Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
411
In e na ional Jou nal o Medical
and Pha maceu ical Resea ch
Online ISSN-2958-3683 | P in ISSN-2958-3675
F equency: Bi-Mon hly
A ailable online on: h ps://ijmp .in/
O iginal A icle
Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo
Pos ope a i e Pain Managemen Following Appendec omy: A P ospec i e
Randomized S udy
Majo D . Bimal Ahluwalia
SAG Specialis , Anaes hesiology, Indi a Gandhi Hospi al, Sec o 9, Dwa ka, New Delhi
A B S T R A C T
Co esponding Au ho :
Majo D . Bimal Ahluwalia
SAG Specialis , Anaes hesiology,
Indi a Gandhi Hospi al, Sec o 9,
Dwa ka, New Delhi
Recei ed: 05-10-2025
Accep ed: 04-11-2025
A ailable online: 16-11-2025
Backg ound: E ec i e pos ope a i e pain managemen emains a c i ical
componen o su gical ca e, signi ican ly in luencing pa ien eco e y and clinical
ou comes. Appendec omy, one o he mos commonly pe o med eme gency
su gical p ocedu es wo ldwide, necessi a es op imal analgesic s a egies o
minimize pos ope a i e discom o and acili a e ea ly mobiliza ion. Bo h en anyl
and amadol a e widely u ilized o pos ope a i e analgesia, ye compa a i e
e idence ega ding hei e icacy and sa e y p o iles in appendec omy pa ien s
emains limi ed.
Me hods: This p ospec i e andomized con olled ial was conduc ed om June
2023 o July 2024 a a e ia y ca e eaching hospi al. A o al o 100 pa ien s
unde going eme gency o elec i e appendec omy we e andomly alloca ed in o wo
equal g oups: G oup F ecei ed in a enous en anyl (1 µg/kg) and G oup T
ecei ed in a enous amadol (1 mg/kg) o pos ope a i e analgesia. Pain in ensi y
was assessed using he Visual Analogue Scale a mul iple ime in e als (0, 2, 4, 6,
12, and 24 hou s pos ope a i ely). Seconda y ou comes included ime o i s escue
analgesia, o al analgesic consump ion, ad e se e ec s, and pa ien sa is ac ion
sco es.
Resul s: The en anyl g oup demons a ed signi ican ly lowe mean VAS sco es
compa ed o he amadol g oup a 2 hou s (2.34±0.82 s 3.76±1.12, p<0.001), 4
hou s (2.68±0.94 s 3.92±1.24, p<0.001), and 6 hou s (3.12±1.08 s 4.28±1.36,
p<0.001) pos ope a i ely. Time o i s escue analgesia was signi ican ly p olonged
in G oup F (4.82±1.26 hou s s 3.34±0.98 hou s, p<0.001). The incidence o nausea
and omi ing was highe in he amadol g oup (34% s 18%, p=0.048), while bo h
g oups showed compa able a es o o he ad e se e ec s. Pa ien sa is ac ion sco es
we e signi ican ly highe in he en anyl g oup (8.24±1.12 s 7.16±1.48, p<0.001).
Conclusion: In a enous en anyl p o ided supe io pos ope a i e analgesia wi h
be e pain con ol, p olonged du a ion o ac ion, and highe pa ien sa is ac ion
compa ed o amadol in pa ien s unde going appendec omy, wi h an accep able
ad e se e ec p o ile. These indings suppo he p e e en ial use o en anyl o
pos ope a i e pain managemen in appendec omy pa ien s.
Copy igh © In e na ional Jou nal o
Medical and Pha maceu ical Resea ch
Keywo ds: In a enous Fen anyl Ve sus, Appendec om, eme gency su gical.
INTRODUCTION
Acu e appendici is ep esen s one o he mos p e alen su gical eme gencies encoun e ed in clinical p ac ice, wi h
appendec omy being pe o med as he de ini i e ea men modali y ac oss all age g oups wo ldwide. The li e ime isk o
de eloping appendici is app oxima es 7-8%, making i a condi ion o subs an ial public heal h signi icance.(1) Despi e
ad ances in su gical echniques, including he widesp ead adop ion o lapa oscopic app oaches, pos ope a i e pain
managemen emains a c i ical de e minan o pa ien eco e y, hospi al leng h o s ay, and o e all clinical ou comes.
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
412
Inadequa e pain con ol ollowing appendec omy can lead o nume ous complica ions including delayed mobiliza ion,
inc eased isk o h omboembolic e en s, p olonged hospi al s ays, and diminished pa ien sa is ac ion.(2)
The pa hophysiology o pos ope a i e pain in ol es a complex in e play o pe iphe al and cen al sensi iza ion
mechanisms. Su gical auma ini ia es an in lamma o y cascade cha ac e ized by he elease o nume ous media o s
including p os aglandins, b adykinin, subs ance P, and cy okines, which sensi ize pe iphe al nocicep o s.(3) This
pe iphe al sensi iza ion, combined wi h cen al ne ous sys em changes, c ea es a s a e o heigh ened pain sensi i i y
ha , i inadequa ely managed, can p og ess o ch onic pain synd omes. The con empo a y unde s anding o pain
mechanisms has led o he de elopmen o mul imodal analgesia s a egies ha a ge di e en componen s o he pain
pa hway, he eby op imizing pain elie while minimizing ad e se e ec s associa ed wi h high-dose single-agen he apy.
Opioid analgesics emain co ne s one agen s in he managemen o mode a e o se e e pos ope a i e pain, unc ioning
p ima ily h ough ac i a ion o µ-opioid ecep o s dis ibu ed h oughou he cen al and pe iphe al ne ous sys ems.
Among he a ious opioid op ions a ailable, en anyl and amadol ep esen wo commonly u ilized agen s wi h dis inc
pha macological p o iles ha wa an compa a i e e alua ion. Fen anyl, a syn he ic opioid, possesses po ency
app oxima ely 80-100 imes g ea e han mo phine and exhibi s apid onse o ac ion, high lipid solubili y, and ela i ely
sho du a ion o e ec .(4) I s pha macokine ic p ope ies make i pa icula ly sui able o acu e pain managemen
scena ios whe e apid analgesia is desi ed. The d ug unde goes ex ensi e hepa ic me abolism p ima ily h ough he
cy och ome P450 3A4 enzyme sys em, p oducing inac i e me aboli es ha a e subsequen ly elimina ed enally.
