Post on 04-Jun-2018
8/13/2019 Physiology of the Newborn
1/30
Modul Bedah Dasar
PHYSIOLOGY OF THE
NEWBORN
Newborns may be classified based on gestational age and weight. Preterm infants are those
born before 37 weeks of gestation. Term infants are those born between 37 and 42 weeks of
gestation, whereas post-term infants hae a gestation that e!ceeds 42 weeks. Newborns
whose weight is below the "#th percentile for age are considered small for gestational age
$%&'(, whereas those whose weight is at or aboe the )*th percentile are large for gestational
age $+&'(. The newborns whose weight falls between these e!tremes are appropriate for
gestational age $'&'(. %&' newborns are thoght to sffer intraterine growth retardation
as a reslt of placental, maternal, or fetal abnormalities. onditions associated with deiation
in intraterine growth are shown in igre"-".
%&' infants hae a body weight below what is appropriate for their age, yet their body length
and head circmference are age appropriate. To classify an infant as %&', the gestational age
mst be confirmed by the physical findings smmari/ed in Table "-".
1
8/13/2019 Physiology of the Newborn
2/30
'lthogh %&' infants may weigh the same as prematre infants, they hae different
physiologic characteristics. 0wing to intraterine malntrition, body fat leels are fre1ently
below " of the total body weight. This lack of body fat increases the risk of cold stress with
%&' infants. ypoglycemia deelops earlier in %&' infants owing to higher metabolic
actiity and redced glycogen stores. The red blood cell $5( olme and the total blood
olme are mch higher in the %&' infant compared with the preterm aerage for gestational
age or the non-%&' fll-term infant. This rise in 5 olme fre1ently leads to
polycythemia, with an associated rise in blood iscosity. 0wing to the ade1ate length of
gestation, the %&' infant has plmonary fnction approaching that of a fll-term infant or
one who is aerage for gestational age. 6nfants born before 37 weeks of gestation, regardless
of birth weight, are considered prematre. The physical e!amination of the prematre infant
reeals that the skin is thin and transparent with an absence of plantar creases. ingers are
soft and malleable, and ears hae poorly deeloped cartilage. 6n females, the labia minora
appear enlarged, bt the labia maora are small. 6n males, the testes are sally ndescended
and the scrotm is ndeeloped. %pecial problems with the preterm infant inclde the
following8
9 :eak sck refle!
9 6nade1ate gastrointestinal absorption
9 yaline membrane disease
9 6ntraentriclar hemorrhage
9 ypothermia
9 Patent dcts arterioss
9 'pnea
9 yperbilirbinemia
2
8/13/2019 Physiology of the Newborn
3/30
SPECIFIC PHYSIOLOGIC PROBLEMS OF THE NEWBORN
etal leels of glcose, calcim, and magnesim are careflly maintained by maternal
reglation. The transition to e!traterine life can hae profond effects on the physiologic
well-being of the newborn.
Glucose Metabols!
The fets maintains a blood glcose ale 7# to *# of the maternal ale by facilitated
diffsion across the placenta. There is a bildp of glycogen stores in the lier, skeleton, and
cardiac mscles dring the later stages of fetal deelopment bt little glconeogenesis. The
newborn mst depend on glycolysis ntil e!ogenos glcose is spplied. 'fter deliery, the
newborn depletes his or her hepatic glycogen stores within 2 to 3 hors. &lycogen stores are
more rapidly redced in prematre and %&' newborns. The newborn is seerely limited in
his or her ability to se fat and protein sbstrates to synthesi/e glcose.
Hypoglycemia
linical signs of hypoglycemia are nonspecific and may inclde a weak or high-pitched cry,
cyanosis, apnea, itteriness, apathy, sei/res, abnormal eye moements, temperatre
instability, hypotonia, and weak sck. %ome infants, howeer, e!hibit no signs, despite
e!tremely low blood glcose leels. ll parenteral caloric spport is achieed with
incremental increases in glcose, sally oer seeral days. 0ccasionally, inslin, #.##" to
#.#" ;
8/13/2019 Physiology of the Newborn
4/30
complicated pregnancies, sch as those of diabetic mothers or those receiing bicarbonate
infsions. alcitonin, which inhibits calcim mobili/ation from the bone, is increased in
prematre and asphy!iated infants. ?!change transfsions or massie transfsions of citrated
blood can reslt in the formation of calcim citrate comple!es, redcing the ioni/ed serm
calcim leels to dangeros or een fatal leels. +ate-onset $@4* hors of age( hypocalcemia
is less fre1ent now that most formlas are low in phosphate. %igns of hypocalcemia may
inclde itteriness, sei/res, cyanosis, omiting, and myocardial depression, some of which
are similar to the signs of hypoglycemia. ypocalcemic infants hae increased mscle tone,
which helps differentiate infants with hypocalcemia from those with hypoglycemia. 6oni/ed
calcim leels are easily determined in most intensie care settings. %ymptomatic
hypocalcemia is treated with "# calcim glconate administered intraenosly at a dosage
of " to 2 m+
8/13/2019 Physiology of the Newborn
5/30
the cord. Newborns with delayed cord clamping hae higher hemoglobin leels.' hematocrit
greater than =# sggests placental transfsion has occrred.
