HIPOGLIKEMIA PADA
NEONATUS
Oleh Rifa
Imaroh 2010730092
Hipoglikemi
adalah keadaan hasil pengukuran kadar glukosa darah kurang dari 45 mg/dL
(2.6 mmol/L). Hipoglikemia adalah masalah metabolik paling umum pada neonatus.
Pada anak-anak, sebuah glukosa darah nilai kurang dari 40 mg / dL (2,2 mmol /
L) merupakan hipoglikemia. Sebuah glukosa plasma tingkat kurang dari 30 mg / dL
(1,65 mmol / L) dalam 24 jam pertama kehidupan dan kurang dari 45 mg / dL (2,5
mmol / L) setelahnya merupakan hipoglikemia pada bayi baru lahir.
Pasien
dengan hipoglikemia mungkin asimtomatik atau mungkin dengan gangguan sistem
saraf pusat (SSP) yang parah dan cardiopulmonary. Manifestasi klinis yang
paling umum dapat mencakup tingkat kesadaran yang berubah, kejang, muntah, unresponsiveness, dan kelesuan. Setiap
anak sakit harus dievaluasi untuk hipoglikemia, terutama ketika anamnesis
mengungkapkan asupan oral berkurang.
Hipoglikemia
berkelanjutan atau berulang pada bayi dan anak-anak memiliki dampak yang besar
pada perkembangan otak normal dan fungsi. Bukti menunjukkan bahwa hipoksemia
dan iskemia berpotensi terjadi hipoglikemia, menyebabkan kerusakan otak yang
permanen dapat mengganggu perkembangan neurologis.
Etiologi
Penyebab
hipoglikemia pada neonatus berbeda sedikit dari pada bayi yang lebih tua dan
anak-anak. Penyebab pada neonatus meliputi berikut:
§ Perubahan sekresi hormon
§ Berkurangnya Substrat cadangan dalam
bentuk glikogen hati
§ Berkurangnya cadangan Otot sumber
asam amino untuk glukoneogenesis
§ Berkurangnya cadangan Lipid
untuk pelepasan asam lemak
Patofisiologi
§ Hipoglikemi sering terjadi
pada BBLR, karena cadangan glukosa rendah.
§ Pada ibu DM terjadi transfer glukosa
yang berlebihan pada janin sehingga respon insulin juga meningkat pada janin.
Saat lahir di mana jalur plasenta terputus maka transfer glukosa berhenti
sedangkan respon insulin masih tinggi (transient hiperinsulinism) sehingga
terjadi hipoglikemi.
§ Hipoglikemi adalah masalah serius
pada bayi baru lahir, karena dapat menimbulkan kejang yang berakibat terjadinya
hipoksi otak. Bila tidak dikelola dengan baik akan menimbulkan kerusakan pada
susunan saraf pusat bahkan sampai kematian.
§ Kejadian hipoglikemi lebih sering
didapat pada bayi dari ibu dengan diabetes melitus.
§ Glukosa merupakan sumber kalori yang
penting untuk ketahanan hidup selama proses persalinan dan hari-hari pertama
pasca lahir.
§ Setiap stress yang terjadi
mengurangi cadangan glukosa yang ada karena meningkatkan penggunaan cadangan
glukosa, misalnya pada asfiksia, hipotermi, hipertermi, gangguan pernapasan.
Diagnosis
Presentasi
klinis hipoglikemia mencerminkan penurunan ketersediaan glukosa untuk SSP serta
stimulasi adrenergik disebabkan oleh tingkat darah menurun atau rendah gula.
Selama hari pertama atau kedua kehidupan, gejala bervariasi dari asimtomatik ke
SSP dan gangguan cardiopulmonary. Kelompok berisiko tinggi yang membutuhkan
skrining untuk hipoglikemia pada satu jam pertama kehidupan meliputi
§ Bayi yang baru lahir yang beratnya
lebih dari 4 kg atau kurang dari 2 kg
§ Besar usia kehamilan (LGA) bayi yang
berada di atas persentil ke-90, kecil untuk usia kehamilan (SGA) bayi di bawah
persentil ke-10, [4] dan bayi dengan pembatasan pertumbuhan intrauterin
§ Bayi yang lahir dari ibu tergantung
insulin (1:1000 wanita hamil) atau ibu dengan diabetes gestasional (terjadi
pada 2% dari wanita hamil)
§ Usia kehamilan kurang dari 37 minggu
§ Bayi yang baru lahir diduga sepsis
atau lahir dari seorang ibu yang diduga menderita korioamnionitis
§ Bayi yang baru lahir dengan gejala
sugestif hipoglikemia, termasuk jitteriness, tachypnea, hypotonia, makan yang
buruk, apnea, ketidakstabilan temperatur, kejang, dan kelesuan
§ Selain itu, pertimbangkan skrining
hipoglikemia pada bayi dengan hipoksia yang signifikan, gangguan perinatal,
nilai Apgar 5 menit kurang dari 5, terisolasi hepatomegali (mungkin
glikogen-penyimpanan penyakit), mikrosefali, cacat garis tengah anterior,
gigantisme, Makroglosia atau hemihypertrophy (mungkin Beckwith-Wiedemann
Syndrome), atau kemungkinan kesalahan metabolisme bawaan atau ibunya ada di
terbutalin, beta blocker, atau agen hipoglikemik oral
§ Terjadinya hiperinsulinemia adalah
dari lahir sampai usia 18 bulan. Konsentrasi insulin yang tidak tepat meningkat
pada saat hipoglikemia didokumentasikan. Hiperinsulinisme neonatal Transient
terjadi pada bayi makrosomia dari ibu diabetes (yang telah berkurang sekresi
glukagon dan siapa produksi glukosa endogen secara signifikan dihambat). Secara
klinis, bayi ini makrosomia dan memiliki tuntutan yang semakin meningkat untuk
makan, lesu intermiten, jitteriness, dan kejang jujur.
