PHARMACOLOGI CAL ANALGESI A I N NEONATES UNDERGOI NG CARDI AC SURGERY
Mar ian a Bu en o1 Am élia Fum ik o Kim ur a2 Cibele Andr ucioli de Mat t os Pim ent a3
Bu en o M, Kim u r a AF, Pim en t a CAM. Ph ar m acological an algesia in n eon at es u n der goin g car diac su r ger y. Rev Lat ino- am Enfer m agem 2008 j ulho- agost o; 16( 4) : 727- 32.
The obj ect iv es of t his st udy w er e t o v er ify t he fr equency of phar m acological analgesia and t he occur r ence of post oper at iv e pain in neonat es under going car diac sur ger y . Met hods: This is a cr oss- sect ional st udy and dat a w er e collect ed fr om 30 m edical char t s of neonat es w ho under w ent car diac sur ger y in a pr ivat e hospit al in t he cit y of São Paulo. Result s: The m aj orit y ( 96.6% ) of neonat es received analgesia: 18 ( 60.0% ) received cont inuous analgesics, fiv e ( 1 6 . 7 % ) r eceiv ed int er m it t ent dr ugs, and six ( 2 0 . 0 % ) r eceiv ed a com binat ion of cont inuous and int erm it t ent analgesics. Fent anyl cit rat e was cont inuously adm inist ered t o 24 ( 80.0% ) neonat es. I nt erm it t ent dipyrone and m orphine was adm inist ered t o t en ( 33.3% ) and one ( 3.3% ) neonat es, respect ively. Pain regist ers were observed in 17 ( 56.7% ) m edical chart s and t he occurrence of pain am ong neonat es who received analgesics w as 53. 4% . Conclusion: Ther e w as no efficacy in phar m acological post oper at iv e pain cont r ol in t he neonat es included in t his st udy.
DESCRI PTORS: new bor n; pain; analgesia; congenit al hear t disease
USO DE FÁRMACOS ANALGÉSI COS EN POSTOPERATORI O DE CI RUGÍ A
CARDI ACA NEONATAL
Los obj et ivos de est e est udio fueron verificar la frecuencia de cobert ura analgésica farm acológica y la aparición de dolor post operat orio en neonat os som et idos a la cirugía cardiaca. Mét odo: se t rat a de un est udio t ransversal con r ecolección de dat os de Hist or ias Clín icas de 3 0 n eon at os som et idos a cir u gía car diaca en u n h ospit al privado de la ciudad de San Pablo. Result ados: La frecuencia de cobert ura analgésica fue de 96,6% , 18( 60,0% ) recibieron analgesia cont inua, cinco ( 16,7% ) int erm it ent e y seis ( 20,0% ) int erm it ent e y cont inua. El cit rat o de fent anil fue adm inist r ado cont inuam ent e a 24 ( 80,0% ) neonat os. Dipir ona y m or fina fuer on adm inist r adas en dosis int erm it ent es a diez ( 33,3% ) y a un ( 3,3% ) neonat os, respect ivam ent e. Fueron ident ificados regist ros de ocur r encia de dolor en 17 ( 56,7% ) Hist or ias Clínicas. La ocur r encia de dolor post oper at or io en r ecién nacidos con cober t ur a analgésica fue 53, 4 % . Conclusión: los dat os apunt an que el abor daj e analgésico adopt ado se m ost r ó ineficaz par a cont r olar el dolor post oper at or io en los neonat os est udiados.
DESCRI PTORES: r ecién nacido; dolor ; analgesia; car diopat ías congénit as
USO DE FÁRMACOS ANALGÉSI COS EM PÓS-OPERATÓRI O DE CI RURGI A
CARDÍ ACA NEONATAL
Os obj et iv os dest e est u do for am v er ificar fr eqü ên cia de cober t u r a an algésica far m acológica e ocor r ên cia de dor pós- oper at ór ia em n eon at os su bm et idos à cir u r gia car díaca. Mét odo: est u do t r an sv er sal com colet a de dados de pront uários de 30 neonat os subm et idos à cirurgia cardíaca em um hospit al privado da cidade de São Paulo. Result ados: a freqüência de cobert ura analgésica foi de 96,6% , 18( 60% ) receberam analgesia cont ínua, cin co ( 1 6 , 7 % ) in t er m it en t e e seis ( 2 0 % ) in t er m it en t e e con t ín u a. O cit r at o d e f en t an il f oi ad m in ist r ad o cont inuam ent e a 24 ( 80% ) neonat os. Dipir ona e m or fina for am adm inist r adas em doses int er m it ent es a dez ( 3 3 , 3 % ) e um ( 3 , 3 % ) neonat o, r espect iv am ent e. For am ident ificados r egist r os de ocor r ência de dor em 1 7 ( 5 6 , 7 % ) pr on t u ár ios. A ocor r ên cia de dor pós- oper at ór ia em r ecém - n ascidos com cober t u r a an algésica f oi 53,4% . Conclusão: os dados apont am que a abordagem analgésica adot ada m ost rou- se ineficaz para cont rolar a dor pós- oper at ór ia nos neonat os est udados.