Pol%c%the!a
' central enos hemoglobin leel greater than 22 g
8/13/2019 Physiology of the Newborn
6/30
affected infants, e!change transfsion is indicated when the total indirect bilirbin leel is
greater than 2# mg
8/13/2019 Physiology of the Newborn
7/30
'au#dce
6n the hepatocyte, bilirbin created by hemolysis is congated to glcronic acid and
rendered water solble. ongated $also known as direct( bilirbin is e!creted in bile.
;ncongated bilirbin interferes with celllar respiration and is to!ic to neral cells.
%bse1ent neral damage is termed kernicterus and prodces athetoid cerebral palsy,
sei/res, sensorineral hearing loss, and, rarely, death. The newborn>s lier has a metabolic
e!cretory capacity for bilirbin that is not e1al to its task. ?en healthy fll-term infants
sally hae an eleated ncongated bilirbin leel. This peaks abot the third day of life at
D.= to 7.# mgs weight. 'lthogh specific
ctoffs defining the need for therapy hae not been niersally accepted, the following
recommendations are consistent with most practice patterns. Phototherapy is initiated for
newborns $"( less than "=## g, when the serm bilirbin leel reaches = mg
8/13/2019 Physiology of the Newborn
8/30
in determination of bilirbin leels for those infants who are less than 2* weeks of gestational
age or weigh less than "### g.6n these patients, the total serm bilirbin measrement shold
still be tili/ed.
Ret#o(ath% o) Pre!aturt%
etinopathy of prematrity $0P( deelops dring the actie phases of retinal asclar
deelopment in the first 3 or 4 months of life. The e!act cases are nknown, bt o!ygen
e!posre $@)3-)=("D and e!treme prematrity are the only risk factors that hae been
repeatedly and conincingly demonstrated. The risk of 0P is probably related to the degree
of immatrity, length of e!posre, and o!ygen concentration. 0P is fond in ".) of
prematre infants in large neonatal nits. etrolental fibroplasia is the pathologic change
obsered in the retina and oerlying itreos after the acte phases of 0P sbsides. ' stdy
condcted by the National 6nstittes of ealth fond that cryotherapy was effectie in
preenting retinal detachment, maclar fold, and retrolental fibroplasia. Treatment of 0P
more recently with laser photocoaglation has been shown to hae the added benefit of
sperior isal acity and less myopia when compared with cryotherapy in long-term follow-
p stdies.5oth treatments redce the incidence of blindness by appro!imately 2= bt do
not increase the chance of good isal acity $F2#
8/13/2019 Physiology of the Newborn
9/30
newborn radiates heat to a cooler srface withot contact with this srface(. 0f these,
radiation is the most difficlt to control. 6nfants prodce heat by increasing metabolic actiity
either by shiering like an adlt or by nonshiering thermogenesis, sing brown fat. 5rown-
fat thermogenesis may be inoled in thermoreglatory feeding and sleep cycles in the infant,
with an increase in body temperatre signaling an increase in metabolic demand.5rown-fat
thermogenesis may be rendered inactie by asopressors, by anesthetic agents, and throgh
ntritional depletion.Thermonetrality $the optimal thermal enironment for the newborn( is
the range of ambient temperatres in which the newborn with a normal body temperatre and
a minimal metabolic rate can maintain a constant body temperatre by asomotor control.
The critical temperature is the temperatre below which a metabolic response to cold is
necessary to replace lost heat. The appropriate incbator temperatre is determined by the
patient>s weight and postnatal age $igs. "-2 and "-3(. or low birth weight infants,
thermonetrality is 34G to 3=G p to D weeks of age and 3"G to 32G ntil "2 weeks of age.
6nfants who weigh 2 to 3 kg hae a thermonetrality /one of 3"G to 34G on the first day of
life and 2)G to 3"G ntil "2 days. Eoble-walled incbators offer the best thermonetral
enironment. adiant warmers cannot preent conection heat loss and lead to higher
insensible water loss. ailre to maintain thermonetrality leads to serios metabolic and
physiologic conse1ences. %pecial care mst be e!ercised to maintain the body temperatre
within normal limits in the operating room.
9
8/13/2019 Physiology of the Newborn
10/30
Fluds a#d Electrol%tes
't "2 weeks of gestation, the fets has a total body water content that is )4 of body weight.
This amont decreases to *# by 32 weeks> gestation and 7* by term $ig. "-4(.
' frther 3 to = redction in total body water content occrs in the first 3 to = days of
life. 5ody water contines to decline and reaches adlt leels $appro!imately D# of body
weight( by "H years of age. ?!tracelllar water also declines by " to 3 years of age. These
water composition changes progress in an orderly fashion in tero. Prematre deliery
re1ires the newborn to complete both fetal and term water nloading tasks. %rprisingly, the
prematre infant can complete fetal water nloading by " week after birth. Postnatal
redction in e!tracelllar flid olme has sch a high physiologic priority that it occrs een
in the presence of relatiely large ariationsn of flid intake.
