Diabetic ketoacidosis - ispad guidelines

Diabetic ketoacidosis

1. Diabetic ketoacidosis-ISPAD guidelines 2022 Dr Arun Raj R AHRI

2. Biochemical criteria -DKA Hyperglycaemia-blood glucose >11mmol/L or 200mg/dl Ketonemia ( blood β hydroxybutyrate ≥3 mmol /L) or moderate or large ketonuria (≥2 +) Venous pH <7.3 or serum bicarbonate <18 mmol /L D K A

3. Pathophysiology:

4. Clinical manifestations of diabetic ketoacidosis:

5. Polyuria/ Nocturia Polydipsia Abdominal pain Tiredness/ Weight loss Vomiting SYMPTOMS

6. CLINICAL FALLACIES: With other features of shock High BP Without oliguria Shock Without chest signs Breathlessness Without loose stools Vomiting With weight loss Good appetite With vomiting and dehydration Polyuria

7. Mild . Moderate . Severe . pH < 7.3 or serum bicarbonate <18 mmol /L 1 pH < 7.2, bicarbonate < 10 mmol /L 2 pH < 7.1, bicarbonate <5 mmol /L 3 Severity of DKA: Based on degree of acidosis

8. Risk factors- DKA 1 2 3 4 Younger age Delayed diagnosis Low socioeconomic status Residence in a country with low prevalence of Type I DM IN Newly diagnosed cases:

9. In Known Diabetes

10. Management priorities: ABC-life support Correction of dehydration-IV fluids Correction of acidosis Reversing ketosis insulin Restoration of euglycemia Avoid complications Identify and treat precipitating events Close monitoring and interventions as needed

11. Emergency assessment-PALS 1. Immediate measurement of blood glucose blood or urine ketones serum electrolytes and blood gases 2. Assessment of level of consciousness . 3.Two peripheral intravenous (IV) catheters should be inserted Management should be conducted in a center experienced in the treatment of DKA

12. Goals of therapy: 12 01 02 05 04 03 Monitor for complications of DKA and its treatment Correct acidosis and reverse ketosis Identify and treat any precipitating event Restore blood glucose to near normal Correction of dehydration

13. Management: Weigh the child Assess severity of dehydration Most useful clinical signs: Prolonged capillary refill time Abnormal skin turgor Other signs-dry mucus membrane, sunken eyes, absent tears, weak pulses, cool extremities( more signs-more severe dehydration ≥10% dehydration-presence of weak or impalpable peripheral pulses, hypotension, oliguria

14. Assess level of consciousness-Glasgow coma scale Intubation should be avoided- increase in pCO 2 during or following intubation above the level patient had been maintaining → CSF pH decrease → cerebral oedema worsen Oxygen- circulatory impairment or shock present Continuous ECG monitoring- evidence of hyper or hypokalemia 2 nd peripheral IV catheter-repeated blood sampling, arterial catheter in critically ill child

15. Avoid placing central venous catheter –high risk of thrombosis Antibiotics to febrile patients –after obtaining appropriate body fluid culture Bladder catheterization not necessary – done if child unconscious, infants or very young children

16. Objectives of fluid and electrolyte replacement therapy: Restore Circulating Volume Replace Na and extracellular water deficit Improve GFR and enhance clearance of glucose and ketones from blood

17. Shock with hemodynamic compromise is rare in pediatric DKA. In mild DKA assume 5%, moderate DKA 7% and severe DKA 10% dehydration Increased serum urea nitrogen and anion gap at presentation are the measures most strongly correlated with volume deficit. The serum sodium concentration is an unreliable measure of the degree of ECF contraction

18. Water and salt deficit must be replaced Iv or oral fluids that may have been given in another facility before assessment should be factored into calculation of deficit and replacement volume

19. Resuscitation fluids: For patients who are volume depleted but not in shock volume expansion (resuscitation) should begin immediately with 0.9% saline , 10 to 20 mL/kg infused over 20-30 minutes to restore the peripheral circulation. If tissue perfusion is poor: The initial fluid bolus volume should be 20 ml/kg . DKA in shock → 0.9% saline in 20 mL/kg boluses infused as quickly as possible through a large bore cannula with reassessment of circulatory status after each bolus. Use crystalloid not colloid .