T amadol, con e sely, ep esen s a cen ally ac ing analgesic wi h a dual mechanism o ac ion ha di e en ia es i om
adi ional opioids. The d ug unc ions bo h as a weak µ-opioid ecep o agonis and as an inhibi o o no epineph ine and
se o onin eup ake, con ibu ing o i s analgesic e icacy h ough complemen a y pa hways.(5) This unique
pha macological p o ile heo e ically o e s ad an ages in e ms o educed espi a o y dep ession and lowe abuse
po en ial compa ed o pu e µ-opioid agonis s. T amadol unde goes hepa ic me abolism ia mul iple cy och ome P450
isoenzymes, pa icula ly CYP2D6, which con e s i o O-desme hyl amadol (M1), an ac i e me aboli e wi h
signi ican ly g ea e opioid ecep o a ini y han he pa en compound. The con ibu ion o his me aboli e o o e all
analgesic e icacy in oduces pha macogene ic conside a ions, as indi iduals wi h poo CYP2D6 me abolize s a us may
expe ience educed analgesic bene i .
The compa a i e e alua ion o hese wo agen s in he speci ic con ex o appendec omy assumes pa icula impo ance
gi en he high olume o hese p ocedu es pe o med globally and he he e ogeneous na u e o pain managemen
p ac ices ac oss di e en heal hca e se ings. P e ious in es iga ions examining opioid analgesics in su gical popula ions
ha e yielded a iable esul s, wi h some s udies demons a ing supe io e icacy o en anyl while o he s ha e sugges ed
compa able e ec i eness be ween agen s.(6) Howe e , many o hese s udies ha e been limi ed by small sample sizes,
he e ogeneous su gical popula ions, inconsis en ou come measu es, o inadequa e assessmen o pa ien -cen e ed
ou comes. Fu he mo e, he li e a u e speci ically add essing pos ope a i e analgesia ollowing appendec omy emains
ela i ely spa se, wi h ew well-designed andomized con olled ials di ec ly compa ing en anyl and amadol in his
su gical popula ion.
Pain assessmen me hodologies ha e e ol ed conside ably, wi h he Visual Analogue Scale (VAS) eme ging as a widely
alida ed and ep oducible ins umen o quan i ying subjec i e pain in ensi y. The VAS ypically consis s o a 10-
cen ime e line wi h endpoin s labeled as 'no pain' and 'wo s imaginable pain,' allowing pa ien s o ma k hei pe cei ed
pain le el along his con inuum.(7) This simple ye e ec i e ool demons a es excellen eliabili y and sensi i i y o
changes in pain in ensi y o e ime, making i pa icula ly sui able o longi udinal pos ope a i e pain assessmen .
Addi ionally, he VAS acili a es s a is ical analysis and c oss-s udy compa isons, enhancing he gene alizabili y o
esea ch indings. Complemen a y ou come measu es including ime o i s escue analgesia, o al analgesic
consump ion, and pa ien sa is ac ion sco es p o ide a comp ehensi e assessmen o analgesic e icacy ha ex ends
beyond simple pain in ensi y measu emen s.
Sa e y conside a ions cons i u e an in eg al componen o analgesic selec ion, as all opioid agen s ca y inhe en isks o
ad e se e ec s ha mus be ca e ully balanced agains he apeu ic bene i s. Common opioid- ela ed ad e se e ec s
include nausea, omi ing, p u i us, u ina y e en ion, cons ipa ion, and espi a o y dep ession, wi h indi idual agen s
demons a ing a ying p opensi ies owa d speci ic side e ec s.(8) Fen anyl, owing o i s high po ency and apid onse ,
ca ies pa icula isk o espi a o y dep ession when adminis e ed in excessi e doses o o opioid-nai e pa ien s.
Howe e , i s ela i ely sho du a ion o ac ion may o e sa e y ad an ages in e ms o e e sibili y should ad e se
e ec s occu . T amadol, while gene ally associa ed wi h lowe isk o espi a o y dep ession compa ed o adi ional
opioids, exhibi s a unique ad e se e ec p o ile ha includes inc eased isk o seizu es, pa icula ly a highe doses o in
pa ien s wi h p edisposing ac o s, and po en ial o se o onin synd ome when combined wi h o he se o one gic
medica ions.(9)
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
413
The economic implica ions o analgesic selec ion me i conside a ion wi hin he b oade con ex o heal hca e esou ce
u iliza ion. Inadequa e pos ope a i e pain con ol has been associa ed wi h p olonged hospi al leng h o s ay, inc eased
nu sing wo kload, highe a es o eadmission, and p og ession o ch onic pain s a es equi ing ongoing medical
managemen .(10) Con e sely, op imal pain managemen acili a ing ea ly mobiliza ion and discha ge can educe o e all
heal hca e cos s while imp o ing pa ien ou comes. The compa a i e cos -e ec i eness o di e en analgesic s a egies
depends no only on d ug acquisi ion cos s bu also on ac o s including ad e se e ec p o iles, nu sing ime
equi emen s o adminis a ion and moni o ing, and impac on hospi al leng h o s ay. These economic conside a ions
assume pa icula ele ance in esou ce-limi ed se ings whe e cos -e ec i eness analyses may in o m o mula y
decisions and clinical p ac ice guidelines.
Pa ien sa is ac ion ep esen s an inc easingly ecognized quali y me ic in heal hca e deli e y, e lec ing no me ely he
echnical success o medical in e en ions bu he holis ic pa ien expe ience encompassing pain con ol, communica ion,
and o e all ca e quali y. In he pos ope a i e se ing, pa ien sa is ac ion co ela es s ongly wi h pe cei ed adequacy o
pain managemen , sugges ing ha e ec i e analgesia cons i u es a undamen al componen o pa ien -cen e ed ca e.
