Diabetic Ketoacidosis

Hyperglycemic Hyperosmolar
State

Dr. Soumar Dutta

PG Trainee
Accident and Critical Care Medicine

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Diabetic Ketoacidosis

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 Introduction
• Acute life threatening complication of DM

• DKA predominantly seen in type 1 DM

• DKA represents body’s response to cellular

starvation due to insulin deficiency & counter
regulatory hormone excess

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DKA

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 Classification
Moderate
Mild DKA Severe DKA
DKA

Plasma glucose > 250 mg/dl > 250 mg/dl > 250 mg/dl

Arterial ph 7.25-7.30 7.0-7.24 < 7.0

Serum
15-18 10-<15 < 10
bicarbonate
Urine ketones + + +
Anion gap >10 >12 >12
Alteration in
alert alert/drowsy stupor/coma
sensorium
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Pathophysiology of DKA

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• Facilitate uptake • Uptake of
of glucose & • Increase amino acids into
conversion into lipogenesis muscle cell
glycogen • Inhibit • Prevents release
• Inhibits lipolysis of amino acids
glycogenolysis & from muscle
gluconeogenesis
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 Pathophysiology
Insulin Deficiency is the primary defect in
patients with DKA

Muscle Hepatocyte Adipose

Glycogen
Glucose
Glucose
Glucose-P
Amino Free
Pyruvate, CO2
Acids fatty
Ketoacids acids
Normal Insulin Activity A&E(VINAYAKA)
 Pathophysiology
Glucagon
Epinephrine
Cortisol
Insulin Growth Hormone

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 Pathophysiology
Glucagon
Insulin Epinephrine
Cortisol
Growth Hormone

Decreased Glucose Utilization

Lipolysis
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 Decreased Utilization
DKA - Early post-prandial
and
Stress-Induced
• Relative Insulin Deficiency hyperglycemia
• Glycogenolysis & gluconeogenesis
• Peripheral glucose uptake

Elevates
blood glucose

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 Pathophysiology
Glucagon
Insulin Epinephrine
Cortisol
Growth Hormone

Gluconeogenesis
Glycogenolysis
Lipolysis
Ketogenesis A&E(VINAYAKA)
 Increased Production &
DKA - Late Decreased Utilization
Fasting
• Insulin Deficiency hyperglycemia

Glycogenolysis
Gluconeogenesis
Hepatic glucose output
Lipolysis: Release FFA -> liver
VLDL & ketones
Ketonemia and hyper TG

Acidosis , Hyperglycemia & Osmotic diuresis

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 Islets of β-cell destruction Insulin Deficiency
Langerhans

rtisol Decreased Glucose Utilization &

Ep i, C o
u cagon Increased Production
Stress G H , G l

Muscle
Amino Glucagon
Adipo- Increased
Acids Liver
cytes Protein
Catabolism
Increased
Ketogenesis
Glucoaneogenesis,
FattyAcids Glycogenolysis
IncreasedLipolysis

Polyuria Threshold
180 mg/dl Hyperglycemia
Volume Depletion
Ketoacidosis
Ketonuria
HyperTG
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 Precipitating factors of DKA
• Omission or reduced • Pulmonary embolism
daily insulin injection • G I hemorrhage
• Infection • Heat related illness
• Pancreatitis • Parenteral/enteral
• Myocardial Infarction alimentation
• Mesentric Ischemia • Rhabdomyolysis
• Renal Insufficeincy • Severe Burns
• CVA
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 Drugs Precipitate DKA
• Diuretics • Glucocorticoids
• Lithium • Neuroleptics
• Beta Blockers • Phenytoin
• Mannitol • Didanosine
• Chlorpromazine • Calcium-channel
• Cimetidine blockers
• Pentamidine

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 Clinical features
Hyperglycemia

Osmotic diuresis and renal loss of Na, K, PO4,

Ca and Mg

Hypovolemia,acidosis and hyperventilation

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 Clinical features
• Increased PGI2 and PGE2peripheral
vasodilation ,nausea, vomiting and abdominal
pain.

