PRACTICAL ISSUES IN MANAGEMENT OF NEONATAL HYPOGLYCEMIA

DR.RHISHIKESH THAKRE

DM (NEO),MD,DNB,FCPS,DCH.

INTRODUCTION

Although there are literally hundreds of papers in the literature focusing on neonatal hypoglycemia this subject remains controversial and puzzling, yet of urgent diagnostic and therapeutic challenge. Controversies continue to involve definition, method and site of sampling, symptoms, significance of asymptomatic status, management and its effect on neurodevelopmental outcome. An attempt is made to answer these issues in the present communication.

WHAT SUGAR VALUE BE TAKEN TO DEFINE HYPOGLYCEMIA ?

Substantial variation in the definition of hypoglycemia not only amongst the pediatricians in general but also among pediatricians within a particular nursery is well known(1). There are four possible approaches to the definition of hypoglycemia in neonate – 1) Statistical II) Clinical III) Neurophysiological and IV) Neurodevelopmental.

There are enough data to support a change in the attitude based on these different approaches to the definition of hypoglycemia.

A blood glucose concentration at/or above 40 mg/dl, preferably in the 54 to 72 mg/dl range represents a more acceptable euglycemic value. (2,3,4,5).

KEY POINT :

1. Monitor carefully any neonate or infant with a blood glucose concentration less than 50 mg/dl.

WHEN SHOULD ONE CLINICALLY SUSPECT HYPOGLYCEMIA IN NEWBORN?

There is no pathognomic sign or symptom of hypoglycemia.These are non-specific in the neonate(4). These include -

i) Lethargy.

ii) Apathy.

iii) Irritability.

iv) Tachypnea.

v) Jitteriness.

vi) Seizures.

vii) Apnea.

viii) Bradycardia.

ix) Cyanosis.

x) Coma.

xi) ASYMPTOMATIC HIGH RISK INFANT.

A similar presentation may be seen in several other disorders, including septicemia, brain injury, severe respiratory distress, and congenital heart disease. Therefore clinical presentations for hypoglycemia are vague, hence high index of suspicion is required. Universal screening for neonatal hypoglycemia is not recommended(6).

KEYPOINTS :

1. Seizures occur in a minority of babies with hypoglycemia. When they do occur, however, they usually imply long standing hypoglycemia(7)

2. Infants with glycogen storage disease can tolerate very low blood glucose concentrations without having significant symptoms(8).

3. Closely monitor those babies at higher risk for hypoglycemia.

HIGH RISK GROUP FOR HYPOGLYCEMIA :

1) PRETERMS.

2) SMALL FOR GESTATION. (SGA)

3) MACROSOMIC.

4) INFANT OF DIABETIC MOTHER. (IDM)

5) ASPHYXIATED BABIES.

6) RHESUS HEMOLYTIC DISEASE

7) HYPOTHERMIA.

8) POLYCYTHEMIA.

9) BECKWITH WIEDMANN SYNDROME

WHAT IS THE OPTIMUM TIME TO SCREEN FOR HYPOGLYCEMIA?

Physiologically, the nadir in blood glucose in newborn takes place at 2 to 3 hours after birth(9). Hence this would be an ideal time for screening an asymptomatic “high risk” newborn. However intrapartum risk factors would warrant early screening.

INTRAPARTUM RISK FACTORS FOR HYPOGLYCEMIA

1) Maternal un-controlled diabetes.

2) Maternal glucose drip.

3) Maternal tocolytic therapy.

4) Maternal use of propronolol / chlorpropamide/ salicylates

/ benzothiazide.

5) Periniatal asphyxia. (Cord blood arterial pH<7.20)

KEY POINTS:

1) There is a normal dip in blood glucose in first 2-4 hours postnatally.

2) Earliest marker for predicting hypoglycemia in the first few hours of life would be cord blood glucose. A high cord glucose would give rise to rebound hypoglycemia in newborn hence would warrant close monitoring immediately following birth.

3) Cord blood glucose should be done in “at risk” neonates especially in SGA and IDM.

4) Monitoring for glucose be done 4 hourly in first 24 hours or whenever baby is symptomatic.

THE MAXIMUM RISK FOR HYPOGLYCEMIA IS IN FIRST 24 HOURS AND DEFINITELY NOT AFTER 72 HOURS, UNLESS IT IS MULTIFACTORIAL IN “AT RISK GROUP”

WHAT BLOOD SAMPLE BE USED FOR DIAGNOSIS OF HYPOGLYCEMIA?

1. For screening purposes reagent strips are commonly used on capillary samples by heel prick, with the help of dextrometer. Reagent strips measure whole blood glucose.

2. Whole blood glucose is 15% lower than plasma levels.

3. It is imperative to measure the level of true glucose rather than the reducing ability of the blood either by glucose oxidase or Nelson and Somogyi methods.