Bayi
dengan hiperinsulinisme neonatal berkepanjangan dapat digambarkan sebagai
berikut:
§ SGA
§ Memiliki asfiksia perinatal
§ Lahir dari ibu dengan toksemia
§ Memiliki tingkat penggunaan glukosa
dan sering membutuhkan infus dextrose untuk jangka waktu lama
§ Hipoglikemia ketotik merupakan suatu
penyakit, jarang, tapi dramatis. Hal ini diamati pada anak-anak muda dari usia
5 tahun, yang biasanya menjadi gejala setelah puasa semalam atau
berkepanjangan, terutama dengan penyakit dan asupan mulut yang buruk. Anak-anak
sering hadir sebagai misterius lesu atau terus terang koma, setelah hanya
ditandai dengan hipoglikemia ketonuria.
Anamenesis
§ Riwayat bayi menderita
asfiksia, hipotermi, hipertermi, gangguan pernapasa
§ Riwayat bayi prematur
§ Riwayat bayi Besar untuk Masa
Kehamilan (BMK)
§ Riwayat bayi Kecil untuk Masa
Kehamilan (KMK)
§ Riwayat bayi dengan ibu Diabetes
Mellitus
§ Riwayat bayi dengan Penyakit Jantung
Bawaan
§ Bayi yang beresiko terkena
hipoglikemia
§ Bayi dari ibu diabetes (IDM)
§ Bayi yang besar untuk masa kehamilan
(LGA)
§ Bayi yang kecil untuk masa kehamilan
(SGA)
§ Bayi prematur dan lewat bulan
§ Bayi sakit atau stress (RDS, hipotermia)
§ Bayi puasa
§ Bayi dengan polisitemia
§ Bayi dengan eritroblastosis
§ Obat-obat yang dikonsumsi ibu,
misalnya sterorid, beta-simpatomimetik dan beta blocker
Pemeriksaan Fisik
§ Manifestasi klinis yang luas dan
dapat hasil dari stimulasi adrenergik atau dari penurunan ketersediaan glukosa
untuk SSP. Tidak seperti anak-anak, bayi tidak dapat memverbalisasi gejala
mereka dan sangat rentan terhadap hipoglikemia.
§ Bayi pada hari pertama atau kedua
kehidupan mungkin asimtomatik atau memiliki mengancam jiwa SSP dan gangguan
cardiopulmonary. Gejala dapat meliputi: hpotonia, lesuan, apatis, malas minum,
kejang, gagal jantung kongestif, sianosis, apnea, hipotermi
§ Manifestasi klinis yang terkait
dengan aktivasi sistem saraf otonom meliputi: Kecemasan, tremulousness,
Diaphoresis, takikardi, anemia, mual, dan muntah
§ Manifestasi klinis dari
hypoglycorrhachia atau neuroglycopenia meliputi:Sakit kepala,Mental
kebingungan, menatap, perubahan perilaku, sulit berkonsentrasi
§ Gangguan visual (misalnya, penurunan
ketajaman, diplopia), Dysarthria, kejang, Ataksia, mengantuk, koma,
stroke(hemiplegia, aphasia), parestesia, pusing, amnesia, decerebrate atau
mengulit sikap
Manifestasi klinis
§ jittery
§ keringat dingin
§ letargi
§ distress nafas
§ Sianosis
§ Kejang atau tremor
§ Letargi dan menyusui yang buruk
§ Apnea atau henti napas
§ Tangisan yang lemah atau bernada
tinggi
§ Hipotermia
§ RDS
Diagnosis banding
§ Insufisiensi adrenal
§ Kelainan jantung
§ Gagal ginjal
§ Penyakit SSP
§ Sepsis, asfiksia
§ Abnormalitas metabolik
(hipokalsemia, hiponatremia, hipernatremia, hipomagnesemia, defisiensi
piridoksin).
§ Fasting
§ Malnutrition
§ Diarrhea
§ Enzymatic defects of glycogen
synthetic pathways
§ Enzymatic defects of glycogenolytic
pathways
§ Enzymatic defects of gluconeogenic
pathways
§ Glucagon deficiency
§ Congenital hyperinsulinism (eg,
nesidioblastosis, leucine sensitive hypoglycemia)
§ Defects of beta cell regulation
§ Large tumors
§ Decreased or absent fat stores
§ Enzymatic defects in fatty acid
oxidation
Penyulit
§ Hipoksia otak
§ Kerusakan sistem saraf pusat
Tatalaksana
§ Monitor Pada bayi yang beresiko (BBLR, BMK,
bayi dengan ibu DM) perlu dimonitor dalam 3 hari pertama : Periksa kadar
glukosa saat bayi datang/umur 3 jam. Ulangi tiap 6 jam selama 24 jam atau
sampai pemeriksaan glukosa normal dalam 2 kali pemeriksaan. Kadar glukosa
≤ 45 mg/dl atau gejala positif tangani hipoglikemia
§ Pemeriksaan kadar glukosa baik,
pulangkan setelah 3 hari penanganan hipoglikemia selesai
§ Hipoglikemia harus diperlakukan
sesegera mungkin untuk mencegah komplikasi kerusakan neurologis. Awal makan
bayi yang baru lahir dengan ASI atau susu formula dianjurkan. Bagi mereka yang
tidak mampu untuk minum, selang nasogastrik dapat digunakan. Andalan terapi
untuk anak-anak yang waspada dengan perlindungan jalan nafas utuh termasuk jus
jeruk pada 20 mL / kg.
