Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Maidanskaia, E. G., Mirra, A., Marchionatti, E. et al. 2023. Antinociceptive, sedative and excitatory effects of intravenous butorphanol administed alone or in combination with detomidine in calves: A prospective, randomized, blinded cross-over study. Animals 13(12), 1943.

The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

Ruíz-López, P., Cuypers, C., Schauvliege, S. 2023. Xylazine infusion during equine colic anesthesia with isoflurane and lidocaine: A retrospective study. Animals 13(18), 2902.

This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements; recovery quality and duration; percentage of death/survival; and days to die/discharge in horses...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Oliveira, A. R., Gozalo-Marcilla, M., Ringer, S. K. et al. 2021. Development, validation, and reliability of a sedation scale in horses (EquiSed). Frontiers in Veterinary Science 8, 611729.

The lack of standardization of sedation scales in horses limits the reproducibility between different studies. This prospective, randomized, blinded, horizontal and controlled trial aimed to validate a scale for sedation in horses (EquiSed). Seven horses...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Kälin, I., Henze, I. S., Ringer, S. K. et al. 2021. Comparison of recovery quality following medetomidine versus xylazine balanced isoflurane anaesthesia in horses: A retrospective analysis. Animals 11(8), 2440.

Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was...

Camargo-dos-Santos, B., Carlos, C. L., Favero-Neto, J. et al. 2021. Welfare in Nile tilapia production: Dorsal fin erection as a visual indicator for insensibility. Animals 11(10), 3007.

In aquaculture, to ensure animal welfare in pre-slaughter and slaughter stages, it is fundamental that fish are insensible. A method for evaluating fish insensibility is based on visual sensibility indicators (VSI) assessment (i.e., self-initiated behavior...

White, K. L., Hird, J. F. R., Taylor, P. M. 2021. Sevoflurane or isoflurane anaesthesia? A prospective, randomised blinded clinical trial in horses undergoing elective surgery. Veterinary Record 189(3), e507.

Background: Isoflurane is the only volatile anaesthetic agent licensed for equine use in the United Kingdom, but sevoflurane is also commonly used. The two agents have rarely been compared for use in clinical elective surgery...

Jorge, S., Ferreira, J. M., Olsson, I. A. S. et al. 2021. Efficacy and behavioral recovery of different anesthetics. Zebrafish 18(5), 330-337.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality...

Espinoza, C., Lomax, S., Windsor, P. 2020. The effect of topical anaesthesia on the cortisol responses of calves undergoing dehorning. Animals 10(2), 312.

Dehorning causes pain and distress to cattle, and there is a need to provide effective and practical analgesia to improve animal welfare. We conducted an experiment to determine the effect of a modified post-operative topical...

Musk, G. C., Ezzy, B. J., Kenchington, L. M. et al. 2020. A comparison of buffered tricaine methanesulfonate (MS-222) and isoeugenol anesthesia for caudal fin clipping in zebrafish (Danio rerio). JAALAS 59(6), 732-736.

The purpose of this study was to compare the safety and efficacy of buffered tricaine methanesulfonate (MS-222) and isoeugenol for the anesthesia of zebrafish undergoing caudal fin clipping. Eighty 9 mo Danio rerio (AB strain)...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...

Hampton, C. E., Riebold, T. W., Mandsager, R. E. 2019. Recovery characteristics of dogs following anesthesia induced with tiletamine-zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintained with isoflurane. Journal of the American Veterinary Medical Association 254(12), 1421-1426.

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol. DESIGN...

Martins, T., Valentim, A., Pereira, N. et al. 2019. Anaesthetics and analgesics used in adult fish for research: A review. Laboratory Animals 53(4), 325–341.

The number of fish used in research has increased in the last decades. Anaesthesia is required when fish must be held immobile and it is crucial to promote fish welfare, because these vertebrates can show...

