Sao Paulo Med. J. vol.114 número2

-

R E V I E W

&

U P D A T IN G

M a ria C ris tin a K o rb a g e d e A ra u jo , F la v io A d o lfo C o s ta V a z , J o s e L a u ro A ra u jo R a m o s

P ro g re ss in p h o to th e ra p y

University of Siio Paulo Medical School. Siio Paulo, Brazil

T he purpose. of this article is to present a recent advance in phototherapy em ployed on new born babies w ith jaundice. T he efficacy of this treatm ent depends on the intensity of em itted light; it is believed that a dose betw een 6 -12 nm is necessary. T he usefulness of phototherapy in healthy, full-term infants is currently being questioned. T herefore, the adequate use of this therapy should be em pha-sized until a consensus is reached on its advantages and disadvantages.

U N IT E R M S : P hototherapy, new born. Jaundice. Irradiation, efficacy.

IN T R O D U C T IO N

E

b y C R A M E R ,v e r s in c e th e in tro d u c tio ns e v e ra l m o d e ls h a v e b e e n p ro p o s e d .o f p h o to th e ra p y in 1 9 5 8 H o w e v e r, th e p h y s ic a l a n d c h e m ic a l a lte ra tio n s th a t o c c u r in th is fo rm o f th e ra p y fo r n e w b o rn b a b ie s w ith ja u n d ic e w e re n o t e v id e n t u n til 1 9 8 5 , w h e n M c D O N A G H

a n d L IG H T E R c la rifie d th e s e a lte ra tio n s u s in g m o re a d v a n c e d m e th o d o lo g y .

B iliru b in , a lo n g w ith m e la n in a n d o th e r h e m e g ro u p d e riv e d .s u b s ta n c e s , a re lig h t-a b s o rb in g p ig m e n ts . T h e v is ib le s p e c tru m , b e tw e e n 4 2 0 a n d 4 8 0 n a n o m e te rs , is b e s t a b s o rb e d b y b iliru b in .

W h e n a p h o to s e n s itiv e m o le c u le a b s o rb s lig h t, it re c e iv e s a d e te rm in e d q u a n tity o f lu m in o u s e n e rg y . A fte r

A d d re s s fo r c o rre s p o n d e n c e : M a ria C ris tin a K o rb a g e d e A ra u jo

H o s p ita l U n iv e rs ita rio - U S P - C id a d e U n iv e rs ita ria Av . L in e u P re s te s , 2565 -B u ta n ta

S a o P a u lo /S P - B ra s il - C E P 0 5 5 0 8 -9 0 0

re c e iv in g a p h o to n , a n e le c tro n w ill im m e d ia te ly m o v e to a h ig h e r-e n e rg y o rb it, th u s b e c o m in g s tim u la te d . T h is m o le c u le m a y th e n re a c t tw ic e , fo rm in g th e p h o to p ro d u c ts .2o

P h o to th e ra p y c a u s e s tw o ty p e s o f re a c tio n

1 - P H O T O -O X ID A T IO N , w h ic h c a u s e s fra g m e n -ta tio n in th e s tru c tu re o f th e b iliru b in m o le c u le .

2 - P H O T O IS O M E R IZ A T IO N , w h ic h tra n s fo rm s th e u n a lte re d b iliru b in m o le c u le in to h y d ro s o lu b le is o m e rs .

In P H O T O -O X ID A T IO N , s tim u la te d b iliru b in (a fte r th e a b s o rp tio n o f th e p h o to n ) e n v e lo p e s a n o x y g e n m o le c u le , w h ic h is th e n tra n fo rm e d in to a fre e ra d ic a l c a p a b le o f d e s tro y in g n a tiv e b iliru b in , p ro d u c in g fiv e re n a l e x c re tio n p ro d u c ts . T h is is a s lo w re a c tio n a n d o c c u rs in s m a ll q u a n titie s , w ith d o s a g e s in th e u rin e o f b e tw e e n 2 -9 m g /IY

P H O T O IS O M E R IZ A T IO N is fa s te r, a n d tw o d iffe re n t p ro d u c ts c a n b e fo rm e d w h ic h a re e lim in a te d b y th e liv e r: th e s tru c tu ra l is o m e r (Iu m iru b in ) a n d th e c o n fig u ra tio n is o m e r. L u m iru b in is fo rm e d b y n e w b o n d s