• Vomiting maladaptive response to counter

acidosis exacerbates the potassium losses

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 Signs of DKA
• Dehydration
• Hyperventilation
• Ketotic breath
• Tachycardia and hypotension
• Disturbed conscious state and shock
• Alteration of consciousness correlate better with
elevated serum osmolality (>320 mOsm/L) than with
severity of metabolic acidosis

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 Symptoms

• Polyuria

• Polydipsia

• Nausea and vomiting

• Abdominal Pain

• Breathing difficulty

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Lab Investigations
• Serum glucose
• Serum electrolytes
• Complete blood count
• Renal function test
• Serum & urine ketones
• Blood gas analysis

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Lab Investigations
• Blood cultures
• Sputum collection
• Urine analysis & Culture
• Liver function tests & Coagulation profiile
• Cardiac enzymes
• Thyroid function tests
• Toxicological Screening

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 Radiology

• Chest X ray

• ECG

• USG Abdomen

• CT Head

• Lumbar Puncture

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 Corrected Sodium

Measured Na + 1.6 (Glucose-100)

100
•Na+ depressed 1.6 mEq/L per 100 mg%
glucose rise above 100 mg/dl.

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 Corrected Sodium

Example:
Na+ = 123 meq/L and Glucose = 1,250 mg/dl

Measured Na + 1.6 (Glucose-100)

100
= 123 + 1.6 (1250-100)
100
Corrected Na+ = 123 + 18 = 141 meq/L
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 Serum Osmolarity

2(Na) + Glucose + BUN

18 2.8

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D/D

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Management of DKA

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 Goals of Treatment

• Volume Repletion
• Reversal of metabolic consequences of
insulin insufficiency
• Correction of acid-base & electrolyte
imbalances
• Recognition & Treatment of precipitating
causes
• Avoidance of complications

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Management of DKA

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 Approach to therapy
• Correcting the hyperosmolar state and
dehydration is the initial aim of therapy.
• Insulin therapy should be undertaken only
after the patient is stable hemodynamically .

Glucose and H2O

H2O lost in urine Loss of ECF, vascular collapse and death

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 Fluid Resuscitation
• Single most important step
• Fluid deficit around 100ml/kg (5-10L)
• Helps in Restore I/V volume
• Perfuse vital organs
• Increase GFR
• Decrease serum Glucose & Ketone levels
• To restore normal tonicity

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Fluid balance in diabetic
hyperosmolarity
ECF = 14 L ICF = 28 L

ECF ICF

H2O

ECF hyperosmolar from ICF autotransfusion

Osmotic Diuresis

H2O

Osmotic Diuresis ECF and ICF both hyperosmolar

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 Fluid Resuscitation
• NS most frequently administered fluid
• 1 litre in 30 min
• 2 litres in 2 hours
• 2 litres in 2-6 hours
• 2 litres in 6-12 hours

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 Fluid Resuscitation
• 2–3 L of 0.9% saline over first 1–3 h (10–15
mL/kg per hour)

• 0.45% saline at 150–300 mL/h; change to 5%

glucose and 0.45% saline at 100–200 mL/h
when plasma glucose reaches 250 mg/dl.

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 Fluid Resuscitation

•CVP guided fluids should be considered for

elderly & those with heart disease

•Excess fluid may lead to ARDS & cerebral

edema

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 Insulin therapy

Mechanism of Action:
• Inhibit gluconeogenesis, lipolysis, catabolic
hormone secretion, production of ketoacids
• Promote potassium, glucose & phosphate
uptake in tissues

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 Insulin therapy
• Ideal way to administer insulin by continuous
infusion of small doses of regular insulin
0.1unit/kg/hr once hypokalemia is excluded.

• I/M or S/C administration of regular insulin

should be avoided as insulin absorption may be
erratic in volume depleted & vasocostricted
patient

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 Insulin therapy
• Goal is to decrease Glucose by 50-75mg/dl/hr.

• Infusion should continue until anion gap normalized

• S/C insulin should bridge for atleast one hour before

discontinuation of I/V insulin

• Insulin administration should be W/H if K <3.3 mEq

till K is supplemented A&E(VINAYAKA)
 DKA: Switch to S.C. insulin
Can consider switch to SC insulin when:

• AG normalized
• BS < 250 mg/dl
• Insulin IV requirements < 2U/h
• Patient able to eat
• Hemodynamically stable

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 DKA: Switch to S.C. insulin
• Overlap insulin IV with 1st SC insulin by 2-4h
to avoid recurrent ketosis

• T2 DM patients with DKA:

• Don’t necessarily have to be continued on
insulin
• Once acute stress resolved, many do well on
OHA

