IN THE NAME OF GOD

DKA Management M. Hashemipour بهمن 1395 Pediatric Endocrinologist Isfahan university of medical sciences بهمن 1395

Case study کودک 6 ساله ای با وزن 20 کیلو گرم با تنفس تند به اورژانس وارد شده در بدو ورود شما چیست؟ PH=6.9 ,CO3H= 5 NA=135 K=5.5 BS=624

DKA Defined Plasma glucose >200 mg/dl Arterial pH <7.30 Bicarbonate level <15 mEq/l ketonemia>3 mmol/L Moderate ketonuria Pediatr Clin N Am 2005 Pediatric Diabetes 2014 ISPAD clinical practice consensus guidelines 2014

severe moderate mild parameter 10-15 6-10 3-5 <5 <10 <15 Volume deficit(%) <5 <10 <15 Co3 H <7.1 <7.2 <7.3 PH >600 400-600 300-400 Blood sugar >30 ≥30 ≥25 BUN Pediatric Diabetes 2014 Endocrinology and Metabolism clinics of north America 2006 ISPAD clinical practice consensus guidelines 2014

How to Treat DKA

How to Assess severity of Dehydration Prolonged capillary refill time Abnormal skin turgor Abnormal respiratory pattern sunken eyes, absent tears weak pulses, and cool extremities level of consciousness Pediatric Diabetes 2014

Lab Measurement Blood gases Blood or urine ketones serum electrolytes Full blood count Blood urea nitrogen, creatinine Serum osmolality ECG for baseline evaluation of potassium Pediatric Diabetes 2014

The goals of therapy improvement of circulatory volume and tissue perfusion Correct acidosis and reverse ketosis slowly Reduction of serum glucose and plasma osmolarity

The goals of therapy identification and prompt treatment of comorbid precipitating causes. correction of electrolyte imbalance Improved glomerular filtration increase clearance of glucose and ketones from the blood

کودک 6 ساله ای با وزن 20 کیلو گرم با تنفس تند به اورژانس وارد شده در بدو ورود PH=6.9 ,CO3H= 5 NA=135 K=5.5 BS=624

چه درجه ای از DKA مطرح است درمان را چگونه آغاز می کنید؟ کنترل قند خون با انسولین چگونه است؟ قند خون در چه سطحی باید حفظ شود؟ میزان ونوع مایع دریافتی به بیمار چگونه خواهد بود؟

Severe DKA

Step1 Fluid Therapy

Step2 Evaluation of predisposing factors

Step3 Adding K to IV fluid after urination

Step4 Insulin therapy

Step5 Bicarbonate therapy??????

Step6 Monitoring Vital sign Level of consciousness

Volume Expansion Shock? 0.9% NaCl 20 ml/kg bolus. Repeat if necessary No Shock 0.9 % NaCl 10 ml/kg /h over 1-2 hours

Volume Expansion Repeated if Shock Hypotension Delay capillary refilling Decrease tissue perfusion Not exceed 30 ml/kg

Fluid therapy Maintenance Deficit Abnormal ongoing loss

Fluid deficit Grade of dehydration 5% to 10% In mild to moderately DKA, fluid deficits 30 to 50 mL/kg. In moderate to severe DKA, fluid deficits 50 to 100mL/kg.

Fluid therapy To replace the estimated fluid deficit evenly Over36- 48 h. ISPAD clinical practice consensus guidelines 2014

Milwaukee formula Iv rate= 85cc/kg+maintenance- bolus÷ 23hr Iv rate= 85* 20 +1500-300 ÷ 23hr Iv rate= 126 cc /hr Nelson 2014

Second Method First day 1.5-2 times the 24 h maintenance requirements with isotonic solution 0.9% saline,Ringer’s lactate for at least 4–6 h Then half salin 0.45% salin Pediatric Diabetes 2014 ISPAD clinical practice consensus guidelines 2014

second Method WT= 20kg Maintenance =1500cc Fluid requirement for DKA=2*1500 Fluid requirement for DKA=1.5*1500

Pediatric Fluid therapy Usually 1.5 times the 24 h maintenance requirements Urinary losses should not be added to the calculation of replacement fluids Pediatrics 2004;113;133-140 Pediatric Diabetes 2014 ISPAD clinical practice consensus guidelines 2014

