DIABETIC KETOACIDOSIS. and ISPAD classification

DKA with ISPAD classification

1. DIABETIC KETOACIDOSIS PROTOCOL ISPAD 2018

2. INTRODUCTION DKA results either from absolute insulin deficiency or from relative insulin deficiency in the settings of high levels of counter regulatory hormones stimulated by infection or other illness . DKA is characterised by hyperglycemia , ketosis and acidosis . Cerebral edema is the most frequent serious complication of DKA in children and is most frequent cause of morbidity and mortality from DKA .

3. HOW TO IDENTIFY A PATIENT OF DKA BIOCHEMICAL CRITERIA HYPERGLYCEMIA ( BG >11 mmol /L or 200 mg/dl ) Venous PH < 7.3 or Sr HCO3 <15 mmol /L Ketonemia or ketoneuria a) BOHB > 3 mmol /l b) urine ketone > 2 + Venous PH is most important parameter in diagnosing DKA even in euglycemic ketoacidosis .

4. CLINICAL FEATURES TACHYCARDIA DROWSINESS TACHYPNEA ALTERED SENSORIUM SIGNS OF DEHYDRATION DEEP SIGHING RESPIRATION NAUSEA /VOMITING PAIN ABDOMEN BREATH SMELLS OF ACETONE BLURRING OF VISION CONFUSION

5. EMERGENCY ASSESMENT SEVERITY ASSESMENT ISPAD MILD MODERATE SEVERE PH < 7.3 < 7.2 <7.1 HCO3 <15 < 10 < 5

6. Emergency assessment of DKA follows PALS guidelines It includes – Immediate measurement of blood glucose Blood/ urine ketone Serum electrolytes Blood gases Weight ( current weight , not from previous hospital record ) Blood count

7. SEVERITY OF DEHYDRATION In children ( 1month – 5 yr ) 1) CRT 2) Skin turgor MILD MODERATE SEVERE 5% 7 % 10%

8. Signs of dehydration 1)dry mucous membrane 2) sunken eyes 3) absent tears 4) cold extremeties > 10 % dehydration present as hypotension / impalpable or weak peripheral pulse / oliguria

9. Asses level of consciousness Put 2 intravenous catheter Give oxygen to patient if presents in circulatory impairement or shock Cardiac monitoring by EEG ( T waves changes in hypo / hyperkalemia ) Antibiotics - for febrile patients ( after obtaining cultures positive) Bladder catheterisation – it is not necessary indicated 1) unconscious child 2) unable to void on demand ( infants and very ill young children)

10. MISINTERPRETATIONS When hyperchloremia develops, a persisting base deficit or low bicarbonate concentration can be erroneously interpreted as being due to ongoing ketosis . Acidifying effect of chloride can mask recognition of resolution of ketoacidosis . To asses correctly the ketoacidosis – Measurement of bedside BOHB levels

11. MONITORING VITAL SIGNS ( HR /RR/BP ) GCS BLOOD GLUCOSE ( 2-4 HR ) SERUM ELECTROLYTES ( 2- 4 HRLY ) Serum sodium increases due to loss of urinary free water as manifestation of DI BLOOD GAS ( 2- 4 HRLY ) INPUT /OUPUT MONITERING ( EVERY HOURLY ) BODY WEIGHT MEASUREMENT ( OD)

12. MONITOR FOR CEREBRAL EDEMA Onset of headache after starting treatment for DKA or worsening of headache . Inappropiate slowing of HR Recurrent vomiting Change in neurogical status ( restlessness ,irritability , increase drowsiness, confusion ,incontinence) Neurological sign – a ) cranial nerve palsies b) abnormal pupillary response

13. INVESTIGATION SERUM GLUCOSE SERUM ELECTROLYTES ( INCLUDING SR HCO3) RFT SERUM OSMOLALITY ABG CBC ( increase WBC is feature of stress response of DKA not indicative of infection) HbA1C ( optional) SERUM Calcium/phosphorus /magnesium/ alumin ( optional)

14. MANAGEMENT GOALS OF THERAPY Correct acidosis /reverse ketosis Correct dehydration Restore blood glucose to near normal Monitor for complication of DKA and its treatment related complication Identify and treat any precipitating event