DESCRI TORES: r ecém - n ascido; dor ; an algesia; car diopat ias con gên it as
1 RN, Doct oral st udent , e- m ail: m aribueno@hot m ail.com ; 2 RN, Facult y, e- m ail: fum iko@usp.br; 3 RN, Full Professor, e- m ail: parpca@usp.br. Universit y of
São Paulo School of Nursing, Brazil.
I NTRODUCTI ON
N
e o n a t a l p e r i o d i s a p h a s e o f i n t e n s e a d j u st m e n t a n d ch a n g e i n o r g a n s a n d sy st e m s,especially in t h e cir cu lat or y an d r espir at or y sy st em
due t o t he adj ust m ent t o t he ext raut erine environm ent .
The occurrence of cardiac m alform at ions m akes t hese
ad j u st m en t s h ar d er, in ad d it ion t o con t r ib u t in g t o
i n cr e a se i n m o r b i d i t y a n d m o r t a l i t y o f n e o n a t e s.
Accor ding t o t he t y pe of abnor m alit y, neonat es m ay
possibly require surgical int ervent ion in t he first days
of life t o sur vive.
S u r g i c a l p r o c e d u r e s t o c o r r e c t c a r d i a c
ab n or m alit ies m ay b e com p lex an d lead t o sev er e
post oper at iv e ( PO) pain, due t o sur gical incision and
t h e ex t en siv e m an eu v er of or g an s an d t issu es. I n
t urn, in t he PO period, newborns ( NB) undergo several
ot her invasive and painful procedures such as venous
and art ery punct ure t o collect blood sam ples, frequent
t racheal aspirat ion, as well as t he devices m aint ained
su ch as t r ach eal can u la, dr ain s, v ascu lar cat h et er s,
t enckoff cat het er, am ong ot her s( 1), w hich cont r ibut es
t o t he occur r ence of pain.
Fo r t h e s e n e w b o r n s , p a i n m a y l e a d t o
t achycardia, result ing in hem odynam ic com prom ising,
supr av ent r icular t achy ar r hy t hm ias, and hy per t ension,
t hat m ay cause a cr it ical and int oler able incr ease in
t he vent ricular post load( 2). I t is also known t hat pain
in t h e n eon at al p er iod m ay b r in g f u t u r e r esu lt s in
m ot or, cog n it iv e an d af f ect iv e r esp on se an d it can
cau se ch an g es i n t h e p ai n t h r esh o l d an d i n l o cal
sensibilit y( 3 ).
Cir cu it s r esp on sib le f or in h ib it ion an d p ain
m odulat ion ar e st ill im m at ur e in NB( 4), j ust ify ing t he
im p or t an ce of ad op t in g m easu r es t o con t r ol p ain ,
especially in t he PO per iod.
Prescribing analgesics is a m edical at t ribut ion,
however, nurses m ust offer NB proper cont rol of pain,
w hich includes not only assessing t he pain, but also
a s s e s s i n g t h e e f f e c t i v e n e s s o f p h a r m a c o l o g i c a l
analgesia prescribed and adm inist ered. Thus, t o know
t h e t y pes of an algesic em ploy ed, t h e dose, t im e of
a c t i o n , m e t a b o l i s m a n d e x c r e t i o n , t h e r o u t e o f
ad m in ist r at ion , t h e p ossib le d r u g in t er act ion s, t h e
adv er se ef f ect s of an algesic an d ot h er m edicat ion s
adopt ed by t he m edical t eam is a necessary m easure.
How ev er, t h e lit er at u r e p oin t s ou t t h at t h e
pr escr ipt ion of an algesic m edicat ion t o n eon at es is
st ill parsim onious. I n a st udy reviewing chart s, it was
assessed t hat 70.0% of adult s received PO analgesia,
and only 30.0% of children ( from one day of life t o 14
y ear s old) r eceiv ed ph ar m acological an algesia( 5 ).
Assessm ent of children’s chart s ( bet ween zero
and 10 years old) showed t hat only 2.0% of pat ient s
received all doses prescribed of analgesics during PO( 6).
Analysis perform ed in 933 charts of neonates undergoing
surgical procedures showed t he absence of assessm ent
records of pain and analgesia in 86.0 %(7).
