Perioperative enhanced recovery after surgery (ERAS) for non-malignant gynaecological conditions.

We will follow the methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions [ 37 , 38 ] and adhere to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 Statement for reporting [ 39 ]. We have developed our protocol's Background and Methods sections according to the guidance from these resources. We will include published and unpublished randomised controlled trials (RCTs), cluster‐RCTs, and cross‐over trials (only data from their first phase before cross‐over) assessing the effect of ERAS protocols in women undergoing any gynaecological surgery for non‐malignant conditions, including those undergoing caesarean section. We will exclude quasi‐randomised and pseudo‐randomised studies. We will also include data from conference abstracts and contact their investigators for additional information, whenever necessary. We will apply no restrictions regarding the year of dissemination or language of publication [ 40 ]. We will include studies of adult women undergoing elective surgeries for non‐malignant gynaecological conditions, such as fibroids, endometriosis, and others like adenomyosis, endometrial polyps, benign ovarian tumours and cysts (and other gynaecological benign tumours), chronic pelvic pain/pelvic inflammatory disease, uterine and/or vaginal wall prolapse, incontinence, abnormal uterine bleeding, and Bartholin's cysts. We will also include studies on women undergoing caesarean section [ 41 ]. We will include studies on women undergoing surgery for both malignant and non‐malignant reasons only if the subset of participants undergoing surgery for non‐malignant conditions is > 75% of the overall study population, if these provide separate outcome data on non‐malignant surgeries within their published report, or if such data become available after correspondence with the authors. If we include trials with mixed populations, we will investigate their effect by excluding them within dedicated sensitivity analyses. We will not apply any restrictions in terms of settings. We will exclude studies with a purely paediatric population (below 18 years of age), or those only involving women undergoing emergency procedures or surgery purely due to malignant aetiology, as the latter is the focus of another Cochrane review [ 29 ]. We will include studies that include a mixture of included and excluded populations only if they contain published data on the population of interest or if such unpublished data become available after contacting their authors. Considering the substantial clinical heterogeneity of the populations studied in this review and the significant differences in surgical procedures, we will also examine the effect of perioperative ERAS protocols separately for each type of surgery (e.g. caesarean section, hysterectomy, myomectomy, etc.), if possible [ 29 ]. We will include all variations of ERAS protocols as specified by the researchers. Considering that all ERAS protocols are evidence‐based multidisciplinary approaches aiming at optimised perioperative care, they should consist of combinations of different domains. As per the Cochrane review by Chau et al [ 29 ], we will classify the ERAS domains as defined by the ERAS Society [ 21 ]. The 17 clinical domains can be categorised as preoperative, intraoperative, and postoperative, depending on the timing of their implementation relative to the surgery [ 21 , 22 ]. Some of these are labelled as 'perioperative' because their components may be applied at more than one time point. Each one of these domains is further defined in the Description of the intervention and how it might work section: Preoperative domains: Pre‐admission information, education, and counselling Pre‐operative optimisation Prehabilitation (not applicable to our population of interest) Avoidance of routine preoperative bowel preparation Avoidance of pre‐anaesthetic medication: this refers to the ERAS recommendation to limit the routine use of sedatives and anxiolytics before surgery unless specifically indicated (e.g. for extreme anxiety or other medical reasons). Many conventional approaches still use benzodiazepines or other medications before anaesthesia induction. Still, ERAS protocols generally aim to avoid these due to their potential impact on delayed recovery and prolonged hospital stays. Perioperative nausea and vomiting prophylaxis Carbohydrate loading and avoidance of fasting Perioperative surgical site infection reduction bundles Perioperative prevention of blood clot formation in the veins (i.e. venous thromboembolism prophylaxis) Domains during the operation: Standard anaesthetic protocols Goal‐directed fluid therapy Minimally invasive surgery Standard anaesthetic protocols and intraoperative multimodal analgesia Goal‐directed fluid therapy Minimally invasive surgery Postoperative domains: Early feeding Prevention of postoperative ileus Opioid‐sparing multimodal postoperative analgesia Early cessation of urinary drainage via catheters Early mobilisation Preoperative domains: Pre‐admission information, education, and counselling Pre‐operative optimisation Prehabilitation (not applicable to our population of interest) Avoidance of routine preoperative bowel preparation Avoidance of pre‐anaesthetic medication: this refers to the ERAS recommendation to limit the routine use of sedatives and anxiolytics before surgery unless specifically indicated (e.g. for extreme anxiety or other medical reasons). Many conventional approaches still use benzodiazepines or other medications before anaesthesia induction. Still, ERAS protocols generally aim to avoid these due to their potential impact on delayed recovery and prolonged hospital stays. Perioperative nausea and vomiting prophylaxis Carbohydrate loading and avoidance of fasting Perioperative surgical site infection reduction bundles Perioperative prevention of blood clot formation in the veins (i.e. venous thromboembolism prophylaxis) Domains during the operation: Standard anaesthetic protocols Goal‐directed fluid therapy Minimally invasive surgery Standard anaesthetic protocols and intraoperative multimodal analgesia Goal‐directed fluid therapy Minimally invasive surgery Postoperative domains: Early feeding Prevention of postoperative ileus Opioid‐sparing multimodal postoperative analgesia Early cessation of urinary drainage via catheters Early mobilisation Chambers et al [ 42 ], who examined the domains of ERAS protocols with a specific focus on colorectal surgery, and the Cochrane review by Chau et al in the field of gynaecologic oncology [ 29 ], considered an ERAS approach eligible if it encompassed a minimum of four domains. We have decided to apply a stricter definition and increase this threshold to a minimum of eight clinical ERAS domains. This decision ensures that the included studies will reflect a more comprehensive implementation of ERAS principles, maintaining the integrity of the ERAS approach and maximising its clinical relevance. Given that positive outcomes are likely best achieved when multiple ERAS elements are implemented, this threshold will help distinguish true ERAS protocols from conventional perioperative care. Prehabilitation does not apply to this review's population and will be excluded from the evaluated domains [ 21 ]. The four domains related to ERAS management will also be excluded from the evaluated domains [ 21 , 29 ]. We will exclude studies with ambiguous definitions or inconsistent implementation of their ERAS protocols or implementation of fewer than eight ERAS domains. If any, we will report such studies in the 'Characteristics of excluded studies' section, explicitly recording their ambiguities and justifying their exclusion. We will consider conventional perioperative care, which usually lacks the organised interdisciplinary ERAS approach and entails conventional surgical and recovery procedures, as the comparator. Adapting the definition by Chau et al [ 29 ], this traditional or standard care approach may contain no domains of an ERAS protocol, contain some domains of an ERAS protocol yet without the required standardisation or the minimum required number of eight domains, or correspond to the approach implemented before the introduction of a formal ERAS protocol. Some conventional care approaches may already include ERAS‐like domains, making it difficult to distinguish between true ERAS and conventional care. To mitigate this, we will attempt to extract how many ERAS‐like domains are included in the comparator arms whenever possible. While conventional care varies across institutions, it typically includes combinations of mechanical and antibiotic bowel preparation, overnight preoperative fasting, intravenous fluids before anaesthesia, placement of pelvic drains or nasogastric tubes, and initiation of a graduated oral intake until the return of bowel sounds [ 29 ]. These aspects distinguish it from ERAS protocols, which focus on early recovery and multimodal interventions. When we find a clear description of the comparator and identify ERAS elements incorporated into conventional perioperative care, we plan to conduct a sensitivity analysis excluding studies with four, five, six, or seven ERAS elements in the comparator arm. In other words, we plan to examine whether keeping only studies with three or fewer ERAS elements in their conventional perioperative care affects the results. This will help assess whether studies with a potentially major overlap between the interventions substantially affect the conclusions. The comparison of this review will be the following: Perioperative ERAS protocols versus conventional perioperative care Perioperative ERAS protocols versus conventional perioperative care Since similar populations are covered, our outcomes