From: Subject: MANAGEMENT OF DIABETIC KETO ACIDOSIS Date: Wed, 4 Oct 2006 16:47:53 +0530 MIME-Version: 1.0 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: file://C:\WINNT\Profiles\Administrator\Desktop\1sep\paediatrics\Diabetic_Keto.htm X-MimeOLE: Produced By Microsoft MimeOLE V5.00.2314.1300 MANAGEMENT OF = DIABETIC KETO ACIDOSIS

MANAGEMENT OF = DIABETIC KETO=20 ACIDOSIS IN CHILDREN

Dr. S Sushama = Bai MD, DCH, FIMSA, FIAP

Professor and Head of = Pediatrics

Pushpagiri Institute = of Medical=20 Sciences and Research Centre

Thiruvalla, Kerala = =96 689 101

Phone (R) 0481 = 2597461

Email : drsushamabai@rediffmail.com

After reading this = article,=20 the doctor should be able to

1. = Diagnose DKA and = grade the=20 severity.

2. = Define the = diagnostic=20 criteria.

3. = Know the basic = metabolic=20 changes in DKA.

4. = Provide effective = therapy=20 simplified in 15 steps.

5. = Manage DKA in = underserved=20 areas.

6. = Prevent Keto = acidosis in=20 diabetic children.

Background

=20

=20 Diabetic Keto Acidosis (DKA) is the commonest endocrine emergency = of=20 childhood and adolescence. In a teaching hospital the incidence is 6.2 / = 1000 of=20 pediatric admissions while the incidence of newly diagnosed diabetes is = only 2.8=20 / 1000 (1). It is a potentially fatal but reversible situation with = appropriate=20 treatment. Diagnosis of DKA is easy if suspected, but often delayed in = children=20 since rarely suspected.

Clinical=20 Diagnosis

=20 D K A is to be considered as the differential diagnosis or = coexisting=20 situation in any sick child with

Attered=20 sensorium due to convulsions, hemorrhage, infections, hepatic or renal = failure, trauma.=20
Acute=20 abdomen as appendicitis, peritonitis, pyelonephritis, blunt injury.=20
Breathlessness=20 as in asthma, pneumonia, pneumothorax, metabolic disorder.=20
Circulatory=20 failure=20
Dehydration.=20
Drug=20 intoxication=20
Fatigue=20
Sepsis=20 syndrome

Diagnostic = Criteria of DKA=20 (2) (3) (4)

=B7 =20 Hyper glycemia =96 Blood = glucose (BG)=20 > 250mg/dL with glycosuria

=B7 =20 Metabolic acidosis =96 Venous pH < 7.35,=20 HCO₃ < 20 mEq/L

=B7 =20 Ketosis = = -=20 Ketonemia > 1: 2 dilution positive with ketonuria

Estimation of=20 beta hydroxy butyrate (> 300 mmol/L) is more reliable to assess = ketosis since=20 in severe dehydration with hyper osmolarity metabolisation of = betahydroxy=20 butyrate to acetoacetate and acetone may be delayed. Only the latter two = are=20 detectable by nitroprusside test in serum and urine (5).

Metabolic=20 Changes

&nbs= p; =20 The basic defect in D K A is insulinopenia and subsequent release = of=20 stress hormones resulting in hyperglycemia. BG above the renal threshold = (>180 mg/dL) results in osmotic diuresis. Net effect is dehydration = (5 =96 10=20 %) and dyselectrolytemia due to urinary loss and body compensatory = mechanisms.=20 The approximate loss of electrolytes at the time of admission are sodium = 10mEq/kg, potassium 5mEq/Kg, and calcium and phosphorus 4mEq/Kg each. = Loss of=20 potassium continues for many days even after correction of acidosis.

Clinical = Grading

=20 Clinical grading of D K A (See Box) is important to prioritize = the=20 treatment, to prognosticate and to anticipate complications (1,5)

Box - D K A =96 = Clinical=20 Grading

Mild

Moderate

Severe

Vague Symptoms

Fatigue

pH 7.25-7.35

Drowsy

Some dehydration

Kussmaul breathing

pH 7.15-7.25

Coma

Severe dehydration

Circulatory,

Respiratory or

Renal failure

pH < = 7.15

Requirements for = Managing=20 DKA

Well=20 equipped PICU with central oxygen supply, noninvasive monitors and = infusion=20 pumps.=20
Tertiary=20 care facility with 24hours laboratory service.=20
Trained=20 staff nurses.

But these are = beyond=20 expectation in most situations. However, if a trained staff nurse is = available,=20 with minimum facilities (Glucometer, bedside oxygen, fluids and drugs) D = K A can=20 be successfully managed.

