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 ha e 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 abo e the )*th percentile are large for gestational age $+&'(. The newborns whose weight falls between these e!tremes are appropriate for gestational age $'&'(. %&' newborns are tho,ght to s,ffer intra,terine growth retardation as a res,lt of placental, maternal, or fetal abnormalities. -onditions associated with de iation in intra,terine growth are shown in .ig,re "-".

%&' infants ha e a body weight below what is appropriate for their age, yet their body length and head circ,mference are age appropriate. To classify an infant as %&', the gestational age m,st be confirmed by the physical findings s,mmari/ed in Table "-".

'ltho,gh %&' infants may weigh the same as premat,re infants, they ha e different physiologic characteristics. 0wing to intra,terine maln,trition, body fat le els are fre1,ently below "2 of the total body weight. This lack of body fat increases the risk of cold stress with %&' infants. 3ypoglycemia de elops earlier in %&' infants owing to higher metabolic acti ity and red,ced glycogen stores. The red blood cell $45-( ol,me and the total blood ol,me are m,ch higher in the %&' infant compared with the preterm a erage for gestational age or the non-%&' f,ll-term infant. This rise in 45ol,me fre1,ently leads to polycythemia, with an associated rise in blood iscosity. 0wing to the ade1,ate length of gestation, the %&' infant has p,lmonary f,nction approaching that of a f,ll-term infant or one who is a erage for gestational age. 6nfants born before 37 weeks of gestation, regardless of birth weight, are considered premat,re. The physical e!amination of the premat,re infant re eals that the skin is thin and transparent with an absence of plantar creases. .ingers are soft and malleable, and ears ha e poorly de eloped cartilage. 6n females, the labia minora appear enlarged, b,t the labia ma7ora are small. 6n males, the testes are ,s,ally ,ndescended and the scrot,m is ,nde eloped. %pecial problems with the preterm infant incl,de the following8 9 :eak s,ck refle! 9 6nade1,ate gastrointestinal absorption 9 3yaline membrane disease 9 6ntra entric,lar hemorrhage 9 3ypothermia 9 Patent d,ct,s arterios,s 9 'pnea 9 3yperbilir,binemia

SPECIFIC PHYSIOLOGIC PROBLEMS OF THE NEWBORN

.etal le els of gl,cose, calci,m, and magnesi,m are caref,lly maintained by maternal reg,lation. The transition to e!tra,terine life can ha e profo,nd effects on the physiologic well-being of the newborn. Glucose Metabol s! The fet,s maintains a blood gl,cose al,e 7#2 to *#2 of the maternal al,e by facilitated diff,sion across the placenta. There is a b,ild,p of glycogen stores in the li er, skeleton, and cardiac m,scles d,ring the later stages of fetal de elopment b,t little gl,coneogenesis. The newborn m,st depend on glycolysis ,ntil e!ogeno,s gl,cose is s,pplied. 'fter deli ery, the newborn depletes his or her hepatic glycogen stores within 2 to 3 ho,rs. &lycogen stores are more rapidly red,ced in premat,re and %&' newborns. The newborn is se erely limited in his or her ability to ,se fat and protein s,bstrates to synthesi/e gl,cose. Hypoglycemia -linical signs of hypoglycemia are nonspecific and may incl,de a weak or high-pitched cry, cyanosis, apnea, 7itteriness, apathy, sei/,res, abnormal eye mo ements, temperat,re instability, hypotonia, and weak s,ck. %ome infants, howe er, e!hibit no signs, despite e!tremely low blood gl,cose le els. .,ll parenteral caloric s,pport is achie ed with incremental increases in gl,cose, ,s,ally o er se eral days. 0ccasionally, ins,lin, #.##" to #.#" ;<kg<min, is gi en intra eno,sly to maintain normoglycemia and may be helpf,l in achie ing anabolism in infants of ery low birth weight. Calc u! -alci,m is contin,o,sly deli ered to the fet,s by acti e transport across the placenta. 0f the total amo,nt of calci,m transferred, 7=2 occ,rs after 2* weeks> gestation. This obser ation partially acco,nts for the high incidence of hypocalcemia in e!tremely preterm infants. 'ny neonate has a tendency for hypocalcemia d,e to limited calci,m stores, renal immat,rity, and relati e hypoparathyroidism secondary to s,ppression by high fetal calci,m le els. %ome infants are at f,rther risk for neonatal calci,m dist,rbances d,e to the presence of genetic defects, pathologic intra,terine conditions, or birth tra,ma. Newborn calci,m le els ,s,ally reach their nadir 24 to 4* ho,rs after deli ery, when parathyroid hormone responses become effecti e. 3ypocalcemia is defined as an ioni/ed calci,m le el of less than " mg<d+. 't greatest risk for hypocalcemia are preterm infants, newborns re1,iring s,rgery, and infants of
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complicated pregnancies, s,ch as those of diabetic mothers or those recei ing bicarbonate inf,sions. -alcitonin, which inhibits calci,m mobili/ation from the bone, is increased in premat,re and asphy!iated infants. ?!change transf,sions or massi e transf,sions of citrated blood can res,lt in the formation of calci,m citrate comple!es, red,cing the ioni/ed ser,m calci,m le els to dangero,s or e en fatal le els. +ate-onset $@4* ho,rs of age( hypocalcemia is less fre1,ent now that most form,las are low in phosphate. %igns of hypocalcemia may incl,de 7itteriness, sei/,res, cyanosis, omiting, and myocardial depression, some of which are similar to the signs of hypoglycemia. 3ypocalcemic infants ha e increased m,scle tone, which helps differentiate infants with hypocalcemia from those with hypoglycemia. 6oni/ed calci,m le els are easily determined in most intensi e care settings. %ymptomatic hypocalcemia is treated with "#2 calci,m gl,conate administered intra eno,sly at a dosage of " to 2 m+<kg o er "# min,tes while monitoring the electrocardiogram. 'symptomatic hypocalcemia is best treated with calci,m gl,conate in a dose of =# mg of elemental calci,m per kilogram per day added to the maintenance fl,idA " m+ of "#2 calci,m gl,conate contains ) mg of elemental calci,m. -alci,m mi!ed with sodi,m bicarbonate forms an insol,ble precipitate. 6f possible, parenteral calci,m sho,ld be gi en thro,gh a central eno,s line. Ma"#es u! Bagnesi,m is acti ely transported across the placenta. 3alf of the total-body magnesi,m is in the plasma and soft tiss,es. 3ypomagnesemia is obser ed with growth retardation, maternal diabetes, after e!change transf,sions, and with hypoparathyroidism. Bagnesi,m and calci,m metabolism are interrelated. The same infants at risk for hypocalcemia are also at risk for hypomagnesemia. :hene er an infant who has sei/,res that are belie ed to be associated with hypocalcemia does not respond to calci,m therapy, magnesi,m deficiency sho,ld be s,spected and confirmed by obtaining a ser,m magnesi,m le el. ?mergent treatment consists of magnesi,m s,lfate sol,tion, 2= to =# mg<kg 6C e ery D ho,rs, ,ntil normal le els are obtained. Blood $olu!e Total 45ol,me is at its highest point at deli ery. ?stimation of blood ol,me for premat,re infants, term neonates, and infants is s,mmari/ed in Table "-2. 5y abo,t 3 months of age, total blood ol,me per kilogram is nearly e1,al to ad,lt le els. The newborn blood ol,me is affected by shifts of blood between the placenta and the newborn before clamping
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the cord. Newborns with delayed cord clamping ha e higher hemoglobin le els. ' hematocrit greater than =#2 s,ggests placental transf,sion has occ,rred.

Pol%c%the! a ' central eno,s hemoglobin le el greater than 22 g<d+ or a hematocrit al,e greater than D=2 d,ring the "st week of life is defined as polycythemia. 'fter the central eno,s hematocrit al,e reaches D=2, f,rther increases res,lt in rapid e!ponential increases in blood iscosity. Neonatal polycythemia occ,rs in infants of diabetic mothers, infants of mothers with to!emia of pregnancy, or %&' infants. Polycythemia is treated ,sing a partial e!change of the infant>s blood with fresh whole blood or =2 alb,min. This is fre1,ently done when the hematocrit is greater than D=2. -apillary hematocrits are poor predictors of only. &#e! a 'nemia present at birth is d,e to hemolysis, blood loss, or decreased erythrocyte prod,ction. hemolytic anemia 3emolytic anemia is most often a res,lt of placental transfer of maternal antibodies that are destroying the infant>s erythrocytes. This can be determined by the direct -oombs test. The most common se ere anemia is 4h incompatibility. 3emolytic disease in the newborn prod,ces 7a,ndice, pallor, and hepatosplenomegaly. The most se erely affected infants manifest hydrops. This massi e edema is not strictly related to the hemoglobin le el of these infants. '50 incompatibility fre1,ently res,lts in hyperbilir,binemia b,t rarely ca,ses anemia. -ongenital infections, hemoglobinopathies $sickle cell disease(, and thalassemias prod,ce hemolytic anemia. 6n a se erely affected infant with a positi ereacting direct -oombs test res,lt, a cord hemoglobin le el of less than "#.= g<d+, or a cord bilir,bin le el of greater than 4.= mg<d+, immediate e!change transf,sion is indicated. .or less se erely
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iscosity.

