTION OF DKA
• Serum glucose < 200mg/dL
and any 2 of the following
• Serum Bicarbonate > 15
• pH > 7.3
• anion gap < 12
 HOW TO AVOID CEREBRAL
EDEMA
• SLOW REDUCTION OF OSMOLARITY DURING TREATMENT
• AVOID LARGE VOLUMES OF HYPOTONIC FLUID
• DROP BLOOD GLUCOSE SLOWLY DURING THE TREATMENT
• DO NOT ALLOW PLASMA SODIUM TO FALL DURING TREATMENT
• AVOID UNNECESSARY BICARBONATE DURING TREATMENT
• AVOID HYPOXIA,HYPOKALEMIA
 DIFFERENTIAL DIAGNOSIS
• Alcoholic ketoacidosis
• Starvation ketoacidosis
• Renal failure
• Lactic acidosis
• Ingestions –Salicylates, Ethylene glycol , Methanol
 EUGLYCEMIC DKA
• Glucose less than 250mg/dl
• Risk factors
• Patient presenting shortly after receiving insulin
• Type1 DM
• Patients with impaired gluconeogenesis such as alcohol abuse or liver failure
• Low caloric intake or starvation
• Depression
• Pregnancy
• SGLT2 inhibitors
• Hyperosmolar, non ketotic coma : older,
prolonged course, prominent mental status change,
Serum glucose much higher, little or no AG
• Alcoholic & starvation ketoacidosis: milder
ketosis, S. βHB <3mEq/L
• HCO3 >18mEq/L
• Glucose low or normal
 DKA IN CKD
• CKD on dialysis can present with DKA with normal or
increased volume status— not require IV fluids

• If evidence of intravascular volume depletion is present—

careful administration of boluses of 250 ml of normal saline
and close monitoring of haemodynamics and lab parameters.

• IV Insulin is mainstay of treatment — initial dose 0.05

U/kg/hour.

• Serum potassium < 3.3 — administration of KCl

• Bicarbonate is recommended when pH < 6.9

• Hemodialysis is needed in profound acidosis and significant

volume overload or severe hyperkalemia