Download Glucose - South Dakota Perinatal Association

Lisa A. Lubbers, RN MSN CNP
October 16, 2014
South Dakota Perinatal Association
 No
financial interest
1.
• Identify 3 risk factors for
hypoglycemia in neonates
2.
• Identify 3 main factors
impacting blood glucose
after birth
3.
• Identify 3 symptoms of
hypoglycemia in neonates
 Primary
fuel for the body-brain has higher
demand for glucose
 Brain can’t store adequate amounts in the
form of glycogen like liver, skeletal/cardiac
muscle can
 Needs a steady supply
 Irreversible neuronal injury can result from
hypoglycemia
 Hypoglycemic brain more vulnerable to
damaging effects of ischemia

-sick infants have increased requirements
 Glycogenesis-process
by which unneeded
glucose is converted to glycogen for storage
 Glycogenolysis-process which causes the
breakdown of glycogen back into glucose
 Gluconeogenesis-production of glucose in the
liver by means of nonglucose precursors like
lactate, pyruvate, glycerol, and amino acids
 Insulin-secreted
by pancreatic BETA cells in
response to increase in plasma glucose


Decreases blood glucose by promoting glycogen
formation, suppressing hepatic glucose release,
driving peripheral uptake of glucose.
Doesn’t control entry of glucose in the brain or
liver
 Glucagon-secreted


by pancreatic ALPHA cells
Promotes glycogenolysis and gluconeogenesis
Opposes effect of insulin by raising blood glucose
 Other
counter regulatory hormones-cortisol,
growth hormone, catecholamines
 Fetus
stores glucose as glycogen and
develops enzymatic process for mobilization
of stored energy prior to birth

Limited ability to convert glycogen to glucose as
a fetus so relies on placental transfer (facilitated
diffusion) of glucose to meet energy demands
 Fetus
is capable of gluconeogenic activity
using lactate if needed to meet metabolic
demands in utero
 When the cord is cut enzymes activate the
breakdown of glycogen back into glucose
molecules in the infants body
After
Delivery
In Utero
High insulin : glucagon
ratio -Suppresses lipolysis
{subcutaneous fat}
-Glycogen deposition
{
last 30% fetal life}
High glucagon : insulin
ratio
{
catecholamine release}
-Release of glucose
from glycogen
-Term infants have
enough hepatic
glucose for 10 hours
-Induces enzymes for
gluconeogenesis
•Occurs about4-6 h of
age
•Enzymes reach Adult
levels by 1-2 wk-slower
in preterm
 Immediate
postnatal drop is physiologic
 Balance between hepatic glucose output and
substrate uptake
 Hepatic output dependent on adequate
glycogen stores, endogenous gluconeogenic
precursors, normal functioning gluconeogenic
and glycogenolytic systems and normal
endocrine system
 At birth, glycogen stores greater than adults,
but 2x greater basal glucose utilization
equals rapid depletion
 Hormonal
and enzymatic activities in FETUS
promote anabolism and substrate accretion
 Hormonal and enzymatic activities in
NEWBORN provide for glucose homeostasis
after abrupt interruption of maternal glucose
supply-this needs to occur in the course of
seconds!
 Metabolized

Production of energy-via glycolysis




several different ways in BODY:
Aerobic Metabolism-1 molecule of glucose yields 36
molecules of ATP for energy
Anaerobic Metabolism-1 molecule of glucose yields 2
molecules
Storage as glycogen
Conversion to gluconeogenic precursors
 Brain
:glucose is completely oxidized to
provide 99% of cerebral energy production

Brain is another story-dependent on enzymes and
reactions


GLUT proteins transport glucose across blood brain
barrier into brain cells
During hypoglycemia ketone bodies, lactate,
glycerol, and AA can also be converted to
pyruvate and citric acid cycle—so another source
but not efficient
http://davisdialogues.blogspot.com/2011_08_01_archive.html
 Glucose
requirement for a healthy near
term/term infant is 5-8 mg/kg/min (D10W at
80 ml/kg/day gives a GIR of 5.5mg/kg/min)
 Many other factors can contribute to
requirements-may need much more
 App: glucose infusion rate calculator
 GIR (mg/kg/min)= IV rate X %dextroseX.167
wt in kg
 Preterm
Infants
 Small For Gestational Age (SGA)
 IDM
 Large for Gestational Age (LGA)
 Stressed/Sick Infants
 Maternal Medications
 Other