Third method Begin with 0.9% NaCl. Weight (kg) Infusion rate (ml/kg/h) 4 – 9 6 10 – 19 5 20 – 39 4 40 - 59 3.5 60 - 80 3 ISPAD clinical practice consensus guidelines 2014

Forth method No transport available ORS 5 ml/kg/h Give . as fruit juice or coconut water if ORS is not available. Give SC insulin 0.05 U/kg every 1-2 hours 0.025 U/kg if < 5 years ISPAD clinical practice consensus guidelines 2014

Improved condition? Decreasing blood glucose AND decreasing ketones in urine indicate resolving of acidosis

ساعت 6 درمان قند خون بیمار 250 است نوع و میزان مایع 6 ساعت بعدی را بنویسید

Second Method Iv rate= 85cc/kg+maintenance- bolus÷ 23hr Iv rate= 85* 20 +1500-300 ÷ 23hr Iv rate= 126 cc /hr

مایع 6 ساعت بعدی 126*6 = 756 cc دکستروز5% همراه با 75 میلی اکی والان سدیم درلیتر در واقع در مایع فوق 56 میلی اکی والان سدیم باید باشد بنابر این در مایع فوق 81 سی سی سدیم کلراید 20% می ریزیم هر 1 سی سی سدیم کلراید 20% حاوی 3.2 میلی اکی والان سدیم است

Fluid therapy Dextrose 5% was added in 0.45% NS to the rehydrating solution once the blood glucose fell to200- 300 mg/dL Pediatr Crit Care Med 2004 Endocrinol Metab Clin N Am 2006 Pediatric Diabetes 2014 ISPAD clinical practice consensus guidelines 2014

Glucose concentration during DKA plasma glucose typically decreases At a rate of 40-90 mg /dl/h Depending on the timing and amount of glucose administration

When we add dextrose? If blood glucose falls very rapidly >90 mg/dl/h) after initial fluid expansion Consider adding glucose even before plasma glucose has decreased to 300 mg/dl

When we add dextrose? Acidosis with BS 100-200mg/dl Add%7.5 dextrose to solution Insulin should be continue

When we add dextrose? Acidosis with BS <100mg/dl Add%10 dextrose to solution Insulin should be continue

When we discontinue intravenous fluids? . Administration of intravenous fluids should be continued until acidosis is corrected and a patient can tolerate fluids and food. Pediatr Clin N Am 52 (2005) 1147– 1163

Fluid therapy Maintain the blood glucose 100 and 200 mg/dL.

When we added potassium? At same time as insulin treatment After urination Pediatr Crit Care Med 2004 Vol. 5, No. 5

Potassium The plasma potassium concentration should be rechecked every 1 to 2 hours if the plasma concentration is outside the normal range.

Potassium potassium 40meq/li k<3mEq/l insulin should be hold temporary Give 0.5 -1mmol/kg/h iv and oral Endocrinol Metab Clin N Am 35 (2006) 725–751

K>5 meq/l Don’t give K till reversal of k<5meq/l

Indication of Bicarbonate therapy life-threatening hyperkalemia. severe acidosis pH<6.9 Hypotension shock Arrhythmia

Bicarbonate Therapy After 2-3hours of hydration if severe acidaemia pH <7.0 or bicarbonate <5 mEq A state of shock it may be appropriate to use bicarbonate Give 1meq/kg over 1 hour ISPAD clinical practice consensus guidelines 2014

Biochemical& Clinical monitoring Critical Observations Hourly blood glucose Hourly fluid input & output Neurological status at least hourly Electrolytes 2 hourly after start of IV therapy Monitor ECG for T-wave changes

Biochemical& clinical monitoring Repeated 2–4 h, or more frequently, as clinically indicated

insulin therapy Begin with 0.05–0.1 U/kg/h 1–2 h after starting fluid replacement therapy

insulin therapy IV dose 0.1 U/kg/h (0.05 U/kg if < 5 years SC or IM Every 1-2 hours Dose 0.1 U/kg (0.05U/kg if < 5 years ISPAD clinical practice consensus guidelines 2014

Insulin therapy The administration of insulin without fluid replacement in such patients with hypotension may aggrevate Hypotension Shock Hypokalemia Cerebral oedema

درمان وریدی با انسولين روش اول– مداوم درمان وریدی با انسولين روش اول– مداوم ابتدا در cc50 نرمال سالين ، 5واحد انسولين كريستال مي ريزيم و براي بيمارh /0.1iu/kg انسولين شروع مي كنيم تا قند خون به 300 برسد.