Therefore, decisions to perform e!change transf,sions sho,ld be based on central hematocrits

affected infants, e!change transf,sion is indicated when the total indirect bilir,bin le el is greater than 2# mg<d+. hemorrhagic anemia %ignificant anemia can de elop from hemorrhage that occ,rs d,ring placental abr,ption. 6nternal bleeding $intra entric,lar, s,bgaleal, mediastinal, intra- abdominal( in infants can also often lead to se ere anemia. ;s,ally, hemorrhage occ,rs ac,tely d,ring deli ery, and the newborn occasionally re1,ires transf,sion. Twin-twin transf,sion reactions can prod,ce polycythemia in one newborn and profo,nd anemia in the other. %e ere cases can lead to death in the donor and hydrops in the recipient. anemia of prematurity Eecreased 45- prod,ction fre1,ently contrib,tes to anemia of premat,rity. ?rythropoietin is not released ,ntil a gestational age of 3# to 34 weeks has been reached. These infants, howe er, ha e large n,mbers of erythropoietin-sensiti e 45- progenitors. 4esearch has foc,sed on the role of recombinant erythropoietin in treating anemia in preterm infants. %,ccessf,l increases in hematocrit le els ,sing recombinant erythropoietin may ob iate the need for blood transf,sions and red,ce the risk of bloodborne infections and reactions. %t,dies s,ggest that ro,tine ,se of erythropoietin is probably helpf,l for the ery low birth weight infant $F7=# g(, b,t its reg,lar ,se for other preterm infants does not likely significantly red,ce the transf,sion rate. He!o"lob # 't birth, nearly *#2 of circ,lating hemoglobin is fetal. :hen infant erythropoiesis res,mes at abo,t 2 to 3 months of age, most new hemoglobin is ad,lt. :hen the o!ygen le el is 27 mm 3g, =#2 of the bo,nd o!ygen is released from ad,lt hemoglobin $P=#(. Therefore, the P=# of ad,lt hemoglobin is 27 mm 3g. 4ed,ction of hemoglobin>s affinity for o!ygen allows more o!ygen to be released into the tiss,es at a gi en o!ygen le el. .etal hemoglobin has a P=# al,e D to * mm 3g higher than that of ad,lt hemoglobin. This higher P=# al,e allows more efficient o!ygen deli ery from the placenta to the fetal tiss,es. 6n this sit,ation, the hemoglobin e1,ilibri,m c,r e is considered to be shifted to the left of normal. This increase in P=# is belie ed to be d,e to the fail,re of fetal hemoglobin to bind 2,3-diphosphoglycerate to the same degree as does ad,lt hemoglobin. This is somewhat of a disad antage to the newborn beca,se lower peripheral o!ygen le els are needed before o!ygen is released from fetal hemoglobin. 5y 4 to D months of age in a term infant, the hemoglobin e1,ilibri,m c,r e grad,ally shifts to the right and the P=# al,e appro!imates that of a normal ad,lt.
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'au#d ce 6n the hepatocyte, bilir,bin created by hemolysis is con7,gated to gl,c,ronic acid and rendered water sol,ble. -on7,gated $also known as direct( bilir,bin is e!creted in bile. ;ncon7,gated bilir,bin interferes with cell,lar respiration and is to!ic to ne,ral cells. %,bse1,ent ne,ral damage is termed kernicterus and prod,ces athetoid cerebral palsy, sei/,res, sensorine,ral hearing loss, and, rarely, death. The newborn>s li er has a metabolic e!cretory capacity for bilir,bin that is not e1,al to its task. ? en healthy f,ll-term infants ,s,ally ha e an ele ated ,ncon7,gated bilir,bin le el. This peaks abo,t the third day of life at D.= to 7.# mg<d+ and does not ret,rn to normal ,ntil the "#th day of life. ' total bilir,bin le el greater than 7 mg<d+ in the first 24 ho,rs or greater than "3 mg<d+ at any time in f,llterm newborns often prompts an in estigation for the ca,se. 5reast-fed infants ,s,ally ha e ser,m bilir,bin le els " to 2 mg<d+ greater than form,la-fed infants. The common ca,ses of prolonged indirect hyperbilir,binemia are listed in Table "-3.

Pathologic 7a,ndice within the first 3D ho,rs of life is ,s,ally d,e to e!cessi e prod,ction of bilir,bin. 3yperbilir,binemia is managed based on the infant>s weight. 'ltho,gh specific c,toffs defining the need for therapy ha e not been ,ni ersally accepted, the following recommendations are consistent with most practice patterns. Phototherapy is initiated for newborns $"( less than "=## g, when the ser,m bilir,bin le el reaches = mg<d+A $2( "=## to 2### g, when the ser,m bilir,bin le el reaches * mg<d+A or $3( 2### to 2=## g, when the ser,m bilir,bin le el reaches "# mg<d+. .orm,la-fed term infants witho,t hemolytic disease are treated by phototherapy when le els reach "3 mg<d+. .or hemolytic- related hyperbilir,binemia, phototherapy is recommended when the ser,m bilir,bin le el e!ceeds "# mg<d+ by "2 ho,rs of life, "2 mg<d+ by "* ho,rs, "4 mg<d+ by 24 ho,rs, or "= mg<d+ by 3D ho,rs. 'n absol,te bilir,bin le el that triggers e!change transf,sion is still not established, b,t most e!change transf,sion decisions are based on the ser,m bilir,bin le el and its rate of rise. The ,se of transc,taneo,s de ices for meas,rement of plasma bilir,bin le els has become increasingly common. 3owe er, these de ices ha e limited reliability and acc,racy
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in determination of bilir,bin le els for those infants who are less than 2* weeks of gestational age or weigh less than "### g. 6n these patients, the total ser,m bilir,bin meas,rement sho,ld still be ,tili/ed. Ret #o(ath% o) Pre!atur t% 4etinopathy of premat,rity $40P( de elops d,ring the acti e phases of retinal asc,lar de elopment in the first 3 or 4 months of life. The e!act ca,ses are ,nknown, b,t o!ygen e!pos,re $@)32-)=2("D and e!treme premat,rity are the only risk factors that ha e been repeatedly and con incingly demonstrated. The risk of 40P is probably related to the degree of immat,rity, length of e!pos,re, and o!ygen concentration. 40P is fo,nd in ".)2 of premat,re infants in large neonatal ,nits. 4etrolental fibroplasia is the pathologic change obser ed in the retina and o erlying itreo,s after the ac,te phases of 40P s,bsides. ' st,dy cond,cted by the National 6nstit,tes of 3ealth fo,nd that cryotherapy was effecti e in pre enting retinal detachment, mac,lar fold, and retrolental fibroplasia. Treatment of 40P more recently with laser photocoag,lation has been shown to ha e the added benefit of s,perior is,al ac,ity and less myopia when compared with cryotherapy in long-term follow,p st,dies. 5oth treatments red,ce the incidence of blindness by appro!imately 2=2 b,t do not increase the chance of good is,al ac,ity $F2#<4#(. The 'merican 'cademy of Pediatrics g,idelines recommend that all infants who recei ed o!ygen therapy who weigh less than "=## g and are fewer than 32 weeks> gestation, and selected infants with a birth weight between "=## and 2### g or gestational age of more than 32 weeks with an ,nstable clinical co,rse, incl,ding those re1,iring cardiorespiratory s,pport and who are belie ed by their attending pediatrician or neonatologist to be at high risk, sho,ld ,ndergo a screening e!amination for 40P. ' re-e!amination sched,le determined by the e!amining ophthalmologist, based on is,al e!amination findings, sho,ld be closely followed. Ther!ore"ulat o# ' homeotherm is a mammal that can maintain a constant deep body temperat,re. 'ltho,gh h,mans are homeothermic, newborns ha e diffic,lty maintaining constant deep body temperat,re owing to their relati ely large s,rface area, poor thermal reg,lation, and small mass to act as a heat sink. 3eat loss may occ,r from $"( e aporation $a wet newborn or a newborn in contact with a wet s,rface(, $2( cond,ction $direct skin contact with a cool s,rface(, $3( con ection $air c,rrents blowing o er the newborn(, and $4( radiation $the
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newborn radiates heat to a cooler s,rface witho,t contact with this s,rface(. 0f these, radiation is the most diffic,lt to control. 6nfants prod,ce heat by increasing metabolic acti ity either by shi ering like an ad,lt or by nonshi ering thermogenesis, ,sing brown fat. 5rownfat thermogenesis may be in ol ed in thermoreg,latory feeding and sleep cycles in the infant, with an increase in body temperat,re signaling an increase in metabolic demand. 5rown-fat thermogenesis may be rendered inacti e by asopressors, by anesthetic agents, and thro,gh n,tritional depletion. Thermone,trality $the optimal thermal en ironment for the newborn( is the range of ambient temperat,res in which the newborn with a normal body temperat,re and a minimal metabolic rate can maintain a constant body temperat,re by asomotor control. The critical temperature is the temperat,re below which a metabolic response to cold is necessary to replace lost heat. The appropriate inc,bator temperat,re is determined by the patient>s weight and postnatal age $.igs. "-2 and "-3(. .or low birth weight infants, thermone,trality 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 ha e a thermone,trality /one of 3"G to 34G- on the first day of life and 2)G to 3"G- ,ntil "2 days. Eo,ble-walled inc,bators offer the best thermone,tral en ironment. 4adiant warmers cannot pre ent con ection heat loss and lead to higher insensible water loss. .ail,re to maintain thermone,trality leads to serio,s metabolic and physiologic conse1,ences. %pecial care m,st be e!ercised to maintain the body temperat,re within normal limits in the operating room.