PO analgesia is ext rem ely im port ant t o assist
su r g i ca l p a t i en t s( 8 ), i n cl u d i n g n eo n a t es; h o w ev er,
st u d i es sh o w p o o r a n a l g esi a i n t h e p ed i a t r i c a g e
group. Clinical experience wit h NB undergoing cardiac
s u r g e r i e s s h o w s t h a t e v e n u n d e r t h e u s e o f
pharm acological analgesia and sedat ives given in PO,
signs indicat ing pain cont inued.
Such observat ion encouraged us t o m ake t he
p r e s e n t s t u d y, w h o s e o b j e c t i v e s w e r e : a s s e s s
f r eq u en cy of NB r eceiv in g an alg esics, id en t if y t h e
analgesic approach, and check t he frequency of painful
r e sp o n se i n n e o n a t e s b e t w e e n t h e 2 4t h a n d 4 7t h
com plet e hour s of PO of car diac sur ger y.
MATERI ALS AND METHODS
Cr oss- sect ional st udy w it h r et r ospect ive dat a
c o l l e c t i o n , p e r f o r m e d i n a p r i v a t e m e d i u m - s i z e
hospit al, locat ed in t he West side of t he cit y of São
Paulo ( SP) , and t hat is a reference in neonat al cardiac
surgery. Dat a were collect ed as of t he records in chart s
of neonat es undergoing cardiac surgery from July 2001
t o Decem ber 2005. Collect ion and dat a analysis were
per for m ed fr om Oct ober and Decem ber 2 0 0 5 .
Ch a r t s o f n e o n a t e s u n d e r g o i n g c a r d i a c
surgery and wit h gest at ional age ≥ 35 weeks at birt h
were included in t he st udy. We have excluded deat hs
in t he first 48 hours, and NB wit h diagnoses of ot her
m alfor m at ions besides t he car diac one.
Va r i a b l e s s t u d i e d w e r e : t y p e o f
p h ar m aco l o g i cal an al g esi a ad m i n i st er ed , d o se ( i n
m cg/ k g/ h or m g/ k g/ h) adm inist er ed t y pe of infusion
( cont inuous or int erm it t ent ) , assessm ent of pain, and
diagn oses of pain . Recor ds m ade bet w een t h e 2 4t h
and t he 47t h PO hour w er e assessed. Recor ds of t he
f ir st 2 4 PO h ou r s h av e b een ex clu d ed b ecau se of
r esidual effect s of anest hesia used in t he sur ger y.
D a t a co l l e ct i o n w a s p e r f o r m e d a s o f t h e
v it al dat a cont r ol and nur sing not es) . Regar ding t he
assessm ent of pain, t his pr ocess w as inser t ed, in a
syst em at ized fashion, on t he Neonat al I nt ensive Care
Unit of NB in Novem ber, 2003. Before t hat , t here was
n o st an dar dizat ion r egar din g assessm en t of pain in
NB, and t he clinical nurse was in charge of prescribing
m et h od s an d in t er v als b et w een p ain assessm en t s.
The way records were m ade was t he responsibilit y of
t he nur sing t eam ( gener ally, not es consider ed som e
specific signs as pain indicat or s, for ex am ple cr y ing,
agit at ion, t ight facial m uscles, increase in heart rat e,
f all in sat u r at ion ) . As of Nov em ber, 2 0 0 3 , Neon at al
I nfant Pain Scale – NI PS( 9) st art ed being used for pain
assessm en t . Th is is a scale v alid at ed in 1 9 9 3 t h at
considers t he following param et ers in t he assessm ent
of p ain : f acial ex p r ession , cr y, b r eat h in g p at t er n s,
arm s, legs, and st at e of arousal of NB; it s score ranges
fr om 0 t o 7 and pain is consider ed w hen scor es ar e
higher t han 3( 9). Addit ionally, we hav e adopt ed specific
paper t o record pain and t he relief m et hods em ployed.
W i t h t h i s , a s s e s s m e n t m e t h o d s h a v e b e e n
s t a n d a r d i z e d , h o w e v e r, i n t e r v a l s b e t w e e n p a i n
assessm ent s cont inue t o be pr escr ibed accor ding t o
t he need check ed by t he clinical nur se.
La t e r, d a t a w a s t r a n s c r i b e d t o t h e t o o l
dev eloped for t he st udy, st or ed in a Micr osoft Excel
spr eadsheet and assessed by t he pr ogr am Epi- I nfo,
v er sion 6 . 4 .
Dat a collect ion w as st ar t ed aft er assessm ent
and appr ov al by t he Et hical Resear ch Com m it t ee of
t he Hospit al w her e t he st udy w as conduct ed.