overlap with the relevant outcomes of the Cochrane review by Chau et al [ 29 ]. The critical outcomes of the review will be: Length of postoperative hospital stay (i.e. the time from surgery to discharge measured in days) as an outcome reflecting potential benefit. Postoperative complications (i.e. any complication occurring within 30 days after the operation, such as surgical site infections, bleeding, wound or anastomosis breakdown of the stitches, postoperative fever, atelectasis, pneumonia, bowel obstruction, paralytic ileus, urinary tract retention or infection, incisional hernia, deep vein thrombosis, and pulmonary embolism, etc.) as an outcome reflecting potential harm. These will include grade 1 to 4 complications as categorised by the Clavien‐Dindo classification system [ 43 ]. Length of postoperative hospital stay (i.e. the time from surgery to discharge measured in days) as an outcome reflecting potential benefit. Postoperative complications (i.e. any complication occurring within 30 days after the operation, such as surgical site infections, bleeding, wound or anastomosis breakdown of the stitches, postoperative fever, atelectasis, pneumonia, bowel obstruction, paralytic ileus, urinary tract retention or infection, incisional hernia, deep vein thrombosis, and pulmonary embolism, etc.) as an outcome reflecting potential harm. These will include grade 1 to 4 complications as categorised by the Clavien‐Dindo classification system [ 43 ]. The important outcomes of the review will be the following [ 44 ]: Early (within 30 days after the operation) and late (within three months after the operation) postoperative all‐cause death (also corresponding to Clavien‐Dindo grade 5 complication). Normal bowel function , assessed as the first postoperative bowel movement (i.e. time to first flatus) or the complete normal bowel function (i.e. time to first defaecation). Readmission to the hospital within a 30‐day time frame postoperatively. In addition, the following patient‐reported outcomes (PROs): Quality of life , measured within a three‐month timeframe postoperatively using validated general quality of life scales such as the EuroQol‐ 5 Dimension (EQ‐5D), the Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36), and the World Health Organization Quality of Life‐100 (WHOQOL‐100). Although these tools contain domains related to pain or discomfort, they measure it inside the context of general postoperative quality of life. We aim to record the overall scores instead of domain‐specific scores. Considering their applicability in surgical research, the SF‐36 will be preferred over the EQ‐5D, which will be preferred over the WHOQOL‐100. If a study reports multiple scales within the same hierarchy level (e.g. variants of the WHOQOL), we will prioritise the most frequently reported measure across the included studies. Pain , measured within the first 30 days postoperatively through scales, such as the visual analogue scale (VAS) or the numeric rating scale (NRS). If a study provides pain (or discomfort) scores in the context of a general quality of life scale, we will not record these as data on this outcome, which requires measurement via pain‐specific scales. The VAS will be preferred over the NRS since it is the most commonly used tool in postoperative studies due to its simplicity, ease of administration, and high reliability. Satisfaction with hospital care , measured within six weeks after discharge by any standardised questionnaire, such as the Hospital Consumer Assessment of Healthcare Providers (HCAPHPS). HCAPHPS will be prioritised over other relevant standardised tools. Early (within 30 days after the operation) and late (within three months after the operation) postoperative all‐cause death (also corresponding to Clavien‐Dindo grade 5 complication). Normal bowel function , assessed as the first postoperative bowel movement (i.e. time to first flatus) or the complete normal bowel function (i.e. time to first defaecation). Readmission to the hospital within a 30‐day time frame postoperatively. In addition, the following patient‐reported outcomes (PROs): Quality of life , measured within a three‐month timeframe postoperatively using validated general quality of life scales such as the EuroQol‐ 5 Dimension (EQ‐5D), the Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36), and the World Health Organization Quality of Life‐100 (WHOQOL‐100). Although these tools contain domains related to pain or discomfort, they measure it inside the context of general postoperative quality of life. We aim to record the overall scores instead of domain‐specific scores. Considering their applicability in surgical research, the SF‐36 will be preferred over the EQ‐5D, which will be preferred over the WHOQOL‐100. If a study reports multiple scales within the same hierarchy level (e.g. variants of the WHOQOL), we will prioritise the most frequently reported measure across the included studies. Pain , measured within the first 30 days postoperatively through scales, such as the visual analogue scale (VAS) or the numeric rating scale (NRS). If a study provides pain (or discomfort) scores in the context of a general quality of life scale, we will not record these as data on this outcome, which requires measurement via pain‐specific scales. The VAS will be preferred over the NRS since it is the most commonly used tool in postoperative studies due to its simplicity, ease of administration, and high reliability. Satisfaction with hospital care , measured within six weeks after discharge by any standardised questionnaire, such as the Hospital Consumer Assessment of Healthcare Providers (HCAPHPS). HCAPHPS will be prioritised over other relevant standardised tools. The important outcomes of interest will cover both potential benefits and areas of harm to ensure a balanced overview of the evidence base following relevant guidance. In particular, normal bowel function and PROs will reflect potential benefits, while death and readmission will reflect potential areas of harm. If we exclude studies based on outcomes, we will ensure that these outcomes have not been measured rather than simply not reported. Regarding the economic outcomes and our secondary objective, we will create a brief economic commentary following the guidelines of the Campbell and Cochrane Economics Methods Group [ 45 ]. This commentary will examine the degree to which the main results of relevant economic evaluations suggest that ERAS could be considered favourable or unfavourable from an economic standpoint when executed in different contexts and settings. We will not make any definitive statements about the cost‐effectiveness of ERAS that would apply universally. While not enabling us to make definitive conclusions, the evidence collected and synthesised within this economic commentary alongside our clinical outcomes will provide useful information for healthcare decision‐making and potentially inform and encourage new economic analyses [ 45 ]. To achieve this, we will summarise key findings from full economic evaluations comparing ERAS protocols with conventional perioperative care in women undergoing gynaecological surgery for non‐malignant conditions. These evaluations will include: Cost‐effectiveness analyses (CEAs) and cost‐utility analyses (CUAs) , which report incremental cost‐effectiveness ratios (ICERs) (i.e. costs per life‐years gained (LYGs), quality‐adjusted life years (QALYs) gained, or disability‐adjusted life years (DALYs) averted due to the implementation of ERAS compared to conventional perioperative care). We will also report the cost‐effectiveness thresholds , which these economic evaluations will provide as reference values for interpreting their findings. Cost‐effectiveness thresholds vary by country, health system, and disease burden. Cost‐benefit analyses (CBAs) , which express their findings in monetary terms (net benefits in currency). We will record the monetised net benefits (MNBs) to determine the net financial return on implementing ERAS. Cost‐effectiveness analyses (CEAs) and cost‐utility analyses (CUAs) , which report incremental cost‐effectiveness ratios (ICERs) (i.e. costs per life‐years gained (LYGs), quality‐adjusted life years (QALYs) gained, or disability‐adjusted life years (DALYs) averted due to the implementation of ERAS compared to conventional perioperative care). We will also report the cost‐effectiveness thresholds , which these economic evaluations will provide as reference values for interpreting their findings. Cost‐effectiveness thresholds vary by country, health system, and disease burden. Cost‐benefit analyses (CBAs) , which express their findings in monetary terms (net benefits in currency). We will record the monetised net benefits (MNBs) to determine the net financial return on implementing ERAS. We will record the following cost outcomes: Direct costs , which will be further divided into: Medical , such as costs related to hospital stay, medications, surgical procedures, and follow‐up care. Non‐medical , such as patient and family costs (e.g. out‐of‐pocket expenses and home care or other informal caregiving costs), costs related to transportation, and other sector direct costs incurred outside the healthcare system. Indirect costs : Productivity impacts, including lost wages due to work absenteeism, or reduced work capacity. Direct costs , which will be further divided into: Medical , such as costs related to hospital stay, medications, surgical procedures, and follow‐up care. Non‐medical , such as patient and family costs (e.g. out‐of‐pocket expenses and home care or other informal caregiving costs), costs related to transportation, and other sector direct costs incurred outside the healthcare system. Indirect costs : Productivity impacts, including lost wages due to work