Fa m Hosp. 2016;40(1):44-51
ORIGINALES
E ec o a single dose o lidocaine and ke amine on
in aope a i e opioids equi emen s in pa ien s unde going
elec i e gynecological lapa o omies unde gene al anes hesia.
A andomized, placebo con olled pilo s udy
Jusse Te esa Ga cía-Na ia1, Ja ie To ne o López1, Juan José Egea-Gue e o2, Ángel
Vilches A enas3 and Tibu cio Vázquez Gu ié ez1
1Hospi al Uni e si a io Nues a Seño a de Valme, Uni e sidad de Se illa, Se illa. 2Ins i u o de Biomedicina de Se illa (IBiS),
Hospi al Uni e si a io Vi gen del Rocío, CSIC, Uni e sidad de Se illa, Unidad de Neu oc í icos, Se illa. 3Ins i u o de Biomedicina
de Se illa (IBiS), Hospi al Uni e si a io Vi gen del Rocío, CSIC, Uni e sidad de Se illa, Depa amen o de Medicina P e en i a y
Salud Pública, Se illa. Spain.
* Au o pa a co espondencia.
Co eo elec ónico: jusse .ga cia@ heb on.ne (Jusse Te esa Ga cía-Na ia).
Recibido el 3 de junio de 2015; acep ado el 9 de diciemb e de 2015. DOI: 10.7399/ h.2016.40.1.9339
Abs ac
Backg ound and goal o s udy: he e is e idence ha pe iope-
a i e in a enous ke amine and lidocaine educe pos ope a i-
e pain, pos ope a i e opioids consump ion, sho ens hospi al
s ay and accele a es in es inal unc ion eco e y. Howe e , i
has no been s udied he bene icial e ec s in he in aope a-
i e pe iod. The aim o his s udy was o e alua e he e ec
o a single dose o lidocaine and ke amine on in aope a i e
opioids equi emen s in pa ien s unde going elec i e gyneco-
logical lapa o omies unde gene al anes hesia.
Ma e ials and me hods: we pe o med a single-cen e, p os-
pec i e, andomized, double-blinded, placebo-con olled
s udy. We included 33 pa ien s (11 in he ke amine g oup, 11
in he lidocaine g oup and 11 in he placebo g oup). Pos o-
pe a i e analgesia was accomplished by pa ien -con olled
mo phine. Pa ien s we e andomly assigned o ecei e ei he a
1.5 mg/kg o 2% lidocaine, 0.5 mg/kg o 5% ke amine o
0.9% saline bolus. The p ima y ou come was he opioids con-
sump ion du ing su ge y. The seconda y ou comes included:
eme gence ime, pain sco es, opioids consump ion wi hin 24 h
a e su ge y and side e ec s.
Resul s: dec eased in aope a i e opioids equi emen s we e
no ed in he expe imen al g oups (ke amine: 402.3 ± 106.3
E ec o de una dosis de lidocaína y ke amina sob e el
consumo in aope a o io de opioides en pacien es
some idas a ci ugía ginecológica elec i a bajo anes esia
gene al. Es udio pilo o alea o izado y con olado con
placebo.
Resumen
In oducción y obje i os del es udio: exis e e idencia de que la
adminis ación pe iope a o ia de ke amina y lidocaína in a enosa
educe el dolo y el consumo de opioides pos ope a o io, aco a
la es ancia hospi ala ia y acele a la ecupe ación de la unción in-
es inal. Sin emba go, no se han es udiado los e ec os bene icio-
sos en el pe íodo in aope a o io. El obje i o de es e es udio ue
e alua el e ec o de una única dosis de lidocaína y ke amina sob e
el consumo in aope a o io de opioides en pacien es some idas a
ci ugía ginecológica elec i a bajo anes esia gene al.
Ma e ial y mé odos: es udio p ospec i o, alea o izado, doble
ciego, con olado con placebo en un solo cen o. Se incluye on
33 pacien es (11 en el g upo ke amina, 11 en el g upo lidocaí-
na y 11 en el g upo placebo). Pa a la analgesia pos ope a o ia
se u ilizó una bomba PCA (Analgesia Con olada po el Pacien-
e ) de mo ina. Los pacien es ue on asignados al aza a uno
de los es g upos de es udio: 1,5 mg/kg de lidocaína al 2%,
0,5 mg/kg de ke amina al 5% o solución salina 0.9%. La a ia-
ble p incipal del es udio ue el consumo de opioides du an e la
ci ugía. Las a iables secunda ias ue on: iempo de educción
de la anes esia, in ensidad del dolo , consumo de opioides en
las 24 ho as pos e io es a la ci ugía y e ec os ad e sos.
Resul ados: se obse ó una disminución del consumo in aope-
a o io de opioides en los g upos ke amina (402,3 ± 106,3) y
006_9339 E ec o a single dose o lidocaine.indd 44 30/1/16 5:51
E ec o a single dose o lidocaine and ke amine on in aope a i e opioids… Fa m Hosp. 2016;40(1):44-51 - 45
and lidocaine: 397.7 ± 107.5, compa ed wi h saline:
561.4 ± 97.1); p = 0.001. We ound a posi i e co ela ion be-
ween in aope a i e opioids consump ion and eme gence
ime ( = 0.864, p < 0.001). The e was no signi ican di e en-
ce be ween he g oups in VAS pain sco es a es wi hin he
i s 24 pos ope a i e hou s. To al mo phine consump ion wi-
hin 24 h a e su ge y did no di e signi ican ly among he
g oups (placebo: 27.54 ± 11.75; ke amine: 30.95 ± 7.88; lido-
caine 34.77 ± 10.25; p = 0.26). Pos ope a i e nausea and omi-
ing we e mo e common in placebo g oup (i was obse ed in
3 subjec s in ke amine g oup, in 5 subjec s in lidocaine g oup
and in 9 subjec s in placebo g oup; p = 0.027).