causes:
Persistent neonatal hyperinsulinism and
nesidioblastosis (AR caused by regulatory defects
in beta cell function)
Beckwith Wiedemann-unknown cause
Inborn errors of carbohydrate, protein, or lipid
metabolism
Endocrine deficiencies (hypopituitarism)
Several new genetic mutations have been
identified
Iatrogenic –umbilical arterial catheter position
near pancreas (high T 6-9 low L3-4)
 The





most common causes:
Preterm
SGA
LGA
IDM
Sick infants
Majority of glycogen stored in 3rd trimester
 Available stores rapidly depleted
 At TERM 5-8% of liver and muscle weight is
glycogen storage
 Immature counter regulatory response to low
glucose concentrations
 Preterm, SGA




lack adipose required for ketone production
or unable to mobilize free fatty acids from adipose
Preterm-may not have enzymes required for he
breakdown of glycogen into glucose (glycogenolysis)
 Less
than 10% for weight
 Causes









Placental insufficiency-chronic stress
Chromosome/genetic abnormalities
Metabolic disorders
Intrauterine viral infection
Multiple gestation
Nutritional status
Maternal chronic illness/stress
Ingestion of drugs/toxins
Some maternal medications
 Low
glycogen and fat stores
 Inadequate metabolic control
 Chronically stressed fetus may use most of
the placentally transferred glucose for
growth and survival
 Greater
than 90%
 Insulin is a growth hormone-suppresses
glucagon response
 Causes hyperinsulinemia r/t:



Undiagnosed GDM (ethnicity, PCOS, family hx of
Type II DM)
Inborn errors
Endocrine disorders
 Glucose
crosses placenta/insulin does not
 Fetal glucose level 70-80% of mother’s
 Infant produces insulin in response to higher
blood sugars
 At cord clamping, glucose supply is gone but
insulin production in infant remains elevated
 The expected nadir is more rapid than non
IDM infants (1-6 hours)
 May take several days to down regulate
insulin production
 Fetal



hyperglycemia=increased production
Insulin
IGF-1
Leptin
 All
lead to stimulation of fetal growth
 Higher
energy needs
 Hypoxic infants may rely on anaerobic
glycolysis (inefficient-large amount of
glucose used for low yield)
 Aerobic metabolism yields 38 ATP per
molecule of glucose
 Anaerobic yields 2 ATP per molecule of
glucose
 Therefore, rapidly deplete stores

Current literature does not endorse a particular
number (40,45,47,50)

Symposium on Pediatric Endocrinology 2014->45 for
symptomatic infants and >65 for hyperinsulinism
Blood glucose level can only approximate
cerebral glucose level
 All agree treatment for symptomatic infants
 Goal is to screen infants in high risk groups-and
intervene appropriately
 At risk infants may need to be screened
differently depending on their risk factors
 Consider an evidence based algorithm for your
facility

 Glucose
goals may vary depending on disease
process, chronological age
 Consider goal of 50 mg/dl after 24 hours of
age-especially if high risk category
 If requiring high GIR, consider weaning IV for
glucose levels >60 mg/dl
 Potential
disruption in bonding/breastfeeding
 Repeated heel sticks
 Invasive procedures
 Uncertainty in what “right” number should
be
 Discrepancy in bedside POC and lab glucose
values-POC underestimates
 Variation in specimen handling and
obtainment
 Infants
at risk may have their first low
glucose concentrations after 3 normal
measurements and even after 24 hours of
age


3 normal measures don’t ensure complete
transition
Consider including 24 hour check into algorithms
 Need
to be certain infant maintains normal
glucoses on routine diet for at least 3
feed/fast cycles prior to discharge
Screening for and management of postnatal glucose homeostasis in late-preterm
(LPT 34–3667 weeks) and term small-for-gestational age (SGA) infants and infants
who were born to mothers with diabetes (IDM)/large-for-gestational age (LGA) infants.
Committee on Fetus and Newborn Pediatrics
2011;127:575-579
©2011 by American Academy of Pediatrics



Most neonates are free of symptoms-development of symptoms
can be ameliorated by presence of alternative substrates
Many symptoms can be linked to other issues
General
Abnormal cry
 Poor feeding
 Hypothermia
 diaphoresis


Neurologic






Tremors/jitteriness
Irritability
Lethargy
Hypotonia
seizures
Cardio respiratory
Tachypnea
 Apnea
 cyanosis