10
8/13/2019 Physiology of the Newborn
11/30
Glomerular Filtration Rate
The glomerlar filtration rate $&( of newborns is slower than that of adlts. 3# rom 2"
m+
8/13/2019 Physiology of the Newborn
12/30
The patients were diided into three grops by condition8 $"( moderate srgical conditions,
sch as colostomies, laparotomies, and intestinal atresiaA $2( seere srgical conditions, sch
as midgt olls or gastroschisisA and $3( necroti/ing enterocolitis with perforation of the
bowel or bowel necrosis re1iring e!ploration. No InormalJ rine otpt e!ists for a gienneonate. 6deal rine otpt can be estimated by measring the osmolar load presented to the
kidney for e!cretion and calclating the amont of rine necessary to clear this load, if the
rine is maintained at an isotonic leel of 2*# m0sm
8/13/2019 Physiology of the Newborn
13/30
Illustrative !amples
#su))ce#t )lud
' "-kg prematre infant, dring the first * hors postoperatiely, has #.3 m+
8/13/2019 Physiology of the Newborn
14/30
? Na less than 2 sally indicates a prerenal case of oligria, whereas greater than 3
sally implies a renal case $e.g., acte tblar necrosis(. This patient is in acte renal
failre. The plan is to restrict flids to insensible losses pls measred losses for the ne!t 4
hors and to then reassess the plan sing both rine and serm stdies.
P+LMON&RY SYSTEM OF THE NEWBORN
The dichotomos branching of the bronchial tree is sally completed by "D weeks>
gestation. No actal aleoli are seen ntil 24 to 2D weeks> gestation. Therefore, shold the
fets be deliered at this age, the air-blood srface area for gas diffsion is limited. 5etween
24 and 2* weeks, the cboidal and colmnar cells become flatter and start differentiating into
type 6 $lining cells( and
8/13/2019 Physiology of the Newborn
15/30
single dose ia an endotracheal tbe an aerage of "2 mintes after birth. The patients who
receied %ranta demonstrated less seere radiographic changes at 24 hors of age
compared with infants who receied placebo. oweer, there was no clinical difference at 7
and 2* days after treatment compared with placebo. 6n the ?!osrf Neonatal stdy, the
prematre infants were randomi/ed to receie one dose of the artificial srfactant or air
placebo. 6n this stdy a significant redction was noted in the srfactant-treated infants
compared with the control grop in all of the following8 nmber of deaths attribted to
hyaline membrane disease, incidence of plmonary air leaks, o!ygen re1irements, and mean
airway pressre. 'n ncontrolled case series, in which srfactant was gien to fll-term
newborns with pnemonia and meconim aspiration, showed a significant improement in
o!ygenation after treatment.'lthogh these and other reports are promising, frther stdies
are needed to determine the most effectie dose, the nmber of doses, and the optimal timing
for srfactant treatment. egardless, srfactant therapy is an important addition to the
plmonary care of the preterm newborn. 0ne mlticenter stdy reported that srfactant
therapy early in the corse of fll-term newborn respiratory failre reslted in a significantly
lower re1irement for e!tracorporeal membrane o!ygenation and prodced no additional
morbidity. Prophylactic treatment as well as resce treatment with srfactant has proed to
redce the incidence and seerity of respiratory distress syndrome, air leaks, and mortality in
preterm infants $F3# weeks> gestational age(.34 'dditionally, infants sspected of respiratory
distress syndrome hae been shown to hae improed otcomes with early $F2 hor(
administration of srfactant when compared with delayed treatment $2-D hors(.This strategy
has been shown to be particlarly beneficial in those infants with a low rate of e!posre to
antenatal steroids.%eeral recent mlticenter stdies compared the efficacy and complication
rates of synthetic erss calf-lng cannla srfactant therapies for neonatal respiratory
failre. 5oth natral and synthetic srfactant hae been shown to be effectie in the treatment
and preention of respiratory distress syndrome. 6n comparatie trials with synthetic
srfactant, natral srfactant has demonstrated earlier improement in entilator
re1irements, fewer pnemothoraces, a marginal decrease in bronchoplmonary dysplasia,
and decreased mortality.Natral srfactant has been noted to hae a marginal increase in
intraentriclar hemorrhage, bt withot a difference in more serios $grade 3 to 4(
intraentriclar hemorrhage. oweer, spport e!ists for the synthetic srfactant
preparations. This spport is based on the theoretical adantage of a possibly redced risk of
intraentriclar hemorrhage, less e!posre to animal antigen with sbse1ent reactions, and
lower oerall cost. Newer-generation synthetic srfactant preparations containing peptides15
8/13/2019 Physiology of the Newborn
16/30
that mimic the action of hman srfactant protein-5 $%P-5( are crrently being inestigated.