B

=

B iliru b in P b

=

P h o to b iliru b in L R

=

L u m iru b in A L B

=

A lb u m in

O x B = O x id iz in g P ro d u c ts

Number and Type of Lamps

T raditional phototherapy equipm ent recom m ended by m ost of the studies5.18.27 requires 8 to 12 lam ps. Irradiation is directly proportional to the num ber of lam ps used in conventional phototherapy equipm ent.3o M ost of the equipm ent used in our hospitals have only 6

fluorescent lam ps, w hich directly interferes w ith the final result.4.28.31

R ecently, som e services have used

equipm ent w ith only one halogen lam p,

irradiating in the 23 m w /cm 2/nm range. T his type of lam p concentrates em itted light in a sm all

IR R A D IA T IO N

Irradiation of a surface w ithin a determ ined range of the spectrum is expressed in m icrow atts / cm 2 /nm (m w / cm 2/nm ). T he greater the irradiation, the greater the efficacy of phototherapy. 18Several authors6.1O .12.27consider that irradiation around 6 m w /cm 2/nm is low intensity, and that irradiation around 12 m w /cm 2/nm is high intensity. C O ST A R IN O et al.6 dem onstrated that the form ation of lum irubin is m uch higher w ith high-intensity irradiation; how ever, form ation of the configuration isom er did not show any significant difference based on the type of irradiation used (Figs. 2 - 3). Increasing irradiation beyond the statu ration point does not raise efficacy, and for M A ISE L S, 18this point should be 23 m w /cm 2/nm , w hile for T A N ,31.18.27this point should be 40 m w /cm 2/ nm . C A R V A L H 03 recently reported that phototherapy equipm ent in R io de Janeiro does not em it m ore than 3

m w /cm 2/nm , w hich is m uch low er than that

recom m ended by the literature, and concludes

that new born babies w ith jaundice are

receiving irradiation, but are not being treated appropriately. It seem s likely that a sim ilar situation is occurring in other hospitals.28

Irradiation depends on factors such as: age.23 R ecent studies6.10.11have evaluated the efficacy of phototherapy by m easuring the photoproducts through high pressure liquid chrom atography. H ow ever, the efficacy depends on the quantity of energy released by the light of the w ave-length corresponding to bilirubin absorption. T his energy is the irradiation, w hich depends on the num bers of lam ps, type of light, tim e of use, distance from the source, and other interfering factors.

K id n e y U rin e

O x B ...---.O x B

h h+_.

O x B ---/--"'-.O x B

E fficient phototherapy reduces indirect bilirubin by 1 - 2 m g every 24 hours of use, regardless of gestational

E F F IC A C Y

F ig u re 1 - A d a p te d fro m M c D o n a g h & L ig h tn e r, 1 9 8 5 .

betw een the C H -C H 2 groups of one ring and the adjacent ring w hich involves the carbons from positions 2 and 7.

L um irubin is a stable product w ith a slow form ation and rapid excretion, so great quantities do not accum ulate in the circulation (varying from 1 to 14 percent); nevertheless it seem s to be the m ain efficacy factor of phototherapy.6.8.9 T he form ation of this isom er varies according to the quantity of energy em itted by the light. 10T he configuration isom er is form ed after a 180 degree rotation of the term inal ring on its axle, exposing its polar segm ent (N H and C O O H ) to the exterior of the m olecule. T his usually involves carbons 4 and 15, w hereas carbon IS is one hundred tim es m ore involved than carbon 4, and the product of this type of isom erization is alm ost exclusively isom er 4Z , 15E Y T his is form ed rapidly, has a slow excretion, and accum ulates in the circulation. It can be m easured by high pressure liquid chrom atography and corresponds to approxim ately 15 - 20 percent of the total bilirubin.6 .lo.11.12 The form ation of this isom er does not depend on lum inous intensity.6 H ow ever, this isom er is unstable, and can revert to the native bilirubin form , especially in the biliary channels. Figure I show s the reactions that are initiated by light.

~ •••••••••••••••••••••••••••••• _---_._. __•••••••••• _•••••••••••• _-j

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F ig u re 2 - F o rm a tio n o f th e c o n fig u ra tio n is o m e r, a c c o rd in g to irra d ia tio n .

f l u o r e s c e n t l a m p s . I t w o u l d s e e m s a f e r i f w e f o u n d o u t m o r e a b o u t t h i s t y p e o f l a m p b e f o r e u s i n g i t r o u t i n e l y f o r p h o t o t h e r a p y .