Conclusion: ou esul s do no suppo he use o in aope a i-
e single dose o lidocaine o ke amine o educe pos ope a i e
pain and pos ope a i e opioids consump ion a e open gyne-
cological su ge y. Howe e , hey seem o dec ease in aope a-
i e opioids equi emen s and sho en eme gence ime. Ne e -
heless, hese indings should be alida ing in u he s udies
wi h la ge sample size.
KEY WORDS
Ke amine; Lidocaine; Analgesic agen s; Pe iope a i e pe iod;
Lapa o omy
Fa m Hosp. 2016;40(1):44-51
lidocaína (397,7 ± 107,5) en e al g upo placebo (561,4 ±
97,1); p = 0,001. Se encon ó una co elación posi i a en e
el consumo in aope a o io de opioides y el iempo de despe -
a ( = 0,864, p <0,001). No hubo di e encias signi ica i as
espec o a la in ensidad del dolo en eposo en las 24 ho as
pos e io es a la ci ugía. El consumo o al de mo ina en las
p ime as 24 ho as as la ci ugía no di i ió signi ica i amen e
en e los g upos (placebo: 27,54 ± 11,75; ke amina: 30,95 ±
7,88; lidocaína 34,77 ± 10,25; p = 0,26). Las náuseas y ómi-
os pos ope a o ios ue on más ecuen es en el g upo placebo
(se obse ó en 3 pacien es del g upo ke amina, en 5 del g upo
lidocaína y en 9 del g upo placebo; p = 0,027).
Conclusión: Nues os esul ados no apoyan el uso de una única
dosis in aope a o ia de lidocaína o ke amina pa a disminui el
dolo pos ope a o io y el consumo de opioides as ci ugía gi-
necológica abie a. Sin emba go, si pa ece disminui los eque-
imien os in aope a o ios de opioides y aco a el iempo de
educción de la anes esia. No obs an e, es os esul ados deben
se alidados en u u os es udios con mayo amaño mues al.
PALABRAS CLAVE
Ke amina; Lidocaína; Fá macos analgésicos; Pe íodo
pe iope a o io; Lapa o omía
Fa m Hosp. 2016;40(1):44-51
In oduc ion
Opioids a e widely used in he pe iope a i e pe iod
because o hei p o ound analgesic e ec . Howe e ,
his d ug can be associa ed wi h undesi able side e ec s,
which may include espi a o y dep ession, hypo ension,
seda ion, nausea and omi ing, u ina y e en ion and
pos ope a i e ileus1-3. Side e ec s ela ed wi h analge-
sia in su gical pa ien s can be p oblema ic and can lead
o inc eased ins i u ional cos s, longe hospi al leng h o
s ay, and an o e all inc ease in pa ien dissa is ac ion4-6.
Gi en he mul iplici y o mechanisms in ol ed in pain
pa hophysiology, an app op ia e app oach would be a
mul imodal analgesia egimen ha uses a combina ion
o opioids and mul iple agen s aiming a augmen ing
hei ecip ocal e ec s7-9.
One medica ion ha has shown p omise in p o iding
analgesia e ec is lidocaine. This is an amide local anes-
he ic agen ha wo ks by blocking sodium channels in
he neu al cascade. Recen in es iga ions sugges ha
in a enous lidocaine may be bene icial in biochemical
pain p ocesses4,6,10-12.
Al hough he exac mechanism and analgesic-spa ing
e ec o pa en e ally adminis e ed lidocaine is unclea ,
some au ho s specula e ha i ac s mo e as an an ihype-
algesic han as a di ec analgesic. Is known cen al sen-
si iza ion o be induced by he mechanosensi i e noci-
cep o class o ecep o s. These nocicep o s a e known
o be sensi i e o small-dose lidocaine10.
Mo eo e , impo an mechanisms in he genesis o
pain include N-me hyl-D-aspa a e ecep o (NMDAR)
ac i a ion and up- egula ion and in lamma o y espon-
ses in he spinal co d13-15. In his ega d, ke amine, a
non-compe i i e an agonis o he N-me hyl-D-aspa a-
e (NMDA) ecep o , has ecei ed inc eased in e es in
ecen yea s as an analgesic o acu e pain managemen .
A ela i ely high dose, ke amine p oduces anes hesia,
whe eas a sub-anes he ic dose, i is a po en analgesic.
Low doses o ke amine ha e been p oposed o p e en
opioid ole ance and opioid-induced-hype algesia16,17.
The e ec o ke amine on pe iope a i e in lamma o y
esponses has been s udied in pa ien s unde going o al
hip a h oplas y, hys e ec omy, ho aco omy, ca diac and
spine su ge y18-22.
Thus, hese agen s could ha e an impo an analgesic
e ec no only in he pos ope a i e pe iod, bu also in
he in aope a i e pe iod. The e o e, he main objec i e
o his s udy was o e alua e he e ec o a single dose
o lidocaine and ke amine on in aope a i e opioids e-
qui emen s in pa ien s unde going elec i e gynecologi-
cal lapa o omies unde gene al anes hesia.