Jacobsen, J. V., Steen, K., Nilssen, K. J. 2019. Anaesthetic efficacy of Aqui-S, Benzoak, and MS-222 on lumpfish (Cyclopterus lumpus) fries. Impact from temperature, salinity, and fasting. PLOS ONE 14(1), e0211080.

Large numbers of lumpfish are produced for the Norwegian salmon industry and are used to combat sea lice infestations. Periodically high mortality of farmed lumpfish demonstrates the need to improve farming conditions and animal welfare...

Glover, C. N., Newton, D., Bajwa, J. et al. 2019. Behavioural responses of the hagfish Eptatretus stoutii to nutrient and noxious stimuli. Scientific Reports 9, 13369.

The suitability of a traditional testing paradigm (e.g. choice chamber) for assessing chemosensory behaviour in the Pacific hagfish, Eptatretus stoutii, was examined. Actively-swimming hagfish, tested at night, showed no preference for any region of a...

Ehrlich, O., Karamalakis, A., Krylov, A. J. et al. 2019. Clove oil and AQUI-S efficacy for zebrafish embryo, larva, and adult anesthesia. Zebrafish 16(5), 451-459.

Since the use of the zebrafish Danio rerio genetic model organism within the scientific research community continues to grow rapidly, continued procedural refinement to support high-quality, reproducible research and improve animal welfare remains an important...

Lucrezia Costa, G., Nastasi, B., Spadola, F. et al. 2019. Effect of levobupivacaine, administered intraperitoneally, on physiological variables and on intrasurgery and postsurgery pain in dogs undergoing ovariohysterectomy. Journal of Veterinary Behavior 30, 33-36.

The aim of this study was to evaluate intraoperative and postoperative efficacy and cardiovascular effects of levobupivacaine compared with bupivacaine, administered intraperitoneally in dogs undergoing ovariohysterectomy surgery. Thirty female dogs were divided into three groups...

Chatigny, F., Creighton, C. M., Stevens, E. D. 2018. Intramuscular infiltration of a local anesthetic, lidocaine, does not result in adverse behavioural side effects in rainbow trout. Scientific Reports 8, 10250.

Fish are a useful animal model for research, but our improvement in some aspects of their welfare has not kept pace with their increased popularity for this use. For example, researchers rarely use analgesics. We...

Jarrett, M. A., Bailey, K. M., Messenger, K. M. et al. 2018. Recovery of horses from general anesthesia after induction with propofol and ketamine versus midazolam and ketamine. Journal of the American Veterinary Medical Association 253(1), 101-107.

OBJECTIVE To evaluate quality of recovery from general anesthesia in horses after induction with propofol and ketamine versus midazolam and ketamine. DESIGN Prospective randomized crossover study. ANIMALS 6 healthy adult horses. PROCEDURES Horses were premedicated...

Pounder, K. C., Mitchell, J. L., Thomson, J. S. et al. 2018. Physiological and behavioural evaluation of common anaesthesia practices in the rainbow trout. Applied Animal Behaviour Science 199, 94-102.

Anaesthetic drugs are commonly administered to fish in aquaculture, research and veterinary contexts. Anaesthesia causes temporary absence of consciousness and may reduce the stress and/or pain associated with handling and certain invasive procedures. The rainbow...

Chatigny, F., Groman, D. B., Martinson, S. A. et al. 2018. Evaluation of tissue changes following intramuscular infiltration of lidocaine in rainbow trout Oncorhynchus mykiss. Journal of Fish Biology 92(4), 888-900.

Rainbow trout Oncorhynchus mykiss were infiltrated with either saline or lidocaine adjacent to the dorsal fin to assess histopathological changes. Infiltration was done as if it were being used as a local anaesthetic. Tissue lesions...

Chance, R. J., Cameron, G. A., Fordyce, M. et al. 2018. Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar. Journal of Fish Biology 93(6), 1069-1081.

Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research...

Schmitz, S., Tacke, S., Guth, B. et al. 2017. Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters. PLOS ONE 12(3), e0174423.

Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with...