6n recent randomi/ed, mlti-center trials, +cinactant $Eiscoery +aboratories, :arrington,
P'(, an %P-5 proteinMcontaining synthetic srfactant, was similar in efficacy and safety in
the preention and treatment of respiratory distress syndrome when compared with porcine-
deried $poractant alpha( srfactant, was more effectie than nonprotein synthetic
preparations, and reslted in decreased respiratory distress syndromeMrelated mortality rates
erss the boine-deried %ranta. 6t is hoped that ftre stdies will proide additional
insight into the appropriate applications of the aailable agents.
Mo#tor#"
ontinos monitoring of physiologic indices proides data that assist in assessing response
to therapy and trends that may be sed to predict catastrophe. Bany episodes of Isdden
deteriorationJ in critically ill patients are iewed, in retrospect, as changes in the clinical
condition that had been occrring for some time.
"rterial #lood Gases and $erived Indices
'rterial o!ygen tension $Pao2( is most commonly measred by obtaining an arterial blood
sample and by measring the partial pressre of o!ygen with a polarographic electrode.
Eefining normal parameters for Pao2 depends on the matration and age of the patient. 6n the
term newborn, the general definition for hypo!ia is a Pao2 less than == mm g, whereas that
for hypero!ia is a Pao2 greater than *# mm g. apillary blood samples are Iarteriali/edJ by
topical asodilators or heat to increase blood flow to a peripheral site. 5lood mst be freely
flowing and collected 1ickly to preent e!posre to the atmosphere. 5lood flowing
slggishly and e!posed to atmospheric o!ygen falsely raises the Pao2 from a capillary
sample, especially in the range of 4# to D# mm g. apillary blood p and carbon dio!ide
tension $Pco2( correlate well with arterial samples, e!cept when perfsion is poor. Pao2 is the
least reliable of all capillary blood gas determinations. 6n patients receiing o!ygen therapy
in whom Pao2 e!ceeds D# mm g, the capillary Pao2 correlates poorly with the arterial
measrement. 6n newborns, mbilical artery catheteri/ation can proide arterial access. The
catheter tip shold rest at the leel of the diaphragm or below +3. The second most fre1ently
sed arterial site is the radial artery. omplications of arterial blood sampling inclde
repeated blood loss and anemia. hanges in o!ygenation are sch that intermittent blood gas
sampling may miss critical episodes of hypo!ia or hypero!ia. 5ecase of the drawbacks of
e!-io monitoring, seeral in-io monitoring systems hae been sed.
16
8/13/2019 Physiology of the Newborn
17/30
%ulse &!imetry
The noninasie determination of o!ygen satration $%ao2( gies moment-to-moment
information regarding the aailability of o!ygen to the tisses. 6f the Pao2 is plotted against
the o!ygen satration of hemoglobin, the %-shaped hemoglobin dissociation cre is obtained
$ig. "-=(.
eferring to this cre, hemoglobin is =# satrated at 2= mm g Pao2 and )# satrated
at =# mm g. Plse o!imetry has a rapid $= to 7 seconds( response time, re1ires no
calibration, and may be left in place continosly. Plse o!imetry is not possible if the patient
is in shock, has peripheral asospasm, or has asclar constriction de to hypothermia.
6naccrate readings may occr in the presence of andice, direct high-intensity light, dark
skin pigmentation, and greater than *# fetal hemoglobin. 0!imetry is not a sensitie gide
to gas e!change in patients with high Pao2 de to the shape of the o!ygen dissociation cre.
's an e!ample, on the pper hori/ontal portion of the cre, large changes in Pao2 may occr
with little change in %ao2. 'n o!imeter reading of )= cold represent a Pao2 between D#
and "D# mm g. ' stdy to compare %ao2 from plse o!imetry with Pao2 determined from
indwelling arterial catheters has shown that %ao2 greater than or e1al to *= corresponds to
a Pao2 greater than == mm g and that %ao2 less than or e1al to )# corresponds to a Pao2
less than *# mm g.4* &idelines for monitoring infants sing plse o!imetry hae beensggested for the following three conditions8 ". 6n the infant with acte respiratory distress
withot direct arterial access, satration limits of *= $lower( and )2 $pper( shold be set.
2. 6n the older infant with chronic respiratory distress who is at low risk for retinopathy of
prematrity, the pper satration limit may be set at )=A the lower limit shold be set at
*7 to aoid plmonary asoconstriction and plmonary hypertension. 3. 5ecase the
concentration of fetal hemoglobin in newborns affects the accracy of plse o!imetry, infants
with arterial access shold hae both Pao2 and %ao2 monitored closely. ' graph shold be
17
8/13/2019 Physiology of the Newborn
18/30
kept at the bedside docmenting the %ao2 each time the Pao2 is measred. +imits for %ao2
alarm can be changed becase the characteristics of this relationship change.