Flu ds a#d Electrol%tes 't "2 weeks of gestation, the fet,s has a total body water content that is )42 of body weight. This amo,nt decreases to *#2 by 32 weeks> gestation and 7*2 by term $.ig. "-4(.

' f,rther 32 to =2 red,ction in total body water content occ,rs in the first 3 to = days of life. 5ody water contin,es to decline and reaches ad,lt le els $appro!imately D#2 of body weight( by "H years of age. ?!tracell,lar water also declines by " to 3 years of age. These water composition changes progress in an orderly fashion in ,tero. Premat,re deli ery re1,ires the newborn to complete both fetal and term water ,nloading tasks. %,rprisingly, the premat,re infant can complete fetal water ,nloading by " week after birth. Postnatal red,ction in e!tracell,lar fl,id ol,me has s,ch a high physiologic priority that it occ,rs e en in the presence of relati ely large ariationsn of fl,id intake.
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Glomerular Filtration Rate The glomer,lar filtration rate $&.4( of newborns is slower than that of ad,lts.3# .rom 2" m+<min<".73 m2 at birth in the term infant, &.4 1,ickly increases to D# m+<min<".73 m2 by 2 weeks of age. &.4 reaches ad,lt le els by "H to 2 years of age. ' preterm infant has a &.4 that is only slightly slower than that of a f,llterm infant. 6n addition to this difference in &.4, the concentrating capacity of the preterm and the f,ll-term infant is well below that of the ad,lt. 'n infant responding to water depri ation increases ,rine osmolarity to a ma!im,m of only D## m0sm<kg. This is in contrast to the ad,lt, whose ,rine concentration can reach "2## m0sm<kg. 6t appears that the difference in concentrating capacity is d,e to the insensiti ity of the collecting t,b,les of the newborn to antidi,retic hormone. 'ltho,gh the newborn cannot concentrate ,rine as efficiently as the ad,lt, the newborn can e!crete ery dil,te ,rine at 3# to =# m0sm<kg. Newborns are ,nable to e!crete e!cess sodi,m, an inability tho,ght to be d,e to a t,b,lar defect. Term infants are able to conser e sodi,m, b,t premat,re infants are considered Isalt wastersJ beca,se they ha e an inappropriate ,rinary sodi,m e!cretion, e en with restricted sodi,m intake. Insensible Water Loss 6nsensible water loss from the l,ngs can be essentially eliminated by h,midification of inspired air. Transepithelial water loss occ,rs by the diff,sion of water molec,les thro,gh the strat,m corne,m of the skin. 0wing to the immat,re skin, preterm infants of 2= to 27 weeks> gestation can lose more than "2# m+<kg<day of water by this mechanism. Transepithelial water loss decreases as age increases. Neonatal Fluid Requirements To estimate fl,id re1,irements in the newborn re1,ires an ,nderstanding of $"( pree!isting fl,id deficit or e!cess, $2( metabolic demands, and $3( losses. 5eca,se these factors change 1,ickly in the critically ill newborn, fre1,ent ad7,stments in fl,id management are necessary. 3o,rly monitoring of intake and o,tp,t allows early recognition of fl,id balance that will affect treatment decisions. This dynamic approach re1,ires two components8 an initial ho,rly fl,id intake that is safe and a monitoring system to detect the patient>s response to the treatment program selected. ' table of initial ol,mes e!pressed in rates of milliliters per kilogram per 24 ho,rs for ario,s s,rgical conditions has been de eloped as a res,lt of a st,dy of a large gro,p of infants followed d,ring their first 3 postoperati e days $Table "-4(.

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The patients were di ided into three gro,ps by condition8 $"( moderate s,rgical conditions, s,ch as colostomies, laparotomies, and intestinal atresiaA $2( se ere s,rgical conditions, s,ch as midg,t ol ,l,s or gastroschisisA and $3( necroti/ing enterocolitis with perforation of the bowel or bowel necrosis re1,iring e!ploration. No InormalJ ,rine o,tp,t e!ists for a gi en neonate. 6deal ,rine o,tp,t can be estimated by meas,ring the osmolar load presented to the kidney for e!cretion and calc,lating the amo,nt of ,rine necessary to clear this load, if the ,rine is maintained at an isotonic le el of 2*# m0sm<d+ $Table "-=(.

'fter administering the initial ho,rly ol,me for 4 to * ho,rs, depending on the newborn>s condition, he or she is reassessed by obser ing ,rine o,tp,t and concentration. :ith these two factors, it is possible to determine the state of hydration of most newborns and their responses to the initial ol,me. 6n more diffic,lt cases, changes in serial ser,m sodi,m $Na(, blood ,rea nitrogen $5;N(, creatinine, and osmolarity along with ,rine Na, creatinine, and osmolarity make it possible to assess the infant>s response to the initial ol,me and to ,se fl,id stat,s to g,ide the ne!t 4 to * ho,rs> fl,id intake.

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Illustrative !amples #su)) c e#t )lu d ' "-kg premat,re infant, d,ring the first * ho,rs postoperati ely, has #.3 m+<kg<hr of ,rine o,tp,t. %pecific gra ity is ".#2=. Pre io,s initial ol,me was = m+<kg<hr. %er,m 5;N has increased from 4 mg<d+ to * mg<d+A hematocrit al,e has increased from 3=2 to 372, witho,t transf,sion. This child is dry. The treatment is to increase the ho,rly ol,me to 7 m+<kg<hr for the ne!t 4 ho,rs and to monitor the s,bse1,ent ,rine o,tp,t and concentration to reassess fl,id stat,s. #a((ro(r ate a#t d uret c hor!o#e res(o#se ' 3-kg newborn with congenital diaphragmatic hernia d,ring the first * ho,rs postoperati ely has a ,rine o,tp,t of #.2 m+<kg<hr, with a ,rine osmolarity of 3D# m0sm<+. The pre io,s initial ol,me was "2# m+<kg<day $"= m+<hr(. The ser,m osmolarity al,e has decreased from 3## m0sm preoperati ely to 27* m0sm<+A and 5;N has decreased from "2 to * mg<d+. The inappropriate antidi,retic hormone response re1,ires red,ction in fl,id ol,me from "2# to )# m+< kg<day for the ne!t 4 to * ho,rs. 4epeat ,rine and ser,m meas,rements will g,ide the f,rther ad7,stment of fl,id administration. o*erh%drat o# ' 3-kg newborn, 24 ho,rs after operati e clos,re of gastroschisis, had an a erage ,rine o,tp,t of 3 m+<kg<hr o er the pre io,s 4 ho,rs. E,ring that time period, the infant recei ed fl,ids at a rate of "*# m+<kg<day. The specific gra ity of the ,rine has decreased to ".##DA ser,m 5;N is 4 mg<d+A hematocrit al,e is 3#2, down from 3=2 preoperati ely. The total ser,m protein concentration is 4.# mg<d+, down from 4.= mg<d+. This child is being o erhydrated. The treatment is to decrease the fl,ids to 3 m+<kg<hr for the ne!t 4 ho,rs and then to reassess ,rine o,tp,t and concentration. re#al )a lure ' =-kg infant with se ere sepsis secondary to 3irschspr,ng>s enterocolitis has had a ,rine o,tp,t of #." m+<kg<hr for the past * ho,rs. The specific gra ity is ".#"2A ser,m sodi,m, "=# mg<d+A 5;N, 2= mg<d+A creatinine, ".= mg<d+A ,rine sodi,m, "3# m?1A and ,rine creatinine, 2# mg<d+. .ractional Na e!cretion $.? Na( is shown by the following e1,ation8 .?NaK $;Na L P-r( K"3# L ".= $PNa( L $;-r(K "=# 2# K ")=<3### L "## K D.=2$ normal K 22 to32(
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.? Na less than 22 ,s,ally indicates a prerenal ca,se of olig,ria, whereas greater than 32 ,s,ally implies a renal ca,se $e.g., ac,te t,b,lar necrosis(. This patient is in ac,te renal fail,re. The plan is to restrict fl,ids to insensible losses pl,s meas,red losses for the ne!t 4 ho,rs and to then reassess the plan ,sing both ,rine and ser,m st,dies.

