Physiological and Beha io al E ec s o Con inuous Remi en anil-Xylazine
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Adminis a ion in Donkeys
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Kássia Fe nanda A aújo Damascenoa, And essa Nunes Mou aa, La issa de San ’Ana Al esa,
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Ka h yn Nób ega A co e dea, He be Reis A agãoa, Je son Ma ques Ca alcan ea, Valé ia
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Ve as de Paulaa
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a Depa men o Animal Science, Uni e sidade Fede al Ru al do Semi-Á ido (UFERSA),
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BR110 Km 47 s/n, P.O. Box 137, P esiden e Cos a e Sil a, Mosso ó – RN, B azil, 59625-900.
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ABSTRACT
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Backg ound: Remi en anil and xylazine a e d ugs ha can allow s anding equine su ge y when
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in con inuous in usion. The li e a u e p esen s no epo s o his associa ion in donkeys.
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Objec i es: To e alua e he beha io al, seda i e, and ca dio espi a o y e ec s o con inuous
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in a enous in usion o emi en anil and xylazine in donkeys. S udy design: Expe imen al,
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p ospec i e, non-blinded s udy. Me hods: 10 donkeys we e seda ed wi h an in a enous bolus
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o xylazine (0.8 mg/kg). A e 3 minu es, con inuous in usions o xylazine (0.65 mg/kg/h) and
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emi en anil (6 µg/kg/h) we e adminis e ed o 60 minu es. Ca dio espi a o y physiological
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pa ame e s, ec al empe a u e, gas oin es inal mo ili y, and seda ion and a axia sco es we e
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e alua ed by a simple desc ip i e scale a M0 (baseline) and e e y 5 minu es, up o M60 (60
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min), wi h sco es 0-3. Head heigh conce ning he g ound was also e alua ed. Dunne and
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F iedman s a is ical es s (p < 0.05) we e used. Resul s: Hea a e (p = 0.049) and espi a o y
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a e (p = 0.001) dec eased signi ican ly a M10 and M5, espec i ely, compa ed o M0. The e
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was a signi ican dec ease in sys olic (p = 0.04), mean (p = 0.02), and dias olic (p = 0.03) blood
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p essu e a M15 compa ed o M0. The capilla y e ill ime a M20 was s a is ically di e en (p
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= 0.001) om M0. The head heigh in ela ion o he g ound educed signi ican ly om M5 (p
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= 0.001) o M60. Sa is ac o y seda ion was ob ained om M15 o M60. A e s opping he
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in usion, all donkeys eco e ed success ully (7.1 ± 2.4 minu es). No ad e se e ec s we e
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obse ed du ing and a e he in usion. P ima y limi a ions: No pain ul s imulus o su gical
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p ocedu e was pe o med. Conclusions: Combining emi en anil and xylazine a he doses used
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caused adequa e seda ion and sho eco e y ime. Remi en anil did no cause exci a ion in he
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donkeys. Fu u e s udies a e necessa y o es he p o ocol wi h pain ul s imuli.
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Keywo ds: Asinine; Equine; Remi en anil; Seda ion.
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1 In oduc ion
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Donkeys (Equus asinus) a e us ic animals whose impo ance is o en neglec ed due o
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hei speci ic cha ac e is ics, bo h in mo phophysiological and pha macological pe spec i es,
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as well as hei empe amen .1 Thus, some s udies ha e e alua ed he e ec s o d ugs on
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donkeys2,3. Howe e , p o ocols o his species a e s ill sca ce.