Unde s anding pa ien p e e ences and expe iences wi h di e en analgesic egimens can in o m clinical decision-making
and acili a e sha ed decision-making p ocesses ha inco po a e pa ien alues alongside clinical e idence.
Despi e he widesp ead clinical use o bo h en anyl and amadol o pos ope a i e analgesia, signi ican gaps pe sis in
he e idence base ega ding hei compa a i e e ec i eness in speci ic su gical popula ions. The he e ogenei y o
published s udies in e ms o dosing egimens, iming o adminis a ion, ou come measu es, and ollow-up du a ions
limi s he abili y o d aw de ini i e conclusions ega ding op imal analgesic selec ion. Addi ionally, many exis ing
s udies ha e ocused p ima ily on pain in ensi y as he sole ou come measu e, neglec ing o he clinically ele an
endpoin s such as unc ional eco e y, quali y o li e, and long- e m ou comes. This knowledge gap unde sco es he need
o well-designed compa a i e e ec i eness esea ch ha inco po a es comp ehensi e ou come assessmen and adequa e
s a is ical powe o de ec clinically meaning ul di e ences be ween in e en ions.
The p esen s udy was he e o e concei ed o add ess hese limi a ions h ough a p ospec i e andomized con olled ial
design compa ing in a enous en anyl e sus amadol o pos ope a i e pain managemen in pa ien s unde going
appendec omy. By employing igo ous me hodology including andom alloca ion, s anda dized dosing p o ocols,
alida ed ou come measu es, and comp ehensi e sa e y assessmen , his in es iga ion aimed o gene a e high-quali y
e idence o in o m clinical p ac ice ega ding op imal analgesic selec ion in his common su gical popula ion. The
indings o his s udy ha e po en ial implica ions no only o immedia e pos ope a i e ca e bu also o he de elopmen
o e idence-based ins i u ional p o ocols and clinical p ac ice guidelines add essing pos ope a i e pain managemen in
su gical pa ien s.
AIMS AND OBJECTIVES
The p ima y aim o his p ospec i e andomized con olled ial was o compa e he analgesic e icacy o in a enous
en anyl e sus amadol o pos ope a i e pain managemen in pa ien s unde going appendec omy. The s udy sough o
de e mine which agen p o ided supe io pain con ol as assessed by Visual Analogue Scale sco es a mul iple ime
in e als du ing he i s 24 hou s ollowing su ge y. Addi ionally, he in es iga ion aimed o e alua e he du a ion o
analgesia p o ided by each agen as measu ed by ime o i s escue analgesia equi emen .
The seconda y objec i es encompassed comp ehensi e assessmen o sa e y p o iles including incidence and se e i y o
ad e se e ec s such as nausea, omi ing, espi a o y dep ession, p u i us, and seda ion in bo h ea men g oups. The
s udy also aimed o e alua e o al pos ope a i e analgesic consump ion, pa ien sa is ac ion sco es, and any di e ences in
eco e y pa ame e s be ween he wo g oups. Fu he mo e, he in es iga ion sough o iden i y any demog aphic o
clinical ac o s ha migh p edic di e en ial esponse o ei he analgesic agen , he eby in o ming pe sonalized analgesic
selec ion s a egies in clinical p ac ice.
MATERIALS AND METHODS
S udy Design and Se ing
This p ospec i e andomized s udy was conduc ed in he Depa men o Su ge y in collabo a ion wi h he Depa men o
Anaes hesiology a a e ia y ca e eaching hospi al o e a pe iod o 13 mon hs om June 2023 o July 2024. The s udy
p o ocol ecei ed app o al om he Ins i u ional E hics Commi ee p io o commencemen , and he ial was egis e ed
wi h he Clinical T ials Regis y. All p ocedu es pe o med in his s udy we e in acco dance wi h he e hical s anda ds o
he ins i u ional esea ch commi ee and wi h he 1964 Helsinki Decla a ion and i s la e amendmen s.
Sample Size Calcula ion
Sample size calcula ion was pe o med using s a is ical so wa e based on an icipa ed di e ences in mean Visual
Analogue Scale sco es be ween g oups. Assuming a clinically signi ican di e ence o 1.0 poin on he VAS scale, wi h a
s anda d de ia ion o 1.5, alpha e o o 0.05, and desi ed powe o 80%, he minimum equi ed sample size was
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
414
calcula ed as 45 pa ien s pe g oup. To accoun o po en ial d opou s and p o ocol iola ions, a o al o 100 pa ien s we e
en olled, wi h 50 pa ien s andomly alloca ed o each ea men g oup.
Pa ien Selec ion
Adul pa ien s aged 18-65 yea s scheduled o eme gency o elec i e appendec omy we e sc eened o eligibili y.
Inclusion c i e ia comp ised con i med diagnosis o acu e appendici is based on clinical examina ion and adiological
in es iga ions, Ame ican Socie y o Anes hesiologis s physical s a us classi ica ion I o II, and p o ision o w i en
in o med consen o s udy pa icipa ion. Exclusion c i e ia included known hype sensi i i y o en anyl o amadol,
his o y o opioid abuse o dependence, ch onic pain condi ions equi ing egula analgesic use, signi ican hepa ic o
enal dys unc ion, p egnan o lac a ing women, pa ien s wi h con aindica ions o gene al anaes hesia, his o y o seizu e
diso de s, pa ien s ecei ing monoamine oxidase inhibi o s o selec i e se o onin eup ake inhibi o s, and inabili y o
comp ehend o u ilize he Visual Analogue Scale o pain assessmen .
Randomiza ion and Blinding
Eligible pa ien s who p o ided in o med consen we e andomly alloca ed o ei he G oup F ( en anyl) o G oup T
( amadol) using compu e -gene a ed andom numbe sequences. The andomiza ion sequence was concealed in
sequen ially numbe ed, sealed, opaque en elopes ha we e opened only a e pa ien en ollmen by an independen
esea ch coo dina o no in ol ed in pa ien ca e o ou come assessmen . While he anaes hesiologis adminis e ing he
s udy medica ion was necessa ily awa e o g oup alloca ion, pos ope a i e pain assessmen s we e conduc ed by ained
nu sing s a blinded o ea men assignmen . The s a is ical analys emained blinded o g oup alloca ion un il
comple ion o da a analysis.