absenteeism, or reduced work capacity. We will search for relevant trials in the following electronic databases [ 46 ]: CENTRAL (Cochrane Central Register of Controlled Trials), via the Cochrane Register of Studies Online (CRSO) web platform, from inception onwards; PubMed (MEDLINE) – via the PubMed interface, from inception onwards; Scopus – via the Elsevier Scopus database, from inception onwards; ClinicalTrials.gov, via the ClinicalTrials.gov registry, from inception onwards; WHO International Clinical Trials Registry Platform (ICTRP), via the WHO ICTRP portal, from inception onwards. CENTRAL (Cochrane Central Register of Controlled Trials), via the Cochrane Register of Studies Online (CRSO) web platform, from inception onwards; PubMed (MEDLINE) – via the PubMed interface, from inception onwards; Scopus – via the Elsevier Scopus database, from inception onwards; ClinicalTrials.gov, via the ClinicalTrials.gov registry, from inception onwards; WHO International Clinical Trials Registry Platform (ICTRP), via the WHO ICTRP portal, from inception onwards. For the identification of RCTs in PubMed, we will use the PubMed format of the sensitivity‐maximising version (2008 revision) of the Cochrane Highly Sensitive Search Strategy filter for identifying randomised trials in MEDLINE, as this is presented in Chapter 4 of the Cochrane Handbook for Systematic Reviews of Interventions [ 46 ] and its technical supplement [ 47 ]. We will apply no language or date restrictions to our search algorithm. We will adhere to Cochrane's best practices for literature searching and search strategy development, ensuring that relevant studies are identified. The full search strategy, which was developed by the authors and whose keywords on ERAS were adapted from the Cochrane review by Chau et al [ 29 ], is provided in Supplementary material 1 . According to the proper guidance, Embase is recommended as part of a comprehensive search strategy. However, we do not have institutional or individual access to Embase. To mitigate this, we will include Scopus, which indexes a wide range of biomedical literature, including many journals that are also covered in Embase. Additionally, we will conduct forward and backward citation tracking to ensure that relevant studies not indexed in our searched databases are identified. An information specialist will not support this review, but the authors will follow all the appropriate guidance. We will review the reference lists of retrieved studies, relevant reviews, and conference proceedings from major conferences to identify additional references [ 46 ]. We will also search relevant grey literature sources, including the first 200 records from the Google Scholar database. We will also search the Epistemonikos database ( https://www.epistemonikos.org/ ), a multilingual database of health evidence and the largest source of systematic reviews. Furthermore, we will consult experts in the field to identify ongoing or existing studies. To ensure the integrity of the included studies, we will check PubMed for retracted studies and studies of concern, including expressions of concern, errata, corrigenda, and retractions. We will exclude any identified problematic studies from our review. We will conduct a supplementary search for economic evidence using a combination of approaches. First, we will check reference lists and track forward citations from eligible studies identified for inclusion in the main review. Next, we will search the NHS Economic Evaluation Database (NHS EED) using keyword terms relating to ERAS. Finally, we will apply the specialist search filters of the Campbell and Cochrane Economics Methods Group [ 45 ] to the records retrieved from one or two selected general electronic biomedical literature databases searched for the main review. We will select studies, import their data into RevMan Web [ 48 ], and analyse the data according to the Cochrane Handbook for Systematic Reviews of Interventions [ 38 , 46 , 49 , 50 ] We will use the Rayyan online software to screen the records found in the electronic databases [ 51 ]. After removing the duplicates using EndNote 20 [ 52 ], sets of review authors (DG, AB, MP, AK, and IT) will independently screen the titles and abstracts of all articles retrieved. We will exclude studies that do not meet the inclusion criteria and will retrieve the full texts of the remaining potentially eligible studies. Sets of independent review authors (DG, AB, MP, AK, and IT) will evaluate these full texts to identify the included and ongoing studies of this review. For the excluded studies, they will document the reasons for exclusion in the 'Characteristics of excluded studies' table. For any disagreements during both stages, we will involve a third review author (CSS) [ 46 ]. When the eligibility of a study is not certain, we will contact the study authors to request additional clarification. With the help of Cochrane, we will translate studies unknown to the review authors' language and assess them for eligibility. We will present the entire selection process in a PRISMA flow chart. A review author (MP) will assess the identified economic evaluations using the same eligibility criteria as for the rest of the review. Sets of independent review authors (DG, AB, M Papageorgakopoulou, AK, and IT) will independently extract study characteristics and outcome data from the reports of each included study into a pre‐defined and piloted Microsoft Excel form. A review author will import the data, and the other review author of each set will validate the imported values against the extraction form. We will translate studies unknown to the review authors' language via Cochrane. We will resolve any disagreements during the data collection process through discussion and, if discrepancies persist, a third review author (CSS) will be consulted [ 49 , 50 ]. For RCTs with multiple reports, we will use the main report as the reference and will supplement it with additional data from the secondary publications. If it is necessary to obtain additional methodological details or data, we will contact the authors of the included studies via email. If we receive no reply or insufficient data, we will send a second email within 20 days after the first communication. The extraction form will encompass the following data items: General information and study details: Identifiers of the report and study Names of the review authors extracting data and extraction date Funding sources for the study Declarations of interest of the primary investigators Country and income level per the World Bank's classification Study centre(s) Study period Corresponding author's contact details Trial registration information. Study methods: Study design: parallel, cluster, or cross‐over trial Recruitment and sampling procedures Enrolment start and end dates Details on random sequence allocation and concealment Details on masking of participants Length of follow‐up Methods of handling missing data (e.g. imputations). Participants: Age (mean, standard deviation (SD) of the overall group and each intervention group) Demographic information (i.e. race and ethnicity), where available Prognostic factors for surgical recovery at baseline (i.e. smoking, mean, SD of body mass index (BMI), comorbidities, and the American Society of Anaesthesiology (ASA) classification of the overall group and each intervention group) Inclusion and exclusion criteria The total number of participants randomised The number of participants assigned to each intervention group The condition that is surgically treated (including pregnancy in the case of caesarean section) The type of surgery (e.g. hysterectomy, myomectomy, caesarean section, etc.) The type of surgical approach (open, MIS (e.g. robot‐assisted, laparoscopic, vaginal, etc.)) The surgeon's level of training, especially in minimally invasive approaches (i.e. fellowship‐trained or not) Interventions: Components of the ERAS protocols according to the guidelines of the ERAS Society (see also Description of the intervention and how it might work ; Types of interventions ) and the timing of their implementation Description of the comparator perioperative care protocols and recording of the number of their ERAS domains to ensure that these are indeed traditional care approaches rather than ERAS Compliance of each centre with ERAS and standard perioperative care protocols, if available Description of co‐interventions, if applied Outcomes: Definition Time point of measurement Measurement scales of pain, quality of life, and satisfaction with hospital care Raw outcome data (i.e. number of events in each group and number of total participants in the group for which the outcome was measured for dichotomous outcomes, and mean, standard deviation, and total participants in the group for which the outcome was measured for continuous or discrete outcomes such as scales). Economic evidence, including basic data on the characteristics of each identified economic evaluation, and brief text extracts summarising their principal findings [ 45 ]: Study design (i.e. trial‐based, model‐based, or hybrid) Economic perspective (e.g. patient, healthcare payer, societal) Time horizon and discount rate Country Currency (e.g. USD, GBP, EUR) Price year Cost components (i.e. direct medical, direct non‐medical, or indirect) Economic evaluation type (i.e. CEA, CUA, CBA) Health outcome measure used (i.e. QALYs, DALYs) Primary findings (i.e. ICERs for CEAs and CUAs and MNBs for CBAs) Reference values for interpretation (i.e. cost‐effectiveness thresholds) Notes (i.e. verbatim text on the authors’ main conclusions and interpretation of findings, limitations noted by authors, uncertainty surrounding the principal conclusions, or sensitivity analysis results) to be presented descriptively in