The Veterinary Journal 192 (2012) 193–198

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The Veterinary Journal

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The use of xylazine hydrochloride in an analgesic protocol for claw treatmentof lame dairy cows in lateral recumbency on a surgical tipping table

Awad Rizk a,b, Sarah Herdtweck a, Jennifer Offinger a,⇑, Henning Meyer a, Adel Zaghloul b, Juergen Rehage a

a Clinic for Cattle, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, D-30173 Hannover, Germanyb Department of Surgery, Anaesthesiology and Radiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516 Dakahlia, Egypt

a r t i c l e i n f o

Article history:Accepted 27 May 2011

Keywords:XylazineLocal anaesthesiaPainClawCattle

1090-0233/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.tvjl.2011.05.022

⇑ Corresponding author. Tel.: +49 511 856 7280.E-mail address: Jennifer.Offinger@tiho-hannover.d

a b s t r a c t

The objective of this study was to investigate the effect of xylazine on the stress and pain response oflame cows undergoing claw treatment in lateral recumbency (LR). Twenty-four lame, German Hol-stein–Friesian cows were included in a prospective, blinded, placebo-controlled clinical case study. Cowswere randomly allocated to two groups (n = 12) and either treated with xylazine (0.05 mg/kg BW, IM) oran equal volume of saline (controls) 15 min before placing them in LR. Before surgical treatment, eachcow received retrograde intravenous local anaesthesia (LA). Over a period of 6 h, heart rate (HR), respi-ratory rate (RR), plasma concentrations of cortisol, glucose, lactate and non-esterified fatty acids (NEFA)were determined at preset time intervals and the animals’ behaviour was recorded via video recordingand pedometer.

All xylazine-treated cows showed signs of mild sedation, a reduced pain response on insertion of theneedle for LA, reduced ear flicking during surgery, reduced lameness score and longer standing periodsas well as improved appetite in the first hour postoperatively. Mean HR and RR, as well as plasma con-centrations of NEFA were significantly reduced after xylazine treatment. Cortisol concentrations weresignificantly lower in xylazine-treated cows after being placed in LR but were similar to controls duringsurgery. The use of a low dose of xylazine in the analgesic protocol for the treatment of lame cows in LRalleviates stress and potentiates the analgesic effects of LA.

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Introduction

Claw disorders are responsible for 90% of lameness in dairy cattle(van Amstel and Shearer, 2006) and as such are a major concern, notonly because of their impact on productivity (Amory et al., 2008) butalso because the associated tissue trauma is perceived as painful bythe affected animal (Whay et al., 1998). Pain management in farmanimals has not progressed to the same extent as in companion ani-mal practice and remains a challenge for the veterinary profession(Short, 2003). The stoical nature of cattle often prevents theirexpression of pain, delaying the detection of claw lesions by farmersand resulting in treatment regimes which ignore the pain experi-enced by the cow (Wells et al., 1993; Whay et al., 2002).

In human and animal medicine, it is well recognised that themost effective analgesia is provided by the use of a combinationof agents, acting on different nociceptive pathways and thus result-ing in an additive or synergistic analgesic effect (Kehlet andWilmore, 2002; Anderson and Muir, 2005a,b). This ‘multimodalanalgesia’ reduces individual doses of analgesics and minimises

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e (J. Offinger).

side effects. However, such an approach is often neglected in cattle(Jin and Chung, 2001; Valverde and Gunkel, 2005; Hudson et al.,2008) although it can be particularly useful during surgical manip-ulations of the bovine digit, as it not only allows the surgeon tooperate safely, but also prevents the sensitisation of pain in the ani-mal and enhances convalescence (Anderson and Muir, 2005a,b;Starke et al., 2008).

Intravenous (IV) regional analgesia (IVRA) is the technique ofchoice for surgery of the distal bovine limb (Antalovsky, 1965;Heppelmann et al., 2009), as it has a rapid onset, is easy to performand more reliable than local nerve blocks. IVRA is a type of localanaesthesia and during multimodal pain management may be sup-plemented by sedatives or the use of non-steroidal anti-inflamma-tory drugs (NSAIDs). The a2 agonist xylazine is commonly used incattle due to its analgesic and sedative properties (Greene andThurmon, 1988). However, while the analgesic effects are rela-tively short lived (<1 h, the sedative effects can last for up to24 h, thus rendering it unsuitable for long-term pain management(Valverde and Gunkel, 2005; Stafford et al., 2003). Nevertheless, itcan be administrated to relieve stress, keep the animal calm on thesurgical table and provide short-term analgesia (Thurmon and Ko,1997; Starke et al., 2008).