Anaes he ic P o ocol
All pa ien s unde wen s anda dized p eope a i e e alua ion including de ailed his o y, physical examina ion, and
ele an labo a o y in es iga ions. Pa ien s we e kep nil pe o al o a leas 6 hou s p io o su ge y. In he ope a ing
oom, s anda d moni o ing including elec oca diog aphy, non-in asi e blood p essu e, pulse oxime y, and capnog aphy
was es ablished. Anaes hesia was induced wi h in a enous p opo ol (2 mg/kg) and en anyl (2 µg/kg), wi h muscle
elaxa ion achie ed using a acu ium (0.5 mg/kg). Following acheal in uba ion, anaes hesia was main ained wi h
iso lu ane in oxygen-ai mix u e, wi h addi ional doses o a acu ium adminis e ed as needed. All pa ien s ecei ed
in a enous ondanse on (4 mg) app oxima ely 30 minu es be o e comple ion o su ge y o p ophylaxis agains
pos ope a i e nausea and omi ing.
S udy In e en ion
A he comple ion o su ge y, immedia ely be o e e e sal o neu omuscula blockade, pa ien s ecei ed he assigned
s udy medica ion. G oup F pa ien s ecei ed in a enous en anyl a a dose o 1 µg/kg, dilu ed in 10 mL no mal saline
and adminis e ed slowly o e 2-3 minu es. G oup T pa ien s ecei ed in a enous amadol a a dose o 1 mg/kg,
simila ly dilu ed in 10 mL no mal saline and adminis e ed o e 2-3 minu es. The s udy medica ions we e p epa ed by he
anaes hesiologis in iden ical sy inges o main ain blinding o ou come assesso s. A e e e sal o neu omuscula
blockade wi h neos igmine (0.05 mg/kg) and glycopy ola e (0.01 mg/kg), pa ien s we e ex uba ed and ans e ed o he
pos -anaes hesia ca e uni o moni o ing.
Ou come Assessmen
The p ima y ou come measu e was pain in ensi y assessed using he Visual Analogue Scale a p ede ined ime in e als:
immedia ely upon a i al in he pos -anaes hesia ca e uni (0 hou s), and a 2, 4, 6, 12, and 24 hou s pos ope a i ely. The
VAS consis ed o a 10-cm ho izon al line wi h endpoin s labeled 'no pain' (0) and 'wo s imaginable pain' (10), and
pa ien s ma ked hei pe cei ed pain le el on his line. The dis ance om he 'no pain' endpoin o he pa ien 's ma k was
measu ed in cen ime e s o yield a nume ical pain sco e. Pa ien s we e amilia ized wi h he VAS sco ing sys em du ing
he p eope a i e pe iod o ensu e accu a e assessmen .
Seconda y ou comes included ime o i s escue analgesia, de ined as he in e al om adminis a ion o s udy
medica ion o pa ien eques o addi ional pain elie . When pa ien s epo ed VAS sco es exceeding 4 o speci ically
eques ed addi ional analgesia, escue medica ion consis ing o in a enous diclo enac sodium (75 mg) was adminis e ed.
I pain pe sis ed despi e escue medica ion, addi ional amadol (50 mg in a enous) was adminis e ed as needed. To al
analgesic consump ion du ing he 24-hou s udy pe iod was eco ded o all pa ien s. Ad e se e ec s including nausea,
omi ing, espi a o y dep ession ( espi a o y a e less han 10 b ea hs pe minu e), seda ion (assessed using Ramsay
Seda ion Scale), p u i us, and u ina y e en ion we e sys ema ically documen ed. Pa ien sa is ac ion wi h pain
managemen was assessed a 24 hou s pos ope a i ely using an 11-poin nume ical a ing scale anging om 0
(comple ely dissa is ied) o 10 (comple ely sa is ied).
Follow-up P o ocol
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
415
All pa ien s we e moni o ed con inuously in he pos -anaes hesia ca e uni o he i s 6 hou s pos ope a i ely, du ing
which i al signs, pain sco es, and ad e se e ec s we e eco ded a egula in e als. Subsequen ly, pa ien s we e
ans e ed o he su gical wa d whe e moni o ing con inued wi h pain assessmen s a 12 and 24 hou s. Nu sing s a
esponsible o pain assessmen s ecei ed s anda dized aining in VAS adminis a ion and ad e se e ec ecogni ion
p io o s udy commencemen . Any se ious ad e se e en s we e immedia ely epo ed o he p incipal in es iga o and
ins i u ional e hics commi ee. Pa ien s we e ollowed un il hospi al discha ge o ensu e comple e da a collec ion and o
moni o o any delayed ad e se e ec s.
S a is ical Analysis
S a is ical analysis was pe o med using SPSS so wa e e sion 26.0 (IBM Co p., A monk, NY, USA). Da a we e
assessed o no mali y using he Shapi o-Wilk es . Con inuous a iables wi h no mal dis ibu ion we e exp essed as
mean ± s anda d de ia ion and compa ed be ween g oups using independen samples - es . Con inuous a iables wi h
non-no mal dis ibu ion we e exp essed as median wi h in e qua ile ange and compa ed using Mann-Whi ney U es .
Ca ego ical a iables we e exp essed as equencies and pe cen ages and analyzed using chi-squa e es o Fishe 's exac
es as app op ia e. Pain sco es a di e en ime in e als we e compa ed using epea ed measu es analysis o a iance
wi h pos -hoc Bon e oni co ec ion o mul iple compa isons. Time o i s escue analgesia was analyzed using Kaplan-
Meie su i al analysis wi h log- ank es o g oup compa ison. A p- alue o less han 0.05 was conside ed s a is ically
signi ican o all analyses. All s a is ical es s we e wo- ailed, and con idence in e als we e calcula ed a he 95% le el.
