Objective Surgery is an integral part of many experimental studies. Aseptic and minimal invasive surgical technique and optimal perioperative and post-operative care are prerequisites to achieve surgical success and best possible animal welfare outcomes. Good surgical practice cannot only improve the animal’s postoperative recovery, but also study outcome and validity. There seems to be a lack of implementation of good surgical practice during rodent surgery. The aim of this systematic review is to identify, critically evaluate and compare the currently recommended standards and underlying guidelines for rodent surgery—and finally to compile a comprehensive guideline of good surgical practice for rodent surgery.
Search strategy PubMed, Embase and Web of Science were searched to identify guidelines published in peer-reviewed journals. To identify grey literature and unpublished guidelines, we will perform a Google search for published guidelines and search laboratory animal sciences books for relevant book chapters. Additionally, we will conduct a survey among animal researchers enquiring about the guidelines they use.
Screening and study selection For publications retrieved by the systematic search, unique references are screened by two reviewers, first for eligibility based on title and abstract and subsequently for final inclusion based on full text. Eligibility of books is based on title and content, final inclusion based on chapter full text. Guidelines are either retrieved by Google searches or a survey. Google searches will be conducted by at least four of the authors. Thereafter, guidelines will be screened by two of the authors.
Data extraction and synthesis We will extract data from publications, book chapters and guidelines. Based on the extracted data, we will perform a descriptive synthesis of the bibliographical details, guideline development and endorsement, and the prevalence of individual recommendations, including subgroup analysis of the guidance per continent or country and differences between peer-reviewed versus non-peer-reviewed guidance.
- biomedical research
- models, animal
- standard of care
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Strengths and limitations of this study
We use a systematic approach in order to obtain a more unbiased view on guidelines available for rodent surgery.
We have defined inclusion and exclusion criteria in our protocol and blind the reviewers during data extraction.
We try to review available information most comprehensively, not only including journal articles but also grey literature like book chapters and guidelines available in different formats.
Our approach might be limited by the heterogeneity of the available information making it impossible to perform meta-analytical analyses on parameters.
A number of internal guidelines might stay undetected because colleagues might not be able or allowed to share them.
Many experimental animal studies involve surgical procedures to induce a disease model, implant devices or to collect tissue or organ samples. Regardless of the surgical procedure, good surgical practice is the prerequisite for a successful outcome. Good surgical practice involves, but is not limited to (1) adequate surgical training prior to the planned surgery, (2) proper perioperative and postoperative care, (3) approved protocols of anaesthesia and analgesia, (4) approved surgical protocols and (5) the application of the principles of surgical asepsis. In its entirety, good surgical practice will result in safe, fast, minimally invasive and reproducible surgery, consequently minimising perioperative complications and improving post-surgical recovery as well as the validity of study outcomes.1–3
It is generally accepted in human as well as veterinary surgery, that aseptic technique used during surgery minimises the contamination with micro-organisms and thus prevents postoperative wound infection.3 4 The principles of good surgical practice were introduced nearly 200 years ago and—although methods, equipment and agents constantly were and still are refined throughout the years—surgical hand washing, sterile gowning and glowing as well as decontamination of the patient’s skin before surgery and the usage of sterile equipment is now standard practice in humans.5 6 However, protocols for surgical hygiene and good practice are not species-specific, and therefore, should be used regardless of performing surgery on human or animal patients of any size.
The legal requirements to perform experimental surgery are identical for rodents and large animals. For experimental rodent surgery, however, additional considerations must be taken into account, for example, large numbers of surgeries to be performed (‘batch surgery’), the use of genetically modified or immunocompromised rodents, the need for a specific (micro)surgical set up and dedicated instruments due to the animals’ small size. Additionally, there is often a very limited number of surgical assistants available.7–10
However, for rodents, the hygiene standards applied during surgery seem to be much lower, although it is known that rodents can develop (subclinical) wound infections and septicaemia—as they are used as infection models.11–13 Nevertheless, there seems to be a lack of implementation of good surgical practice during experimental rodent surgery. Therefore, the aim of this systematic review is to identify, critically evaluate and compare current guidelines describing good surgical practice for experimental rodent surgery. The results of this study will be used to compile a comprehensive guideline of good surgical practice for rodent surgery, which will then be promoted via laboratory animal organisations and societies as well as implemented into surgical training offers.
Materials and methods
This protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis-Protocol14 guidelines as far as possible (some elements, for example risk of bias assessment and meta-analysis, are not applicable to this systematic review of guidelines). At the time of submission of this protocol, full-text screening had been started, but not completed.