194 A. Rizk et al. / The Veterinary Journal 192 (2012) 193–198

We have recently reported that pre-emptive low dose applica-tion of xylazine can alleviate the stress of cows placed in LR forpainless claw trimming with statistically significant, but clinicallynegligible, effects on cardio-respiratory function (Rizk et al.,2009). The aim of the present study was to investigate the effectof pre-emptive application of xylazine as a component of the anal-gesic protocol on the stress and pain response of lame cows under-going surgical treatment of claw lesions in LR.

Material and methods

The study was approved by the Animal Care Committee of the Federal State ofLower Saxony, Germany (research permit number 33.9-42502-05-08A573).

Study design

The trial was as a blinded, randomised, prospective and placebo-controlled clin-ical study in lame cows. Studied cows were randomly assigned to either a xylazineor placebo treated group before claw surgery and examined for hormonal, meta-bolic and behavioural stress responses before, during, and after claw surgery in lat-eral recumbency.

Selection of animals, housing and feeding

The study was conducted on 24 clinically lame German Holstein Friesian cows,which were either non-pregnant or no more than 3–4 months pregnant, with anaverage weight of 531 ± 85.5 kg (mean ± SD) and an average age of 4.4 ± 1.5 years.All cows were lame due to a sole ulcer in one claw of one hind limb and were re-ferred to the Clinic for Cattle, University of Veterinary Medicine Hannover, Ger-many, for surgical treatment.

Claw trimming was undertaken in all cows. In eight animals (four per group) aseptic arthritis of the distal interphalangeal joint was diagnosed. These cows weretreated by resection of the affected joint (Starke et al., 2007) and received systemicantibiotic treatment for 5 days (10 mg/kg BW of ampicillin twice daily; Animedica).In the remaining cows, treatment included exposure of the sole defect by paring offloose and adjacent horn, providing smooth transition from the pododerm to thehealthy horn, application of PVP-iodine ointment (Betaisodona, Albrecht) and ban-daging. After surgery a wooden block was fixed to the healthy claw of the affectedfoot.

Exclusion criteria included the presence of other diseases such as displacementof the abomasum, ketosis and acute stages of mastitis or endometritis. The anam-nesis of every cow was carefully investigated for the administration of steroidalor non-steroidal analgesics within 1 week of admission to the clinic. Cows werekept in individual free stalls (4.5 � 4.5 m) on straw bedding and were fed a dietbased on hay and concentrates according to maintenance.

Experimental procedures

A 20 cm indwelling venous catheter (WVI Jugular catheter, Walter Veterinär-Instrumente) was introduced into the right jugular vein for repeated blood sam-pling and removed after the last blood sample was taken. Before the diagnosis ofthe claw disorder, lame cows were randomly allocated to either IM injection ofxylazine (0.05 mg/kg BW; Rompun, Bayer AG) or an equal volume of sterile salinesolution (0.9% sodium chloride solution, B. Braun) (n = 12 for both groups). Xylazineor placebo treatments were performed in the stable. Fifteen minutes later cowswere moved to the surgical theatre and turned into LR for initial claw examination,then, 20 min after start of LR, retrograde IV local anaesthesia with 20 mL of 2% pro-caine (Procasel, Selectavet) was given to all cows after application of a rubber tour-niquet above the fetlock joint (Antalovsky, 1965), surgical claw treatment was thenundertaken based on the clinical presentation.

Blood samples were collected from the jugular vein into heparin and fluoridecoated tubes (Sarstedt AG & Co.) before treatment (baseline), 15 min after cowswere turned into LR (before LA), at the end of LR, as well as 1 and 3 h after LR. Bloodsamples were centrifuged at 1500 g immediately after collection and plasma storedat �20 �C until analysis. At the same intervals HR, RR, lameness and sedation scoreswere determined.