'arbon $io!ide (ension
'rterial carbon dio!ide tension $Paco2( is a direct reflection of gas e!change in the lngs and
of the metabolic rate. 6n most clinical sitations, changes in Paco2 are de to changes in
entilation. or this reason, serial measrement of Paco2 is a practical method to assess the
ade1acy of entilation. The discrepancy among enos, capillary, and arterial carbon
dio!ide tensions is not great nder most conditions, althogh one stdy noted a significant
increase in Paco2 in enos samples compared with simltaneos arterial samples. 5ecase it
is possible to monitor Paco2 and p satisfactorily with enos or capillary blood samples and
becase plse o!imetry is now commonly sed to assess o!ygenation, many infants with
respiratory insfficiency no longer re1ire arterial catheters for monitoring.
nd)tidal 'arbon $io!ide
Beasring e!pired 02 by capnography proides a noninasie means of continosly
monitoring aleolar Pco2. apnometry measres 02 by an infrared sensor either placed in
line between the entilator circit and the endotracheal tbe or off to the side of the air flow,
both of which are applicable only to the intbated patient. ' comparatie stdy of end-tidal
02 in critically ill neonates demonstrated that both sidestream and mainstream end-tidal
02 measrements appro!imated Paco2.:hen the mainstream sensor was inserted into the
breathing circit, the Paco2 increased an aerage of 2 mm g. 'lthogh this is not likely to
significantly affect infants who are entilated, it might create fatige in weaning infants from
mechanical entilation. The accracy of the end-tidal 02 is diminished with small
endotracheal tbes.
'entral *enous 'atheter
6ndications for central enos catheter placement inclde $"( hemodynamic monitoring, $2(
inability to establish other enos access, $3( TPN, and $4( infsion of inotropic drgs or
other medications that cannot be gien peripherally. Beasrement of central enos pressre
to monitor olme stats is fre1ently sed in the resscitation of a critically ill patient. '
catheter placed in the sperior ena caa or right atrim measres the filling pressre of the
right side of the heart, which sally reflects left atrial and filling pressre of the left
entricle. 0ften, a wide discrepancy e!ists between left and right atrial pressre when
plmonary disease, oerwhelming sepsis, or cardiac lesions are present. To tili/e the data
effectiely, continos measrements mst be taken with a pressre transdcer connected to
a catheter accrately placed in the central enos system. Positie-pressre entilation,18
8/13/2019 Physiology of the Newborn
19/30
pnemothora!, abdominal distention, or pericardial tamponade all eleate central enos
pressre.
%ulmonary "rtery 'atheter
The plmonary artery pressre catheter has altered the care of the child with seere
cardioplmonary derangement by allowing direct measrement of cardioasclar ariables at
the bedside. The indications for plmonary catheter placement are listed in Table "-D.
:ith this catheter, it is possible to monitor central enos pressre, plmonary artery
pressre, plmonary wedge pressre, and cardiac otpt. ' 4- rench, doble-lmen catheter
and a =- to *- rench, triple-lmen catheter are aailable. The catheter is sallyplaced by
perctaneos methods $as in the adlt( e!cept in the smallest pediatric patient, in whom a
ctdown is sometimes re1ired. :hen the tip of the catheter is in a distal plmonary artery
and the balloon is inflated, the reslting pressre is generally an accrate reflection of left
atrial pressre becase the plmonary eins hae no ales. This plmonary IwedgeJ
pressre represents left entriclar filling pressre, which is sed as a reflection of preload.
The monitors display phasic pressres, bt treatment decisions are made based on the
electronically deried mean central enos pressre. ' low plmonary wedge pressre
sggests that blood olme mst be e!panded. ' high or normal plmonary wedge pressre
in the presence of contined signs of shock sggests left entriclar dysfnction. ardiac
otpt is sally measred in liters per minte. :hen related to body srface area, the otpt
is represented as the cardiac inde!+ which is simply the cardiac otpt diided by the body
srface area. The normali/ed cardiac inde! allows the ealation of cardiac performance
withot regard to body si/e. The sal resting ale for cardiac inde! is between 3.= and 4.=
+
8/13/2019 Physiology of the Newborn
20/30
8/13/2019 Physiology of the Newborn
21/30
flowing past the tip of the catheter. The waelengths of light are chosen so that both
o!yhemoglobin and deo!yhemoglobin are measred to determine the fraction of hemoglobin
satrated with o!ygen. The system re1ires either in-itro calibration by reflecting light from
a standardi/ed target that represents a known o!ygen satration or in-io calibration by
withdrawing blood from the plmonary artery catheter and measring the satration by
laboratory co-o!imetry. Bi!ed enos o!ygen satration ales within the normal range
$D*-77( indicate a normal balance between o!ygen spply and demand, proided that
asoreglation is intact and distribtion of peripheral blood flow is normal. Cales greater
than 77 are most commonly associated with syndromes of asodereglation, sch as sepsis.
