Dr Fathi El Sewi Diabetic Ketoacidosis DKA It

Dr. Fathi El Sewi

Diabetic Ketoacidosis (DKA) It is a life threatening but reversible complication of type 1 diabetes due to absolute insulin deficiency. Ketoacidosis: High anion gap metabolic acidosis due to excessive blood concentration of ketone bodies (Ketoanion).

Pathogenesis of DKA A-The basic underlying mechanisms are: -Absolute deficiency of circulating insulin. - secretion of insulin counterregulatory hormones; glucagon, adrenaline, cortisol and growth hormone.

B-This leads to disturbances in the following physiological processes: - glucose utilization (hyperglycemia). - proteolysis ( amino acids, glutamine and alanine). - lipolysis ( glycerol and FFAs). - glycogenolysis (breakdown of muscle glycogen lactate). - gluconeogensis (glutamine & alanine & glycerol & lactate are the precursors).

C-This results in the following metabolic abnormalities: 1 -Hyperglycemia. 2 -Hyperketonemia: 2 main mechanisms: a- Production of ketone bodies (ketogenesis): -Increase FFAs hepatic uptake FFAs enter the mitochondria oxidation to form acetoacetic acid. -Large part of acetoacetic acid reduced to -hydroxy butyric acid ( -HBA). -Small part of acetoacetic acid is decarboxylated to acetone. The 3 ketone bodies are released to the blood in a ratio between acetoacetic acid to -HBA of 8 : 1. b- Utilization of ketone bodies.

D-The consequences of these metabolic abnormalities are: a-Hyperglycemia: -Osmotic diuresis. -Excessive urinary losses of H 2 O & Na, K. -Dehydration and hypotension. b-Hyperketonemia: -Ketonuria. - Blood acidity (acetoacetic acid and -HBA are strong acids). -Obligate losses of sodium and potassium due to urinary excretion of ketone bodies (salt) alkaline reserve. -Acetone is a CNS anaesthetic.

E-Electrolytes and acid base disturbances during DKA: a-Serum K: Usually high (hyperkalemia) secondary to: 1 -Shift of K from intracellular to extracellular compartment due to: -Insulin deficiency and hyperglycemia. -Extracellular hyperosmolarity. -Acidosis. - Catabolism and breakdown of cellular protein. 2 -Impaired cellular uptake of K.

b-Serum sodium: Usually low secondary to: -Hyperglycemia leads to osmotic flux of H 2 O from intracellular to extracellular space. -Obligate sodium loss with ketonuria. c-Metabolic acidosis: Secondary to: - Production and utilization of strong acids; acetoacetic acid and -HBA. - Alkaline reserve (sodium and K losses).

Clinical features of DKA A-Symptoms of DKA: 1 -Classic symptoms of hyperglycemia: short period of time: Polyuria, polydipsia, wt loss and thirst. 2 -Other symptoms: - General weakness, malaise and lethargy. -Nausea, vomiting and abdominal pain. - Perspiration. - Disturbed consciousness and confusion. 3 -Symptoms of underlying infections or other conditions; fever, abdominal pain, dysuria, chest pain…etc. •

B- Physical signs of DKA: a-General signs: Ill appearance and disturbed consciousness. b-Signs of dehydration: -Skin: Dry, hot, flushed, and loss of skin turgor. -Tongue: Dry (sometimes woody tongue). -Eyes: Sunken eyes and dark circles under the eyes. c-Vital signs: -Tachycardia, hypotension and tachypnea. d-Specific signs: -Ketotic breath: A strong, fruity breath odour (similar to nail polish remover or acetone). -Acidotic breath (Kussmaul's respiration): deep and rapid. -Abdominal tenderness.

Diagnostic criteria of mild to moderate DKA: • Blood glucose > 300 mg/dl. • Mild to moderate dehydration. • Ketonuria: mild (+) to moderate (++). • Serum bicarbonate < 15 m Eq/L. • p. H is acidic (Metabolic acidosis): Arterial < 7. 3. Or Venous < 7. 25.