Cardio-respiratory parameters

Heart rate was recorded by counting the heart beats for 1 min by auscultation,RR by counting thoracic excursions for 1 min and rectal temperature was recordedusing a digital thermometer.

Analysis of endocrine and metabolic measures

Chemiluminescent enzyme immunoassay (Cortisol-Immulite 1000-Test, Sie-mens Healthcare Diagnostics) was used for cortisol analysis. Glucose, nonesterifiedfatty acids, beta-hydroxybutyrate and lactate were measured using an automatedanalyser (ABX Pentra 400, Horiba ABX Diagnostics) and commercial test kits. Na+,K+ and Cl� were measured by ion-sensitive electrodes. The strong ion difference(SID) was calculated according using SID = [Na+] + [K+] � [Cl�] (Constable, 1999).

Behaviour recording

Behaviour was recorded using a portable digital video camera (Samsung VPMX20/EDC) fixed above the tipping table and adjusted to allow the simultaneousrecording of one ear, the head, all four legs and the tail of the cow. Recordings tookplace starting 10 min before treatment (at rest in the stable), while moving the ani-mals to the surgical theatre and back (camera hand held), and while turning cowsinto and out of LR on the surgical tipping table. In addition to video recordings, atrained observer recorded and analysed the cows‘ behaviour according to Table 1.Sedation was documented by a score system modified after Fierheller et al.(2004) using five characteristically clinical indicators of sedation (change from ini-tial attitude, head lowering, ptosis, ptyalism and ability to stand; score 1: no, 2:mild, 3: moderate, 4: severe, 5: extremely severe). Feed consumption (% of 1 h)was recorded and lameness was scored according to Sprecher et al. (1997).

Pedometer

Pedometers (190 g, 96 � 81 � 31 mm, Ice Tag System, Ice Robotics) were usedto determine the proportion of time (% of 1 h) an animal was either standing or ly-ing, and to record the amount of steps taken in a given period (Trenel et al., 2009).Recordings were made for a period of 1 h before treatment and over a period of 4 hafter treatment.

Statistical analysis

Data were analysed using SAS version 9.1 for Windows (SAS institute) and arepresented as means ± SD. To estimate the main effects and interactions of groupsand time, a two way analysis of variance for repeated measurements was used.When the global F-test was significant groups were compared for statistical differ-ences at each time point using LSMeans while differences within a group betweeneach measurement and the baseline were tested using the paired t test. Behaviouralfrequencies were tested for group differences by Fisher’s test and scores by Wilco-xon rank-sum test. The level of significance was set at P < 0.05.

Results

In each group we found one cow which exhibited unvarying lowplasma cortisol concentrations (<2 ng/L; close to the detectionlimit) during the entire experimental period, indicating no stress-induced response of the HPA axis. Despite affirmations of the own-ers that these animals had not been treated with glucocorticoidsprior to admission to the clinic, we concluded that the cattle couldhave received dexamethasone which can suppress the response ofthe HPA axis (Heinrich et al., 2009). Since glucocorticoids affectseveral metabolic parameters and have anti-inflammatory proper-ties these two cows were excluded from further data analysis, thusall analyses are carried out on 22 cows.

Cardio-respiratory parameters

The mean HR and RR were significantly decreased after xylazinetreatment during and after LR compared to control cows andbaseline (Table 2), whereas both parameters remained almostunchanged in the control group.

Endocrine and metabolic measures

Mean plasma concentrations of cortisol were significantly lower(P < 0.001) in xylazine treated cows after being placed in LR butwere similar to those of the controls during surgery. Postopera-tively no difference in plasma cortisol concentrations was observedbetween the groups (Table 2). Xylazine treatment induced a signif-icant elevation of mean plasma glucose concentrations over a

Table 1Clinical description of behavioural signs modified after Galindo and Broom (2002) and Molony and Kent (1997). LA, local anaesthesia; LR, lateral recumbency.