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 Potassium Correction
• K+ defecit: 3-5 mEq/Kg (350 mEq for 70Kg)
• Normal to high serum K+

Ketoacidosis
H+ H+

K+ K +

Insulin
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 Potassium Correction
• Deficiency is due to

• Decreased insulin levels

• Metabolic Acidosis
• Osmotic Diuresis
• Frequent Vomitting

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 Goal of K Replacement

• To maintain a normal extracellular K+ conc during

the acute phase of therapy and to replace intra-
cellular deficits over a period of days

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 K Supplementation
Serum Potassium < 3 mEq/L Give 60mEq/l to IVF
3-3.9 mEq/L 40mEq/l to IVF
4-5.4 mEq/L 20 mEq/L to IVF
> 5.5 mEq/L No Replacement necessary

Verify Normal kidney function &

Urine output before treatment
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 Bicarbonate

• Routine use of supplemental bicarbonate in

Rx of DKA is not recommended
• Can be given if PH Is less than 6.9

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 ADA Recommendation
If PH 6.9-7.0 50mEq of NaHCo3+200ml sterile
water+10mEq KCl over 1 hour

If Ph <6.9 100mEq of NaHCo3+400ml sterile

water+10mEq KCl over 2 hours

Repeat dose of bicarb every 2 hours till PH>7

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 Theoretical Advantages

• In case of severe acidosis

• Improve myocardial contractility

• Improve catecholamine tissue response

• Decrease work of breathing

• In case of Hyperkalemia

• Elevate ventricular fibrillation threshold

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 Disadvantages

• Severe & worsening hypokalaemia

• Paradoxical CNS acidosis

• Impair oxyhemoglobin dissociation

• Hypertonicity

• Sodium overload

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 Disadvantages

• Delayed recovery from ketosis

• Elevation of lactic levels

• Precipitation of cerebral edema / Pulmonary

edema
• Thrombophlebitis

• Require Central venous cannulation

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 Hypophosphatemia
• Most severe 24-48 hours after treatment
• Treatment If Levels <1.0 mg/dl
• C/F
• Hypoxia
• Rhabdomyolysis
• Hemolysis
• Respiratory failure
• Cardiac Dysfunction

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 Hypophosphatemia

• IV (K2PO4 ) : 1ml/hr. (4.4 mEq potassium +

93 mg phosphate )

• S/E
• Hyperphosphatemia
• Hypocalcemia
• Hypomagnesemia
• Metastatic soft tissue calcification
• Hypernatremia
• Osmotic diuresis A&E(VINAYAKA)
 Hypomagnesemia
• Inhibit parathyroid hormone secretion
• hypocalcaemia & hyper phosphatemia

• Supplementation if Mg <1.2 mg/dl

• Can give Oral Magnesium oxide

or
• Parenteral Magnesium sulphate
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 Monitoring

• Periodical assessment of vital signs

• Level of consciousness

• Hourly urine output

• Serum glucose Q1H

• Serum Potassium Q2H

• Regular assessment of anion gap

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Complications of DKA

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DKA in Pediatrics

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 Criteria for diagnosis
• Hyperglycemia:
CBG > 300mg/dl.

• Metabolic acidosis:
pH < 7.25 – 7.30
HCO3- < 15 mEq/L
• Ketonemia

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 Clinical features

• Polyuria • Confusion
• Polydipsia • Visual changes
• Polyphagia
• Abdominal pain
• Nausea and vomiting
• Rapid weight loss
• Fatigue

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 Signs
• Dehydration
• Tachycardia
• Hypotension
• Kussmaul respiration (rapid & deep)
• Sweet, fruity odour on the breath
• LOC/Coma (look for cerebral edema)

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 Treatment goals
• Establish good perfusion status
• Reverse the acidosis
• Correct electrolyte disturbances
• Control hyperglycemia
• Ketonemia

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Treatment

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 Correction of acidosis
Don’t use bicarbonate as
• It will increase chances of cerebral edema
by 4 times.
• can lead to volume overload,
hypernatremia, paradoxical cerebral
acidosis, accelerated K+ loss

Is there any role for bicarbonate in DKA?

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 Indication for bicarbonate
• pH < 7.0
• Hemodynamically unstable
• Not responding to fluids
• Depressed cardiac contractilty
• Poor perfusion

Dose: 0.5 – 2 mEq/kg over 1-2 hrs

Stop correction once pH >7.0
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 Major complication of DKA
• Cerebral Edema: most dreaded complication
• 57-87% of all pediatric DKA-associated
deaths
• More in < 5yrs Rare in > 20 yrs.