We aim to include all (types of) records describing guidelines on good surgical practice for rodents, regardless of language, publication status or date of publication. Languages included will be Dutch, English, French and German. Records not focusing on general surgical practice, but rather describing the details of a certain surgical intervention will not be considered. For both title and abstract and full-text screening, the following exclusion criteria are used: (1) not on animals (eg, human/in vitro); (2) not a guideline (eg, primary animal study); (3) not on surgery (eg, LAS guideline on another topic) and (4) on surgery, but not on rodents.
Publications in peer-reviewed journals
PubMed and Embase (via Ovid) were searched from inception to 3 September 2021, to identify guidance on good surgical practice for rodent surgery published in peer-reviewed journals (figure 1). The comprehensive search strategy was based on the protocol published by Vollert et al.15 Search strings were based on the search components “guidelines”, “surgery” and “rodents”. The full comprehensive search strings are shown in tables 1 and 2. We will also manually search laboratory animal science handbooks used by our team and researchers in our network for additional potentially relevant book chapters containing guidance on rodent surgery.
Grey literature (book chapters and unpublished guidelines)
We will search laboratory animal sciences books for relevant book chapters. Books will be included based on their title and content, the relevant chapters will be screened by two of the authors, the final inclusion will be based on the chapter full-text. In addition to published guidelines, we anticipate that researchers may also use unpublished (institutional) guidelines or protocols for rodent surgery. We will therefore supplement our systematic search of published literature with two strategies to identify grey literature. First, we will perform a Google search to identify (institutional) guidelines posted on, for example, university websites. We will use various combinations and variations on the following search terms: rodent, mouse, rat, surgery, aseptic, guidance, guidelines and protocol (in Dutch, English, French and German) and will screen at least the first 50 search results for each search performed. Google searches will be performed by at least four authors with at least four different computers to take into account that search engines customise to computers. Second, we will attempt to obtain local institutional guidelines by approaching animal researchers in our extended network or through learnt societies such as the Federation of European Laboratory Animal Science Associations, the European College for Laboratory Animal Medicine, the European Society of Laboratory Animal Veterinarians, Norway’s National Consensus Platform for the advancement of the 3 Rs (Norecopa), NC3R and Understanding Animal Research with a request to (anonymously) submit guidelines for rodent surgery.
Screening and study selection
For publications, duplicates were removed from the combined comprehensive search results using ASYSD (https://camarades.shinyapps.io/RDedup/). Screening of unique records is performed using the Rayyan platform (https://rayyan.qcri.org/). In both screening phases, each record is screened independently by two reviewers (PS and either KEW, FG or SZ), who are blinded to each other’s decisions, but not to the authors of the records being screened. Discrepancies will be resolved through discussion, or, if no consensus can be reached, a third reviewer will serve as arbiter.
We will attempt to obtain full-text versions of all included articles through open access, interlibrary loan or by contacting authors directly. Articles for which no full-text version can be obtained will be excluded from the review. We will check the reference lists of included studies and book chapters and relevant reviews for additional eligible references based on title, which will then undergo screening as described above.
For grey literature, potentially relevant book chapters and documents obtained by Google search as well as submitted by survey respondents will be included based on their title, content and structure of the relevant chapters by the reviewer retrieving them. Details on the source, title, author or institute of the records will be recorded in a spreadsheet and duplicates will be detected manually. Eligible records will then be assessed by a second reviewer for final inclusion. All included records will be then distributed to two independent reviewers and screened based on full-text using the same exclusion criteria as described above.
Data extraction and synthesis
From each included record (ie, publications, book chapters or guidelines), we will extract bibliographical details, for example, first author, country of institute of the first author and year of publication and journal. From each record, we will then extract all its individual guidance elements as individual recommendations. Based on the experience of the review team, a preliminary list of individual recommendations has been created (see tables 3 and 4), and we will extract data on whether or not guidelines contain these recommendations. Second, we will record any additional recommendations not yet included in the list. Across guidelines, the elements will be ranked based on the frequency of appearance across the included guidelines. Finally, we will extract characteristics pertaining to the development of and support for the record, to come to a diligence classification (table 5).
All data will be extracted by one reviewer and checked for errors by a second reviewer. In case of discrepancies, the initial two reviewers will attempt to reach consensus through discussion. If consensus cannot be reached, a third reviewer will serve as arbiter. Subsequently, we will perform a descriptive synthesis of the bibliographical details, characteristics of guideline development and endorsement, and the prevalence of (themes of) individual recommendations. We will perform subgroup analysis of the guidance per continent, within Europe per country and differences between peer-reviewed versus non-peer-reviewed guidance.
Contributors All authors (FG, TB, KEW, MRH, SZ and PS) contributed to the conception, planning and design of the described systematic review protocol. PS and KEW drafted the manuscript and FG, TB, MRH and SZ revised it critically. PS submitted the manuscript.
Funding This work is supported by a Swiss 3RCC grant (Project OC-2018-002).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.