Journal of Feline Medicine & Surgery Volume Issue 2015 [Doi 10.1177%2F1098612X15598550] Bruniges,...

8162019 Journal of Feline Medicine amp Surgery Volume Issue 2015 [Doi 1011772F1098612X15598550] Bruniges N Taylorhellip

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Journal of Feline Medicine and Surgery

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DOI 1011771098612X15598550

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IntroductionThe Royal Society for the Prevention of Cruelty to

Animals Greater Manchester Animal Hospital (GMAH)performs approximately 1500 cat castrations per annum(D Yates unpublished data) Anaesthetic protocols thatreduce recovery time are beneficial as the period whenclose monitoring is required is shorter and postanaes-thetic hypothermia1 as well as the risk of anaestheticmortality in the postoperative period2 are reducedRapid recovery would also benefit hospital management by enabling earlier postsurgical discharge reducing stafftime in monitoring recovery and potentially allowing ahigher daily intake of cats for neutering

A further consideration facing cat shelter neutering

programmes is the need for surgery on very young

animals Up to 80 of cat litters in the UK are unplanned3 In an effort to improve cat population control and pre-

vent unwanted litters it is recommended that prepuber-tal gonadectomy is performed in kittens⩽6 months old4 lsquoPaediatricrsquo can be considered aslt6 months old in termsof metabolic differences and analgesic requirements5

Injectable anaesthesia for adultcat and kitten castration effects ofmedetomidine dexmedetomidine

and atipamezole on recovery

Natalie Bruniges1 Polly M Taylor2 and David Yates3

AbstractObjectives Rapid recovery from injectable anaesthesia benefits cat shelter neutering programmes The effects

of medetomidine dexmedetomidine and atipamezole on recovery were evaluated in adult cats and kittens

(⩽

6 months old)Methods One hundred healthy male cats (age range 2ndash66 months weight range 07ndash53 kg) admitted for

neutering were randomly allocated to groups of 25 Anaesthesia was induced with 60 mgm2 ketamine 180 microgm2

buprenorphine 3 mgm2 midazolam and either 600 microgm2 medetomidine (groups M and MA) or 300 microgm2

dexmedetomidine (groups D and DA) intramuscularly (IM) Groups MA and DA also received 15 mgm2 atipamezole IM

after 40 mins Preparation time surgical time and times to sternal recumbency and standing were recorded Data were

analysed using the KruskallndashWallis test unpaired t -tests and ANOVA Statistical significance was deemed to be P ⩽005

Results Groups did not differ significantly in age body weight preparation or surgical time The time to sternal

recovery in group MA (64 983217 34 mins) was less than in group M (129 983217 32 mins) and in group DA it was less than

in group D (54 983217 6 mins vs 110 983217 27 mins) (P lt0001) There were no differences in duration of recovery to sternal

recumbency between groups M and D or MA and DA The time to standing in group MA (79 983217 51 mins) was less

than in group M (150 983217 38 mins) (P lt0001) and in group DA it was less than in group D (70 983217 22 mins vs 126983217 27

mins) (P lt001) Time to standing in group D (126 983217 27 mins) was less than in group M (150 983217 38 mins) (P lt005)

Time to standing in groups DA and MA were not different Kittens recovered faster than adults after atipamezoleMinimal adverse effects were seen

Conclusions and relevance Atipamezole reliably reduced recovery time after anaesthesia incorporating either

dexmedetomidine or medetomidine however the choice of dexmedetomidine or medetomidine had little effect

Recovery was faster in kittens

Accepted 8 July 2015

1 Small Animal Teaching Hospital Neston UK2 Taylor Monroe Gravel Head Farm Ely UK3 RSPCA Greater Manchester Animal Hospital Salford UK

Corresponding author

Natalie Bruniges BSc BVSc MRCVS Anaesthesia Department

Small Animal Teaching Hospital Leahurst Campus Chester High

Road Neston CH64 7TE UK

Email nbrunigeshotmailcouk

JFM001011771098612X15598550Journalof FelineMedicineand SurgeryBruniges et al

Original Article

at UNIV OF LETHBRIDGE on October 16 2015 jfmsagepubcomDownloaded from



2 Journal of Feline Medicine and Surgery

There are important physiological differences betweenkittens (lsquopaediatricsrsquo) and adult cats that warrant consid-eration for anaesthesia for elective prepubertal neuter-ing Paediatric physiology and its implications for kittenanaesthesia include limited cardiovascular compensa-tion higher relative tissue oxygen consumption and a

higher body surface area to mass ratio resulting in ahigher risk of hypothermia under anaesthesia4 Cardiacoutput is predominantly dependent on heart rate in pae-diatrics owing to a higher proportion of non-contractiletissue and hence a predetermined stroke volume46 Paediatric animals also have an immature sympatheticnervous system7 These factors will affect the choice ofanaesthetic protocol for paediatrics that have limitedcapacity to compensate for drug-induced bradycardiaand are therefore likely to develop hypotension particu-larly with α2-adrenoceptor agonists and opioids47 Additionally as tissue oxygen consumption is increasedin paediatrics it is recommended that oxygen is pro-vided throughout surgery even if anaesthetic depth isadequate without inhalational gases47 Other pharmaco-logical considerations for paediatric anaesthesia includehypoalbuminaemia which may enhance the effects ofhighly protein-bound drugs such as propofol anddiazepam and immature hepatic enzyme systemswhich may reduce the rate of drug metabolism46 Benzodiazepines stimulate appetite and their use duringanaesthesia may promote feeding on recovery8 This isparticularly valuable in kittens in helping to preventhypoglycaemia and hypothermia4 In spite of the appar-ent physiological disadvantage there is recent evidence

that kittens demonstrated fewer behavioural signs ofpain and a faster return to normal behaviour postneuter-ing than adult cats supporting the move towards pro-grammes for kitten neutering9