Behaviour Description (definition)

During LR Before, during and after LAEar flicking Vigorous movement of one or both of the ears independent of a head shaking (n/10 min)Head shaking All exaggerated movements of the head without any discernible reason (n/10 min).Kicking Attempts to use front or hind limbs during lying on a tipping table (n/10 min)Tail wagging Rapid tail movement from side to side (n/10 min)Vocalisation Occurrence of each vocal sound as a pain related behaviour (n/10 min)Tooth grinding Score of teeth crushing as a pain indicator (score 1: no, to 5: highly severe)During LAResponse to needle insertion Determination of pain response on venous needle insertion: score 0, nil; 5, highly severe defence reaction

Table 2Heart and respiratory rate, serum cortisol, plasma non-esterified fatty acids (NEFA), glucose, lactate, and strong ion difference (SID) (Mean ± SD) of cows following treatment withxylazine (n = 11; 0.05 mg/kg BW) and placebo (controls; n = 11, equal volume of saline) measured at baseline in the standing cow at the stable, during lateral recumbency (LR);after 15 min and at the end of surgery as well as 1 and 3 h post-operatively.

Variable Groups LR Post op. Effects

Baseline +15 min LRend +1 h +3 h

Heart rate (beats/min) Controls 81 ± 11 86 ± 17 85 ± 13 80 ± 11 80 ± 11 G 0.09Xylazine 82 ± 8 62 ± 8 68 ± 9 78 ± 8 83 ± 13 T 0.003Group difference 0.92 <0.001 <0.001 0.62 0.61 G � T <0.001

Respiratory rate (breaths/min) Controls 44 ± 13 47 ± 10 50 ± 14 42 ± 14 49 ± 18 G 0.003Xylazine 35 ± 10 20 ± 12 31 ± 16 33 ± 12 36 ± 13 T 0.025Group difference 0.11 <0.001 0.010 0.10 0.06 G � T 0.014

Cortisol (ng/mL) Controls 20.3 ± 12.2 42.1 ± 10.9 40.9 ± 23.8 9.68 ± 6.02 6.97 ± 4.90 G 0.10Xylazine 15.8 ± 10.7 17.8 ± 12.4 42.6 ± 23.5 10.3 ± 6.66 7.79 ± 5.75 T <0.001Group difference 0.37 <0.001 0.87 0.81 0.72 G � T 0.021

Glucose (mmol/L) Controls 4.38 ± 0.87 4.62 ± 1.02 4.98 ± 1.2.3 5.18 ± 1.83 4.53 ± 1.30 G 0.006Xylazine 4.64 ± 0.83 8.27 ± 2.89 8.76 ± 3.27 8.06 ± 3.04 5.37 ± 1.87 T <0.001Group difference 0.48 0.008 0.002 0.014 0.23 G � T <0.001

NEFA (lmol/L) Controls 559 ± 445 842 ± 477 840 ± 381 490 ± 310 542 ± 389 G 0.042Xylazine 448 ± 157 397 ± 105 687 ± 307 283 ± 157 234 ± 147 T <0.001Group difference 0.32 0.007 0.31 0.06 0.024 G � T 0.044

L(+)-Lactate (mmol/L) Controls 1.55 ± 0.92 1.88 ± 1.05 1.58 ± 0.95 0.81 ± 0.25 0.62 ± 0.16 G 0.08Xylazine 0.98 ± 0.40 0.85 ± 0.27 1.28 ± 1.08 0.86 ± 0.63 0.64 ± 0.41 T <0.001Group difference 0.07 0.005 0.49 0.82 0.92 G � T 0.050

SID (mEq/L) Controls 40.4 ± 2.2 41.6 ± 2.3 42.5 ± 1.6 40.1 ± 2.1 40.2 ± 1.7 G 0.15Xylazine 41.6 ± 1.8 43.9 ± 1.6 43.2 ± 2.3 41.5 ± 2.5 40.3 ± 2.7 T <0.001Group difference 0.18 0.012 0.40 0.17 0.94 G � T 0.054

2f-analysis of variance: T, time effect; G, group effect; T � G, time � group effect.Bold values differ significantly (P < 0.05) from baseline.

