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. 
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...

Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

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...

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...

Rexroat, E. K., Haughton, C. L., Fox, K. 2023. Using a cost-effective, efficient method to train young dogs to cooperate for multiple blood collection procedures in a pharmacokinetics study. Laboratory Animal Science Professional 11(6) (November/December), 34-36.

Behavioral testing slings, such as the Pavlov sling, offer an effective form of restraint for beagles while minimizing stress. Although these slings provide effective restraint, their high cost makes them less likely to be considered...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

Elane, G. L., Portela, D. A., Hobbs, K. J. et al. 2023. Sedated cesarean sections are associated with increased kid survival compared to general anesthesia in goats: Retrospective cohort of 45 cases (2011–2021). Journal of the American Veterinary Medical Association 261(3), 391–396.

OBJECTIVE To determine whether anesthesia type (sedation or general anesthesia) affects kid survival to discharge in caprine cesarean sections (C-sections). ANIMALS Retrospective cohort of 99 caprine C-sections (2011–2021). PROCEDURES All surgeries were performed via left...

Martin-Flores, M., Nugen, S. A., Boesch, J. M. et al. 2023. Low-dose epidural anesthesia decreases the use of intraoperative systemic analgesics in goats undergoing lower urinary tract surgery. Journal of the American Veterinary Medical Association 261(8), 1147–1151.

OBJECTIVE To test whether the use of low-dose epidural anesthesia (EA) in goats undergoing lower urinary tract surgery reduces the requirements of perioperative analgesics, contributes to intraoperative hypotension, and improves postoperative comfort during the first...

Webb, J. K., Keller, K. A., Chinnadurai, S. K. et al. 2023. Use of alfaxalone in bearded dragons (Pogona vitticeps): Optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography. Journal of the American Veterinary Medical Association 261(1), 126–131.

OBJECTIVE Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has...

Molinaro, H. G., Anderson, G. S., Gruny, L. et al. 2022. Use of blood lactate in assessment of manual capture techniques of zoo-housed crocodilians. Animals 12(3), 397.

Species-specific welfare indicators are important in promoting positive welfare for zoo animals. Reptiles are a notoriously understudied group in regards to behavior, welfare needs, and husbandry requirements. Using opportunistically obtained samples, we evaluated how blood...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Johansson, Ö, Kachel, S., Weckworth, B. 2022. Guidelines for telemetry studies on snow leopards. Animals 12(13), 1663.

Animal-borne tracking devices have generated a wealth of new knowledge, allowing us to better understand, manage and conserve species. Fitting such tracking devices requires that animals are captured and often chemically immobilized. Such procedures cause...

Bethell, E. J., Khan, W., Hussain, A. 2022. A deep transfer learning model for head pose estimation in rhesus macaques during cognitive tasks: Towards a nonrestraint noninvasive 3Rs approach. Applied Animal Behaviour Science 255, 105708.

Head orientation is a measure of attention used in behavioral psychological research with non-human primates. It is used across a broad range of disciplines and settings, from the field to the laboratory. Field methods are...

Jacob, G., Katti, H., Cherian, T. et al. 2021. A naturalistic environment to study visual cognition in unrestrained monkeys. eLife 10, e63816.

Macaque monkeys are widely used to study vision. In the traditional approach, monkeys are brought into a lab to perform visual tasks while they are restrained to obtain stable eye tracking and neural recordings. Here...

Williams, W. O., Baneux, P. 2022. Humane Intervention Points: Refining endpoint terminology to incorporate non-euthanasia intervention options to improve animal welfare and preserve experimental outcomes. Laboratory Animals 56(5), 482-489.

Consideration of The Three R’s (Replacement, Reduction, and Refinement) is essential when setting Humane Endpoints; however, a common interpretation assumes that Humane Endpoints are timepoints to perform euthanasia. This interpretation is not always consistent with...

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...

Nunamaker, E. A., Davis, S., O’Malley, C. I. et al. 2021. Developing recommendations for cumulative endpoints and lifetime use for research animals. Animals 11(7), 2031.

Research animals are important for scientific advancement, and therefore, their long-term welfare needs to be monitored to not only minimize suffering, but to provide positive affective states and experiences. Currently, there is limited guidance in...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

Falendysz, E. A., Calhoun, D. M., Smith, C. A. et al. 2020. Outside the box: Working with wildlife in biocontainment. ILAR Journal 61(1), 72-85.

Research with captive wildlife in Animal Biosafety Level 2 (ABSL2) and 3 (ABSL3) facilities is becoming increasingly necessary as emerging and re-emerging diseases involving wildlife have increasing impacts on human, animal, and environmental health. Utilizing...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

Hempstead, M. N., Waas, J. R., Stewart, M. et al. 2020. Can isoflurane and meloxicam mitigate pain associated with cautery disbudding of 3-week-old goat kids? Animals 10(5), 878.

We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does (mean ± SD, 21 ± 3 days old) were randomly allocated...

Larson, C. M., Wilcox, G. L., Fairbanks, C. A. 2019. Defining and managing pain in stroke and traumatic brain injury research. Comparative Medicine 69(6), 510–519.

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other...