15. FLUID THERAPY

16. DEFICIT FLUID REPLACEMENT DEFICIT = MILD ( 5% i.e 50 ml/kg) MODERATE ( 7% i.e 70 ml/kg) SEVERE ( 10 % i.e 100 ml/kg ) Maintenance fluid calculation by HOLIDAY SEGAR FORMULA ( calculated for 48 hr ) TOTAL FLUID TO BE GIVEN = DEFICIT + MAINTENANCE - BOLUS 47

17. RESUSCITATION FLUID TYPE OF FLUID – 0.9% NS ( colloid is not recommended in treatment of DKA ) DOSE – 10mL/KG Rarely in patient with DKA with shock rapidly restore circulatory volume with isotonic saline with 20 ml/kg infused as quickly as possible with large bore cannula Reassessment of circulatory shock after each bolus . DURATION – over 30 – 60 MINS ( if tissue perfusion is poor initial fluid bolus is given more rapidly over 15 – 30 mins ) .

18. DEFICIT FLUID REPLACEMENT TYPE OF FLUID – 0.9 % NS / 0.45% NS / Balanced salt solution ( RL / Hartmann’s solution / Plasmalyte ) Decision of fluid replacement to be made based on clinical judgement of patient hydration status ,serum sodium and osmolality . DURATION – 24 or 48 hrs REPLACEMENT OF URINARY LOSSES – not routinely recommended ( required in rare circumstances ) .

19. Sodium content of fluid should be increased if measured serum sodium concentration is low and does not rise appropriately as plasma glucose concentration . HYPERCHLOREMIA - The use of large amounts of chloride-rich fluids (combined with preferential renal excretion of ketones over chloride) may be associated with the rapid development of hyperchloremia 121–123 (defined as a ratio of chloride : sodium [ Cl − :Na+ ] > 0.79124) and hyperchloremic metabolic acidosis .

20. The chloride load can be reduced by not giving potassium as potassium chloride (use potassium acetate instead) and by using fluids such Ringer's lactate or Plasmalyte in which a portion of the chloride is replaced by lactate or acetate . Calculation of anion gap ( 2 limitation of hyperchloremia - mixed metabolic acidosis ( hyperchloremic and ketotic ), and the degree of hyperchloremic acidosis is not quantifiable ) Chloride induced base = (plasma sodium − plasma chloride − 32) deficit

21. INSULIN THERAPY DKA is caused by a decrease in the effective circulating insulin level associated with increases in counter-regulatory hormone concentrations. Rehydration alone frequently causes a marked decrease in blood glucose concentration . Insulin therapy is essential to restore normal cellular metabolism, to suppress lipolysis, ketogenesis and to normalize blood glucose concentrations .

22. WHEN TO START - Start insulin infusion at least 1 hour after starting fluid replacement therapy ( after the patient has received initial volume expansion ) . Correction of insulin deficiency Dose: 0.05 to 0.1 unit/kg/h ( eg , one method is to dilute 40 units regular [soluble] insulin in 39 mL normal saline i.e 1 unit = 1 Ml Route of administration IV An IV bolus should not be used at the start of therapy (increase the risk of cerebral edema, can precipitate shock by rapidly decreasing osmotic pressure, and can exacerbate hypokalemia )

23. Rate of decrease – 2- 5 mmol /L/h If BSL falls rapidly i.e > 5 mmol /L/h after initial fluid expansion , consider adding glucose even before plasma glucose decrease to >7mmol/l ( 300 mg/dl) . If IV insulin administration is not possible – In patient of uncomplicated DKA consider giving s/c rapidly acting insulin ( peripheral circulation should be good ) Dose – initially – s/c – 0.3 u/kg after 1 hr 0.1 u/kg every hour or 0.15 - .20 u /kg every 2- 3 hr .

24. Short acting insulin can also be used s/c every 4 hrs . Dose – 0.8 – 1 u/kg /day for 24 hrs – divided by 6 . RESOLUTION OF DKA -1) pH >7.30 2) serum bicarbonate >15 mmol /L, BOHB <1 mmol /L 3) closure of the anion gap .

25. POTASSIUM REPLACEMENT Potassium losses occur by following mechanism – Transcellular shifts caused by hypertonicity (increased plasma osmolality causes solvent drag in which water and potassium are drawn out of cells) . Acidosis Glycogenolysis Proteolysis secondary to insulin deficiency Potassium is lost from the body from vomiting and osmotic diuresis.

26. Volume depletion causes secondary hyperaldosteronism , which promotes urinary potassium excretion. At presentation serum potassium levels may be normal, increased or decreased . If hypokalemia persists despite a maximum rate of potassium replacement, then the rate of insulin infusion can be reduced .

27. Profound hypokalemia (<2.5 mmol /L) in untreated DKA is rare and necessitates vigorous potassium replacement while delaying the start of insulin therapy until serum potassium levels are >2.5 mmol /L to reduce the risk of cardiopulmonary and neuromuscular compromise .

28. PHOSPHATE REPLACEMENT Depletion of intracellular phosphate occurs as a result of osmotic diuresis . Plasma phosphate levels fall after starting treatment and this is exacerbated by insulin ( which promotes entry of phosphate into cells)

29. SYMPTOMS OF HYPOPHASTEMIA Metabolic encephalopathy (irritability, paresthesias , confusion, seizures, coma). Impaired myocardial contractility Respiratory failure due to weakness of the diaphragm Muscle dysfunction with proximal myopathy, dysphagia and ileus; rare Hematologic effects include hemolysis , decreased phagocytosis and granulocyte chemotaxis , defective clot retraction, and thrombocytopenia. Acute hypophosphatemia in a patient with pre-existing severe phosphate depletion can lead to rhabdomyolysis .

30. Administration of phosphate may induce hypocalcemia . Potassium phosphate salts may be safely used as an alternative to or combined with potassium chloride or acetate .

31. ACIDOSIS Severe acidosis is reversible by fluid and insulin replacement . Fluid replacement - improves tissue perfusion and renal function, thereby increasing the excretion of organic acids . Insulin – it stops further ketoacid production and allows ketoacids to be metabolized .

32. BICARBONATE THERAPY INDICATION - Bicarbonate administration may be beneficial in the rare patient with life-threatening hyperkalemia or unusually severe acidosis ( vpH <6.9) that has compromised cardiac contractility . DOSE - 1 to 2 mmol /kg over 60 minutes .

33. CHECK LIST FOR NONRESOLVING ACIDOSIS Check IV Line Check insulin infusion and priming ( check expiry ) Check fluid calculations Check renal function Hyperchloremic metabolic acidosis and IEM Methylmalonic academia Replace urine output Appropriate fluid bolus Focus of infection and its treatment Hypophosphatemia Hyperthyroidism

34. TRANSITION TO SC INSULIN First SC injection should be given 15 to 30 minutes (with rapid-acting insulin) or 1 to2 hours (with regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed . SLIDING SCALE – BSL < 90 – NO INSULIN 90- 180 – 0.1 U/Kg 180 – 270 – 0.24 U/Kg 270 – 360 – 0.34 U /Kg >360 – 0.54 U /Kg

35. ISPAD 2014 DEFICIT FLUID REPLACEMENT – 0.9%NS MAINTENANCE FLUID DURATION -48 HRS INSULIN THERAPY - ISPAD 2018 .45% - 0.9 % NS 24 – 48 HRS Increase the insulin dose if the expected rate of biochemical improvement does not occur

36. ISPAD 2014 IN CASES WHERE IV INSULIN IS NOT POSSIBLE – Give s/c rapid acting insulin . ISPAD 2018 For less severe DKA (pH >7.1-7.2), 0.05 U/kg/h (0.03 U/kg/h for age<5 years with mild DKA) is usually sufficient to resolve the acidosis . S/C rapid acting insulin as well as S/c regular insulin can also be used .

37. ISPAD 2014 POTASSIUM - ISPAD 2018 Profound hypokalemia (<2.5 mmol /L) necessitates vigorous potassium replacement while delaying the start of insulin therapy until serum potassium levels are >2.5 mmol /L to reduce the risk of cardiopulmonary and neuromuscular compromise .

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