A. Rizk et al. / The Veterinary Journal 192 (2012) 193–198 195

period of about 1 h compared to controls (P < 0.001; Table 2). Meanplasma NEFA concentrations remained significantly lower in xyla-zine treated cows during LR and after surgery (P = 0.044; Table 2).Mean plasma lactate concentration tended to be higher in controlsduring LR compared to xylazine-treated cows (P = 0.050). In bothgroups lactate decreased significantly (P < 0.001) below baselinelevels after LR (Table 2). The mean plasma SID was increased inboth groups during LR compared to baseline (P < 0.001) and tendedtowards greater values in the xylazine-treated cows than in con-trols (P = 0.054; Table 2).

Behavioural monitoring

Mean sedation score was greater in the xylazine-treated cowscompared to controls before LR (P = 0.002), but no group differ-ences were seen after LR (Table 3). One hour after claw treatment,mean lameness score in the xylazine group was lower (P = 0.044)than in the control cows (Table 3).

In xylazine-treated cows, the evaluation of the pedometerrecordings in the first hour after claw treatment revealed a signif-icantly higher (P = 0.004) percentage of standing than in controls.The mean number of steps per min during the standing periods

was not statistically significant (P = 0.13) between the groups(Table 3).

During the insertion of the needle for LA, xylazine treated cowsexhibited a lower (P = 0.010) pain response compared to controls(Table 4). After the LA (during claw treatment) ear flicking wasnoted more often (P = 0.009) in controls than in cows of the xyla-zine group. All other behavioural indices did not differ significantlyduring the period of LR (Table 4).

On returning to their stall after claw treatment, most of thecows from the xylazine group started to consume the offered feedimmediately. In the first hour after the surgical intervention, thetime (in % of 1 h) cows spent consuming feed was numerically,but not significantly greater in xylazine treated cows comparedto controls (mean of controls ± SD: 24 ( 14; Xylazine-group39 ± 21; P = 0.07).

Discussion

In agreement with Pesenhofer et al. (2006), and as reported inour preceding study (Rizk et al., 2009), the process of being turnedand fixed in LR is perceived as stressful by cows. The stress re-sponse is reflected by a rise in plasma cortisol, glucose and NEFA

Table 3Lameness and sedation scores and results of pedometer recordings (time standing and number of steps per min; mean ± SD) of cows following treatment with xylazine (n = 11;0.05 mg/kg BW) and placebo (controls; n = 11, equal volume of saline) measured pre (baseline) in the standing cow at the stable (1 h before treatment and during moving tooperation hall), as well as 1, 2 and 3 h post-operatively.

Variable Groups Pre op. Post op. Effects

�1 h Moving to op. +1 h +2 h +3 h

Lameness (score) Controls 2.8 ± 1.0 2.7 ± 1.0 2.8 ± 0.8 3.2 ± 0.6 3.1 ± 0.9Xylazine 3.0 ± 0.9 2.5 ± 0.6 2.1 ± 0.4 3.0 ± 0.8 3.0 ± 0.8Group difference 0.56 0.51 0.044 0.84 0.85

Sedation (score) Controls 1.0 ± 0.0 2.9 ± 1.5 2.8 ± 1.0 2.5 ± 1.0 1.4 ± 0.3Xylazine 1.2 ± 0.3 5.5 ± 1.4 3.6 ± 1.0 2.8 ± 0.6 1.3 ± 0.5Group difference 0.16 0.002 0.11 0.15 0.65

Pedometer standing (%/h) Controls 51.8 ± 35.0 ND 29.5 ± 22.8 23.3 ± 21.1 32.8 ± 31.8 G 0.033Xylazine 55.9 ± 33.8 ND 61.0 ± 24.9 38.1 ± 25.8 44.1 ± 27.3 T 0.007Group difference 0.77 0.004 0.13 0.37 G � T 0.42

Steps (steps/min) Controls 1.0 ± 0.5 ND 1.0 ± 0.9 0.7 ± 0.6 0.8 ± 0.7 G 0.13Xylazine 1.0 ± 0.9 ND 1.6 ± 1.0 1.3 ± 0.9 1.2 ± 0.8 T 0.28Group difference G � T 0.37

2f-analysis of variance: T, time effect; G, group effect; T � G, time � group effect.Bold values differ significantly (P < 0.05) from baseline.Sedation was documented by a score system modified after Fierheller et al. (2004, scores 1–5, nil to very severe sedation).Lameness was scored according to Sprecher et al. (1997, scores 1–5, normal to very severe lameness).