Time of Use

A f t e r 1 h o u r 's u s e , w h i t e f l u o r e s c e n t l a m p s s h o w a n i m p o r t a n t d e c r e a s e i n i r r a d i a n c e o f a p p r o x i m a t e l y 2 5 p e r c e n t ; 4 .1 8 a f t e r t h i s , i r r a d i a n c e c o n t i n u e s t o d e c r e a s e p r o g r e s s i v e l y a n d , a t 2 0 0 0 h o u r s , i s d o w n t o 4 4 p e r c e n t o f t h e i n i t i a l i r r a d i a n c e . T h e r e i s n o p r e c i s e d a t a i n s e v e r a l s t u d i e s 4 .1 8 .2 6 .2 7w h i c h c o u l d p r e m i t a f i n a l c o n c l u s i o n a s t o t h e i d e a l t i m e f o r t h e u s e o f t h e p h o t o t h e r a p y l a m p s . M o n i t o r i n g t h e e f f i c a c y o f t r e a t m e n t a n d p e r i o d i c m e a s u r i n g o f i r r a d i a n c e u t i l i z i n g a p p r o p r i a t e e q u i p m e n t , w h i c h a l r e a d y e x i s t s o n t h e m a r k e t , m a y b e m o r e u s e f u l t h a n f r e q u e n t r e p l a c e m e n t s o f l a m p s .

F ig u re 3 - F o rm a tio n o f L u m iru b in , a c c o rd in g to irra d ia tio n .

a n d n o n - u n i f o r m a r e a .3 1

C O S T A R I N O e t a l .6 u s e d a t u n g s t e n h a l o g e n l a m p o f 2 5 0 W o n p r e m a t u r e b a b i e s w i t h p h y s i o l o g i c j a u n d i c e , a n d n o t i c e d a n i n c r e a s e i n t h e f o r m a t i o n o f l u m i r u b i n w h e n a p p l i e d i r r a d i a t i o n w e n t f r o m

6 t o 1 2 m w / c m 2 / n m .

T h e r e i s d o u b t a s t o t h e a d v a n t a g e s a n d d i s a d v a n t a g e s o f t h e s i d e e f f e c t s o f h i g h i r r a d i a t i o n s ( h i g h e r t h a n t h e p r e v i o u l y m e n t i o n e d v a l u e s ) ,8 . I ll. 3 1 t h e

t y p e o f f i l t e r u s e d i n t h e n e w e q u i p m e n t o n t h e m a r k e t , n o t t o t h e m e n t i o n t h e a s a t y e t u n k o w n s i d e e f f e c t s o f t h i s k i n d o f l a m p . R e c e n t l y , H O L T R O P e t a l .1 5 u s e d m o d e r a t e i n t e n s i t y h a l o g e n l a m p s , a v e r a g i n g 7 m w / c m 2 / n m , o n l o w - w e i g h t n e w b o r n b a b i e s , a n d c o m p a r e d t h i s t r e a t m e n t w i t h t r a d i t i o n a l e q u i p m e n t u t i l i z i n g

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Color o f the Light

C R A M E R o r i g i n a l l y u s e d a s e t o f 8 b l u e 4 0 W f l u o r e s c e n t l a m p s .2 6 S i n c e t h e n , s e v e r a l s t u d i e s h a v e b e e n c a r r i e d o u t t o d e t e r m i n e t h e b e s t k i n d o f l a m p . H o w e v e r , s t u d i e s v a r y g r e a t l y a s t o t h e t y p e o f g a s u s e d ( i o d i n e , f l u o r i d e , n e o n , t u n g s t e n ) , a n d a s t o t h e w a t t a g e a n d n u m b e r o f e a c h l a m p , w h i c h m a k e s c o m p a r i s o n s d i f f i c u l t . G r e e n l i g h t h a s a h i g h e r w a v e l e n g t h t h a n t h e s p e c i a l b l u e ; h o w e v e r ,

in vivo

s t u d i e s d e m o n s t r a t e d t h a t s p e c i a l b l u e m a y b e a l i t t l e b e t t e r t h a n g r e e n , a l t h o u g h n o t m u c h .8 E N N E V E R d e e m s t h e r e i s n o d i f f e r e n c e b e t w e e n t h e c o l o r o f t h e l a m p s , a n d t h a t b l u e l i g h t m a y n o t b e a s g o o d a s a c o n v e n t i o n a l w h i t e l a m p . G r e e n l i g h t i s l e s s g e n o t o x i c b e c a u s e t h e w a v e l e n g t h i s g r e a t e r t h a n 4 5 0 n m , a n d s e e m s t o p e n e t r a t e t h e s k i n b e t t e r t h a n o t h e r l i g h t c o l o r s .x T h e r e d o e s n o t s e e m t o b e a c o n f i r m e d b e t t e r l i g h t c o l o r a m o n g t h e s t u d i e s .8 .9 .1 2 .2 7L i g h t w i t h a w a v e l e n g t h l e s s t h a n 3 5 0 n m i s g e n o t o x i c a n d m u s t b e a v o i d e d ; w h i t e l i g h t e m i t s w a v e s i n t h i s r a n g e a n d f i b e r g l a s s p r o t e c t i o n m u s t b e u s e d a s a f i l t e r f o r t h i s l i g h t s p e c t r u m .2 7

I n s u m m a r y , w h i t e l i g h t , w h i c h i s t h e m o s t w i d e l y e m p l o y e d .a n d t h e m o s t e a s i l y f o u n d , s e e m s t o b e s a t i s f a c t o r y , a s l o n g a s e n e r g y e m i s s i o n i s k e p t a b o v e 6

m w / c m 2 / n m .