;ncompensated changes in 02 satration, hemoglobin leel, or cardiac otpt lead to a
decrease in %02. ' sstained decrease in %02 greater than "# shold lead to measring
%ao2, hemoglobin leel, and cardiac otpt to determine the case of the decline.The most
common sorces of error in measring %02 are calibration and catheter malposition. The
most important concept in %02 monitoring is the adantage of continos monitoring,
which allows early warning of a deeloping problem. 'lthogh most clinical e!perience has
been with plmonary artery catheters, right atrial catheters are more easily placed and may
ths proide better information to detect hemodynamic deterioration earlier and permit more
rapid treatment of physiologic derangements. ' stdy has shown that when o!ygen
consmption was monitored and maintained at a consistent leel, the right atrial enos
satration was thoght to be an e!cellent measre.
SHOC,
%hock is a state in which the cardiac otpt is insfficient to delier ade1ate o!ygen to meet
metabolic demands of the tisses. ardioasclar fnction is determined by preload, cardiac
contractility, heart rate, and afterload. %hock may be classified broadly as hypoolemic,
cardiogenic, or septic.
H%(o*ole!c Shoc-
Preload is a fnction of the olme of blood presented to the entricles. 5ecase of the
impracticality of measring olme, preload is commonly monitored by atrial pressre
measrements. 6n most clinical sitations, right atrial pressre or central enos pressre is
the inde! of cardiac preload. 6n sitations in which left entriclar or right entriclar
compliance is abnormal, or in certain forms of congenital heart disease, right atrial pressre
may not correlate well with left atrial pressre. 6n infants and children, most shock sitations
21
8/13/2019 Physiology of the Newborn
22/30
are the reslt of redced preload secondary to flid loss, sch as from diarrhea, omiting, or
trama. Cirtally all forms of pediatric shock hae significant intraasclar and fnctional
interstitial flid deficits. ypoolemia reslts in decreased enos retrn to the heart. Preload
is redced, cardiac otpt falls, and the oerall reslt is a decrease in tisse perfsion.
6nasie infection and hypoolemia are the most common cases of shock in both children
and adlts. The first step in treating all forms of shock is to correct e!isting flid deficits.
6notropic drgs shold not be initiated ntil ade1ate intraasclar flid olme has been
established. The speed and olme of the infsate are determined by the patient>s responses,
particlarly changes in blood pressre, plse rate, rine otpt, and central enos pressre.
%hock reslting from acte hemorrhage is initially treated with the administration of "# to 2#
m+s lactate soltion or normal saline as flid bolses. 6f the patient does not
respond, a second bols of crystalloid is gien. Typespecific or crossmatched blood is gien
as needed. The choice of resscitation flid in shock that reslts from sepsis or from loss of
e!tracelllar flid $from conditions sch as peritonitis, intestinal obstrction, and pancreatitis(
is less clear. 0r initial resscitation flids inclde inger>s lactate or normal saline in older
infants and children and half-strength inger>s or #.= normal saline in the newborn. Eespite
or relctance to se colloid-containing soltions for shock, we make an e!ception in the
desperately ill newborn or prematre infant with septicemia. To correct the redced serm
factors, for e!ample in those children with a coaglopathy, we se fresh fro/en plasma or
specific factors as the resscitation flid. The rate and olme of resscitation flid gien is
adsted based on data obtained from monitoring the effects of the initial resscitation. 'fter
the initial bols is gien, the ade1acy of the replacement is assessed by monitoring rine
otpt, rine concentration, plasma acidosis, o!ygenation, arterial pressre, central enos
pressre, and plmonary wedge pressre, if indicated. :hen cardiac failre is present,
contined igoros deliery of large olmes of flid may case a frther increase in preload
to the failing myocardim and accelerate the downhill corse. 6n this setting, as otlined
preiosly, inotropic agents are gien while monitoring cardiac and plmonary fnction.
Cardo"e#c Shoc-
Byocardial contractility is sally e!pressed as the eection fraction, which is the proportion
of entriclar olme that is pmped. Byocardial contractility is redced with hypo!emia
and acidosis. 6notropic drgs increase cardiac contractility bt hae their best effect when
hypo!emia and acidosis are corrected. 'drenergic receptors are important in reglating
calcim fl!, which, in trn, is important in controlling myocardial contractility. The - and
O-adrenergic receptors are proteins present in the sarcolemma of myocardial and asclar22
8/13/2019 Physiology of the Newborn
23/30
smooth mscle cells. O" receptors are predominantly in the heart and, when stimlated, reslt
in increased contractility of myocardim. O2 receptors are predominantly in respiratory and
asclar smooth mscle. :hen stimlated, these receptors reslt in bronchodilation and
asodilation. "-'drenergic receptors are located on asclar smooth mscle and reslt in
asclar constriction when stimlated. 2-'drenergic receptors are fond mainly on
prenctional sympathetic nere terminals. The concept of dopaminergic receptors has also
been sed to accont for the cardioasclar effects of dopamine not mediated throgh or O
receptors. 'ctiation of dopaminergic receptors reslts in decreased renal and mesenteric
asclar resistance and, sally, increased blood flow. The most commonly sed inotropic
drgs are listed in Table "-7.