Ma e ials and Me hods
This was a single-cen e, p ospec i e, andomized,
double-blinded, placebo-con olled design. The pa ien s
we e ec ui ed o pa icipa ion in he s udy a e app o-
al o he p o ocol by he local medical e hics commi ee
o Nues a Seño a de Valme Uni e si y Hospi al, Se ille,
Spain. In o med w i en consen was ob ained om all
pa icipan s acco ding o he Decla a ion o Helsinki.
Thi y- h ee emale, aged 18-55 yea s, unde going
elec i e open gynecological su ge y unde gene al anes-
hesia we e en olled in he s udy.
006_9339 E ec o a single dose o lidocaine.indd 45 19/2/16 6:38
46 - Fa m Hosp. 2016;40(1):44-51 Jusse Te esa Ga cía-Na ia e al.
Exclusion c i e ia we e: age <18 yea s o >55 yea s,
p eexis ing ch onic pain equi ing ea men , con ain-
dica ion o ke amine o lidocaine, oncologic su ge y,
his o y o signi ican neu ological o psychia ic disease
(e.g., inc eased c anial p essu e, seizu e diso de equi-
ing medica ion wi hin he p e ious 2 yea s, psychosis),
subs an ial hepa ic (alanine amino ans e ase o aspa -
a e amino ans e ase >2 imes no mal) o enal impai -
men (se um c ea inine >2 mg/dL) and p e ious subs an-
ce abuse.
The p ima y ou come was he opioids consump ion
du ing su ge y. The seconda y ou comes we e he eme -
gence ime, pain sco es, opioids consump ion wi hin 24
h a e su ge y and side e ec s.
Pa ien s we e andomly assigned, using compu e -ge-
ne a ed andom numbe s and concealed opaque en e-
lopes o ecei e ei he , a 1.5 mg/kg o 2% lidocaine, 0,5
mg/kg o 5% ke amine o 0.9% saline bolus.
The day o su ge y, coded 10-mL sy inges o lidocai-
ne, ke amine, o saline we e p epa ed by he nu se in
he Pos -Anes hesia Ca e Uni (PACU). Each sy inge was
indis inguishable om he o he , and only he nu se who
p epa ed he sy inges was awa e o hei ac ual compo-
si ion. The anes hesiologis in cha ge, he su geon, he
nu sing s a and he pa ien s we e blind o he g oup
assignmen un il he conclusion o he s udy.
E e y pa ien was admi ed one day be o e su ge y
acco ding o ins i u ional s anda ds. In he ope a ing
oom, in a enous access was secu ed, and ou ine mo-
ni o ing was es ablished using an elec oca diog am,
non-in asi e blood p essu e, hea a e, oxygen sa u a-
ion and end- idal ca bon dioxide (E CO2) (Da ex-Ohme-
da S/5 Compac C i ical Ca e Moni o ; GE Heal hca e).
All pa ien s we e p eoxygena ed wi h 100% oxygen ia
acemask o 3 o 5 minu es be o e induc ion o anes-
hesia. Anes hesia was induced wi h an in a enous
adminis a ion o 1-2 mg o midazolam, 2 μg/kg o
0.005% en anyl and 2 mg/kg o 1% p opo ol. O o a-
cheal in uba ion was acili a ed wi h 0,6 mg/kg o 1%
ocu onium and espi a o y equency and idal olume
we e adjus ed o main ain he E CO2 be ween 32 o 35
mmHg. Dexame hasone 4 mg i. could be adminis e ed
du ing induc ion o anes hesia in all pa ien s wi h mode-
a e o high isk o pos ope a i e nausea and omi ing
(PONV), acco ding Ap el’s model23,24.
Main enance o anes hesia was accomplished using
p opo ol acco ding o he Bispec al Index (BIS) and ad-
di ional en anyl was adminis e ed as needed du ing
anes hesia wi h a 20% inc ease in blood p essu e o i
he hea a e was g ea e han 100 bea s/min. The o-
al amoun o en anyl used we e eco ded a he end
o he p ocedu e. Rocu onium boluses we e gi en o
in aope a i e muscle elaxa ion o main ain a mode a e
neu omuscula block o ain-o - ou s imula ion (TOF).
The anes he is adminis e ed lidocaine, ke amine, o
saline bolus 5 minu es be o e he su gical incision.
Ap oxima ely 15 o 30 minu es be o e skin closu e 4
mg o 0,2% ondanse on, 2g o 40% me amizol and
50 mg o 2,5% dexke op o en we e adminis e ed in all
g oups. Neu omuscula blockade was an agonized using
IV neos igmine, 0.05 mg/kg, and a opine 0.015 mg/kg
a e he eappea ance o T4 in he TOF.
Eme gence ime om anes hesia was collec ed (me-
asu ed in minu es om discon inua ion o p opo ol in-
usions o he momen a which he pa ien awoke and
endo acheal ube was emo ed).
A e emo al o he endo acheal ube, subjec s we e
anspo ed o he PACU. To al su gical ime (measu ed
in minu es om su gical incision o skin closu e) was e-
co ded.
On admission o he PACU, a pos ope a i e pain was
assessed as soon as he subjec was ale and able o
answe ques ions. A le el o abdominal pain was as-
sessed using a 0 o 10 Ve bal Analogue Scale (VAS), in
which a a ing o “0” indica ed “absence o pain” and
a sco e o “10” indica ed he “wo s pain imaginable”.
VAS also was eco ded a 2, 4, 8 and 24 h pos ope a i-
ely.