 Confirm
with STAT lab blood glucose but
DON’T delay treatment in symptomatic
infant

Tend to be 10-20% higher than whole blood (POC)
values
 Follow
up checks are imperative
 Should
be feed within 1 hour of age
 Screen 30 minutes after feed
 Consider gavage feeding if not
nursing/nippling well
Glucose less than 25 mg/dL (birth to 4 hours) or
less than 35 mg/dL (4-24 hours):feed and
recheck 1 hour after feeding
 If still less than 25 or 35:treat with intravenous
glucose infusion and/or 2ml/kg D10W bolus

D10W at 80 ml/kg/day give GIR of 5.5 mg/kg/min
 Merits of bolus are debatable, may stimulate insulin
and this may pose risk for rebound hypoglycemia
 Goal: 40-50 mg/dL


If hyperinsulinism is suspected consider insulin
level, serum ketone bodies, and free fatty acids
to confirm diagnosis-if persistent hypoglycemia
beyond 24 hours of age
 Infants
with hyperinsulinemia may require
>12 mg/kg/min IV glucose to maintain
euglycemia!
 Central IV access if using >12.5% dextrose
 Worry about fluid overload
 Weaning



Stable glucose 12-24 h
Follow preprandial glucose
Decrease infusion rate 10-20% each time glucose
>50-60 mg/dl

Hydrocortisone
Decreased peripheral utilization
 Stimulates gluconeogenesis
 ? Consider when needing >15 mg/kg/min


Glucagon







Rapid rise in glucose
Must have adequate glycogen stores (not premies or
SGA)
Temporizing measure
200 mcg/kg IV, SC, IM
Response within 20 min-1 hr
Lasts up to 2 hours
Watch for rebound hypoglycemia
 Diazoxide-inhibits



secretion of insulin
Treatment of persistent (more than a few days)
or severe hypoglycemia d/t hyperinsulinism
Positive response usually 48-72h
Sodium and fluid retention is common
 Somatostatin
(octreotide)-inhibitor of growth
hormone, glucagon, and insulin
 Pancreatectomy

Sugar Babies Study-published 9/2013

Randomized, double blind, placebo controlled







Stratified by maternal diabetes and birth weight
Twins assigned independently
Placebo was carboxymethyl cellulose gel
Large enrollment group (514)-242 became
hypoglycemic and were randomized
New Zealand
40% dextrose gel with and without feeding
Focus on at risk infants





35 weeks or older
48 hours of age or less
IDM
SGA
LGA
 Keep
mom and baby together
 Potentially no interruption in breastfeeding
 Decrease use of formula
 Easy to administer
 Low cost
 BG
measurements at 1h, q3-4h ac for 1st 24 h
then q 6-8h ac for next 24 h
 Continuous glucose monitor placed SQ as
soon after birth as possible and remained for
at least 48h or up to 7days until
hypoglycemia resolved
 Breast fed (or syringe fed expressed BM)
 Formula fed offered up to 60 ml/kg/day 1st
day and 90 ml/kg/day on 2nd day
 Dry
baby’s mouth with gauze
 Squirt a small amount of dextrose gel into a
small cup
 Using a syringe draw up 0.5 ml/kg (200
mg/kg) of gel
 Using a gloved finger dispense ½ the dose
onto the buccal mucosa of one cheek and
massage thoroughly
 Repeat with the other ½ dose in the other
cheek
 Encourage the infant to feed
 Blood
glucose checked 30 min after
administration
 If continued hypoglycemia repeat
 If reoccurrence treat again, up to 6 doses of
gel in 48 hours

Primary outcome-treatment failure


Blood glucose less than 47 mg/dL 30 min after the
second of 2 doses of gel
Secondary outcome









Admission to NICU
Frequency of breastfeeding
Volume of breast milk/formula
IV dextrose
Dextrose gel
Method of feeding at 2 weeks
Incidence of rebound or recurrent
hypoglycemia(glucose <47mg/dL after successful tx)
Time to achieve glucose >47 mg/dL
Duration of glucose < 47 mg/dL
 Infants
in the dextrose gel group less likely
to be admitted for hypoglycemia
 Treatment babies less likely to receive
additional dextrose
 Rebound hypoglycemia uncommon and
similar in frequency in both groups
 Recurrent hypoglycemia less common in
babies in the dextrose gel group
 Total duration of low glucose concentrations
not significantly reduced with dextrose gel
 Treatment was well tolerated
 No serious adverse events





