Abst ract
Submitted: August 1st, 2016
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Accepted: February 27, 2017
Com par ison of t w o com binat ions of
opioid and non- opioid analgesics for
acut e per iradicular abscess:
a random ized clinical t r ial
Acut e periradicular abscess is a condit ion charact erized by t he form at ion and propagat ion of pus in t he periapical t issues and generally associat ed w it h debilit at ing pain. Obj ect ive: The aim of t his st udy was t o com pare t he overall analgesic effect iveness of t wo com binat ions of opioid and non- opioid analgesics for acut e periradicular abscess. Mat erial and Met hods: This st udy included 26 pat ient s w ho sought em ergency care in a Brazilian dent al school. The pat ient s ZHUHUDQGRPO\GLYLGHGLQWRWZRJURXSV&R$F±RUDOSUHVFULSWLRQRIFRGHLQH PJSOXVDFHWDPLQRSKHQPJHYHU\KIRUGD\VRU7U$F±RUDO prescript ion of t ram adol hydrochloride ( 37.5 m g) plus acet am inophen ( 500 m g) on t he sam e schedule. Tw o fact ors w ere evaluat ed: ( 1) pain scores recorded by t he pat ient s in a pain diary 6, 12, 24, 48, and 72 h aft er t reat m ent , using t he Visual Analogue Scale; and ( 2) t he occurrence of adverse effect s. Result s: I n bot h groups, t here was a reduct ion in pain scores over t im e. For t he Co/ Ac JURXSWKHUHZDVDVLJQL¿FDQWUHGXFWLRQLQWKHVFRUHVDQGKRXUV DIWHUWUHDWPHQW3,QWKH7U$FJURXSWKHVFRUHVVLJQL¿FDQWO\GHFUHDVHG over t im e from t im e point 6 h ( P< 0.05) . Com paring t he pain at each t im e SRLQWWKHJURXSVZHUHQRWVLJQL¿FDQWO\GLIIHUHQW3!LHERWKWUHDWPHQWV w ere effect ive in cont rolling pain caused by APA; how ever, t he com binat ion of Tr/ Ac caused m ore adverse react ions as t w o pat ient s had t o st op using t he m edicat ion. Conclusion: This st udy suggest s t hat , considering bot h analgesic HI¿FDF\DQGVDIHW\WKHFRPELQDWLRQRIFRGHLQHDQGDFHWDPLQRSKHQLVPRUH effect ive t o cont rol m oderat e t o severe pain from acut e periradicular abscesses.
Ke yw or ds: Analgesia. Codeine. Periapical abscess. Tram adol. Visual analog
scale. Manuela Favarin SANTINI1
Ricardo Abreu da ROSA1
Maria Beatriz Cardoso FERREIRA2
Maria Isabel FISCHER3
Erick Miranda SOUZA4
Marcus Vinícius Reis SÓ1
http://dx.doi.org/10.1590/1678-7757-2016-0407
1Universidade Federal do Rio Grande do Sul, Departamento de Odontologia Conservadora, Porto
Alegre, RS, Brasil.
2Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento
de Farmacologia, Porto Alegre, RS, Brasil.
3Universidade Federal do Rio Grande do Sul, Departamento de Produção e Controle de
Medicamentos, Porto Alegre, RS, Brasil.
4Universidade Federal do Maranhão, Departamento de Odontologia II, São Luís, MA, Brasil.
I nt r oduct ion
Acut e per iradicular abscess ( APA) is a condit ion
charact er ized by t he for m at ion and pr opagat ion of
pus in t he per iapical t issues as a dir ect im m
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Cl i n i cal si g n s i n cl u d e sw el l i n g , ed em a an d i t i s
generally associat ed w it h debilit at ing pain20, 26. The
clin ical ap p r oach t o r ed u ce p ain in APA p at ien t s
includes t he m andat ory need t o ident ify t he locat ion of
t he suppurat ive m ass26,QLWLDOO\SXVFDQEHFRQ¿QHG t o t h e p er iod on t al lig am en t sp ace, f acilit at in g a
drainage t hr oughout t he canal. When pus is locat ed
in t r aosseou sly, an ex pan sion of t h e cor t ical bon e
( i. e., sw ellin g ) is p r esen t , w h ich m ak es p at ien t s
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t he per iost eum and invades t he subm ucosal space
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a r educt ion in pain int ensit y. At t his phase, a sur gical
drainage of pus is an effect ive possibilit y26.