RESULTS
Pa ien Demog aphics and Baseline Cha ac e is ics
A o al o 100 pa ien s we e en olled in he s udy and andomly alloca ed in o wo g oups o 50 pa ien s each. All
en olled pa ien s comple ed he s udy p o ocol wi hou any d opou s o p o ocol iola ions. The demog aphic and
baseline clinical cha ac e is ics a e p esen ed in Table 1. Bo h g oups we e compa able wi h espec o age, gende
dis ibu ion, body mass index, Ame ican Socie y o Anes hesiologis s physical s a us classi ica ion, and du a ion o
su ge y. The e we e no s a is ically signi ican di e ences be ween g oups in any baseline pa ame e , con i ming
success ul andomiza ion and compa able s udy g oups.
(See Table 1)
Pain In ensi y Assessmen
Visual Analogue Scale sco es a a ious ime in e als a e p esen ed in Table 2. Immedia ely pos ope a i ely, bo h
g oups demons a ed compa able pain sco es (G oup F: 1.86±0.74 s G oup T: 1.92±0.68, p=0.674). Howe e ,
s a is ically signi ican di e ences eme ged a subsequen ime poin s. A 2 hou s pos ope a i ely, he en anyl g oup
showed signi ican ly lowe mean VAS sco es compa ed o he amadol g oup (2.34±0.82 s 3.76±1.12, p<0.001). This
signi ican di e ence pe sis ed a 4 hou s (2.68±0.94 s 3.92±1.24, p<0.001) and 6 hou s (3.12±1.08 s 4.28±1.36,
p<0.001) pos ope a i ely. By 12 hou s, pain sco es emained lowe in he en anyl g oup, hough he di e ence was less
p onounced (3.84±1.22 s 4.42±1.54, p=0.038). A 24 hou s pos ope a i ely, bo h g oups showed compa able pain
in ensi y (4.12±1.38 s 4.36±1.62, p=0.425), likely e lec ing he in luence o escue analgesia adminis a ion in bo h
g oups.
(See Table 2)
Rescue Analgesia Requi emen s
Analysis o escue analgesia equi emen s e ealed signi ican di e ences be ween g oups as shown in Table 3. The
mean ime o i s escue analgesia was signi ican ly longe in G oup F compa ed o G oup T (4.82±1.26 hou s s
3.34±0.98 hou s, p<0.001), indica ing p olonged du a ion o e ec i e analgesia wi h en anyl. The p opo ion o pa ien s
equi ing escue analgesia wi hin he i s 4 hou s was signi ican ly lowe in he en anyl g oup (28% s 56%, p=0.004).
To al analgesic consump ion du ing he 24-hou s udy pe iod, including bo h s udy medica ion and escue analgesia, was
signi ican ly lowe in G oup F. Kaplan-Meie su i al analysis demons a ed ha pa ien s in he en anyl g oup had
signi ican ly longe analgesic du a ion compa ed o hose in he amadol g oup (log- ank es p<0.001).
(See Table 3)
Ad e se E ec s P o ile
The incidence o ad e se e ec s in bo h g oups is de ailed in Table 4. Nausea and omi ing ep esen ed he mos
commonly obse ed ad e se e ec s, wi h signi ican ly highe incidence in he amadol g oup compa ed o he en anyl
g oup (34% s 18%, p=0.048). The se e i y o nausea was gene ally mild o mode a e in bo h g oups, wi h only wo
pa ien s in he amadol g oup equi ing addi ional an ieme ic medica ion beyond he p ophylac ic ondanse on. P u i us
was obse ed mo e equen ly in he en anyl g oup, hough he di e ence did no each s a is ical signi icance (14% s
8%, p=0.303). Seda ion sco es, assessed using he Ramsay Seda ion Scale, we e compa able be ween g oups a all ime
in e als, wi h mos pa ien s main aining a sco e o 2-3 indica ing app op ia e seda ion le els. No pa ien s in ei he g oup
expe ienced clinically signi ican espi a o y dep ession, de ined as espi a o y a e below 10 b ea hs pe minu e o
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
416
oxygen sa u a ion below 90% on oom ai . One pa ien in he en anyl g oup and wo pa ien s in he amadol g oup
expe ienced u ina y e en ion equi ing ca he e iza ion, bu his di e ence was no s a is ically signi ican (p=0.558).
(See Table 4)
Pa ien Sa is ac ion and Reco e y Pa ame e s
Pa ien sa is ac ion sco es assessed a 24 hou s pos ope a i ely a e p esen ed in Table 5. The en anyl g oup
demons a ed signi ican ly highe mean sa is ac ion sco es compa ed o he amadol g oup (8.24±1.12 s 7.16±1.48,
p<0.001). When ca ego ized in o sa is ac ion le els, 74% o pa ien s in G oup F epo ed high sa is ac ion (sco es 8-10)
compa ed o 52% in G oup T (p=0.019). Reco e y pa ame e s including ime o i s ambula ion and hospi al leng h o
s ay showed a o able ends in he en anyl g oup, hough hese di e ences did no achie e s a is ical signi icance. The
mean ime o i s ambula ion was 8.4±2.6 hou s in G oup F e sus 9.8±3.2 hou s in G oup T (p=0.062), while mean
hospi al leng h o s ay was 2.8±0.9 days e sus 3.1±1.1 days espec i ely (p=0.145).
(See Table 5)
Hemodynamic Pa ame e s
Hemodynamic pa ame e s including hea a e, sys olic blood p essu e, and dias olic blood p essu e we e moni o ed a
egula in e als h oughou he s udy pe iod as shown in Table 6. Bo h g oups main ained s able hemodynamic p o iles
wi h no clinically signi ican di e ences in mean hea a e o blood p essu e measu emen s a any ime poin . The
s abili y o i al signs in bo h g oups con i med he hemodynamic sa e y o he analgesic egimens employed. No
pa ien s equi ed in e en ions o hemodynamic ins abili y a ibu able o s udy medica ions. Mean a e ial p essu e
emained wi hin no mal physiological ange in bo h g oups h oughou he obse a ion pe iod, wi h no ins ances o
signi ican hypo ension o hype ension equi ing ea men .