§ Bagi mereka yang tidak bisa
melindungi jalan napas mereka atau tidak dapat minum, rute nasogastrik,
intramuskular, intraosseous, atau IV dapat digunakan untuk obat berikut
digunakan untuk meningkatkan kadar glukosa: dekstrosa, glukagon, diazoxide, dan
octreotide. Laporan kasus telah menunjukkan bahwa nifedipin dapat membantu
untuk mempertahankan normoglikemia pada anak dengan PHHI.
§ Kortisol tidak boleh digunakan,
karena memiliki manfaat akut minimal dan dapat menunda diagnosis penyebab
hipoglikemia. Kortisol merangsang glukoneogenesis dan menyebabkan penurunan
penggunaan glukosa, yang mengarah ke peningkatan glukosa darah secara
keseluruhan dan dapat menutupi penyebab sebenarnya dari hipoglikemia.
Anti-hipoglikemik : Obat ini meningkatkan kadar
glukosa darah
§ Dekstrosa Dextrose adalah pengobatan pilihan.
Hal ini diserap dari usus, mengakibatkan peningkatan pesat dalam kadar glukosa
darah bila diberikan secara oral. Berikan IV dekstrosa untuk bayi dari ibu
diabetes dengan hiperinsulinemia neonatal sementara selama beberapa hari sampai
hiperinsulinemia mereda. Hindari hiperglikemia membangkitkan pelepasan insulin
cepat, yang bisa menyebabkan hipoglikemia rebound. Bayi SGA dan mereka dengan
toksemia ibu atau asfiksia perinatal memerlukan tingkat dextrose infus IV lebih
dari 20 mg / kg / menit untuk mengontrol tingkat. Pengobatan mungkin diperlukan
untuk 2-4 minggu.
§ Diazoxide (Proglycem) Diazoxide meningkatkan glukosa darah
dengan menghambat pelepasan insulin pankreas dan mungkin melalui efek
extrapancreatic. Efek hiperglikemia dimulai dalam waktu satu jam dan biasanya
berlangsung maksimal 8 jam dengan fungsi ginjal normal. Diazoxide dilaporkan
efektif pada bayi SGA dan pada mereka dengan toksemia ibu atau asfiksia
perinatal.
§ Octreotide (Sandostatin)Octreotide adalah analog long-acting
dari somatostatin yang menekan sekresi insulin untuk pengelolaan jangka pendek
hipoglikemia.
§ Glukagon (Glukagon Darurat Kit,
GlucaGen) Glukagon
dapat digunakan untuk mengobati hipoglikemia sekunder untuk hiperinsulinemia
dan dapat diberikan kepada pasien tanpa akses IV awal. ML masing-masing berisi
1 mg (yaitu, 1 U). Konsentrasi glukosa maksimal terjadi antara 5-20 menit
setelah pemberian IV dan sekitar 30 menit setelah intramuskular (IM)
administrasi.
§ Penanganan hipoglikemia dengan
gejala :
ü Bolus glukosa 10% 2 ml/kg pelan-pelan
dengan kecepatan 1 ml/menit
ü Pasang jalur iv D10 sesuai kebutuhan
(kebutuhan infus glukosa 6-8 mg/kg/menit).
Contoh : BB 3 kg, kebutuhan glukosa 3 kg x 6 mg/kg/mnt = 18 mg/mnt = 25920
mg/hari. Bila dipakai D 10% artinya 10 g/100cc, bila perlu 25920 mg/hari atau
25,9 g/hari berarti perlu 25,9 g/ 10 g x 100 cc= 259 cc D 10%/hari.
§ Atau cara lain dengan GIR
Konsentrasi glukosa tertinggi untuk
infus perifer adalah 12,5%, bila lebih dari 12,5% digunakan vena sentral. Untuk
mencari kecepatan Infus glukosa pada neonatus dinyatakan dengan GIR.