RESULTS
For t y - t w o ch ar t s f r om n eon at es u n der goin g
cardiac surgery have been ident ified, 30 of t hem m et
t he eligibilit y cr it er ia of t he st udy. The gr oup st udied
p r esen t ed m ean g est at ion al ag e at b ir t h of 3 7 . 6 4
w eek s, w it h a ± 1.15 st andar d dev iat ion, and m ean
weight at birt h was 2885.5 gram s, ± 573.9 gram s. The
m aj o r i t y o f n eo n at es ( 7 0 . 0 % ) u n d er w en t su r g i cal
procedure in t he first week of life and in 73.3% st ernal
sur gical incision w as per for m ed.
Of t h e 3 0 n eon at es, 2 9 ( 9 6 . 7 % ) r ecei v ed
som e t ype of pharm acological analgesia in t he period
s t u d i e d . Th e u s e a n d t h e w a y o f a d m i n i s t e r i n g
phar m acological analgesia ar e pr esent ed on Table 1
b elow .
Table 1 – Form s of adm inist ering analgesics prescribed
on t he 1st PO. São Paulo, 2001 t o 2005
s c i s e g l a n a f o n o i t a r t s i n i m d a f o m r o f d n a e s
U N %
s e
Y 29 96.7%
s u o u n it n o C e t a r t i c l y n a t n e
F 18 60.0
t n e t t i m r e t n I e n o r y p i
D 5 16.7
t n e t t i m r e t n i d n a s u o u n it n o C e n o r y p i d d n a e t a r t i c l y n a t n e
F 5 16.7
e n i h p r o m d n a e t a r t i c l y n a t n e
F 1 3.3
o
N 1 3.3%
I t is seen t hat t he use of cont inuous analgesia
p r ev ailed am on g NB w it h p h ar m acolog ic an alg esia,
t ot aling 24 ( 80.0% ) . I n t he int erval from t he 24t h and
30t h hour, 24 ( 80.0% ) neonat es r eceiv ed cont inuous
an algesia; at t h e en d of t h e per iod st u died, at t h e
4 7 t h h o u r, f r e q u e n cy d e cr e a se d t o 2 0 n e o n a t e s
( 6 6 . 6 % ) .
Const ant doses of fent anyl were adm inist ered
t o 8 neonat es ( 26.7% ) , during t he period st udied; on
t h e ot h er h an d, t h er e w as a lar ge v ar iat ion on t h e
doses used in 16 neonat es ( 53.3% ) during t he period
st udied, as pr esent ed by Figur e 1.
Figur e 1 – Max im um and m inim al doses of fent any l
ci t r a t e i n m cg / k g / h , a d m i n i st e r e d i n co n t i n u o u s
infusion. São Paulo, 2001 - 2005
Ta b l e 2 p r e s e n t s d e s c r i p t i v e s t a t i s t i c a l
analysis of dat a r efer r ing t o m inim um and m axim um
dose of cont inuous fent any l cit r at e.
s e s o
D Mean Median Mode Maximum Minimum Standard -n o i t a i v e D m u m i x a
M 3.205 2.260 1.0 9.0 0.180 2.610
m u m i n i
M 2.093 1.830 1.0 7.8 0.180 1.832
Table 2 – Descript iv e st at ist ics referring t o m axim um
and m inim um dose of Fent any l cit r at e in m cg/ Kg/ h,
cont inuously adm inist er ed. São Paulo, 2001 t o 2005.
0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00 8,00 9,00 10,00
1 5 6 7 8 9 1112 14 15 16 17 18 20 21 22 23 24 25 26 27 282930
Newborns identification
Dose
Maximum dose
Adm inist rat ion of int erm it t ent m edicat ion was se e n i n 1 1 N B ( 3 6 . 6 % ) . Te n n e o n a t e s ( 3 3 . 3 % )
r eceiv ed dipy r one and 1 ( 3. 3% ) r eceiv ed m or phine, t ot aling 28 doses of drugs adm inist ered int erm it t ent ly.
Tab le 3 sh ow s d ist r ib u t ion of d oses of in t er m it t en t dr ugs adm inist er ed t o neonat es st udied.
Table 3 – Dist r ibut ion of doses of int er m it t ent dr ugs
adm inist er ed t o neonat es, accor ding t o int er v als, on t he 1st PO. São Paulo, 2001 – 2005
D o ses o f d i p y r o n e a d m i n i st er ed w er e, o n
av er ag e, of 2 4 . 4 3 6 m g / k g , w it h m ed ian of 2 1 . 7 3 0 an d st an d ar d d ev i at i o n o f 1 3 . 9 2 0 . Mi n i m u m d o se
ad m in ist er ed w as 1 5 . 6 2 0 an d m ax im u m d ose w as
8 9 . 2 8 0 m g / k g . m o r p h i n e d o ses ad m i n i st er ed w er e const ant , 0. 08 m g/ Kg/ dose.
