R5 PED2 - ANATOMI FISIOLOGI DAN FARMAKOLOGI NEONATUS.pptx

ANATOMI
FISIOLOGI
FARMAKOLOGI
NEONATUS

Outline
Airway and
Respiratory
01 Cardiovascular
02 Renal
03
Digestive, Metabolism
Endocrine, Temperature
Regulation
04 Hematologic and
immune system
05

neonates
0–1 months
infants
1–12
months
toddlers
12–24
months
young
children
2–12 years
Morgan & Mikhail’s Clinical Anesthesiology, 6ed

Airway and
Respiratory
01
5 major anatomic
differences
Tounge
Position of larynx
Epiglottis
Vocal cord
Subglottis

Airway and
Respiratory
01
Head, Tounge
• larger head and tongue
• Relatively large in proportion to the rest of the oral
cavity and therefore more easily obstructs the airway
• narrower nasal passages
make neonates and young infants obligate
nasal breathers until about 5 months of
age.

Airway and
Respiratory
01
Position of
Larynx
• anterior and cephalad larynx (the glottis
is at level of C4 versus C6 in adults)
• proximity of the tongue base to the
more superior larynx 🡪 more acute
angle between the plane of the tongue
and the plane of the glottic opening 🡪
makes visualization of laryngeal
structures more difficult
• Straight laryngoscope blade facilitates
visualization of an infant's larynx

Airway and
Respiratory
01
Epiglottis,
vocal cord
• Neonate : Long, omega-shaped Ω
epiglottis, pearly white vocal cords
• The shape of epiglottis 🡪 more
difficult to directly lift in the neonate
and infant with the tip of a
laryngoscope blade
• The vocal folds (cords) in an infant :
angled, the anterior insertion is more
caudad than the posterior insertion,
whereas in the adult is perpendicular
to the trachea 🡪 leads to difficulty
with tracheal intubation, especially
with the nasal approach
Cote, A Practice of Anesthesia for Infants and Children, 6ed

Airway and
respiratory
01
Subglottis
• Narrowest point : cricoid cartilage in children
< 5 years of age awake (adult 🡪rima
glottidis/vocal cords)
• The cricoid and thyroid cartilages reach adult
proportions by 10 to 12 years 🡪 eliminating both
the angulation of the vocal cords and the narrow
subglottic area.
• In contrast, in a child, it is common for an ETT to
pass easily through the vocal folds (glottic
opening) but not through the subglottic region
(lihat gambar)

Airway and
Respiratory
01
Muscles, ribs,
diaphragma
• Compared with older children and adults, neonates and
infants have weaker intercostalmuscles and weaker
diaphragms (due to a paucity of type I fibers) and less
efficient ventilation, more horizontal and pliable ribs, and
protuberant abdomens
• their cartilaginous rib cage makes their chest wall very
compliant.

Airway and
respiratory
01
VT, dead space,
airway resistance
• Tidal volume and dead space per kilogram are nearly
constant during development.
• The presence of fewer, smaller airways produces
increased airway resistance
RR
• Respiratory rate is increased in neonates and gradually falls
to adult values by adolescence
WOB
• The work of breathing is increased and respiratory
muscles easily fatigue (As the WOB increases,
diaphragmatic displacement must also increase to
overcome these deficiencies and maintain the tidal
volume) Morgan & Mikhail’s Clinical Anesthesiology, 6ed

Airway and
respiratory
01
Volume, the principal factor
that determines lung
compliance
Chest wall compliance
Increase age :

Airway and
Respiratory
01
Alveoli
• The alveoli are fully mature (increase size and number) by
about 8 years of age.
• Neonates and infants have fewer and smaller alveoli, reducing
lung compliance

The FRC (or, more appropriately, Vr)
of young infants at static conditions
(e.g., apnea, under general
anesthesia, or paralysis) decreases
to 10% - 15% of TLC, a level
incompatible with normal gas
exchange because of airway closure,
atelectasis, and V/Q imbalance
In awake infants and young children,
however, FRC is dynamically maintained
by a number of mechanisms for
preventing the collapse of the lung
FRC in young infants is therefore dynamically
determined; there is no fixed level of FRC
FRC normalized to weight (per kg)
is constant throughout development
Smith's Anesthesia for Infants and Children, 7 ed