I n t he t r eat m ent of APA, besides t he local clinical
appr oach , w h ich r elies on su r gical access an d/ or
r oot canal debr idem ent and pr ov ide pus drainage,
a sy st em ic m edicat ion oncom ing t hat involves t he
use of analgesics and ant ibiot ics is also consider ed.
Ant ibiot ics can be pr escr ibed as a com plem ent ar y
m easu r e especially f or abscesses associat ed w it h
sy st em ic involvem ent , including fever, m alaise and
ly m phadenopat hy ; dissem inat ing infect ions r esult ing
in cellu lit is, p r og r essiv e d if f u se sw ellin g , an d / or
t r ism us; and abscesses in m edically com pr om ised
pat ient s at incr eased r isk of a secondar y infect ion
follow ing bact er em ia1, 24, 26. I n APA cases, analgesia
b ecom es ch allen g in g b ecau se t h e im m u n olog ical
m echanism s of pain have alr eady been t r igger ed. I t
is generally accept ed t he use of non- st er oidal ant
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Ahm ad, et al.2 ( 1997) found t hat t herapeut ic doses of
NSAI Ds w er e m or e effect ive t han t he com binat ion of
acet am inophen ( 600- 650 m g) and codeine ( 60 m g) in
t he t reat m ent of pain caused by t he ext ract ion of t hird
m olar s. How ever, for pain m anagem ent of infect ious
diseases, t he use of NSAI Ds m ay m ask clinical signs of
infect ion1. Ther efor e, in t he pr esence of infect ion and
pain w it h m oderat e t o sever e int ensit y, t he com bined
use of oral opioids ( such as codeine or t ram adol) and
non- opioids ( such as acet am inophen or aspir in) is
consider ed m or e appr opr iat e13, even t hough t her e is
a clear lack of clinical ev idence t o suppor t using t hese
dr ug com binat ions in pain cont r olling, especially in
APA cases.
Codein e/ acet am in oph en is t h e m ost fr equ en t ly
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for t he m anagem ent of m oderat e- t o- sev er e acut e
p a i n2 8. H o w e v e r, t h e t r a m a d o l / a c e t a m i n o p h e n
com binat ion has also been pr oposed as an alt er nat ive
t o cont r ol acut e pain22. The use of t ram adol has been
p r ov en ef f ect iv e in t r eat in g som e cases of acu t e
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in t he t r eat m ent of acut e pain of dent al or igin ar e
not w ell charact er ized. Because APA is an infect ious
pr ocess of dent al or igin t hat m ight spaw n a sever e
debilit at ing pain ex per ience t o t he pat ient , it seem s
r elevant t o com par e t he overall effect iveness of t he
t wo com binat ions of opioid/ non- opioid m edicat ions, as
indicat ed by t he analgesic effect and t he incidence of
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differ ence in analgesic effect iveness is pr esent w hen
com bining t hese t w o opioids ( codeine or t ram adol)
w it h acet am inophen ( non- opioid) t o m anage pain in
pat ient s w it h APA.
Mat er ial and Met hods
This st udy was appr oved by t he Et hics Com m it t ee
o f t h e Fed er a l Un i v er si t y o f Ri o Gr a n d e d o Su l
( 12671913.1.0000.5347) .
Th i s d o u b l e b l i n d , co d e i n e / a ce t a m i n o p h e n
-cont r olled parallel design clinical t r ial was conduct ed
follow ing t he Consolidat ed St andar ds of Repor t ing
Tr i a l s ( CONSORT) 2 0 1 0 g u i d e l i n e . Th e sa m p l e
consist ed of APA pat ient s w ho sought em er gency car e
at t he dent al school of t he Federal Univer sit y of Rio
Grande do Sul. Diagnosis was est ablished based on
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of APA w er e obt ained aft er subj ect ive ex pr essions
r epor t ed by t he pat ient .