Kecepatan Infus (GIR) = glucosa
Infusion Rate
GIR (mg/kg/min) = Kecepatan cairan (cc/jam) x konsentrasi
Dextrose (%)
6 x berat (Kg)
Contoh : Berat bayi 3 kg umur 1 hari
Kebutuhan 80 cc/jam/hari = 80
x 3 = 240 cc/hari = 10 cc/jam
GIR = 10 x 10 (Dextrose 10%) = 100 = 6
mg/kg/min
6 x 3
18
ü Periksa glukosa darah pada : 1 jam
setelah bolus dan tiap 3 jam
ü Bila kadar glukosa masih < 25
mg/dl, dengan atau tanpa gejala, ulangi seperti diatas
§ Bila kadar 25-45 mg/dl, tanpa gejala
klinis :
ü Infus D10 diteruskan
ü Periksa kadar glukosa tiap 3 jam
ü ASI diberikan bila bayi dapat minum
§ Bila kadar glukosa ≥ 45 mg/dl dalam
2 kali pemeriksaan
ü Ikuti petunjuk bila kadar glukosa
sudah normal
ü ASI diberikan bila bayi dapat minum
dan jumlah infus diturunkan pelan-pelan
ü Jangan menghentikan infus secara
tiba-tiba
§ Kadar glukosa darah < 45
mg/dl tanpa GEJALA
ü ASI teruskan
ü Pantau, bila ada gejala manajemen
seperti diatas
ü Periksa kadar glukosa tiap 3 jam
atau sebelum minum, bila :
§ Kadar < 25 mg/dl, dengan atau
tanpa gejala tangani hipoglikemi
§ Kadar 25-45 mg/dl naikkan frekwensi
minum
§ Kadar ≥ 45 mg/dl manajemen sebagai
kadar glukosa normal
§ Kadar glukosa normal IV teruskan
ü IV teruskan
ü Periksa kadar glukosa tiap 12 jam
Bila
kadar glukosa turun, atasi seperti diatas
§ Bila bayi sudah tidak mendapat IV,
periksa kadar glukosa tiap 12 jam, bila 2 kali pemeriksaan dalam batas normal,
pengukuran dihentikan.
§ Persisten hipoglikemia (hipoglikemia
lebih dari 7 hari)
ü konsultasi endokrin
ü terapi : kortikosteroid
hidrokortison 5 mg/kg/hari 2 x/hari iv atau prednison 2 mg/kg/hari per oral,
mencari kausa hipoglikemia lebih dalam.
ü bila masih hipoglikemia dapat
ditambahkan obat lain : somatostatin, glukagon, diazoxide, human growth hormon, pembedahan. (jarang dilakukan)
Daftar
Pustaka
§ Wilker RE. Hypoglycemia and
hyperglycemia Dalam: Cloherty JP, Stark AR, eds. Manual of neonatal care; edisi
ke-5. Boston : Lippincott Williams & Wilkins, 2004; 569-76
§ Raghuveer TS, Garg U, Graf WD.
Inborn errors of metabolism in infancy and early childhood: an update. Am Fam Physician. Jun 1 2006;73(11):1981-90.
NEONATAL HYPOGLYCEMIA
Neonatal hypoglycemia, defined as a plasma glucose level of less
than 30 mg/dL (1.65 mmol/L) in the first 24 hours of life and less than 45
mg/dL (2.5 mmol/L) thereafter, is the most common metabolic problem in
newborns. Major long-term sequelae include neurologic damage resulting in
mental retardation, recurrent seizure activity, developmental delay, and
personality disorders. Some evidence suggests that severe hypoglycemia may
impair cardiovascular function.
Infants in the first or second day of life may be asymptomatic or
may have life-threatening central nervous system (CNS) and cardiopulmonary
disturbances. Symptoms can include the following:
·
Hypotonia
·
Lethargy, apathy
·
Poor feeding
·
Jitteriness, seizures
·
Congestive heart failure
·
Cyanosis
·
Apnea
·
Hypothermia
Clinical manifestations associated with activation of the
autonomic nervous system include the following:
·
Anxiety, tremulousness
·
Diaphoresis
·
Tachycardia
·
Pallor
·
Hunger, nausea, and
vomiting
Clinical manifestations of hypoglycorrhachia or neuroglycopenia
include the following:
·
Headache
·
Mental confusion,
staring, behavioral changes, difficulty concentrating
·
Visual disturbances (eg,
decreased acuity, diplopia)
·
Dysarthria
·
Seizures
·
Ataxia, somnolence, coma
·
Stroke (hemiplegia,
aphasia), paresthesias, dizziness, amnesia, decerebrate or decorticate
posturing
Diagnosis
Laboratory studies
·
Serum or plasma glucose levels
·
Serum insulin
·
Urine: Obtain a first-voided urine dipstick for ketones; send
urine for organic acid analysis
·
Screening for metabolic errors: Electrospray ionization-tandem
mass spectrometry in asymptomatic persons allows earlier identification of
clearly defined inborn errors of metabolism, including aminoacidemias, urea
cycle disorders, organic acidurias, and fatty acid oxidation disorders
Angiography
The detection of adenomas by celiac angiography has had
limited success. The chance of detecting a tumor blush must be balanced against
the potential risk of causing vascular trauma in infants younger than 2 years.
Management
Hypoglycemia should be treated as soon as possible to
prevent complications of neurologic damage. Early feeding of the newborn with
breast milk or formula is encouraged. The mainstay of therapy for children who
are alert with intact airway protection includes orange juice at 20 mL/kg.
For patients who cannot protect their airway or are unable
to drink, nasogastric, intramuscular, intraosseous, or intravenous (IV) routes
can be employed for the following drugs used to raise glucose levels: dextrose,
glucagon, diazoxide, and octreotide. Start a 5% or 10% dextrose drip when
hypoglycemia is recurrent.
Surgery
Surgical exploration usually is undertaken in severely
affected neonates who are unresponsive to glucose and somatostatin therapy.
