DR.ANAND DESHPANDEMBBS, DCH , DNB [PAEDS]

Consultant Pediatrician ,

•Consultant : Deenanath Mangeshkar Hospital, •Pune

Hon. Asso.Professor Pediatrics, BJGMC PG Teacher MUHS

•Past President IAP Pune

Refractory Hypoglycemia

Dr Anand DeshpandeConsultant Pediatrician

Deenanath Mangeshkar Hospital, Pune

Hon. Associate professor Pediatrics

B J Medical college Pune

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Neonatal Hypoglycaemia

• The most common metabolic disorder of

neonatal period and infancy.

• One of the most preventable cause of

neurological sequelae.

• Requires early diagnosis and prompt intervention

• Exact value at which brain damage occurs ???

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Operational threshold (defined by consensus)

Plasma / whole blood glucose at which clinicians

should consider intervention.

• A blood glucose level (BGL) < 40 mg/dl (plasma glucose level< 45 mg/dl)

• WHO

BGL < 45mg/dl (2.2mmol/L) Hypoglycemia

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Transitional neonatal hypoglycaemia (TNH)

• BGL as low as 30 mg/dl within 1-2 hrs of birth

common in normal

• Occurs in up to 10% of normal newborns

• Represent physiological adaptation to post natal life.

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The levels of insulin falls initially and remains in the basal range for several days without demonstrating the usual brisk response to physiologic stimuli like enteral glucose.

Clinical Manifestations

Features d/t autonomic disturbancesJitteriness

• Tremors

• Pallor and cyanosis

Features d/t cerebral glucopenia• Staring

• Refusal to feed

• Lethargy

• Convulsion

• Apnea8

WHOM TO SCREEN ??

• Birth wt <2kg, GA < 35wks.

• SGA

• LGA

• IDM

• Sick neonate

• Family h/o hypoglycaemia

• Congenital syndromes

• Parenteral nutrition

• Haemolytic disease of newborn 9

Schedule Of Glucose Monitoring

• At Risk Neonates- 2, 6, 12, 24, 48, 72 hrs life.

• Sick Neonates- Every 6-8 hours.

• Neonates On Parenteral Nutrition-

• 1st 72hrs : Every 6-8hrs.

• After 72hrs : Once a day.

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Management Of HypoglycaemiaAsymptomatic

BSL 20-40mg/dl : trial of oral feeds,

Repeat BSL after 1hr

Role of Dextrose Gels

BSL <20 mg/dl: IV Dextrose @6mg/kg/min11

Management Of HypoglycemiaSymptomatic

IV bolus 10% dextrose 2ml/kg

Continuous infusion @ GIR 6-8 mg/kg/min

Increase by 2mg/kg/min,every 30mins

(max 12mg/kg/min)

Continue infusion till 24 hrs after stabilisation,

then taper and stop once GIR 4, BSL >50 consistently12

GIR Calculator

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Recurrent/Resistant Hypoglycemia

• Blood glucose level low despite a GIR 12mg/kg/min

• Stabilisation not achieved despite 7 days of

parenteral glucose therapy.

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Causes Of Recurrent/Resistant Hypoglycemia

Hyperinsulinism(most common cause)

Congenital Acquired

Genetic mutation

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IDM

IUGR

PIH

Birth asphyxia

Polycthemia

Rh incompatibilty

Normoinsulinaemic hypoglycaemia

Counterregulatory hormone deficiency

eg. cortisol def, GH def .

IEM

• Glycogen Storage Disease

• Galactosemia

• Fatty acid oxidation def (MCAD)

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Diagnosis Of Hyperinsulinism

• Based on critical sample i,e when BGL<40 or GIR of 12 is reqd

Critical sample should include

1. Glucose

2. Insulin (>2mIU/ml)

3. Cortisol

4. Beta hydroxy butyrate (<2 mmol/L)

5. Free fatty acid (<1.5mmol/L)

6. Glucagon

(inadequate response to 0.1mg/kg iv glucagon)

*Figures in bracket s/o hyperinsulinism18

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• Besides increasing GIR for resistant hypoglycaemia,certain drugs may be tried.