Sam ple size was calculat ed based on t he out com e
of Meh r v ar zf ar, et al.1 8 ( 2 0 1 2 ) , in w h ich , am on g
ot her m edicat ion, t ram adol has been com par ed t o
an ibu pr of en - based pill. Wit h t h e aid of Open Epi
2.3, a t w o- m eans based com par ison was used w it h
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st at ist ical pow er and rat io 1. The r esult s indicat ed t he
need for 10 pat ient s per gr oup in or der t o obser ve a
Populat ion
Pat ient s eligible for inclusion in t he ex per im ent
included 18+ year s- old adult s diagnosed w it h APA
and r epor t ing spont aneous pain gr eat er t han 40 m m
as m easur ed in t he 0- 100 m m Visual Analogue Scale
( VAS) ( m oder at e t o sev er e pain )1 2. Pat ien t s w er e
excluded if t hey had t aken analgesics or ant ibiot ics
w it hin 4 hour s pr ior t o em er gency sur ger y, r epor t ed
aller gy t o t he dr ugs used in t his st udy, had a hist or y
of gast r ic ulcer, liver or k idney disease, uncont r olled
diabet es m ellit u s or epilepsy, pr egn an cy or w er e
br east feeding.
I nt er vent ion
All endodont ic pr ocedur es, per for m ed by t he sam e
invest igat or ( M.F.S.) w er e st andar dized. Anest hesia
w as in d u ced w it h 2 % lid ocain e w it h ep in ep h r in e
1 : 1 0 0 , 0 0 0 . Pu lp al ch am b er w as accessed u n d er
r u bber dam isolat ion . Nex t , sept ic- t ox ic con t en t s
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Maillefer ; Ballaigues, Vaud, Sw it zer land) and 2.5%
sodium hypochlorit e ( NaOCl) ( Farm ácia Marcela; Port o
Alegr e, RS, Brazil) . Then, t he cor onal por t ions of t he
canals were enlarged wit h a LA Axxess drill ( Sybroendo;
Orange, Califor nia, USA) and t he w or k lengt h was
elect r onically det er m ined by t he apex locat or Apex
DSP ( Sept odont ; Par is, Î le- de- France, France) . The
apical par t of each r oot canal was pr epar ed t o a size
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w er e pr ofusely r insed w it h 5 m L of 2.5% NaOCl and
dr ied w it h paper point s. A st er ilized cot t on pellet was
placed in t he access cav it y and subsequent ly r est or ed
w it h t he glass ionom er cem ent Vit r o Fil ( Nova DFL;
Taquara, RJ, Brazil) . Finally, t he occlusion was checked.
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consent for m out lining t he pr ocedur e and it s possible
r isk s. Subsequent ly, pat ient s w er e allocat ed t o one of
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dose oral t ablet cont aining codeine/ acet am inophen
( 30 m g/ 500 m g) ever y 4 hour s for 3 day s, or Tr / Ac,
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t ram adol/ acet am inophen ( 37. 5 m g/ 325 m g) ever y
4 hour s for 3 day s. I nst r uct ions on how t o per for m
t he pain r ecor dings using t he VAS w er e given t o each
pat ient . An assist ant accom panied t he pat ient s w hile
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Th e pat ien t s r eceiv ed a pain diar y, con t ain in g
t h e VAS, a n d a sea l ed p a ck a g e w i t h t h e o t h er
doses of m edicat ion . I f pat ien t s ex per ien ced pain
t hat was not cont r olled by t he t est ed m edicat ions,
t hey w er e inst r uct ed t o t ake addit ional m edicat ion
( acet am inophen 500 m g, ever y 4 hour s) using under
an on- dem and schem e.
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t he pain diar y. To indir ect ly check adher ence t o t he
t r eat m ent plan, pat ient s w er e also asked t o r et ur n
t he m edicat ion package. Num erical values obt ained at
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dose adm inist rat ion) for each pat ient w er e r ecor ded.
I n ca se s t h a t d r a i n a g e w a s n o t p o ssi b l e o r
i n t h e p r e se n ce o f sy st e m i c sy m p t o m s ( f e v e r,
lym phadenopat hy, sw elling or t rism us) , 21 am oxicillin
capsules ( 500 m g) w er e pr escr ibed and given orally
ever y 8 hour s for 7 day s.
Random izat ion and blinding pr ocedur es
The random allocat ion sequence was per for m ed
using random t able num bers generat ed at random izer.
or g. A phar m acist encapsulat ed t he dr ugs in ident ical
capsules, and packaged in whit e bot t les num bered 1 t o
26. I nfor m at ion on dr ug adm inist rat ion was descr ibed
on t he label. An assist ant w ho was blinded t o t he aim
and t he pr ot ocol of t he st udy generat ed t he num ber s
using a spr eadsheet pr ogram ( Micr osoft Excel) .