Near-total resection of 85-90% of the pancreas is recommended for presumed
congenital hyperinsulinism, which is most commonly associated with an
abnormality of beta-cell regulation throughout the pancreas. Risks include the
development of diabetes.
Background
Hypoglycemia is the most common metabolic problem in
neonates. In children, a blood glucose value of less than 40 mg/dL (2.2 mmol/L)
represents
hypoglycemia.
A plasma glucose level of less than 30 mg/dL (1.65 mmol/L) in the first 24
hours of life and less than 45 mg/dL (2.5 mmol/L) thereafter constitutes
hypoglycemia in the newborn.
Patients
with
hypoglycemia may be asymptomatic or may present
with severe central nervous system (CNS) and cardiopulmonary disturbances. The
most common clinical manifestations can include altered level of consciousness,
seizure, vomiting, unresponsiveness, and lethargy. Any acutely ill child should
be evaluated for hypoglycemia, especially when history reveals diminished oral
intake. (See History and Physical Examination.)
Sustained or repetitive hypoglycemia in infants and
children has a major impact on normal brain development and function. Evidence
suggests that hypoxemia and ischemia potentiate hypoglycemia, causing brain
damage that may permanently impair neurologic development. (See Prognosis.)
Causes of hypoglycemia in neonates differ slightly from
those in older infants and children. The causes in neonates include the
following (see Etiology):
·
Inappropriate changes in hormone secretion
·
Inadequate substrate reserve in the form of hepatic glycogen
·
Inadequate muscle stores as a source of amino acids for
gluconeogenesis
·
Inadequate lipid stores for the release of fatty acids
Causes
of hypoglycemia found in all ages include gram-negative
sepsis,
endotoxin shock, and ingestions, including of salicylates, alcohol,
hypoglycemic agents, or beta-adrenergic blocking agents.
Excluding
insulin therapy, almost all hypoglycemia in childhood occurs during fasting.
Postprandial hypoglycemia is rare in children in the absence of prior
gastrointestinal (GI) surgery. Management efforts are directed toward the
immediate normalization of glucose levels and the identification and treatment
of the various causes.
Patient education
Provide
genetic counseling for families with affected children, including information
about a possible 25% risk of recurrence. Educate pregnant women with diabetes.
Glucose metabolism
Normal
blood glucose is very narrowly regulated, usually from 80-90 mg/dL (4.4-5
mmol/L). Glucose levels increase transiently after meals to 120-140 mg/dL
(6.6-7.7 mmol/L). Feedback systems return the glucose concentration rapidly
back to the preprandial level, usually within 2 hours after the last absorption
of carbohydrates.
Insulin and glucagon are the important hormones in the
immediate feedback control system of glucose. When blood glucose increases
after a meal, the rate of insulin secretion increases and stimulates the liver
to store glucose as glycogen. When cells (primarily liver and muscle) are
saturated with glycogen, additional glucose is stored as fat.
When blood glucose levels fall, glucagon secretion
functions to increase blood glucose levels by stimulating the liver to undergo
glycogenolysis and release glucose back into the blood. (See the diagram
below.)
Normal
hypoglycemic counterregulation.
In starvation, the liver maintains the glucose level via
gluconeogenesis. Gluconeogenesis is the formation of glucose from amino acids
and the glycerol portion of fat. Muscle provides a store of glycogen and muscle
protein breaks down to amino acids, which are substrates utilized in
gluconeogenesis in the liver. Circulating fatty acids are catabolized to ketones,
acetoacetate, and B-hydroxybutyrate and can be used as auxiliary fuel by most
tissues, including the brain.
The hypothalamus stimulates the sympathetic nervous system,
and epinephrine is secreted by the adrenals, causing the further release of
glucose from the liver. Over a period of hours to days of prolonged
hypoglycemia, growth hormone and cortisol are secreted and decrease the rate of
glucose utilization by most cells of the body.
In the newborn, serum glucose levels decline after birth
until age 1-3 hours, then they spontaneously increase. Liver glycogen stores
become rapidly depleted within hours of birth, and gluconeogenesis, primarily
from alanine, can account for 10% of glucose turnover in the newborn infant by
several hours of age.
Etiologi
The causes of
neonatal hypoglycemia include the following:
·
PHHI
·
Limited
glycogen stores (eg, prematurity, intrauterine
growth retardation)
·
Increased
glucose use (eg, hyperthermia, polycythemia, sepsis, growth
hormone deficiency)
·
Decreased
glycogenolysis, gluconeogenesis, or use of alternate fuels (eg, inborn errors
of metabolism, adrenal insufficiency)
·
Depleted
glycogen stores (eg, asphyxia-perinatal stress, starvation)
With regard to
the last item above, in ketotic hypoglycemia, easily depleted glycogen stores,
in combination with inadequate production of glucose through gluconeogenesis, contribute
to hypoglycemia. Thus, fatty acid oxygenation is required to provide substrate
for gluconeogenesis and ketogenesis. Ketones, the byproduct of fatty acid
metabolism, are found in urine and represent the starved state.
Causes of
hypoglycemia in older infants, children, and teenagers include:
·
Poisonings/drugs
(eg, ethanol, isoniazid, insulin, propranolol, salicylates, oral hypoglycemics,
pentamidine, quinine, disopyramide, unripe ackee fruit, Vacor [rat poison]).