the commentary General information and study details: Identifiers of the report and study Names of the review authors extracting data and extraction date Funding sources for the study Declarations of interest of the primary investigators Country and income level per the World Bank's classification Study centre(s) Study period Corresponding author's contact details Trial registration information. Study methods: Study design: parallel, cluster, or cross‐over trial Recruitment and sampling procedures Enrolment start and end dates Details on random sequence allocation and concealment Details on masking of participants Length of follow‐up Methods of handling missing data (e.g. imputations). Participants: Age (mean, standard deviation (SD) of the overall group and each intervention group) Demographic information (i.e. race and ethnicity), where available Prognostic factors for surgical recovery at baseline (i.e. smoking, mean, SD of body mass index (BMI), comorbidities, and the American Society of Anaesthesiology (ASA) classification of the overall group and each intervention group) Inclusion and exclusion criteria The total number of participants randomised The number of participants assigned to each intervention group The condition that is surgically treated (including pregnancy in the case of caesarean section) The type of surgery (e.g. hysterectomy, myomectomy, caesarean section, etc.) The type of surgical approach (open, MIS (e.g. robot‐assisted, laparoscopic, vaginal, etc.)) The surgeon's level of training, especially in minimally invasive approaches (i.e. fellowship‐trained or not) Interventions: Components of the ERAS protocols according to the guidelines of the ERAS Society (see also Description of the intervention and how it might work ; Types of interventions ) and the timing of their implementation Description of the comparator perioperative care protocols and recording of the number of their ERAS domains to ensure that these are indeed traditional care approaches rather than ERAS Compliance of each centre with ERAS and standard perioperative care protocols, if available Description of co‐interventions, if applied Outcomes: Definition Time point of measurement Measurement scales of pain, quality of life, and satisfaction with hospital care Raw outcome data (i.e. number of events in each group and number of total participants in the group for which the outcome was measured for dichotomous outcomes, and mean, standard deviation, and total participants in the group for which the outcome was measured for continuous or discrete outcomes such as scales). Economic evidence, including basic data on the characteristics of each identified economic evaluation, and brief text extracts summarising their principal findings [ 45 ]: Study design (i.e. trial‐based, model‐based, or hybrid) Economic perspective (e.g. patient, healthcare payer, societal) Time horizon and discount rate Country Currency (e.g. USD, GBP, EUR) Price year Cost components (i.e. direct medical, direct non‐medical, or indirect) Economic evaluation type (i.e. CEA, CUA, CBA) Health outcome measure used (i.e. QALYs, DALYs) Primary findings (i.e. ICERs for CEAs and CUAs and MNBs for CBAs) Reference values for interpretation (i.e. cost‐effectiveness thresholds) Notes (i.e. verbatim text on the authors’ main conclusions and interpretation of findings, limitations noted by authors, uncertainty surrounding the principal conclusions, or sensitivity analysis results) to be presented descriptively in the commentary Sets of independent review authors (DG, AB, MP, AK, and IT) will assess the risk of bias according to Chapter 7 [ 53 ] and Chapter 8 [ 54 ] of the Cochrane Handbook for Systematic Reviews of Interventions using the Cochrane risk of bias assessment tool RoB 2 [ 55 ]. In case of disagreements between the two review authors, there will be a third one to decide (MP or CSS). For the risk of bias assessment of the results of cluster‐RCTs and cross‐over trials, we will use the RoB 2 extensions for cluster‐RCTs and cross‐over trials, respectively [ 56 ]. The RoB 2 tool consists of specific items assessing five domains where bias may occur [ 57 ]: Bias arising from the randomisation process Bias due to deviations from intended interventions Bias due to missing outcome data Bias in the measurement of the outcome Bias in the selection of the reported result Bias arising from the randomisation process Bias due to deviations from intended interventions Bias due to missing outcome data Bias in the measurement of the outcome Bias in the selection of the reported result The two review authors will answer the signalling questions of the RoB 2 tool, following the tool's guidelines and the criteria described in the above‐mentioned chapters of the Cochrane Handbook for Systematic Reviews of Interventions [ 53 , 54 ]. Based on the review authors' answers, the risk of bias in each domain will be defined as 'low', 'some concerns', and 'high'. We will include suitable justifications and references from the trial's text or registered protocol to confirm our answers. We will also justify the proposed judgements using the tool's algorithm. We will reach the overall risk of bias assessment for each outcome of each study, taking into consideration the algorithm's suggestion and the five domain‐level judgements. In any case, the review team may overturn an algorithm's suggestion after proper justification and consensus. The overall risk of bias will be classified as [ 53 , 54 , 55 ]: 'high risk of bias' if the risk of bias was high in at least one domain or some concerns in multiple domains; 'some concerns' if there are some concerns about bias in at least one domain; 'low risk of bias' if the risk of bias was judged as low in all domains. 'high risk of bias' if the risk of bias was high in at least one domain or some concerns in multiple domains; 'some concerns' if there are some concerns about bias in at least one domain; 'low risk of bias' if the risk of bias was judged as low in all domains. If we need further methodological clarifications on the trial protocols or publications, we will contact the principal investigators. We will use the Excel tool of RoB 2 (available at https://www.riskofbias.info/ ) to efficiently store and present all judgements and their justification. This will become available as an online supplemental file in a free repository like Figshare. We will be interested in the effect of assignment to intervention at baseline (i.e. the intention‐to‐treat effect). We will assess the risk of bias for the critical outcomes: Length of postoperative hospital stay Postoperative complications within 30 days after the operation Length of postoperative hospital stay Postoperative complications within 30 days after the operation In addition, we will assess the risk of bias for the following important outcomes, including two PROs: Early postoperative all‐cause death (within 30 days after the operation) Normal bowel function, assessed as the first postoperative bowel movement (i.e. time to first flatus) Readmission to the hospital within 30 days postoperatively Quality of life, measured within a three‐month timeframe postoperatively Pain, measured within the first 30 days postoperatively Early postoperative all‐cause death (within 30 days after the operation) Normal bowel function, assessed as the first postoperative bowel movement (i.e. time to first flatus) Readmission to the hospital within 30 days postoperatively Quality of life, measured within a three‐month timeframe postoperatively Pain, measured within the first 30 days postoperatively We will not critically appraise any economic evaluations and, therefore, will not try to draw any firm or general conclusions concerning the costs or cost‐effectiveness of ERAS compared to conventional perioperative care protocols. For dichotomous outcomes (i.e. postoperative complications, postoperative all‐cause death, and readmission to the hospital) we will use the event numbers in the ERAS and conventional perioperative care groups of each study to calculate odds ratios (ORs). If necessary, we will reverse the direction of the effect in individual studies to ensure consistency across trials. For continuous outcomes (i.e. length of hospital stay, pain, time to first flatus or first defaecation, and quality of life) we will calculate mean differences (MDs) between treatment groups if studies used identical scales for their measurement. If studies used different scales to measure the outcomes (i.e. pain, quality of life), we will compute standardised mean differences (SMDs) [ 58 ]. We will present 95% confidence intervals (95% CIs) for the ORs, MDs, or SMDs. The individual participant will be the primary unit of analysis [ 58 ]. For outcomes in which events may recur, such as postoperative complications and readmissions, each participant will be considered as the unit of analysis (i.e. a participant with more than one readmission will be counted as a single event). Each complication will not be mutually exclusive only in the sensitivity analysis on postoperative complications. If a single trial involves three or more arms (i.e. compares ERAS protocols with different components between one another and to one control arm of conventional perioperative care), we will either divide the control group into equal parts, assuming equal incidence in these groups, or combine multiple ERAS arms to prevent double counting of the data of the control group. If a trial with three or more arms includes irrelevant arms, we will exclude these from the analysis. For cluster‐RCTs, we will extract the intracluster correlation coefficient (ICC) from the trial's data and, if no such data are available, from an RCT or an observational study with a similar population. If none of the above is possible, we will conduct