Therapy

=20 A simplified protocol in 15 steps from A to O, each step = beginning with=20 the letter in alphabetic order will be helpful for systematic treatment = of D K=20 A.

Sick child 0 =9610 = min Steps=20 1- 3 A, B, C =96 Stabilization

1. = A=20 =96 Airway suction

2. = B =96 Breathing =96 Oxygen (50%) = Ventilate

3. = C =96 Circulation =96 RL/NS 20 ml/Kg in 20 =96 60 = minutes if CRFT=20 > 3seconds

Note =96=20 to assess Capillary refill time (CRFT) raise the upper limb = 15⁰ above=20 the level of precordium, gently press the finger pulp or palmar eminence = for 5=20 seconds, release the pressure and observe the time in seconds for return = of=20 color of the blanched area. For a stable child omit steps A, B, C.

10 - 20 min Step=20 4-D

D=20 - Dextrose = assessment=20 by glucometer. Value >250mg/dL suggests D K A. For subsequent = management:

=B7 =20 Calculate body surface area (1 M² =3D = 30Kg)

=B7 =20 Nasogastric aspiration

=B7 =20 Bladder catheterization if comatose &n= bsp; =20 in moderate and severe DKA

=B7 =20 Keep resuscitation kit ready near the child.

20 - 30 min. Step 5 E =96 Electrolyte=20 Estimation

Secure and = maintain a=20 separate venous access for frequent sampling. Initially collect blood = for 15=20 parameters, which include BG, Serum sodium, potassium, chloride, = bicarbonate,=20 venous blood gas (VBG), blood urea, serum creatinine, calcium and = phosphorus,=20 glycosylated hemoglobin (GHB), C peptide, serum amylase, serum lipase = and blood=20 culture. Subsequent laboratory parameters are to be individualized.

30 - 60 min. Step = 6 F Fluid=20 Calculation

=20 Simplified Milwaukee protocol is found to be safe and effective = for=20 children with DKA for the past 20years (3,5). Accordingly the quantity = of fluid=20 recommended is 4 L/M²/day for moderate and severe cases. The = maximum=20 fluid replacement should not exceed the quantity for a child of 75kg. = Duration=20 of fluid therapy should be extended to 36 =96 48 hrs if >4L. After = the initial=20 first hour bolus, the subsequent fluid should be evenly distributed as = shown=20 below-

Rate of=20 infusion for next 23hours =3D Calculated fluid for 24hrs =96 = I^st Hour=20 bolus

&nbs= p; = ; = &= nbsp; &n= bsp; &nb= sp; =20 =20 23 &nbs= p; = ; =20 =3D ml/hr

Type=20 of fluid after the initial bolus of RL/NS should be =BD NS.

1 =96 24- hr =96 = Step 7 G =96=20 Glucose Administration

=20 As the BG reaches 250mg/dL approximately by 6hrs of fluid = therapy,=20 infusion fluid should be changed to a mixture of 5% D : NS =3D 1:1. BG = has to be=20 monitored hourly and ideal fall should be 50 =96 100mg/hr. Since 1 unit = of insulin=20 metabolises 3 =964 gm of glucose, there may be a rapid fall in blood = glucose after=20 starting insulin. If so, concentration of glucose in the infusing fluid = need to=20 be increased upto 10% D : NS =3D 1:1 (3,6). If ready-made fluid = preparations are=20 not available reconstitution should be done using infusion set with = utmost care=20 to prevent contamination. Change over fluid should be prepared = sufficiently=20 early.

1 =96 24- hr. Step = 8 H =96=20 Hypokalemia

=20 Hypokalemia should be anticipated, detected and corrected at the=20 earliest. Easy assessment is by a cardiac monitor or by ECG in Lead II. = Earliest=20 evidence is flat T waves (<2 div) followed by the appearance U wave = and QRS=20 widening. To correct hypokalemia add potassium chloride to IV fluid up = to=20 20mEq/L =20 T

=20 &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; &nb= sp; &nbs= p; = ; =20 U

=20 even if the child has not passed urine. If there is no evidence = of=20 hypokalemia potassium should be withheld till the child has voided. = Insulin=20 infusion should be postponed till the correction of hypokalemia in such=20 patients. (7)

1 =96 24 hr. Step 9=96 I Insulin=20 Administration

=20 Continuous intravenous infusion of regular insulin is advised in = 0.1=20 u/kg/hour dose till blood glucose reaches 150 mg/dL. Insulin dose is = then=20 reduced to 0.05 u /kg/hr to 0.025 u/kg/hr depending on blood glucose = level till=20 acidosis is corrected, child is alert and oral feeds are tolerated. = Switching=20 over to subcutaneous regular insulin (dose 1 u/kg/day divided 6 hourly) = can be=20 implemented at this stage. The first dose should be started along with = food at=20 the regular time. IV insulin infusion =20 should be continued at least 60 minutes after S/C dose to provide = time=20 for S/C insulin to act.