·
Liver
disease (eg, Reye syndrome, hepatitis, cirrhosis, hepatoma)
Hyperinsulinemia
Congenital
hyperinsulinism is most commonly associated with an abnormality of beta-cell
regulation throughout the pancreas. A focal disease, such as isolated islet
adenoma, occasionally causes congenital hyperinsulinism.
Genetic defects
have been delineated and now replace the older terms, such as nesidioblastosis,
leucine-sensitive hypoglycemia, PHHI, and islet dysregulation syndrome. These
defects are in the sulfonylurea receptor (SUR) and the beta-cell potassium
adenosine triphosphate (ATP) channel gene located on the short arm of
chromosome 11.
Drug-induced
hyperinsulinism is secondary to surreptitious insulin administration or the use
of oral hypoglycemic drugs. Exogenous administration of insulin is diagnosed
with low serum levels of C-peptide. The sulfonylureas are commonly prescribed
for adults; thus, they are available to children as unintentional ingestions.
In these cases, hypoglycemia may persist for more than 24 hours. Diazoxide
administration may be helpful by suppressing insulin secretion in severe cases.
Epidemiology
Occurrence in the United
States
The
overall incidence of symptomatic hypoglycemia in newborns varies from 1.3-3 per
1000 live births. Incidence varies with the definition, population, method and
timing of feeding, and the type of glucose assay. Serum glucose levels are
higher than whole blood values. The incidence of hypoglycemia is greater in
high-risk neonatal groups.
Early
feeding decreases the incidence of hypoglycemia. Inborn errors of metabolism
that lead to neonatal hypoglycemia are rare but can be screened in infancy.
The incidences of these
conditions are as follows:
·
Carbohydrate
metabolism disorders (>1:10,000)
·
Fatty
acid oxidation disorders (1:10,000)
·
Hereditary
fructose intolerance (1:20,000 to 1:50,000)
·
Glycogen
storage diseases (1:25,000)
·
Organic
acidemias (1:50,000)
·
Phosphoenolpyruvate
carboxykinase deficiency (rare)
·
Primary
lactic acidosis (rare)
International occurrence
In
a Japanese study, more than 80% of admissions from the nursery to the neonatal
intensive care unit (ICU) after birth were due to apnea or hypoglycemia in
neonates born at 35-36 weeks' gestation.
History
The
clinical presentation of hypoglycemia reflects decreased availability of
glucose for the CNS as well as adrenergic stimulation caused by a decreasing or
low blood sugar level. During the first or second day of life, symptoms vary
from asymptomatic to CNS and cardiopulmonary disturbances.
High-risk
groups who need screening for hypoglycemia in the first hour of life include
the following:
·
Newborns
who weigh more than 4 kg or less than 2 kg
·
Large
for gestational age (LGA) infants who are above the 90th percentile, small for
gestational age (SGA) infants below the 10th percentile,[5] and infants with intrauterine growth restriction
·
Gestational
age less than 37 weeks
·
Newborns
suspected of sepsis or born to a mother suspected of having chorioamnionitis
·
Newborns
with symptoms suggestive of hypoglycemia, including jitteriness, tachypnea,
hypotonia, poor feeding, apnea, temperature instability, seizures, and lethargy
Additionally,
consider hypoglycemia screening in infants with significant hypoxia, perinatal
distress, 5-minute Apgar scores of less than 5, isolated hepatomegaly (possible
glycogen-storage disease), microcephaly, anterior midline defects, gigantism,
macroglossia or hemihypertrophy (possible
Beckwith-Wiedemann
Syndrome), or any possibility of an inborn error of metabolism or whose
mother is on terbutaline, beta blockers, or oral hypoglycemic agents
The
onset of hyperinsulinemia is from birth to age 18 months. Insulin
concentrations are inappropriately elevated at the time of documented
hypoglycemia. Transient neonatal hyperinsulinism occurs in macrosomic infants
of diabetic mothers (who have diminished glucagon secretion and in whom
endogenous glucose production is significantly inhibited). Clinically, these
infants are macrosomic and have increasing demands for feeding, intermittent
lethargy, jitteriness, and frank seizures.
Infants
with prolonged neonatal hyperinsulinism can be described by the following:
·
SGA
·
Having
perinatal asphyxia
·
Born
to mothers with toxemia
·
Having
high rates of glucose use and often requiring dextrose infusion for a prolonged
period of time
Ketotic hypoglycemia is an uncommon, but
dramatic, illness. It is observed in children younger than age 5 years, who
usually become symptomatic after an overnight or prolonged fast, especially
with illness and poor oral intake. Children often present as inexplicably
lethargic or frankly comatose, having only marked hypoglycemia with ketonuria.
Physical Examination
Clinical manifestations are broad and can result from
adrenergic stimulation or from decreased availability of glucose for the CNS.
Unlike older children, infants are not able to verbalize their symptoms and are
particularly vulnerable to hypoglycemia.
Infants in the first or second day of life may be
asymptomatic or have life-threatening CNS and cardiopulmonary disturbances.
