Efficacy of tramadol as analgesic and mixed with ketamine, xylazine as anesthetic in rabbits

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1 Kuf Journl For Veterinry Medicl Sciences Efficcy of trmdol s nlgesic nd mixed with ketmine, xylzine s nesthetic in rits *Smeer A. Aid AL-Redh ** Neern F. Hssn * Deprtment of surgery, college of veterinry medicine, university of Qdsyih, Irq ** Deprtment of pthology nd poultry diseses, college of veterinry medicine, university of Qdsyih, Irq Neern15@gmil.com smeer3hmed@yhoo.com Astrct: This study were performed to evlute the efficcy of Trmdol s nlgesic nd efficcy of using Trmdol in comintion with other drugs like Ketmine nd Xylzine in nesthetic protocols in rits. 15 dult New Zelnd white rits divided to 3 equl groups were nesthetized intrmusculrly in one syringe, group 1 with Trmdol 15 mg/kg B.W, group 2 with Trmdol 15mg/Kg B.W nd Ketmine 30mg/Kg B.W, group 3 with Trmdol 15mg/Kg B.W nd Ketmine 30mg/Kg B.W nd Xylzine 5mg/Kg B.W, physiologic prmeters were evluted including : ody temperture, hert rte, respirtory rte, muscle relxtion, nlgesi nd stges of nesthesi ( Induction of nesthesi, surgicl nesthesi nd recovery time).the most significnt chnges were reported in G3 (T15K30X5) nd this comintion is useful regimen cliniclly for nesthetize rits due to the fst of induction nesthesi nd the long surgicl durtion of nesthesi. Key words: Trmdol, Ketmine, Xylzine, nesthesi, Rits. كفاءة الترامادول كمسكن لأللم وبعد خلطة مع الكيتاين والزايالزين كمخدر في األرانب * سم ر احمد عبد الرضا ** ن ران فل ح حسن * فرع الجراحة والتول د, كل ة الطب الب طري, جامعة القادس ة, العراق ** فرع األمراض وامراض الدواجن, كل ة الطب الب طري, جامعة القادس ة, العراق الخالصة: تمت هذه الدراسة لغرض تق م كفاءة الترامدول كمسكن وكفاءة استخدام الترامدول مع ادو ة اخرى مثل الك تام ن والزا الز ن كبرامج تخد ر ف األرانب. 15 ارنب ناضج ساللة محل ة قسمت الى 3 مجام ع متساو ة تم تخد رها بالحقن ف العضلة ف محقنة واحدة, المجموعة األولى ترامدول 15 ملغم/كغم من وزن الجسم, المجموعة الثان ة ترامدول 15 ملغم/كغم, ك تام ن 33 ملغم/كغم من وزن الجسم,المجموعة الثالثة ترامدول 15 ملغم/كغم, ك تام ن 33 ملغم/كغم و زا الز ن 5 ملغم/كغم من وزن الجسم. تم تق م المعا ر الفسلج ة المتضمنة : درجة حرارة الجسم, معدل ضربات القلب, معدل التنفس, 1

2 Kuf Journl For Veterinry Medicl Sciences درجة األرتخاء العضل, درجة التسك ن وا ظا تم تسج ل ( وقت احداث التخد ر, طول فترة التخد ر الجراح, وقت األفاقة(. معظم التغ رات المعنو ة سجلت ف المجموعة الثالثة )ترامدول 15 ك تام ن 33 زا الز ن 5 ( ملغم/كغم وهذا المز ج عتبر نظام مف د سر ر ا لتخد ر األرانب وذلك لسرعة احداث التخد ر وطول فترة التخد ر الجراح. Introduction: In smll lortory nimls there is no single est method for nesthesi (1). The selection of nesthetic drug or regimen depend on the ville fcilities nd equipments, the type of surgicl procedures, the physicl sttus or temperment of the nimls, the fmilirity of the nesthetist with nesthetic drug, the personnel ville for ssistnce nd the cost of the nesthetic (2,3). Trmdol (Zylol), (Serole), (Trml) is centrlly cting nlgesic drug which hs een in clinicl use in Germny for 17 yers old nd hs lunched in the united kingdom(4). Its used primrily s nlgesic, ut it hs demonstrted usefulness in treting opioid withdrwl in humn eings (5). Trmdol crosses the lood rin rrier nd plcentl rrier nd hs een found to produce humorous positive responses in vertertes including nlgesi for moderte nd sever pin, ntitussive, ntidepressnt, nti-inflmmtory nd immunostimultory effects, n ility to lower glucose in dietes nd locl nesthetic effect (6). Ketmine is one of the dissocitive gents tht cn e used s sole gent for induction nesthesi or in comintion with 2 other gents for induction nd mintennce (7). Its metolized y the liver nd excreted in urine (8). It is n unstisfctory sole gent for surgicl procedures due to the poor muscle relxtion, therefore, it is used in comintion with other gents such s Xylzine or Medetomedine to provide surgicl nesthesi (9). Xylzine is typicl α2 drenoceptors gonist, thizine derivtive drug, widely used s sedtive nd nlgesic drug to tret vrious types of pin in ll species of nimls. It hs sedtive, nlgesic, nesthetic nd muscle relxnt properties in nimls when used lone or in comintion with other gents like Ketmine (10,11). It gives sfe nesthetic effect in horses, cttle, sheep, got, ct nd dogs when co dministrted with Ketmine to induce short period of surgicl nesthesi (12,13). Prenterl nesthetic comintion such s Ketmine / Xylzine hve ecome the gent of choice for nesthesi in the rits ecuse Ketmine nd Xylzine comintion re effective, esily dministered nd inexpensive (14,15). Mteril nd methods: The study performed on 15 helthy dult locl reed rits of oth sexes, divided into 3 equl