نرمال سالين را در ميكروست مي ریزیم و هر 60 قطره آن ، cc 1 است . حال اگر كودكي 20 كيلو باشد و ديابت داشته باشد ، بايد درهر ساعت 20×0/1=2U انسولين بگيرد يعني 20 قطره در دقيقه

How long can we continue? At least until resolution of DKA pH > 7.30 Bicarbonate > 15 mmol/l and/or closure of the anion gap ISPAD clinical practice consensus guidelines 2014

When we increase insulin dose? Not decrease blood ketone Not decrease anion gap Not increase PH

If the child cannot be transported

DKA management with SC &IM insulin Initial dose SC: 0.3 unit/kg Followed SC insulin lispro or aspart 0.1 -0.20 unit/kg every 2 h.

Reduce SC insulin lispro or aspart to 0.05 unit/kg per hour 1-2 if BG falls to <250 mg/dL before DKA has resolved Reduce SC insulin lispro or aspart to 0.05 unit/kg per hour 1-2 Give glucose-containing fluids orally To keep BG 200 mg/dL until resolution of DKA Decreasing urine ketone indicate resolving acidosis

انسولين درماني Mild to moderate DKAدر صورتي که انسولين کريستال یا Novorapid هر 4-2 ساعت زير جلدي تزريق مي کنيم 0.1-0.3IU/KG

Criteria for resolution of DKA includes Glucose <200 mg/dl Serum bicarbonate 18 mEq/l Venous pH of >7.3.

Time of feeding If The patient wishes Conscious No vomiting

Successful Treatment Assess Reassess Assess again Flow sheets Consider CVP monitoring

پس از خروج از کتواسیدوزیس چه می کنید ؟ بهتر است بر اساس غلظت قند خون تصمیم گیری کنیم انسولين کريستال یا Novorapid هر 4 ساعت زير جلدي تزريق مي کنيم

هر 4 ساعت طبق Scale زيرباید انسولین دريافت كند 180 ≤ BS < 300 kg0/1 واحد S/C 300 ≤ BS < 500 kg/0/15 واحد S/C BS ≥ 500 kg0/2 واحد S/C

To prevent rebound hyperglycemia The first SC injection should be given 15–30 min with rapid acting insulin 1–2 hr with regular insulin Before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed

WARNING SIGNS BG falls >90 mg/dL/hour Decreased oxygen saturation Slowing heart rate Irritability Decreased conscious level incontinence Hypoglycemia

Warning signs and symptoms of cerebral edema Change in neurological status specific neurological signs (cranial nerve palsies) Headache Recurrence of vomiting

Warning signs and symptoms of cerebral edema Decrease more than 20 beats/min) not attributable to improved intravascular volume or sleep state Rising diastolic blood pressure>90mmHg

Risk factors of cerebral edema A failure of measured serum sodium levels to rise or a further decline in serum sodium levels with therapy is thought to be a potentially ominous sign of impending cerebral edema Too rapid rise in sodium indicate cerebral edema result of loss of free water in the urine from DI ,is a sign of cerebral herniation

Risk factors of cerebral edema age<5 yr of age More severe acidosis at presentation low pCO2 High blood urea nitrogen New onset diabetes Bicarbonate treatment for correction of acidosis

Risk factors of cerebral edema Longer duration of symptoms Greater volumes of fluid given in the first 4 h Administration of insulin in the first hour of fluid treatment Early fall in glucose-corrected sodium during therapy Greater hypocapnia after adjusting for degree of acidosis

Management Give mannitol, 0.5–1 g/kg IV over 10–15 min, and repeat if there is no initial response in 30 min to 2 h Hypertonic saline 3% 2.5–5 mL/kg over 10-30 minutes Move to ICU Reduce the rate of fluid administration by one-third

Management Elevate the head of the bed. Intubation may be necessary Aggressive hyperventilation (to a pCO2 22 mm Hg] has been associated with poor outcome cranial CT scan

Management Hourly or more frequently as indicated vital signs heart rate, respiratory rate, blood pressure Neurological observations Amount of administered insulin accurate fluid input (including all oral fluid and output. Capillary blood glucose concentration should be measured hourly. serum electrolytes, glucose, blood urea nitrogen, calcium, magnesium, phosphorus, haematocrit, and blood gases should be repeated two to four hourly Urine ketones until cleared or blood β-hydroxybutyrate concentrations

Case 1 6 years old boy with established diabetes mellitus type 1 about 5 days ago. he must be give insulin . He is 20 kg ,he is in prepubertal What’s insulin protocol?