IN T E R F E R E N C E F A C T O R S

A n y o b j e c t p l a c e d b e t w e e n t h e p h o t o t h e r a p y e q u i p m e n t a n d t h e e x p o s e d s u r f a c e m a y i n t e r f e r e w i t h t h e

e ffic a c y o f th e th e ra p y ; th e rm a l b la n k e ts , p la s tic b a g s (u s e d to re d u c e b o d y -h e a t lo s s in lo w -w e ig h t n e w b o rn s ), o r a n o ld , s c ra tc h e d in c u b a to r c o v e r m a y d im in is h th e e ffic a c y o f p h o to th e ra p y .3 .3 1 1

O T H E R T Y P E S O F P H O T O T H E R A P Y

N e o n b la n k e ts h a v e b e e n u s e d o n n e w b o rn b a b ie s w ith ja u n d ic e a n d s tu d ie s h a v e s h o w n a s im ila r o r lo w e r e ffic a c y 3 1 1 .1 4c o m p a re d w ith tra d itio n a l e q u ip m e n t, a lth o u g h th e re is th e a d v a n ta g e o f e lim in a tin g e y e c o v e rin g .1 4 H o w e v e r, m o re s tu d ie s s h o u ld b e u n d e rta k e n , e s p e c ia lly o n th e o x id iz in g e ffe c ts o f lig h t o n b iliru b in .

In vitro

s tu d ie s h a v e d e m o n s tra te d a n in c re a s e o f th e o x y g e n s in g le t fre e ra d ic a l w h e n lig h t w a s p la c e d th re e tim e s c lo s e r to th e b o d y s u rfa c e , c o n tra ry to s tu d ie s w ith n o rm a l n e w b o rn b a b ie s in w h ic h th e s e e ffe c ts w e re le s s im p o rta n t.

S ID E E F F E C T S O F P H O T O T H E R A P Y

M o s t o f th e a d v e rs e e ffe c ts o f p h o to th e ra p y s tu d ie d to d a te s e e m b e n ig n a n d te m p o ra ry e x c e p t p e rh a p s fo r th e g e n o to x ic e ffe c t,5 .1 l).2 7w h ic h h a s n o t y e t b e e n ta k e n in to c o n s id e ra tio n o r m e a s u re d s u ffic ie n tly in c lin ic a l u s e . R e c e n t s tu d ie s , h o w e v e r, h a v e d e m o n s tra te d th e e ffe c t o f p h o to -o x id a tio n o n th e m e m b ra n e o f e ry th ro c y te s ,7 .3 2 .3 3 s u g g e s tin g th a t in th o s e c a s e s th a t a lre a d y h a v e a g e n e tic

T able 1

Levels of indirect bilirubin that suggest the use of phototherapy

A ge in hours

B irthw eigh (g) >24 H s > 48 H s >72 H s

>2500 12 14 16

2001 - 2500 10 12 14

1500 - 2000 6 8 8

< 1500 6 6 6

1) excludes cases of hem olytic disease.

2) in the presum ption of factors such as perinatal hypoxia, acidosia, hyper or hypoglicem ia, central nervous system abnom alitus, hypotherm ia or hypercapm ia, reduce 2 m g% .

p re d is p o s itio n to m e m b ra n e in s ta b ility , a s in s p h e ro c y to s is , p h o to th e ra p y s h o u ld b e u s e d le s s .3 3 T h e u s e o f p h o to th e ra p y o n in fa n ts w ith a d e fic ie n c y o f g lu c o s e 6 -p h o s -p h a te d e h y d ro g e n a s e is c o n tro v e rs ia l;'l).3 3 h o w e v e r, th e re a re s tu d ie s th a t fa v o r th is tre a tm e n t.