P+LMON&RY SYSTEM OF THE NEWBORN

The dichotomo,s branching of the bronchial tree is ,s,ally completed by "D weeks> gestation. No act,al al eoli are seen ,ntil 24 to 2D weeks> gestation. Therefore, sho,ld the fet,s be deli ered at this age, the air-blood s,rface area for gas diff,sion is limited. 5etween 24 and 2* weeks, the c,boidal and col,mnar cells become flatter and start differentiating into type 6 $lining cells( and<or type 66 $gran,lar( pne,mocytes. 5etween 2D and 32 weeks of gestation, terminal air sacs begin to gi e way to air spaces. .rom 32 to 3D weeks, f,rther b,dding of these air spaces occ,rs and al eoli become n,mero,s. 't the same time, the phospholipids that constit,te p,lmonary s,rfactant begin to line the terminal l,ng air spaces. %,rfactant is prod,ced by type 66 pne,mocytes and is e!tremely important in maintaining al eolar stability. The change in the ratio of the amniotic phospholipids, lecithin and sphingomyelin, is ,sed to assess fetal l,ng mat,rity. ' ratio greater than 2 is considered compatible with mat,re l,ng f,nction. 'bsence of ade1,ate s,rfactant leads to hyaline membrane disease or respiratory distress syndrome. 3yaline membrane disease is present in nearly "#2 of all premat,re infants and is the leading ca,se of morbidity and mortality $3#2( among premat,re infants in the ;nited %tates. 0ther conditions associated with p,lmonary distress in the newborn incl,de delayed fetal l,ng absorption $wet l,ng syndrome(, intra,terine aspiration pne,monia $meconi,m aspiration(, and intrapart,m pne,monia. 6n all of these conditions, endotracheal int,bation and mechanical entilation may be re1,ired for hypo!ia, -02 retention, or apnea. Centilator options and management are disc,ssed in -hapter 7. Sur)acta#t %,rfactant deficiency is belie ed to be the ma7or ca,se of hyaline membrane disease. %,rfactant replacement therapy impro es effecti e o!ygenation. Three s,rfactant preparations ha e been ,nder in estigation8 $"( s,rfactant deri ed from bo ine or porcine l,ng, $2( h,man s,rfactant e!tracted from amniotic fl,id, and $3( artificial s,rfactant. B,lticenter-based, randomi/ed trials for modified bo ine s,rfactant $%,r anta( and artificial s,rfactant $?!os,rf Neonatal( ha e been p,blished. 6n one st,dy, %,r anta was gi en as a
14

single dose ia an endotracheal t,be an a erage of "2 min,tes after birth. The patients who recei ed %,r anta demonstrated less se ere radiographic changes at 24 ho,rs of age compared with infants who recei ed placebo. 3owe er, there was no clinical difference at 7 and 2* days after treatment compared with placebo. 6n the ?!os,rf Neonatal st,dy, the premat,re infants were randomi/ed to recei e one dose of the artificial s,rfactant or air placebo. 6n this st,dy a significant red,ction was noted in the s,rfactant-treated infants compared with the control gro,p in all of the following8 n,mber of deaths attrib,ted to hyaline membrane disease, incidence of p,lmonary air leaks, o!ygen re1,irements, and mean airway press,re. 'n ,ncontrolled case series, in which s,rfactant was gi en to f,ll-term newborns with pne,monia and meconi,m aspiration, showed a significant impro ement in o!ygenation after treatment. 'ltho,gh these and other reports are promising, f,rther st,dies are needed to determine the most effecti e dose, the n,mber of doses, and the optimal timing for s,rfactant treatment. 4egardless, s,rfactant therapy is an important addition to the p,lmonary care of the preterm newborn. 0ne m,lticenter st,dy reported that s,rfactant therapy early in the co,rse of f,ll-term newborn respiratory fail,re res,lted in a significantly lower re1,irement for e!tracorporeal membrane o!ygenation and prod,ced no additional morbidity. Prophylactic treatment as well as resc,e treatment with s,rfactant has pro ed to red,ce the incidence and se erity of respiratory distress syndrome, air leaks, and mortality in preterm infants $F3# weeks> gestational age(.34 'dditionally, infants s,spected of respiratory distress syndrome ha e been shown to ha e impro ed o,tcomes with early $F2 ho,r( administration of s,rfactant when compared with delayed treatment $2-D ho,rs(. This strategy has been shown to be partic,larly beneficial in those infants with a low rate of e!pos,re to antenatal steroids. %e eral recent m,lticenter st,dies compared the efficacy and complication rates of synthetic ers,s calf-l,ng cann,la s,rfactant therapies for neonatal respiratory fail,re. 5oth nat,ral and synthetic s,rfactant ha e been shown to be effecti e in the treatment and pre ention of respiratory distress syndrome. 6n comparati e trials with synthetic s,rfactant, nat,ral s,rfactant has demonstrated earlier impro ement in entilator re1,irements, fewer pne,mothoraces, a marginal decrease in bronchop,lmonary dysplasia, and decreased mortality. Nat,ral s,rfactant has been noted to ha e a marginal increase in intra entric,lar hemorrhage, b,t witho,t a difference in more serio,s $grade 3 to 4( intra entric,lar hemorrhage. 3owe er, s,pport e!ists for the synthetic s,rfactant preparations. This s,pport is based on the theoretical ad antage of a possibly red,ced risk of intra entric,lar hemorrhage, less e!pos,re to animal antigen with s,bse1,ent reactions, and lower o erall cost. Newer-generation synthetic s,rfactant preparations containing peptides
15

that mimic the action of h,man s,rfactant protein-5 $%P-5( are c,rrently being in estigated. 6n recent randomi/ed, m,lti-center trials, +,cinactant $Eisco ery +aboratories, :arrington, P'(, an %P-5 proteinMcontaining synthetic s,rfactant, was similar in efficacy and safety in the pre ention and treatment of respiratory distress syndrome when compared with porcinederi ed $poractant alpha( s,rfactant, was more effecti e than nonprotein synthetic preparations, and res,lted in decreased respiratory distress syndromeMrelated mortality rates ers,s the bo ine-deri ed %,r anta. 6t is hoped that f,t,re st,dies will pro ide additional insight into the appropriate applications of the a ailable agents.

Mo# tor #"

-ontin,o,s monitoring of physiologic indices pro ides data that assist in assessing response to therapy and trends that may be ,sed to predict catastrophe. Bany episodes of Is,dden deteriorationJ in critically ill patients are iewed, in retrospect, as changes in the clinical condition that had been occ,rring for some time. "rterial #lood Gases and $erived Indices 'rterial o!ygen tension $Pao2( is most commonly meas,red by obtaining an arterial blood sample and by meas,ring the partial press,re of o!ygen with a polarographic electrode. Eefining normal parameters for Pao2 depends on the mat,ration and age of the patient. 6n the term newborn, the general definition for hypo!ia is a Pao2 less than == mm 3g, whereas that for hypero!ia is a Pao2 greater than *# mm 3g. -apillary blood samples are Iarteriali/edJ by topical asodilators or heat to increase blood flow to a peripheral site. 5lood m,st be freely flowing and collected 1,ickly to pre ent e!pos,re to the atmosphere. 5lood flowing sl,ggishly and e!posed to atmospheric o!ygen falsely raises the Pao2 from a capillary sample, especially in the range of 4# to D# mm 3g. -apillary blood p3 and carbon dio!ide tension $Pco2( correlate well with arterial samples, e!cept when perf,sion is poor. Pao2 is the least reliable of all capillary blood gas determinations. 6n patients recei ing o!ygen therapy in whom Pao2 e!ceeds D# mm 3g, the capillary Pao2 correlates poorly with the arterial meas,rement. 6n newborns, ,mbilical artery catheteri/ation can pro ide arterial access. The catheter tip sho,ld rest at the le el of the diaphragm or below +3. The second most fre1,ently ,sed arterial site is the radial artery. -omplications of arterial blood sampling incl,de repeated blood loss and anemia. -hanges in o!ygenation are s,ch that intermittent blood gas sampling may miss critical episodes of hypo!ia or hypero!ia. 5eca,se of the drawbacks of e!- i o monitoring, se eral in- i o monitoring systems ha e been ,sed.
16

%ulse &!imetry The nonin asi e determination of o!ygen sat,ration $%ao2( gi es moment-to-moment information regarding the a ailability of o!ygen to the tiss,es. 6f the Pao2 is plotted against the o!ygen sat,ration of hemoglobin, the %-shaped hemoglobin dissociation c,r e is obtained $.ig. "-=(.