Out com es
The pr im ar y out com e was t he pain scor es. They
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appoint m ent . Secondary out com es included frequency
of addit ional m edicat ion use and adver se r eact ions
r epor t ed by pat ient s. All infor m at ion was r egist er ed
in t he pain diar y by t he pat ient .
Th e Nu m ber Needed t o Har m ( NNH) , i. e., t h e
num ber of pat ient s receiving Tr/ Ac t reat m ent t o cause
one addit ional pat ient t o be har m ed, com par ed w it h
p at ien t s w h o r eceiv ed Co/ Ac t r eat m en t w as also
calculat ed.
St at ist ical m et hods
The analy ses w er e per for m ed on an int ent ion- t
o-t r eao-t basis. All so-t ao-t iso-t ical analy ses w er e per for m ed
using SPSS v.18.0 ( I BM Cor p.; Ar m onk , New Yor k ,
USA) .
D e scr i p t i v e st a t i st i cs w e r e p e r f o r m e d , w i t h
p r e se n t a t i o n o f d a t a a s a b so l u t e a n d r e l a t i v e
fr equencies, m edian and 25t h and 75t h per cent iles.
St udent ’s t - t est for independent sam ples was used
t o det er m ine differ ences bet w een t he m ean ages for
differ ences bet w een t he gr oups r egar ding gender,
t oot h t y pe, ant ibiot ic use and fr equency of adver se
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t he differ ence bet w een t he m ean init ial pain scor es
bet w een gr oups.
Th e t w o gr ou ps w er e com par ed con sider in g a
score- based evaluat ion in t he sam e t im e int erval using
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used t o com pare t he result s over t im e wit hin t he sam e
gr oup, follow ed by t he m ult iple com par ison t est of
Fr iedm an w hen needed. Differ ences w er e consider ed
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Result s
Table 1 sum m ar izes t he baseline charact er ist ics of
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w it h r espect t o gender ( P= 0.682) , age ( P= 0.350) ,
t oot h t y pe ( P= 0.370) , use of ant ibiot ic ( P= 0.239) or
init ial pain scor e ( P= 0.760) .
Fr om Apr il 2013 t o Decem ber 2014, 27 pat ient s
w er e ev al u at ed as p o t en t i al st u d y p ar t i ci p an t s.
Tw ent y- six pat ient s m et t he inclusion cr it er ia and
agr eed t o par t icipat e in t he clinical t r ial. Out of t hese
26 pat ient s, t hr ee fr om t he Co/ Ac gr oup and one
fr om t he Tr / Ac gr oup did not r et ur n t he pain diar y
and w er e excluded fr om t he st udy. Tw o pat ient s fr om
t he Tr / Ac gr oup show ed w or sening clinical st at us,
sought car e elsew her e and also did not r et ur n t he
pain diar y. Tw o pat ient s fr om t he Tr / Ac gr oup dr opped
out of t r eat m ent due t o t he occur r ence of adver se
r eact ions t hat im pair ed t heir daily act iv it ies and w er e
excluded fr om analy sis of pain scor es, but not fr om
analy sis of adver se effect s ( Table 2) . The num ber of
pat ient s in each gr oup, t ak ing int o account dr opout s
and exclusions, is show n in Figur e 1.
I n bot h gr oups, pain scor es decr eased over t im e.
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at 12, 24, 48 and 72 hour s com par ed t o baseline
( P< 0.05) . The scor es at 48 and 72 hour s w er e also
low er t han t he 6 hour s scor es ( P< 0.05) . I n t he Tr / Ac
gr oup, pain scor es decr eased in all ex per im ent al t im e
point s com par ed t o baseline ( P< 0.05) . The m edian,
25t h and 75t h per cent ile pain scor es at each t im e point
ar e show n in Table 2 and Figur e 2.
For t y per cent of pat ient s in each gr oup used t he
addit ional drug, a num ber t hat is not different bet ween
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addit ional t ablet s per pat ient was used in t he Co/ Ac
and Tr / Ac gr oups, r espect ively.