R ib o fla v in d e fic ie n c y in d u c e d b y p h o to th e ra p y is n o w w e ll-d o c u m e n te d a n d c a n a lte r th e s h o rt fa tty a c id b e ta -o x id a tio n c h a in , th u s lim itin g lip o ly s is in th e liv e r, w h ic h is n e c e s s a ry fo r th e e n e rg e tic m e ta b o lis m in th e n e o n a te p e rio d . N o t a ll fla v o e n z y m e s a re s e n s itiv e to p h o to th e ra p y ; h o w e v e r, rib o fla v in is th e m o s t s u s c e p tib le to lig h t. R ib o fla v in d e fi'c ie n c y s e e m s to b e d ire c tly re la te d to th e d u ra tio n o f p h o to th e ra p y , a n d to b e e n h a n c e d in th e p re m a tu re in fa n t.I.'3 H o w e v e r, th e s ig n ific a n c e o f th is m e ta b o lic a lte ra tio n is n o t y e t v e ry c le a r. 1 6 .1 7 .2 4 .2 5

W H E N T O U S E P H O T O T H E R A P Y

N e w b o rn s w h o w e ig h le s s th a n 1 ,5 0 0 o r 2 ,0 0 0 g ra m s h a v e re c e iv e d p ro p h y la c tic p h o to th e ra p y fro m th e m o m e n t o f b irth in s e v e ra l s tu d ie s . T h e s e b a b ie s a re , a lo n g w ith th o s e w h o h a v e is o im m u n iz a tio n h e m o ly tic d is e a s e , c o n s id e re d to d a y a s th o s e w ith th e g re a te s t ris k o f d e v e lo p in g b iliru b in ic e n c e p h a lo p a th y .2 .5 .IH .2 fiIn th e s e lo w -w e ig h t n e -w b o rn s , p h o to th e ra p y h a s d im in is h e d th e n e e d fo r a n e x s a n g u in e tra n s fu s io n , w h ic h s h o u ld s tim u la te th e u s e o f th e tre a tm e n t.2 fi H o w e v e r, it is n e c e s s a ry to re fle c t o n s o m e fa c ts : firs t, b iliru b in le v e ls m a y e v e n tu a lly b e a c c e p ta b le o r e v e n d e s ira b le fo r th is k in d o f n e w b o rn , c o n s id e rin g th e a n ti-o x id iz in g p o w e r o f b iliru b in , w h ic h h a s a b io lo g ic a l v a lu e in th e n e w b o rn th a t is n o t y e t k n o w n ; s e c o n d , th e in c re a s e d d e h y d ra tio n in n e w b o rn s , w h ic h in c re a s e s th e p e rip h e ric b lo o d flo w , c a u s in g p ro b a b le s a c rific e to o th e r a re a s . W e th e re fo re b e lie v e th a t p ro p h y la c tic p h o to th e ra p y , w h ic h is c u rre n tly a c c e p te d a n d p ra c tic e d , s h o u ld u n d e rg o a rig o ro u s a n d p e rm a n e n t re e v a lu a tio n . It is a ls o c u rre n tly b e lie v e d th a t th e ris k o f e n c e p h a lo p a th y is v e ry lo w o r v irtu a lly n o n -e x is te n t5 . 2 1 . 2 2 .2 fiin h e a lth y n e w b o rn s w ith o u t a p p a re n t h e m o ly tic d is e a s e a n d w e ig h in g m o re th a n 2 ,5 0 0 g ra m s , b u t w h o , h o w e v e r, p re s e n t p h y s io lo g ic ja u n d ic e . M A IS E L S u s e d p h o to th e ra p y in th e 1 9 8 0 's o n th e s e n e w b o rn s a t le v e ls o f 1 2 m g /d l. T o d a y th e s a m e a u th o r,2 1 a c k n o w le d g in g th e n e w p a th s o f re s e a rc h , c o n s id e rs , a s d o o th e r a u th o rs ,2 .5 .2 2 th a t p h o to th e ra p y is a b u s e d in th e s e n e w b o rn s . T h is o v e ru s e ra is e s h o s p ita l e x p e n s e s , s e p a ra te s b a b ie s fro m th e ir m o th e rs , a n d s u b m its th e m to e v e n tu a l ia tro g e n ie s w ith o u t re a lly e v a lu a tin g th e c o n s e q u e n c e s o f th e s e a c ts .