These effects of reduced FRC may be exaggerated by the relatively
higher rate of oxygen consumption of neonates and infants, 6 to 8
mL/kg/min versus 3 to 4 mL/kg/min in adults
Moreover, hypoxic and hypercapnic ventilatory drives are not fully
developed in neonates and infants. In, contrast to adults, hypoxia and
hypercapnia may depress respiration in these patients.
Airway and
Respiratory
01
Low residual volume 🡪 resulting decrease in FRC
limits O2 reserves during periods of apnea (eg,
intubation attempts) and
predisposes neonates and infants to
atelectasis and hypoxemia
High chest wall compliant + smaller
alveoli = promotes chest wall collapse
during inspiration and relatively
low residual volume at expiration
To preserve FRC, the adductor muscles of the larynx act as an
expiratory “valve,” and restrict exhalation in order to
maintain PEEP. This is referred to as “laryngeal braking”

Airway and
respiratory
01
Closing volume is within the range of
tidal breathing in many older
adults and some children < 10 years
Small airways lacking cartilaginous support
depend on radial traction caused by the
elastic recoil of surrounding tissue to keep
them open, patency of these airways
Some airways likely remain
closed throughout tidal
breathing

Cardiovascular
02
• relatively fixed by the immature, noncompliant left ventricle
in neonates and infants 🡪 relatively fixed stroke volume
(1.5mls.kg-1 at birth)
• So increase in cardiac output is achieved through an
increase in heart rate, rather than an increase in stroke
volume as in adults 🡪 This limits the ability to increase the
cardiac output with a fluid challenge in a neonate, and it is
easy to push the neonate into pulmonary oedema if too
much fluid is given. The response to volume loading is more
predictable from 2 years of age.
Stroke Volume

Cardiovascular
02
• very sensitive to changes in heart rate. Basal heart rate is
greater in neonates and infants than in adults
• The relatively large cardiac output (in milliliters per minute per
kilogram) in neonates reflects their greater metabolic rate (on a
weight basis) and oxygen consumption compared with adults.
• cardiac output in both fullterm and preterm neonates = 220-
350 mL/kg/minute (2-3 kali dibanding dewasa), di usia 1 tahun
dst = 204 ± 45 ml/kg/minute
• activation of the parasympathetic nervous system, anesthetic
overdose, or hypoxia (most common cause) 🡪 trigger
bradycardia and profound reductions in cardiac output.
• bradicardy 🡪 can lead to hypotension, asystole, and
intraoperative death.
• It is important to avoid bradycardia. This should be treated
rapidly.
Cardiac output

Cardiovascular
02
• Between the ages of 3 - 8 years : ECG of a child looks similar to that of the
adult, with the exception of right precordial T waves, which are normally
inverted until about age 10 years
ECG

Cardiovascular
02
• There is little change in mean SBP between 6 weeks and
1 year of age and even between 1 year and 6 years
• thereafter, systolic pressure gradually increases with age
• Blood pressure measured in the lower extremity is less
than in the upper extremity in children
Blood pressure

Cardiovascular
02
• Infants are less able to respond to hypovolemia with compensatory
vasoconstriction
• Intravascular volume depletion in neonates and infants may be signaled by
hypotension without tachycardia
Vascular
• There is little change in mean SBP between 6 weeks - 1 year of age and even
between 1 - 6 years, thereafter, systolic pressure gradually increases with age
• Blood pressure measured in the lower extremity is less than in the upper
extremity in children
• Adolescents and adults who were born premature : BP > than who were born
full-term
Blood pressure

Cardiovascular
(extra: sympathetic - parasympathetic nervous system)
02
The nervous system and baroreceptor reflexes
• The parasympathetic components of the cardiovascular system : fully functional
at birth. In the newborn, vagal tone predominates.
• The sympathetic components : are not fully developed until 4 to 6 months of
age
• Baroreflexes to maintain BP and HR which involve medullary vasomotor
centers (pressor and depressor areas) : functional at birth in awake newborn
infant
• Sympathetic nervous system are not fully mature. CV is blunted response to
exogenous catecholamines
• Immature heart is more sensitive to depression by volatile anesthetics and to opioid-
induced bradycardia

01
02
03
04
Function
Immaturity
Creatinine
Clearance
Acid
Reach normal values (corrected for size)
by 6 months of age,
but this may be delayed until the child is
2 years old.
renal immaturity :
▪ ↓ creatinine clearance,
▪ impaired Na retention
▪ impaired glucose excretion
▪ impaired bicarbonate reabsorption
▪ ↓diluting ability, ↓concentrating ability
Renal
03
Creatinine clearance slowly
Increases in neonates,
reaching adult values
between 2 and 3 years of age
Basal acid production in neonates is
comparatively greater than in adults
and they are less able to respond to
an acid load. Endogenous acid production in
small children is between 50% and 100%
greater per kg than adults.