I t i s i m p o r t a n t t o st r e ss t h a t a m o n g NB r e c e i v i n g a n a l g e s i a , 2 1 ( 7 0 . 0 % ) a l s o r e c e i v e d
s e d a t i v e s , a m o n g t h e m , 2 1 ( 7 0 . 0 % ) r e c e i v e d cont inuous and/ or int erm it t ent m idazolam , one ( 3.3% )
r e ce i v e d co n t i n u o u s ci sa t r a cu r i u m b e sy l a t e , o n e ( 3 . 3 % ) r e c e i v e d c o n t i n u o u s c h l o r p r o m a z i n e
hy dr ochlor ide, and one ( 3. 3% ) r eceiv ed int er m it t ent p r op of ol.
Pr e se n ce o f PO p a i n w a s a sse sse d u si n g behavior and physiological indicat or s and NI PS scale,
alon e or t og et h er. Tab le 4 p r esen t s d ist r ib u t ion of
neonat es according t o t he occurrence of pain and use of ph ar m acological an algesia.
Table 4 – Dist r ibut ion of new bor ns accor ding t o t he
o c c u r r e n c e o f p a i n a n d a d m i n i s t r a t i o n o f phar m acological analgesia. São Paulo, 2001 - 2005
n i a p f o e c n e r r u c c O c i s e g l a n a f o e s U s e
Y No Total
N % N % N %
s e
Y 16 53.4 1 3.3 17 56.7
o
N 7 23.3 - - 7 23.3
d r o c e r o
N 6 20.0 - - 6 20.0
l a t o
T 29 96.7 1 3.3 30 100
I t is noticed that only 7 NB (23.3% ) did not present pain in the assessm ent using the scale. One NB (3.3% )
did not receive either continuous or interm ittent analgesia
although it presented record of pain.
DI SCUSSI ON
Becau se of t h e sev er al d elet er iou s ef f ect s
r e su l t i n g f r o m p a i n , i t s t r e a t m e n t d u r i n g PO o f
n eon at al car d iac su r g er y p r esen t s ex t r em e clin ical
r elev an ce. Ad eq u at e con t r ol of p ain d u r in g PO can
r e d u c e m o r b i d i t y a n d m o r t a l i t y o f n e o n a t e s
under going neonat al car diac sur ger ies( 10).
Treat m ent wit h m edicat ion m ust be based on
doses adj ust ed according t o body weight , m at urat ion,
ph y siological dev elopm en t , an d clin ical con dit ion of
n e o n a t e s( 1 1 ). D r u g s m a y b e c o n t i n u o u s o r
int erm it t ent ly adm inist ered. Cont inuous adm inist rat ion
o f o p i o i d s s e e m s p r e f e r r e d o v e r i n b o l u s
ad m in ist r at ion , sin ce it r ed u ces v ar iat ion of ser u m
con cen t r at ion of t h e d r u g , t h u s d ecr easin g t ox icit y
associat ed w it h peak s of concent r at ion( 11).
Most of t h e 2 4 ( 8 0 . 8 % ) n eon at es st u d i ed
received cont inuous pharm acological analgesia during
PO periods and, am ong t hem , 20 NB ( 66.6% ) received
cont inuous drugs during t he period st udied ( up t o t he
47t h PO hour ) . As pr ev iously descr ibed, PO analgesia
is essent ial, how ever, r ecom m endat ions r egar ding it s
dur at ion in new bor ns hav e not been found. The use
of opioids is r ecom m en ded in n eon at es in in t en siv e
c a r e u n d e r g o i n g l a r g e s u r g e r i e s , m e c h a n i c a l
pulm onary vent ilat ion, placem ent of drains or venous
cat h et er s, an d in diseases leadin g t o pain , su ch as
necrot izing ent erocolit is( 10). However, m ust be carefully
used and followed- up by cont inuous m onit oring of vit al
dat a( 11) in an int ensiv e car e env ir onm ent .
Fen t an y l cit r at e w as adm in ist er ed t o all 2 4
new bor ns r eceiv ing cont inuous m edicat ion. This is a
sy nt hesized pheny lpiper idine der iv at iv e opioid, 80 t o
100 t im es m or e pow er ful t han m or phine( 11). I t leads
t o an alg esia b y t h e lin k w it h µ r ecep t or s t h at ar e
specific an d ar e locat ed in br ain an d spin al r egion s
involved in t he m odulat ion and t r ansm ission of pain;
i t i s ex t r em el y f at - sol u b l e an d sp r ead s q u i ck l y t o
t issue m aking it easier for it t o pass t hrough t he
blood-brain barrier( 12). I t present s quick onset , reaching peak
bet ween 5 t o 15 m inut es, and short half life, bet ween
1 and 2 hours( 11).