20. Deficit replacement fluid: With 0.45-0.9% saline/balanced salt solution(Ringer’s lactate, Hartmann’s solution or plasmalyte ) Deficit replacement(DR) +maintenance fluid requirement With added potassium IV rate= (deficit fluid + 2x maintenance)-bolus 48 hours

21. DEFICIT= depends on the degree of dehydration Eg : 10% dehydration in a 10 kg child Deficit= %dehydration X wt (kg) x 10 =10x 10 x 10 = 1000 ml MAINTENANCE FLUID 10 Kg= 100ml/kg= 1000ml

22. So the total requirement calculated for 48 hrs iv fluid= (1000+ 2x 1000)-100 ml/ hr 47 = 60.4 ml/ hr

23. Replace the estimated fluid deficit over 24-48 hours. The use of large amounts of chloride-rich fluids (combined with preferential renal excretion of ketones over chloride) is often associated with development of hyperchloremic metabolic acidosis . Generally asymptomatic and resolves spontaneously.

24. Fluid and electrolyte therapy based on: Clinical assessment of hydration status Calculated effective osmolality: Aim to gradually reduce serum effective osmolality to normal Concomitant increase in serum sodium concentration as serum glucose concentration decreases (sodium should rise by 0.5mmol/L for each 1 mmol /L or 20mg decrease in glucose)

25. Insulin therapy: To suppress lipolysis and ketogenesis To maintain normal blood glucose concentration Essential to restore normal cellular metabolism

26. Start insulin infusion after the patient has received initial volume expansion( 1hr after IV fluid treatment) Dose: 0.05-0.1 U/kg/hour of regular (soluble) insulin Route of administration: Intravenous (IV) An IV insulin bolus should not be used at the start of therapy: can precipitate shock by rapidly decreasing osmotic pressure, and can exacerbate hypokalemia. If IV cannulation is not possible due to severe dehydration, insulin can be administered IM.

27. Same dose until resolution of DKA(pH> 7.30,serum bicarbonate>18 mmol /L, BOHB <1mmol/L, or closure of anion gap) If insulin effect adequate –serum BOHB decrease by approximately 0.5mmol/L/ hr To prevent rapid decrease in plasma glucose concentration and hypoglycaemia, 5% glucose should be added to IV fluid when plasma glucose falls approximately 14-17mmol/L (250-300mg/dl) Use 10% or 12.5% dextrose to prevent hypoglycaemia, while continuing to use insulin infusion

28. SUBCUTANEOUS RAPID ACTING INSULIN ANALOG: Where continuous IV administration not possible/uncomplicated DKA Hourly or 2 hourly rapid acting insulin analogue(insulin lispro / aspart ) Dose SC: 0.15 units/kg every 2 hours (initiated 1 hour after the start of fluid replacement). The dose can be reduced to 0.1 unit/kg every 2 hours if BG continues to decrease by >5 mmol /L (90mg/ dL ) even after adding dextrose .

29. Subcutaneous administration of short-acting (regular ) insulin every 4 hours is another alternative in mild DKA when IV infusion or rapid acting insulin analogs are not available. Starting dose is 0.13-0.17 units/kg/dose of regular insulin every 4 hours (0.8 – 1 unit/kg/day in divided doses) . Dosing frequency may be increased to every 2 or 3 hours if acidosis is not improving.

30. Potassium replacement: The major loss of potassium is from the intracellular pool. 1.Transcellular shifts caused by hypertonicity and acidosis 2.Glycogenolysis and proteolysis secondary to insulin deficiency . Potassium is lost from the body via vomiting and osmotic diuresis. Volume depletion causes secondary hyperaldosteronism , which promotes urinary potassium excretion. In spite of total body depletion, serum potassium levels may be normal, increased or decreased at presentation

31. Renal dysfunction caused by DKA enhances hyperglycemia and reduces potassium excretion, thereby raising serum potassium concentrations at presentation . Administration of insulin and the correction of acidosis drives potassium back into the cells, decreasing serum potassium levels during DKA treatment . Insulin also has an aldosterone like effect leading to increased urinary potassium excretion.

32. High doses administered intravenously for a prolonged periods may contribute to hypokalemia despite potassium administration The duration and dosage of intravenous insulin should be minimized to decrease the risk of hypokalemia. The serum potassium concentration may decrease rapidly during treatment, predisposing the patient to cardiac arrhythmias.