Table 4Behavioural signs in frequencies and scores (Mean ± SD) of xylazine (n = 11; 0.05 mg/kg BW) and placebo (controls; n = 11; equal volume of saline) treated cows observedduring lateral recumbency (LR; before, during and after local anaesthesia, LA) on asurgical tipping table.

Variable Groups BeforeLA

DuringLA

After LA

Response to needleinsertionA

Controls ND 2.2 ± 0.5a ND

(score) Xylazine ND 1.3 ± 0.2b NDTeeth grindingB Controls 1.1 ± 0.3 1.3 ± 0.6 1.6 ± 0.6(score) Xylazine 1.3 ± 0.5 1.2 ± 0.4 1.3 ± 0.5Ear flicking Controls 1.1 ± 0.7 2.3 ± 1.8 1.9 ± 0.8a

(n/10 min) Xylazine 1.1 ± 0.6 1.8 ± 1.7 1.1 ± 0.3b

Head shaking Controls 1.1 ± 0.9 2.3 ± 2.1 1.6 ± 1.2(n/10 min) Xylazine 0.9 ± 0.7 2.4 ± 1.9 1.5 ± 0.7Kicking Controls 0.2 ± 0.2 0.5 ± 0.7 0.2 ± 0.4(n/10 min) Xylazine 0.3 ± 0.5 0.2 ± 0.2 0.3 ± 0.3Tail wagging Controls 0.4 ± 0.5 1.6 ± 1.6 0.6 ± 0.6(n/10 min) Xylazine 0.3 ± 0.3 1.1 ± 0.8 0.7 ± 0.8Vocalisation Controls 0.1 ± 0.1 0.6 ± 0.9 0.2 ± 0.2(n/10 min) Xylazine 0.4 ± 0.5 0.6 ± 1.0 0.4 ± 0.4

Means with different superscripts differ significantly (P < 0.05) among groups.ND, not determined.

A Response to intravenous needle insertion for regional IV local anaesthesia:scores 1–5, none to very severe response.

B Teeth grinding: scores 1–5, none to very severe.

196 A. Rizk et al. / The Veterinary Journal 192 (2012) 193–198

concentrations (Chacon et al., 2005; Mudron et al., 2005) duringLR. The significantly higher mean plasma glucose concentrationsin xylazine treated cows during LR and thereafter are also mostlikely due to xylazine-mediated inhibition of insulin release byactivation of a2-receptors on pancreatic ß-cells (Hsu and Hummel,1981).

In this study, the two main stressors the animals were con-fronted with were handling and pain (Ley et al., 1991; Heinrichet al., 2009). Hence, the results of the cortisol response indicatethat xylazine pre-treatment can prevent the handling stress duringpainless procedures (LR, claw trimming, and diagnostic investiga-tions), yet even when combined with LA, is does not abolish thepain associated with claw surgery. This is not surprising, as it isknown that strong stimulation of nociceptors during the surgicalclaw treatment leads to a direct release of cytokines into the blood-stream which subsequently triggers an endocrine stress response(Imura et al., 1991; Desborough, 2000).

Thus, even though regional IV anaesthesia is regarded as themost effective analgesic regime in surgeries on the distal limb incattle (Antalovsky, 1965), and the analgesic effect of xylazine hasbeen demonstrated in cattle (Lee and Yamada, 2005), the surgicalstress response with subsequent stimulation of the HPA-axis can-not be completely suppressed by the synergistic effect of local ana-esthetics and xylazine (McQuay et al., 1999).

Despite the controversies regarding the value of behaviouralparameters in the assessment of pain in stoical animals such as cat-tle, its use as an addition to metabolic and endocrine data is ac-cepted and applied in many studies evaluating the analgesiceffectiveness of drugs (Molony and Kent, 1997; Galindo andBroom, 2002). The behavioural alterations found in this study(e.g. reduced pain response during the insertion of the needle forLA, less frequent ear flicking during claw surgery, lower lamenessscores and longer standing periods during the first hour after clawtreatment and more common occurrence of immediate feed con-sumption when cows arrived back in their stall) indicate less painperception and improved well-being of the xylazine treated cows(Lin and Riddell, 2003; Laven et al., 2008).