a sensitivity analysis for different ranges of ICCs. We will combine the results of cluster‐randomised trials with the rest of the RCTs only if reasonable homogeneity is present between the studies. Additionally, we will record the number of clusters per group, the total size of clusters per group, and the unit of randomisation. In case of missing data, we will contact the authors of the included studies. In cases of non‐response, we will send a reminder 20 days after the initial communication, as mentioned above [ 58 ]. If we cannot obtain the missing data, we will adopt an imputation approach for the primary outcome of any postoperative complication and present two scenarios: one best‐case scenario (in which no participants whose data are missing experienced at least one complication) and one worst‐case scenario (in which all participants whose data are missing experienced at least one complication). For the rest of the outcomes, we will analyse the available data. If we judge the amount of missing data as considerable within certain studies, we will perform sensitivity analyses excluding these studies to investigate the impact of data loss. We will assess reporting bias by comparing each study's planned outcomes with its reported ones. If study protocols are available, we will compare them with the full publications to evaluate the likelihood of reporting bias. In instances of missing results, we will contact the study authors to obtain additional data. To screen for small‐study effects and publication bias, we will use funnel plots when a sufficient number of studies (more than 10) reporting the same outcome are available. We will make every effort to interpret any major funnel plot asymmetry. If significant asymmetry in the funnel plot suggests publication bias upon visual assessment, we will incorporate this information into our certainty of evidence assessment. If our review includes few studies eligible for meta‐analysis, our ability to detect publication bias will be significantly reduced. If that occurs, we will acknowledge this limitation [ 59 ]. We will perform analyses on the following review comparison: Perioperative ERAS protocols versus conventional perioperative care Perioperative ERAS protocols versus conventional perioperative care We will define ERAS and conventional perioperative care as presented in Types of interventions . We plan to fit random‐effects meta‐analyses due to the anticipated clinical heterogeneity of the included populations and interventions. In particular, we expect variations in the baseline risks for unfavourable prognosis to the surgery, differences in the surgical approaches and the conditions under treatment, differences in the components between the applied ERAS protocols, and variations in the conventional perioperative care approaches. From a clinical standpoint, such differences are expected in practice due to the complexity of perioperative care protocols. However, the same principles of perioperative care apply to different surgeries and surgical approaches, allowing the quantitative synthesis. We will pool ORs for dichotomous outcomes (i.e. postoperative complications, postoperative all‐cause death, and readmission to the hospital) and the MDs or SMDs for continuous or discrete outcomes (i.e. length of hospital stay, pain, time to first flatus or first defaecation, and quality of life ‐ see Measures of treatment effect ). We will estimate between‐study variation using the DerSimonian‐Laird (DL) method and calculate the 95% CI for the summary effect using the Wald‐type method. For each meta‐analysis, we will estimate heterogeneity variances (τ 2 ) and assess the presence of statistical heterogeneity by visually inspecting forest plots and calculating the I² statistic. A value of I² > 50% will indicate substantial heterogeneity [ 60 , 61 ]. The primary analyses will only include studies judged to be of overall low risk of bias for the outcome per the RoB 2 tool. We will organise our results by compiling a 'Study characteristics table' using data collected during the data extraction process. We will illustrate our meta‐analysis results using forest plots generated by RevMan Web [ 48 ]. If we consider that the differences in the populations or the interventions of the studies for an outcome prevent us from drawing clinically meaningful conclusions from their meta‐analysis, we will synthesise the relevant evidence according to the Synthesis without Meta‐analysis (SWiM) guidance [ 62 ]. To address the economic outcomes, we will follow the guidance of the Campbell and Cochrane Economics Methods Group and write a brief narrative commentary in the discussion section of the Cochrane review. We will outline the electronic health economics literature databases that we searched, the number of relevant economic evaluations we identified for each eligible comparison, the descriptive information we gathered from each study, the principal conclusions reported by the authors of each analysis (concerning the base‐case analysis), and the main sources of uncertainty in the authors’ conclusions arising from any sensitivity analyses [ 45 ]. If we detect at least substantial heterogeneity, we will perform subgroup analyses to explore its potential sources and investigate factors that could contribute to variations in the effects of ERAS on the outcomes of interest. If there are fewer than 10 studies in the analysis, we will not emphasise its findings due to insufficient data to provide meaningful results. We will choose the following as stratifying variables: The surgical approach (minimally invasive versus open); if sufficient information is provided, we will also narratively synthesise the economic evidence separately for MIS and open surgeries. The type of surgery for the condition (hysterectomy versus myomectomy versus caesarean section, etc.) The income level (as per the World Bank's classification) of the country in which ERAS was executed (low‐income or lower‐middle‐income versus upper‐middle‐income or high‐income countries) The surgical approach (minimally invasive versus open); if sufficient information is provided, we will also narratively synthesise the economic evidence separately for MIS and open surgeries. The type of surgery for the condition (hysterectomy versus myomectomy versus caesarean section, etc.) The income level (as per the World Bank's classification) of the country in which ERAS was executed (low‐income or lower‐middle‐income versus upper‐middle‐income or high‐income countries) All variables can be either study level or represent within‐study contrasts. We will assess between‐subgroup differences using the methods described in Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions [ 60 ]. We will report the results of subgroup analyses, quoting the Chi 2 statistic and its P value, the I² value of each subgroup, and the P value of the interaction test (significant if less than 0.1). We will take into account all statistical heterogeneity when interpreting the results, especially if we note any variation in the direction of effect. We will use the findings from the subgroup analyses to provide insights into the completeness and applicability of evidence in more specific surgical populations (e.g. women undergoing caesarean section) in our 'Discussion' section. In alignment with Cochrane’s equity guidance, we recognise that healthcare interventions can affect populations differently depending on socioeconomic and regional factors. Considering that the successful implementation of ERAS protocols may depend on adequate healthcare resources and financing, their adoption, implementation, and effectiveness might vary across different income settings [ 33 ]. Differences in health system financing, such as cost‐sharing models and reimbursement structures, may also impact hospitalisation duration and the overall economic burden on patients. To assess potential disparities in access, implementation, and outcomes, we will record and report information on each study setting (see Data extraction and management ). We will further conduct a subgroup analysis based on the World Bank’s classification of countries by income level, comparing low‐income or lower‐middle‐income countries to upper‐middle‐income or high‐income countries. This analysis might help determine whether variations in healthcare infrastructure and financial resources influence ERAS implementation and effectiveness. It could also shed light on whether ERAS protocols may contribute to reducing healthcare disparities by improving recovery time and minimising hospital stays and costs. There are also differences expected in the baseline risk of different population subgroups (e.g. populations of different ethnic backgrounds) of women receiving surgical care for gynaecological conditions. To somewhat address this factor, we will also record and report relevant demographic data (e.g. race, ethnicity) during data extraction (see Data extraction and management ). By aiming to synthesise how and where studies were conducted and which population groups they included, we will assess if the generalisability of our findings is affected and consider the completeness and applicability of the findings to other population groups and settings. To account for arbitrary decisions on study eligibility and data analysis [ 60 ], we will conduct sensitivity analyses for all the critical and important outcomes unless otherwise stated below. In particular, we will examine whether the pooled results are affected if: we exclude studies with mixed populations of participants undergoing surgery for gynaecological cancer and those undergoing surgery for benign conditions; we include studies with an overall high risk of bias or some concerns about bias for the outcome; we exclude conference abstracts; we