Physiology of the Newborn

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


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


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

#.#" ;


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+


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


6/30

affected infants, e!change transfsion is indicated when the total indirect bilirbin leel is

greater than 2# mg


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


8/30

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#


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


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


11/30

Glomerular Filtration Rate

The glomerlar filtration rate $&( of newborns is slower than that of adlts. 3# rom 2"

m+


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


13/30

Illustrative !amples

#su))ce#t )lud

' "-kg prematre infant, dring the first * hors postoperatiely, has #.3 m+


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


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


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


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


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


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.=

+


20/30


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


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


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


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


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


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


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


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


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


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

Documents

Physiology of the Newborn