pinephrine
?pinephrine is an endogenos catecholamine with - and O-adrenergic effects. 't low doses,
the O-adrenergic effect predominates. These effects inclde an increase in heart rate, cardiac
contractility, cardiac otpt, and bronchiolar dilation. 5lood pressre rises, in part, not only
de to increased cardiac otpt bt also de to increased peripheral asclar resistance, which
is noted with higher doses at which -adrenergic effects become predominant. enal blood
flow may increase slightly, remain nchanged, or decrease depending on the balance between
greater cardiac otpt and the changes in peripheral asclar resistance, which lead to
regional redistribtion of blood flow. ardiac arrhythmias can be seen with epinephrine,
especially with higher doses. Eosages for treating compromised cardioasclar fnction
range from #.#= to ".# g
8/13/2019 Physiology of the Newborn
24/30
Isoproterenol
6soproterenol is a O-adrenergic agonist. 6t increases cardiac contractility and heart rate, with
little change in systemic asclar resistance. The peripheral asclar O-adrenergic effect and
lack of a peripheral asclar -adrenergic effect may allow redction of left entriclar
afterload. 6soproterenol>s intense chronotropic effect prodces tachycardia, which can limit
its seflness. 6soproterenol is administered intraenosly at a dosage of #." to #.3
g
8/13/2019 Physiology of the Newborn
25/30
shock has been stdied. Eobtamine infsion significantly increased cardiac inde!, stroke
inde!, and plmonary capillary wedge pressre, and it decreased systemic asclar
resistance. The drg appears more efficacios in treating cardiogenic shock than septic shock.
The adantage of dobtamine oer isoproterenol is its lesser chronotropic effect and its
tendency to maintain systemic pressre. The adantage oer dopamine is dobtamine>s lesser
peripheral asoconstrictor effect. The sal range of dosages for dobtamine is 2 to "=
g
8/13/2019 Physiology of the Newborn
26/30
and release arios mediators into the bloodstream. ?idence now spports the finding that
sbstances prodced by the microorganism, sch as lipopolysaccharide, endoto!in, e!oto!in,
lipid moieties, and other prodcts, can indce septic shock by stimlating host cells to release
cytokines, lekotrienes, and endorphins. ?ndoto!in is a lipopolysaccharide fond in the oter
membrane of gram-negatie bacteria. nctionally, the molecle is diided into three parts8
$"( the highly ariable 0-specific polysaccharide side chain $coneys serotypic specificity to
bacteria and can actiate the alternate pathway of complement(A $2( the -core region $less
ariable among different gram-negatie bacteriaA antibodies to this region cold be cross
protectie(A and $3( lipid-' $responsible for most of the to!icity of endoto!in(. ?ndoto!in
stimlates tmor necrosis factor $TN( and can directly actiate the classic pathway in the
absence of antibody. ?ndoto!in has been implicated as an important factor in the
pathogenesis of hman septic shock and gramnegatie sepsis. Therapy has focsed on
deeloping antibodies to endoto!in to treat septic shock. 'ntibodies to endoto!in hae been
sed in clinical trials of sepsis with ariable reslts. ytokines, especially TN, play a
dominant role in the host>s response. ?ndoto!in and e!oto!in both indce TN release in
io and prodce many other to!ic effects ia this endogenos mediator. TN is released
primarily from monocytes and macrophagesA howeer, it is also released from natral killer
cells, mast cells, and some actiated T lymphocytes. 0ther stimli for its release inclde
irses, fngi, parasites, and interlekin-" $6+-"(. 6n sepsis, the effects of TN release may
inclde cardiac dysfnction, disseminated intraasclar coaglation, and cardioasclar
collapse. TN release also cases the release of granlocyte- macrophage colony-stimlating
factor $&B-%(, interferon alfa, and 6+-". 'ntibodies against TN protect animals from
e!oto!in and bacterial challenge. Preiosly known as the endogenos pyrogen, 6+-" is
prodced primarily by macrophages and monocytes and plays a central role in stimlating a
ariety of host responses, inclding feer prodction, lymphocyte actiation, and endothelial
cell stimlation to prodce procoaglant actiity and to increase adhesieness. 6+-" also
cases the indction of the inhibitor of tisse plasminogen actiator and the prodction of
&B-%. These effects are balanced by the release of plateletactiating factor and
arachidonic metabolites. 6+-2, also known as T-cell growth factor, is prodced by actiated T
lymphocytes and strengthens the immne response by stimlating cell proliferation. 6ts
clinically apparent side effects inclde capillary leak syndrome, tachycardia, hypotension,
increased cardiac inde!, decreased systemic asclar resistance, and decreased left
entriclar eection fraction.%tdies done on dogs hae sggested that, in immatre animals,
septic shock is more lethal and has different mechanisms of tisse inry. These inclde more26
8/13/2019 Physiology of the Newborn
27/30
dramatic aberrations in blood pressre $more constant decline(, heart rate $progressie,
persistent tachycardia(, blood sgar leel $seere, progressie hypoglycemia(, acid-base
stats $seere acidosis(, and o!ygenation $seere hypo!emia(. These changes are significantly
different from those seen in the adlt animals that also e!perience improed srial of
