Diabetic Ketoacidosis

By

Salah Mabruok Khalaf

Master internal medicineMD Medical Oncology

South Egypt Cancer Institute2013

Local seminar Medical Oncology department

Overview

• Definition • Epidemiology• Pathophysiology of DKA• Etiology• Clinical manifestation• Investigations• Differential Diagnosis• Prevention• Treatment• Pitfalls in DKA• A guide protocol

DKA Definition

DKA = 3 letters= triad of D K A

Diabetic glucose >250 mg/dL (usually 500-800)

Keto

ketones producedketones – both in urine and in serumacetoacetate, acetone, betahydroxybutyrate fruity smell, not often encountered in real life)consider that if these criteria aren’t met, it may not be DKA

AcidosisIncreased anion gap, metabolic acidosis; HCO3- <15, pH<7.30

Epidemiology

• Annual incidence in U.S. – 5-8 per 1000 diabetic subjects

• DKA is reported in 2-5% of known type 1 diabetic patients in industrialized countries, while it occurs in 35-40% of such patients in Africa.

• Higher incidence below 5 years• 2.8% of all diabetic admissions are due to DKA• Overall mortality rate ranges from 2-10%

– Higher is older patients

Pathophysiology

Insulin

Counterregulatory hormones

Glucagon, Epinephrine, Cortisol, Growth hormone

Normal

Pathophysiology

Excess counterregulatory hormones

Insulin deficiency

DKA

Insulin Deficiency

Glucose uptakeProteolysis

Lipolysis

Amino Acids

Glycerol Free Fatty Acids

GluconeogenesisGlycogenolysisHyperglycemiaHyperglycemia KetogenesisKetogenesis

AcidosisAcidosisOsmotic diuresis

Dehydration

Excess counterregulatory hormones

Etiology

• Insulin deficiency– Insulin missed dose

– Pancreatitis

– Heavy meal

• Excess Counterregulatory hormones

– Infection i.e. Pneumonia

– MI

– Stroke

– Trauma– Emotional– Pregnancy– Iatrogenic

Insulin Deficiency

Glucose uptakeProteolysis

Lipolysis

Amino Acids

Glycerol Free Fatty Acids

GluconeogenesisGlycogenolysisHyperglycemiaHyperglycemia KetogenesisKetogenesis

AcidosisAcidosis

Osmotic diuresis

PolyuriaPolydipsia

Fruity breath (acetone smell)Kussmaul breathing (acidotic)Mental status changes

DehydrationDry tongue Tachycardia Hypotension Abd pain

Electrolyte imbalance

Clinical manifestations

Clinical manifestations

Special notes

• Abdominal pain

It is more common in children than in adults

It is multifactorial

dehydration of muscle tissue

Delayed gastric emptying

Ileus from electrolyte disturbances

Metabolic acidosis;

It sometimes mimicks acute abdomen

It is classically periumbilical

Differential Diagnosis

• DD of acidotic breathing– Renal failure– Amonia increase in HCF– Hysterical

• DD of diabetic coma– Lactic acidosis– Hyperosmolar non-ketotic coma– Hypoglycemia

• DD of coma in general• DD of acute abdomen

DKA vs. HHS

DKA HHS

Age More in children More in elderly

DM type More in type I More in type II

Glucose > 250 > 600

Ketonuria/emia +++++ + or -

pH <7.3 >7.3

HCO3 <15 >15

S osmolarity Variable Hyperosmolarity

Sensitivity to insulin Variable Sensitive to small dose

DKA vs. HYPOGLYCEMIA

DKA Hypoglycemia

Etiology Insulin deficiency or increased counter-reg hormones

Insulin overdose or hyperinsulinemia

Onset Gradual Acute

Symptoms and signs S of hyperglycemiaS of dehydration S of acidosis

-S of Brain glucopenia- S of sympathetic overactivity

RBS hyperglycemia hypoglycemia

Ketonuria Yes No

Ketonemia Yes No

IV glucose No effect Rapidly recover if early

Golden ruleGolden ruleAny diabetic patient with DKA versus hypoglycemia, give

glucose even before glucose measuring

InvestigationsFor diagnosis

Triad for diagnosis

1.RBS Hyperglycemia > 300 mg/dl

2.Ketonemia and ketonuria

3.Blood gas metabolic acidosis

– pH < 7.35, anion gap (Na + K) – (Cl + Bicarb) > 10, and

Bicarbonate <15 mEq/L

InvestigationsFor diagnosis

• Other findings– Electrolyte serum level

• Hyperkalemia (rarely Hypokalemia), Hyponatremia (rarely Hypernatremia )

– Investigation for the cause such as• Urine Analysis, AMI panel and ECG, Chest x-ray

– Hyperosmolarity• Normal = 285-295 milli-osmoles per kilogram (mOsmol/kg)

• [Glucose] and [BUN] are measured in mg/dL

Investigations

For Monitoring• RBS

– Every 1 hour till RBS reaches 200 mg/dL or less, then every 6 hours

• Urine ketones– Every 8h

• Blood gas after fluid replacement• Electrolyte serum level every 4 hours till correction

Treatment of DKA

• Treatment of predisposing factors• Initial hospital management

– Care of comatosed patients– Fluid and electrolytes replacement– Insulin replacement and glucose administration when needed– Treatment of complications

• Once resolved– Convert to home insulin regimen– Prevent recurrence

Fluids and Electrolytes

• Fluid replacement– Restores perfusion of the tissues– Average fluid deficit 3-6 liters

• Initial resuscitation with saline– 1 L of normal saline over the first ½ hour then– ½ L of normal saline over ½ hour then– ½ L of normal saline over 1 hour then– ½ L of normal saline over 2 hours– Then the rate will depend on clinical judge (BP, CVP,

basal lung crepitation)