Diagnostic criteria of severe DKA: • Blood glucose > 300 mg/dl. • Heavy ketonuria +++ • Severe dehydration. • p. H is acidic: Arterial < 7. Or Venous < 6. 95. • Serum bicarbonate < 10 m. Eq/l. • Anion gap > 12 m. Eq/l (normal gap 7 -8 m. Eq/l) AG = (Na+) – (Cl- + HCO 3)

Urine testing during DKA 1 - Urine glucose conc. Is poorly correlated with BG levels. 2 - Renal threshold for glucose and ketones are increased in DKA & HHS. 3 - Most of the available laboratory urine tests (nitroprusside test) detect only acetoacetate & acetone but not beta–HB. 4 - Beta-HB is the predominant ketones in severe untreated DKA cannot be measured or recognized by the standard nitroprussid test.

5 - When the clinical condition improves with treatment , the urine test results become positive due to the returning predominance of acetoacetate. 6 - So, during follow up of patients with DKA urine test for ketones is better avoided. 7 - Now blood ketone measurements are available and detect beta-HB.

Complications of DKA 1 -Complications of associated illnesses e. g. sepsis or MI. 2 -Adult respiratory distress syndrome. 3 -Thromboembolism (elderly). 4 -Complications of treatment: a-Hypokalemia: Which may lead to: -Cardiac arrhythmias. -Cardiac arrest. -Respiratory muscle weakness.

b-Hypoglycemia. c-Overhydration and acute pulmonary edema: particularly in: -Treating children with DKA. -Adults with compromised renal or cardiac function. -Elderly with incipient CHF.

d-Neurological complications: Cerebral Edema. -It occurs only in children with DKA. -Very dangerous and increases mortality. -The risk is related to the severity, duration and rapid correction of DKA. 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 brain becomes hypertonic towards the extracellular fluids water flows into the cells cerebral edema

Management of DKA • The main lines of management include: A-Primary assessment: -Volume status and degree of dehydration. -Blood pressure and cardiac condition. -Degree of consciousness. -Degree of acidosis. -Precipitating disease

B-Ongoing monitoring: -Blood glucose (using glucometers) every hour. -Electrolytes and p. H every 4 hours. -Urine for glucose and ketones every 4 hours

C-Initiation of treatment: 1 -General measures: -Airway and O 2 inhalation if needed. -IV line. -Urinary Foley's catheter (if in shock). -NGT (Nasogastric Tube): to avoid gastric dilatation and protection from aspiration. -Thrombosis prophylaxis: 5000 units of heparin SC/12 hours. -Empiric use of 3 rd generation cephalosporin antibiotics.

2 -Specific measures: Successful therapy of hyperglycemic crises requires the administration of: a-Fluids: 1 - Correct volume deficit and hypotension. 2 - Improve tissue perfusion. 3 -Improve insulin sensitivity ( insulin counterregulatory hormones). 4 -Improve glomerular filtration rate: i-↑ excretion of large amount of glucose in urine. ii-Clears hyperketonemia. 5 - Correct metabolic acidosis.

b-Insulin: Reversal of metabolic abnormalities : i-Corrects hyperglycemia. ii-Inhibits ketogenesis. c-Potassium: Prevents complications associated with hypokalemia.

Fluid Therapy • The expected volume deficits calculated as: 5 -10% of body wt in DKA (3 -6 liters). 15 % of body wt in NKHH (9 liters). • Replacement therapy should be given within 24 hours after admission: 50% of the deficit in the first 4 hours. 50% of the deficit in the next time for up to 24 hours, guided by ongoing clinical evaluation. • For children and adolescents (less than 20 years): Fluids are given as 10 -20 ml/kg/hour in the first four hours. Then given guided by clinical evaluation

Type of fluid 1 -Normal saline (0. 9% sodium chloride). • Advantages: -Available all the time. -Rapid expansion of extracellular compartment. -Slow decline of extracellular osmolarity. -Slow rate of cerebral edema evolution. • Disadvantages: May accentuate hypernatrimia if present. • Indications: -All cases of DKA. -Initial (1 st 2 liters) in NKHH state.

2 -Half strength saline (0. 45% sodium chloride): Used only if serum corrected sodium is high >145 m. Eq/L. • Corrected sodium level = measured sodium + corrected value. • Corrected value: For every 100 mg/dl BG above the normal baseline of BG 100 mg/dl, Add 1. 6 m. Eq/l Na to the measured serum sodium. • Example: Measured Na = 134 m. Eq/L, BG= 400 mg/dl. Corrected Na value: 3 x 1. 6 m. Eq/L=4. 8 m. Eq/L. The serum corrected Na is: 134+4. 8 = 138. 8 m. Eq/L.