use different ranges of ICCs for cluster‐RCTs, if necessary (see Unit of analysis issues ); we use the event of complication rather than the participant as the unit of analysis for the critical outcome of 'any postoperative complication' to better quantify the morbidity burden; we apply the best‐case and worst‐case scenario imputations for the primary outcome of 'any postoperative complication' in case of missing data (refer to Dealing with missing data ); we exclude studies with considerable missing data regarding the rest of the outcomes (refer to Dealing with missing data ); we only include studies with no more than three clearly recognised ERAS elements in their conventional perioperative care arm (refer to Types of interventions ). we exclude studies with mixed populations of participants undergoing surgery for gynaecological cancer and those undergoing surgery for benign conditions; we include studies with an overall high risk of bias or some concerns about bias for the outcome; we exclude conference abstracts; we use different ranges of ICCs for cluster‐RCTs, if necessary (see Unit of analysis issues ); we use the event of complication rather than the participant as the unit of analysis for the critical outcome of 'any postoperative complication' to better quantify the morbidity burden; we apply the best‐case and worst‐case scenario imputations for the primary outcome of 'any postoperative complication' in case of missing data (refer to Dealing with missing data ); we exclude studies with considerable missing data regarding the rest of the outcomes (refer to Dealing with missing data ); we only include studies with no more than three clearly recognised ERAS elements in their conventional perioperative care arm (refer to Types of interventions ). We will use the GRADEpro GDT software [ 63 ] and follow the guidelines of the GRADE approach [ 64 ] and Chapter 14 of the Cochrane Handbook for Systematic Reviews of Interventions [ 65 ] to assess the overall certainty of the evidence for the critical and most important outcomes of our review, and we will create a summary of findings table. The assessments will regard the following comparison: Perioperative ERAS protocols versus conventional perioperative care Perioperative ERAS protocols versus conventional perioperative care We will assess the certainty of evidence for the critical outcomes: Length of postoperative hospital stay Postoperative complications within 30 days after the operation Length of postoperative hospital stay Postoperative complications within 30 days after the operation And for the important outcomes, including two PROs: Early postoperative all‐cause death (within 30 days after the operation) Normal bowel function, assessed as the first postoperative bowel movement (i.e. time to first flatus) Readmission to the hospital within 30 days postoperatively Quality of life, measured within a three‐month timeframe postoperatively Pain, measured within the first 30 days postoperatively Early postoperative all‐cause death (within 30 days after the operation) Normal bowel function, assessed as the first postoperative bowel movement (i.e. time to first flatus) Readmission to the hospital within 30 days postoperatively Quality of life, measured within a three‐month timeframe postoperatively Pain, measured within the first 30 days postoperatively Sets of independent review authors (DG, AB, M Papageorgakopoulou, AK, and IT) will apply the GRADE criteria to evaluate evidence levels as high, moderate, low, or very low. The definitions for each level of certainty will be based on the GRADE Handbook [ 64 ]. This evaluation will consider five factors for the potential downgrading of the certainty level (i.e. overall risk of bias, inconsistency, imprecision, indirectness, and publication bias). Any disagreements will be resolved through discussion with another review author (CSS or MP). Regarding the 'overall risk of bias' criterion, we will refer to the overall RoB 2 judgement for the outcome to inform the relevant GRADE assessment. We will meticulously justify, document, and incorporate judgements regarding evidence certainty into outcome reporting [ 65 ]. Regarding the economic evidence, after presenting the principal sources of uncertainty in the primary studies' main conclusions based on their sensitivity analyses, we will interpret these results and formulate our conclusions based on a predefined classification of evidence. We will categorise the evidence as inadequate (indicating a lack of evidence), equivocal (indicating ambiguous or conflicting evidence), or consistent (indicating agreement across different studies) [ 45 ]. Due to resource limitations, consumers will not be involved in this review. Nevertheless, and most importantly, we will use outcome sets for the review's outcomes [ 66 ], which were developed with consumer involvement [ 67 ].

When undergoing surgery, patients are expected to stay in the hospital until their physicians deem them ready for discharge. During the recovery period, whether from surgery for fibroids, endometriosis, caesarean section, or any other type of gynaecological surgery for non‐malignant conditions (e.g. adenomyosis, benign tumours or cysts, uterine prolapse), patients may experience delayed mobilisation, postoperative pain, delayed bowel movement, nausea, vomiting, or even infections and blood clots [ 1 , 2 , 3 , 4 ]. In terms of severity, such complications can range from mild, self‐resolving conditions to more severe ones, requiring medical or surgical interventions [ 5 ]. These issues result from the surgery per se and the stress it puts on the patient's body during the perioperative period. Surgical stress refers to all the physiological and metabolic disturbances that lead to changes in a patient's inflammatory, hormonal, genomic, and acute phase reactions during a surgical operation [ 6 ]. The stress response to tissue injury can be generally divided into three phases: the "ebb phase" or "early period", the "flow phase" or "late period", and the restorative phase [ 7 , 8 ]. The first phase occurs during the first 48 hours after surgery. It is marked by an attempt by the body to achieve homeostasis (i.e. stability) by reducing energy demands and functioning in hypodynamic conditions. The second phase is characterised by extreme protein and lipid breakdown and a hyperdynamic state with increased energy and oxygen demands. During this phase, the body attempts to recover from the initial injury. This is followed by the final restorative or anabolic phase when the body attempts to restore its normal state [ 7 , 8 , 9 ]. The above series of events synthesise a physiologic response to trauma, which is caused by the activation of the sympathetic nervous system and adrenal medulla that produce catecholamines (i.e. adrenaline and noradrenaline) and the hypothalamic‐pituitary‐adrenal axis (i.e. the communication between the brain and the adrenal glands) that produces another important stress hormone, cortisol. Due to the catecholamine‐induced inhibition of the insulin‐producing beta cells of the pancreas, the body's response to insulin becomes less effective, a state called "increased insulin resistance" [ 10 , 11 ]. This state, combined with the effect of stress hormones themselves, decreases the cell intake of glucose, leading to increased glucose in the blood (i.e. hyperglycaemia). Hyperglycaemia may negatively impact wound healing, increasing hospital stay, and risk of perioperative infections [ 10 , 11 ]. In parallel with the endocrine hormonal response, there is a bimodal response by the immune system consisting of an initial exaggerated inflammatory response followed by a later compensatory anti‐inflammatory reaction [ 9 ]. Prolonged surgical stress and the resulting hyperglycaemia and immune response may increase perioperative complication rates, prolong the length of hospital stay, and delay the patient's return to daily activities. Perioperative complications themselves may also prolong the hospital stay, leading to a vicious cycle. Given the body's responses to surgery‐induced tissue damage, perioperative care protocols that minimise this stress, reduce the frequency of complications, and speed up the return to normal activities are needed. Apart from increasing complications, exaggerated surgical stress, prolonged hospital stay, and delayed return to normal activities may increase healthcare costs [ 12 ], both direct (i.e. used medical resources, inpatient and outpatient services, prescribed medications, etc.) and indirect (i.e. unemployment, absenteeism due to illness, loss of work productivity, etc.) [ 13 , 14 ]. A systematic review of endometriosis expenditure, published in 2016, found direct costs ranging from USD 1109 in Canada to USD 12,118 per patient per year in the US and indirect costs from USD 3314 in Austria to USD 15,737 per patient per year in the US [ 13 ]. The total reported costs were USD 516.12 million in Austria, USD 1.72 billion in Canada, and USD 78.05 billion in the US. Surgical procedures like the laparoscopic or open removal of endometriotic lesions or hysterectomy are essential contributors to these costs [ 13 ]. A review published in 2017 estimated that management of uterine fibroids in the US costs an estimated USD 34.4 billion annually, with direct costs ranging from USD 4.1 to USD 9.4 billion and indirect costs between USD 1.6 and USD 17.2 billion per year, many of which are related to hysterectomy and myomectomy [ 15 ]. Using the latest available record from nationally representative data after 2010 (i.e. in the period 2010‐18), a study found that 1 in 5 (21.1%) of global births were from caesarean section and that this rate is projected to reach 28.5% by 2030 [ 16 ]. In a multicentre randomised trial conducted in the Netherlands, the participating hospitals reported an average caesarean section cost of USD 5360 [ 17 ]. In Bangladesh, this would cost around USD 276 (equivalent to 22,085 Bangladeshi taka (BDT)) with a nationwide cost of USD 320 million (25,639 million BDT) in 2014, accounting for 66.5% of the country's total delivery costs [ 17 , 18 ]. Many of the aforementioned costs are attributable to surgery and the perioperative period. Cost‐effectiveness studies comparing minimally invasive surgery (MIS) and open surgery have demonstrated reduced overall costs associated with MIS procedures. For instance, one study reported an average cost difference of USD 1174 (P < 0.01) in favour of MIS for non‐cancerous hysterectomy, highlighting the economic advantage of MIS over open surgery [ 19 ]. This supports an investigation into and integration of economic evidence in our review as well as the conduct of subgroup analyses based on the surgical approach. 