Fluids and Electrolytes

• K+ level

– If Hyperkalemia (> 5.5 meqlL)

• initially present

• No treatment as it resolves quickly with insulin drip

– If normal level (3.5-5.5 meqlL)

• Add 26 mmol for each Liter of infused fluid

– If Hypokalemia (<3.5 meqlL)

• Add 39 mmol for each Liter of infused fluid

Fluids and Electrolytes

• Phosphate deficit

– May want to use potassium phosphate

• Bicarbonate

– Not given unless pH <7 or bicarbonate <5 mmol/L or unresolved

acidosis after fluid replacement

– Dose (mmol of NaHco3) = -------------------------------------------

– Dose (No of ampoules of NaHco3) = ----------------------------------------

BW x Becar deficit

150

BW x Becar deficit

6

Fluids and Electrolytes

• Na level:

– Calculate the corrected Sodium (for each 100 mg/dL

glucose above 100, add 1.6 meq/l to Na level)

• If corrected Na is High or Normal use Half NS (250-1000

ml/hr)

• If corrected Na is Low use NS, rate depends on severity of

volume depletion

Insulin Therapy

• Initial dose

– IV bolus of 0.1-0.2 units/kg (~ 10 units) regular insulin

– Infusion insulin at 0.1 units/kg/hr (max 8 units/hr).

• Maintenance dose (Check BG Q1hour, goal is 50-80

mg/dl/hr)

– If falling too rapidly, decrease the rate

– If falling too slowly increase the rate by 50-100%

• Continue IV insulin until urine is free of ketones and

RBS reaches 250-300 mg/dl

Insulin Therapy

• When RBS reaches 250-300 mg/dl

– Decrease the rate of insulin inf to 0.05-0.1 IU/kg/hr (goal

is to keep RBS in this range until the gap closes (normal

gap 7-8 mEq/l) then start home maintenance SC insulin

under umbrella of infused insulin for 2 hours, then

continue on SC insulin only .

Glucose Administration

• Supplemental glucose

– Hypoglycemia occurs

• Insulin has restored glucose uptake

• Suppressed glucagon

– Prevents rapid decline in plasma osmolality

• Rapid decrease in insulin could lead to cerebral edema

• Glucose decreases before ketone levels decrease

• Start glucose when plasma glucose < 300 mg/dl

Insulin-Glucose Infusion for DKA

Blood glucose Insulin Infusion D5W Infusion

<70 0.5 units/hr 150 ml/hr

70-100 1.0 125

101-150 2.0 100

151-200 3.0 100

201-250 4.0 75

251-300 6.0 50

301-350 8.0 0

351-400 10.0 0

401-450 12.0 0

451-500 15.0 0

>500 20.0 0

Complications of DKA

• Infection

– Precipitates DKA

– Leukocytosis can be secondary

to acidosis

• Shock

– If not improving with fluids r/o

MI

• Vascular thrombosis

– Severe dehydration

– Cerebral vessels

– Occurs hours to days after DKA

• Pulmonary Edema

– Result of aggressive fluid

resuscitation

• Cerebral Edema

– First 24 hours due to aggressive

correction of hypoglycemia or

administration of hypotonic

solution

– c/p: Mental status changes

– Tx: Mannitol

– May require intubation with

hyperventilation

Causes of Cerebral Edema

Mechanism:

• The brain adapts by producing intracellular osmoles

(idiogenic osmoles) which stabilize the brain cells from

shrinking while the DKA was developing.

• When the hyperosmolarity is rapidly corrected, the

extracellular fluids is corrected faster than brain cells

– The brain becomes more hypertonic than the extracellular fluids

water flows into the cells cerebral edema

Causes of Cerebral Edema

The many factors have been implicated:

Rapid and/or sharp decline in serum osmolality with

treatment.

High initial corrected serum Na concentration.

High initial serum glucose concentration.

Failure of serum Na to raise as serum glucose falls during

treatment. OsmolalityNa

Glucose

Presentations of Cerebral Edema

Cerebral Edema Presentations include:

Deterioration of level of consciousness.

Headache and blurring of vision

Vomiting

Convulsion.

Treatment of Cerebral Edema

• Reduce IV fluids• Raise foot of Bed• IV Mannitol • Elective Ventilation• Dialysis if associated with fluid overload or renal

failure.• Use of IV dexamethasone is not recommended.

Prevention of DKA

• Never omit insulin

– Cut long acting in half

• Prevent dehydration and hypoglycemia

• Monitor blood sugars frequently

• Monitor for ketosis

• Provide supplemental fast acting insulin

• Treat underlying triggers

• Maintain contact with medical team

Pitfalls in DKA

• Plasma glucose is usually high but not always– DKA can be present with RBS < 300 due to

• Impaired gluconeogenesis– Liver disease

– Acute alcohol ingestion

– Prolonged fasting

– Insulin-independent glucose is high (pregnancy)

• Chronic poor control but taking insulin

• Ketone in urine may be –ve in DKA, but always +ve in blood– Due to measurement of acetoacetic acid in urine not,

betahydroxybuteric acid– Acetone in blood should be done in this case

Pitfalls in DKA

• High WBC may be present without infection

• Infection may be present without fever

• High Creatinine may be present without true renal function: it

may cross react with ketone bodies.

• Blood urea may be elevated with prerenal azotemia

secondary to dehydration.

• Serum amylase is often raised even in the absence of

pancreatitis

Email: salahmab76@yahoo.com salahmab76@gmail.comFacebook: Dr salah mabroukYouTube channel: salahmab1

Mobil: (202) 01004081234

Email: salahmab76@yahoo.com salahmab76@gmail.comFacebook: Dr salah mabroukYouTube channel: salahmab1

Mobil: (202) 01004081234