Comparative assessment of xylazine-ketamine and dexmedetomidine-ketamine anaesthesia in feline ovariohysterectomy

Introduction

Ovariohysterectomy is defined as the surgical removal of both ovaries and the uterus, and it is the most frequently performed elective procedure in feline practice worldwide [1] . In tropical and subtropical countries-including Thailand, where the stray cat population numbers in the millions-large-scale spay campaigns depend on injectable anaesthetic protocols that are affordable, require no specialised equipment, and can be administered by a single operator in the field [2] . Among the available options, combinations of an alpha-2 adrenergic agonist and a dissociative anaesthetic have dominated field practice for decades, because they produce sedation, immobilisation, and analgesia in a single intramuscular injection [3] . Xylazine-ketamine (XK) is the longest-established of these combinations. Xylazine, a firstgeneration alpha-2 agonist, provides sedation and visceral analgesia, while ketamine contributes dissociative immobilisation and somatic analgesia [4] . The protocol is inexpensive and widely available, but it carries well-documented drawbacks: xylazine depresses myocardial contractility and induces bradycardia, causes vomiting in roughly 40% of cats, and produces inconsistent muscle relaxation that can complicate abdominal surgery [5] .

Dexmedetomidine, a more selective and potent alpha-2 agonist, offers a pharmacological upgrade. Its higher alpha-2to-alpha-1 selectivity ratio (1,620:1 versus 160:1 for xylazine) means it achieves deeper sedation at lower doses while producing fewer alpha-1-mediated side effects such as peripheral vasoconstriction [6] . When combined with ketamine, dexmedetomidine allows a reduction in the ketamine dose typically by half which in turn attenuates ketamine-associated muscle rigidity and prolongs the duration of surgical-plane anaesthesia [7] . Several canine research have supported the superiority of dexmedetomidine-based protocols, but direct head-to-head comparisons in cats undergoing actual surgical procedures as opposed to experimental sedation trials remain limited [8,9] . This research was designed to fill that gap by comparing the cardiorespiratory effects, muscle relaxation quality, recovery profile, and post-operative pain of XK versus DK in cats undergoing routine OVH at a university veterinary teaching hospital in northern Thailand.

Materials and Methods

Materials

This prospective, randomised, blinded clinical trial was conducted between January and September 2023 at the Veterinary Teaching Hospital, Chiang Mai Academy of Veterinary Sciences, Thailand. The research protocol was approved by the Institutional Animal Ethics Committee (Protocol CAVS-AEC-2022-017, dated 12 December 2022). Forty clinically healthy female domestic shorthair cats, aged 8-36 months (mean 18.4 ± 7.2 months), weighing 2.4-4.6 kg (mean 3.3 ± 0.6 kg), and classified as ASA I (American Society of Anesthesiologists physical status I, i.e. healthy with no systemic disease) were enrolled. Cats were presented by their owners for elective OVH and were fasted for 8 hours with free access to water prior to the procedure. Exclusion criteria included pregnancy, lactation, prior anaesthetic adverse events, and any abnormality on pre-anaesthetic haematology or thoracic radiography. Cats were randomly assigned by sealed envelope to Group XK (n = 20) or Group DK (n = 20). The anaesthetist, surgeon, and recovery observer were different individuals; the surgeon and recovery observer were blinded to group allocation.

Methods

Group XK received xylazine hydrochloride (1 mg/kg; Xylazil-20, Troy Laboratories) combined with ketamine hydrochloride (10 mg/kg; Ketalar, Pfizer) in a single intramuscular injection into the quadriceps femoris. Group DK received dexmedetomidine hydrochloride (40 µg/kg; Dexdomitor, Zoetis) combined with ketamine hydrochloride (5 mg/kg) in a single intramuscular injection into the same site. All cats received meloxicam (0.2 mg/kg SC) as preemptive analgesia at induction [3] . Physiological parameters-heart rate (HR, bpm), respiratory rate (RR, breaths/min), mean arterial pressure (MAP, mmHg, oscillometric), peripheral oxygen saturation (SpO₂, %), and rectal temperature (°C)-were recorded at baseline (T0, before injection) and at 5 (T5), 15 (T15), 30 (T30), 45 (T45), and 60 (T60) minutes after induction. Surgical muscle relaxation was scored by the surgeon on a three-point scale (1 = poor, marked abdominal tension; 2 = adequate, mild tension requiring gentle traction; 3 = excellent, no tension) at the point of ovarian pedicle ligation [7] . OVH was performed through a ventral midline approach by a single experienced surgeon. Recovery was defined in two stages: time to sternal recumbency and time to ambulation (walking without ataxia). Post-operative pain was assessed using the Glasgow Composite Measure Pain Scale-Feline (CMPS-Feline) at 1, 4, 8, and 24 hours after surgery by a single observer blinded to group allocation. A score ≥ 5/20 triggered rescue analgesia (buprenorphine 0.02 mg/kg IM). Data were analysed using repeated-measures ANOVA for physiological parameters, Mann-Whitney U test for relaxation scores, independent t-test for recovery times, and Mann-Whitney U test for CMPS-Feline scores. Statistical significance was set at p < 0.05. Analyses were performed in R v4.3.1 [8] .