'Enhanced Recovery After Surgery' (ERAS), also known as 'Enhanced Recovery Programme' or 'fast‐track surgery', is an evidence‐based approach aimed at minimising the stress induced by surgery by addressing all aspects of perioperative care, thereby optimising organ function after an invasive procedure [ 20 ]. Nelson et al conducted a comprehensive assessment of ERAS procedures specifically in the population undergoing surgery for gynaecological cancers, which is more closely related to this review's focus [ 21 ]. They identified and listed 21 specific ERAS domains of focus. Of these, 17 domains are directly related to ERAS practices and involve interventions that may be applied before, during, or after surgery [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]: Pre‐admission information, education, and counselling of patients on the details of their operation, the postoperative plan, and the recovery timeframe to engage them, decrease their anxiety, and enhance their compliance with the applied protocols. Preoperative optimisation , including smoking and alcohol cessation and control of chronic conditions such as anaemia to optimise the body before experiencing surgical stress. Prehabilitation , which includes a set of physical, dietary, and psychological interventions directed towards cancer patients between the time of diagnosis and the beginning of acute treatment. This does not apply to this review's population of interest but is mentioned for completeness. Avoidance of routine preoperative bowel preparation as mechanical bowel preparation alone has not been shown to decrease postoperative infections; the latter is mainly achieved by the use of antibiotics instead. Avoidance of the routine administration of pre‐anaesthetic medication (such as sedatives to reduce anxiety before surgery). Nausea and vomiting prophylaxis with a combination of at least two antiemetic agents. Carbohydrate loading and avoidance of fasting , according to which patients should be encouraged to eat a light meal up until six hours before, and consume clear fluids up until two hours before surgery. Prolonged fasting was traditionally supported due to its perceived benefit of reducing aspiration. Adding a carbohydrate loading, instead, aims to manage the hypercatabolic second phase of the stress response [ 9 , 10 ]. This protocol may also mitigate the catecholamine‐induced pancreatic beta‐cell dysfunction, which is exacerbated during fasting [ 10 ]. All in all, carbohydrate loading has been reported to decrease insulin resistance, shorten the hospital stay, and even speed up the return of the bowel to its normal function [ 28 ]. Perioperative surgical site infection reduction bundles , including one or more of the following interventions: Antimicrobial prophylaxis with antibiotics (e.g. first‐generation cephalosporins). Skin preparation according to which patients should bathe using a chlorhexidine‐based antimicrobial soap. Their skin should also be cleansed with chlorhexidine‐alcohol in the operating room just before surgery. These measures aim to decrease bacterial flora around the incision. Avoidance and early removal (ideally within one day after the surgery) of drains (e.g. peritoneal, subcutaneous) and tubes (e.g. nasogastric). Maintenance of normal body temperature during surgery, as low body temperature during the operation can increase the risk of infections. Control of perioperatively increased blood glucose under 200 mg per dL because hyperglycaemia can increase infections. Perioperative prevention of blood clot formation in the veins via mechanical (e.g. stockings or pneumatic compression devices) and/or pharmacological (e.g. with low molecular weight or unfractionated heparin) interventions, especially in the case of long‐lasting surgery. These aim to prevent the formation and dislodgement of venous clots, which can be transferred through the circulation and clog the pulmonary arteries, causing the serious complication of pulmonary embolism. Standard anaesthetic protocols and intraoperative multimodal analgesia , including short‐acting anaesthetics, monitoring of neuromuscular block depth, and complete reversal that aim to minimise postoperative nausea and vomiting and expedite mobilisation. The use of multimodal analgesia through non‐opioid adjuvants such as ketamine, dexmedetomidine, and lidocaine infusions in the intraoperative phase has also been shown to reduce the consumption of opioids measured in morphine‐equivalent daily doses (MEDDs). Avoiding long‐acting opioids reduces their associated postoperative adverse effects, such as delayed return of the bowel to normal function, delayed mobilisation, and prolonged hospital stay. Goal‐directed fluid therapy to maintain perioperative fluid balance and a normal volume of fluids in the body (i.e. euvolemia). Minimally invasive surgery , including laparoscopic, robotic, or vaginal approaches, if possible, to reduce the size of incisions and tissue harm and facilitate healing. Perioperative nutrition , which involves the initiation of regular, even high‐protein, diets within the first 24 hours after surgery. Opioid‐sparing multimodal post‐operative analgesia using non‐opioid oral medications like paracetamol and non‐steroidal anti‐inflammatory drugs, the incisional injection of local anaesthetics such as bupivacaine, or thoracic epidural (i.e. in a space around the thoracic spinal nerves) analgesia to reduce postoperative pain. Opioids are, once again, avoided due to their associated adverse events. Prevention of postoperative ileus (i.e. bowel movement dysfunction) through drinking coffee or chewing gum from the day of the surgery. Urinary drainage via urinary catheters for only a short period, preferably for less than 24 hours postoperatively. Encouragement for early mobilisation and promotion of activity, preferably within the first 24 hours after the surgery, to facilitate the return of bowel function to normal levels, minimise the risk of problems such as the formation of clots in the deep veins of the legs, shorten the hospital stay, and speed up recovery and return to normal activities [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Pre‐admission information, education, and counselling of patients on the details of their operation, the postoperative plan, and the recovery timeframe to engage them, decrease their anxiety, and enhance their compliance with the applied protocols. Preoperative optimisation , including smoking and alcohol cessation and control of chronic conditions such as anaemia to optimise the body before experiencing surgical stress. Prehabilitation , which includes a set of physical, dietary, and psychological interventions directed towards cancer patients between the time of diagnosis and the beginning of acute treatment. This does not apply to this review's population of interest but is mentioned for completeness. Avoidance of routine preoperative bowel preparation as mechanical bowel preparation alone has not been shown to decrease postoperative infections; the latter is mainly achieved by the use of antibiotics instead. Avoidance of the routine administration of pre‐anaesthetic medication (such as sedatives to reduce anxiety before surgery). Nausea and vomiting prophylaxis with a combination of at least two antiemetic agents. Carbohydrate loading and avoidance of fasting , according to which patients should be encouraged to eat a light meal up until six hours before, and consume clear fluids up until two hours before surgery. Prolonged fasting was traditionally supported due to its perceived benefit of reducing aspiration. Adding a carbohydrate loading, instead, aims to manage the hypercatabolic second phase of the stress response [ 9 , 10 ]. This protocol may also mitigate the catecholamine‐induced pancreatic beta‐cell dysfunction, which is exacerbated during fasting [ 10 ]. All in all, carbohydrate loading has been reported to decrease insulin resistance, shorten the hospital stay, and even speed up the return of the bowel to its normal function [ 28 ]. Perioperative surgical site infection reduction bundles , including one or more of the following interventions: Antimicrobial prophylaxis with antibiotics (e.g. first‐generation cephalosporins). Skin preparation according to which patients should bathe using a chlorhexidine‐based antimicrobial soap. Their skin should also be cleansed with chlorhexidine‐alcohol in the operating room just before surgery. These measures aim to decrease bacterial flora around the incision. Avoidance and early removal (ideally within one day after the surgery) of drains (e.g. peritoneal, subcutaneous) and tubes (e.g. nasogastric). Maintenance of normal body temperature during surgery, as low body temperature during the operation can increase the risk of infections. Control of perioperatively increased blood glucose under 200 mg per dL because