2
4
3
1
04
Albumin synthesis starts
at 3-4 months of gestation
and approaches adult values
by birth
Pediatric patients have a larger
surface area per kilogram than
adults (smaller BMI)
Thin skin, low fat content, and a
greater surface area relative to
weight promote greater heat loss to
the environment in neonates.
Prolonged exposure to an
inadequately warmed OK environment,
administration of room temperature iv
or irrigation fluid, and dehumidified
anesthetic gases.
Digestive, Metabolism Endocrine,
Temperature Regulation
Metabolism, its parameters
• Oxygen consumption
• CO2 production
• Cardiac output
• Alveolar ventilation
Correlate
better with
surface area
than with
weight
Hypotermia 🡪 delayed
awakening, cardiac arrhythmias,
respiratory depression, ↑
PVR, and susceptibility to
anesthetics, neuromuscular
blockers, other agents.

Hematologic and
immune system
05
▪ After the third month, the hemoglobin concentration stabilizes at
11.5 - 12 g/dL until about 2 years of age
▪ At birth, neutrophil granulocytes predominate but rapidly decrease
in number so that from the first week of life through 4 years of age,
the lymphocyte is the predominant cell. After the fourth year, the
values approximate adult values.

50-60% 70-75%
NEONATES AND INFANT
Total body water
ADULT
Total body water
Hematologic and
immune system
05
Neonates and infants have a proportionately
greater total water content than adults
Vd for many intravenous drugs
(eg, neuromuscular blockers)
is disproportionately greater in
neonates, infants, and young
children, and the optimal dose
(per
kilogram) is usually greater than
in older children and adults
Disproportionately smaller fat and
muscle prolongs the clinical
duration of action (by delaying
redistribution) of lipid-soluble
drugs such as
propofol and fentanyl.

FARMAKOLOGI NEONATUS
Pediatric Pharmacokinetic
Considerations
1. Size
2. Maturation
3. Organ function
SIZE
• Pediatric drug dosing is typically adjusted on a per-
kilogram basis 🡪 allometric dosing, in which adjustments
for weight are not made in a linear fashion
50th percentile weight (kg) = (Age × 2) + 9
MATURATION
• Maturation changes are generally completed within the
first 2 years of postnatal life

Pediatric Pharmacokinetic
Considerations
1. Size
2. Maturation
3. Organ function
ORGAN FUNCTION
• Morphine clearance is reduced in neonates because of
immature glucuronide conjugation, but clearance was
lower in critically ill neonates than healthier cohorts,
possibly attributable to reduced hepatic function.
• The maturation of creatinine clearance, a marker for GFR,
to reflect the influences of size, maturation, and organ
function.

NEUROMUSCULAR BLOCKERS
• Neonates and infants have a proportionately
greater total water content (70 – 75%) than
adults (50–60%).
• All muscle relaxants generally have a faster
onset
• As a result, the volume of distribution for
many intravenous drugs (eg, neuromuscular
blockers) is disproportionately greater in
neonates, infants, and young children, and the
optimal dose (per kilogram) is usually
greater than in older children and adults.
NMBA : optimal dose
(per kg) is usually
greater

• Children are more susceptible than adults to
cardiac arrhythmias, hyperkalemia,
rhabdomyolysis, myoglobinemia, masseter
spasm, and malignant hyperthermia associated
with succinylcholine.
• Succinylcholine has long been avoided for routine,
elective paralysis for intubation in children and
adolescents 🡪 atropine (0.1 mg minimum) is
prior to succinylcholine in children
Succinylcholine :
avoided for elective
paralysis

• Rocuronium (0.6 mg/kg intravenously) the drug of choice (when an
intravenous relaxant will be used) for routine intubation in pediatric patients
• Atracurium or cisatracurium may be preferred in young infants, particularly
for short procedures, because these drugs consistently display short to
intermediate duration.
• Nondepolarizing blockade can be reversed with neostigmine (0.03–0.07 mg/kg) or
edrophonium (0.5–1 mg/kg) along with an anticholinergic agent (glycopyrrolate,
0.01 mg/kg, or atropine, 0.01–0.02 mg/kg).