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I is common o associa e d ugs o chemically con ain equines, a oiding he
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complica ions and cos s o gene al anes hesia. The ad ene gic alpha2-agonis d ugs p oduce
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seda ion, analgesia, and muscle elaxa ion despi e hei ad e se e ec s.4-6 Among ad ene gic
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alpha2-agonis s, xylazine is he sho es ac ing and may esul in insu icien analgesia o some
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su gical o ou pa ien p ocedu es in mono he apy. In hese ci cums ances, hey a e adminis e ed
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in associa ion wi h opioids o wi h local blocking echniques o imp o e analgesia.7
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Opioids a e use ul in anes hesiology because o hei abili y o dec ease sympa he ic and
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soma ic esponses o ha m ul s imula ion.8 Combina ions o an alpha2-agonis wi h an opioid
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in single o epea ed adminis a ions, o e en as pa o a pe i anes he ic p o ocol, can p o ide
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syne gis ic analgesic e ec s and good seda ion. This associa ion educes he po en ial o
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exci a ion a he le el o he cen al ne ous sys em.9
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Remi en anil is an opioid de i a i e o phenylpipe idine, supplied as emi en anil
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hyd ochlo ide, a lyophilized powde . Animal s udies indica e ha he pha macological
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p ope ies o emi en anil a e simila o hose o o he po en μ-opioid ecep o agonis s, such
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as al en anil.10 Cha ac e ized as a po en opioid o ul a-sho du a ion, i s use has been
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desc ibed in s udies conduc ed in di e en species, whe e i was shown o be a sa e d ug,
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p oducing minimal hemodynamic changes, in addi ion o i s onse o ac ion and apid eco e y
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a e cessa ion o use, ega dless o he du a ion o i s adminis a ion. The e o e, emi en anil
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appea s o be a highly i a able opioid, p o iding p o ound analgesia o e y b ie pe iods in
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which analgesia is necessa y o o p olonged pe iods wi hou he conce n o p olonged
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eco e y.8,12 Some s udies desc ibe i s use in ho ses5,6,12. Howe e , he li e a u e has no
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in o ma ion on he sys emic e ec s o emi en anil in donkeys.
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In his con ex , his s udy aimed o e alua e he physiological and seda i e e ec s o
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con inuous in a enous in usion o emi en anil and xylazine in donkeys om he no heas e n
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egion o B azil. We hypo hesized ha ad e se e ec s would be insigni ican when associa ing
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he d ugs in low doses and con inuous in usion, and he seda ion p o ocol can be conside ed o
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seasonal su gical p ocedu es.
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2 Ma e ial and Me hods
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2.1 Animals
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The s udy condi ions we e submi ed o and app o ed by he Animal Use E hics
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Commi ee (CEUA/UFERSA) unde p o ocol numbe No. 42/22. Ten adul donkeys om he
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no heas e n egion o B azil, se en males and h ee emales, aged 5.3 ± 2.2 yea s and weighing
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120.4 ± 21.4 kg, we e used. The animals we e classi ied as heal hy a e clinical and labo a o y
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examina ion (blood coun , u ea, c ea inine, aspa a e amino ans e ase, alanine
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amino ans e ase, and o al p o eins) o he inclusion c i e ia. A sample calcula ion was
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pe o med based on a pilo s udy wi h h ee animals using he dose p esen ed in he s udy wi h
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ho ses6. The calcula ion was done using GPowe 3.1.9.7. This calcula ion and he mean and
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s anda d de ia ion o seda ion o M5, alpha 0.05, and Powe 0.8 we e compa ed wi h he
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cons an 0 o M0. The animals we e dewo med wi h i e mec in (I omec®, Boeh inge
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Ingelheim), associa ed wi h ichlo on and mebendazole (T ichlo sil pas e®, Vansil), and
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accina ed agains abies ou weeks p io o he s a o he s udy. The animals we e housed in
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g oups o i e, in picke s o 10 x 7 m in he open ai , wi h shade, and ed wi h oluminous g ass
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(Pennise um pu pu eum) and concen a e (g ound co n, soybean meal, whea b an, common
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sal , and calci ic limes one) wice a day, wi h wa e ad libi um. The acclima iza ion o he new
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en i onmen ook ou weeks.
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2.2 Expe imen al s udy
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One day be o e he p ocedu e, he animals we e ans e ed o indi idual s alls. P io o
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he expe imen , hey we e subjec ed o a 12-hou as om solid ood and had access o wa e
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ad libi um.
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Ini ially, he physiological pa ame e s o espi a o y a e (RR) by inspec ion o he cos al
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g id, capilla y e ill ime (CRT), hea a e (HR) by ca diac auscul a ion, ec al empe a u e
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(RT), mean a e ial p essu e (MAP), sys olic blood p essu e (SBP), dias olic blood p essu e
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(DBP) h ough a mul ipa ame ic moni o (mul ipa ame ic moni o , ouch sc een, Del a Li e,
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model DL1000), and gas oin es inal mo ili y by auscul a ion, assessing in es inal bo bo ygmus
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in he do sal and en al quad an s o he igh and le side, we e e alua ed a baseline (M0).