Symptoms can include the following:
·
Hypotonia
·
Lethargy,
apathy
·
Poor
feeding
·
Jitteriness,
seizures
·
Cyanosis
·
Apnea
·
Hypothermia
Clinical manifestations associated with activation of the
autonomic nervous system include the following:
·
Anxiety, tremulousness
·
Diaphoresis
·
Tachycardia
·
Pallor
·
Hunger, nausea, and vomiting
Clinical manifestations of hypoglycorrhachia or
neuroglycopenia include the following:
·
Headache
·
Mental confusion, staring, behavioral changes, difficulty
concentrating
·
Visual disturbances (eg, decreased acuity, diplopia)
·
Dysarthria
·
Seizures
·
Ataxia, somnolence, coma
·
Stroke (hemiplegia, aphasia), paresthesias, dizziness, amnesia,
decerebrate or decorticate posturing
Diagnostic Considerations
Consider the diagnosis of hypoglycemia, especially in a
patient with sustained or repetitive episodes of hypoglycemia with resulting
seizures and mental retardation. Conditions to consider in the differential
diagnosis of hypoglycemia include the following:
·
Fasting
·
Malnutrition
·
Diarrhea
·
Enzymatic defects of glycogen synthetic pathways
·
Enzymatic defects of glycogenolytic pathways
·
Enzymatic defects of gluconeogenic pathways
·
Glucagon deficiency
·
Congenital hyperinsulinism (eg,nesidioblastosis, leucine sensitive
hypoglycemia)
·
Defects of beta cell regulation
·
Large tumors
·
Decreased or absent fat stores
·
Enzymatic defects in fatty acid oxidation
Differential Diagnoses
Workup
Approach Considerations
Fingerstick
glucose levels or bedside testing may lead to
overtreatment of hypoglycemia, because the primary error with the chemically
treated strips is an underestimation of the serum glucose value.
Serum or plasma glucose
levels
Serum glucose level is higher than whole blood glucose
level. Whole blood measurements of glucose may underestimate the plasma glucose
concentration by approximately 10-15%, because red blood cells (RBCs) contain
relatively low concentrations of glucose. Arterial and capillary samples may
overestimate the plasma glucose concentration by 10% in nonfasting patients.
Hold an extra tube of serum or plasma and refrigerate until laboratory glucose
is known.
Serum insulin
When blood glucose is less than 40 mg/dL, plasma insulin
concentration should be less than 5 and no higher than 10 µU/mL. This testing
may not be available in the emergency department.
Urine
Obtain a first voided urine dipstick for ketones. Failure
to find large ketones with hypoglycemia suggests that fat is not being
metabolized from adipose tissue (hyperinsulinism) or that fat cannot be used
for ketone body formation (enzymatic defects in fatty acid oxidation). Send
urine for organic acid analysis.
Screening for
metabolic errors
Electrospray ionization-tandem mass spectrometry in
asymptomatic persons allows earlier identification of clearly defined inborn
errors of metabolism. These disorders include aminoacidemias, urea cycle
disorders, organic acidurias, and fatty acid oxidation disorders. Earlier
recognition of these inborn errors of metabolism has the potential to reduce
morbidity and mortality rates in infants with these conditions.
This testing may not be available in the emergency department.
Imaging studies
The detection of adenomas by celiac angiography has had
limited success. The chance of detecting a tumor blush must be balanced against
the potential risk of causing vascular trauma in infants younger than age 2 years.
This testing may not be available in the emergency department.
Treatment
Approach Considerations
Start a 5% or 10% dextrose drip when hypoglycemia is
recurrent. In terms of prehospital care, stabilize acute, life-threatening
conditions and initiate supportive therapy in patients with hypoglycemia. If a
patient is alert and has intact airway protective reflexes, oral liquids
containing sugar (eg, orange juice) can be administered.
Emergency
department care
Supportive therapy includes oxygen, establishing an
intravenous (IV) line, and monitoring. Seizures unresponsive to correction of
hypoglycemia should be managed with appropriate anticonvulsants. Marked
acidosis (pH < 7.1) suggests shock or serious underlying disease and should
be treated appropriately. The treatment goal is to maintain a blood glucose
level of at least 45 mg/dL (2.5 mmol/L).
For the infant or child who does not drink but has intact
airway protective reflexes, orogastric or nasogastric administration of oral
liquids containing sugar may be performed.
Inpatient care
Any child with documented hypoglycemia not secondary to
insulin therapy should be hospitalized for careful monitoring and diagnostic
testing.
Surgery
If hypoglycemia is diagnosed in an infant younger than 3
months, surgical intervention may be necessary. Surgical exploration usually is
undertaken in severely affected neonates who are unresponsive to glucose and
somatostatin therapy. Near-total resection of 85-90% of the pancreas is
recommended for presumed congenital hyperinsulinism, which is most commonly
associated with an abnormality of beta-cell regulation throughout the pancreas.
Risks include the development of diabetes.
Medication
Hypoglycemia
should be treated as soon as possible to prevent complications of neurologic
damage. Early feeding of the newborn with breast milk or formula is encouraged.
For those unable to drink, a nasogastric tube can be used. The mainstay of
therapy for children that are alert with intact airway protection includes
orange juice at 20 mL/kg.
For
those who cannot protect their airway or are unable to drink, nasogastric,
intramuscular, intraosseous, or IV routes can be employed for the following
drugs used to raise glucose levels: dextrose, glucagon, diazoxide, and
octreotide. Case reports have shown that nifedipine may help to maintain
normoglycemia in children with PHHI.
Cortisol
should not be used, because it has minimal acute benefit and may delay the
diagnosis of the cause of hypoglycemia. Cortisol stimulates gluconeogenesis and
causes decreased use of glucose, which leads to overall elevated blood glucose
and may mask the true cause of hypoglycemia.