Insulin Therapy • Standard low dose insulin regimen: This regimen is the only effective therapy in DKA & NKHH state: 1 -Inhibits ketogenesis and gluconeogenesis. 2 - Presence of insulin resistance state secondary to: a- Stress insulin counterregulatory hormones. b- Ketone bodies & FFAs. c- Hemoconcentration and electrolytes imbalance. d- Hyperosmolarity. e- Infection.

• Type of insulin : Regular : Rapid or short acting insulin U-40 & U-100. • Regimen: Initial bolus: 0. 1 U/kg body wt given IV. Maintenance: 0. 1 U/kg/body wt /hour: a- IV Infusion set: Add 100 units of regular insulin +500 ml saline i. e. every 5 cc fluid contains 1 unit of insulin b-IV infusion set is not available: IM route.

Potassium Therapy • Initially: Mild to moderate hyperkalemia occur in patients with DKA. • Later on: After initiation of: Insulin therapy Correction of acidosis lead to hypokalemia. Volume expansion & hydration

Rational of potassium therapy • In the 1 st 2 liters of fluid add no potassium. • If urine output confirmed add KCl from 3 rd liter on. If serum potassium: < 3 m. Eq/L add 20 – 40 m. Eq KCl/liter to IV saline. 3 -5 m. Eq/L add 10 – 20 m. Eq KCl/liter to IV saline. > 5 m. Eq/L add no potassium. • Patient with oliguria or renal insufficiency: K levels must be frequently monitored with continuous ECG evaluation. • The infusion continues until the patient can tolerate oral potassium supplement (15 CC potassium syrup/ 8 hours).

A Guide Protocol 1 -Establish the diagnosis. 2 -Establish the precipitating disease. 3 -Assess the degree of dehydration: (BP, urine output, skin turgor) 4 -Calculate total fluid deficit: • For DKA: about 3 -6 liters. • For NKHH state: about 9 liters. 5 -Determine the type of fluid as replacement: – Use normal isotonic saline 0. 9% in: a-All cases of DKA. b-Initial (1 st 2 liters) in NKHH state. – Use half strength saline 0. 45% if measured sodium > 145 m. Eq/L.

6 -Order the rehydration program as follow (normal saline): – First 4 hours : 50% of the calculated total fluid deficit. – Next time for up to 24 h: 50% of the calculated total fluid deficit.

7 -Order and start insulin regimen: – Type of insulin: Rapid or short acting insulin. – Initial bolus = 0. 1 unit X BW in Kg / direct IV. – Maintenance = 0. 1 unit X BW in Kg / hour. Infusion set available: Order: Add 100 units of regular insulin to 500 cc saline i. e. every 5 cc contains one unit of insulin, calculate the dose and give by IV drip. Infusion set is not available IM route NB: For IM route: it is important to use a needle that is long enough to insure that the insulin is not given SC

8 -Order potassium replacement regimen: • Type of fluid: potassium chloride ( amp=10 m. Eq). • Aim: K level should be in the range 4 -5 m. Eq/L. If serum potassium: < 3 m. Eq/L add 20 – 40 m. Eq KCl/liter to IV saline. 3 -5 m. Eq/L add 10 – 20 m. Eq KCl/liter to IV saline. > 5 m. Eq/L add no potassium.

9 -Monitoring: – Blood glucose by glucometer every hour. – Urine analysis for glucose and ketones every 4 hours. 10 -Order IV glucose 5% (second line) once blood glucose reaches: < 250 mg/ dl in DKA. < 300 mg/ dl in NKHH state. 11 -Re-evaluate parameters of rehydration establishment: – Stable blood pressure. – Normal urine output. – Clinical signs of rehydration.

12 -Evaluate the criteria for stopping hourly insulin regimen (resolving DKA): – Acidosis corrected clinically and by p. H. – Negative ketonuria. – Eating. – Patient looks good and feels good.

13 -Initiate SC insulin therapy: Give 10 units NPH/SC one hour before stopping hourly insulin regimen a-Patients with newly diagnosed diabetes: Initial dosage is 0. 5 - 0. 8 U/Kg BW/day: calculate the dose and give (2/3) before breakfast and (1/3) before dinner in a ratio (2/3) NPH and (1/3) regular insulin. b-Patients with known diabetes: Initial dosage is the same as the dosage they were receiving before onset of DKA. Monitor blood glucose before and after each meal and at bed time, and upgrade the insulin doses accordingly.

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