Diabetic Ketoacidosis management in pediatrics

Diabetic ketoacidosis management in pediatric age patients

1. WACHEMO UNIVERSITY NEMMCSH DEPARTMENT OF PEDIATRICS SEMINAR PRESENTATION ON Management of D iabetic keto acidosis (DKA)

2. Outline Introduction Pathophysiology Clinical manifestation Diagnosis Treatment complication cerebral edema

3. Introduction DM : a heterogeneous group of disorders in which metabolic disease characterized by hyperglycemia as a cardinal biochemical feature Etiologically Type 1 DM Type 2 DM Other specific types Gestational Diabetes

4. DM Complications Acute DKA HHS Hypoglycemia Chronic Microvacular Nephropathy, Neuropathy, Retinopathy Macrovascular CAD, PAM, Stroke

5. Diabetic ketoacidosis DKA : A state of absolute or relative insulin deficiency resulting in hyperglycemia, dehydration and accumulation of ketone bodies in the blood with subsequent metabolic acidosis . It is an acute and life threatening complication of T1DM Approximately 20–40% of children with new-onset diabetes progress to DKA before diagnosis

6. Risk factor for dka Children with poor metabolic control or previous episodes of DKA Peripubertal and adolescent girls Children with psychiatric disorders, including those with eating disorders Children with difficult or unstable family circumstances Children who omit insulin. Children with limited access to medical services Insulin pump therapy

7. Pathophysiology Excessive glucose production coupled with reduced glucose utilization raises serum glucose. This produces an osmotic diuresis, with loss of fluid and electrolytes, dehydration, and activation of the RAAS with accelerated potassium loss. Increased catabolic processes result in cellular losses of Na, K & P. Increased release of free fatty acids from peripheral fat stores supplies substrate for hepatic ketoacid production that result a metabolic acidosis ensues.

8. Clinical presentation HISTORY Classic triad = polydipsia, polyuria, and weight loss (polyphagia is unusual in children) Nausea, Vomiting and abdominal pain Dehydration manifested by weakness, orthostasis, and further weight loss. lethargy, altered mental status, and in extreme cases, coma.

9. Physical examination Vital signs (tachycardia, tachypnea, hypotension, kussmaul respiration) Hydration status/peripheral perfusion dry mouse, poor skin turgor, sunken eye Acetone-fruity breath Kussmaul respirations(deep, heavy, non-labored rapid breathing) Neurologic status Signs of infection

10. Diagnosis The biochemical criteria for the diagnosis of DKA are: Hyperglycemia (blood glucose >11 mmol/L [≈200 mg/dl]) Venous pH <7.3 or serum bicarbonate <18 mmol/L Ketonemia (blood ß-hydroxybuyrate ≥3 mmol/L) or moderate or large ketonuria.

11. Classification of Diabetic Ketoacidosis

12. Management of DKA Emergency assessment Follow guidline for pediatrics advaced life support Obtain vital signs and measure weight measure blood glucose and blood/urine ketone serum electrolytes and blood gases assessment of level of consciousness insert peripheral intravenous line

13. Goals of therapy Correct acidosis and reverse ketosis Correct dehydration Restore blood glucose to near normal Monitor for complications of DKA and its treatment Identify and treat any precipitating event

14. Principles ABCs Fluid and electrolyte replacement therapy Potasium replacement theraphy Insulin Monitoring Treatment of precipitating factor Prevention and treatment of complications

15. Fluid and electrolyte replacement

16. ... For children who are volume depleted but not in shock, resuscitation should begin immediately with 0.9% saline, 10 to 20 ml/kg infused over 20–30 min. If tissue perfusion is poor the initial fluid bolus volume should be 20 ml/kg. In the rare child with DKA in shock , rapidly restore circulatory volume with 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.

17. ... Subsequent fluid replacement then consists of 0.45% or 0.9% sodium chloride infused at a rate calculated to replace the fluid deficit (after subtracting initial fluid bolus) over 24-48 hr plus maintenance The fluid deficit can be calculated empirically estimated at 5–10% of body weight based upon clinical severity, or by assuming a standard water deficit (85 mL/kg)

18. ... The objectives of fluid and electrolyte replacement therapy are to: • Restore circulating volume • Replace sodium and water deficits • Improve glomerular filtration and enhance clearance of glucose and ketones from the blood.

19. Potassium replacement Children with DKA have total body potassium deficits In spite of total body depletion, serum potassium levels may be normal, increased, or decreased at presentatio n. Potassium replacement is required regardless of the serum potassium concentration, except if renal failure

20. ... Causes of potasium deficit transcellular shifts caused by hypertonicity and acidosis glycogenolysis and proteolysis secondary to insulin defeciency vomiting and osmotic diuresis secondary hyperaldosteronism treatment related

21. ... If the child is hypokalemi c , start potassium replacement at the time of initial volume expansion and before starting insulin therapy. For rare children with initial potassium levels <3.5 mmol/L, defer insulin treatment and give a bolus of potassium (not to exceed 0.5 mmol/Kg/h), along with cardiac monitoring. Otherwise, start-replacing potassium after initial volume expansion and concurrent with starting insulin therapy.