4eferring to this c,r e, hemoglobin is =#2 sat,rated at 2= mm 3g Pao2 and )#2 sat,rated at =# mm 3g. P,lse o!imetry has a rapid $= to 7 seconds( response time, re1,ires no calibration, and may be left in place contin,o,sly. P,lse o!imetry is not possible if the patient is in shock, has peripheral asospasm, or has asc,lar constriction d,e to hypothermia. 6nacc,rate readings may occ,r in the presence of 7a,ndice, direct high-intensity light, dark skin pigmentation, and greater than *#2 fetal hemoglobin. 0!imetry is not a sensiti e g,ide to gas e!change in patients with high Pao2 d,e to the shape of the o!ygen dissociation c,r e. 's an e!ample, on the ,pper hori/ontal portion of the c,r e, large changes in Pao2 may occ,r with little change in %ao2. 'n o!imeter reading of )=2 co,ld represent a Pao2 between D# and "D# mm 3g. ' st,dy to compare %ao2 from p,lse o!imetry with Pao2 determined from indwelling arterial catheters has shown that %ao2 greater than or e1,al to *=2 corresponds to a Pao2 greater than == mm 3g and that %ao2 less than or e1,al to )#2 corresponds to a Pao2 less than *# mm 3g.4* &,idelines for monitoring infants ,sing p,lse o!imetry ha e been s,ggested for the following three conditions8 ". 6n the infant with ac,te respiratory distress witho,t direct arterial access, sat,ration limits of *=2 $lower( and )22 $,pper( sho,ld be set. 2. 6n the older infant with chronic respiratory distress who is at low risk for retinopathy of premat,rity, the ,pper sat,ration limit may be set at )=2A the lower limit sho,ld be set at *72 to a oid p,lmonary asoconstriction and p,lmonary hypertension. 3. 5eca,se the concentration of fetal hemoglobin in newborns affects the acc,racy of p,lse o!imetry, infants with arterial access sho,ld ha e both Pao2 and %ao2 monitored closely. ' graph sho,ld be
17

kept at the bedside doc,menting the %ao2 each time the Pao2 is meas,red. +imits for %ao2 alarm can be changed beca,se 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 l,ngs and of the metabolic rate. 6n most clinical sit,ations, changes in Paco2 are d,e to changes in entilation. .or this reason, serial meas,rement of Paco2 is a practical method to assess the ade1,acy of entilation. The discrepancy among eno,s, capillary, and arterial carbon dio!ide tensions is not great ,nder most conditions, altho,gh one st,dy noted a significant increase in Paco2 in eno,s samples compared with sim,ltaneo,s arterial samples. 5eca,se it is possible to monitor Paco2 and p3 satisfactorily with eno,s or capillary blood samples and beca,se p,lse o!imetry is now commonly ,sed to assess o!ygenation, many infants with respiratory ins,fficiency no longer re1,ire arterial catheters for monitoring. nd)tidal 'arbon $io!ide Beas,ring e!pired -02 by capnography pro ides a nonin asi e means of contin,o,sly monitoring al eolar Pco2. -apnometry meas,res -02 by an infrared sensor either placed in line between the entilator circ,it and the endotracheal t,be or off to the side of the air flow, both of which are applicable only to the int,bated patient. ' comparati e st,dy of end-tidal -02 in critically ill neonates demonstrated that both sidestream and mainstream end-tidal -02 meas,rements appro!imated Paco2. :hen the mainstream sensor was inserted into the breathing circ,it, the Paco2 increased an a erage of 2 mm 3g. 'ltho,gh this is not likely to significantly affect infants who are entilated, it might create fatig,e in weaning infants from mechanical entilation. The acc,racy of the end-tidal -02 is diminished with small endotracheal t,bes. 'entral *enous 'atheter 6ndications for central eno,s catheter placement incl,de $"( hemodynamic monitoring, $2( inability to establish other eno,s access, $3( TPN, and $4( inf,sion of inotropic dr,gs or other medications that cannot be gi en peripherally. Beas,rement of central eno,s press,re to monitor ol,me stat,s is fre1,ently ,sed in the res,scitation of a critically ill patient. ' catheter placed in the s,perior ena ca a or right atri,m meas,res the filling press,re of the right side of the heart, which ,s,ally reflects left atrial and filling press,re of the left entricle. 0ften, a wide discrepancy e!ists between left and right atrial press,re when p,lmonary disease, o erwhelming sepsis, or cardiac lesions are present. To ,tili/e the data effecti ely, contin,o,s meas,rements m,st be taken with a press,re transd,cer connected to a catheter acc,rately placed in the central eno,s system. Positi e-press,re
18

entilation,

pne,mothora!, abdominal distention, or pericardial tamponade all ele ate central eno,s press,re. %ulmonary "rtery 'atheter The p,lmonary artery press,re catheter has altered the care of the child with se ere cardiop,lmonary derangement by allowing direct meas,rement of cardio asc,lar ariables at the bedside. The indications for p,lmonary catheter placement are listed in Table "-D.

:ith this catheter, it is possible to monitor central

eno,s press,re, p,lmonary artery

press,re, p,lmonary wedge press,re, and cardiac o,tp,t. ' 4- .rench, do,ble-l,men catheter and a =- to *- .rench, triple-l,men catheter are a ailable. The catheter is ,s,allyplaced by perc,taneo,s methods $as in the ad,lt( e!cept in the smallest pediatric patient, in whom a c,tdown is sometimes re1,ired. :hen the tip of the catheter is in a distal p,lmonary artery and the balloon is inflated, the res,lting press,re is generally an acc,rate reflection of left atrial press,re beca,se the p,lmonary eins ha e no al es. This p,lmonary IwedgeJ press,re represents left entric,lar filling press,re, which is ,sed as a reflection of preload. The monitors display phasic press,res, b,t treatment decisions are made based on the electronically deri ed mean central eno,s press,re. ' low p,lmonary wedge press,re s,ggests that blood ol,me m,st be e!panded. ' high or normal p,lmonary wedge press,re in the presence of contin,ed signs of shock s,ggests left entric,lar dysf,nction. -ardiac o,tp,t is ,s,ally meas,red in liters per min,te. :hen related to body s,rface area, the o,tp,t is represented as the cardiac inde!+ which is simply the cardiac o,tp,t di ided by the body s,rface area. The normali/ed cardiac inde! allows the e al,ation of cardiac performance witho,t regard to body si/e. The ,s,al resting al,e for cardiac inde! is between 3.= and 4.= +<min<m2. The determination of cardiac o,tp,t by the thermodil,tion techni1,e, which is possible with a %wan-&an/ p,lmonary artery catheter, is widely ,sed and has a good correlation with other methods. 'cc,rate cardiac o,tp,t determination depends on rapid in7ection, acc,rate meas,rement of in7ectant temperat,re and
19