33. Severe hypokalemia (<2.5mmol/L) is an independent marker of poor treatment outcome and mortality Potassium replacement is required regardless of the serum potassium concentration, except if renal failure is present. If hypokalemic -start potassium replacement at time of initial volume expansion, before starting insulin therapy

34. If hyperkalaemic , defer potassium replacement until urine output is documented ECG –hypo(prolonged PR interval, T wave flattening and inversion, ST depression, prominent U waves, apparent long QT interval) /hyperkalaemia( tall, peaked symmetrical T waves, shortening of QT interval)

35. If given with initial rapid volume expansion- give 20mmol/L Then 40mmol/L(potassium phosphate/chloride /acetate) Potassium chloride alone-risk of hyperchloremic metabolic acidosis. Should continue throughout IV fluid therapy Maximum 0.5mmol/kg/ hr If hypokalemia persists-rate of insulin infusion can be reduced

36. Phosphate: Depletion of intracellular phosphate ,lost due to osmotic diuresis , reduced renal tubular reabsorption of phosphate and a shift of intracellular phosphate to the extracellular compartment as a result of metabolic acidosis Plasma phosphate level falls after starting treatment, exacerbated by insulin(entry of phosphate into cells) Do not have symptoms until plasma phosphate <1mg/dl(0.32mmol/L) Clinical manifestations due to intracellular depletion-decreased intracellular ATP and decrease in2,3-DPG ,increases affinity of hemoglobin to oxygen-

37. Hypophosphatemia: Manifestations include- Metabolic encephalopathy Impaired myocardial contractility Respiratory failure-diaphragm weakness Proximal myopathy Dysphagia, ileus Hemolysis,decreased phagocytosis ,defective clot retraction, thrombocytopenia

38. Acidosis: Reversible by fluid and insulin replacement Insulin stops further ketoacid production , ketoacid metabolized,generates bicarbonates Bicarbonate therapy not indicated- cause- paradoxical CNS acidosis, hypokalemia Bicarbonate beneficial only rarely with life threatening hyperkalaemia, severe acidosis(<6.9),compromised cardiac contractility If given-dose-1-2 mmol /kg over 60minutes

39. Complications of therapy: Cerebral oedema Hypokalemia Hyperchloremic acidosis Hypoglycaemia Inadequate rehydration

40. Oral fluids and SC insulin: Substantial clinical improvement-start oral fluids Change to SC insulin –once ketoacidosis resolved, oral intake tolerated A dose of basal (long or intermediate acting )insulin should be administered in addition to rapid or short acting insulin Most convenient time to change to SC insulin is just before meal time

41. To prevent rebound hyperglycaemia, first SC insulin should be given 15-30minutes (with rapid acting insulin) or 1-2 hours (with regular insulin)before stopping insulin infusion to allow sufficient time for insulin to be absorbed After transitioning to SC insulin frequent blood glucose monitoring required to avoid hyper or hypoglycaemia.

42. Monitoring Hourly vital signs (HR, RR, BP) Hourly neurological observation(GCS)-warning signs and symptoms of cerebral edema Onset or worsening of head ache after starting DKA treatment Inappropriate slowing of HR Recurrence of vomiting Change in neurological status Rising BP Decreased SpO2 Rapidly increasing serum sodium concentration(loss of urinary free water due to interruption of blood flow to pituitary by cerebral herniation)

43. Morbidity and mortality Cerebral injury Hypokalemia Hypocalcemia , hypomagnesemia Severe hypophosphatemia Hyperchloremic alkalosis Hypoglycaemia ARDS Pneuomthorax Pneumomediastinum Subcutaneous emphysema Rhabdomyolysis Ischemic bowel necrosis AKI Acute pancreatitis Dural sinus thrombosis Cerebral infarction Venous thrombosis Pulmonary embolism Sepsis Pulmonary oedema Aspiration pneumonia Rhino cerebral /pulmonary mucormycosis

44. Cerebral edema : Rapid fluid administration with abrupt change in osmolality correlates with degree of dehydration and hyperventilation at presentation

45. Increased risk in- Younger age New onset DM Longer duration of symptoms Greater hypocapnia Increased BUN Severe acidosis Bicarb treatment for correction Early decrease in serum osmolality Attenuated rise in serum sodium concentration Greater volume of fluid in first 4 hours

46. Treatment: Head end elevation to 30deg Mannitol -0.5-1 g/kg IV over 10-15 minutes Hypertonic saline - 2.5-5 mL/kg over 10-15 minutes. 3% Hypertonic saline 2.5 mL/kg is equimolar to mannitol 0.5 g/kg Fluid adjusted-reduce to 2/3 rd CT only to rule out other pathologies Intubation if necessary

47. HHS- hyperglycemic hyperosmolar state Criteria: 1.Plasma glucose conc > 33.3mmol/L(600mg/dl) 2. Venous Ph >7.25/ arterial pH>7.3 3. Serum bicarbonate >15mmol/L 4. Small ketonuria , absent to mild ketonemia 5. Effective serum osmolality >320mOsm/kg