A he same ime poin s, seda ion (was sco ed as 1 =
ale , 2 = asleep, ale a e a ousal, 3 = asleep, d owsy
a e a ousal, 4 = asleep, di icul o ouse, and 5 = una-
ousable), hallucina ions, p u i us, incidence o any nau-
sea o omi ing, ileus, espi a o y dep ession and any
signs and symp oms o unexpec ed o majo side e ec s
we e assessed. Resea ch pe sonnel, blind o he alloca-
ion, eco ded hese a iables.
The amoun o in aope a i e opioid use was eco -
ded. Pa ien s we e connec ed o mo phine-PCA and
mo phine was gi en in a enously du ing he i s 24 h
in boluses o 1,5 mg using Pa ien Con olled Analgesia
(PCA), wi h a minimum in e al o 10 min be ween wo
doses. No o he analgesics we e used. The analgesic e-
qui emen s o he i s 24 hou s we e eco ded.
S a is ical Analysis
The dis ibu ion o da a was de e mined using he
Kolmogo o -Smi no analysis.
Da a we e exp essed as mean (s anda d de ia ions),
and nonpa ame ic da a as median (in e qua ile an-
ge). Ca ego ical da a we e compa ed among g oups
using chi-squa e es and Fishe exac es . Pa ame ic
da a we e compa ed using an unpai ed s uden ’s - es ,
and nonpa ame ic da a using a Mann-Whi ney es . To
compa e nume ical a iables be ween mo e han wo
g oups ANOVA was conduc ed. Da a ha we e no no -
mally dis ibu ed we e compa ed among g oups using a
K uskal-Wallis es . The ela ionship be ween nume ical
a iables was calcula ed using he Pea son co ela ion
coe icien . A P alue o <0.05 was conside ed s a is i-
cally signi ican . All s a is ical analyses we e conduc ed
using so wa e om he S a is ical Package o he Social
Sciences (SPSS, Ve sion 18.0, Chicago, IL, USA).
006_9339 E ec o a single dose o lidocaine.indd 46 30/1/16 5:51
E ec o a single dose o lidocaine and ke amine on in aope a i e opioids… Fa m Hosp. 2016;40(1):44-51 - 47
Resul s
Thi y- h ee pa ien s we e analyzed (11 in he ke ami-
ne g oup, 11 in he lidocaine g oup and 11 in he place-
bo g oup). All subjec s comple ed he p o ocol wi hou
unexpec ed o majo side e ec s. Pa ien low h ou-
ghou he s udy, acco ding o he CONSORT s a emen ,
is shown in igu e 1.
The e we e no di e ences in age, weigh , heigh ,
body mass index o du a ion o su ge y be ween ea -
men g oups (Table 1).
Dec eased in aope a i e en anyl equi emen s we e
no ed in he expe imen al g oups compa ed wi h he
con ol g oup (Figu e 2). Howe e , he ke amine g oup
and lidocaine g oup did no di e signi ican ly among
hem (p = 1.00).
The eme gency ime was signi ican ly longe in he
placebo g oup (11.64 ± 2.11) compa ed o ke amine
g oup (8.91 ± 2.21, p = 0.004) and o he g oup ha e-
cei ed lidocaine (7.91 ± 1.37, p < 0.001). Howe e , he e
we e no signi ican di e ences in eme gency ime be-
ween ke amine and lidocaine g oups (p = 0.270) (Fi-
gu e 3). As shown in igu e 4, we ound a posi i e co-
ela ion be ween in aope a i e en anyl consump ion
and eme gence ime ( = 0.864, p < 0.001). The highes
in aope a i e en anyl equi emen s obse ed in he
placebo g oup compa ed o o he g oups, was p obably
a condi ion ha may ha e con ibu ed o an inc ease in
eme gency ime in his g oup.
Mo phine PCA was used o 24 h by 11 pa ien s in
each g oup. Table 2 shows he mo phine consump ion
o g oups du ing he i s 24 pos ope a i e hou s. The
mean ± SD o al mo phine consump ion did no di e sig-
ni ican ly among g oups (placebo g oups 27.54 ± 11.75,
ke amine g oup 30.95 ± 7.88 and lidocaine g oup
34.77 ± 10.25; p = 0.260). The e was no di e ence be-
ween he g oups in VAS pain sco es a es om 0 o 24
hou s pos ope a i ely. A end owa d lowe VAS sco es
was no ed a 24 hou s a e su ge y in all g oups (Table 2).
No pa ien s complained o hallucina ions, dyspho ia
o diso ien a ion. Seda ion sco es we e simila among
g oups, and no pa ien had a sco e mo e han 2. S a-
is ically signi ican di e ence in he incidence o PONV
was ound be ween g oups. PONV was obse ed in 3
En olmen
Assessed o eligibili y (n=39)
Randomised (n=33)
Alloca ion
Excluded (n=6)
No mee ing inclusion c i e ia (n=0)
Declined o pa icipa e (n=6)
O he easons (n=0)
Los o ollow-up (n=0)
Discon inued in e en ion (n=0)
Analysed (n=11)
Excluded om analysis (n=0) Analysed (n=11)
Excluded om analysis (n=0)
Los o ollow-up (n=0)
Discon inued in e en ion (n=0)
Follow-up
Los o ollow-up (n=0)
Discon inued in e en ion (n=0)
Analysis
Analysed (n=11)
Excluded om analysis (n=0)
Lidocaine g oup (n=11)
Alloca ed o in e en ion (n=11)
Recei ed alloca ed in e en ion (n=11)
Did no ecei e alloca ed in e en ion (n=0)
Ke amine g oup (n=11)
Alloca ed o in e en ion (n=11)
Recei ed alloca ed in e en ion (n=11)
Did no ecei e alloca ed in e en ion (n=0)
Placebo g oup (n=11)
Alloca ed o in e en ion (n=11)
Recei ed alloca ed in e en ion (n=11)
Did no ecei e alloca ed in e en ion (n=0)
Figu e 1. Consolida ed S anda ds o Repo ing T ials (CONSORT) low cha .
