Effect of Saline Dilution on Propofol Injection Pain: Comparison with Lidocaine

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1 ORİJİNAL ARAŞTIRMA Effect of Saline Dilution on Propofol Injection Pain: Comparison with Lidocaine Hüseyin ŞEN, MD, a Ömer YANARATEŞ, MD, b Ali SIZLAN, MD, b Mehmet MUTLU, MD, a Sezai ÖZKAN, MD, a Güner DAĞLI, MD a a Department of Anesthesiology and Reanimation, Gülhane Medical Academy Haydarpaşa Education and Research Hospital, İstanbul b Department of Anesthesiology and Reanimation, Gülhane Medical Academy, Ankara Ge liş Ta ri hi/re ce i ved: Ka bul Ta ri hi/ac cep ted: Ya zış ma Ad re si/cor res pon den ce: Hüseyin ŞEN, MD Gülhane Medical Academy Haydarpaşa Education and Research Hospital, Department of Anesthesiology and Reanimation, İstanbul, TÜRKİYE/TURKEY drhuseyinsen@hotmail.com ABS TRACT Ob jec ti ve: Re cent at tempts aim to dec re a se pro po fol-in du ced pa in eit her with phar ma - co lo gic or nonp har ma co lo gic met hods. The aim of this study was to find out whet her sa li ne di lu ti on had a fa vo rab le ef fect on pro po fol in jec ti on pa in and to com pa re the ef fect of sa li ne di lu ti on with that of li do ca i ne. Material and Met hods: 200 pa ti ents we re ran do mi zed in to fo ur gro ups. In gro up 1, only pro po fol so lu ti on with a con cen tra ti on of 10 mg/ml was used; in gro up 2, the so lu ti on com pri sed 10 mg/ml pro po fol and 2 mg/ml li do ca i ne; in gro up 3, only pro po fol so lu ti on 5 mg/ml and in gro up 4, pro po fol so lu ti on 2.5 mg/ml we re used. Pa in du ring in duc ti on with pro po fol was sco red using a 4-po - int ver bal ra ting sca le. Re sults: Ver bal ra ting sca le sco res (VRSs) of the gro ups we re sig ni fi cantly dif fe - rent (p< 0.001). When gro ups we re com pa red in pa irs, gro up 2 had bet ter anal ge si a than gro ups 1, 3 and 4 for all VRS va lu es (all p values < 0.001); gro up 3 and gro up 4 we re si mi lar (all p values > 0.05) and each had bet ter anal ge si a than gro up 1 (all p values < 0.001). Conc lu si ons: We sug gest that sa li ne di lu ti on can be used to al le vi a te pro po fol-in du ced pa in. Alt ho ugh li do ca i ne se ems to be mo re ef fec ti ve, ac com pan - ying fac tors that wo uld ma ke the use of phar ma co lo gi cal ad juncts con tra in di ca ted may out we igh. The - re fo re, in such ca ses, sa li ne can be used sa fely. Key Words: Pro po fol; pa in; li do ca i ne ÖZET Amaç: Pro po fo le bağ lı en jek si yon ağ rı sı nı azalt ma ya yö ne lik son ça lış ma lar far ma ko lo jik ve ya far ma ko lo jik ol ma yan yön tem ler le ya pıl mak ta dır. Bu ça lış ma nın ama cı, izo to nik sod yum klo rür ile pro po fol di lüs yo nu nun, pro po fo le bağ lı ola rak olu şan en jek si yon ağ rı sı üze rin de ki et ki si ni araş tır mak ve bu nu li do ka in ile kar şı laş tır mak tır. Ge reç ve Yön tem ler: 200 has ta ran do mi ze çift-kör yön tem le dört gru ba ay rıl dı. Bi rin ci grup ta, stan dart ola rak kul la nı lan 10 mg/ml kon san tras yon da pro po fol çö - zel ti si kul la nıl dı; ikin ci grup ta, 10 mg/ml kon san tras yon da pro po fol ve 2 mg/ml li do ka in içe ren çö - zel ti ka rı şı mı kul la nıl dı; üçün cü grup ta, 5 mg/ml