Th er e w as n o d if f er en ce b et w een t h e g r ou p s
r e g a r d i n g t h e f r e q u e n c y o f a d v e r s e r e a c t i o n s
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ex per ienced at least one adver se r eact ion, including
Co/Pa (n=10)
Tr/Pa (n=10)
P
Characteristic
Gender 0.628a
Male 2 (20%) 4 (40%)
Female 8 (80%) 6 (60%)
Age (year) 0.350b
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Minimum - maximum 26 - 67 18 - 68
Tooth type 0.370a
Monorradicular 4 (40%) 7 (70%) Polirradicular 6 (60%) 3 (30%)
Use of antibiotic 0.239a
Yes 5 (50%) 7 (70%)
No 5 (50%) 3 (30%)
Initial pain score 0.760c
Median (P25/ P75) 90.5 (71.2/100) 81.5 (72.2/ 98.5)
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bStudent´s t-test for independent samples cMann-Whitney U test
Table 1- Baseline characteristics of the two groups: codeine and acetaminophen combination (Co/Ac) and tramadol and acetaminophen
dizziness, dr ow siness, nausea, headache, vom it ing
and ot her s ( Table 3) . The NNH for each gr oup was
1.25.
Discussion
The com bined use of analgesics is indicat ed t o
cont r ol pain of m oderat e t o sever e int ensit y22. Clinical
t r ials have show n t hat t he com binat ion of analgesics
w it h d if f er en t m ech an ism s of act ion can p r ov id e
gr eat er pain r elief t han t he indiv idual use of each
dr ug8,10,16,18.
The m ax im um daily dosage of paracet am ol is 4
gram s, bear ing in m ind t hat , aft er t he adm inist rat ion
of 1 g, t he analgesic effect w ears off w it hin an average
of 6 hour s.This dosage m ust not be exceeded, even if
it becom es necessar y t o r educe t he int er val bet w een
t w o doses t o 4 hour s15.
I n a m et a- analysis t hat used t hird m olar ext ract ion
as a p ain m od el1 7, t h e t r am ad ol/ acet am in op h en
com binat ion ( 75 m g/ 650 m g) was super ior t o t he sole
use of t ram adol or acet am inophen and t o placebo wit h
r egar ds t o t he int ensit y and durat ion of analgesia.
Using t he sam e pain m odel, Macleod, et al.16 ( 2002)
f ou n d t h at p ain in t en sit y w as sig n if ican t ly low er
af t er 1 2 h ou r s in pat ien t s w h o r eceiv ed codein e/
acet am inophen ( 30 m g/ 1. 0 m g) t han r epor t ed for
pat ient s r eceiv ing acet am inophen alone.
I n t he pr esent st udy, no differ ence bet w een t he
n Initial 6 h 12 h 24 h 48 h 72 h Pa
Co/Ac 10 90.5 (71.25/100) 10.5 (0/ 60.5) 6 (0/ 36.5) 1.5 (0/ 31.7) 0 (0/ 7.7) 0 (0/ 4) Tr/Ac 8 88.5 (74.25/ 99.5) 9.5 (0.5/ 62.25) 5.5 (0/ 62.5) 6 (0/ 39.5) 0.5 (0/ 28) 0 (0/ 20) Pb 0.733 0.59 0.545 0.676 0.312 0.427
aFriedman test bMann-Whitney U test
Table 2 - Median and 25th/75th percentiles of pain scores (mm) before (initial) and after administration of codeine and acetaminophen
combination (Co/Ac) and tramadol and acetaminophen combination (Tr/Ac)
analgesic com binat ions w it h r espect t o pain r elief
was obser ved over 72 hour s ( P> 0.05) . Bot h Co/ Ac
and Tr / Ac t r eat m ent s w er e able t o decr ease t he pain
scor es over t im e. Ther efor e, t he hy pot hesis set was
par t ially accept ed. I n a st udy by Sm it h, et al.27 ( 2003)
t he effect s of t ram adol/ acet am inophen ( 37.5 m g/ 325
m g) and codeine/ acet am inophen ( 30 m g/ 300 m g)
in cont r olling pain aft er or t hopedic and abdom inal
sur ger ies in a placebo- cont r olled random ized clinical
t r ial w er e sim ilar, as obser ved her ein. I n t he dent al
lit erat ur e, t he analgesic com binat ions st udied in t he
pr esen t w or k w er e pr ev iou sly com par ed t o ot h er
opioids such as hydr ocodone w it h acet am inophen10,11.
A s i g n i f i c a n t l y h i g h e r p a i n r e l i e f p r o v i d e d b y
hydrocodone/ acet am inophen was observed com pared
t o codeine/ acet am inophen ( 30 m g/ 300 m g)10, whereas
a sim ilar effect was found when com pared t o t ram adol/
acet am inophen ( 75 m g/ 650 m g)11.