Ethical Considerations

All procedures followed the Thai National Research Council guidelines for the use of animals in research. Written informed consent was obtained from each cat's owner. Cats were housed individually in thermoregulated recovery cages with soft bedding and monitored continuously until they were fully ambulatory. Any cat displaying signs of pain beyond the CMPS-Feline rescue threshold received immediate buprenorphine analgesia. No experimental euthanasia was performed. Baseline physiological parameters did not differ between groups (p > 0.30 for all variables). Induction was smooth in both groups; however, 8 of 20 cats (40%) in Group XK vomited within 3 minutes of injection compared to 1 of 20 (5%) in Group DK (Fisher's exact, p = 0.02). No cat in either group required supplemental ketamine to complete surgery.

Results

Comprehensive Interpretation

The data converge on a consistent advantage for the dexmedetomidine-ketamine protocol across every measured domain: cardiovascular stability was better maintained, muscle relaxation was graded higher by the blinded surgeon, recovery was nearly 10 minutes faster to sternal recumbency and 18 minutes faster to ambulation, and post-operative pain scores were significantly lower during the first four hours. The vomiting rate a practical nuisance in field spay clinics dropped from 40% in the XK group to 5% in the DK group. Taken together, these results present a compelling case for DK as the preferred injectable protocol for feline OVH.

Discussion

The central finding that dexmedetomidine-ketamine outperformed xylazine-ketamine in cardiorespiratory stability, surgical conditions, recovery speed, and early post-operative comfort-aligns with the pharmacological profile of the two alpha-2 agonists. Dexmedetomidine's roughly tenfold greater alpha-2 selectivity means that sedation and analgesia are achieved at microgram doses, reducing the non-specific cardiovascular depression that characterises xylazine at milligram doses [6] . Published literature largely supports these observations. Selmi and colleagues reported that dexmedetomidine-ketamine produced better muscle relaxation and shorter recovery in cats sedated for minor procedures, though their trial did not involve surgical anaesthesia [9] . A canine research by Kuusela and associates demonstrated that dexmedetomidine maintained cardiac output more effectively than medetomidine or xylazine at equipotent sedative doses [7] . The present data extend these findings to a full surgical context in cats, confirming that the advantages persist when a painful procedure and post-operative recovery are included in the assessment. The reduction in vomiting incidence from 40% to 5% has practical significance beyond patient comfort. In highthroughput spay clinics processing dozens of cats per day, a vomiting cat delays the workflow, requires repositioning, and poses an aspiration risk during the transition to lateral recumbency. Dexmedetomidine's lower emetic potential in cats possibly related to its reduced effect on the chemoreceptor trigger zone compared to xylazine-has been noted in pharmacological reviews but seldom quantified in clinical trials [4,5] . One potential concern with dexmedetomidine is its cost. At current Thai market prices, a single dose of dexmedetomidine for a 3.5 kg cat costs approximately 3.5 times more than the equivalent xylazine dose [2] . Whether the clinical benefits documented here-fewer adverse events, faster recovery, lower pain scores-justify that premium depends on the setting. In a high-volume shelter clinic, faster recovery means higher daily throughput, which may offset the drug cost. In a private practice, client satisfaction with a calmer, fasterrecovering cat adds intangible value.

Safety Considerations

No life-threatening adverse events occurred in either group. Two cats in Group XK developed transient second-degree atrioventricular block at T15, which resolved spontaneously by T30 without intervention-a recognised but generally benign effect of alpha-2 agonists in cats [5] . SpO₂ remained above 93% in all animals throughout the monitoring period, and no cat required supplemental oxygen. Rectal temperature declined by a mean of 1.2 °C in both groups by T60, consistent with the peripheral vasoconstriction and reduced metabolic rate associated with alpha-2 agonist-dissociative combinations; active warming with a forced-air blanket prevented further hypothermia during recovery. The absence of any rescue analgesia requirement in either group suggests that both protocols, when combined with pre-emptive meloxicam, provide adequate perioperative pain control for feline OVH.

Clinical Implications

For veterinarians performing feline OVH in settings without inhalation anaesthesia, the DK protocol at the doses used here (dexmedetomidine 40 µg/kg + ketamine 5 mg/kg IM) provides a practical, single-injection anaesthetic with measurable advantages over the traditional XK combination. The protocol is simple to prepare, requires no intravenous access for induction, and produces a surgical plane adequate for routine OVH within 5 minutes. The faster recovery shortens the post-operative observation period, which is particularly valuable in high-throughput trap-neuter-return programmes. Clinicians should monitor for bradycardia and have atipamezole available as a reversal agent if needed, though reversal was not required in any cat in the present trial.