3 Kuf Journl For Veterinry Medicl Sciences groups injected intrmusculrly in one syringe s follows: Group 1 injected with 15mg/Kg Body weight Trmdol (T15), Group 2 injected with Trmdol 15mg/kg B.W, Ketmine 30mg/Kg B.W (T15K30), Group 3 injected with Trmdol 15mg/Kg B.W, Ketmine 30mg/Kg B.W nd Xylzine 5mg/Kg B.W (T15K30X5). The following physiologicl prmeters were evluted including: ody temperture, hert rte, respirtory rte, degree of muscle relxtion, degree of nlgesi y recording efore dministrtion the drug t (time 0) then 5,10,20,25,30,45,60 minutes fter drug dministrtion lso induction of nesthesi, surgicl nesthesi nd recovery time were recorded. * Trr 100 (50mg/ml), Trmdol (100mg/ml), the mpoule contin 2 ml meph. * Ketmine ELSod 500 (50mg/ml) the vil contin 10ml, ELSod phrm, Aleppo Syri. * Rompun 2% (Xylzine), (20mg/ml) the vil contin 50ml, Byer Germny. Sttisticl Anlysis: All dt of the experiment were nlyzed sttisticlly using the Completely Rndomized Design (CRD) (Single Fctor), (16), nd Duncn multiple rnge test ws used to determined the differences mong mens of tretment (17). Results: There is no significnt differences P 0.01 & 0.05 etween the groups in the ody temperture in the time ( 0, 5, 10, 30, 45 & 60), while there ws high significnt difference P 0.01 & 0.05 etween group 2 nd group 1 in the time of 20 minute nd no significnt different P 0.01 & 0.05 etween group 2 nd group 3, lso there ws no significnt different P 0.01 & 0.05 etween group 1 nd group 3 in the time of 20 minutes (tle 1). Tle ( 1) Show the chnges in ody temperture within ( 0, 5, 10, 20, 30, 45 nd 60) minutes in group 1 tht nesthetized with Trmdol, group 2 nesthetized with Trmdol & Ketmine nd group 3 nesthetized with Trmdol, Ketmine & Xylzine. 3

4 Kuf Journl For Veterinry Medicl Sciences Time (minutes) Group 1 ody temperture ± ± ± ± ± ± ±0.09 Group 2 ody temperture ± ± ± ± ± ± ± 0.17 Group 3 ody temperture ± ± ± ± ± ± ± 0.35 There ws significnt differences P 0.01 & 0.05 in G2 compring with G 1 nd there ws no significnt differences P 0.01 & 0.05 etween G2 nd G 3, lso there ws significnt differences P 0.01 & 0.05 in G 3 compring with G 1 in the hert rte (tle 2). Tle ( 2) Show the hrt rte within ( 0, 5, 10, 20, 30, 45 nd 60) minutes in group 1 tht nesthetized with Trmdol, group 2 nesthetized with Trmdol & Ketmine nd group 3 nesthetized with Trmdol, Ketmine & Xylzine. Time ( minutes) Group 1 hert rte Group 2 hert rte Group 3 hert rte ± ± ± ± ± ± ± ± ± ± ± ± ± ± 7.31 c ± ± ± ± ± ± ± 8.51 There ws no significnt differences P 0.01 & 0.05 etween group 1, 2 nd 3 in the respirtory rte within (0, 5, 10, 20, 30, 45 nd 60) minutes. 4