• Samples need to be taken to investigate the cause before introduction of drugs

Investigations To Be Done In Resistant Hypoglycaemia

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BLOOD URINE

Serum insulin levels, c peptide

thyroid hormones

Urine ketones

Serum cortisone levels Urine reducing substances

GH levels Urine GCMS

Serum ammonia

CASE 1

Baby details-

Full term

Male Child

Date of birth : 12/11/19

Birth weight : 3.6 kg

Mode of delivery : LSCS i/v/o previous previous LSCS

Mother’s Details-

G6A4

Gestation Diabetes Mellitus on Insulin 21

• Clinical Course –

Baby admitted in NICU with asymptomatic hypoglycaemia

(BGL 18) started with full oral feeds & IV fluid D10% with

GIR of 6 mg/kg/min.

Repeat Blood glucose level (BGL) still lowShifted to IV

fluid D12.5 % with GIR of 8 mg/kg/min.

After 24 hours of IV glucose therapy, 2 consecutive BGLs >

50 mg/dl infusion tapered off at the rate of 2 mg/kg/min

every 6 hourly and subsequently stopped. 22

Non persistent/ transient hyperinsulinaemic hypoglycaemia.

• Responded well to parenteral glucose therapy.

• Didnt require critical sample and investigation.

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CASE 2 Baby Details –

Fullterm (39 + 2 weeks)

Date of birth : 03/04/14

Birth weight : 4.22 kg

Mode of delivery : LSCS i/v/o Meconium Stained Liquor

Mother’s Details –

Gravida 3

Bad obstetric history – 2 neonatal deaths, cause unknown

2nd degree Consanguinity

Pregnancy uneventful24

• Clinical Course –

Baby NCIAB, bag and mask ventilation given for 10 sec, admitted in NICU.

On admission – baby pink, euthermic, hairy pinna +,

lethargic, vitals normal, mild respiratory distress +.

Blood glucose level (BGL) with glucose strips –

was not recordable.

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Baby had one seizure episodeIV fluids D10% started with GIR of 6 mg/kg/min along with trophic oral feeds

GIR was increased by 2mg/kg/min upto 16 by DOL 4 despite which baby failed to maintain BGL

Critical sample was sent –Insulin 69.4 mIU/L, Glucose 45 mg/dl Cortisol 110.

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• Baby was started on oral diazoxide @ 10 mg/kg/day later shifted to inj octreotide@10mcg/kg/day after which BGL maintained,

IV fluids were weaned and stopped.

Child still receives injection octreotide monthly.

PET Scan done

Diffuse uptake of dye in pancreas

s/o islet cell hyperplasia

most likely Nesidioblastosis / PHHI

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F-DOPA PET Scan was done - Diffuse uptake of dye in

pancreas s/o islet cell hyperplasia – most likely

Nesidioblastosis/PHHI

F Dopa PET Scan: 100 % specificity and 75 % sensitivity

in detecting focal disease

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Pancreatic beta cell and insulin secretion

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AGENT DOSES ADMINISTRA

TIONSIDE

EFFECTS

Calcium channel blocker

0.25 -0.8 mg/kg/day

Orally, q 8hrly Hypotension,long term safety not known

Diazoxide 10-15mg/kg/day(max 30mg/kg/day)

Oral,q 8hrly Hirsutism,fluid retention,cardiac failure,GI disturbances

Octreotide 7-12mcg/kg/day(max 40mcg/kg/day)

Subcutaneous,q 4-6hrly

Cholelithiasis

Glucagon Bolus 0.5-1mgInfusion 1-20mcg/kg/hr

Intermittent bolusContinuous infusion

HyponatraemiaThrombocytopenia

DexamethasoneHydrocortisone

0.25mg/kg/dose1-2.5mg/kg/dose

Intravenous q12hrlyIntravenous q 6hrly

Growth suppressionHypertension

CASE 3

Baby Details –Fullterm

Male child

Date of birth : 27/10/10

Birth weight : 2.7 kg

Mode of delivery : LSCS

i/v/o fetal distress

Mother’s Details –

Primigravida

No significant history32

•Clinical Course

Baby had seizures on day 1 of life, BSL done – was low.