1 =9624 hr. Step = 10 =96 J Joined=20 Infusion

=20 Instead of separate IV lines for fluid and insulin, joined = infusion=20 through a single line will prevent hypo or hyperglycemia (3). For this,=20 calculate the fluid for =BD = - 1 hr=20 depending on the patients weight and transfer to measured volume set or = infusion=20 pump. Add the calculated dose of insulin for the same period to this = fluid and=20 adjust the rate for =BD - 1hr. This will enable one to assess correctly = the fluid=20 and insulin intake for every =BD - 1 hr. For the first infusion an = excess of 25ml=20 has to be prepared to flush the tubings.

1 - 24 hr. Step 11 = K =96=20 Ketoacid Correction

=20 Ketoacidosis gets corrected with fluid and insulin infusion. The = definite=20 indications for bicarbonate therapy are symptomatic hyperkalemia, = (revealed by=20 tented T waves in ECG and cardiac irregularity), circulatory failure and = renal=20 failure. Blood pH < 7 without clinical signs of organ function = impairment is=20 not a definite indication. Dose of bicarbonate is 0.5 =96 1mEq/kg (max = 50mEq) in=20 1:1 dilution in sterile water to be administered in 60 minutes through = separate=20 IV line. (2) Rebound hypokalemia and cerebral edema should be = anticipated.

2- 24 hr Step 12 =96L =96 Laboratory=20 Reports

=20 If lab services are ideal results will be ready by 2 hrs and = appropriate=20 corrections in therapy should be made. First priority is for correction = of=20 potassium. If the serum potassium value is < 5.6 mEq/L potassium in = IV fluid=20 should be increased to 40mEq/L. In addition oral potassium (2mEq/kg/day = in=20 divided doses) should be supplemented for several days. Corrected sodium = is the=20 next to asses as shown below-

Corrected=20 Sodium =3D Measured Na + = 1.6 Measured glucose - = 100

&n= bsp; =20 &nbs= p; = ; = &= nbsp; =20 100

If the value exceeds = 150mEq/L,=20 duration of fluid correction should be extended to 36 hours and bolus = volume=20 replacement if needed in between should be with =BD NS. Calcium (50mg = /kg/day) and=20 phosphorus (25mg/kg/day) should be started as soon as child tolerates = oral.

Beyond 2 hrs Step 13=96 M=20 Monitoring

Till recovery = maintain a=20 flowchart for proper follow up as shown in figure. Vitals, GCS, Pupil = size, BG,=20 ECG, insulin dose and I/O chart are to be monitored hourly till BG is = 250mg/dL.=20 Thereafter all parameters except BG need be monitored 4 =96 6 hourly. BG = should be=20 monitored hourly till the child is stable and free of acidosis. VBG (pH, = PCO₂, HCO₃) and SE (Na, K, Cl, HCO₃) = need be=20 evaluated 4 hourly. Urine glucose and acetone are to be evaluated 4 = hourly or=20 with each void. Mannitol should be kept ready to counter act cerebral = edema.=20 Spuriously high level of serum creatinine can occur without renal = failure in=20 ketoacidosis.

Date

Time=20

TPR

GCS

Pupils=20

Na=20

pCO2

HCO3

ser

Ins

1/0

Fig. = D K A=20 Flowchart

2 =96 48hrs Step 14 N=96 Normal Oral = Intake

=20

=20 Indications for discontinuing IVF are correction of dehydration, = child=20 stable on oral feeds, venous pH > 7.3, SNa 135 =96 = 145 mEq/Land=20 clearance of ketonuria.

2 =96 48hrs Step 15 =96 O=96 Other=20 Parameters

=20 These are coma care, detection and treatment of infections = (especially=20 vulvovaginitis), frequent monitoring, reevaluation of clinical and lab=20 parameters and individualized alteration in protocol. Less severe cases = will be=20 fit for early weaning from IV fluids and continuous IV insulin infusion = may not=20 be required.

2 =96 48hrs. Problems=20 Encountered

=20 Cerebral edema, hyperosmolar non-ketotic coma (HNC) and = hypoglycemic coma=20 are the common problems encountered in D K A.