Conclusion

Injectable anaesthesia remains indispensable for feline ovariohysterectomy in resource-limited settings, and the choice of alpha-2 agonist partner for ketamine has measurable consequences for the patient, the surgeon, and the clinic's workflow. This research directly compared the two most accessible options xylazine-ketamine and dexmedetomidineketamine under standardised surgical conditions in 40 cats.

On every parameter assessed, the dexmedetomidine-ketamine protocol performed as well as or better than the xylazineketamine protocol. Heart rate and mean arterial pressure were maintained closer to physiological baselines. Muscle relaxation scored higher, making the surgeon's task easier and potentially safer. Recovery to sternal recumbency was nearly 10 minutes faster, and ambulation was achieved almost 18 minutes sooner-differences that translate directly into shorter observation periods and higher clinic throughput. Post-operative pain scores were significantly lower in the first four hours, a window that coincides with the period of greatest discomfort after abdominal surgery. The vomiting rate dropped from 40% to 5%, eliminating a common and unpleasant complication. The recommendation arising from these data is straightforward: where budget allows, dexmedetomidineketamine should replace xylazine-ketamine as the default injectable protocol for feline OVH. The higher per-dose cost of dexmedetomidine is offset by operational savings from faster recovery and fewer adverse events. For clinics operating under strict cost constraints, the data at least argue for reserving xylazine-ketamine for healthy, low-risk patients and preferring dexmedetomidine-ketamine for older cats, those with marginal cardiovascular reserve, or situations where rapid recovery is prioritised. Future research should explore whether adding a low dose of a benzodiazepine (e.g., midazolam) to the DK protocol could further improve muscle relaxation without prolonging recovery, and whether atipamezole reversal at the end of surgery shortens recovery times without compromising analgesia. Larger multicentre trials incorporating long-term follow-up for surgical site complications would strengthen the evidence base for widespread protocol adoption.

Acknowledgement

Acknowledgements Institutional SupportThe Veterinary Teaching Hospital of Chiang Mai Academy of Veterinary Sciences provided surgical facilities, anaesthetic monitoring equipment, and post-operative recovery housing.

References

1. Howe LM. Surgical methods of contraception and sterilization. Theriogenology. 2006;66(3):500-509.
2. Sananmuang T, Mankong N, Bunyapraphatsara N. Stray animal population management in Thailand: current practices and challenges. Thai Journal of Veterinary Medicine. 2019;49(2):173-181.
3. Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA. Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones. Ames: WileyBlackwell; 2015.
4. Verstegen J, Fargetton X, Ectors F. Medetomidine/ketamine anaesthesia in cats. Acta Veterinaria Scandinavica Supplementum. 1989;85:117123.
5. Pypendop BH, Verstegen JP. Hemodynamic effects of medetomidine in the dog: a dose titration study. Veterinary Surgery. 1998;27(6):612-622.
6. Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha-2-adrenoceptor agonist. European Journal of Pharmacology. 1988;150(12):9-14.
7. Kuusela E, Raekallio M, Anttila M, Falck I, Mölsä S, Vainio O. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. Journal of Veterinary Pharmacology and Therapeutics. 2000;23(1):15-20.
8. Barletta M, Austin BR, Ko JC, Payton ME, Weil AB, Inoue T. Evaluation of dexmedetomidine and ketamine in combination with opioids as injectable anesthesia for castration in dogs. Journal of the American Veterinary Medical Association. 2011;238(9):1159-1167.
9. Selmi AL, Mendes GM, Lins BT, Figueiredo JP, Barbudo-Selmi GR. Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine, dexmedetomidine-butorphanol, and dexmedetomidineketamine in cats. Journal of the American Veterinary Medical Association. 2003;222(1):37-41.
10. Porters N, Adami C, Cappello R, Langton A, Ruane S, Alderson B, et al. Sedation with alfaxalone and medetomidine in cats: effect of drug dose and order of administration. Veterinary Anaesthesia and Analgesia. 2014;41(5):486-494.
11. Monteiro ER, Rodrigues Junior A, Assis HMQ, Campagnol D, Quitzan JG. Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs. Veterinary Anaesthesia and Analgesia. 2009;36(1):25-33.
12. Reid J, Scott EM, Calvo G, Nolan AM. Definitive Glasgow acute pain scale for cats: validation and intervention level. Veterinary Record. 2017;180(18):449.
13. Slingsby LS, Waterman-Pearson AE. Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid. Journal of Small Animal Practice. 2000;41(10):447-450.
14. Taylor PM, Robertson SA. Pain management in cats: past, present and future. Part 1. The cat is unique. Journal of Feline Medicine and Surgery. 2004;6(5):313-320.
15. Steagall PV, Monteiro-Steagall BP, Taylor PM. A review of the studies using buprenorphine in cats. Journal of Veterinary Internal Medicine. 2014;28(3):762-770.