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 Reasons for Cerebral Edema
• Over aggressive fluid correction
• Failure of Na+ to rise with fall of glucose
during treatment
• Cerebral ischemia due to severe dehydration
and hypocarbia

Onset : 6-12 hrs. after onset of therapy

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 Clinical features

• Severe headache
• Seizures
• Papilledema
• Respiratory arrest
• Altered mental status

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 Hyperglycemia
Hyperosmolar State (HHS)

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 Introduction
• A metabolic emergency that occurs in
diabetic patient usually Type 2 Diabetes
Mellitus

• Characterised by uncontrolled hyperglycemia

that induces hyperosmolar state and
dehydration without significant ketoacidosis.

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 Diagnostic features
• Plasma glucose level of 600 mg/dL or greater

• Effective serum osmolality of 320 mOsm/kg

or greater

• Profound dehydration (8-12 L) with elevated

serum urea nitrogen (BUN)-to-creatinine ratio

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 Diagnostic features
• Small ketonuria and absent-to-low ketonemia

• Bicarbonate concentration greater than 15

mEq/L

• Some alteration in consciousness

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 DKA Vs. HHS
DKA HHS
Glucose 250-600 >600
Sodium 125-135 135-145
Potassium Normal/inc Normal
Bicarbonate <15meq/l Normal/slightly
reduced
Arterial pH <7.3 >7.3
Anion gap Increased Normal/slightly
increased
pCO2 20-30 Normal
Osmolality 300-320 >320
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 Causes
• Dehydration Drugs
• Pneumonia and UTI • Diuretics
• Counter-regulotary • B-blocker
hormone (e.g cortisol, • Histamine(H2)
cathecolamine, glucagon) Blocker
• Dialysis • Anti-psychotics
• TPN Clozapine, Olanzapine
• Non-compliance to OHA • Alcohol and cocaine
or insulin therapy

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Concomitant illness

Pathophysiology
Circulating insulin
& of counter-
regulatory hormones
Dehydration

renal clearance and

peripheral utilization Loss of electrocyte
of glucose and water

Hyperglycemia Osmotic diuresis

Hyperosmolarity Intracellular dehydration

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 Clinical features
• Occurs only in type 2 DM

• Could be initial presentation of the diabetic state

• Elderly

• Obtundation to coma

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 Clinical features
• Severe dehydration invariable

• May have associated lactic acidosis due to

hypoxia

• Precipitating factors similar to DKA

• Mortality rate is high

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 Symptoms
Symptoms of hyperglycemia :
Polydipsia
Polyuria
Lethargic
Others :
Weight loss
Loss of consciousness

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 Symptoms
A wide variety of focal and global neurologic
changes may be present :

• Drowsiness and lethargy

• Delirium
• Coma
• Focal or generalized seizures
• Visual changes or disturbances
• Hemiparesis
• Sensory deficits

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 Physical examination

Dehydrated : dry skin, lips, mucous membrane,

loss skin turgor

Vital sign : tachycardia (early dehydration),

hypotension (later), temperature

Systemic examination to ruled out the cause.

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 Differential diagnosis
• Alcoholic ketoacidosis
• Delirium (altered mentation)
• Dementia
• Overdose
• Thyrotoxicosis (tachycardia, fever,
dehydration)

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 Lab studies
• Plasma glucose
Hyperglycemia: CBG : > 600 mg/dl
• ABG
PH> 7.3
HCO3>15 mmol/l
• Serum osmolality
>320 mmol/l

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 Others
• Urine-analysis
• Exclude UTI
• Proteinuria
• Plasma ketone
• Plasma electrolyte
• Renal function test( Creatinine &BUN)
• CBC
• Creatine kinase
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 Imaging studies
Chest radiograph
• Exclude pnuemonia
• Cardiomegaly
CT scan of the head
• Exclude haemorrhagic stroke, subdural
haematoma
• Look for cerebral edema

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 Management
Treatment Goals:

• Correction of hypovolemia
• Identify and treating underlying cause
• Correcting electrolyte abnormalities
• Gradual correction of hyperglycemia and
osmolarity
• Frequent monitoring
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Management

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References

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Thank You

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