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. 
Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

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...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Miller, R., Grott, A., Patzkéwitsch, D. et al. 2023. Behavior of piglets in an observation arena before and after castration with local anesthesia. Animals 13(3), 529.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

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...

Jones, B. L., McClain, A. M., Sportelli, J. J. et al. 2023. Return of sound production as a biomarker of bottlenose dolphin emergence from anesthesia. Animals 13(15), 2531.

(1) Background: When a human or animal is recovering from general anesthesia, their medical team uses several behavioral and physiological parameters to assess their emergence from the unconscious state to complete wakefulness. However, the return...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

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...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

Whoriskey, S., Pearson, L. E., Harris, H. S. et al. 2022. Using a combination of midazolam and butorphanol is a safe and effective reversible field sedation protocol for Weddell seal (Leptonychotes weddellii) pups. Vet Record 191(11), e2238.

Background: Weddell seals (Leptonychotes weddellii) are a well-studied species of phocid with an apparent sensitivity to immobilising agents. Mortality as high as 31% has been reported during field immobilisation. This study investigated the use of...

Coutant, M., Malmkvist, J., Kaiser, M. et al. 2022. Piglets’ acute responses to local anesthetic injection and surgical castration: Effects of the injection method and interval between injection and castration. Frontiers in Veterinary Science 9, 1009858.

Although applied in some countries, efficacy of local anesthetics based on procaine to mitigate acute responses to piglet castration remains questioned. This paper presents results from a factorial study examining the effects of two methods...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Söbbeler, F. J., Wendt, S., Briese, A. et al. 2022. Comparative study of pain-related responses of male piglets up to seven days of age to the application of different local anaesthetics and subsequent castration. Animals 12(20), 2833.

To evaluate pain responses to intratesticular and subscrotal injection of three local anaesthetics and their efficacy during castration a randomized controlled study was conducted. In groups of 20 piglets, procaine (2%), lidocaine (2%), or mepivacaine...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Skade, L., Kristensen, C. S., Nielsen, M. B. F. et al. 2021. Effect of two methods and two anaesthetics for local anaesthesia of piglets during castration. Acta Veterinaria Scandinavica 63, 1.

Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the “Danish quality scheme”; a voluntary initiative taken by the...

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...

Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...

Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...

Chang, L.-J., Ko, J. C., Weil, A. B. et al. 2021. Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol, tiletamine-zolazepam-xylazine-butorphanol, and ketamine-detomidine-butorphanol in pigs. Journal of the AVMA 258(8), 883-891.

OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a...

Argüelles, J., Echaniz, M., Bowen, J. et al. 2021. The impact of a stress-reducing protocol on the quality of pre-anaesthesia in cats. Veterinary Record 188(12), e138.

Introduction: Transport to the clinic is a major source of stress for cats. The process involves being put into a carrier, driven in a car and handled. Cats are therefore removed from the safe-haven of...