I t is t he opioid of choice in pediat rics due t o
i t s l a r g e s a f e t y m a r g i n a n d t h e b e n e f i t s o n
h e m o d y n a m i c s t a b i l i t y( 1 3 ). Fo r t h i s r e a s o n ,
adm inist r at ion t o hem ody nam ically unst able pat ient s
is suggest ed( 11).
e v i t a r e p o -t s o P l a v r e t n I s g u r d t n e t t i m r e t n i f o s e s o D e n o r y p i
D Morphine
N % N %
4
2 thto29thhour 6 20.0 -
-0
3 thto35thhour 6 20.0 1 3.3
6
3 thto41sthour 5 16.7 1 3.3
2
Re c o m m e n d e d d o s e s r a n g e f r o m 0 . 5 t o
2 m cg/ k g/ h con t in u ou s f en t an y l cit r at e f or n eon at es
in UTI N( 1 , 1 1 ). Esp ecially f or PO of n eon at al car d iac
s u r g e r y, d o s e s b e t w e e n 1 a n d 3 m c g / k g / h a r e
suggest ed( 10). Dat a present ed on Pict ure 1 show t hat
6 NB ( 2 0 . 0 % ) r eceiv ed m in im u m doses of f en t an y l
cit rat e bet ween 0.18 and 1 m cg/ kg/ h, and 5 ( 16.6% )
m axim um doses bet ween 0.18 and 1m cg/ kg/ h, lower
t han t hose r ecom m ended by t he lit er at ur e.
Treat m ent wit h fent anyl cit rat e, however, has
si d e e f f e ct s, a n d a m o n g t h e m t h e f o l l o w i n g a r e
h ig h lig h t ed : seizu r es, d if f icu lt y b r eat h in g , t h or acic
r ig id it y, h y p ot en sion an d b r ad y car d ia, n au sea an d
v om it ing, decr ease in int est inal m ot ilit y, const ipat ion
a n d u r i n a r y r e t e n t i o n( 1 , 1 1 - 1 2 ). Th e r e m a y a l so b e
p h y s i c a l d e p e n d e n c y a n d n e o n a t a l a b s t i n e n c e
sy n dr om e r esu lt in g f r om con t in u ou s in f u sion of t h e
m edicat ion : t h e em ploy m en t of f en t an y l cit r at e f or
ov er t hr ee day s r equir es gr adual decr ease of doses
u n t i l i t i s su sp e n d e d , a n d t h e a d m i n i st r a t i o n o f
m e t h a d o n e , a sy n t h e si ze d o p i o i d w i t h p r o p e r t i e s
sim ilar t o t hose of m or phine, w hich is r ecom m ended
if abst inence sy ndr om e occur s.
I nt er m it t ent analgesics w er e adm inist er ed in
1 1 n e o n a t e s ( 3 6 . 6 % ) . Th e u s e o f d i p y r o n e ,
int erm it t ent drug used in 10 ( 91.0% ) of t he 11 NB, is
n o t r e c o m m e n d e d b y t h e Fo o d a n d D r u g
A d m i n i s t r a t i o n s i n c e 1 9 9 8 * . Cl i n i c a l s t u d i e s
r ecom m en d in g t h e ad m in ist r at ion of d ip y r on e an d
specific doses for neonat e hav e not been found.
Mor phine, descr ibed in t he lit er at ur e as t he
m o st co m m o n l y u se d o p i o i d i n cl i n i ca l p r a ct i ce ,
p r o b a b l y b e c a u s e i t i s m o r e f a m i l i a r t o
professionals( 11), was adm inist ered only t o one of t he
neonat es st udied. This opioid also pr ovides analgesia
t h r ou g h t h e lin k w it h µ r ecep t or s. I t also p r esen t s
quick onset , around 5 m inut es, and t he peak is reached
in 10 t o 30 m inut es; it s half- life r anges fr om 3 t o 8
hour s( 11). Recom m ended doses for adm inist r at ion of
int er m it t ent m or phine in neonat es r anges fr om 0. 05
an d 0 . 1 m g / k g( 1 ). Fo l l o w i n g r eco m m en d at i o n s, t h e
neonat es of t he pr esent st udy r eceiv ed int er m it t ent
doses of m or phine of 0. 08m g/ k g.