PROPOFOL
• After weight-adjustment of dosing, infants
and young children require larger doses of
propofol because of a larger volume of
distribution compared with adults.
• A disproportionately smaller fat and muscle
mass in neonates prolongs the clinical
duration of action (by delaying
redistribution) of lipid-soluble drugs such
as propofol and fentanyl.
larger doses of propofol
Lipid soluble drugs :
delaying redistribution
🡪 prolong duration of
action

PROPOFOL
• Recovery following a continuous infusion may be more rapid.
• Rates of infusion propofol for maintenance of anesthesia (up to 250 mcg/kg/min).
• Propofol is not recommended for prolonged sedation of critically ill pediatric patients in
the intensive care unit (ICU) 🡪 “propofol infusion syndrome” at doses (>5 mg/kg/h) :
a. Rhabdomyolysis
b. Metabolic acidosis
c. Hemodynamic instability
d. Hepatomegaly
e. Multiorgan failure. Morgan & Mikhail’s Clinical Anesthesiology, 6ed

THIOPENTAL
• Children require relatively larger doses of thiopental compared with adults
• The thiopental induction dose for neonates is 3 to 4 mg/kg compared with 5 to 6 mg/kg
for infants.
KETAMINE
• Neonates and infants may require slightly larger doses of ketamine, than
adults, but any actual difference, if present, is very small.
MIDAZOLAM
• Midazolam has the fastest clearance of all the benzodiazepines, but its
clearance is significantly reduced in neonates compared with older children.

DEXMEDETOMIDINE
• Dexmedetomidine has been used widely for sedation and as a supplement to
general anesthesia in children.
• In patients without an intravenous line, dexmedetomidine can be given
intranasally (1–2 mcg/kg) for sedation.

OPIOID
• Opioids appear to be more potent in
neonates than in older children and adults.
• Morphine sulfate, particularly in repeated
doses, should be used with caution in
neonates because hepatic conjugation is
reduced and renal clearance of morphine
metabolites is decreased.
• Remifentanil clearance is increased in
neonates and infants but elimination
halflife is unaltered compared with adults.
Morphine sulfate,
particularly in repeated
doses, should be used
with caution

• Increased intraabdominal pressure and
abdominal surgery may further reduce
hepatic blood flow 🡪 impair renal drug
handling, hepatic metabolism, and biliary
excretion of drugs in neonates and young
infants.
• Neonates also have decreased drug
binding to proteins, notably for local
anesthetics and many antibiotics. In the
case of bupivacaine, an increase in free drug
likely increases the risk of systemic toxicity.
Binding protein ↓ :
LA and antibiotic,
risk of systemic toxicity ↑

Rapid increase in alveolar
anesthetic concentration,
speeds inhalation
induction.
• This greater minute ventilation-to-
FRC ratio contributes to a rapid
increase in alveolar anesthetic
concentration that, combined with
relatively greater blood flow to the
brain, speeds inhalation induction.
• Furthermore, the blood/gas coefficients of volatile anesthetics are reduced in
neonates compared with adults, contributing to faster induction times and
potentially increasing the risk of accidental overdosage.

blood pressure :
sensitive to volatile anesthetics 🡪
myocardial depressants
• The blood pressure of neonates and infants
appears to be especially sensitive to
volatile anesthetics ec less-well-
developed compensatory mechanisms (eg,
vasoconstriction, tachycardia) and greater
sensitivity of the immature myocardium to
myocardial depressants.
• Sevoflurane appears to produce the least respiratory depression. Sevoflurane is the
preferred agent for inhaled induction in pediatric anesthesia.
• Emergence is fast following desflurane or sevoflurane, but both agents are
associated with agitation or delirium upon emergence, particularly in young
children. Because of the latter, some clinicians switch to isoflurane for
maintenance anesthesia following a sevoflurane induction
Sevoflurane :
preferred agent for inhaled
induction

R5 PED2 - ANATOMI FISIOLOGI DAN FARMAKOLOGI NEONATUS.pptx

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