006_9339 E ec o a single dose o lidocaine.indd 47 30/1/16 5:51
48 - Fa m Hosp. 2016;40(1):44-51 Jusse Te esa Ga cía-Na ia e al.
subjec s in ke amine g oup, in 5 subjec s in lidocaine
g oup and in 9 subjec s in placebo g oup (p = 0.027).
Rega ding i ching, he e was no signi ican di e ence
among g oups (p > 0.05). No o he ad e se e en s we e
obse ed in he pos ope a i e pe iod. The e we e no su -
gical complica ions.
Discussion
This s udy shows 2 main indings. Fi s , a small in-
a enous single dose o lidocaine and ke amine gi en
be o e skin incision educes in aope a i e opioids e-
qui emen s in pa ien s unde going gynecological lapa-
o omies unde gene al anes hesia. Second, he subjec s
in he lidocaine and ke amine g oups had subs an ially
Table 1. Pa ien s’ cha ac e is ics and ope a i e de ails
ASA physical s a us
I
II
III
n (%)
10 (30.3)
21 (63.6)
2 (6.1)
Placebo
(n=11)
Lidocaine
(n=11)
Ke amine
(n=11) P alue
Age (y ) 45.2 ± 4.2 46.4 ± 6.2 43.1 ± 7.2 0.43
Weigh (kg) 73.1 ± 12.1 68.3 ± 6.8 65.3 ± 14.9 0.30
Heigh (cm) 160 ± 0.1 161 ± 0.1 160 ± 0.1 0.88
BMI (kg/m2)28.4 ± 4.4 25.6 ± 2.4 25.3 ± 5.0 0.17
Placebo
(n=11)
Lidocaine
(n=11)
Ke amine
(n=11) P alue
Du a ion o su ge y (min) 91.4 ± 20.1 82.8 ± 14.0 88.2 ± 17.4 0.51
Da a a e p esen ed as numbe s (%) and mean (±SD). ASA, Ame ican Socie y o Anaes hesiologis s. BMI, Body Mass Index.
1.100
1.000
900
800
700
600
500
400
300
200
IOP Fen anyl consump ion (µg)
Placebo Ke amine Lidocaine
P=0.001
P=1.00
Figu e 2. In aope a i e opioids consump ion.
IOP: In aope a i e. In ke amine g oup: 402.3 ± 106.3. In lido-
caine g oup: 397.7 ± 107.5. In placebo g oup: 561.4 ± 97.1
Figu e 3. The anes he ic eme gence ime in s udy g oups.
The eme gency ime was signi ican ly longe in he placebo
g oup (11.64 ± 2.11) compa ed o ke amine g oup (8.91 ± 2.21,
p = 0.004) and o he g oup ha ecei ed lidocaine (7.91 ± 1.37,
p < 0.001).
16
14
12
10
8
6
Anes he ic eme gence ime (min)
Placebo Ke amine Lidocaine
Figu e 4. Eme gence ime acco ding o in aope a i e en anyl
consump ion.
A posi i e ela ion could be app ecia e be ween a iables.
16
14
12
10
8
6
4
2
0
Anes he ic eme gence ime (min)
Fen anyl consump ion (µg)
0 100 200 300 400 500 600 700 800
006_9339 E ec o a single dose o lidocaine.indd 48 30/1/16 5:51

E ec o a single dose o lidocaine and ke amine on in aope a i e opioids… Fa m Hosp. 2016;40(1):44-51 - 49
sho e eme gence ime han he placebo g oup. These
indings a e pa icula ly impo an in he ambula o y su -
ge y popula ion because hese pa ien s do no ha e he
s uc u ed suppo o a hospi al s a and a e, he e o e,
expec ed o ha e a as e eco e y.
In ou s udy, no in a enous in usion o lidocaine
and ke amine was use, an aspec ha di e en ia es his
s udy om mos p e ious esea ches. The lack o signi i-
can di e ences be ween he g oups in VAS pain sco es
and opioids consump ion om 0 o 24 hou s pos ope a-
i ely may be in luenced by his ac .
Lidocaine egimens a y amongs he s udies inclu-
ded in ou s udy. Mos o he s udies ha e epo ed
lowe pain sco es and dec eased pos ope a i e opioids
equi emen used in a enous in usion o lidocaine a -
e bolus dosing25-30. The hal -li e o lidocaine has been
epo ed o be abou 100 minu es ollowing bolus in-
jec ion o in usions las ing less han 12 hou s, showing
mo e linea pha macokine ics31. The e o e, a e a single
dose o lidocaine he dip in concen a ions o below he
he apeu ic ange occu s 1-3 hou s a e i s adminis a-
ion32.
When sys emic lidocaine is adminis e ed in he ope-
a i e pe iod, i likely p e en s he induc ion o cen al
hype algesia10. G igo as A e al.33, who obse ed a de-
c ease he incidence o pe sis en pain a e b eas su -
ge y, highligh his ac .
Sys ema ic e iew o mul iple s udies documen ed a
educ ion in pe iope a i e pain when IV lidocaine in u-
sions supplemen gene al anes he ics4. Howe e , he e
a e also excep ions, Wue h ich PY e al.34 ound ha sys-
emic pe iope a i e lidocaine adminis a ion o e 24 h
did no in luence opioid consump ion a e lapa oscopic
enal su ge y.