almost D## $"*.= s. 3." hors( compared with the prematre animal. The neonate>s host
defense can sally respond sccessflly to ordinary microbial challenge. oweer, defense
against maor challenges appears limited and proides an e!planation for the high mortality
rate with maor neonatal sepsis. 's in adlts, the immne system consists of for maor
components8 cell-mediated immnity $T cells(, complement system, antibody-mediated
immnity $5 cells(, and macrophage-netrophil phagocytic system. The two most important
deficits in newborn host defenses that seem to increase the risk of bacterial sepsis are the
1antitatie and 1alitatie changes in the phagocytic system and the defects in antibody-
mediated immnity. The proliferatie rate of the granlocyte-macrophage precrsor has been
reported to be at near-ma!imal capacity in the neonate. oweer, the netrophil storage pool
is markedly redced in the newborn compared with the adlt. 'fter bacterial challenge,
newborns fail to increase stem cell proliferation and soon deplete their already redced
netrophil storage pool. Nmeros initro abnormalities hae been demonstrated in neonatal
polymorphonclear netrophils, especially in times of stress or infection.These abnormalities
inclde decreased deformability, chemota!is, phagocytosis, 3b receptor e!pression,
adherence, bacterial killing, and depressed o!idatie metabolism. hemota!is is impaired in
neonatal netrophils in response to arios bacterial organisms and antigen-antibody
comple!es.&ranlocytes are actiated by their interaction with endothelial cells followed by
entry into secondary lymphoid tisses ia the endothelial enles. 6nitial adhesion of
granlocytes is dependent on their e!pression of +-selectin, a cell adhesion molecle
e!pressed on the granlocyte cell srface. ?alation of cord blood has demonstrated a
significantly lower e!pression of +-selectin on granlocyte srfaces when compared with
older newborn $= days old( and adlt samples, indicating a depressed leel of interaction with
asclar endothelial cells at the initial stage of adhesion. 'lthogh phagocytosis has
additionally been demonstrated to be abnormal in neonatal phagocytes, it appears that this
phenomenon is most likely secondary to decreased opsonic actiity rather than an intrinsic
defect of the neonatal polymorphonclear netrophils. rrently, there is inconclsie
eidence to spport or refte the rotine se of granlocyte transfsions in the preention or
treatment of sepsis in the neonate. Preterm and term newborns hae poor responses to arios
antigenic stimli, redced gamma globlin leels at birth, and redced maternal27
8/13/2019 Physiology of the Newborn
28/30
immnogloblin spply from placental transport. 'lmost 33 of infants with a birth weight
less than "=## g deelop sbstantial hypogammagloblinemia.6g' and 6gB are also low de
to the inability of these two immnogloblins to cross the placenta. Neonates, therefore, are
sally more ssceptible to pyogenic bacterial infections becase most of the antibodies that
opsoni/e pyogenic bacterial capslar antigens are 6g& and 6gB. 6n addition, neonates do not
prodce type-specific antibodies, which appears to be secondary to a defect in the
differentiation of 5 lymphocytes into immnogloblin-secreting plasma cells and T
lymphocyteMmediated facilitation of antibody synthesis. 6n the term infant, total hemolytic
complement actiity, which measres the classic complement pathway, constittes
appro!imately =# of adlt actiity.0wing to lower leels of factor 5, the actiity of the
alternatie complement pathway is also decreased in the neonate. ibronectin, a plasma
protein that promotes reticloendothelial clearance of inading microorganisms, is deficient
in neonatal cord plasma. ;sing intraenos immnogloblins $6C6&s( for the prophyla!is and
treatment of sepsis in the newborn, especially the preterm, low birth weight infant, has been
stdied in nmeros trials with aried otcomes. 6n one stdy, a grop of infants weighing
"=## g was treated with =## mg
8/13/2019 Physiology of the Newborn
29/30
normal baseline leel by 24 hors.ecent stdies confirm the efficacy and safety of &-%
therapy for neonatal sepsis and netropenia.0ther stdies hae demonstrated no long-term
aderse hematologic, immnologic, or deelopmental effects from &-% therapy in the
septic neonate. Prolonged prophylactic treatment in the ery low birth weight neonate with
recombinant &B-% has been shown to be well tolerated and hae a significant decrease in
the rate of nosocomial infections. onfirmatory stdies are crrently being performed. The
crrent recommended daily pediatric dose is = ,gs disease.6n septic shock, asopressin has
profond effects on increasing blood pressre in intraasclar depleted states. The
mechanisms behind this obseration appear to be mediated by the ability of asopressin to
potentiate the catecholamine effects on blood essels. %eeral obserational and
nonrandomi/ed prospectie stdies hae demonstrated the efficacy of terlipressin, an arginine
asopressin analog, to be effectie as resce therapy in catecholamine-resistant shock in29
8/13/2019 Physiology of the Newborn
30/30
children and neonates. ' single randomi/ed, dobleblinded, placebo-controlled stdy has
been condcted that demonstrated a beneficial effect of asopressin in recalcitrant septic
shock.
Ta