A d v e r s e e f f e c t s r e s u l t i n g f r o m t h e
adm inist r at ion of m or phine ar e: difficult y br eat hing,
c e n t r a l n e r v o u s s y s t e m d e p r e s s i o n , i n c r e a s e i n
i n t r a cr a n i a l p r e ssu r e , b r a d y ca r d i a , a r r h y t h m i a s,
p er i p h er a l v a so d i l a t i o n , h y p o t en si o n , d ecr ea se i n
gast r oint est inal t ract m ot ilit y, const ipat ion, nauseas,
vom it ing, biliary t ract spasm s, release of ant i- diuret ic
h o r m o n e , u r i n a r y r e t e n t i o n , h i s t a m i n e r e l e a s e ,
phy sical dependency( 1 , 1 1 ).
Ra n d o m i z e d c l i n i c a l t r i a l s r e c e n t l y
p u b l i sh ed( 1 4 - 1 5 ) al so p o i n t o u t t h e i m p ai r m en t s o n
n e u r o l o g i c a l d e v e l o p m e n t i n p r e t e r m n e w b o r n s
r eceiv ing cont inuous m or phine, com par ed t o placebo
or t o t hose r eceiv ing it int er m it t ent ly, r esult s should
be point ed out and show t he need for furt her st udies
on t he use of m orphine in NB.
Alt h ou g h d r u g s h av e b een ad m in ist er ed in
29 NB, 17 ( 56.7% ) of t hem were in pain. The absence
o f p r o t o c o l s a n d s t a n d a r d i z a t i o n r e g a r d i n g PO
a n a l g e si a i s e v i d e n ce d b y t h e se v e r a l a n a l g e si c
sch em es ad op t ed , as w ell as t h e d oses in f er ior t o
t hose r ecom m ended by ot her st udies w it h neonat es,
w hich can hav e cont r ibut ed t o t he high incidence of
pain despit e t he use of drugs.
Eigh t NB ( 2 6 . 7 % ) r eceiv ed on ly an algesics,
eit h er con t in u ou sly or in t er m it t en t ly ; t h e r em ain in g
2 1 n eon at es ( 7 0 . 0 % ) r eceiv ed sedat iv es associat ed
w i t h a n a l g e s i c s . A d m i n i s t r a t i o n o f s e d a t i v e s i s
effect iv e as an adj uv ant t r eat m ent in PO analgesia,
a n d i t sh o u l d n o t b e r ep l a cea b l e( 1 0 ). No n e o f t h e
n e o n a t e s r e c e i v e d o n l y s e d a t i v e s , a n d t h e
ad m in ist r at ion of sed at iv es can r ed u ce b eh av ior al
r e s p o n s e s r e s u l t i n g f r o m p a i n w h i c h m a y h a v e
influenced on t he assessm ent of pain per for m ed.
One neonat e ( 3.3% ) did not receive any kind
of pharm acological analgesia during PO, not following
form al guidelines( 1) t hat recom m end t he use of opioids,
especially, m or phine and fent any l cit rat e.
CONCLUSI ON
Frequency of t he use of analgesics on t he 1st
PO w a s 9 6 . 7 % . Fe n t a n y l c i t r a t e w a s t h e m o s t
fr equ en t ly con t in u ou sly adm in ist er ed an algesic, an d
8 ( 26. 7% ) neonat es r eceiv ed const ant doses dur ing
t h e 1 st PO. Si x t een ( 5 3 . 4 % ) r ecei v ed d o ses t h at
ranged from 0.18m cg/ kg/ h t o 9m cg/ kg/ h. I nt erm it t ent
dipy r one w as adm inist er ed t o 1 0 neonat es ( 3 3 . 3 % )
in doses ranging from 5.62m g/ kg t o 89.28m g/ kg. Only
one NB ( 3.3% ) received int erm it t ent m orphine at t he
0 . 0 8 m g / k g d o s e . D e s p i t e t h e a d m i n i s t r a t i o n o f
analgesics, m ost neonat es ( 56.7% ) present ed PO pain.
Ther e w as no consensus on t he m edicat ions
adm inist er ed, as w ell as t he associat ions and doses
adm inist er ed at PO of neonat al car diac sur ger y.
FI NAL CONSI DERATI ONS
Fent any l cit r at e and m or phine ar e indicat ed
for analgesia in neonat es. Their beneficial effect s have
b een p r ov ed , as w ell as t h eir sh or t - t er m s ad v er se
effect s. However, long- t erm adverse effect s from t heir
use hav e not been pr ov en y et .
Ev en t hough pain causes sev er al delet er ious
effect s in NB, we m ust consider t he occurrence of side
effect s from t he m edicat ion adm inist ered. The im pact
of t h ese d r u g s on sev er al or g an s an d sy st em s of
neonat es m ust be also considered, since t hey are st ill
being for m ed, especially t he cent r al ner vous syst em .
Treat m ent of PO pain in neonat es undergoing
car diac sur ger y m ust occur aft er specific assessm ent
t o ch eck t h e pr esen ce of pain . Specific in st r u m en t s
( su ch as NI PS scale, u sed in t h e ser v ice st u d ied ) ,
physiological and behavior changes t hat can be relat ed
t o pain ar e im por t ant t ools for assessm ent .