انسولين بعد از غذا انسولين پايه قند خون صبحانه ناهار شام

0.7×20=14 total dose age Unit/kg Target premeal BS Basal insulin <5 years 0.6-0.7 100-200 25-30 5-12 years 0.7-1 80-150 40-50 12-18 years 1-1.2 70-130 0.7×20=14 total dose

Insulin regimen (analogues basal-bolus) Bolus3iU Bolus: 2 iU Basal: 7 iU Bolus: 2 iU Insulin in blood There may be a need for injecting isophane bd, rather than od when using quick acting analogues in a basal bolus regimen 6 7 8 9 10 11 12 1 2 3 4 5 time Breakfast Lunch Evening Meal Sleep

پايان

Satisfactory outcomes have been reported using an alternative simplified method: after an initial fluid bolus of 20 mL/kg of normal saline, 0.675% saline (3/4 normal saline, 115.5 mmol sodium) is infused at 2–2.5 times the usual maintenance rate of fluid administration regardless of the degree of dehydration, and decreased to 1–1.5 times the maintenance rate after 24 h, or earlier if acidosis resolved, until urine ketones are negative

ubsequentfluid management (deficit replacement) should be with an isotonic solution (0.9% saline, Ringer’s lactate or Plasmalyte) for at least 4–6 h

(sodium should rise by 0.5 mmol/L for each 1 mmol/L decrease in glucose concentration)

Initial dose SC: 0.3 unit/kg, followed 1 h later by SC insulin lispro or aspart at 0.1 unit/kg every hour, or 0.15–0.20 units/kg every 2 h. ◦ If BG falls to <14 mmol/L (250 mg/dL) before DKA has resolved, reduce SC insulin lispro or aspart to 0.05 unit/kg per hour to keep BG≈11 mmol/L (200 mg/dL) until resolution of DKA.

The starting potassium concentration in the infusate should be 40 mmol/L. Subsequent potassium replacement therapy should be based on serum potassium measurements. ◦ If potassium is given with the initial rapid volume expansion, a concentration of 20 mmol/L should be used

The maximum recommended rate of IV potassium replacement is usually 0.5 mmol/kg/h. • If hypokalemia persists despite a maximum rate of potassium replacement, then the rate of insulin infusion can be reduced

hypophosphatemia Metabolic encephalopathy (irritability, paresthesias, confusion, seizures, coma); impaired myocardial contractility and 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 preexisting severe phosphate depletion can lead to rhabdomyolysis

To prevent rebound hyperglycemia, the first SC injection should be given 15–30 min (with rapidacting insulin) or 1–2 h (with regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin to be absorbed

degree of edema that develops during DKA correlates with the degree of dehydration and hyperventilation at presentation,CEREBRAL HYPOPERFUSION but not with factors related to initial osmolality or osmotic changes during treatment

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

Major criteria • Altered mentation/fluctuating level of consciousness • Sustained heart rate deceleration (decrease more than 20 beats/min) not attributable to improved intravascular volume or sleep state • Age-inappropriate incontinence

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

The appearance of diabetes insipidus, manifested by increased urine output with a concomitant marked increase in the serum sodium concentration, reflecting loss of free water in the urine, is a sign of cerebral herniation causing interruption of blood flow to the pituitary gland

Treatment of cerebral edema • Initiate treatment as soon as the condition is suspected. • Reduce the rate of fluid administration by one-third. • Give mannitol, 0.5–1 g/kg IV over 10–15 min, and repeat if there is no initial response in 30 min to 2 h (210–212). • Hypertonic saline (3%), suggested dose 2.5–5 mL/kg over 10–15 min, may be used as an alternative to mannitol, especially if there is no initial response to mannitol

BARAYE HAR 1 MMOL KAHESH GHAND NA 0.5 MMOL AFZAYESH MIYABAD