5 Kuf Journl For Veterinry Medicl Sciences Tle ( 3) Show the respirtory rte within ( 0, 5, 10, 20, 30, 45 nd 60) minutes in group 1 tht nesthetized with Trmdol, group 2 nesthetized with Trmdol & Ketmine nd group 3 nesthetized with Trmdol, Ketmine & Xylzine. Time minutes Group 1 Respirtion/minute ± ± ± ± ± ± ± 3.51 Group 2 Respirtion/minute ± ± ± ± ± ± ± 5.52 Group 3 Respirtion/minute ± ± ± ± ± ± ± 6.98 There ws no significnt differences P 0.01 & 0.05 etween group 1, 2 nd 3 in the degree of muscle relxnt within (0 nd 30) minutes, lso there ws significnt differences P 0.01 & 0.05 in G 2 nd G3 compring with G 1 in muscle relxnt within ( 5, 10 nd 20 ) minutes nd there ws no significnt differences P 0.01 & 0.05 etween G2 nd G 3 ( tle 4). Tle ( 4) Show the degree of muscle relxnt within ( 0, 5, 10, 20 nd 30) minutes in group 1 tht nesthetized with Trmdol, group 2 nesthetized with Trmdol & Ketmine nd group 3 nesthetized with Trmdol, Ketmine & Xylzine. Time minutes Group 1 Degree of Muscle relxnt ± ± Group 2 Degree of Muscle relxnt 2.20 ± ± ± 0.51 Group 3 Degree of Muscle relxnt 2.00 ± ± ±

6 Kuf Journl For Veterinry Medicl Sciences There ws no significnt differences P 0.01 & 0.05 etween group 1, 2 nd 3 in the degree of nlgesi within (0, 10 nd 30) minutes, lso there ws significnt differences P 0.01 & 0.05 in G 2 nd G3 compring with G 1 in degree of nlgesi within ( 20 ) minutes nd there ws no significnt differences P 0.01 & 0.05 etween G2 nd G 3, lso there ws significnt differences P 0.01 & 0.05 in G 2 compring with G 1 nd G3 within ( 5 ) minutes nd there ws no significnt differences P 0.01 & 0.05 etween G 1 nd G 3 ( tle 5). Tle ( 5) Show the degree of nlgesi within ( 0, 5, 10, 20 nd 30) minutes in group 1 tht nesthetized with Trmdol, group 2 nesthetized with Trmdol & Ketmine nd group 3 nesthetized with Trmdol, Ketmine & Xylzine. Time Group 1 ( minutes) Anlgesi ± ± ± Group 2 Anlgesi 2.40 ± ± ± ± 0.00 Group 3 Anlgesi 1.40 ± ± ± ± 0.24 There is no significnt differences P 0.1 %, 0.5 % etween G 2 nd G 3 in the induction of nesthesi nd the surgicl nesthesi, nd there ws high significnt difference P 0.01 & 0.05 in the recovery time ( wlk time) in G 3 in contrst with G 2 ( tle 6). Tle ( 6 ) Show the stges of nesthesi/ minutes in Group2 tht nesthetized with Trmdol + Ketmine nd Group 3 tht nesthetized with Trmdol + Ketmine + Xylzine. Stges of nesthesi in ody temperture in minutes Induction of nesthesi Surgicl nesthesi Recovery Time (Wlk T.) G ± ± ± 1,81 G3 2.8 ± ± ±

