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Management Guideline for

Diabetic Ketoacidosis of

Childhood and Adolescence 2544

Diabetic Ketoacidosis (DKA)

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insulin insulin 1. Hyperglycemia glucose gluconeogenesis glycogenolysis glucose (underutilization) 2. Ketosis lipolysis ketogenesis ketonemia 3. Hypertriglyceridemia free fatty acid 4. Osmotic diuresis hyperglycemia glucose, sodium potassium electrolyte imbalance 5. Volume depletion hyperglycemia, glucosuria osmotic diuresis dehydration

type I DM DKA

- (hyperglycemia) (polydipsia), (polyuria), (nocturnal enuresis) - , (weight loss), (weakness)

(stress) precipitating factor DKA (Kussmaul breathing) metabolic acidosis (coma) dehydration acetone DKA

1. Serum glucose >250 mg/dl 2. Acidosis : HCO3

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1. 2. . blood glucose ( ketone ) . urine ketone glucose . blood gas pH, pCO2, base excess (), arterial pH venous pH 0.05 3. (assessment of degree of dehydration)

DKA 1. 0.9% NaCl, 0.45% NaCl, 5% dextrose

0.3% NaCl, 2.5% dextrose 0.45% NaCl 2. electrolyte KCl vial (1 ml = 2 mmol), KH2PO4 vial (1 ml = K 2 mmol) PO4 , NaHCO3 vial (1 ml = HCO3 1 mmol)

3. insulin short acting insulin regular insulin (RI)

4. Intravenous-drip set 5. Infusion pump 6. Flow sheet 7. (blood glucose meter) (test strips)

ketone (ketodiastix) initial investigation For DKA 1. Glucose ketone 2. Serum electrolyte, BUN, Cr, Ca, PO4 CBC

3. Blood gas ( severe DKA, coma) capillary arterial blood gas 4. EKG hypo hyperkalemia For precipitating cause

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1. Hemoculture 2. Urinalysis

3. CXR if indicated For DM

1. HbA1c 2. Insulin C-peptide

3. Insulin autoantibody (IAA), Islet cell antibody (ICA), Anti GAD 2, 3 () DKA 1. fluid dehydration

. degree of dehydration DKA dehydration 7 10 % . impending shock , , initial rehydration 0.9% NaCl 10 20 ml/kg/hr 1 2 50 ml/kg 4 . fluid maintenance + deficit (7 10%) 36 48 (fluid dehydration fluid initial rehydration 1-2 .. ) 0.45% NaCl ( 0.9% NaCl 0.45% NaCl hypernatremia ) fluid 24 4 // 1. 0.9% NaCl 2. corrected serum Na (Na < 130 mmol/L) ( Na) 0.9% NaCl serum electrolyte 3. increased intracranial pressure hypernatremia (Na >150 mmol/L) deficit 48 0.45% NaCl fluid osmolality fluid cerebral edema

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. KCl initial rehydration insulin injection renal failure / hyperkalemia serum K > 6 mmol/L KCl 3 . fluid balance re-evaluate fluid status 2 3 . NPO DKA ( mild DKA ) 2. insulin replacement insulin initial rehydration regular insulin (RI) 2 1) Continuous low-dose intravenous insulin infusion method . regular insulin 0.1 unit/kg/hr insulin infusion RI 50 unit 0.9 % NaCl 500 ml RI 1 unit 10 ml 1 ml RI 0.1 unit RI 50 unit 50 ml 1 ml RI 1 unit insulin infusion infusion pump dose insulin side line fluid insulin plastic infusion set insulin insulin infusion 30 50 ml saturate binding site 1. insulin IV bolus insulin infusion 2. initial rehydration RI infusion 50-200 mg/dl dehydration RI

. blood glucose 75 100 mg/dl . monitor hypoglycemia bedside blood glucose 1 . blood glucose 250-300 mg/dl rehydration fluid 5% dextrose 0.45% NaCl

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insulin infusion dextrose blood glucose 120- 250 mg/dl . Insulin infusion acidosis ketonemia insulin 5% dextrose blood glucose 150- 250 mg/dl blood glucose ( 150 mg/dl) insulin ( 0.05 unit/kg/hr) dextrose 7.5 10% ketonemia acidosis insulin insulin infusion subcutaneous (SC) insulin SC dose -1 insulin infusion insulin rebound hyperglycemia 2) Intramuscular (IM) insulin administration . RI 0.1 unit/kg IM 1 blood glucose 250 300 mg/dl RI 0.25 - 0.5 unit/kg SC 4 6 infusion pump severe acidosis, peripheral perfusion insulin . insulin IM continuous insulin infusion 1-2 . fluid replacement 1) 3. potassium (K) . Potassium insulin DKA total body K K initial rehydration K 6 mmol/L EKG tall peak T wave

Serum K (mmol/L) K fluid 1 (mmol)

< 3.5 60 3.5 5.4 40 5.5 6 20

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K 0.3 mmol/Kg/hr . K KCl KH2PO4 DKA phosphate phosphate 2,3-diphosphoglycerate shift oxyhemoglobin dissociation curve oxygen hyperchloremia ( phosphate) . severe acidosis serum K < 3 mmol/L severe potassium depletion K insulin cardiac arrhythmia severe hypokalemia KCl 20 30 mmol fluid 1 3 4. sodium (Na)

serum Na DKA blood glucose corrected sodium

Corrected Na = Na (mmol/L) + (Blood glucose (mg/dl)100)x 1.6

100 serum Na 150 mmol/L hypernatremia hyperosmolar Na glucose cerebral edema fluid deficit 48 corrected Na 160 mmol/L hyperlipidaemia psuedohyponatremia 5. bicarbonate (HCO3) . acidosis fluid dehydration insulin bicarbonate HCO3 cerebral edema

(1)

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(2) Severe acidosis pH < 7.0 blood gas HCO3 < 8 mmol/L

HCO3 deficit

7.5% NaHCO3 (ml) = 1/3 x0.3 x base excess x BW (kg) intravenous drip blood gas NaHCO3

7.5% NaHCO3 (ml) = 0.3 x BW (kg) x (10-HCO3)

HCO3 10 mmol/L . bicarbonate paradoxical cerebral acidosis, shift to the left of oxyhemoglobin dissociation curve peripheral oxygen availability severe hypokalemia K monitor EKG 6. phosphate (PO4) DKA PO4 deficit serum PO4 acidosis insulin serum PO4 PO4 PO4 hypocalcemia serum PO4 1 mg/dl PO4 KH2PO4 20-30 mmol/L serum Ca PO4 7. monitor

DKA ICU

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. vital sign neurosign 1 . . blood glucose 1 . . serum electrolyte, blood gas () 2 4 . . intake output 2 4 . . urine ketone 6 . 250 mg/dl . serum BUN, Cr, Ca, PO4 severe DKA . flowsheet . naso-gastric tube urinary catheter 8. precipitating factor

antibiotics routine DKA bacterial infection urinalysis, urine culture, CXR, hemoculture, tuberculin test 9. DKA . Hypoglycemia continuous insulin infusion monitor blood glucose . Persistent acidosis HCO3 < 10 mmol/L 8 10 hyperglycemia - insulin insulin insulin intramuscular intravenous infusion - Imbalanced fluid intake - Infection - hyponatremia, hypokalemia hyperchloremic acidosis chloride - Insulin . Hypokalemia K acidosis K shift K

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K K muscle weakness . Intracranial complication brain edema 24 < 5 brain edema decreased sensorium, sudden and severe headache, incontinence, vomiting, disorientation, agitation, changes in vital signs, pupillary change, ophthalmoplegia, papilledema, seizures

< 5 severe DKA 1) monitor ICU 2) cerebral edema

- Mannitol 1 2 g/kg intravenous infusion - Intubation hyperventilation

coma - Monitor neurological sign CT brain

DKA

1. fluid replacement ( ) metabolic blood glucose 7.3 serum HCO3 > 15 mmol/L ketosis

2. insulin infusion metabolic blood glucose < 300 mg/dl, pH > 7.3 serum HCO3 > 15 mmol/L regular insulin subcutaneous 0.25 0.5 unit/kg insulin infusion

3. subcutaneous regular insulin subcutaneous regular insulin 0.25 0.5 unit/kg/dose

3 1 2 acidosis regular insulin intermediate acting insulin (NPH) total dose insulin 0.7 1.0 unit/kg/day 2 3

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( NPH : regular insulin 2 : 1) 1 3 ( NPH : regular insulin 1 : 1) 4. carbohydrate 50 55% , fat 25 30%, protein 1520% 5. ketone blood glucose , , , , 3 hypoglycemia urine ketone blood glucose > 250 mg/dl insulin 70 180 mg/dl 6. DKA . . Insulin insulin . . . hypoglycemia hyperglycemia . 1 2 1. , . : , , , , (). 3. : , 2542 : 2203-15. 2. . Diabetic ketoacidosis : , , , , , (). 3. : , 2542 : 2216-23. 3. Brink SJ. Presentation and ketoacidosis. In : Kelnar CJH. (ed). Childhood and adolescent

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diabetes. 1st ed . London. Chapman Hall, 1995:213-39. 4. Fairchild J. Insulin infusion protocol for diabetic ketoacidosis in childhood and adolescence. Diabetes Center, The Ray William Institute of Pediatric Endocrinology, Pediatric and Metabolic Jan 1990. 5. Brenchley S, Govindji A. Dietary management of children with diabetes. In : kelnar CJH (ed). Childhood and adolescent diabeties, 1st ed. Candon. Chapman Hall. 1995:271-81. 6. Kuzuya T. Diabetic ketoacidosis and nonketotic hyperglycemia. In : Turtle JR et al.(ed) Diabetes in the new millennium. Sydney: The Pot Still Press, 1999: 297-306. 7. Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J,

et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001; 344:264-9.

8. International Society for Pediatric and Adolescent Diabetes. Diabetic ketoacidosis. In :

Consensus guidelines 2000. Zeist : Medical forum international, 2000:63-73. 9. American Diabetes Association. Hyperglycemic crises in

patients with diabetes mellitus. Diab Care 2001; 24(Suppl 1):S83-90. 10. White NH. Diabetic ketoacidosis in children. Endocrinol

Metab Clin North Am 2000; 29:657-82.

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