REFERENCES
1. Anand KJ, I nt ernat ional Evidence- Based Group for Neonat al
Pa i n . Co n s e n s u s s t a t e m e n t f o r t h e p r e v e n t i o n a n d
m an agem en t of pain in t h e n ew bor n . Ar ch Pediat r Adolesc
Me d 2 0 0 1 ; 1 5 5 ( 2 ) : 1 7 3 - 8 0 .
2. Wessel DL. Hem odynam ic r esponses t o per ioper at ive pain
and st ress in infant s. Crit Care Med 1993; 21( 9 Suppl) : S361- 2.
3. Grunau RE, Holst i L, Pet ers JWB. Long- t erm consequences
of pain in hum an neonat es. Sem in Fet al Neonat Med 2006;
1 1 : 2 6 8 - 7 5 .
4. Anand KJS. Clinical im port ance of pain and st ress in pret erm
n eon at es. Biol Neon at e 1 9 9 8 ; 7 3 : 1 - 9 .
5. Bey er JE, DeGood DE, Ashley LC, Russel GA. Pat t er ns of
post operat ive analgesic use w it h adult s and children follow ing
car d iac su r g er y. Pain 1 9 8 3 ; 1 7 ( 1 ) : 7 1 - 8 1 .
6. Burokas L. Fact ors affect ing nurses’ decisions t o m edicat e
p e d i a t r i c p a t i e n t s a f t e r c a r d i a c s u r g e r y. H e a r t Lu n g
1 9 8 5 ; 1 4 ( 4 ) : 3 7 3 - 9 .
7. Purcell-Jones G, Dorm on F, Sum ner E. The use of opioids in
n eon at es. A r et r ospect iv e st u dy of 9 3 3 cases. An aest h esia
1 9 8 7 ; 4 2 ( 1 2 ) : 1 3 1 6 - 2 0 .
8. Chaves LD, Pim ent a CAM. Cont role da dor pós- operat ória:
co m p a r a çã o e n t r e m é t o d o s a n a l g é si co s. Re v La t i n o - a m
En f er m agem 2 0 0 3 m ar ço- abr il; 1 1 ( 2 ) : 2 1 5 - 9 .
9. Law r ence J, Alcock D, McGr at h PJ, McMur r ay SB, Dulber g
C. The developm ent of a t ool t o assess neonat al pain. Neonat al
Net w 1 9 9 3 ; 1 2 ( 6 ) : 5 9 - 3 .
1 0 . S t r a f f o r d M , Z u c k e r H . Pa i n m a n a g e m e n t i n t h e
post oper at iv e congenit al hear t disease. Pr og Pediat r Car diol
1 9 9 5 ; 4 ( 1 ) : 1 6 9 - 7 6 .
1 1 . Tad d io A. Op ioid an alg esia f or in f an t s in t h e n eon at al
in t en siv e car e u n it . Clin Per in at ol 2 0 0 2 ; 2 9 ( 3 ) : 4 9 3 - 9 .
1 2 . W a y W L, Fi e l d s HL, Sch u m a ch e r MA. An a l g é si co s &
ant agonist as opióides. I n: Kat zung BG. Far m acologia básica
& clínica. 8. ed. Rio de Janeiro ( RJ) : Guanabara Koogan; 2003.
p . 4 4 6 - 6 2 .
1 3 . Hick ey PR, Han sen DD, Wessel DL, Lan g P, Jon as RA,
Elix son EM. Blu n t in g of st r ess r espon ses in t h e pu lm on ar y
c i r c u l a t i o n o f i n f a n t s b y f e n t a n i l . A n e s t h A n a l g
1 9 8 5 ; 6 4 ( 1 2 ) : 1 1 3 7 - 4 2 .
14. Sim ons SHP, Van Dij k M, Van Lingen RA, Rooft hooft D,
Du iv en v oor d en HJ, Jon g en eel N, et al. Rou t in e m or p h in e
infusion in pret erm new borns w ho received vent ilat ory support .
JA MA 2 0 0 3 ; 2 9 0 ( 1 8 ) : 2 4 1 9 - 2 7 .
15. Anand KJ, Hall RW, Desai N, Shephar d B, Ber gqv ist LL,
Young TE, et al. Effect s of m or phine analgesia in vent ilat ed
p r et er m n eo n at es: p r i m ar y o u t co m es f r o m t h e NEOPAI N
r an d om ized t r ial. Lan cet 2 0 0 4 ; 3 6 3 ( 9 4 2 2 ) : 1 6 7 3 - 8 2 .