The fr equency of addit ional dr ug use was also not
a discrim inat ing fact or am ong groups. I n bot h groups,
four pat ient s ( 40% ) t ook addit ional acet am inophen.
Endodont ic lit erat ur e lack s infor m at ion about t he use
of addit ional dr ugs in cont r olling pain of endodont ic
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use of addit ional dr ugs as a way t o evaluat e analgesic
HI¿FDF\'D&RVWD$UD~MRHWDO6 ( 2012) , for inst ance, found no differ ences in t he fr equency of addit ional
dr ug use bet w een nim esulide and t ram adol t r eat m ent
gr oups. On t he ot her hand, Jung, et al.14 ( 2004) found
t hat only pat ient s in t he t ram adol/ acet am inophen
group used addit ional drugs ( 3% ) com pared wit h t hose
r eceiv ing codeine/ acet am inophen/ ibupr ofen.
I n t h i s st u d y, b o t h g r o u p s p r esen t ed si m i l ar
fr equency of adver se r eact ions, w hich is in line w it h
WKH¿QGLQJVRI6PLWKHWDO27 ( 2003) . How ever, four pat ient s fr om t he Tr / Ac gr oup w er e lost dur ing
follow-up due t o an adver se r eact ion. Tw o pat ient s ( 20% )
did not t olerat e t he side effect s and t w o ( 20% ) sought
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of dr ugs t est ed. Ther efor e, consider ing overall safet y,
t he Co/ Ac com binat ion could be t aken as super ior t o
Tr / Ac gr oup, w hich par t ially r ej ect t he or iginally set
K\SRWKHVLV7KHVHGDWDVXJJHVWWKDWWKHVDIHW\SUR¿OH
of bot h associat ion s m ay be dif f er en t an d f u t u r e
st udies m ust assess t his out com e. How ever, because
in t h is st u dy t h e sam ple size calcu lat ion w as n ot
perform ed for t his out com e ( i.e. safet y) , t he result can
be a r eal differ ence bet w een t r eat m ent s or a st at ist ic
t y pe I I er r or ( bet a) .
Opioid analgesics ar e useful agent s for t r eat ing
Figure 2- Graph of pain scores at each time point
Dizziness Drowsiness Nausea Headache Emesis Others
Co/Ac 5/10 8/10 6/10 1/10 2/10 1/10
Tr/Ac 4/10 6/10 4/10 1/10 2/10 0/10
Pa § 0.628 0.656 § § §
a&KLVTXDUHWHVW
Table 3-7KHIUHTXHQF\RIDGYHUVHUHDFWLRQVUHSRUWHGGXULQJWKHXVHRIFRGHLQHDQGDFHWDPLQRSKHQFRPELQDWLRQ&R$FDQGWUDPDGRO
pain of var ious et iologies, how ever, adver se effect s
ar e pot ent ial lim it at ions t o t heir use. I n a sy st em at ic
r ev iew, Moor e, et al.2 1 ( 2 0 0 0 ) con clu ded t h at t h e
addit ion of 60 m g codeine t o acet am inophen produced
addit ional pain r elief, but it m ay be accom panied by
side effect s, such as dr ow siness and dizziness. The
param et er used t o evaluat e t he incr eased r isk of an
adver se event associat ed w it h a dr ug int er vent ion is
t he NNH. I n t his clinical t r ial, t he NNH pr esent ed for
each gr oup w as 1. 25, Cit r om e and Ket t er5 ( 2013)
DI¿UPHG WKDW D 11+ LQ WKH UDQJH RI PD\
be accept able for adver se event s t hat m ay lead t o
discont inuat ion, but ar e not associat ed w it h ser ious
im m ed iat e h ealt h r isk s. Ed w ar d s, et al.9 ( 2 0 0 2 )
calculat ed t he NNH for t ram adol and t ram adol plus
acet am inophen in r elat ion t o a placebo and found
t hat for single- dose oral t ram adol or t ram adol plus
acet am inophen t he NNH for a pat ient t o r epor t any
adver se effect w er e 5.0 and 5.4, r espect ively. These
t r eat m ent s had high incidences of dizziness, nausea
DQG YRPLWLQJ 6LJQL¿FDQWO\ PRUH QDXVHD GL]]LQHVV
an d v om it in g w as r ep or t ed w it h sin g le- d ose or al
t ram adol or t ram adol plus acet am inophen t han w it h
placebo9.
