IN THE NAME OF GOD

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

Case study کودک 6 ساله ای با وزن 20 کیلو گرم با تنفس تند به اورژانس وارد شده در بدو ورود تصمیم 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

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 1-within first 12 hours ½Deficit +½ Maintenance 2- within next 12 hours 1̸ 4Deficit + ½ Maintenance To replace the estimated fluid deficit evenly Over36- 48 h. ISPAD clinical practice consensus guidelines 2014

First Method WT=20kg Maintenance =1500cc Deficit =100 *20 2000cc مایع 12 ساعت اول 750+1000=1750 مایع 12ساعت بعدی 750+500=1250 در واقع در 12 ساعت دوم و سوم بیمار هر بارcc 1250 مایع دریافت می کند

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

Third Method First day 1.5-2 times the 24 h maintenance requirements 10- 20ml · kg-1 · h with isotonic solution 0.9% saline,Ringer’s lactate for at least 4–6 h Then half salin 0.45% salin The second day 1-1.5 times the 24 h maintenance requirements Pediatric Diabetes 2014 ISPAD clinical practice consensus guidelines 2014

Third 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

Volume Expansion 10-20 ml/kg NS within 60-120 minutes

Volume Expansion Repeated 10ml/kg if Shock Hypotension Delay capillary refilling Decrease tissue perfusion

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 درلیتر سدیم 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

Fluid therapy Acidosis with BS 100-200mg/dl Add%7.5 dextrose to solution Insulin should be continue

Fluid therapy Acidosis with BS <100mg/dl Add%10 dextrose to solution Insulin should be continue

Fluid therapy . 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.

Fluid therapy NS with added potassium was used 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 K=3-4 40mEq/l K=4-5 20mEq/l 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

Bicarbonate Therapy After 2-3hours of hydration if pH <7.0 or bicarbonate <5 mEq Give 1meq/kg over 1 hour

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

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

WARNING SIGNS BG falls >90 mg/dL/hour Headache Slowing heart rate Irritability Decreased conscious level incontinence specific neurological signs Hypoglycemia

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

Insulin therapy The administration of insulin without fluid replacement in such patients with hypotension may aggrevate hypotension

درمان با انسولين روش اول– مداوم ابتدا در cc100 نرمال سالين ، 10 واحد انسولين كريستال مي ريزيم و براي بيمار 0.1iu/kg انسولين شروع مي كنيم تا قند خون به 300 برسد. پس از آن درمان به طريق زیررا بر اساس درجه اسيدوز با يكي از دو روش ذيل ادامه مي دهيم اگر اسيدوز باقي باشد دوز انسولين را با نصف ادامه مي دهيم اگر اسيدوز بر طرف شده باشد ، انسولين مداوم قطح مي گردد.

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

DKA management with SC &IM insulin Initial dose SC: 0.3 unit/kg, Followed SC insulin lispro or aspart 0.20 units/kg every 2 h. if BG falls to <250 mg/dL before DKA has resolved Reduce SC insulin lispro or aspart to 0.05 unit/kg per hour To keep BG200 mg/dL until resolution ofDKA.

انسولين درماني Mild to moderate DKA1-در صورتي که هر 4-3 ساعت زير جلدي تزريق مي کنيم0.25IU/KG انسولين کريستال

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 ؟ 0.25iu/kg انسولین کریستال هر 4-6 ساعت می دهیم

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 and symptoms of cerebral edema Change in neurological status specific neurological signs (cranial nerve palsies) Headache Decreased oxygen saturation Recurrence of vomiting Blood glucose falls > (90 mg//hour

Warning signs and symptoms of cerebral edema Inappropriate slowing of heart rate Decrease more than 20 beats/min) not attributable to improved intravascular volume or sleep state Rising 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

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 10–15 min Restrict IV fluids by one-third Move to ICU Consider cranial imaging

پايان

Amount of administered insulin. • Hourly (or more frequently as indicated) accurate fluid input(including all oral fluid)and output. • Capillary blood glucoseconcentration should be measured hourly

Laboratory tests: serum electrolytes, glucose, blood urea nitrogen, calcium, magnesium, phosphorus, hematocrit, and blood gases should be repeated 2–4 h, or more frequently, as clinically indicated, in more severe cases. • Blood BOHB concentrations, if available, every 2 h

The objectives of fluid and electrolyte replacement therapy are: • Restoration of circulating volume • Replacement of sodium and the ECF and intracellular fluid deficit of water • Improved glomerular filtration with enhanced clearance of glucose and ketones from the blood

he objectives of fluid and electrolyte replacement therapy are: • Restoration of circulating volume • Replacement of sodium and the ECF and intracellular fluid deficit of water • Improved glomerular filtration with enhanced clearance of glucose and ketones from the bloo

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

infuse fluid each day at a rate that seldom exceeds 1.5–2 times the usual daily maintenance requirement

Start insulin infusion 1–2 h after starting fluid replacement therapy; i.e., after the patient has received initial volume expansion

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

If BG falls very rapidly (>5 mmol/L/h) after initial fluid expansion, consider adding glucose even before plasma glucose has decreased to 17 mmol/L (300 mg/dL).

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

Disruption of the blood–brain-barrier has been found in cases of fatal cerebral edema associated with DKA (196, 197), which further supports the view that cerebral edema is not simply caused by a reduction in serum osmolality

increased risk of cerebral edema include Younger age (198) • New onset diabetes (170, 198) • Longer duration of symptoms or an early fall in glucose-corrected sodium during therapy (83–85, 202). • Greater volumes of fluid given in the first 4 h (88, 200, 202). • Administration of insulin in the first hour of fluid treatment

Greater hypocapnia at presentation after adjusting for degree of acidosis (85, 183, 200). • Increased serum urea nitrogen at presentation (85, 183). • More severe acidosis at presentation (88, 201, 202). • Bicarbonate treatment for correction of acidosis (85, 203). • A marked early decrease in serum effective osmolality (99, 202). • An attenuated rise in serum sodium concentration

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

WARNING SIGNS: blood glucose falls >5 mmol/l/hour (90 mg/d L) headache, slowing heart rate, irritability, decreased conscious level, incontinence, specific neurological signs Exclude hypoglycaemia Is it cerebral edema

Management Give mannitol 0.5-1 g/kg or hypertonic saline Restrict IV fluids by one-third Call senior staff Move to ICU Consider cranial imaging only after patient stabilised

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