The acu e analgesic e ec s o ke amine a e gene ally
belie ed o be media ed h ough he blockade o phen-
cyclidine binding si e o N-me hyl-d- aspa a e (NMDA)
ecep o s o he nocicep i e neu ons. In addi ion, a-
ious s udies, including clinical and p eclinical esea ch,
ha e shown ha ke amine has an an i-in lamma o y
e ec 35,36. Howe e , is cu en ly unclea i he an i-in-
lamma o y e ec i is media ed by NMDA o non-NM-
DA mechanisms.
One e iew concluded ha a single bolus dose o ke-
amine dec eased IV and epidu al opioids equi emen s
in se en o 11 s udies37. A mo e ecen Coch ane e iew
analyzed 37 s udies (2240 pa ien s) and ound ha su-
banes he ic ke amine doses we e e ec i e in educing
24 h mo phine equi emen s and he incidence o PONV;
he ad e se e ec s we e mild o absen 38. Ou esul s
showed a lowe incidence o PONV in he ke amine
g oup, bu he e was no di e ence in opioid consump-
ion a 24 hou s pos ope a i ely.
Ke amine combined wi h opioids po en ia es analge-
sia, hus educing he need o la ge opioids doses39,40. I
has been es ima ed ha pain is educed by 20-45%39,41,42.
Neshe N e al.42 ha e demons a ed ha e en smalle IV
doses (≤ 250 mcg/kg) e ec i ely con olled opioid- esis-
an pain, al hough i was associa ed wi h a b ie pe iod
o seda ion (< 2 min) immedia ely a e he IV injec ion,
bu wi h no psychomime ic e en s.
The da a o ke amine use a ailable in he li e a u e
has led o conclude ha i can educe pos ope a i e pain
in ensi y, based on Le el A e idence. The incidence o i s
bene i in educing pos ope a i e nausea and omi ing
(PONV) has been con i med by Le el B e idence, and he
e ec on lowe ing he equi ed dose o mo phine by 30-
50% by Le el A e idence43. Rega ding ad e se e en s,
ke amine inc eased he incidence o neu opsychia ic
e ec s (eg, hallucina ions) and dec eased he incidence
o pos ope a i e nausea and omi ing, bu did no al e
he incidence o seda ion o o he side e ec s16.
The limi a ions o his s udy include eliance on he
accu acy o pa ien sel - epo ed da a and eliance on a
con enience sample ec ui ed om 1 cen e, which may
limi he gene alisabili y o he esul s. Ou s udy was
es ic ed o women by na u e o he su ge y. Rega ding
ad e se e en s, we conside a la ge sample o pa ien s
would be needed o d aw conclusions. Finally, al hough
he moni o ing o neu omuscula blockade was pe o -
med in all pa ien s, he ain-o - ou was no collec ed, a
poin o be conside ed in u u e s udies.
Table 2. Mo phine consump ion a 24 hou s and pos ope a i e VAS sco es
Placebo
(n=11)
Ke amine
(n=11)
Lidocaine
(n=11) P alue
24 h Mo phine consump ion 27.54 ± 11.75 30.95 ± 7.88 34.77 ± 10.25 0.260
VAS sco es
On admission o he PACU 6 (5-6) 5 (5-6) 5 (5-7) 0.332
2 hou s 5 (3-6) 5 (4-5) 5 (4-5) 0.664
4 hou s 4 (3-4) 4 (3-4) 5 (4-5) 0.125
8 hou s 3 (3-4) 4 (4-4) 3 (3-4) 0.776
24 hou s 2 (1-3) 2 (1-3) 2 (1-3) 0.846
Da a a e epo ed as mean (±SD) and median (IR). VAS, Visual Analogue Scale. PACU, Pos -Anes hesia Ca e Uni .
006_9339 E ec o a single dose o lidocaine.indd 49 30/1/16 5:51
50 - Fa m Hosp. 2016;40(1):44-51 Jusse Te esa Ga cía-Na ia e al.
In summa y, ou esul s do no suppo he use o in-
aope a i e single dose o lidocaine o ke amine o e-
duce pos ope a i e pain and pos ope a i e opioids con-
sump ion a e open gynecological su ge y. Howe e ,
hey seem o dec ease in aope a i e opioids equi e-
men s and sho en eme gence ime, pa icula ly impo -
an in he ambula o y su ge y popula ion. Ne e heless,
hese indings should be alida ing in u he s udies
wi h la ge sample size.
Con lic o in e es
None decla ed.
Funding
This s udy was suppo ed by ins i u ional and depa -
men al esou ces.
Bibliog aphy
1. Whi e PF. The changing ole o non-opioid analgesic echniques in
he managemen o pos ope a i e pain. Anes h Analg 2005;101(5
Suppl):S5-22.
2. B own AK, Ch is o PJ, Wu CL. S a egies o pos ope a i e pain
managemen . Bes P ac Res Clin Anaes hesiol 2004;18:703-17.
3. Joshi GP. Mul imodal analgesia echniques and pos ope a i e eha-
bili a ion. Anes hesiol Clin No h Ame ica 2005;23:185-202.
4. McCa hy GC, Megalla SA, Habib AS. Impac o in a enous lido-
caine in usion on pos ope a i e analgesia and eco e y om su -
ge y: a sys ema ic e iew o andomized con olled ials. D ugs
2010;70:1149-63.