PRACTICAL POINTS:

1. Dextrostix reagent strip (Bayer Corp) in the package insert warns that its use is not intended for neonatal blood sample(10).We have been using Haemo-Glukotest 20800R (Boehringer Mainheim UK). It has no comments on newborn use.

2. Reagent strips are subject to false positive and false negative results.

False positive

- Low hematocrit values (<35%)

- Contamination with iso propylalcohol.

False negative

- High hematocrit values (>55%)

- Glucose values > 200mg/dl.

- Hyperglycemic- hyperosmolar states with or without ketosis.

- Delay in lab analysis.

3. Do not perform blood glucose determination by reagent strip at temperature below 18 degree C or above 35 degree C.

4. The glucose level can fall by 14-18 mg/dl per hour in a blood sample that awaits analysis.

WHEN SHOULD ACTIVE INTERVENTION BE STARTED?

1.PREVENTION OF HYPOGLYCAEMIA IS THE THERAPEUTIC GOAL.

Hence active intervention must be started in labor room ensuring all

babies receive breastfeeds in first half hour of life.

2. If a reagent strip shows a concentration less than 40 mg/dl, treatment should not be delayed while one is awaiting confirmation of hypoglycemia by lab analysis.

3. A confirmatory lab glucose determination is required before one can diagnose hypoglycemia.

WHAT INTERVENTIONS BE DONE IN HYPOGLYCEMIC NEONATE?

1. Ensure neutral thermal environment.

2. Secure an IV access.Collect blood for basic investigations.

3. If symptomatic give a bolus of 2- 4 cc/kg, IV, 10% Dextrose.

If asymptomatic do not give bolus as it may cause rebound hypoglycemia.

4. Start glucose infusion with 10% Dextrose at 6mg/kg/mt preferably using a infusion pump.

5. Check blood glucose level after 30 mts.

6. If low, increment glucose infusion rate by Sion Hospital Formula. Following changes in infusion rate check glucose after 30 min.

7. Calculate separately glucose infusion rate (mg/kg/min) and fluid requirement (cc/kg/day).

8. Need for glucose > 12 mg/kg/min or > 12.5%D to maintain euglycemia suggests refractory (intractable) hypoglycemia.

9. Start HYDROCORTISONE 5 mg/kg/dose, IV, 12 hrly, Collect sample for insulin and cortisol before giving hydrocortisone.

10. Consider GLUCAGON, 0.1 mg/kg/ dose, IV/IM as a temporary measure to raise blood glucose or when IV access is difficult.

11. Consider DIAZOXIDE l0 mg/kg/day, q8hr.

12. Evaluate for underlying aetiology.

Treat underlying specific cause.

AT RISK NEWBORN

ANTICIPATION AND PREVENTION

HYPOGLYCEMIA

GLUCOSE INFUSION RATE (GIR)

CALCULATE GLUCOSE AND FLUID RATE

INCREMENT OF GIR, IF HYPOGLYCEMIC.

USE OF HYDROCORTISONE/DIAZOXIDE/ OCTREOTIDE.

TAPPERING OF GIR

REFRACTORY HYPOGLYCEMIA

AETIOLOGIC EVALUATION.

PROTOCOL FOR MANAGEMENT OF HYPOGLYCEMIA :

AT RISK NEWBORN

· First feed within half hour of birth.

· Provide thermo-neutral environment.

· Reagent strip monitoring.

Reagent strip < 40 mg%

· IV Access.

· Collect blood for lab

· B glucose < 40 mg %

( In case of difficulty in IV access give glucagon, 0.1 mg/kg )

SYMPTOMATIC ASYMPTOMATIC

2-4 cc/kg 10% D NO BOLUS.

IV infusion of 6-8 mg/kg/mt. IV infusion of 6-8 mg/kg/mt.

LOW BLOOD GLUCOSE NORMAL BLOOD GLUCOSE

-Make increments in glucose infusion. - Continue glucose infusion (see SION HOSPITAL FORMULA) - Tappering of GIR.

-The glucose level should be checked after 30 min of each change, in

infusion.

-The maximal glucose concentration is usually limited to 12.5%D to

safeguard against the risk of thrombophlebitis in peripheral line.

-Calculate separately glucose intake (mg/kg/min) and fluid requirements

(cc/kg/day) depending upon the daily fluid requirements.The concentration of dextrose solution to be infused can be worked out to provide the desired amount of constant delivery of glucose.

-Need for > 12 mg/kg/mt of GIR or > 12.5%D suggests refractory

hypoglycemia.

-The concentration of glucose and rate of infusion are increased as

necessary to maintain a normal glucose level using central line.