22. ... If the child is hyperkalemic, defer potassium replacement therapy until urine output is documented Begin infusion with non-potassium fluids, remeasure potassium hourly, and begin potassium infusion when serum potassium is below 5.5 mmol/L

23. ... The starting potassium concentration in the infusate should be 40 mmol/L. subsequent potassium replacement therapy should be based on serum potassium measurements Potassium phosphate may be used together with potassium chloride or acetate

24. Insulin therapy Using infusion Start insulin infusion 1 h after initiation of IV fluid treatment An initial insulin "bolus" or loading dose is unnecessary 0.05–0.1 U/kg/h at least until resolution of DKA Add 5% glucose to the IV fluid if plasma glucose falls to 250–300 mg/dl 10% or 12.5% glucose may be needed if plasma glucose falls below 150 mg/dl

25. ... If continous IV infusion not possible Rapid acting insulin 0.15 units/kg every 2 h SC Regular insulin 0.13–0.17 units/kg/dose every 4h SC Increase to 0.5 units/kg every 6 hour SC

26. ... Any child can be easily transitioned to oral intake and subcutaneous insulin when DKA has resolved total CO2 > 15 mEq/L; pH >7.30 sodium stable between 135 and 145mEq/L anion gap closed no emesis

27. Starting Doses of Subcutaneous Insulin Starting dose may range from 0.4 -1.2 units/kg/day Depends on factors like age, pubertal stage, and presence or absence of DKA Prepubertal children without DKA can be started on a dose of 0.4-­0.6 units/kg/day Pubertal adolescents presenting with DKA may need up to1-­1.2 units/kg/day

28. Overview Insulin types

29. Benefits of insulin therapy to restore normal cellular metabolism to suppress lipolysis and ketogenesis to normalize blood glucose concentrations

30. 5. clinical and biochemical monitoring Hourly Vital signs (heart rate, respiratory rate, blood pressure) Neurological assessment Amount of administered insulin Accurate fluid input (including all oral fluid) and output. Capillary blood glucose concentration

31. … every 2–4 h Serum electrolytes, blood urea nitrogen, calcium, magnesium, phosphate, and blood gases Blood BOHB concentrations

32. Complications Mortality Permanent severe neurological sequelae Renal tubular damage and AKI Hypokalemia Hypoglycemia DVT Pulmonary embolism Rhinocerebral or pulmonary mucormycosis Aspiration pneumonia Pulmonary edema

33. … Hypocalcemia, hypomagnesemia Severe hypophosphatemia Hyperchloremic acidosis Hypochloremic alkalosis Other central nervous system complications Adult respiratory distress syndrome (ARDS) Pneumothorax, pneumomediastinum and subcutaneous emphysema Rhabdomyolysis Ischemic bowel necrosis Acute pancreatitis

34. Cerebral edema The incidence of clinically overt DKA-related cerebral injury is 0.5%– 0.9% and the mortality rate is 21%–24%. more recent evidence about its pathogensis suggests that cerebral hypoperfusion and the hyperinflammatory state caused by DKA play central roles.

35. Risk factors Younger age New onset diabetes Longer duration of symptoms Greater hypocapnia at presentation after adjusting for degree of acidosis Increased serum urea nitrogen at presentation More severe acidosis at presentation Bicarbonate treatment for correction of acidosis An attenuated rise in measured serum sodium concentrations during therapy Greater volumes of fluid given in the first 4 hours Administration of insulin in the first hour of fluid treatment

36. Warning signs and symptoms Headache & slowing of heart rate Change in neurological status (restlessness,irritability, increased drowsiness, incontinence) Specific neurological signs (e.g., cranial nerve palsies) Rising blood pressure Decreased O2 saturation Clinically significant cerebral edema usually develops within the first 12 hours after treatment has started , but can occur before treatment has begun or, rarely, may develop as late as 24–48 hours after the start of treatment.

37. Diagnosis Diagnostic criteria Abnormal motor or verbal response to pain Decorticate or decerebrate posture Cranial nerve palsy (especially III, IV, and VI) Abnormal neurogenic respiratory pattern (e.g. grunting, tachypnea, Cheyne-Stokes respiration, apneusis)

38. Major criteria Altered mentation, confusion, fluctuating level of consciousness Sustained heart rate deceleration (decrease more than 20 beats per minute) not attributable to improved intravascular volume or sleep state Age-inappropriate incontinence

39. Minor criteria Vomiting Headache Lethargy or not easily arousable Diastolic blood pressure > 90 mmHg Age <5

40. Diagnosis One diagnostic criteri a , two major criteria, or one major and two minor criteria have a sensitivity of 92% and a false positive rate of only 4%. Signs that occur before treatment should not be considered in the diagnosis. Neuroimaging is not required for diagnosis.

41. Treatment Mannitol, 0.5–1 g/kg IV over 10–15 min. The effect should be apparent after 15 min. If necessary, the dose can be repeated after 30 min. Hypertonic saline (3%), suggested dose 2.5–5 ml/kg over 10–15 min, may be used as an alternative to mannitol, or in addition to mannitol if there has been no response to mannitol within 15–30 min.

42. Prevention Diabetic education Increase awareness of professionals and families about managing sick days and insulin pump failures Identifying high-risk individuals through family history, genetic, and immunologic screening Psychological counselling

43. References Nelson text book of pediatrics 22 nd edition ISPAD Clinical Practice Consensus Guidelines 2022 Uptodate

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