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A e M0, icho omy and an isepsis o he jugula ein we e pe o med o ca he e iza ion,
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using a 16-gauge ca he e coupled o a 3-way s opcock.
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Subsequen ly, he animals ecei ed a 0.8 mg·kg-1 bolus o xylazine (xylazine
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hyd ochlo ide 2%, Syn ec®) adminis e ed wi hin 60 seconds by in usion pump (RS700 VET,
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RZVET®) and, a e 3 minu es, con inuous in usions o xylazine and emi en anil ( emi en anil
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hyd ochlo ide, Eu o a ma®) we e ini ia ed a he a es 0.65 mg/kg/h and 6 µg/kg/h,
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espec i ely, and discon inued o e 60 minu es a e h ee minu es o he ini ial xylazine bolus
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(Figu e 1).
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XYLAZINE
BOLUS
3 MIN AFTER
XYLAZINE
BOLUS
63 MIN AFTER
XYLAZINE
BOLUS
BEGINNING OF CI
XYLAZINE AND
REMIFENTANIL
END OF CI
XYLAZINE
AND
REMIFENTANIL
Figu e 1. Linea ep esen a ion o he beginning and end o xylazine and emi en anil
in usions in donkeys.
Adap ed om Pala ols e al., 2020.
The same physiological pa ame e s e alua ed a M0 (HR, RR, CRT, RT, MAP, SBP,
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and DBP) we e moni o ed e e y 5 minu es un il 60 minu es a e d ug adminis a ion (M60).
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Gas oin es inal mo ili y was e alua ed 15 min, 1h, 4h, 8h, and 24h a e he in usions (M60).
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The head heigh abo e he g ound was measu ed using a ape measu e g adua ed in
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cen ime e s om 0 o 160 cm, which was ixed o he la e al ba o he physical con ainmen
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unk o e alua e seda ion. The dis ance be ween he g ound and he mandibula symphysis was
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measu ed be o e beginning he ins umen a ion, in an en i onmen ee o ex e nal s imuli,
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conside ing he head heigh o he animal a M0. Seda ion was also e alua ed using a simple
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desc ip i e scale, assessing he le el o seda ion and a axia,5,13 wi h sco es om 0 o 3 o bo h
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i ems (Table 1).
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Table 1: Simple desc ip i e scale (SDS) sco ing sys em o seda ion and a axia (FUNCIA e al., 2016)5.
SEDATION
SCORE
SIGNS
0
No seda ion. The animal is ale , wi h no mal pos u e and esponse o con ac wi h
he e alua o . No mal objec ion o in e en ion.
1
Ligh seda ion. Head lowe ed, acial muscles elaxed, and lowe lip hanging.
Some esponse o in e en ion.
2
Mode a e seda ion. Head lowe ed owa ds he loo and swinging he hind legs.
Sligh esponse o in e en ion.
3
Ma ked seda ion. T ies o becomes ecumben . No esponse o in e en ion.
ATAXIA
SCORE
SIGNS
0
No a axia. The animal s ands and walks no mally; can o a e wi h o ce.
1
Mild A axia. The animal can walk, bu wi h some lack o limb con ol.
2
Mode a e a axia. The animal can only walk wi h suppo , s agge s, bu a oids
alling.
3
Ma ked a axia. The animal canno walk wi hou dange o alling, s agge s, alls,
u ns o e .
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The pa ien 's quali y and o al eco e y ime we e e alua ed om he end o he
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in usions o he ime he pa ien p esen ed wi h a sco e o ze o o seda ion and minimal a axia.
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The seda ion sco e was assessed e e y wo minu es a e s opping he con inuous in usion o
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xylazine and emi en anil.
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Any need o mo e d ugs o seda ion, dec eased adminis a ion, o any unexpec ed
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e ec would be epo ed om he i s xylazine bolus un il eco e y.
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2.3 S a is ical Analysis
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Da a we e exp essed as mean ± s anda d de ia ion, median, minimum, and maximum
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alues using he SAS V8 s a is ical p og am (Sys em o Windows - SAS Ins i u e Ca y, No h
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Cali o nia; USA). A e e i ying he pa ame ic assump ions, s a is ical di e ences be ween
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he imes s udied (M0 – M60) we e e i ied h ough analysis o a mixed-e ec s model o
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epea ed measu es (P oc Mixed o he SAS p og am) o each a iable s udied, ollowed by he
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Dunne es . The baseline momen (T0) was used as he base compa ison a iable.