REFRACTORY HYPOGLYCEMIA:

(Need for GIR >12 mg/kg/mt or >12.5%D)

1. Start HYDROCORTISONE 5 mg/kg/dose IV, 12 hrly Before administering hydrocortisone collect blood sample for insulin and cortisol level.

2. Consider GLUCACON, 0.1 mg/kg/dose, 1M/IV 2-3 hrly as a temporary measure as it mobilizes glucose for only 2-3 hours (to ensure euglycemia)

3. Consider OCTREOTIDE 2-4 mg/kg/d, q 12 w.

4. Search for underlying aetiology

5. Treat for specific conditon.

TAPPERING (4)

1. When glucose level crosses 60 mg/dl glucose infusion rate is gradually tappered with decrements of 2 mg/kg/min every 12 hourly, till glucose infusion rate comes down to 6 mg/kg/min with satisfactory blood glucose values > 50 mg/dl.

2. Oral feeds are gradually introduced when glucose infusion is being tappered depending upon infant condition.

3. The infant is completely weaned off intravenous infusion when blood glucose values are stable at an infusion of 4 mg/kg/min.

4. Continue hydrocortisone until the infant is stable for 48hr off IV fluid. This usually takes for 5 to 7 days.

KEY POINTS :

1. Oral glucose or feeding alone are not enough once hypoglycemia has occurred because oral glucose is more likely to stimulate insulin release as compared to intravenous glucose infusion. (12)

2. Bolus administration is not recommended in asymptomatic babies.

3. Before proceeding further, check patency of IV line, and ensure glucose rate is delivered by infusion pump.

Sion hospital formula for calculation of glucose infusion rate (GIR).

1.CALCULATION OF GLUCOSE INFUSION RATE WITH 10% D

FIRST DIGIT OF FLUID RATE (ML/KG/DAY) X 7

10

( OR FIRST TWO DIGITS IF FLUID RATE = OR > 100 ml/kg/day )

EXAMPLE : IF PATIENT IS GETTING 70 ML / KG/ DAY OF 10% D GIR = 7X7 = 4.9 mg/kg/min

10

IF PATIENT IS GETTING 110 ML/KG/DAY OF 10% D GIR = 11X7 = 7.7mg/kg/min 10

2.TO INCREASE THE GIR BY 1 mg/kg/min

ADD 2 ML /KG OF 25% D TO EACH 8 HR DRIP (OR 1.5 ML / KG TO A 6-HR DRIP)

EXAMPLE :

ADD 2 ML / KG OF 25% D TO EACH 8 – HR DRIP IN THE EXAMPLES ABOVE TO INCREASE THE GIR FROM 4.9 TO 5.9 mg/kg/min IR FROM 7.7 mg/kg/min to 8.7 mg/kg/min

3.WHILE USING FORMULA 2, TO ENSURE THAT THE CONCENTRATION OF THE DRIP DOES NOT EXCEED 12.5% D

DO NOT EXCEED THE GIR BY THE FIRST DIGIT OF THE FLUID RATE (ML/KG/DAY) (OR FIRST TWO DIGITS IF FLUID RATE = OR > 100 ml/kg/day)

EXAMPLE :

FOR THE PATIENT GETTING 70 ML/KG/DAY DO NOT EXCEED 7 mg/ kg/ min AND FOR THE PATIENT GETTING 110 ML/KG/DAY DO NOT EXCEED 11 mg / kg/min

NOTE :

a) The total fluid increases by 0.25 ml/kg/hour for every 1 mg/kg/min increase in GIR

b) While using formula 3, if a further increase in GIR is required increase the total fluid (ml/kg/min

ADVANTAGES OF THESE FORMULAE :

1. Easy, accurate and quick to calculate at the bedside.

2. The GIR can be increased slowly by 1 mg/kg/min to the required amount.

3. Mixing of solutions to prepare different concentrations of dextrose solutions is avoided

NEURODEVELOPMENTAL OUTCOME OF HYPOGLYCEMIA

1. There is no single value below which brain injury definitely occurs.

(Schwartz K. Neonatal hypoglycemia – Back to basics in diagnosis and treatment. Diabetes 40:71, 1991.

2. The absence of overt symptoms at low glucose levels does not rule out CNS injury.

3. More the depth of hypoglycemia and longer its duration more adverse is the neurologic sequalae.

CLINICAL EVALUATION

- Family history.

- Intrapartum risk factors

- Course of illness.

APPEARANCE

i) Macrosomic : LGA/IDM/Hyperinsulinemic states.

ii) SGA

iii) Preterm.

iv) Sick baby

CLINICAL CLUES

i) Plethora - Polycythemia

ii) Midline defects, cholestatic jaundice,micropenis - Hypopitutrism

iii) Ambigous genitalia – Cong. adrenal hyperplasia

iv) Cataracts - IU infections/Galactosemia.