1138

F ig u re 4 - D a ily a v e ra g e o f b iliru b in e m ia in N B s in p h o to th e ra p y a n d th e c o n tro l g ro u p ; b irth w e ig h t ~ 2 5 0 0 g .

t h e o r i e s o f b i l i r u b i n i c e n c e p h a l o p a t h y , i n w h i c h h e a l t h y ,

f u l l - t e r m i n f a n t s ( o b v i o u s l y w i t h o u t a n y s i g n o f h e m o l y t i c

d i s e a s e ) h a v e a l o w r i s k o f h a r m .2 1

T h u s , w e w i s h t o e m p h a s i z e t h e f a c t t h a t

r e c o m m e n d a t i o n s f o r p h o t o t h e r a p y m u s t b e s t r i c t e r , s i n c e

i t s e e m s t o b e o v e r u s e d i n h e a l t h y , f u l l - t e r m n e w b o r n s . I t

i s a b s o l u t e l y e s s e n t i a l , w h i l e u s i n g t h i s m e t h o d , t o c o n t r o l

t h e e f f i c a c y o f t h e e q u i p m e n t b y u s i n g a n a d e q u a t e n u m b e r

o f l a m p s w i t h i r r a d i a t i o n w i t h i n e s t a b l i s h e d s t a n d a r d s , a n d

b y u s i n g f i l t e r s t o p r e v e n t g e n o t o x i c e f f e c t s .

I t i s n e c e s s a r y t o p r o m o t e t h e a d e q u a t e u s e , a n d

p r e v e n t t h e a b u s e o f p h o t o t h e r a p y , i n o r d e r t o p r o t e c t o u r

p a t i e n t s f r o m s u c h a n a d e q u a t e m e t h o d , w h i c h , w h e n

i m p r o p e r l y u s e d , c o u l d l o s e t h e c r e d i b i l i t y i t h a s o b t a i n e d

i n o v e r t h i r t y y e a r s o f e x p e r i e n c e .

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T h e U n i t e d S t a t e s N a t i o n a l I n s t i t u t e o f C h i l d H e a l t h

a n d D e v e l o p m e n t h a s c o n d u c t e d a m u l t i c e n t e r s t u d y o f

p h o t o t h e r a p y o n n e w b o r n s w i t h j a u n d i c e .2 3 I n t h o s e

w e i g h i n g m o r e t h a n 2 5 0 0 g r a m s ( 1 4 0 N B s ) , p h o t o t h e r a p y

w a s u s e d c o n t i n u o u s l y w h e n e v e r b i l i r u b i n e m i a w a s a b o v e

1 3 m g / d l , w i t h a n a v e r a g e o f 1 5 m g / d . T h e b a b i e s w e r e o n

a v e r a g e 6 0 - h o u r s o l d . T h e e q u i p m e n t , t h e f l u o r e s c e n t

d a y l i g h t t y p e , w a s u s e d f o r 2 0 0 0 h o u r s a t a n a v e r a g e

i r r a d i a n c e o f 1 4 m m / c m 2 / n m ; t h e r e w a s a s i g n i f i c a n t

d e c r e a s e i n t h e l e v e l s o f b i l i r u b i n e m i a i n n e w b o r n s p l a c e d

u n d e r p h o t o t h e r a p y c o m p a r e d w i t h t h e c o n t r o l g r o u p .

H o w e v e r , t h i s d e c r e a s e w a s o n l y s i g n i f i c a n t i n t h e f i r s t 2 4

h o u r s o f u s e ( 2 .3 m g / d l i n t h e s t u d y g r o u p a n d 0 .4 7 m g / d l

i n t h e c o n t r o l g r o u p ) a n d d i d n o t i n t e r f e r e i n t h e d u r a t i o n

o f t h e b i l i r u b i n e m i a i n t h e s e n e w b o r n ( F i g . 4 ) . S C H E I D T 2 9

a n d t h e o t h e r m a i n i n v e s t i g a t o r s i n t h i s s t u d y f o l l o w e d

t h e s e n e w b o r n s f o r a p e r i o d o f 6 y e a r s t o i n v e s t i g a t e t h e i r

n e u r o p s y c h o l o g i c a n d m o t o r d e v e l o p m e n t , h e a r i n g a n d

i n t e l l i g e n c e q u o t i e n t . T h e r e w a s n o s i g n i f i c a n t d i f f e r e n c e

a m o n g s t t h e n e w b o r n s ( w i t h o r w i t h o u t p h o t o t h e r a p y ) i n

a n y o f t h e s e a r e a s . T h e c o n c l u s i o n o f t h e g r o u p w a s t h a t

p h o t o t h e r a p y w a s e f f i c i e n t f o r t h e c o n t r o l o f

h y p e r b i l i r u b i n e m i a , w i t h n o e v i d e n c e o f a d v e r s e e f f e c t s

i n s i x y e a r s o f f o l l o w - u p . P E R L M A N ,2 6 a f t e r c r i t i c a l l y

a n a l y z i n g t h i s f o l l o w - u p s t u d y , s t a t e d t h a t i t w o u l d b e

c o r r e c t t o s a y t h a t j a u n d i c e w i t h t h e p h o t o t h e r a p y d i d n o t

l e a d t o g r e a t e r b r a i n d a m a g e t h a n j a u n d i c e w i t h o u t

p h o t o t h e r a p y . T h i s i s i n a g r e e m e n t w i t h t h e n e w l y - r e v i s e d

D O E S T H E IN D IC A T IO N O F

P H O T O T H E R A P Y W IT H H IG H E R L E V E L S IN

H E A L T H Y T E R M IN F A N T S C A U S E S ID E

E F F E C T S T H A T A R E N O T D E T E C T E D IN

T H E N E O N A T E P E R IO D ?