hyperglycaemia can increase infections. Perioperative prevention of blood clot formation in the veins via mechanical (e.g. stockings or pneumatic compression devices) and/or pharmacological (e.g. with low molecular weight or unfractionated heparin) interventions, especially in the case of long‐lasting surgery. These aim to prevent the formation and dislodgement of venous clots, which can be transferred through the circulation and clog the pulmonary arteries, causing the serious complication of pulmonary embolism. Standard anaesthetic protocols and intraoperative multimodal analgesia , including short‐acting anaesthetics, monitoring of neuromuscular block depth, and complete reversal that aim to minimise postoperative nausea and vomiting and expedite mobilisation. The use of multimodal analgesia through non‐opioid adjuvants such as ketamine, dexmedetomidine, and lidocaine infusions in the intraoperative phase has also been shown to reduce the consumption of opioids measured in morphine‐equivalent daily doses (MEDDs). Avoiding long‐acting opioids reduces their associated postoperative adverse effects, such as delayed return of the bowel to normal function, delayed mobilisation, and prolonged hospital stay. Goal‐directed fluid therapy to maintain perioperative fluid balance and a normal volume of fluids in the body (i.e. euvolemia). Minimally invasive surgery , including laparoscopic, robotic, or vaginal approaches, if possible, to reduce the size of incisions and tissue harm and facilitate healing. Perioperative nutrition , which involves the initiation of regular, even high‐protein, diets within the first 24 hours after surgery. Opioid‐sparing multimodal post‐operative analgesia using non‐opioid oral medications like paracetamol and non‐steroidal anti‐inflammatory drugs, the incisional injection of local anaesthetics such as bupivacaine, or thoracic epidural (i.e. in a space around the thoracic spinal nerves) analgesia to reduce postoperative pain. Opioids are, once again, avoided due to their associated adverse events. Prevention of postoperative ileus (i.e. bowel movement dysfunction) through drinking coffee or chewing gum from the day of the surgery. Urinary drainage via urinary catheters for only a short period, preferably for less than 24 hours postoperatively. Encouragement for early mobilisation and promotion of activity, preferably within the first 24 hours after the surgery, to facilitate the return of bowel function to normal levels, minimise the risk of problems such as the formation of clots in the deep veins of the legs, shorten the hospital stay, and speed up recovery and return to normal activities [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Four domains are related to ERAS management [ 21 , 29 ]: Monitoring of patient‐reported outcomes (PROs), including functional recovery , which necessitates consistently collecting and documenting PROs using validated instruments to understand functional recovery in a patient‐centred manner. Symptom burden assessment can also be used to guide postoperative care. ERAS role in pelvic exenteration and hyperthermic intraperitoneal chemotherapy (HIPEC) , which requires especially high‐volume centres to gather and record evidence on the effect of an ERAS programme on patients undergoing complex procedures like pelvic exenteration and HIPEC surgery. This is likely not applicable to this review's population. Discharge pathways , which involve routine interventions to enhance detailed postoperative education for patients and caregivers prior to discharge, facilitating patient‐centred discharge planning and minimising unplanned hospital visits during the immediate post‐discharge period. Audit and reporting , including reports that explore the relationship between compliance with individual ERAS domains and ERAS outcomes. Monitoring of patient‐reported outcomes (PROs), including functional recovery , which necessitates consistently collecting and documenting PROs using validated instruments to understand functional recovery in a patient‐centred manner. Symptom burden assessment can also be used to guide postoperative care. ERAS role in pelvic exenteration and hyperthermic intraperitoneal chemotherapy (HIPEC) , which requires especially high‐volume centres to gather and record evidence on the effect of an ERAS programme on patients undergoing complex procedures like pelvic exenteration and HIPEC surgery. This is likely not applicable to this review's population. Discharge pathways , which involve routine interventions to enhance detailed postoperative education for patients and caregivers prior to discharge, facilitating patient‐centred discharge planning and minimising unplanned hospital visits during the immediate post‐discharge period. Audit and reporting , including reports that explore the relationship between compliance with individual ERAS domains and ERAS outcomes. What distinguishes ERAS protocols from conventional perioperative care is that all or most of these interventions are applied together and, more systematically, through the collaborative effort of a multidisciplinary surgical team [ 20 ]. Interestingly, the different ERAS domains may share a common target. For instance, oral carbohydrate loading, minimally invasive surgery, early postoperative feeding, and thoracic epidural analgesia aim to decrease insulin resistance, while drinking coffee or chewing gum from the day of surgery, normal volume of body fluids, early postoperative feeding, and opioid‐sparing analgesia are targeted at expediting the bowel's return to its normal function [ 21 ]. In any case, the ultimate goals of all these interventions are to shorten the hospital stay, reduce postoperative pain and analgesic use, minimise complications and hospital readmissions, and optimise and expedite postoperative recovery, rehabilitation, and return to normal activities [ 22 , 23 , 30 ]. From an economic perspective, improving these outcomes might reduce the direct and indirect costs of the perioperative period [ 31 , 32 ] and, therefore, the total economic burden of caesarean section and benign gynaecological conditions requiring surgical treatment. Whether all these goals are achieved by ERAS more or less efficiently compared to standard perioperative care will be investigated by this Cochrane review. Finally, considering that the concurrent implementation of many of these domains requires adequate healthcare financing, the execution of ERAS protocols might differ between higher‐ and lower‐income countries [ 33 ]. Although several trials and a Cochrane review [ 29 ] on the implementation of ERAS in gynaecological cancer surgeries have been conducted and relevant ERAS guidelines have been published [ 34 ], there is limited evidence and no specific guidelines on the use of ERAS in women undergoing caesarean section or other benign gynaecological surgeries. Although previous systematic reviews of studies on benign gynaecological surgeries have been published [ 3 , 35 , 36 ], this review aims to complement the existing literature by following a published protocol, more clearly and strictly defining ERAS and the included population, performing adequate trial registry searches, and assessing the risk of bias and certainty of evidence for the perioperative outcomes of interest. Additionally, given the economic impact of caesarean section and surgeries for conditions like endometriosis or uterine fibroids, it is important to summarise and critically evaluate the current economic evidence from implementing ERAS in these settings compared to conventional perioperative care protocols. It is important to mention that the incremental cost‐effectiveness of ERAS protocols varies across different surgical specialties and healthcare settings. From an economic perspective, ERAS might have a small or large incremental effect compared to no intervention by reducing perioperative complications, hospital stays, readmission rates, and follow‐up periods. However, the incremental cost of ERAS is typically low, and its cost‐effectiveness is significantly high. Although additional expenses such as hiring additional nursing staff or staff training are required, the overall long‐term cost‐savings for the healthcare system, including decreased hospitalisation, decreased number of operations, etc., are substantial. With this in mind, we conclude that there is a high probability that economic evidence could influence potential clinical decisions in this field. According to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions , economic evidence is considered a medium priority to investigate in our review, and it will be a secondary objective alongside clinical outcomes in decision‐making [ 12 , 13 , 37 ].

To assess the effects of perioperative ERAS protocols compared to traditional perioperative care for women undergoing surgery due to non‐malignant gynaecological conditions and to review the availability and key findings of health economic evaluations of ERAS, summarising their principal conclusions.

Supplementary materials are available with the online version of this article: 10.1002/14651858.CD016165. Supplementary materials are published alongside the article and contain additional data and information that support or enhance the article. Supplementary materials may not be subject to the same editorial scrutiny as the content of the article and Cochrane has not copyedited, typeset or proofread these materials. The material in these sections has been supplied by the author(s) for publication under a Licence for Publication and the author(s) are solely responsible for the material. Cochrane accordingly gives no representations or warranties of any kind in relation to, and accepts no liability for any reliance on or use of, such material. Supplementary material 1 Search strategies