ol,me, and absence of

sh,nting. 5eca,se

entilation affects the flow into and o,t of the right

entricle, three

in7ections sho,ld be made at a consistent point in the entilatory cycle, typically at end e!piration. Eoppler meas,rement of aortic flow elocity allows meas,rement of cardiac o,tp,t by the following form,la8 -ardiac o,tp,t $m+<min( K Bean aortic blood flow elocity $cm<sec( L 'ortic cross - sectional area $cm2( L D# 'ortic cross-sectional area is determined by standard ,ltrasonographic techni1,es. ;sing this cross-sectional meas,rement, p,lsed Eoppler aortic flow elocity is meas,red by a transd,cer placed at the s,prasternal notch, in the esophag,s, or in the trachea to deri e cardiac o,tp,t. %t,dies are ,nderway to determine if cardiac o,tp,t meas,red by this techni1,e correlates well with thermodil,tion or the .ick method in critically ill pediatric patients. Pre io,s st,dies ha e shown that cardiac o,tp,t meas,red by intermittent Eoppler meas,rement at the s,prasternal notch was not of s,fficient reliability to be employed for hemodynamic monitoring in critically ill children. 6mpedance cardiography $bioimpedance( is another nonin asi e techni1,e that meas,res stroke ol,me on a beat-by-beat basis. 5ioimpedance employs a lowle el c,rrent applied to the thora!, where changes in the ol,me and elocity of blood flow in the thoracic aorta res,lt in detectable changes in thoracic cond,cti ity. Pre io,s application of this techni1,e in critically ill patients met with only limited s,ccess. +ate refinements in electrode config,ration, algorithms, and microprocessors ha e prod,ced more acceptable res,lts. %t,dies in pigs demonstrated a good correlation of bioimpedancederi ed cardiac o,tp,t with thermodil,tional cardiac o,tp,t o er a wide hemodynamic range. These techni1,es ha e yet to be alidated or pro ed effecti e in children. 'nother st,dy concl,ded that ,sing right-sided heart catheters in treating critically ill ad,lt patients in an increased mortality. 3owe er, a consens,s committee report doc,ments the contin,ed safety and efficacy of right-sided heart catheters in the care of critically ill children. *enous &!imetry Bi!ed eno,s o!ygen sat,ration $% 02( is an indicator of the ade1,acy of o!ygen s,pply and demand in perf,sed tiss,es. 0!ygen cons,mption is defined as the amo,nt of o!ygen cons,med by the tiss,e as calc,lated by the .ick e1,ation8 0 -ons,mption K -ardiac o,tp,t L 'rterial - eno,s o!ygen content difference 4eflectance spectrophotometry is c,rrently ,sed for contin,o,s eno,s o!imetry. B,ltiple wa elengths of light are transmitted at a known intensity by means of fiberoptic b,ndles in a special p,lmonary artery or right atrial catheter. The light is reflected by red blood cells
20

flowing past the tip of the catheter. The wa elengths of light are chosen so that both o!yhemoglobin and deo!yhemoglobin are meas,red to determine the fraction of hemoglobin sat,rated with o!ygen. The system re1,ires either in- itro calibration by reflecting light from a standardi/ed target that represents a known o!ygen sat,ration or in- i o calibration by withdrawing blood from the p,lmonary artery catheter and meas,ring the sat,ration by laboratory co-o!imetry. Bi!ed eno,s o!ygen sat,ration al,es within the normal range $D*2-772( indicate a normal balance between o!ygen s,pply and demand, pro ided that asoreg,lation is intact and distrib,tion of peripheral blood flow is normal. Cal,es greater than 772 are most commonly associated with syndromes of asodereg,lation, s,ch as sepsis. ;ncompensated changes in 02 sat,ration, hemoglobin le el, or cardiac o,tp,t lead to a decrease in % 02. ' s,stained decrease in % 02 greater than "#2 sho,ld lead to meas,ring %ao2, hemoglobin le el, and cardiac o,tp,t to determine the ca,se of the decline. The most common so,rces of error in meas,ring % 02 are calibration and catheter malposition. The most important concept in % 02 monitoring is the ad antage of contin,o,s monitoring, which allows early warning of a de eloping problem. 'ltho,gh most clinical e!perience has been with p,lmonary artery catheters, right atrial catheters are more easily placed and may th,s pro ide better information to detect hemodynamic deterioration earlier and permit more rapid treatment of physiologic derangements. ' st,dy has shown that when o!ygen cons,mption was monitored and maintained at a consistent le el, the right atrial eno,s sat,ration was tho,ght to be an e!cellent meas,re.

SHOC,
%hock is a state in which the cardiac o,tp,t is ins,fficient to deli er ade1,ate o!ygen to meet metabolic demands of the tiss,es. -ardio asc,lar f,nction is determined by preload, cardiac contractility, heart rate, and afterload. %hock may be classified broadly as hypo olemic, cardiogenic, or septic. H%(o*ole! c ShocPreload is a f,nction of the ol,me of blood presented to the entricles. 5eca,se of the impracticality of meas,ring ol,me, preload is commonly monitored by atrial press,re entric,lar or right entric,lar meas,rements. 6n most clinical sit,ations, right atrial press,re or central eno,s press,re is the inde! of cardiac preload. 6n sit,ations in which left compliance is abnormal, or in certain forms of congenital heart disease, right atrial press,re may not correlate well with left atrial press,re. 6n infants and children, most shock sit,ations
21

are the res,lt of red,ced preload secondary to fl,id loss, s,ch as from diarrhea, omiting, or tra,ma. Cirt,ally all forms of pediatric shock ha e significant intra asc,lar and f,nctional interstitial fl,id deficits. 3ypo olemia res,lts in decreased eno,s ret,rn to the heart. Preload is red,ced, cardiac o,tp,t falls, and the o erall res,lt is a decrease in tiss,e perf,sion. 6n asi e infection and hypo olemia are the most common ca,ses of shock in both children and ad,lts. The first step in treating all forms of shock is to correct e!isting fl,id deficits. 6notropic dr,gs sho,ld not be initiated ,ntil ade1,ate intra asc,lar fl,id ol,me has been established. The speed and ol,me of the inf,sate are determined by the patient>s responses, partic,larly changes in blood press,re, p,lse rate, ,rine o,tp,t, and central eno,s press,re. %hock res,lting from ac,te hemorrhage is initially treated with the administration of "# to 2# m+<kg of 4inger>s lactate sol,tion or normal saline as fl,id bol,ses. 6f the patient does not respond, a second bol,s of crystalloid is gi en. Typespecific or crossmatched blood is gi en as needed. The choice of res,scitation fl,id in shock that res,lts from sepsis or from loss of e!tracell,lar fl,id $from conditions s,ch as peritonitis, intestinal obstr,ction, and pancreatitis( is less clear. 0,r initial res,scitation fl,ids incl,de 4inger>s lactate or normal saline in older infants and children and half-strength 4inger>s or #.= normal saline in the newborn. Eespite o,r rel,ctance to ,se colloid-containing sol,tions for shock, we make an e!ception in the desperately ill newborn or premat,re infant with septicemia. To correct the red,ced ser,m factors, for e!ample in those children with a coag,lopathy, we ,se fresh fro/en plasma or specific factors as the res,scitation fl,id. The rate and ol,me of res,scitation fl,id gi en is ad7,sted based on data obtained from monitoring the effects of the initial res,scitation. 'fter the initial bol,s is gi en, the ade1,acy of the replacement is assessed by monitoring ,rine o,tp,t, ,rine concentration, plasma acidosis, o!ygenation, arterial press,re, central eno,s press,re, and p,lmonary wedge press,re, if indicated. :hen cardiac fail,re is present, contin,ed igoro,s deli ery of large ol,mes of fl,id may ca,se a f,rther increase in preload to the failing myocardi,m and accelerate the downhill co,rse. 6n this setting, as o,tlined pre io,sly, inotropic agents are gi en while monitoring cardiac and p,lmonary f,nction. Card o"e# c ShocByocardial contractility is ,s,ally e!pressed as the e7ection fraction, which is the proportion of entric,lar ol,me that is p,mped. Byocardial contractility is red,ced with hypo!emia and acidosis. 6notropic dr,gs increase cardiac contractility b,t ha e their best effect when hypo!emia and acidosis are corrected. 'drenergic receptors are important in reg,lating calci,m fl,!, which, in t,rn, is important in controlling myocardial contractility. The N- and O-adrenergic receptors are proteins present in the sarcolemma of myocardial and asc,lar
22

smooth m,scle cells. O" receptors are predominantly in the heart and, when stim,lated, res,lt in increased contractility of myocardi,m. O2 receptors are predominantly in respiratory and asc,lar smooth m,scle. :hen stim,lated, these receptors res,lt in bronchodilation and asodilation. N"-'drenergic receptors are located on asc,lar smooth m,scle and res,lt in asc,lar constriction when stim,lated. N2-'drenergic receptors are fo,nd mainly on pre7,nctional sympathetic ner e terminals. The concept of dopaminergic receptors has also been ,sed to acco,nt for the cardio asc,lar effects of dopamine not mediated thro,gh N or O receptors. 'cti ation of dopaminergic receptors res,lts in decreased renal and mesenteric asc,lar resistance and, ,s,ally, increased blood flow. The most commonly ,sed inotropic dr,gs are listed in Table "-7.

pinephrine ?pinephrine is an endogeno,s catecholamine with N- and O-adrenergic effects. 't low doses, the O-adrenergic effect predominates. These effects incl,de an increase in heart rate, cardiac contractility, cardiac o,tp,t, and bronchiolar dilation. 5lood press,re rises, in part, not only d,e to increased cardiac o,tp,t b,t also d,e to increased peripheral asc,lar resistance, which is noted with higher doses at which N-adrenergic effects become predominant. 4enal blood flow may increase slightly, remain ,nchanged, or decrease depending on the balance between greater cardiac o,tp,t and the changes in peripheral asc,lar resistance, which lead to regional redistrib,tion of blood flow. -ardiac arrhythmias can be seen with epinephrine, especially with higher doses. Eosages for treating compromised cardio asc,lar f,nction range from #.#= to ".# Pg<kg<min. ?!cessi e doses of epinephrine can ca,se worsening cardiac ischemia and dysf,nction from increased myocardial o!ygen demand.
23