Treatment more effective than feeding alone for
reversal of hypoglycemia in at risk late preterm and
term babies in the first 48 hours
Babies who received dextrose gel less likely to be
admitted to NICU for management of hypoglycemia,
to receive additional dextrose gel or formula feeds,
or to be fed formula at 2 weeks of age
Dextrose gel didn’t increase the risk of rebound or
recurrent hypoglycemia
Initial concern for dextrose gel adversely affecting
breastfeeding, but this wasn’t demonstrated
Dextrose gel should be considered for first line
management of late preterm and term hypoglycemic
babies in the first 48 hours of life
Dextrose gel can be a useful ADJUNCT in the
evaluation and management of hypoglycemia
 Multidisciplinary
team-pediatricians,
neonatologists, nurse practitioners,
dieticians, lactation consultants, nursing,
pharmacists
 Algorithm provides GUIDELINE
Asymptomatic Infant With Risk
Factors
•POCT at one hour >45 continue
feeds and check 2 additional
prefeed POCT
•POCT at one hour <45- apply
dextrose gel and feed again
(breast or formula supplement)
Initiate feed
within 1 hour
2 hour serum
blood glucose
•If <20 apply dextrose gel
and feed immediately, plan
for other intervention
•21-44 apply dextrose gel and
feed immediately recheck
serum and POCT 30 min
after feed
•>45 continue feeds and
check POCT prefeed x 2
•On all at risk infants
•If less than 50 supplement 2040 ml every feed and obtain
prefeed POCT.
24 hour
check
Symptomatic Infant
•Apply dextrose gel and
feed immediately
•If unable to feed apply gel
while placing IV
<45
IV fluids
•D10W at 80 ml/kg/day
•Consider 2 ml/kg bolus
•Every 30 min-1hr until
stable
•May need increasing GIR
•May need supplement if
unable to maintain POCT
•Follow at 24 hours no
matter what
POCT
 Glucose
is an important fuel
 Several reasons why infants are at risk
 No uniform consensus on definition
 All agree to treat symptomatic infants
 Most important to have a uniform strategy
at your facility
 New adjunct-dextrose gel
 Kris
Karlsen-STABLE program
 Carmen Henke, RN NNP-BC
 [email protected]







American Academy of Pediatrics (2011). Clinical Report: Postnatal
Glucose Homeostasis in Late Preterm and Term Infants. Pediatrics.
127(3)575-579.
Arya, V.B., Senniappan, S., Guemes, M., Hussain, K. (2014). Neonatal
Hypoglycemia. Indian Journal of Pediatrics. 81(1):58-65.
Gardner, S.L. et al.. Merenstein and Gardner’s Handbook of Neonatal
Intensive Care. 7th edition. 2011:Mosby
Harris, D.L., Weston, P.J., Signal, M., Chase, J.G., and Harding, J.E.
(2013). Dextrose gel for neonatal hypoglycaemia (the Sugar Babies
Study): a randomised, double-blind, placebo-controlled trial. The
Lancet. 1-7. doi.10.1016/s0140-6736(13)61645-1.
Hawden, J.M. (2013). Definition of neonatal hypoglycemia: time for a
rethink? Archives of Disease in Childhood Fetal and Neonatal Edition.
98:F382-383.
Karlson, K.A. (2013). The S.T.A.B.L.E. Program: Pretransport/Postresuscitation Stabilization Care of Sick Infants Guidelines for Neonatal
Healthcare Providers. 6th ed.
McGowan, J.E. (2006). Neonatal Nutrition and Metabolism (2nd ed).
(2006). Cambridge University Press.





Rozance, P.J. (2014). Update on neonatal
hypoglycemia. Current Opinions in Endocrinology
Diabetes and Obesity, 21:45-50.
Rozance, P.J. (2012). Editorial: Neonatal
Hypoglycemia-Answers, but More Questions.
161(5):775-776.
Tin, W. (2014). Defining neonatal hypoglycaemia: A
continuing debate. Seminalrs in Fetal and Neonatal
Medicine, 19:27-32. doi.org/j.siny.2013.09.003.
UpToDate (2014). Neonatal Hypoglycemia. Retrieved
January 16, 2014 from
http://www.uptodate.com/contents/neonatalhypoglycemia
Verklan, M.T. and Walden, M.(4th ed.). Core
Curriculum for Neonatal Intensive Care Nursing.
Saunders Elsevier (2010).