Most clinical t rials have assessed t he m anagem ent of
endodont ic pain using a single oral dose schem e3,4,18,19,25,
ZKLFKDOORZVDPRUHVSHFL¿FHYDOXDWLRQRIDQDOJHVLF HI¿FDF\ DQG UHVWULFWV WKH DVVHVVPHQW RI DGYHUVH
r eact ions over a lim it ed per iod of t im e. I n cont rast ,
WKLVVWXG\SUHVFULEHGWKHWHVWHGFRPELQDWLRQVLQ¿[HG
doses, ever y 4 hour s over 3 day s. This schem e allow s
HYDOXDWLRQ RI WKH DQDOJHVLF HI¿FDF\ DQG IUHTXHQF\
of adver se r eact ions m or e closely t o a r eal clinical
set t ing, as w ell as t he analy sis of pat ient com pliance.
Sadeghein, et al.25 ( 1999) observed t hat ket orolac ( 10
m g) was m or e effect ive t han codeine/ acet am inophen
( 15 m g/ 325 m g) in cont r olling pain caused by acut e
a p i ca l p er i o d o n t i t i s. Nev er t h el ess, t h e ex t er n a l
validit y of t hese r esult s is quest ionable because for
t he baseline pain int ensit ies r epor t ed by t he aut hor s
( gr eat er t han 70 m m on VAS) , t he em ployed doses
of codeine and acet am inophen w er e low, even w hen
used in com binat ion.
Dur ing t he phase of abscess developm ent , t he pus
is aim ing t o r each t he ex t er ior t hr ough t he bone or
per iodont al t issue, w hich ex plains t he pain r epor t ed
by t he pat ient . Pr ost rat ion and pain lead t he pat ient
t o t he clinic, how ever, t his sit uat ion does not happen
and t hen t his clinical condit ion rem ains for several days
r egar dless t he use of analgesics and ant ibiot ics7. I n
t his phase, drainage does not produce m uch im pact , it
does not subst ant ially r educe pain and edem a. Thus,
m ost pat ient s had post operat iv e pain and needed
analgesics23.
I t is also im por t ant t o em phasize t hat t he analy sis
w as per f or m ed on an in t en t ion - t o- t r eat basis, as
r efer r ed in t he m et hodology. Our aim was t o pr ov ide
ex t er nal validit y t o t he st udy, since in clinical pract ice
an alg esics ar e p r escr ib ed t o p at ien t s d ev elop in g
abscess t h at u se an t ibiot ics or n ot . Nev er t h eless,
frequency of ant ibiot ics use com parison was perform ed
in b ot h g r ou p s, sin ce t h is cou ld cau se con f u sion
w hen analy zing t he analgesic r esponse ( Table 1) . I n
KRPRJHQHLW\ WHVW VWDWLFDOO\ VLJQL¿FDQW GLIIHUHQFHV
w er e not obser ved in r egar d t o t he use in t he st udy
gr oups ( Chi Squar e Test , P> 0.05) .
7KHUHIRUHWKHLGHQWL¿FDWLRQRIDV\VWHPLFWKHUDS\
t hat pr esent s an overall analgesic effect iveness as
PHDVXUHGE\LWVDQDOJHVLFHI¿FLHQF\DQGVDIHW\LVDQ
im port ant clinical subj ect t o im prove t reat m ent qualit y
of acut e endodont icallyabscessed pat ient s.
Conclusions
The pr esent random ized clinical t r ial indicat ed t hat
Tr/ Ac and Co/ Ac t reat m ent present ed sim ilar analgesic
HI¿FDF\ ZKHQ XVHG WR FRQWURO SDLQ FDXVHG E\ $3$ +RZHYHU7U$FKDVDZRUVHVDIHW\SUR¿OHWKDQ&R
Ac, r esult ing in a gr eat er fr equency of abandoning
t r eat m ent due t o ineffect iv eness or int olerance t o
adver se effect s.
Acknow ledgm ent s
7KHDXWKRUVGHQ\DQ\FRQÀLFWVRILQWHUHVWUHODWHG
t o t his st udy. This st udy was support ed by grant s from
t he Coor dinat ion of Higher Educat ion and Graduat e
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