Isoproterenol 6soproterenol is a O-adrenergic agonist. 6t increases cardiac contractility and heart rate, with little change in systemic asc,lar resistance. The peripheral asc,lar O-adrenergic effect and lack of a peripheral asc,lar N-adrenergic effect may allow red,ction of left entric,lar afterload. 6soproterenol>s intense chronotropic effect prod,ces tachycardia, which can limit its ,sef,lness. 6soproterenol is administered intra eno,sly at a dosage of #." to #.3 Pg<kg<min. $opamine Eopamine is an endogeno,s catecholamine with O-adrenergic, N-adrenergic, and dopaminergic effects. 6t is both a direct and an indirect O-adrenergic agonist. Eopamine elicits positi e inotropic and chronotropic responses by direct interaction with the O receptor $direct effect( and by stim,lating the release of norepinephrine from the sympathetic ner e endings, which interacts with the O receptor $indirect effect(. 't low dosages $F3 Pg<kg<min(, the dopaminergic effect of the dr,g predominates, res,lting in red,ced renal and mesenteric asc,lar resistance and impro ed blood flow to these organs. The O-adrenergic effects become more prominent at intermediate dosages $3 to "# Pg<kg<min(, prod,cing a higher cardiac o,tp,t. 't relati ely high dosages $@"= to 2# Pg<kg<min(, the N-adrenergic effects become prominent with peripheral asoconstriction. ?!perience with the ,se of dopamine in pediatric patients s,ggests that it is effecti e in increasing blood press,re in neonates, infants, and children. The precise dosages for these desired hemodynamic effects are not known. The effects of low dosages of dopamine on blood press,re, heart rate, and renal f,nction were st,died in "* hypotensi e, preterm infants. The blood press,re and di,retic effects were obser ed at 2, 4, and * ,g<kg<min. ?le ations in heart rate were seen only at * Pg<kg<min. .,rther work is needed to better characteri/e the pharmacokinetics and pharmacodynamics of dopamine in children, especially in newborns. 4ecent clinical e idence has demonstrated some beneficial effects from orally administered le odopa for treating cardiac fail,re in pediatric patients. 5eca,se enteral medications for heart fail,re are c,rrently limited to digo!in and di,retics, ,sing le odopa may impro e o,r ability to treat heart fail,re witho,t ,sing parenteral ionotropes.

$obutamine Eob,tamine, a synthetic catecholamine, has predominantly O-adrenergic effects with minimal N-adrenergic effects. The hemodynamic effect of dob,tamine in infants and children with
24

shock has been st,died. Eob,tamine inf,sion significantly increased cardiac inde!, stroke inde!, and p,lmonary capillary wedge press,re, and it decreased systemic asc,lar resistance. The dr,g appears more efficacio,s in treating cardiogenic shock than septic shock. The ad antage of dob,tamine o er isoproterenol is its lesser chronotropic effect and its tendency to maintain systemic press,re. The ad antage o er dopamine is dob,tamine>s lesser peripheral asoconstrictor effect. The ,s,al range of dosages for dob,tamine is 2 to "= Pg<kg<min. 0ne st,dy fo,nd dob,tamine significantly increased systemic blood flow in preterm infants when compared with dopamine. 3owe er, it did not demonstrate differences in o,tcomes. The combination of dopamine and dob,tamine has been increasingly ,sed. 3owe er, little information regarding their combined ad antages or effecti eness in pediatric patients has been p,blished. -ilrinone Bilrinone, a phosphodiesterase inhibitor, is a potent positi e inotrope and asodilator that has been shown to impro e cardiac f,nction in infants and children. The proposed action is d,e, in part, to an increase in intracell,lar cyclic adenosine monophosphate and calci,m transport secondary to inhibition of cardiac phosphodiesterase. This effect is independent of O-agonist stim,lation and, in fact, may act synergistically with a O agonist to impro e cardiac performance. Bilrinone increases cardiac inde! and o!ygen deli ery witho,t affecting heart rate, blood press,re, or p,lmonary wedge press,re. Bilrinone is administered as a 7=-Pg<kg bol,s followed by inf,sion of #.7= to ".# Pg<kg<min.