(See Table 6)
TABLES
Table 1: Demog aphic and Baseline Clinical Cha ac e is ics
Pa ame e
G oup F (Fen anyl) n=50
G oup T (T amadol) n=50
Age (yea s)
36.4 ± 12.8
38.2 ± 14.1
Gende (Male/Female)
28/22
31/19
BMI (kg/m²)
24.6 ± 3.2
25.1 ± 3.6
ASA S a us (I/II)
38/12
35/15
Du a ion o Su ge y (minu es)
48.6 ± 12.4
46.8 ± 13.2
Values exp essed as Mean ± SD o numbe s. BMI: Body Mass Index; ASA: Ame ican Socie y o Anes hesiologis s. No
signi ican di e ences be ween g oups (p>0.05 o all pa ame e s).
Table 2: Visual Analogue Scale Sco es a Di e en Time In e als
Time Poin
G oup F (n=50)
G oup T (n=50)
p- alue
0 hou s
1.86 ± 0.74
1.92 ± 0.68
0.674
2 hou s
2.34 ± 0.82
3.76 ± 1.12
<0.001*
4 hou s
2.68 ± 0.94
3.92 ± 1.24
<0.001*
6 hou s
3.12 ± 1.08
4.28 ± 1.36
<0.001*
12 hou s
3.84 ± 1.22
4.42 ± 1.54
0.038*
24 hou s
4.12 ± 1.38
4.36 ± 1.62
0.425
Values exp essed as Mean ± SD. *S a is ically signi ican (p<0.05). VAS sco es ange om 0 (no pain) o 10 (wo s
imaginable pain).
Table 3: Rescue Analgesia Requi emen s
Pa ame e
G oup F (n=50)
G oup T (n=50)
Time o i s escue analgesia (hou s)
4.82 ± 1.26
3.34 ± 0.98
Pa ien s equi ing escue analgesia <4 hou s
14 (28%)
28 (56%)
To al pa ien s equi ing escue analgesia
32 (64%)
42 (84%)
Mean numbe o escue doses (24h)
1.24 ± 0.86
1.88 ± 1.12
Values exp essed as Mean ± SD o numbe (pe cen age). p<0.001 o ime o i s escue analgesia; p=0.004 o pa ien s
equi ing escue analgesia <4 hou s.
Table 4: Ad e se E ec s P o ile
Ad e se E ec
G oup F (n=50)
G oup T (n=50)
Nausea and Vomi ing
9 (18%)
17 (34%)*
P u i us
7 (14%)
4 (8%)
Excessi e Seda ion (Ramsay >4)
3 (6%)
2 (4%)
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
417
Respi a o y Dep ession
0 (0%)
0 (0%)
U ina y Re en ion
1 (2%)
2 (4%)
Values exp essed as numbe (pe cen age). *p=0.048 s a is ically signi ican . All o he compa isons p>0.05.
Table 5: Pa ien Sa is ac ion Sco es and Reco e y Pa ame e s
Pa ame e
G oup F (n=50)
G oup T (n=50)
Pa ien Sa is ac ion Sco e (0-10)
8.24 ± 1.12
7.16 ± 1.48
High Sa is ac ion (Sco e 8-10)
37 (74%)
26 (52%)
Time o Fi s Ambula ion (hou s)
8.4 ± 2.6
9.8 ± 3.2
Hospi al Leng h o S ay (days)
2.8 ± 0.9
3.1 ± 1.1
Values exp essed as Mean ± SD o numbe (pe cen age). p<0.001 o pa ien sa is ac ion sco e; p=0.019 o high
sa is ac ion a e; p>0.05 o eco e y pa ame e s.
Table 6: Hemodynamic Pa ame e s
Time Poin
Pa ame e
G oup F
G oup T
0 hou s
Hea Ra e (bpm)
82.4 ± 10.2
84.6 ± 11.4
2 hou s
Hea Ra e (bpm)
78.6 ± 9.8
80.2 ± 10.6
6 hou s
Hea Ra e (bpm)
76.8 ± 9.4
78.4 ± 10.2
0 hou s
SBP (mmHg)
128.4 ± 12.6
126.8 ± 13.4
6 hou s
SBP (mmHg)
122.6 ± 11.8
124.2 ± 12.4
Values exp essed as Mean ± SD. bpm: bea s pe minu e; SBP: Sys olic Blood P essu e. No signi ican di e ences
be ween g oups a any ime poin (p>0.05).
DISCUSSION
The p esen p ospec i e andomized con olled ial demons a ed ha in a enous en anyl p o ided supe io
pos ope a i e analgesia compa ed o amadol in pa ien s unde going appendec omy, as e idenced by signi ican ly lowe
pain sco es, p olonged du a ion o analgesia, educed escue analgesic equi emen s, and highe pa ien sa is ac ion
sco es. These indings con ibu e aluable e idence o he ongoing discou se ega ding op imal analgesic selec ion o
pos ope a i e pain managemen in su gical popula ions and ha e impo an implica ions o clinical p ac ice in he se ing
o appendec omy.(11)
The supe io analgesic e icacy o en anyl obse ed in his s udy aligns wi h se e al p e ious in es iga ions examining
opioid analgesics in a ious su gical con ex s. Rawal e al. conduc ed a compa a i e s udy o en anyl and amadol o
pos ope a i e analgesia ollowing abdominal su ge y and epo ed signi ican ly lowe pain sco es in he en anyl g oup,
consis en wi h he indings o he p esen in es iga ion.(12) Simila ly, Kuma and colleagues demons a ed ha en anyl
p o ided mo e e ec i e analgesia han amadol ollowing lapa oscopic cholecys ec omy, wi h pa ien s ecei ing
en anyl expe iencing signi ican ly longe du a ion o analgesia and educed equi emen o supplemen al
analgesics.(13) The pha macological basis o en anyl's supe io e icacy likely ela es o i s high a ini y o µ-opioid
ecep o s, apid onse o ac ion, and po en analgesic p ope ies ha enable e ec i e supp ession o nocicep i e
ansmission a bo h spinal and sup aspinal le els.