Anti-hypoglycemic Agents
These
agents elevate blood glucose levels.
Dextrose
is the treatment of choice. It is absorbed from the intestine, resulting in a
rapid increase in blood glucose concentration when administered orally. Give IV
dextrose to infants of diabetic mothers with transient neonatal
hyperinsulinemia for several days until hyperinsulinemia abates. Avoid
hyperglycemia evoking prompt insulin release, which may produce rebound
hypoglycemia. SGA infants and those with maternal toxemia or perinatal asphyxia
require dextrose IV infusion rates of more than 20 mg/kg/minute to control
levels. Treatment may be necessary for 2-4 weeks.
Hypoglycemia
PO:
As adults; 10-20 g as a single dose
IV:
0.5-1 g/kg up to 25 g
Dilute
before IV administration, may give more concentrated solution peripherally in
emergency (ie, 12.5-25%)
Diazoxide
increases blood glucose by inhibiting pancreatic insulin release and possibly
through an extrapancreatic effect. A hyperglycemic effect starts within an hour
and usually lasts a maximum of 8 hours with normal renal function. Diazoxide is
reportedly effective in SGA infants and in those with maternal toxemia or
perinatal asphyxia.
Dosing Forms & Strengths
oral
suspension
50mg/mL
Hypoglycemia
Indicated
for hypoglycemia due to hyperinsulinism associated with leucine sensitivity,
islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet
cell adenoma, or adenomatosis
Newborn/infant:
10 mg/kg/day PO divided q8hr initially; typical dosage range is 8-15 mg/kg/day
PO divided q8-12hr
Children:
3 mg/kg/day PO divided q8hr initially; typical dose range is 3-8 mg/kg/day PO
divided q8-12hr
Octreotide
is a long-acting analog of somatostatin that suppresses insulin secretion for
the short-term management of hypoglycemia.
Dosing Forms & Strengths
injectable
solution
·
0.05mg/mL
·
0.1mg/mL
·
0.2mg/mL
·
0.5mg/mL
·
1mg/mL
depot
injection
·
10mg/kit
·
20mg/kit
·
30mg/kit
Acromegaly
Solution:
50 mcg SC q8hr initially; titrate up to 500 mcg SC q8hr if necessary; after
successful treatment with solution for 2 weeks, initiate treatment with
suspension (depot injection)
Suspension
(depot injection): 20 mg IM (gluteal) every 4 weeks for 3 months; titrate up or
down to 10-30 mg IM every 4 weeks, depending on response; not to exceed 40 mg,
as follows
Symptoms
controlled: If GH < 1 ng/mL and IGF-1 normal, decrease dose to 10 mg IM
every 4 weeks; if GH < 2.5 ng/mL and IGF-1 normal, maintain dose at 20 mg IM
every 4 weeks
Symptoms
uncontrolled: If GH > 2.5 ng/mL or IGF-I elevated, increase dose to 30 mg IM
every 4 weeks; if symptoms persist, increase to 40 mg IM
Dosing
Considerations
·
Monitor
IGF-1 levels every 2 weeks to guide titration; goal: GH levels <5 ng/mL or
IGF-1 levels <1.9 units/mL (men) and <2.2 units/mL (women)
·
Monitor
IGF-1 or GH levels every 6 months
·
Withdraw
drug yearly for 4 weeks (solution) or 8 weeks (suspension) from patients who
have undergone irradiation to assess
Glucagon
may be used to treat hypoglycemia secondary to hyperinsulinemia and can be
administered to patients without initial IV access. Each mL contains 1 mg (ie,
1 U). Maximal glucose concentration occurs between 5-20 minutes after IV
administration and about 30 minutes after intramuscular (IM) administration.
Dosing Forms & Strengths
injection,
powder
1mg/vial
Hypoglycemia
Indicated
for severe hypoglycemic reactions in patients with diabetes treated with
insulin
Administer
oral glucose/IVdextrose to replete glycogen stores
GlucaGen
·
<25
kg or <6-8 years old and weight unknown: 0.5 mL SC/IM/IV
·
>25
kg or older than 6-8 years and weight unknown: 1 mL SC/IM/IV
Glucagon
Emergency Kit
·
<20
kg: 0.5 mg SC/IM/IV q20min PRN, OR 0.2-0.3 mg/kg SC/IM/IV q20min PRN
·
>20
kg or older than 6-8 years: 1 mg SC/IM/IV q20min PRN
Prognosis
Hypoglycemia
is the most common metabolic problem in neonates. Still, the level or duration
of hypoglycemia that is harmful to an infant's developing brain is not known.
Major long-term sequelae include neurologic damage resulting in mental
retardation, recurrent seizure activity, developmental delay, and personality
disorders. Some evidence suggests that severe hypoglycemia may impair
cardiovascular function.
Remission
of congenital hyperinsulinism generally does not occur, but the severity of the
disease may decrease with time.
Sumber:
http://emedicine.medscape.com/article/802334-workup
Hilarie Cranmer, MD, MPH, FACEP
Director of Disaster Response, MGH Center for Global Health; Attending
Physician, Department of Emergency Medicine, Massachusetts
General Hospital; Assistant Professor, Harvard Medical School and School of
Public Health