5. He oede S, Peche S, Schönhe ME, Kauli z G, Hahnenkamp K,
F iess H, Bö ige BW, Baue H, Dijkg aa MG, Du ieux ME, Ho-
llmann MW. Sys emic lidocaine sho ens leng h o hospi al s ay
a e colo ec al su ge y: a double-blinded, andomized, place-
bo-con olled ial. Ann Su g 2007; 246:192-200
6. G oudine SB, Fishe HAG, Kau man RP J , e al. In a enous lidocai-
ne speeds he e u n o bowel unc ion, dec eases pos ope a i e
pain, and sho ens hospi al s ay in pa ien s unde going adical e-
opubic p os a ec omy. Anes h Analg. 1998;86:235-9.
7. Ca s ensen M, Molle AM. Adding ke amine o mo phine o
in a enous pa ien con olled analgesia o acu e pos ope a i-
e pain: a quali a i e e iew o andomized ials. B J Anaes h
2010;104:401-6.
8. Bonne F, Ma e E. Pos ope a i e pain managemen and ou come
a e su ge y. Bes P ac Res Clin Anaes hesiol 2007;21:99-107.
9. Chelly JE, Ploskanych T, Dai F, Nelson JB. Mul imodal analgesic
app oach inco po a ing pa a e eb al blocks o open adical e-
opubic p os a ec omy: a andomized double-blind placebo-con-
olled s udy. Can J Anaes h 2011;58:371-8.
10. Koppe W, Weigand M, Neumann F, Si l R, Schue le J, Schmelz
M, He ing W. Pe iope a i e in a enous lidocaine has p e en i e
e ec s on pos ope a i e pain and mo phine consump ion a e
majo abdominal su ge y. Anes h Analg 2004;98:1050-1055.
11. Fa ag E, Ghob ial M, Sessie DI, Dal on JE, Liu J, Lee JH, Zaky
S, Benzel E, Bingaman W, Ku z A. E ec o pe iope a i e in a-
enous lidocaine adminis a ion on pain, opioid consump ion,
and quali y o li e a e complex spine su ge y. Anes hesiology
2013;119:932-40.
12. G igo as A, Lee P, Sa a F, Sho en G. Pe iope a i e in a enous
lidocaine dec eases he incidence o pe sis en pain a e b eas
su ge y. Clin J Pain 2012;28:567-72.
13. Pe enko AB, Yamaku a T, Baba H, Shimoji K. The ole o N-me-
hyl-D-aspa a e (NMDA) ecep o s in pain: a e iew. Anes h Analg
2003;97:1108-16.
14. Robe s J, Ossipo MH, Po eca F. Glial ac i a ion in he os o-
en omedial medulla p omo es descending acili a ion o media e
in lamma o y hype sensi i i y. Eu J Neu osci 2009;30:229-41.
15. Wiesele -F ank J, Maie SF, Wa kins LR. Cen al p oin lamma o y
cy okines pain enhancemen . Neu osignals 2005;14:166-74.
16. La che A, Laulin JP, Cele ie E, Le Moal M, Simonne G. Acu e ole-
ance associa ed wi h a single opia e adminis a ion: in ol emen
o N-me hyl-d-aspa a e-dependan pain acili a o y sys ems. Neu-
oscience 1998;84:583-9.
17. Kissin I, B igh CA, B adley EL J . The e ec o ke amine on
opioid-induced acu e ole ance: can i explain educ ion o opioid
consump ion wi h ke amine-opioid analgesic combina ions?
Anes h Analg 2000;91:1483-8.
18. Ma ínez V, Cyme man A, Ben Amma , Flaud JF, Rapon C, Poin-
dessous F, Jude T, Chau in M, Bouhassi a D, Sessie D, Mazoi X,
Fle che D. The analgesic e iciency o combined p egabalin and
ke amine o o al hip a h oplas y: a andomised, double-blind,
con olled s udy. Anaes hesia 2014;69:46-52.
19. G ady MV, Mascha E, Sessie DI, Ku z A. The e ec o pe iope a i e
in a enous lidocaine and ke amine on eco e y a e abdominal
hys e ec omy. Anes h Analg. 2012 No ;115(5):1078-84.
20. Mendola C, Camma o a G, Ne o R, Cecci G, Pis e na A, Fe-
an e D, Casadio C, Della Co e F. S+ -ke amine o con ol o
pe iope a i e pain and p e en ion o pos ho aco omy pain sy-
nd ome: a andomized, double-blind s udy. Mine a Anes esiol.
2012;78:757-66.
21. Wel e s ID, Feu e MK, P eiss V, Mülle M, Scholz S, Kwapisz M,
Mogk M, Neuhäuse C. Con inuous S-(+)-ke amine adminis a ion
du ing elec i e co ona y a e y bypass g a su ge y a enua es
p o-in lamma o y cy okine esponse du ing and a e ca diopul-
mona y bypass. B J Anaes h. 2011;106:172-9.
22. Lo us RW, Yeage MP, Cla k JA, B own JR, Abdu WA, Sengup a
DK, Beach ML. In aope a i e ke amine educes pe iope a i e opia-
e consump ion in opia e-dependen pa ien s wi h ch onic back
pain unde going back su ge y. Anes hesiology. 2010;113:639-46.
23. Ap el CC, Roewe N, Ko ila K. How o s udy pos ope a i e nausea
and omi ing. Ac a Anaes hesiol Scand 2002;46:921-28.
24. Ap el CC, Lää ä E, Koi u an a M, G eim CA, Roewe N. A simpli-
ied isk sco e o p edic ing pos ope a i e nausea and omi ing:
conclusions om c oss- alida ions be ween wo cen e s. Anes he-
siology 1999;91:693-700.