Injectable anaesthetic protocols incorporatingα2-adrenoceptor agonists are frequently used for neuteringprogrammes in both feral and domestic cat popula-tions41011 Medetomidine the 11 racemic mixture of theD-isomer dexmedetomidine and the L-isomer levome-detomidine has been widely used in cats since its intro-duction in 199412 Several studies have demonstratedthat only the D-isomer is pharmacologically active at

clinically relevant doses and that levomedetomidine hasno biological activity13ndash15 However in vitro studiesshowed that the L-isomer possesses weak partial α2-adrenoceptor agonist or inverse α2-adrenoceptor agonist(negative antagonist) properties1617 Therefore the phar-macological activity of levomedetomidine in a clinicalsetting is unclear It has been suggested that the absenceof levomedetomidine from commercial formulations ofdexmedetomidine may provide more predictable anal-gesia and sedation than the racemic mixture15

A number of studies have compared the sedative andphysiological effects of medetomidine and dexmedeto-midine in dogs and cats One investigation in 212

client-owned dogs demonstrated that medetomidineand dexmedetomidine produced comparable levels ofsedation and analgesia but there was some suggestionthat analgesia was marginally better with dexmedetomi-dine12 The same authors performed a study in 120 cli-ent-owned cats and concluded that medetomidine and

dexmedetomidine (at half the medetomidine dose) pro-duced similar sedation and analgesia18 They alsoreported that atipamezole fully reversed the clinicaleffects of dexmedetomidine18 These results are in agree-ment with an earlier laboratory study in cats comparingthree intramuscular (IM) doses of dexmedetomidinewith medetomidine at twice the respective dose (dexme-detomidine 25 50 and 75 microgkg medetomidine 50 100and 150 microgkg) which found that dexmedetomidineproduced pharmacodynamic effects equal to those ofmedetomidine in cats19 This study concluded that theanaesthetic effects of medetomidine were most likelydue to its dexmedetomidine isomer

With particular relevance to anaesthesia of kittens both medetomidine and dexmedetomidine negativelyaffect regulation of body temperature which may delayrecovery time especially in younger animals2021 Bothmedetomidine and dexmedetomidine may cause a rela-tive hyperglycaemia during anaesthesia by reducingendogenous insulin secretion2223 Prevention of hypo-glycaemia is important as this could contribute to pro-longed recovery424

Our study had three objectives firstly to comparerecovery times following medetomidine or dexmedeto-midine when included in an established injectable gen-

eral anaesthetic protocol for feline castration secondlyto determine if inclusion of atipamezole altered therecovery time and thirdly if recovery times of the abovewere varied in paediatric vs adult patients

Materials and methodsThe study was approved by the Animal Health TrustClinical Research Ethics Committee and writteninformed owner consent was obtained in all cases Onehundred entire male cats of any age (minimum 300 g body weight) or breed that were presented to GMAH forcastration on four predesignated days in July 2013 were

included A full clinical examination was carried out onall cats at admission to ensure that they were healthy(American Society of Anesthesiologistsrsquo classification Ior II) Any sick animals cryptorchid males and allfemales admitted for neutering on these predesignateddates were excluded

The anaesthetic protocol was based on the GMAHlsquoquadrsquo anaesthetic protocol for prepubertal cat neuteringdosing according to body surface area (BSA) 60 mgm2 ketamine (Ketaset Zoetis) 180 microgm2 buprenorphine(Vetergesic Alstoe UK) 3 mgm2 midazolam (HypnovelRoche) and 600 microgm2 medetomidine (Domitor ElancoAnimal Health)425 This equates to equal volumes of




Bruniges et al 3

each agent given in a single IM injection to induce anaes-thesia BSA was calculated as follows BSA 983101 (K 983255 BW23)100 where BSA is measured in m2 bodyweight(BW) in kg and K983101 104 (cats)4

Cats were randomly allocated into four groups of 25using wwwrandomizerorgformhtm as follows group

M ndash lsquoquadrsquo with 600 microgm2 medetomidine (Domitor1 mgml Elanco Animal Health) group MA ndash lsquoquadrsquo with600 microgm2 medetomidine and 15 mgm2 atipamezole(Antisedan Elanco Animal Health) 40 mins later group Dndash lsquoquadrsquo with 300 microgm2 dexmedetomidine in place ofmedetomidine (Dexdomitor 05 mgml Elanco AnimalHealth) group DA ndash lsquoquadrsquo with 300 microgm2 dexmedeto-midine in place of medetomidine and 15 mgm2 atipam-ezole 40 mins later

The four drugs in the lsquoquadrsquo protocol were mixed inone syringe immediately before administration into thequadriceps muscle Surgery began as soon as anaestheticdepth was considered sufficient using normal clinicalcriteria Although the lsquoquadrsquo protocol provides multi-modal analgesia in the form of medetomidine (or dex-medetomidine) ketamine and buprenorphine all catsadditionally received 3 mgm2 meloxicam (MetacamBoehringer Ingelheim) and 02 mlkg long-acting amox-icillin (Betamox LA Norbrook) subcutaneously immedi-ately after induction

Oxygen was provided via mask inhalation using aninfant T-piece at 400 mlkgmin throughout the proce-dure and surgery was performed on an operating tablepreheated to 37 ordmC Isoflurane was administered if anaes-thesia was insufficient Bilateral scrotal incisions were

made and open castration was performed Scrotal skinincisions were left to heal by secondary intention Thesurgical procedure was very short (generally lt3 mins)and anaesthetic monitoring was restricted to observa-tion of vital signs (respiration mucous membrane colourand adequacy of anaesthesia) without formal recording

Time of the lsquoquadrsquo injection was recorded as well aspreparation time (time from injection to commencingsurgery) total surgical time (from first scrotal incision toremoval of second testis) time to first sternal recumbency and time to first standing Cats in groups MA andDA received IM atipamezole 40 mins after the initial

injection of the lsquoquadrsquo and cats in groups M and D wereallowed to recover spontaneously Artificial tears(Viscotears Novartis) were applied to the eyes to pre-vent corneal drying All cats were allowed to recover inindividual kennels preheated to 37ordmC once in sternalrecumbency the temperature was reduced to 25ordmC andfood was offered

One veterinary surgeon prepared and administeredthe anaesthetics (DY) and a second (NB) performed allthe surgeries throughout the study Recovery was moni-tored and recorded by a member of the hospital nursingstaff under the direction of the anaesthetising vet The

treatment group allocation was not revealed to the nurs-ing staff or the surgeon

Statistical analyses

Data are described as mean983217 SD unless otherwise statedThe treatment groups were compared as follows groupM with MA group M with D group MA with DA andgroup D with DA ANOVA and post-hoc Tukeyrsquos testwere used to compare normally distributed data that ispreparation time KruskallndashWallis and post-hoc Dunnrsquosmultiple comparisons were used for the remaining datathat were not normally distributed Recovery time in kit-tens (⩽6 months old) was compared with adults(gt6 months old) within each group using unpaired

t-tests Statistical significance was set at P ⩽

005 Statisticalanalyses were performed using GraphPad Prism version60b for Mac

Power calculations (GraphPad Statmate 2) were basedon data previously collected in the clinic These indi-cated that 25 cats per group would give 80 power todetect a difference of 20 mins in recovery time

ResultsThe majority (95) of the cats presented for castrationwere domestic shorthair or longhair cats and 5 werepedigree breeds (two Ragdolls two Tonkinese and one

Havana) Overall mean age was 135 months (range80 weeks minus55 years) Details of abnormalities detectedat preanaesthetic examination are shown in Table 1 (allcases were included in the study)

Demographic data including mean 983217 SD age body-weight and BSA for the study cats is shown in Table 2There was no significant difference in age or bodyweightof cats between the groups Mean 983217 SD preparationtime surgery time injection to sternal recumbency andinjection to first standing times are shown in Table 3There was no significant difference in preparation timeor surgical time between the groups

Table 1 Abnormalities detected in study cats during thepreanaesthetic examination

Illnessinjury Cats affected (n)

Gingivitis 1

Cat bite abscesswound 3

Mild diarrhoea 3Mucoid conjunctivitis 2

Systolic heart murmur 1

Long bone fracture 1

Degloving paw injury 1

FIV positive on FASTest 3

Fleasflea dirt 20

FASTest (Megacor)

FIV 983101 feline immunodeficiency virus





Time to sternal recumbency in group MA (64983217 34 mins)was significantly shorter than in group M (129983217 32 mins)and significantly shorter in DA (54 983217 6 mins) thanin group D (110 983217 27 mins) (P lt0001) There was no

significant difference in time to sternal recumbency between groups M and D nor between groups MAand DA Time to first standing in group MA (79983217 51 mins)was significantly shorter than in group M (150983217 38 mins)(P lt0001) and significantly shorter in group DA (70 983217 22mins) than in group D (126 983217 27 mins) (P lt001) Meantime to first standing in group D (126 983217 27 mins) wassignificantly shorter than in group M (150 983217 38 mins)(P lt005) Time to standing in groups DA and MA wasnot significantly different (Figure 1) None of the cats ingroups MA or DA reached sternal recumbency beforeadministration of atipamezole

Forty-one of the cats were⩽

6 months old eight werein group M 13 were in group MA nine were in group Dand 11 were in group DA Of these 41 cats three hadmild diarrhoea within 10 mins of IM injection one vom-ited on induction one twitched the hindlimbs slightlyafter the first incision (no isoflurane required) and one ofthe kittens with diarrhoea required isoflurane because ofpurposeful hindlimb movement and pedal withdrawalreflex No adverse effects were reported in the remaining36 cats and all 41 recovered uneventfully

Mean 983217 SD times to sternal recumbency and firststanding between kittens ⩽6 months old and cats gt6

months in each group are shown in Table 4 Kittens reachedsternal recumbency in group DA sooner (51 983217 5 mins)than adults (57 983217 5 mins) (P 983101 0017) Time to sternalrecumbency was not different in the other groups

(P 983101 08099 in group M P 983101 01416 in group MA andP 983101 06859 in group D) Kittens in group MA stoodsooner (56 983217 8 mins) than adults (103 983217 67 mins)(P 983101 0002) but there was no difference in the othergroups (P 983101 04319 in group M P 983101 02305 in group Dand P 983101 01338 in group DA)

Adverse effects and complications that occurred dur-ing anaesthesia or surgery are reported in Table 5 Themost common adverse effect during this study was vom-iting within 5 mins of anaesthetic injection (5 inci-dence) despite the recommendation of an overnightfast Animals that vomited were equally distributed between the groups One cat developed a small scrotalhaematoma postoperatively but recovered uneventfullyand was discharged that evening with no further prob-lems No lasting side effects or complications were notedin any of the cats after recovery from general anaesthesiaand all were discharged the same day

DiscussionThis study fulfilled our first two aims of evaluating theeffects on recovery of incorporating medetomidine dex-medetomidine or atipamezole into the lsquoquadrsquo protocolIn this study atipamezole markedly reduced recovery

Table 2 Patient variables measured for each of the four treatment groups

Group (n 983101 25)

Patient variable M MA D DA

Age (months) 14 983217 13 13 983217 14 15 983217 15 13 983217 16

Bodyweight (kg) 32 983217 13 27 983217 14 32 983217 11 29 983217 14BSA (m2) 022 983217 007 019 983217 007 022 983217 005 021 983217 007

Data are mean 983217 SD

Group M 983101 quad with medetomidine no atipamezole group MA 983101 quad with medetomidine atipamezole after 40 mins group D 983101 quad with

dexmedetomidine no atipamezole group DA 983101 quad with dexmedetomidine atipamezole after 40 mins BSA 983101 body surface area

Table 3 Study variables measured for each of the four treatment groups

Group (n 983101 25)

Study variable M MA D DA

Preparation time (mins) 16983217

4 15983217

4 17983217

3 16983217

5Surgery time (mins) 24 983217 06 27 983217 08 25 983217 07 26 983217 08

Injection to sternal (mins) 129 983217 32 64 983217 34 110 983217 27 54 983217 6

Injection to standing (mins) 150 983217 38 79 983217 51 126 983217 27 70 983217 22



dexmedetomidine no atipamezole group DA 983101 quad with dexmedetomidine atipamezole after 40 mins




Bruniges et al 5

times but only minor differences were detected betweenthe effects of medetomidine and dexmedetomidineThere was also a trend towards faster recoveries in cats⩽6 months old than in adults fulfilling our third aim ofevaluating recovery in paediatric animals and furtherallaying some of the apprehension concerning anaesthe-sia of kittens for prepubertal neutering

Atipamezole was administered only after 40 mins toallow the effect of ketamine to abate This was in accord-ance with the Ketaset (Zoetis) datasheet which recom-mends that atipamezole is administered 45 mins afterinduction when using medetomidine in combinationwith ketamine and butorphanol This is expected toensure a smooth recovery26

Previous studies have focused on clinical efficacy andsafety of dexmedetomidine in cats and have measuredsedation analgesia and muscle relaxation as well asmonitoring heart rate respiratory rate and rectal

Figure 1 Time (mins mean 983217 SD) to (a) sternal recumbency and (b) standing after intramuscular injection of the lsquoquadrsquo

anaesthetic Mean 983217 SD shown for illustration only Analysis performed using non-parametric methods Significant difference

between groups joined by brackets (P lt005 P lt001 P lt0001) Group M 983101 quad with medetomidine no atipamezole

group MA 983101 quad with medetomidine atipamezole after 40 mins group D 983101 quad with dexmedetomidine no atipamezole

group DA 983101 quad with dexmedetomidine atipamezole after 40 mins

Table 4 Time to sternal recumbency and time to first standing for cats ⩽6 months old and cats gt6 months old in eachof the four treatment groups

Group Time to sternal (mins) Time to standing (mins)

⩽6 months old gt6 months old ⩽6 months old gt6 months old

M 127 983217 36 (n 983101 8) 130 983217 31 (n 983101 17) 141 983217 32 (n 983101 8) 155 983217 41 (n 983101 17)

MA 54 983217 8 (n 983101 13) 74 983217 47 (n 983101 12) 56 983217 8 (n 983101 13) 103 983217 67 (n 983101 12)

D 107 983217 37 (n 983101 9) 112 983217 20 (n 983101 16) 117 983217 38 (n 983101 9) 131 983217 18 (n 983101 16)

DA 51 983217 5 (n 983101 11) 57 983217 5 (n 983101 14) 62 983217 19 (n 983101 11) 75 983217 23 (n 983101 14)

Data are mean 983217 SDSignificant difference (P lt005) between kittens and cats in that treatment group


dexmedetomidine no atipamezole group DA 983101 quad with dexmedetomidine atipamezole after 40 mins n 983101 number of cats within each age

bracket in each group

Table 5 Adverse effectscomplications reported in studycats

Adverse effect complication

Catsaffected (n)

Treatment group(s)of affected cats

Vomiting 5 MA MA D DA DA

Diarrhoea 3 MA D D

Hindlimb twitchafter incision

3 M DA DA

Ataxia on standing 2 MA MA

Requirement for

isoflurane

1 D

Scrotal haematoma 1 DA

Panting during

recovery

1 DA

Group M 983101 quad with medetomidine no atipamezole group MA

983101 quad with medetomidine atipamezole after 40 mins group D 983101

quad with dexmedetomidine no atipamezole group DA 983101 quad with

dexmedetomidine atipamezole after 40 mins





temperature after administration18192728 The aim of ourstudy was to focus on the effect of the two isomers andatipamezole on recovery times There was some sugges-tion from our results that replacing medetomidine withdexmedetomidine in the lsquoquadrsquo reduced recovery timeMean time to sternal was reduced by 19 mins (without

atipamezole) and 10 mins (with atipamezole) Meantime to standing was reduced by 24 mins (without ati-pamezole) and 9 mins (with atipamezole) Howeveronly time to standing without atipamezole was signifi-cantly different The study had 80 power to detect areal difference in time to sternal and to standing of20 mins and was therefore underpowered to establishwhether the difference in recovery time to sternal wasreal Although shortening the recovery time by approxi-mately 20 mins using dexmedetomidine could be benefi-cial a reduction of much less than this seems unlikely tohave obvious clinical benefit A larger study may haveanswered the question of whether time to sternal wasreally shorter with dexmedetomidine but would haveadded little to the clinical relevance Regardless ofwhether dexmedetomidine or medetomidine was usedatipamezole reduced recovery times by approximately1 h in this study Clearly this has more clinical relevancethan the difference between medetomidine and dexme-detomidine Shorter recovery time reduces the durationof anaesthesia thereby reducing the risk of anaesthesia-related mortality the postoperative period has beenidentified as the most common point of anaesthetic-related mortality particularly within the first 3 h aftersurgery2

The results from this investigation concur with find-ings in earlier studies that atipamezole is effectivewhether or not levomedetomidine is present with dex-medetomidine12 Previous studies have demonstratedalmost identical clinical effects of dexmedetomidine andmedetomidine and so it would be logical to expectrecovery time to be similar as demonstrated in the pre-sent study18 However Granholm et al suggested thatalthough levomedetomidine is pharmacologically inac-tive its presence in racemic medetomidine might impactupon both the pharmacodynamic and pharmacokineticeffects of dexmedetomidine18 They reported that 90ndash180 mins

after IM administration cats given dexmedetomidine(without atipamezole) overall had higher heart rates andmore normal pulse characteristics than those receivingmedetomidine Additionally once peak effect had devel-oped the analgesia and sedation scores were consist-ently lower for dexmedetomidine than medetomidine18 Although none of these differences were statistically sig-nificant Granholm et al suggested that these data mayhave clinical relevance as they might reflect a differencein metabolism and hence a faster recovery after the peakeffect from dexmedetomidine compared to medetomi-dine18 It is conceivable that the trend for faster recovery

after dexmedetomidine found in our study may have been a result of differences in metabolism between dex-medetomidine and the racemic mixture

Adverse effects were limited and none was life threat-ening Vomiting at induction of general anaesthesia wasthe most frequent adverse event with an incidence of

5 Vomiting and nausea are commonly reported sideeffects in cats after administration of α2-adrenoceptoragonists due to central sensitisation of the area pos-trema29 The incidence in this study was much lowerthan previously reported after dexmedetomidine incats2830 The reason for this is unknown but could be aresult of the lower doses of α2-adrenoceptor agonistsused in this study compared with others Fasting priorto general anaesthesia was requested for all cats inthis study but there is little firm evidence to date to sug-gest that withholding food affects the incidence ofα2-adrenoceptor agonist-induced vomiting in cats28

Almost half of the cats in the present study were⩽6 months old They were randomly allocated betweenthe four treatment groups and there was no evidencethat they were more adversely affected than the adultsoverall Of the 16 reported occurrences of adverse effectsin this study only six occurred in cats ⩽6 months oldAdditionally their recovery time was consistentlyshorter than in adults reaching significance in bothgroups given atipamezole Adverse effects occurring inthe younger animals ndash vomiting diarrhoea requirementfor isoflurane and hindlimb twitching ndash were of too lowan incidence to associate with any drug protocol Threehad diarrhoea after induction and one of these three was

the only animal in the study to require isoflurane due toinadequate anaesthetic depth Of the three cats withdiarrhoea one was in group MA and two were fromgroup D The two in group D were 14-week-oldTonkinese kittens from the same litter with a previoushistory of diarrhoea so this was probably unrelated tothe anaesthetic It is not clear why the one cat neededisoflurane the most likely explanation is that it did notreceive its full lsquoquadrsquo dose IM It is unlikely that one catreceiving 1 isoflurane for 3 mins would affect the meanrecovery time of the group Isoflurane is rapidly exhaledand had little time for accumulation in the body31

Additionally this catrsquos recovery to both sternal recumbency and standing fell within 2 SD of the group meanPrevious studies evaluating medetomidine and dex-

medetomidine in cats all report a decrease in body tem-perature181927 This is due to both decreased heatproduction with reduced muscle activity and to thedirect effects of α2-adrenoceptor agonists on thermoreg-ulation20 This highlights the importance of maintaining body temperature during and after procedures usingthese drugs Body temperature was not measured in thisstudy and its contribution to recovery time is unknownHowever preheated operating tables and recovery




Bruniges et al 7

kennels were used for all cats in an attempt to preventhypothermia throughout anaesthesia and to minimisethe effect of this variable on recovery time Surgical andhence anaesthetic time another potential variable thatwould affect recovery time was kept consistent byincluding only routine cat castrations in the study

Two cats in the study had pre-existing pathologicalconditions a fractured tibia and a forelimb deglovinginjury respectively which both required examinationand application of supportive dressing under anaesthe-sia These injuries may have delayed time to standing but exclusion of their data did not affect the results ofstatistical analysis Both of these cats were randomlyallocated to group DA Recovery time to sternal recumbency and standing in the cat with the fractured tibiafell within 2 SD of the group mean but recovery time tostanding in the cat with the degloving injury waslonger

ConclusionsAtipamezole given 40 mins after induction of anaesthe-sia with the lsquoquadrsquo combination significantly reducedrecovery time when either medetomidine or dexme-detomidine were incorporated in the protocol Replacingmedetomidine with dexmedetomidine had limitedeffect on the duration of recovery Overall there was atrend towards faster recovery in kittens compared withadults particularly when atipamezole was used thusproviding some evidence to assuage concerns regardingfeline paediatric anaesthesia Further studies to assessalternative timing and dosage of atipamezole would be

worthwhile

Conflict of interest The authors do not have any potential

conflicts of interest to declare

Funding This research received no specific grant from any

funding agency in the public commercial or not-for-profit sec-

tors

References 1 Redondo JI Suesta P Gil L et al Retrospective study of

the prevalence of postanaesthetic hypothermia in cats Vet

Rec 2012 170 206

2 Brodbelt DC Blissit KJ Hammond RA et al The risk ofdeath the confidential enquiry into perioperative small

animal fatalities Vet Anaesth Analg 2008 35 365ndash373

3 Welsh CP Gruffydd-Jones TJ Roberts MA et al Poor

owner knowledge of feline reproduction contributes to

the high proportion of accidental litters born to UK pet

cats Vet Rec 2014 174 118

4 Joyce A and Yates D Help stop teenage pregnancy Early-

age neutering in cats J Feline Med Surg 2011 13 3ndash10

5 Mathews KA Analgesia for the pregnant lactating and

neonatal to pediatric cat and dog J Vet Emerg Crit Care

2005 15 273ndash284

6 Holden D Paediatric patients In Seymour C and Duke-

Novakovski T (eds) BSAVA manual of canine and feline

anaesthesia and analgesia 2nd ed Gloucester British Small

Animal Veterinary Association 2007 pp 296ndash302

7 Grandy JL and Dunlop CI Anesthesia of pups and kittens J Am Vet Med Assoc 1991 198 1244ndash1250

8 Morris HV Nilsson S Dixon CI et al Alpha 1- and alpha-2

containing GABA receptor modulation is not necessaryfor benzodiazepine-induced hyperphagia Appetite 2009

52 675ndash683

9 Polson S Taylor PM and Yates D Effects of age and repro-

ductive status on postoperative pain after routine ovario-

hysterectomy in cats J Feline Med Surg 2014 16 170ndash176

10 Williams LS Levy JK Robertson SA et al Use of the anes-

thetic combination of tiletamine zolazepam ketamine

and xylazine for neutering feral cats J Am Vet Med Assoc

2002 220 1491ndash1495

11 Harrison KA Robertson SA Levy JK et al Evaluation of

medetomidine ketamine and buprenorphine for neuter-

ing feral cats J Feline Med Surg 2011 13 896ndash902

12 Granholm M McKusick BC Westerholm FC et al Evalu-ation of the clinical efficacy and safety of intramuscular

and intravenous doses of dexmedetomidine and medeto-

midine in dogs and their reversal with atipamezoleVet Rec 2007 160 891ndash897

13 Virtanen R Savola JM Saano V et al Characterization of

the selectivity specificity and potency of medetomidine

as an α2-adrenoreceptor agonist Eur J Pharmacol 1988 150

9ndash14

14 Savola JM and Virtanen R Central α2-adrenoreceptors are

highly stereoselective for dexmedetomidine the dextro

enantiomer of medetomidine Eur J Pharmacol 1991 195

193ndash199

15 Kuusela E Raekallio M Antilla M et al Clinical effects

and pharmacokinetics of medetomidine and its enantio-mers in dogs J Vet Pharmacol Ther 2000 23 15ndash20

16 Jansson CC Marjamaumlki A and Luomala K Coupling of

humanα2-adrenoreceptor subtypes to regulation of cAMP

production in transfected S115 cells Eur J Pharmacol 1994

266 165ndash174

17 Jansson CC Kukkonen JP and Naumlsman J Protean agonism

at α2-adrenoreceptors Mol Pharmacol 1998 53 963ndash968

18 Granholm M McKusick BC Westerholm FC et al Evalu-

ation of the clinical efficacy and safety of dexmedeto-

midine in cats and their reversal with atipamezole Vet

Anaesth Analg 2006 33 214ndash223

19 Ansah OB Raekallio M and Vainio O Comparison of three

doses of dexmedetomidine with medetomidine in catsfollowing intramuscular administration J Vet Pharmacol

Ther 1998 21 380ndash387

20 MacDonald E Scheinin H and Scheinin M Behavioural

and neurochemical effects of medetomidine a novel vet-

erinary sedative Eur J Pharmacol 1988 158 119ndash127

21 Clarke-Price S Inadvertent perianesthetic hypothermia in

small animal patients Vet Clin Small Anim Epub ahead of

print 23 May 2015 DOI 101016jcvsm201504005

22 Ambrisko TD and Hikasa Y Neurohormonal and meta-

bolic effects of medetomidine compared with xylazine in

beagle dogs Can J Vet Res 2002 66 42ndash49





23 Ghimire LV Muszkat M Sofowora GG et al Variation

in the α(2A) adrenoceptor gene and the effect of dexme-

detomidine on plasma insulin and glucose Pharmacogenet

Genomics 2013 23 479ndash486

24 Sinclair RCF and Faleiro RJ Delayed recovery of con-

sciousness after anaesthesia Cont Edu Anaes Crit Care Pain

2006 6 114ndash118

25 Polson S Taylor PM and Yates D Analgesia after felineovariohysterectomy under midazolam-medetomidine-

ketamine anaesthesia with buprenorphine or butor-

phanol and carprofen or meloxicam a prospective

randomised clinical trial J Feline Med Surg 2012 14

553ndash559

26 National Office of Animal Health Ketaset 100 mgml

solution for injection NOAH compendium datasheet

httpwwwnoahcompendiumcouk (2015 accessed

June 20 2015)

27 Selmi AL Mendes GM Lins BT et al Evaluation of the

sedative and cardiorespiratory effects of dexmedetomi-

dine dexmedetomidine-butorphanol and dexmedetomi-

dine-ketamine in cats J Am Vet Med Assoc 2003 222 37ndash41

28 McSweeney PM Martin DD Ramsey DS et al Clinical

efficacy and safety of dexmedetomidine used as a pre-

anesthetic prior to general anesthesia in cats J Am Vet Med

Assoc 2012 240 404ndash412 29 Hikasa Y Akiba T Iino Y et al Central alpha-adrenocep-

tor subtypes involved in the emetic pathway in cats Eur J

Pharmacol 1992 229 241ndash251

30 Santos LCP Ludders JW Erb HN et al A randomized

blinded controlled trial of the antiemetic effect of ondan-

setron on dexmedetomidine-induced emesis in cats Vet


31 Dugdale A Veterinary anaesthesia principles to practice

1st ed Oxford Wiley-Blackwell 2010 p 69





There are important physiological differences betweenkittens (lsquopaediatricsrsquo) and adult cats that warrant consid-eration for anaesthesia for elective prepubertal neuter-ing Paediatric physiology and its implications for kittenanaesthesia include limited cardiovascular compensa-tion higher relative tissue oxygen consumption and a

higher body surface area to mass ratio resulting in ahigher risk of hypothermia under anaesthesia4 Cardiacoutput is predominantly dependent on heart rate in pae-diatrics owing to a higher proportion of non-contractiletissue and hence a predetermined stroke volume46 Paediatric animals also have an immature sympatheticnervous system7 These factors will affect the choice ofanaesthetic protocol for paediatrics that have limitedcapacity to compensate for drug-induced bradycardiaand are therefore likely to develop hypotension particu-larly with α2-adrenoceptor agonists and opioids47 Additionally as tissue oxygen consumption is increasedin paediatrics it is recommended that oxygen is pro-vided throughout surgery even if anaesthetic depth isadequate without inhalational gases47 Other pharmaco-logical considerations for paediatric anaesthesia includehypoalbuminaemia which may enhance the effects ofhighly protein-bound drugs such as propofol anddiazepam and immature hepatic enzyme systemswhich may reduce the rate of drug metabolism46 Benzodiazepines stimulate appetite and their use duringanaesthesia may promote feeding on recovery8 This isparticularly valuable in kittens in helping to preventhypoglycaemia and hypothermia4 In spite of the appar-ent physiological disadvantage there is recent evidence

that kittens demonstrated fewer behavioural signs ofpain and a faster return to normal behaviour postneuter-ing than adult cats supporting the move towards pro-grammes for kitten neutering9

Injectable anaesthetic protocols incorporatingα2-adrenoceptor agonists are frequently used for neuteringprogrammes in both feral and domestic cat popula-tions41011 Medetomidine the 11 racemic mixture of theD-isomer dexmedetomidine and the L-isomer levome-detomidine has been widely used in cats since its intro-duction in 199412 Several studies have demonstratedthat only the D-isomer is pharmacologically active at

clinically relevant doses and that levomedetomidine hasno biological activity13ndash15 However in vitro studiesshowed that the L-isomer possesses weak partial α2-adrenoceptor agonist or inverse α2-adrenoceptor agonist(negative antagonist) properties1617 Therefore the phar-macological activity of levomedetomidine in a clinicalsetting is unclear It has been suggested that the absenceof levomedetomidine from commercial formulations ofdexmedetomidine may provide more predictable anal-gesia and sedation than the racemic mixture15

A number of studies have compared the sedative andphysiological effects of medetomidine and dexmedeto-midine in dogs and cats One investigation in 212

client-owned dogs demonstrated that medetomidineand dexmedetomidine produced comparable levels ofsedation and analgesia but there was some suggestionthat analgesia was marginally better with dexmedetomi-dine12 The same authors performed a study in 120 cli-ent-owned cats and concluded that medetomidine and

dexmedetomidine (at half the medetomidine dose) pro-duced similar sedation and analgesia18 They alsoreported that atipamezole fully reversed the clinicaleffects of dexmedetomidine18 These results are in agree-ment with an earlier laboratory study in cats comparingthree intramuscular (IM) doses of dexmedetomidinewith medetomidine at twice the respective dose (dexme-detomidine 25 50 and 75 microgkg medetomidine 50 100and 150 microgkg) which found that dexmedetomidineproduced pharmacodynamic effects equal to those ofmedetomidine in cats19 This study concluded that theanaesthetic effects of medetomidine were most likelydue to its dexmedetomidine isomer

With particular relevance to anaesthesia of kittens both medetomidine and dexmedetomidine negativelyaffect regulation of body temperature which may delayrecovery time especially in younger animals2021 Bothmedetomidine and dexmedetomidine may cause a rela-tive hyperglycaemia during anaesthesia by reducingendogenous insulin secretion2223 Prevention of hypo-glycaemia is important as this could contribute to pro-longed recovery424

Our study had three objectives firstly to comparerecovery times following medetomidine or dexmedeto-midine when included in an established injectable gen-

eral anaesthetic protocol for feline castration secondlyto determine if inclusion of atipamezole altered therecovery time and thirdly if recovery times of the abovewere varied in paediatric vs adult patients

Materials and methodsThe study was approved by the Animal Health TrustClinical Research Ethics Committee and writteninformed owner consent was obtained in all cases Onehundred entire male cats of any age (minimum 300 g body weight) or breed that were presented to GMAH forcastration on four predesignated days in July 2013 were

included A full clinical examination was carried out onall cats at admission to ensure that they were healthy(American Society of Anesthesiologistsrsquo classification Ior II) Any sick animals cryptorchid males and allfemales admitted for neutering on these predesignateddates were excluded

The anaesthetic protocol was based on the GMAHlsquoquadrsquo anaesthetic protocol for prepubertal cat neuteringdosing according to body surface area (BSA) 60 mgm2 ketamine (Ketaset Zoetis) 180 microgm2 buprenorphine(Vetergesic Alstoe UK) 3 mgm2 midazolam (HypnovelRoche) and 600 microgm2 medetomidine (Domitor ElancoAnimal Health)425 This equates to equal volumes of




Bruniges et al 3





















Gingivitis 1







Fleasflea dirt 20

FASTest (Megacor)
















Group (n 983101 25)


Age (months) 14 983217 13 13 983217 14 15 983217 15 13 983217 16






Group (n 983101 25)



4 15983217

4 17983217

3 16983217










Bruniges et al 5












M 127 983217 36 (n 983101 8) 130 983217 31 (n 983101 17) 141 983217 32 (n 983101 8) 155 983217 41 (n 983101 17)