O u r s u g g e s t i o n s f o r t h e u s e s o f p h o t o t h e r a p y a r e

i n T a b l e 1 , e x c l u d i n g h e m o l y t i c d i s e a s e s , b e c a u s e w e

b e l i e v e p h o t o t h e r a p y m a y b e m o r e l i b e r a l l y

r e c o m m e n d e d i n t h e s e c a s e s t h a n w h a t i s s u g g e s t e d b y

t h e t a b l e , d u e t o i t s i m p o r t a n t r o l e i n r e d u c i n g t h e n e e d

f o r e x s a n g u i n e t r a n s f u s i o n s .

RESUMO

o

objetivo deste artigo e apresentar ao leitor os avan90s nos conhecim entos sobre a fototerapia em pregada em recem

-nascidos ictericos. A eficacia desta form a terapeutica depende diretam ente da intensidade de luz em itida pelos aparelhos e

acredita-se que seja necessaria um a dose entre 6 a 12 um /cm 3/nanom etro. A tualm ente a indica98.0 da fototerapia tem sido

questionada em recem -nascidos de term o e sadios, porem 0 uso adequado desta terapia deve ser preconizado ate que se

tenha um "concensus" sobre as vantagens e desvantagens do seu em prego.

REFERENCES

1. A m in H ~, Shukla A K , Snyder F, Fung E , A nderson N M ,

Parsons, H G . T he signficance of phototherapy-induced

riboflavin deficiency in the full-term neonate. B ioi

N eonate 1992;61 :76-81.

2. B eaudry M A . T he use of phototherapy for neonatal

hyperbilirubinem ia. C M A J 1986; 134: 1237-45.

3. C aravalho M , L opes JM A . Fototerapia nos hospitais publicos

do R io de Janerio. J Pediatria 1991;67(5/6):157-162.

4. C aravalho M , L opes JM A . Q ual

e

0 tem po de vida util de

H im pada fluorescentes para fototerapia? J Pediatria

1991 ;67(5/6): 151-6.

5. C ockington R A . A guide to the use of phototherapy in the

m anagem ent of neonatal byperbilirubinem ia. J Pediatric

1979;95(2):281-5.

6. C ostarino A , E nnever JF, B uam gart S, Speck W T , Polin

R A . B ilirubin photoisom erization in prem ature neonates

under low - and high-dose phototherapy. Pediatrics

1985;75(3):519-22.

7. D eziel M , G irotti A . Photodynam ic action of bilirubin on

liposom es and erythrocyte m em branes. J B ioI C hern

1980;255( 17):8192-6.

8. E nnever JF. B lue light, green light, w hite light, m ore light:

T reatm ent of neonatal jaundice. C lin Perinatol

1990: 17(2):467-81

9. E nnever JF, K nox I, Spec W T . D ifferences in bilirubin

isom er com position in infants treated w ith green and w hite

light phototherapy. J Pediatrics 1986; 109: 119-22.

10. E nnever JE Phototherapy for neonatal jaundice. Photochem

Photobiol 1988;47(6):871-6.

II. E nnever JF, K nox I, D enne C S, Spec W T . Phototherapy

for neonatal jaundice: "in vivo"clearance of bilirubin

photoproducts. Pediatr R es 1985; 19(2):205-8.

12. E nnever JF. Phototherapy for neonatal jaundice. In: Polin

R A , Fox W A , eds. Fetal and neonatal physiology.

. Philadelphia: W .B . Saunders, 1991: 1165-72.

13. G rom ish D S, L opez R , C ole H S, C operm an JM . L

ight-(phototherapy) induced riboflavin deficiency in the neonate.

J Pediatrics 1977;90(1):118-22.

14. H oltrop PC , M adison K , M aisels JM . A clinical trail of

fiberoptic phototherapy vs. conventional phototherapy. A

J D C 1992; 146:235-7.

15. H oltrop PC , R uedizueli K , M aisels JM . D ouble versus

single phototherapy in low birthw eight new borns. Pediatrics

1992;5(5):674-7.