On examination hyperpigmentation, normal genitalia

Investigations done –

Serum Cortisol – 3.98 (54-287), S 17 – OH Progesterone – raised, S ACTH – 1250 (10-70pg/ml), S Testosterone – 0.47 (3-10ng/ml)

CT Abdomen – Adrenal Gland not visualised

MRI Brain – Normal pituitary gland

Serum Electrolytes – Within normal range

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Treatment –

Started with inj hydrocortisone @ 5mg/kg/day and IV D 10 %

Shifted to oral tablet Hysone

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Congenital Adrenal Hypoplasia

• Frequent cause of adrenal failure in boys.

• Failure of development of adrenal cortex.

• Onset in infancy or 1st year of life.

• Mutation of NROB 1 gene / DAX 1 protein.

• X linked recessive inheritance.

• Hypogonadotropic hypogonadism

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CASE 4• Baby Details –

Fullterm

Birth weight : 2.8 kg

Mode of delivery : LSCS i/v/o previous LSCS

Mother’s Details –

3rd degree consanguineous marriage

G4L1A1D1

D1 – Male child died due to liver disease – jaundice on day of life 15 with abdominal distension, poor feeding & lethargy. USG – Gall bladder not seen, but HIDA scan excretory ? Biliary atresia. Died at 2 months of age

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• Clinical Course –

BCIAB, shifted with mother, started on BF + topfeed, developed icterus DOL 2,had hyperbilirubinemia phototherapy and discharged thereafter.

Baby readmitted and referred to NICU DMH on DOL 15with icterus, lethargy and poor feeding along with hypoglycemia.

On examination – baby was icteric, mild hepatomegaly, other systemic examination were normal.

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• Investigations Direct hyperbilirubinemia (total 13.8, direct 5.16), Deranged coagulation profile (PT – 55/INR 4.47, aPTT 90), SGOT/PT – 79/77, ALP - 1720, GGT – 61, Protein - 7.2 (albumin 3.5), Serum electrolytes 137/6.2, Ammonia 159, Lactate – 7.2, Serum ketones – absent, Urine acetone – negative, urine NGRS+ve.

USG Abdomen done – gall bladder not visualised.

Ophthalmic examination revealed –

b/l eyes nuclear sclerosis with normal fundus.38

Baby was started on ISOMIL (non lactose containing milk substitute), injection meropenem & Vit. A, D, E, K

Blood culture revealed candida positivity – started on injection fluconazole, also urine culture was positive for klebsiella pneumoniae sensitive to colistin and was started with same.

Galactose Epimerase enzyme assay was normal

GALT (Galactose – 1 – phosphouridyl transferase) enzyme assay was low.

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GALACTOSEMIA

• 2 forms( classic/complete transferase deficiency and partial transferase deficiency)

• Starts from 2nd half of 1st wk of life

• Accumulation of galactose 1P (injury to kidney,liver,brain)

• Newborns present with heptaomegaly,cholestasis,seizures,gram -ve sepsis,cataract

• Injury may begin prenatally d/t transplacental glucose transfer

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GALACTOSEMIA

• 2 forms( classic/complete transferase deficiency &partial transferase deficiency).

• Starts from 2nd half of 1st wk of life.

• Accumulation of galactose 1P (injury to kidney,liver,brain)

• Newborns present with hypoglycaemia, heptaomegaly,

• cholestasis,seizures,gram -ve sepsis,cataract.

• Injury may begin prenatally d/t transplacental galactose

transfer.

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CONCLUSION

• Hypoglycaemia is a biochemical sign of a variety of diorders of varying degrees of significance.

• It presents either with non specific symptoms or asymptomatically.

• It can have profound long term neurological consequences (20% of PHHI cause significant brain damage)

• The critical sample being drawn when the patient is hypoglycaemic is crucial to make the diagnosis.

• Treatment depends on the underlying condition.

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