pro po fol kon san tras yo nu ola cak şekil de sod yum klo rür ile di lüs yo nu ya pı lan çö zel ti kul la nıl dı; dör dün cü grup ta ise 2.5 mg/ml pro po fol kon san tras yo - nu ola cak şekil de izo to nik sod yum klo rür ile di lüs yo nu ya pı lan çö zel ti kul la nıl dı. Pro po fol ile ya pı lan in dük si yon es na sın da olu şan ağ rı dört nok ta sö zel de ğer len dir me ska la sı kul la nı la rak ya pıl dı. Bul gu lar: Dört nok ta sö zel de ğer len dir me ska la sı na gö re, dört gru bun de ğer le ri bir bi rin den fark lıy dı (p< 0.001). Grup lar iki şer iki şer kar şı laş tı rıl dı ğın da, sö zel de ğer len dir me ska la sı na gö re grup 2, grup 1, 3 ve 4 e gö - re da ha iyi anal je zi sağ la dı (tüm p değerleri <0.001); grup 3 ve grup 4 ün bul gu la rı ben zer bu lun du (tüm p değerleri > 0.05) ve her iki si de grup 1 ile kı yas lan dı ğın da da ha iyi anal je zi sağ la dı (tüm p değerleri < 0.001). So nuç: Pro po fo lün izo to nik sod yum klo rür ile di lüs yo nu, pro po fol en jek si yon ağ rı sı nı azalt - mak ta dır. Bu nun la bir lik te pro po fo le li do ka in ila ve si, pro po fo lün izo to nik sod yum klo rür ile di lüs yo - nu na gö re pro po fol en jek si yon ağ rı sı nı azalt ma da da ha et kin dir. Li do ka in gi bi far ma ko lo jik ajan la rın kul la nı la ma dı ğı du rum lar da, pro po fo lün izo to nik sod yum klo rür ile di lüs yo nu, pro po fo le bağ lı en jek - si yon ağ rı sı nı azalt mak için gü ven le kul la nı la bi lir. Anah tar Ke li me ler: Pro po fol; ağ rı; li do ka in :150-4 Cop yright 2009 by Tür ki ye Kli nik le ri ropofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anesthetics. It was formulated in a concentration of 10 mg/ml and causes pain or discomfort on injection in 28-90% of pati- 150

2 Anaesthesiology and Reanimation ents. 1-3 Re cent at tempts ai med to dec re a se the pro - po fol-in du ced pa in eit her with phar ma co lo gic or nonp har ma co lo gic met hods. 4-8 The for mer com pri - sed pret re at ment with li do ca i ne, ke ta mi ne, thi o - pen tal, re mi fen tanyl, nit ric oxi de, me toc lop ra mi de, flur bip ro fen, ep hed rin or ace ta mi nop hen On the ot her hand, nonp har ma co lo gic ap pro ac hes inc lu - ded co o ling or war ming pro po fol, di lu ting and injec ting it in to a lar ge ve in. The con cen tra ti on of fre e pro po fol in the aqu e o us pha se is tho ught to be parti cu larly as so ci a ted with in jec ti on pa in. 18 Pro po fol usu ally is ava i lab le in a con cen tra ti on of 1.0% pro - po fol in a li pid emul si on con ta i ning 10% trigl yce ri - des. Di lu ti on with a con si de rably hig her qu an tity of li pid emul si on or with dex tro se 19,20 we re at temp - ted; ho we ver, to our best no ti ce, di lu ti on of pro po - fol with sa li ne was not re por ted in the re le vant li te ra tu re. The re fo re, the two go als of this cur rent study was to find out whet her sa li ne di lu ti on had a fa vo rab le ef fect on pro po fol in jec ti on as so ci a ted pa - in and to com pa re the ef fects of sa li ne di lu ti on with sa li ne and li do ca i ne com bi na ti on on pro po fol in du - ced pa in. MATERIAL AND MET HODS The study had a pros pec ti ve, ran do mi zed, do ub - le-blind de sign. All pa ti ents ga ve in for med consent and the study was ap pro ved by the lo cal et hics com mit te e. 200 pa ti ents (ASA-I/II, aged bet we en ye ars) who we re un der go ing ge n- e ral anest he si a for elec ti ve sur gi cal in ter ven ti ons we re ran do mi zed in to fo ur gro ups. Pa ti ents with any of the fol lo wing we re exc lu ded: al lergy to pro po fol, psychi at ric or ne u ro lo gic di sor der, li - ver/re nal di se a se, ASA II I-IV, age be low 20 or abo ve 60. No ne of the pa ti ents re ce i ved pre me di ca ti on inc lu ding any anal ge sic or se da ti ve drugs be fo re Şen et al sur gery. All sub jects we re mo ni to ri zed in the ope - ra ti on ro om in a stan dard way (elec tro car di og - raphy, non-in va si ve ar te ri al blo od pres su re and pul se oxi me ter). A 20-ga u ge cat he ter was pla ced in to the lar ge dor sal ve in of the hand. Stan dard pro po fol (pro po fol 1% Fre se ni us) so lu ti on (10 mg/ml) was di lu ted with 0.9% NaCl. The syrin ges we re pre pa red in ro om tem pe ra tu re and pro po fol was gi ven with an in fu si on pump by a per son nel blin ded to the study gro ups. All gro ups we re de sig - ned to ad mi nis ter pro po fol 2 mg/kg wit hin 3 min. In gro up 1, only pro po fol so lu ti on 10 mg/ml was used; in gro up 2, the so lu ti on com pri sed 10mg/mL pro po fol and 2 mg/ml li do ca i ne; in gro up 3, only pro po fol 5 mg/ml and in gro up 4, pro po fol so lu ti - on 2.5 mg/ml we re used. Pa in du ring in duc ti on with pro po fol was sco - red using a 4-po int VRS (Tab le 1). 6 Pa ti ents we re as ked to ra te the ir pa in at the in jec ti on si te af ter infu si on of ¼ of the so lu ti on, af ter ½ of the so lu ti on and, if hypno sis has not en su ed, af ter ¾ of the solu ti on. Statistical Analysis Sta tis ti cal analy sis was do ne with SPSS for Windows Re sults we re gi ven as me an ± stan dard de vi a ti on and per cen ta ges. One-way ANO VA test was used to com pa re con ti nu o us va ri ab les. Chisqu a re test and Kol mo go rov-smir nov Z we re used for ca te go ri cal va ri ab les. Tu key test was used for post hoc com pa ri son. Sta tis ti cal sig ni fi can ce was set at p< RE SULTS De mog rap hic fe a tu res of the pa ti ents we re sum ma - ri zed in Tab le 2. Me an va lu es for age, he ight and we - ight and dis tri bu ti on of the pa ti ents ac cor ding to sex and ASA we re si mi lar bet we en the gro ups (all p va l- u es > 0.05). Ver bal ra ting sca le sco res of the pa ti ents TABLE 1: 4-point verbal rating scale. 0 No pain Negative response to questioning 1 Mild pain Pain reported only in response to questioning without any behavioral signs (ie, no spontaneous expression of pain) 2 Moderate pain Pain reported only in response to questioning and accompanied by a behavioral sign or symptom (ie, expression of pain) reported spontaneously without questioning 3 Severe pain Strong verbal response or response accompanied by facial grimacing, arm withdrawal 151

3 Şen ve ark. Anesteziyoloji ve Reanimasyon TABLE 2: Demographic features of the patients (mean ± SD). Group 1 (n= 50) Group 2 (n= 50) Group 3 (n= 50) Group 4 (n= 50) p Age (year) ± ± ± ± * Weight (kg) ± ± ± ± * Height (cm) ± ± ± ± * ASA (I/II) 50/0 46/4 45/5 44/ *** Sex (male/female) 28/22 26/24 24/26 26/ ** *ANOVA test, ** chi-square test, *** Kolmogorov-Smirnov Z test ASA: American Society of Anesthesiologists. we re gi ven in Tab les 3, 4, and 5. Gro ups sho wed diffe ren ce with re gard to VRS sco res (p< 0.001). When gro ups we re com pa red in pa irs, gro up 2 had bet ter anal ge si a than gro ups 1, 3 and 4 for all VRS va lu es (all p va lu es < 0.001); gro up 3 and gro up 4 we re si - mi lar (all p va lu es > 0.05) and each had bet ter analge si a than gro up 1 (all p va lu es < 0.001). DIS CUS SI ON In this study, we ai med to find out whet her di lu ti - on of pro po fol with sa li ne dec re a sed the pa in as so - ci a ted with its in jec ti on and we com pa red the ef fect of sa li ne di lu ti on with sa li ne and li do ca i ne com bi na ti on on pa in sco res. Ove rall, sa li ne had favo rab le ef fects ir res pec ti ve of the amo unt of di lu - ti on. Ho we ver, sa li ne di lu ti on was not su pe ri or to con co mi tant li do ca i ne use. Fu ji i et al com pa ra ti vely stu di ed the ef fi cacy of li do ca i ne, me toc lop ra mi de, and flur bip ro fen for re du cing pa in on in jec ti on of pro po fol. 14 The me di - an pa in sco re was less in pa ti ents who had re ce i ved li do ca i ne, me toc lop ra mi de or flur bip ro fen than in tho se who re ce i ved pla ce bo. The in ci den ce and se - ve rity of pa in we re not sig ni fi cantly dif fe rent bet - we en the li do ca i ne-, me toc lop ra mi de-, and flur bip ro fen-tre a ted gro ups. In anot her study by Can bay et al, iv ace ta mi nop hen was ef fec ti ve, alt - ho ugh not as much as li do ca i ne, in dec re a sing the in ci den ce of pa in du ring iv in jec ti on of pro po fol. 17 In our study, ad di ti on of li do ca i ne was su pe ri or to sa li ne di lu ti on. Va ri o us nonp har ma co lo gi cal in ter ven ti ons we - re tes ted to eli mi na te pro po fol-in du ced pa in. Dec re - a sing the con cen tra ti on in the aqu e o us pha se of pro po fol emul si on by di lu ting with ad di ti o nal solvents or chan ging the li pid car ri er we re shown to re- TABLE 3: Verbal rating scale scores of patients after infusion of ¼ of the solution (0%) (74.0%) (48.0%) (34.0%) (6.0%) (26.0%) (28.0%) (40.0%) (70.0%) (0%) (24.0%) (26.0%) (24.0%) (0%) (0%) (0%) TABLE 4: Verbal rating scale scores of patients after infusion of ½ of the solution (0%) (80.0%) (48.0%) (36.0%) (6.0%) (20.0%) (28.0%) (36.0%) (34.0%) (0%) (18.0%) (18.0%) (60.0%) (0%) (6.0%) (10.0%) TABLE 5: Verbal rating scale scores of patients after infusion of ¾ of the solution (0%) (80.0%) (48.0%) (36.0%) (6.0%) (20.0%) (28.0%) (36.0%) (26.0%) (0%) (18.0%) (16.0%) (68.0%) (0%) (6.0%) (12.0%) 152

4 Anaesthesiology and Reanimation du ce the pa in on in jec ti on. 19 The hig her con tent of li pids we re sug ges ted to be the ma in re a son for re du - cing the in ci den ce of pa in eit her in chil dren or in adults. 1,18,21 On the ot her hand, ad di ti on of 5% dextro se in Rin ger s ace ta te was shown to be com pa rab - le to li do ca i ne in dec re a sing pro po fol-in du ced pa in. 20 Ac cor ding to our re sults, eit her form of sa li ne di lu - ti on was shown to dec re a se pro po fol in du ced pa in. The in ci den ce and in ten sity of pro po fol-as so - ci a ted pa in se ems to be af fec ted by many fac tors li ke cat he ter si ze and si te of in ser ti on, vo lu me, tem pe ra tu re and spe ed of in jec ti on, and con cen - tra ti on of pro po fol in the aqu e o us pha se of the pre - pa ra ti on. Alt ho ugh the mec ha nism of pa in is not well un ders to od, pro po fol is known to ir ri ta te the skin, mu co us mem bra nes, and ve no us in ti ma. 22 By an in di rect ac ti on on the en dot he li um, it al so acti va tes the kal lik re in-ki nin system, the reby produ cing ve no us di la ti on and hyper per me a bi lity, in cre a sing the con tact bet we en pro po fol and the fre e ner ve en dings. 23 In our study, pro po fol ad mi - Şen et al nis tra ti on was per for med with stan dard 20-G cat - he ters for a cons tant pe ri od from a lar ge ve in on the dor sum of the hand. The re fo re, the ef fects of the afo re men ti o ned fac tors we re not elu ci da ted in our study; ho we ver, we be li e ve that sa li ne di lu ti - on might ha ve af fec ted vi a di rect and in di rect ways, dec re a sing the amo unt of pro po fol in contact with the ve no us in ti ma and the kal lik re in-ki - nin system. To sum ma ri ze, ac cor ding to our re sults, we may conc lu de that sa li ne di lu ti on can be used to al le vi a te pro po fol in du ced pa in. Alt ho ugh li do - ca i ne se ems to be mo re ef fec ti ve in this re gard, ac com pan ying fac tors that wo uld ma ke the use of phar ma co lo gi cal ad juncts con tra in di ca ted, may out we igh (e.g. pa ti ents al ler gic to li do ca i ne; ocu log yric/ex trap yra mi dal signs du e to pre vi o us me toc lop ra mi de use; ast hma, re nal fa i lu re or gastric ul ce ra ti on for nons te ro i dal an ti-inf lam ma - tory drugs). In such ca ses, sa li ne can be used sa fely. 1. Kle ment W, Arndt JO. Pa in on in jec ti on of pro - po fol: ef fects of con cen tra ti on and di lu ent. Br J Ana esth1991;67(3): Lyons B, Lo han D, Flynn C, McCar roll M. Mo - di fi ca ti on of pa in on in jec ti on of pro po fol. A com pa ri son of pet hi di ne and lig no ca i ne. Ana - est he si a 1996;51(4): Tan CH, On si ong MK. Pa in on in jec ti on of pro - po fol. Ana est he si a1998;53(5): Do e nic ke AW, Ro i zen MF, Ra u J, O'Con nor M, Kug ler J, Klotz U, et al. Phar ma co ki ne tics and phar ma cody na mics of pro po fol in a new sol vent. Anesth Analg 1997;85(6): Ra u J, Ro i zen MF, Do e nic ke AW, O'Con nor MF, Strohsc hne i der U. Pro po fol in an emul si on of long- and me di um-cha in trigl yce ri des: the effect on pa in. Anesth Analg 2001;93(2): McCrir rick A, Hun ter S. Pa in on in jec ti on of pro po fol: the ef fect of in jec ta te tem pe ra tu re. Ana est he si a 1990;45(6): Sto kes DN, Rob son N, Hut ton P. Ef fect of dilu ting pro po fol on the in ci den ce of pa in on injec ti on and ve no us se qu e la e. Br J Ana esth 1989;62(2): McCul loch MJ, Le es NW. As sess ment and mo di fi ca ti on of pa in on in duc ti on with pro po - fol (Dip ri van). Ana est he si a 1985;40(11): REFERENCES 9. Pi card P, Tramèr MR. Pre ven ti on of pa in on in jec ti on with pro po fol: a qu an ti ta ti ve syste - ma tic re vi ew. Anesth Analg 2000;90(4): Uğur B, Erpek G, Aydın ON. [The effect of subanesthetic ketamine on propofole related pain and hemodynamic changes]. Turkiye Klinikleri J Anest Reanim 2005;3(2): Agar wal A, An sa ri MF, Gup ta D, Pan dey R, Ra za M, Singh PK, et al. Pret re at ment with thi - o pen tal for pre ven ti on of pa in as so ci a ted with pro po fol in jec ti on. Anesth Analg 2004;98(3): Ao u ad MT, Sid dik-say yid SM, Al-Ala mi AA, Ba ra ka AS. Mul ti mo dal anal ge si a to pre vent pro po fol-in du ced pa in: pret re at ment with re - mi fen ta nil and li do ca i ne ver sus re mi fen ta nil or li do ca i ne alo ne. Anesth Analg 2007;104(6): Beh T, Splin ter W, Kim J. In chil dren, nit ro us oxi de dec re a ses pa in on in jec ti on of pro po fol mi xed with li do ca i ne. Can J Ana esth 2002; 49(10): Fu ji i Y, Ita ku ra M. Com pa ri son of li do ca i ne, me toc lop ra mi de, and flur bip ro fen axe til for redu cing pa in on in jec ti on of pro po fol in Ja pa - ne se adult sur gi cal pa ti ents: A pros pec ti ve, ran do mi zed, do ub le-blind, pa ral lel-gro up, pla - ce bo-con trol led study. Clin Ther 2008;30(2): Fu ji i Y. Pret re at ment with flur bip ro fen axe til and ve no us occ lu si on to re du ce pa in du ring in jec ti on of pro po fol. Can J Ana esth 2004;51 (10): Che ong MA, Kim KS, Cho i WJ. Ep hed ri ne redu ces the pa in from pro po fol in jec ti on. Anesth Analg 2002;95(5): Can bay O, Ce le bi N, Arun O, Ka ra göz AH, Sa ri ca oğ lu F, Oz gen S. Ef fi cacy of in tra ve - no us ace ta mi nop hen and li do ca i ne on pro - po fol in jec ti on pa in. Br J Ana esth 2008;100 (1): Do e nic ke AW, Ro i zen MF, Ra u J, Kel ler mann W, Babl J. Re du cing pa in du ring pro po fol injec ti on: the ro le of the sol vent. Anesth Analg 199;82(3): Du bey PK, Ku mar A. Pa in on in jec ti on of li pidfre e pro po fol and pro po fol emul si on con ta i ning me di um-cha in trigl yce ri de: a com pa ra ti ve study. Anesth Analg 2005;101(4): No na ka A, Ta ma ki F, Su ga wa ra T, Oguc hi T, Kas hi mo to S, Ku ma za wa T. [Pre mi xing of 5% dex tro se in Rin ger's ace ta te so lu ti on with pro - po fol re du ces in ci den ce and se ve rity of pa in on pro po fol in jec ti on]. Ma su i 1999;48(8):

5 Şen ve ark. 21. Soltész S, Si lo mon M, Gräf G, Menc ke T, Bo - u la a dass S, Mol ter GP. Ef fect of a 0.5% di lu - ti on of pro po fol on pa in on in jec ti on du ring in duc ti on of anest he si a in chil dren. Anest he - si o logy 2007;106(1): Sun NC, Wong AY, Ir win MG. A com pa ri son of pa in on in tra ve no us in jec ti on bet we en two pre - pa ra ti ons of pro po fol. Anesth Analg 2005;101(3): Anesteziyoloji ve Reanimasyon 23. Co der re TJ, Katz J, Vac ca ri no AL, Mel zack R. Con tri bu ti on of cen tral ne u rop las ti city to pat ho lo gi cal pa in: re vi ew of cli ni cal and expe ri men tal evi den ce. Pa in 1993;52(3):

Comparison of 0.5% Levobupivacaine and 0.5% Bupivacaine for Retrobulbar Anesthesia in Cataract Surgery

ORİJİNAL ARAŞTIRMA Comparison of 0.5% Levobupivacaine and 0.5% Bupivacaine for Retrobulbar Anesthesia in Cataract Surgery Recep AKSU, MD, a Cihangir BİÇER, MD, a Abdullah ÖZKIRIŞ, MD, b Halit MADENOĞLU,