16. L ucas A , B ates, C J. T ransient riboflavin depletion in

preterm infants. A rch D is C hild 1984;59:837-41.

17. L ucas A , B ates, C J. O ccurrence and significance of

riboflavin deficiency in preterm infants. B ioi N eonate

1987;52: 113-8.

18. M aisels, M J. In: A very neonatology pathophysiology and

m anagem ent of the new born, 3rd ed. N eonatal Jaundice.

Philadelphia: J.B . L ippincott C o., 1987:534-629.

19. M eloni T , C orti R , N aitana A F, A rese P. T he lack of effect

of phototherapy on red cell riboflavin status and

glucose-6-phosphate dehydrogenase activity in norm al and G

-6-PF-deficient subjects w ith neonatal jaundice. J Pediatrics

1982; 100(6):972-4.

20. M cD onagh A f, L ightner D A . "L ike a Shrivelled B lood

O range" - B ilirubin,jaundice, and phototherapy. Pediatrics

1985;75(3):443-54.

21. N ew m an T , M aisels M J. D oes hyperbilirubinem ia dam age

the brains of healthy, full-term infants? C lin Perinatol

1990; 117(2):331-57.

22. N ew m an T , M aisels M J. E valuation and treatm ent of

jaundice in the term new born: a kinder, gentler approach.

Pediatrics 1992;89(5):809-18.

23. N ational Institute of C hild H ealth and H um an D evelopm ent.

T he developm ent of random ized, controlled trails of

phototherapy for neonatal hyperbilirubinem ia. Pediatrics

1985;75:385-441.

24. Parson H G , D ias V c . Intram itochondrial fatty acid

m etabolism : riboflavin deficiency and energy production.

B iochem C ell B ioI 1990;69:490-7 .

1140

2 5 . P a tte r s o n B E , B a te s C J , H a llid a y D , L u c a s A . 1 - 1 3 C -o c ta n -o a te o x id a tio n , e n e r g y e x p e n d itu r e a n d v ita m in B 2 s u p p le m e n t in p r e m a tu r e in f a n ts . A c ta P a e d ia tr S c a n d

1 9 8 9 ;7 8 :7 8 0 - 1 .

2 6 . P e r lm a n M . T h e N I C H D P h o to th e r a p y S tu d y . P e d ia tr ic s 1 9 9 0 ;8 6 ( 5 ) :8 1 1 - 1 2 .

2 7 . P o lin R A . T h e M a n a g m e n t o f n e o n a ta l h y p e r b ilir u b in e m ia : R a tio n a l u s e o f p h o to th e r a p y . B io I N e o n a te

I 9 9 0 ;5 8 ( s u p p l) :3 2 - 4 3 .

2 8 . R a m o s J L A . E d ito r a l. J P e d ia tr ic a 1 9 9 1 ;6 7 ( 5 /6 ) .

2 9 . S c h e id t P , B r y la D , N e ls o n K B , H ir tz D G , H o f f m a n H J . P h o to th e r a p y f o r n e o n a ta l h y p e r b ilir r u b in e m ia : A s ix -y e a r f o llo w - u p o f th e N a ~ io n a l I n s titu te o f C h ild H e a lth a n d H u m a n D e v e lo p m e n t C lin ic a l T r ia l. P e d ia tr ic s 1 9 9 0 ;8 5 ( 4 ) :4 5 5 - 6 3 .

3 0 . S tu tc h f ie ld P R , M o d i N , W e in d lin g A M . P h o to th e r a p y a n d th e u s e o f h e a t s h ie ld s in v e r y lo w b ir th w e ig h t in f a n ts . A r c h D is C h ild 1 9 8 8 ;6 3 :5 5 2 - 4 .

3 1 . T a n K L . P h o to th e r a p y f o r n e o n a ta l ja u n d ic e . C lin P e r in a to l 1 9 9 1 ;( 3 ) :4 2 3 - 3 9 .

3 2 . T o z z i E , T o z z i- C ia n c a r e lli M G , D i G iu lio A , D ' A lf o n s o A , F a r e llo G , S p e n n a ti G F , M a tte is F . I n v itr o a n d in v iv o e f f e c ts o f e r y th o c y te p h o to th e r a p y o n n e w b o r n s . B io I N e o n a te 1 9 8 9 ;5 6 :2 0 4 - 9 .

3 3 . W o n g W y , P o w w a r s D R , A b d a lla C , W u P Y K . P h o to th e r a p y f a ilu r e in ja u n d ic e n e w b o r n s w ith h e r e d ita r y s p h e r o c y to s is . A c ta P a e d ia tr S c a n d 1 9 9 0 ;7 9 :3 6 8 - 9 .