25. Kuo CP, JaoSW, Chen KM, Wong CS, Yeh CC, Sheen MJ, Wu CT.
Compa ison o he e ec s o ho acic epidu al analgesia and i. .
in usion wi h lidocaine on cy okine esponse, pos ope a i e pain
and bowel unc ion in pa ien s unde going colonic su ge y. B J
Anaes h 2006;97:640-6.
26. Ya deni IZ, Beilin B, Maybu d E, Le inson Y, Bessie H. The e ec
o pe iope a i e in a enous lidocaine on pos ope a i e pain and
immune unc ion. Anes h Analg 2009;109:1464-9.
27. Kaba A, Lau en SR, De oz BJ, Sessie DI, Du ieux ME, Lamy ML,
Jo is JL. In a enous lidocaine in usion acili a es acu e ehabili a-
ion a e lapa oscopic colec omy. Anes hesiology 2007;106:11-8.
28. Lauwick S, Kim do J, Michelagnoli G, Mis ale i G, Feldman L,
F ied G, Ca li F. In aope a i e in usion o lidocaine educes pos o-
pe a i e en anyl equi emen s in pa ien s unde going lapa osco-
pic cholecys ec omy. Can J Anaes h 2008;55:754-60.
29. McKay A, Go schalk A, Ploppa A, Du ieux ME, G o es DS. Sys-
emic lidocaine dec eased he pe iope a i e opioid analgesic e-
qui emen s bu ailed o educe discha ge ime a e ambula o y
su ge y. Anes h Analg 2009;109:1805-8.
30. De Oli ei a GS J , Fi zge ald P, S eiche LF, Ma cus RJ, McCa hy
RJ. Sys emic Lidocaine o Imp o e Pos ope a i e Quali y o Re-
co e y A e Ambula o y Lapa oscopic Su ge y. Anes h Analg
2012;115:262-7.
006_9339 E ec o a single dose o lidocaine.indd 50 30/1/16 5:51
E ec o a single dose o lidocaine and ke amine on in aope a i e opioids… Fa m Hosp. 2016;40(1):44-51 - 51
31. Rowland M, Thomson PD, Guicha d A, Melmon KL. Disposi-
ion kine ics o lidocaine in no mal subjec s. Ann N Y Acad Sci
1971;179:383-98.
32. Aps C, Bell JA, Jenkins BS, Poole-Wilson PA, Reynolds F. Logical
app oach o lidocaine he apy. B Med J 1976;1:13-5.
33. G igo as A, Lee P,Sa a F, Sho en G. Pe iope a i e in a enous
lidocaine dec eases he incidence o pe sis en pain a e b eas
su ge y. Clin J Pain 2012;28:567-72.
34. Wue h ich PY, Rome o J, Bu kha d FC, Cu a olo M. No bene i
om pe iope a i e in a enous lidocaine in lapa oscopic enal su -
ge y: a andomised, placebo-con olled s udy. Eu J Anaes hesiol
2012;29:537-43.
35. Loix S, De Kock M, Henin P. The an i-in lamma o y e ec s o ke-
amine: s a e o he a . Ac a Anaes hesiol Belg 2011;62:47-58.
36. Dale O, Somogyi AA, Li Y, Sulli an T, Sha i Y. Does In aope a-
i e Ke amine A enua e In lamma o y Reac i i y Following Su -
ge y? A Sys ema ic Re iew and Me a-Analysis. Anes h Analg
2012;115:934-43.
37. Sub amaniam K, Sub amaniam B, S einb ook RA. Ke amine as ad-
ju an analgesic o opioids: a quan i a i e and quali a i e sys ema-
ic e iew. Anes h Analg 2004;99:482-95. Re iew.
38. Bell RF, Dahl JB, Moo e RA, Kalso E. Pe iope a i e ke amine o
acu e pos - ope a i e pain: a quan i a i e and quali a i e sys-
ema ic e iew (Coch ane Re iew). Ac a Anaes hesiol Scand
2005;49:1405-28.
39. Kollende Y, Bickels J, S ocki D, Ma uoani N, Chazan S, Ni kin A,
Melle I, Weinb um AA. Subanaes he ic ke amine spa es pos ope-
a i e mo phine and con ols pain be e han s anda d mo phi-
ne does alone in o hopaedic-oncological pa ien s. Eu J Cance
2008;44:954-62.
40. A oyo-No oa CM, Figue oa-Ramos MI, Miaskowski C, Padilla
G, Paul SM, Rod íguez-O iz P, S o s NA, Pun illo KA. E ica-
cy o small doses o ke amine wi h mo phine o dec ease p o-
cedu al pain esponses du ing open wound ca e. Clin J Pain
2011;27:561-6.
41. Ca s ensen M, Mølle AM. Adding ke amine o mo phine o
in a enous pa ien -con olled analgesia o acu e pos ope a i-
e pain: a quali a i e e iew o andomized ials. B J Anaes h
2010;104:401-6.
42. Neshe N, Eks ein MP, Paz Y, Ma ouani N, Chazan S, Weinb oum
AA. Mo phine wi h adju an ke amine s highe dose o mo -
phine alone o immedia e pos ho aco omy analgesia. Ches
2009;136:245-52.
43. Sa oia G, Alampi D, Aman ea B, Amb osio F, A cioni R, Be i M, e
al. Pos ope a i e pain ea men SIAARTI Recommenda ions 2010.
Sho e sion. Mine a Anes esiol 2010;76:657-67.
006_9339 E ec o a single dose o lidocaine.indd 51 30/1/16 5:51