Howe e , he li e a u e also con ains s udies epo ing con as ing indings ega ding he compa a i e e icacy o hese
agen s. Deshmukh e al. ound no signi ican di e ence in analgesic e icacy be ween en anyl and amadol o
pos ope a i e pain managemen ollowing gynecological su ge ies, sugges ing ha he ela i e e ec i eness o hese
agen s may a y depending on he speci ic su gical p ocedu e, pa ien popula ion, and analgesic dosing egimen
employed.(14) The disc epancy be ween s udies unde sco es he impo ance o con ex -speci ic e alua ion o analgesic
s a egies and highligh s he alue o p ocedu e-speci ic esea ch such as he p esen in es iga ion ocusing speci ically
on appendec omy pa ien s. Va ia ions in su gical auma, in lamma o y esponses, and indi idual pain pe cep ion may
con ibu e o di e en ial analgesic equi emen s ac oss di e en su gical p ocedu es.
The signi ican ly p olonged ime o i s escue analgesia obse ed in he en anyl g oup cons i u es an impo an clinical
inding wi h p ac ical implica ions o pos ope a i e ca e managemen . Ex ended du a ion o e ec i e analgesia educes
nu sing wo kload associa ed wi h equen analgesic adminis a ion, dec eases pa ien dis ess associa ed wi h ecu en
pain episodes, and may con ibu e o imp o ed sleep quali y and o e all eco e y expe ience.(15) The mean ime o
escue analgesia o 4.82 hou s in he en anyl g oup compa ed o 3.34 hou s in he amadol g oup ep esen s a clinically
meaning ul di e ence ha could in luence decisions ega ding iming o nu sing assessmen s and an icipa o y pain
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
418
managemen s a egies. This inding sugges s ha en anyl may o e p ac ical ad an ages in e ms o educed equency
o analgesic adminis a ion and associa ed cos sa ings ela ed o medica ion p epa a ion and nu sing ime.
The ad e se e ec p o ile obse ed in his s udy e ealed impo an di e ences be ween he wo analgesic agen s ha
me i conside a ion in clinical decision-making. The signi ican ly highe incidence o nausea and omi ing in he
amadol g oup compa ed o he en anyl g oup ep esen s a clinically ele an inding, as pos ope a i e nausea and
omi ing cons i u e dis essing complica ions ha nega i ely impac pa ien sa is ac ion and may delay hospi al
discha ge.(16) This obse a ion con as s wi h he adi ional no ion ha amadol exhibi s a mo e a o able
gas oin es inal side e ec p o ile compa ed o pu e opioid agonis s. The mechanism unde lying amadol-associa ed
nausea may ela e o i s se o one gic ac i i y and po en ial e ec s on chemo ecep o igge zone ac i a ion. P ophylac ic
an ieme ic s a egies may equi e g ea e emphasis when amadol is selec ed as he p ima y analgesic agen .
Con e sely, he end owa d highe incidence o p u i us in he en anyl g oup, hough no s a is ically signi ican in his
s udy, ep esen s a well- ecognized ad e se e ec o µ-opioid agonis s ha clinicians should an icipa e and manage
app op ia ely. The mechanism o opioid-induced p u i us emains incomple ely unde s ood bu likely in ol es bo h
cen al and pe iphe al media o elease, including his amine-dependen and his amine-independen pa hways.(17) The
absence o espi a o y dep ession in bo h g oups, despi e he use o po en opioid analgesics, likely e lec s app op ia e
dosing, ca e ul pa ien selec ion excluding hose wi h signi ican como bidi ies, and close pos ope a i e moni o ing. This
sa e y inding p o ides eassu ance ega ding he use o hese agen s in he immedia e pos ope a i e pe iod when
adminis e ed a app op ia e doses wi h adequa e moni o ing.
Pa ien sa is ac ion sco es demons a ed signi ican ly highe a ings in he en anyl g oup, e lec ing no me ely supe io
pain con ol bu he holis ic pa ien expe ience encompassing com o , unc ional abili y, and pe cei ed quali y o ca e.
The impo ance o pa ien sa is ac ion as a quali y me ic in heal hca e deli e y has gained inc easing ecogni ion, wi h
egula o y bodies and acc edi a ion o ganiza ions inco po a ing pa ien - epo ed ou comes in o quali y assessmen
amewo ks.(18) The obse ed di e ence in sa is ac ion sco es be ween g oups likely e lec s he supe io analgesic
e icacy o en anyl, educed incidence o nausea and omi ing, and po en ially o he unmeasu ed ac o s con ibu ing o
o e all pa ien com o . Heal hca e sys ems inc easingly ecognize ha e ec i e pain managemen cons i u es no me ely
a clinical obliga ion bu an essen ial componen o pa ien -cen e ed ca e ha in luences pa ien pe cep ions o heal hca e
quali y.
The a o able ends obse ed in seconda y ou comes including ime o i s ambula ion and hospi al leng h o s ay in he
en anyl g oup, hough no achie ing s a is ical signi icance, sugges po en ial bene i s ex ending beyond immedia e pain
con ol. Ea ly mobiliza ion ollowing su ge y has been associa ed wi h educed complica ions including enous
h omboembolism, pulmona y complica ions, and ileus, while sho e hospi al s ays educe heal hca e cos s and pa ien
exposu e o nosocomial in ec ions.(19) The mechanis ic link be ween supe io analgesia and hese seconda y ou comes
likely in ol es imp o ed pa ien com o enabling ea lie ambula ion, educed opioid consump ion minimizing side
e ec s ha impai mobili y, and o e all enhanced eco e y acili a ing ea lie discha ge eadiness. Fu u e s udies wi h
la ge sample sizes and longe ollow-up pe iods may cla i y whe he hese ends ansla e in o s a is ically signi ican
di e ences wi h clinical and economic implica ions.
Cos -e ec i eness conside a ions, hough no o mally assessed in his s udy, me i discussion in he con ex o analgesic
selec ion. While en anyl ypically ca ies highe medica ion acquisi ion cos s compa ed o amadol, comp ehensi e
economic analysis mus accoun o mul iple ac o s including o al analgesic consump ion, nu sing ime o medica ion
adminis a ion, managemen o ad e se e ec s, hospi al leng h o s ay, and long- e m ou comes including ch onic pain
de elopmen .(20) The educed escue analgesic equi emen s, lowe incidence o nausea and omi ing, and ends owa d
sho e hospi al s ay obse ed wi h en anyl may o se highe medica ion cos s when analyzed om a heal hca e sys ems
pe spec i e. Fo mal cos -e ec i eness analyses inco po a ing hese mul iple dimensions would p o ide aluable
in o ma ion o o mula y decisions and ins i u ional p ac ice guideline de elopmen .
Se e al me hodological s eng hs enhance he alidi y and clinical applicabili y o hese indings. The p ospec i e
andomized con olled design wi h adequa e sample size, s anda dized anes he ic and su gical p o ocols, alida ed
ou come measu es, sys ema ic ad e se e ec moni o ing, and comp ehensi e s a is ical analysis p o ides obus e idence
ega ding compa a i e analgesic e icacy. The single-cen e design enabled consis en implemen a ion o s udy p o ocols
and s anda diza ion o pe iope a i e ca e, educing con ounding a iables ha migh obscu e ea men e ec s. The
inclusion o pa ien -cen e ed ou comes including sa is ac ion sco es alongside adi ional e icacy measu es p o ides a
comp ehensi e assessmen o analgesic pe o mance ha e lec s con empo a y emphasis on pa ien - epo ed ou comes
in clinical esea ch.
Ce ain limi a ions o his in es iga ion wa an acknowledgmen and conside a ion in in e p e ing he esul s. The single-
cen e design, while enabling p o ocol s anda diza ion, may limi gene alizabili y o o he heal hca e se ings wi h
Majo D . Bimal Ahluwalia, e al. Compa a i e E icacy O In a enous Fen anyl Ve sus T amadol Fo Pos ope a i e
Pain Managemen Following Appendec omy: A P ospec i e Randomized S udy. In . J Med. Pha m. Res., 6 (6): 411‐420,
2025
419
di e en pa ien popula ions, su gical echniques, o pe iope a i e ca e p o ocols. The s udy ocused on appendec omy
pa ien s speci ically, and ex apola ion o indings o o he su gical p ocedu es should be unde aken cau iously gi en
po en ial di e ences in su gical auma, in lamma o y esponses, and pain cha ac e is ics ac oss di e en ope a ions. The
ela i ely sho 24-hou ollow-up pe iod, while app op ia e o assessing acu e pos ope a i e analgesia, p ecludes
e alua ion o longe - e m ou comes including ch onic pain de elopmen , quali y o li e impac s, and la e ad e se e ec s.
The single-dose s udy design, hough clinically ele an o immedia e pos ope a i e analgesia, does no add ess
ques ions ega ding epea ed dosing, cumula i e e ec s, o al e na i e dosing egimens ha migh op imize analgesic
ou comes.
Fu u e esea ch di ec ions should add ess hese limi a ions and explo e se e al impo an ques ions ha emain
unanswe ed. Mul icen e ials encompassing di e se heal hca e se ings and pa ien popula ions would enhance
gene alizabili y o indings and enable e alua ion o how ins i u ional ac o s in luence analgesic ou comes. Compa a i e
s udies examining di e en doses o bo h agen s could iden i y op imal dosing s a egies ha maximize analgesic bene i
while minimizing ad e se e ec s. In es iga ion o hese analgesics in o he common su gical p ocedu es would expand
he e idence base o analgesic selec ion ac oss su gical special ies. Longe - e m ollow-up s udies assessing ou comes
including ch onic pain de elopmen , unc ional eco e y, quali y o li e, and heal hca e esou ce u iliza ion would
p o ide comp ehensi e e alua ion o analgesic s a egies om bo h pa ien and heal hca e sys em pe spec i es. Finally,
pha macogene ic s udies examining how gene ic polymo phisms in d ug-me abolizing enzymes and opioid ecep o s
in luence analgesic esponse could ad ance p ecision medicine app oaches o pos ope a i e pain managemen .
CONCLUSION
This p ospec i e andomized con olled ial demons a ed ha in a enous en anyl p o ided supe io pos ope a i e
analgesia compa ed o amadol in pa ien s unde going appendec omy, as e idenced by signi ican ly lowe pain in ensi y
sco es a ea ly pos ope a i e ime poin s, p olonged du a ion o e ec i e analgesia, educed equi emen s o escue
analgesics, and highe pa ien sa is ac ion a ings. The en anyl g oup also demons a ed a mo e a o able ad e se e ec
p o ile wi h signi ican ly lowe incidence o nausea and omi ing, he mos common dis essing pos ope a i e
complica ion encoun e ed in bo h g oups. The hemodynamic s abili y obse ed in bo h g oups con i med he
ca dio ascula sa e y o hese analgesic egimens when adminis e ed a app op ia e doses wi h adequa e moni o ing.
These indings suppo he p e e en ial use o in a enous en anyl o e amadol o pos ope a i e pain managemen
ollowing appendec omy in app op ia ely selec ed pa ien s wi hou con aindica ions o opioid he apy. The supe io pain
con ol, ex ended analgesic du a ion, imp o ed pa ien sa is ac ion, and accep able sa e y p o ile associa ed wi h en anyl
make i an op imal choice o immedia e pos ope a i e analgesia in his common su gical popula ion. Clinical p ac ice
guidelines and ins i u ional p o ocols o pos ope a i e pain managemen ollowing appendec omy should conside
inco po a ing hese e idence-based indings o op imize pa ien ou comes and sa is ac ion while main aining app op ia e
sa e y s anda ds.
Decla a ion:
Con lic s o in e es s: The au ho s decla e no con lic s o in e es .
Au ho con ibu ion: All au ho s ha e con ibu ed in he manusc ip .
Au ho unding: Nill
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