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Nonpa ame ic da a we e analyzed using he me hod desc ibed by F iedman. The signi icance
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le el conside ed was 5%.
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3 Resul s
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The seda ion and a axia ob ained we e sa is ac o y in all animals h oughou he
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p ocedu e, soon a e xylazine adminis a ion. A e 20 minu es, mode a e a axia and seda ion
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we e obse ed, wi h a median seda ion and a axia sco e o 2 o bo h pa ame e s emaining
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h oughou he p ocedu e. The heigh o he head in ela ion o he g ound was signi ican ly
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lowe (p = 0.001) a baseline du ing he en i e in usion ime (Table 2).
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Table 2 - Mean ± s anda d de ia ion (SD) o seda ion sco e, a axia sco e, and head heigh o donkeys submi ed o
con inuous in usion o emi en anil and xylazine o 60 minu es.
Va iables
Measu es
M0
M5
M10
M15
M20
M30
M45
M60
Seda ion
sco e
(0-3)
Mean
± SD
0
± 0
0.9
± 0.6**
1.0
± 0.5**
1.2
± 0.4**
1.6
± 0.2*
1.7
± 0.5*
1.9
± 0.3*
1.9
± 0.3*
Median
0
1
1
1
2
2
2
2
Min - max
0 - 0
0 - 2
0 - 2
1 - 2
1 - 2
1 - 2
1 - 2
1 - 2
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A axia
sco e
(0-3)
Mean
± SD
0
± 0
0.8
± 0.6**
1.0
± 0.5**
1.1
± 0.6**
1.6
± 0.5*
1.7
± 0.5*
1.8
± 0.4*
1.9
± 0.3*
Median
0
1
1
1
2
2
2
2
Min - max
0 - 0
0 - 2
0 - 2
0 - 2
1 - 2
1 - 2
1 - 2
1 - 2
Head
heigh
(cm)
Mean
± SD
83.0
± 9.5*
28.7
± 28.3**
28.78
± 33.1**
18.11
± 25.3**
16
± 22.2**
17
± 21.3**
16.56
± 21.4**
14.44
± 17.3**
Median
82.5
15
15
5
5
10
5
10
Min - max
65 - 100
0 - 85
0 - 84
0 - 78
0 - 69
0 - 63
0 - 63
0 - 56
*, ** Di e en as e isks on he same line indica e s a is ically signi ican di e ence (p < 0.05 - Dunne ).
HR dec eased signi ican ly (p = 0.049) en minu es a e xylazine adminis a ion and i s
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con inuous in usion wi h emi en anil (M10), while RR dec eased signi ican ly (p = 0.001) a e
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5 minu es o he xylazine bolus (M5). MAP (p = 0.02), SBP (p = 0.04), and DBP (p = 0.03)
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dec eased signi ican ly om M15, while RT emained s able h oughou he p ocedu e (Table
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3).
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Table 3 - Mean alues ± s anda d de ia ion (SD) o hea a e (HR), espi a o y a e (RR), sys olic blood p essu e
(SBP), mean a e ial p essu e (MAP), dias olic p essu e (DBP), capilla y e ill ime (CRT), and ec al empe a u e (RT)
o donkeys submi ed o con inuous in usion o emi en anil and xylazine in 60 minu es.
Va iables
Measu es
M0¥
M5
M10
M15
M20
M30
M45
M60
HR
(bpm)
Mean
± SD
44.4
±6.2*
40.9
±6.1*
39.8
±7.9**
39.3
±7.1**
39.5
±9 **
37.1 ±8.4
**
38
±7.8 **
41.5
±13.6 **
RR (bpm)
Mean
± SD
34.3
±7.6 *
18.0
±9.0**
15.3
±7.8**
14.1
±7.9**
13.8
±6.5**
11
±5.1**
9.8
±5.7 **
10.5±6.3**
†SBP
(mmHg)
Mean
± SD
166.8
±23.5 *
160.7
±34.2 *
153.7
±28.5 *
137.6
±34.4 **
136.3
±28.3 **
144.8
±32.8**
147.3
±39.9**
131.7
±30.3**
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