7 Kuf Journl For Veterinry Medicl Sciences Discussion: There ws no effect of Trmdol on ody temperture, while (TK), (TKX) decrese the ody temperture t 20 minutes this result supported y ( 18,19)who found tht Trmdol hs limited effect on therml threshold. The ddition of Xylzine cuse decrese of rectl temperture (20) s in our study, the α 2 gonist depresses the thermoregultory mechnisms in the ody nd either hypothermi or hyperthermi occurs depending on the temperture of environment (21), theses results occurred ecuse of the loss of norml thermoregultory mechnism due to the relese of monomines in the nterior hypothlmus since the nor drenline lowers nd S hydroxyl tryptmine (5HT) hypothlmus (22). Trmdol group hd no effect on hert rte while (TK) nd (TKX) groups cuse decrese in HR these results gree with (23,24), Trmdol hs miniml crdiovsculr effects in humn nd nimls, while TK nd TKX groups decrese the hert rte t the first 5 minutes followed y grdul increse until it reched to the norml or less thn norml t 60 minutes, these results were consistent with previous studies (25,26). In ll groups there were no significnt chnges in respirtory rte, (27) found tht there ws no effect on respirtory rte when Trmdol is used in humn, While TKX decrese RR ut no significnt chnges in spite of Ketmine ction on CNS depression (28). Trmdol hs no effect on degree of muscle relxtion while the comintion etween TK, TKX produce muscle relxtion in the time of 5, 10, 20 minutes nd there were no muscle relxtion in the time of 30 minutes, tht mke these regimens unsuitle for surgicl opertions which tke long time specilly dominl surgery, ecuse of Ketmine produce profound nlgesi with dose etween 11 44mg/Kg without muscle relxtion (29), using Xylzine in comintion with Trmdol nd Ketmine cuse CNS depression which led to generl nesthesi in 5, 10, 20 minutes nd muscle relxtion (30), these results re supported y (31,32). Trmdol not give nlgesi in rits in 0, 30 minutes while in 5, 10, 20 minutes cuse mild nlgesi, this result gree with (33). The nlgesi occurs due to the nlgesic ctivity of Trmdol which interferes with nordrenline nd serotoniergic trnsmission nd inhiits the neurl reuptke of nordrenline (34). The comintion etween Ketmine nd Trmdol increse the nlgesic effects in 5, 20 minutes only, these results re in gree with (29,30), who found tht the dministrtion of Ketmine 22mg/Kg B.W prolong the durtion 7

8 Kuf Journl For Veterinry Medicl Sciences of nlgesi etween minutes. Adding Xylzine to TK produce nlgesi in 20 minutes only, this result gree with (35,36) lso these results re in greement with (37). There ws no chnges in the induction of nesthesi, surgicl nesthesi nd recovery time in TK group while TKX cuse significnt increse in recovery time which is too long, this result gree with (34). In conclusion : using Trmdol, TK dose not produce musculr relxtion, while dding of Xylzine to TK give good surgicl nesthesi mking this protocol suitle cliniclly for nesthesi in rits for dignostic procedure nd for minor surgicl opertions. References: 1. McKelvery, D. nd Holling Shed, K.W. (1994): Smll niml nesthesi 1 st ed. Mosy's fundmentl of veterinry technology, Pp: Al Fredo, G.G. ; Gem, S. nd Jun, C.I. (2005): Effects of riturte dministrtion of heptic nd renl iochemicl prmeters in NewZelnd White rits. Deprtment of physiology, University of Mdrid Spin. 3. Min, S. K.; Seong, M. J.; Je Hk, P.; Tchi, C. N. nd Kng, M. S. (2004): Reversl of Medetomedine Ketmine comintion nesthesi in rits y Atipmezole. 4. Myers, D. (2005): Trmdol Seminrs. Avin nd Exotic pet medicine, 14: Trescot, A. M.; Dtt, S.; Lee, M. nd Husen, H. (2008): opioid Phrmcology. Pin Physicin, 11: Gorono, S. nd Slotzki, A. (2004): Clinicl Phrmcology of Trmdol. Clin. Phrm. Cokinet, 43: Hll, L.W. nd Clrke, K.W. (1991): Veterinry Anesthesi 9 th ed. London: Billere Tindll, Pp: Thurmon, J. C.; Trnquilli, W.J. nd Benson, G.J. (1996): Lum nd Jones veterinry nesthesi. 3 rd ed. Bltimore: Ad, T.A. (2002): Cudl epidurl injection of Xylzine in Cttle. Al Qdsyih. J. Vet. Med. Sci., 2 (1): Al Kttn, L.M.D. (1999): Using of lph 2 drenergic gonist Xylzine nd Medetomedine for injection in epidurl spce in gots. MSC. Thesis university of Mosul Irq. 11. Hrcourt Brown, F. (2002): Textook of Rits medicine. 1 st ed. Butter Worth Heinemnn. Pp:

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11 Kuf Journl For Veterinry Medicl Sciences 35. Aid AL-Redh, S. A. (2007): A comprtive study for using different progrms from neurolep nlgesi nd neurolep nesthesi in rits. MSC. Thesis. Veterinry Med. College. Bghdd University Irq. 36. Gurnni, A.; Shrm, P.K.; Rutele, R. S. nd Bhttchy, A. (1996): Anlgesi for cute musculoskeletl trum, low dose sucutneous fusion of Ketmine. Anesth. Intensive cre, 24: Snford,T.D. nd Coly, E.D. (1980): Effect of Xylzine nd Ketmine on lood pressure, hert rte nd respirtory rte in rits. L. Anim. Sci, 30: