Prepubertal Gonadectomy in Shelter Cats: Nathalie Porters
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Prepubertal gonadectomy in shelter cats: Anaesthesia, surgery and effect of age at time of gonadectomy on health and behaviour Nathalie Porters Dissertation submitted in the fulfillment of the requirements for the degree of Doctor in Veterinary Sciences (PhD), Faculty of Veterinary Medicine Ghent University 2014 Promoter Prof. Dr. Hilde de Rooster Co-promoters Prof. Dr. Ingeborgh Polis Dr. Christel Moons Department of Medicine and Clinical Biology of Small Animals Faculty of Veterinary Medicine Ghent University This PhD was funded by the Federal Public Service of Health, Food Chain Safety and Environment for 3 years, by the Facultaire Commissie Wetenschappelijk Onderzoek (FCWO) of the Faculty of Veterinary Medicine for 6 months, and by the Bijzonder Onderzoeksfonds (BOF) of Ghent University for 6 months. Printing and distribution of this thesis was enabled through the support of: Porters, Nathalie Prepubertal gonadectomy in shelter cats: anaesthesia, surgery and effect of age at time of gonadectomy on health and behaviour Universiteit Gent, Faculteit Diergeneeskunde Vakgroep Geneeskunde en Klinische Biologie van de Kleine Huisdieren ISBN: 9789058643827 Table of Contents Table of Contents List of abbreviations 1 TABLE OF CONTENTS 5 GENERAL INTRODUCTION 3 1. Introduction 5 2. Anaesthesia and surgery 7 2.1. The paediatric patient: anaesthesia- and surgery-related concerns 7 2.2. Criteria for anaesthetic and surgical protocols in shelter medicine 9 3. Gonadal hormones, gonadectomy and physical development 14 3.1. Urogenital disorders 14 3.2. Growth-related problems 15 3.3. Overweight 17 3.4. Immune regulation 19 4. Feline behaviour and gonadectomy 20 4.1. Feline biology and social organization 20 4.2. Feline developmental stages and socialization 21 4.3. Behaviour problems in cats 23 4.4. Gonadectomy and cat behaviour 24 5. Conclusion 25 SCIENTIFIC AIMS 27 RESEARCH STUDIES 31 CHAPTER 1: Prepubertal gonadectomy in cats: different injectable anaesthetic combinations and comparison with gonadectomy at traditional age 35 1. Abstract 37 2. Introduction 38 3. Materials and Methods 38 3.1. Animals 39 3.2. Anaesthesia 39 3.3. Surgical Procedures 42 3.4. Data Recording 42 3.5. Statistical Analysis 46 4. Results 46 5. Discussion 54 6. Conclusion 56 7. Funding 57 8. Acknowledgements 57 CHAPTER 2: Sedative and antinociceptive effects of dexmedetomidine combined with buprenorphine after oral transmucosal or intramuscular administration in cats 59 1. Abstract 61 2. Introduction 62 3. Materials and methods 63 3.1. Animals 63 3.2. Study protocol 63 Table of Contents 3.3. Sedative and nociceptive testing 63 3.4. Adverse and physiologic effects 65 3.5. Statistical analyses 65 4. Results 66 5. Discussion 68 6. Conclusion 70 CHAPTER 3: Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats 71 1. Abstract 73 2. Introduction 74 3. Materials and Methods 75 3.1. Animals 75 3.2. Study Protocol 75 3.3. Drug analysis 76 3.4. Pharmacokinetic analysis 78 3.5. Statistical analysis 78 4. Results 79 5. Discussion 84 6. Conclusion 86 CHAPTER 4: Prepubertal gonadectomy in cats: different surgical techniques and comparison with gonadectomy at traditional age 87 1. Abstract 89 2. Introduction 90 3. Materials and Methods 90 3.1. Animals 91 3.2. Anaesthetic Protocols 92 3.3. Surgical Procedures 92 3.4. Data Recording 94 3.5. Statistical Analysis 95 4. Results 95 5. Discussion 98 6. Conclusion 101 7. Funding 101 8. Acknowledgements 102 CHAPTER 5: Relationship between age at time of gonadectomy and health issues in adopted shelter kittens 103 1. Abstract 105 2. Introduction 106 3. Materials and Methods 107 3.1. Animals 107 3.2. Short-term follow-up 108 3.3. Long-term follow-up 109 3.4. Statistical Analysis 109 4. Results 110 4.1. Short-term follow-up 110 4.2. Long-term follow-up 112 5. Discussion 115 6. Conclusion 118 7. Funding 118 8. Acknowledgements 118 Table of Contents CHAPTER 6: Prepubertal gonadectomy affects body weight, body condition score and plasma leptin concentrations in young adult cats 119 1. Abstract 121 2. Introduction 122 3. Material and Methods 123 4. Results 125 5. Discussion 125 6. Conclusion 126 7. Funding 127 8. Acknowledgements 127 CHAPTER 7: Development of behaviour in adopted shelter kittens following gonadectomy performed at an early age or at a traditional age 129 1. Abstract 131 2. Introduction 132 3. Materials and Methods 134 3.1. Animals 134 3.2. Post adoption survey instrument 135 3.3. (Potentially) undesirable behaviour 136 3.4. Statistical Analysis 137 4. Results 140 5. Discussion 152 6. Conclusion 156 7. Funding 156 8. Acknowledgements 156 GENERAL DISCUSSION 157 1. The controversy is not about whether to perform gonadectomy in cats, but when … 159 2. Limitations and reflections 171 3. Perspectives 174 SUMMARY 175 SAMENVATTING 187 REFERENCES 199 CURRICULUM VITAE 219 BIBLIOGRAPHY 223 DANKWOORD 227 List of Abbreviations List of Abbreviations 4AVet multidimensional pain scoring system AUC area under the plasma concentration-time curve BCS body condition score Cmax maximal plasma concentration COX cyclo-oxygenase DB dexmedetomidine-buprenorphine DIVAS dynamic and interactive visual analogue scale FPS federal public service FLUTD feline lower urinary tract disease HPLC high-performance liquid chromatography HR heart rate IM intramuscular IV intravenous K10 elimination rate constant K12 elimination rate constant from central to peripheral compartment K21 elimination rate constant from peripheral to central compartment Ka absorption rate constant LC-MS/MS liquid chromatography coupled to tandem mass spectrometry LOD limit of detection LOQ limit of quantification MBK medetomidine-buprenorphine-ketamine MNT mechanical nociceptive threshold MRT mean residence time N Newton NRS numerical rating scale NSAID non-steroidal anti-inflammatory drug OR odds ratio OTM oral transmucosal PPG prepubertal gonadectomy REF reference range RIA radio immuno assay RR respiration rate 1 List of Abbreviations SC subcutaneous SD standard deviation SEM standard error of the mean SPO2 peripheral arterial haemoglobin oxygen saturation T rectal temperature t1/2a absorption half-life t1/2e elimination half-life (one-compartmental model) t1/2α elimination half-life (two-compartmental model; first slope) t1/2β elimination half-life (two-compartmental model; second slope) TAG traditional age gonadectomy Tmax time to maximal plasma concentration UPLC ultra performance liquid chromatography 2 GENERAL INTRODUCTION 3 General Introduction 4 General Introduction 1. Introduction In today’s Western society of working couples and urban dwellers, cats are deemed to be ideal pets offering affection and companionship while needing less care and commitment than dogs (Mertens & Schär 1986; Olm & Houpt 1988; Heath 2007; Casey & Bradshaw 2008). In most European countries, cats even outnumber dogs as companion animals (Batson 2008). According to a report of the Federal Public Services (FPS) Economy, Statistics, there were 1,974,000 cats compared to 1,167,000 dogs in Belgium in 2008. The real numbers will undoubtedly be higher since unowned cats and dogs (in shelters or stray) were not included. Despite their popularity, cats are relinquished in large numbers to animal shelters. In 2012, 31,434 cats, including 21,175 stray animals, were admitted to 79 shelters in Belgium, of which 16,180 were adopted, 1,193 were reunited with their owner and 11,208 were euthanized due to illness, feral status, lack of shelter capacity, … (FPS 2012). According to the literature, various reasons are given by owners for relinquishing cats to shelters, the main ones being owner circumstances (e.g. moving house, divorce, owner illness or death, …), owner allergy, and cat behaviour and/or medical problems (Luke 1996; New et al. 1999; Neidhart & Boyd 2002; Shore et al. 2003; Casey et al. 2009). A significant proportion of shelter cats, however, consists of stray adults and, more importantly, kittens (Luke 1996; Casey et al. 2009). The latter emphasizes the need for a neutering policy regarding cats and for educating owners about feline reproduction and the avoidance of accidental and/or unwanted litters. Cats are prolific breeders due to sexual maturity occurring as early as 4 months of age (Jemmett & Evans 1977; Jackson 1984), a seasonally polyestrous breeding structure (Gorman et al. 2002; Kutzler 2007), an induced ovulation following single or multiple copulations (Concannon et al. 1980; Kutzler 2007), a relatively short gestation length of 67 days (Root et al. 1995) and a highly adaptable nature to survive (Levy 2011). It is estimated that free- roaming cats can produce 1.4 litters per year with a median of 3 kittens in one litter (range, 1 to 6) (Nutter et al. 2004). Non-surgical (Kutzler & Wood 2006) and surgical methods (Howe 2006) can be used for contraception in cats. Hormonal approaches resulted in the progestin-based ‘Pills for pets’ which were developed in Europe in 1963 (ACC&D 2013). Their long-term use in cats is limited due to life-altering side effects (higher increase in mammary tumours and endometrial hyperplasia) (Munson 2006). Moreover, the limited duration of contraception makes this 5 General Introduction approach less reliable in shelter medicine, but also in privately owned cats when owners do not administer the drugs consistently. Other avenues for non-surgical pet contraception are being explored: chemical castration methods based on an injection of zinc gluconate (Oliveira et al. 2013) or calcium chloride in the testes (Jana & Samanta 2011) and contraceptive vaccines for male and female animals (Levy 2011; Levy et al. 2011). To date, however, surgical gonadectomy (i.e. the removal of the ovaries in females and testes in males) remains the most reliable and the only permanent method with rapid onset for reproduction control in cats (ACC&D 2013). Furthermore, other potential benefits have been associated with gonadectomy. For example, neutered cats are less likely to display sex hormone-related behaviours (e.g. urine spraying and fighting, unwanted heat) that are often undesirable to owners (Hart & Barrett 1973; Hart & Cooper 1984; Patronek et al.