=20 Cerebral=20 edema manifests 4 =96 12 hrs after starting therapy as the = child=20 reveals clinical and biochemical improvement. Child complaints of = headache,=20 becomes irritable and there is rapid deterioration in GCS. Heart and = respiratory=20 rates become slow and BP increases (Cushings triad). Pupils become = dilated and=20 unreactive. The main differential diagnosis is hypoglycemia in which = tachycardia=20 and hypotension are the features and pupils will be normal. Cerebral = edema=20 should be treated as an emergency with 30⁰ elevation of head, = hyperventilation (bag and mask is adequate) and IV 20% mannitol 2ml/kg = in 5=20 minutes. A repeat dose may be required sometimes. The period of = rehydration=20 should be prolonged to 36 =96 48hrs.

=20

=20 HNC is rare in children. Features are coma, blood glucose = >=20 800mg/dL, minimal ketosis and serum osmolality > 350 mOSm/kg (S. Osm = =3D 2 [Na=20 + K] + [BG/18] + [Bu/2.8]). Rehydration period in HNC should be = prolonged to=20 > 48hrs and for bolus volume replacement =BD NS is recommended.

=20 Hypoglycemia is=20 an iatrogenic complication and can occur in D K A in two situations-(1) = When=20 separate infusion lines are used for fluid and insulin and fluid = infusion fails=20 while insulin infusion continues, (2) Rapid fall in blood glucose due to = IV=20 insulin. Features are sweating, altered sensorium and convulsions. = Treatment is=20 oral or parenteral administration of 10 =96 15 gm of glucose, followed = by=20 continuation of parenteral fluid or normal diet with repeated BG = monitoring, 30=20 minutes later and then hourly till the BG is stable.

Management of D K=20 A in medically underserved areas

=20 In situations where lab services, premixed fluids and infusion = pumps are=20 not available, a compromise in treatment is obviously needed. The = calculated=20 fluid as per Milwaukee protocol can be administered by drip infusion. = Plain=20 insulin can be administered intra muscularly in dose of 0.1u/Kg/hr (3). = If=20 transportation is not possible glycemic control can be achieved with = hourly=20 administration of 1M regular insulin. If the child is to be transported = to a=20 higher center after the initial bolus fluid, the IV fluid recommended is = 5 D :=20 NS =3D 1:1 with 20mEq/L Kcl instead of =BD NS.

Prevention of=20 DKA

=20 Ketoacidosis in previously diagnosed diabetic child can be = prevented by=20 educating parents for regular 6 hourly home glucose monitoring and = implementing=20 sick day regeme. Urine acetone should be checked at home if BG exceeds = 300mg/dL.=20 If BG >250mg/dL 20% of daily requirement of insulin should be given = as plain=20 insulin in addition to usual insulin dose. Child should be encouraged to = take=20 plenty of oral fluids. If the oral intake is less, the usual dose of = insulin can=20 be reduced but should not be omitted. Medical consultation should be = sought at=20 the earliest.

Outcome = Mortality following DKA = is <5%=20 if individualized treatment is carried out. Apart from the complications = mentioned, death may occur due to cerebral venous thrombosis, upper GI = bleed and=20 ARDS.=20

Summary

=20

D K A is the commonest endocrine emergency of = childhood. The=20 situation is potentially fatal but is reversible with appropriate = management. An=20 established protocol appropriate for the institution with individualized = variation in treatment will help the pediatrician to manage the = condition=20 efficiently.

References

Statistics = 2004.=20 Department of Pediatrics. Pushpagiri Institute of Medical Sciences and = Research Centre, Thiruvalla, Kerala, India.=20
Menon P.S.N. = Diabetes=20 Mellitus. In Ghai Essential Pediatrics. Eds. Ghai O P, Piyush G, Paul = V. K.=20 6^th Edn. 2004. Published by Dr. O P Ghai, Delhi. Pp 468 =96 = 477=20
Felner E1, = White P C.=20 Management of Diabetic Keto acidosis. Recent Advances in Pediatrics- = 20. Ed.=20 David T.J. The Royal Society of Medicine Press Ltd., 1 Wimpole Street, = London=20 WIG UAE, UK. Pp 113 =96 124.=20
Man=20 Mohan K.K. Diabetes on the College Campus. Pediatr Clin N Am 2005; 52: = 279 =96=20 305.=20
Alemzadeh.=20 R, Wyatt D.T. Diabetes Mellitus in children. In Nelson Text book of=20 Pediatrics. 17^th Edn. 2004. Behrman etal. Elsevier, New = Delhi=20 110024. Pp 1947 =96 1972=20
Kelner=20 C J H, Bulter GE Diabetes Mellitus In Forfar and Arneils Text book of=20 Pediatrics. Eds McIntosh, Helms, Smyth 6^th Edn 2003. = Churchill=20 Livingstone, London wiT 4LP. Pp 533 =96 546.=20
Powers=20 AC. Diabetes Mellitus In Harrisons Principles of Internal Medicine=20 16^th Edn. 2005. Eds Kasper etal USA Pp 2152 - 2180 =