Se(t c Shoc'fterload represents the force against which the left entricle m,st contract to e7ect blood. 6t is related to systemic asc,lar resistance and myocardial wall stress. %ystemic asc,lar resistance is defined as the systemic mean arterial blood press,re min,s right arterial press,re di ided by cardiac o,tp,t. -ardiac contractility is affected by systemic asc,lar resistance and afterload. 6n general, increases in afterload red,ce cardiac contractility and decreases in afterload increase cardiac contractility. %eptic shock is a distrib,ti e form of shock that differs from other forms of shock. -ardiogenic and hypo olemic shock lead to increased systemic asc,lar resistance and decreased cardiac o,tp,t. %eptic shock res,lts from a se ere decrease in systemic asc,lar resistance and a generali/ed maldistrib,tion of blood and leads to a hyperdynamic state. The pathophysiology of septic shock begins with a nid,s of infection. 0rganisms may in ade the bloodstream, or they may proliferate at the infected site
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and release ario,s mediators into the bloodstream. ? idence now s,pports the finding that s,bstances prod,ced by the microorganism, s,ch as lipopolysaccharide, endoto!in, e!oto!in, lipid moieties, and other prod,cts, can ind,ce septic shock by stim,lating host cells to release cytokines, le,kotrienes, and endorphins. ?ndoto!in is a lipopolysaccharide fo,nd in the o,ter membrane of gram-negati e bacteria. .,nctionally, the molec,le is di ided into three parts8 $"( the highly ariable 0-specific polysaccharide side chain $con eys serotypic specificity to bacteria and can acti ate the alternate pathway of complement(A $2( the 4-core region $less ariable among different gram-negati e bacteriaA antibodies to this region co,ld be cross protecti e(A and $3( lipid-' $responsible for most of the to!icity of endoto!in(. ?ndoto!in stim,lates t,mor necrosis factor $TN.( and can directly acti ate the classic pathway in the absence of antibody. ?ndoto!in has been implicated as an important factor in the pathogenesis of h,man septic shock and gramnegati e sepsis. Therapy has foc,sed on de eloping antibodies to endoto!in to treat septic shock. 'ntibodies to endoto!in ha e been ,sed in clinical trials of sepsis with ariable res,lts. -ytokines, especially TN., play a dominant role in the host>s response. ?ndoto!in and e!oto!in both ind,ce TN. release in i o and prod,ce many other to!ic effects ia this endogeno,s mediator. TN. is released primarily from monocytes and macrophagesA howe er, it is also released from nat,ral killer cells, mast cells, and some acti ated T lymphocytes. 0ther stim,li for its release incl,de ir,ses, f,ngi, parasites, and interle,kin-" $6+-"(. 6n sepsis, the effects of TN. release may incl,de cardiac dysf,nction, disseminated intra asc,lar coag,lation, and cardio asc,lar collapse. TN. release also ca,ses the release of gran,locyte- macrophage colony-stim,lating factor $&B--%.(, interferon alfa, and 6+-". 'ntibodies against TN. protect animals from e!oto!in and bacterial challenge. Pre io,sly known as the endogeno,s pyrogen, 6+-" is prod,ced primarily by macrophages and monocytes and plays a central role in stim,lating a ariety of host responses, incl,ding fe er prod,ction, lymphocyte acti ation, and endothelial cell stim,lation to prod,ce procoag,lant acti ity and to increase adhesi eness. 6+-" also ca,ses the ind,ction of the inhibitor of tiss,e plasminogen acti ator and the prod,ction of &B--%.. These effects are balanced by the release of plateletacti ating factor and arachidonic metabolites. 6+-2, also known as T-cell growth factor, is prod,ced by acti ated T lymphocytes and strengthens the imm,ne response by stim,lating cell proliferation. 6ts clinically apparent side effects incl,de capillary leak syndrome, tachycardia, hypotension, increased cardiac inde!, decreased systemic asc,lar resistance, and decreased left entric,lar e7ection fraction. %t,dies done on dogs ha e s,ggested that, in immat,re animals, septic shock is more lethal and has different mechanisms of tiss,e in7,ry. These incl,de more
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dramatic aberrations in blood press,re $more constant decline(, heart rate $progressi e, persistent tachycardia(, blood s,gar le el $se ere, progressi e hypoglycemia(, acid-base stat,s $se ere acidosis(, and o!ygenation $se ere hypo!emia(. These changes are significantly different from those seen in the ad,lt animals that also e!perience impro ed s,r i al of almost D##2 $"*.= s. 3." ho,rs( compared with the premat,re animal. The neonate>s host defense can ,s,ally respond s,ccessf,lly to ordinary microbial challenge. 3owe er, defense against ma7or challenges appears limited and pro ides an e!planation for the high mortality rate with ma7or neonatal sepsis. 's in ad,lts, the imm,ne system consists of fo,r ma7or components8 cell-mediated imm,nity $T cells(, complement system, antibody-mediated imm,nity $5 cells(, and macrophage-ne,trophil phagocytic system. The two most important deficits in newborn host defenses that seem to increase the risk of bacterial sepsis are the 1,antitati e and 1,alitati e changes in the phagocytic system and the defects in antibodymediated imm,nity. The proliferati e rate of the gran,locyte-macrophage prec,rsor has been reported to be at near-ma!imal capacity in the neonate. 3owe er, the ne,trophil storage pool is markedly red,ced in the newborn compared with the ad,lt. 'fter bacterial challenge, newborns fail to increase stem cell proliferation and soon deplete their already red,ced ne,trophil storage pool. N,mero,s in itro abnormalities ha e been demonstrated in neonatal polymorphon,clear ne,trophils, especially in times of stress or infection. These abnormalities incl,de decreased deformability, chemota!is, phagocytosis, -3b receptor e!pression, adherence, bacterial killing, and depressed o!idati e metabolism. -hemota!is is impaired in neonatal ne,trophils in response to entry into secondary lymphoid tiss,es ario,s bacterial organisms and antigen-antibody ia the endothelial en,les. 6nitial adhesion of comple!es. &ran,locytes are acti ated by their interaction with endothelial cells followed by gran,locytes is dependent on their e!pression of +-selectin, a cell adhesion molec,le e!pressed on the gran,locyte cell s,rface. ? al,ation of cord blood has demonstrated a significantly lower e!pression of +-selectin on gran,locyte s,rfaces when compared with older newborn $= days old( and ad,lt samples, indicating a depressed le el of interaction with asc,lar endothelial cells at the initial stage of adhesion. 'ltho,gh phagocytosis has additionally been demonstrated to be abnormal in neonatal phagocytes, it appears that this phenomenon is most likely secondary to decreased opsonic acti ity rather than an intrinsic defect of the neonatal polymorphon,clear ne,trophils. -,rrently, there is inconcl,si e e idence to s,pport or ref,te the ro,tine ,se of gran,locyte transf,sions in the pre ention or treatment of sepsis in the neonate. Preterm and term newborns ha e poor responses to ario,s antigenic stim,li, red,ced gamma glob,lin le els at birth, and red,ced maternal
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imm,noglob,lin s,pply from placental transport. 'lmost 332 of infants with a birth weight less than "=## g de elop s,bstantial hypogammaglob,linemia. 6g' and 6gB are also low d,e to the inability of these two imm,noglob,lins to cross the placenta. Neonates, therefore, are ,s,ally more s,sceptible to pyogenic bacterial infections beca,se most of the antibodies that opsoni/e pyogenic bacterial caps,lar antigens are 6g& and 6gB. 6n addition, neonates do not prod,ce type-specific antibodies, which appears to be secondary to a defect in the differentiation of 5 lymphocytes into imm,noglob,lin-secreting plasma cells and T lymphocyteMmediated facilitation of antibody synthesis. 6n the term infant, total hemolytic complement acti ity, which meas,res the classic complement pathway, constit,tes appro!imately =#2 of ad,lt acti ity. 0wing to lower le els of factor 5, the acti ity of the alternati e complement pathway is also decreased in the neonate. .ibronectin, a plasma protein that promotes retic,loendothelial clearance of in ading microorganisms, is deficient in neonatal cord plasma. ;sing intra eno,s imm,noglob,lins $6C6&s( for the prophyla!is and treatment of sepsis in the newborn, especially the preterm, low birth weight infant, has been st,died in n,mero,s trials with aried o,tcomes. 6n one st,dy, a gro,p of infants weighing "=## g was treated with =## mg<kg of 6C6& each week for 4 weeks and compared with infants who were not treated with 6C6&. The mortality rate was "D2 in the 6C6&-treated gro,p compared with 322 in the ,ntreated gro,p. 'nother recent analysis e!amined the role of 6C6& to pre ent and treat neonatal sepsis. ' significant benefit was noted from the prophylactic ,se of 6C6& to pre ent sepsis in low birth weight premat,re infants. 3owe er, ,sing 6C6& to treat neonatal sepsis prod,ced a greater than D2 decrease in the mortality rate. ' re iew of ") randomi/ed controlled trials fo,nd a 32 decrease in the incidence of neonatal sepsis in preterm infants witho,t a significant difference in allca,se and infection-related mortality when prophylactic 6C6& was administered. 5ased on the marginal red,ction of neonatal sepsis witho,t a red,ction in mortality, ro,tine ,se of prophylactic 6C6& cannot be recommended. -olony-stim,lating factors are a family of glycoproteins that stim,late proliferation and differentiation of hematopoietic cells of ario,s lineages. &B--%. and gran,locyte colony-stim,lating factor $&--%.( ha e similar physiologic actions. 5oth stim,late the proliferation of bone marrow myeloid progenitor cells, ind,ce the release of bone marrow ne,trophil storage pools, and enhance mat,re ne,trophil effect or f,nction. Preliminary st,dies of &B--%. in neonatal animals demonstrate enhancement of ne,trophil o!idati e metabolism, as well as priming of neonatal ne,trophils for enhanced chemota!is and bacterial killing. 5oth &B--%. and &--%. ind,ce peripheral ne,trophilia within 2 to D ho,rs of intraperitoneal administration. This enhanced affinity for ne,trophils ret,rns to
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normal baseline le el by 24 ho,rs. 4ecent st,dies confirm the efficacy and safety of &--%. therapy for neonatal sepsis and ne,tropenia. 0ther st,dies ha e demonstrated no long-term ad erse hematologic, imm,nologic, or de elopmental 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 ha e a significant decrease in the rate of nosocomial infections. -onfirmatory st,dies are c,rrently being performed. The c,rrent recommended daily pediatric dose is = ,g<kg<dose gi en s,bc,taneo,sly. ;ni1,e to the newborn in septic shock is the persistence of fetal circ,lation and res,ltant p,lmonary hypertension. 6n fact, the rapid administration of fl,id can f,rther e!acerbate this iss,e by ca,sing leftto- right sh,nting thro,gh a patent d,ct,s arterios,s and s,bse1,ent congesti e heart fail,re from entric,lar o erload. 6nfants in septic shock with a new heart m,rm,r sho,ld recei e indomethacin and ,ndergo a cardiac echocardiogram to e al,ate the heart. ' single instit,tion randomi/ed trial demonstrated an impro ed o,tcome from entric,lar o erload with pento!ifylline in e!tremely premat,re infants. The critical care of a patient in septic shock can be challenging. %eptic shock has a distincti e clinical presentation and is characteri/ed by an early compensated stage where one can see a decreased systemic asc,lar resistance, an increase in cardiac o,tp,t, tachycardia, warm e!tremities, and an ade1,ate ,rine o,tp,t. +ater in the clinical presentation, septic shock is characteri/ed by an ,ncompensated phase in which the patient de elops a decrease in intra asc,lar ol,me, myocardial depression, high asc,lar resistance, and a decreasing cardiac o,tp,t. -are of these patients is based on the principles of so,rce control, antibiotics, and s,pporti e care. Patients with se ere septic shock often do not respond to con entional forms of ol,me loading and cardio asc,lar s,pporti e medications. 4ecently, the administration of arginine asopressin has been shown to decrease mortality in ad,lt patients with recalcitrant septic shock. Casopressin, also known as antidi,retic hormone, is made in the posterior pit,itary and plays a primary role in water reg,lation by the kidneys. The ;.%. .ood and Er,g 'dministration $.E'(-appro ed ,ses of asopressin and its deri ati es are for diabetes. 0ther nonM.E'-appro ed ,ses for asopressin incl,de gastrointestinal hemorrhage and in bleeding disorders s,ch as type 6 on :illebrand>s disease.6n septic shock, asopressin has profo,nd effects on increasing blood press,re in intra asc,lar depleted states. The mechanisms behind this obser ation appear to be mediated by the ability of asopressin to potentiate the catecholamine effects on blood essels. %e eral obser ational and nonrandomi/ed prospecti e st,dies ha e demonstrated the efficacy of terlipressin, an arginine asopressin analog, to be effecti e as resc,e therapy in catecholamine-resistant shock in
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children and neonates. ' single randomi/ed, do,bleblinded, placebo-controlled st,dy has been cond,cted that demonstrated a beneficial effect of asopressin in recalcitrant septic shock.

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