Even though the longer standing periods may possibly be inter-preted as a reluctance of animals to lie down as a result of the seda-tion, there is no evidence for such behaviour, especially when theanimals are back in their familiar surroundings. For other behav-ioural parameters such as teeth grinding, head shaking, kicking, tailwagging and vocalisation, only subtle, non-significant group differ-

ences were noted between xylazine-treated animals and controls.In our experience and that of Molony and Kent (1997) cows whichare used to human contact and handling only exhibit these behav-ioural responses after being exposed to severely painful procedureswithout prior appropriate analgesia.

The stress-provoked cortisol and catecholamine release com-monly induces lipolysis and thereby increased plasma NEFA con-centrations (Chacon et al., 2005; Mudron et al., 2005). Inagreement with a previous study, where cows also experienced astress challenge by fixation in LR, plasma NEFA concentrations re-mained significantly lower during and after LR after xylazine pre-treatment. The suppression of stress-induced lipolysis may bemediated by both central and peripheral a2-adrenoceptors as pre-viously reported for calves (Scholtysik et al., 1998), dogs (Ambriskoand Hikasa, 2002), cats (Kanda and Hikasa, 2008), and humans(Vikman et al., 1996). This effect of xylazine may be of particularimportance in early lactation when cows frequently exhibit en-

A. Rizk et al. / The Veterinary Journal 192 (2012) 193–198 197

hanced lipomobilisation and are prone to the development of fattyliver (Drackley, 1999).

In the present study cows treated with xylazine showed signif-icantly lower mean HR and RR during LR compared to baseline andcontrols. This is in accordance with other studies where thedepressive effect of a2-agonists on cardio-respiratory functionwas demonstrated (Picavet et al., 2004; Nandi et al., 2008); a2-ago-nists also lead to dose dependent reduced cardiac output, reducedmean arterial blood pressure, increased vascular resistance, de-creased arterial oxygen partial pressure and saturation and to in-creased arterial partial pressure of carbon dioxide (Meyer et al.,2010). Similar effects on cardio-respiratory depression are pro-voked by LR (Wagner et al., 1990; Tagawa et al., 1994; Rizk et al.,2009). In a previous study it was demonstrated that a low doseof xylazine (0.05 mg/kg BW) aggravates the effects of LR on respi-ratory depression and that arterial oxygen saturation can drop be-low the critical value of 92% (Wagner et al., 1990). It appears likelythat the increased mean SID, which was seen particularly in xyla-zine-treated cows during LR, reflects metabolic compensation ofthe presumed increase in the arterial partial pressure of carbondioxide (Constable, 1999).

Small increases in blood lactate concentration have been previ-ously reported in cattle undergoing surgery. These have beenattributed to stress-induced vasoconstriction and reduced tissueoxygenation (El-Ghoul and Hofmann, 2002; Mudron et al., 2005).However, in contrast to our previous work, in the present studyplasma lactate concentrations did not increase significantly duringthe stress induced by LR and claw treatment, and plasma lactateremained lower in cows treated with xylazine than in controls.Thus, we have no indication of reduced tissue oxygenation in cowsof either group in this study. However, as xylazine treatment with0.05 mg/kg BW aggravates the respiratory depression induced byLR (Rizk et al., 2009), we believe that before higher xylazine dosesare used for cows undergoing claw surgeries in LR a more thoroughinvestigation of the dose related effects of xylazine on respiratorydepression should be undertaken.

Conclusions

Pre-emptive treatment with 0.05 mg/kg BW xylazine reducedthe hormonal and metabolic stress response and had short termmild analgesic effects when given prior to surgical treatment oflame cows in LR. Thus, xylazine appears to be an appropriate sed-ative for stress alleviation in cows placed in LR and can be used asan analgesic in a multimodal analgesic protocol for claw surgery.We believe that the benefits of sedation and analgesia outweighthe mild cardio-respiratory depression resulting from low dosexylazine.

Conflict of interest statement

The study was initiated by the authors and, upon request,financially supported by Bayer-Animal Health Care, Leverkusen,Germany. Bayer-Animal Health Care had no influence on study de-sign, evaluation and interpretation of results and manuscriptcomposition.

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