MA 54 983217 8 (n 983101 13) 74 983217 47 (n 983101 12) 56 983217 8 (n 983101 13) 103 983217 67 (n 983101 12)

D 107 983217 37 (n 983101 9) 112 983217 20 (n 983101 16) 117 983217 38 (n 983101 9) 131 983217 18 (n 983101 16)

DA 51 983217 5 (n 983101 11) 57 983217 5 (n 983101 14) 62 983217 19 (n 983101 11) 75 983217 23 (n 983101 14)







Catsaffected (n)



Diarrhoea 3 MA D D


3 M DA DA


Requirement for

isoflurane

1 D


Panting during

recovery

1 DA























Bruniges et al 7




worthwhile





tors



Rec 2012 170 206











2005 15 273ndash284








52 675ndash683







2002 220 1491ndash1495










9ndash14




193ndash199






266 165ndash174









Ther 1998 21 380ndash387




















2006 6 114ndash118





553ndash559




June 20 2015)




















Bruniges et al 3





















Gingivitis 1







Fleasflea dirt 20

FASTest (Megacor)
















Group (n 983101 25)


Age (months) 14 983217 13 13 983217 14 15 983217 15 13 983217 16






Group (n 983101 25)



4 15983217

4 17983217

3 16983217










Bruniges et al 5












M 127 983217 36 (n 983101 8) 130 983217 31 (n 983101 17) 141 983217 32 (n 983101 8) 155 983217 41 (n 983101 17)

MA 54 983217 8 (n 983101 13) 74 983217 47 (n 983101 12) 56 983217 8 (n 983101 13) 103 983217 67 (n 983101 12)

D 107 983217 37 (n 983101 9) 112 983217 20 (n 983101 16) 117 983217 38 (n 983101 9) 131 983217 18 (n 983101 16)

DA 51 983217 5 (n 983101 11) 57 983217 5 (n 983101 14) 62 983217 19 (n 983101 11) 75 983217 23 (n 983101 14)







Catsaffected (n)



Diarrhoea 3 MA D D


3 M DA DA


Requirement for

isoflurane

1 D


Panting during

recovery

1 DA























Bruniges et al 7




worthwhile





tors



Rec 2012 170 206











2005 15 273ndash284








52 675ndash683







2002 220 1491ndash1495










9ndash14




193ndash199






266 165ndash174









Ther 1998 21 380ndash387




















2006 6 114ndash118





553ndash559




June 20 2015)































Group (n 983101 25)


Age (months) 14 983217 13 13 983217 14 15 983217 15 13 983217 16






Group (n 983101 25)



4 15983217

4 17983217

3 16983217










Bruniges et al 5












M 127 983217 36 (n 983101 8) 130 983217 31 (n 983101 17) 141 983217 32 (n 983101 8) 155 983217 41 (n 983101 17)

MA 54 983217 8 (n 983101 13) 74 983217 47 (n 983101 12) 56 983217 8 (n 983101 13) 103 983217 67 (n 983101 12)

D 107 983217 37 (n 983101 9) 112 983217 20 (n 983101 16) 117 983217 38 (n 983101 9) 131 983217 18 (n 983101 16)

DA 51 983217 5 (n 983101 11) 57 983217 5 (n 983101 14) 62 983217 19 (n 983101 11) 75 983217 23 (n 983101 14)







Catsaffected (n)



Diarrhoea 3 MA D D


3 M DA DA


Requirement for

isoflurane

1 D


Panting during

recovery

1 DA























Bruniges et al 7




worthwhile





tors



Rec 2012 170 206











2005 15 273ndash284








52 675ndash683







2002 220 1491ndash1495










9ndash14




193ndash199






266 165ndash174









Ther 1998 21 380ndash387




















2006 6 114ndash118





553ndash559




June 20 2015)




















Bruniges et al 5












M 127 983217 36 (n 983101 8) 130 983217 31 (n 983101 17) 141 983217 32 (n 983101 8) 155 983217 41 (n 983101 17)

MA 54 983217 8 (n 983101 13) 74 983217 47 (n 983101 12) 56 983217 8 (n 983101 13) 103 983217 67 (n 983101 12)

D 107 983217 37 (n 983101 9) 112 983217 20 (n 983101 16) 117 983217 38 (n 983101 9) 131 983217 18 (n 983101 16)

DA 51 983217 5 (n 983101 11) 57 983217 5 (n 983101 14) 62 983217 19 (n 983101 11) 75 983217 23 (n 983101 14)







Catsaffected (n)



Diarrhoea 3 MA D D


3 M DA DA


Requirement for

isoflurane

1 D


Panting during

recovery

1 DA























Bruniges et al 7




worthwhile





tors



Rec 2012 170 206











2005 15 273ndash284








52 675ndash683







2002 220 1491ndash1495










9ndash14




193ndash199






266 165ndash174









Ther 1998 21 380ndash387




















2006 6 114ndash118





553ndash559




June 20 2015)



































Bruniges et al 7




worthwhile





tors



Rec 2012 170 206











2005 15 273ndash284








52 675ndash683







2002 220 1491ndash1495










9ndash14




193ndash199






266 165ndash174









Ther 1998 21 380ndash387




















2006 6 114ndash118





553ndash559




June 20 2015)



























2006 6 114ndash118





553ndash559




June 20 2015)


















Journal of Feline Medicine & Surgery Volume Issue 2015 [Doi 10.1177%2F1098612X15598550] Bruniges,...

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Transcript of Journal of Feline Medicine & Surgery Volume Issue 2015 [Doi 10.1177%2F1098612X15598550] Bruniges,...