Evaluating the Impact of Enhanced Recovery After Surgery Protocols on Surgical Outcomes Following Bariatric Surgery—A Systematic Review and Meta-analysis of Randomised Clinical Trials

Background Enhanced recovery after surgery (ERAS) programmes are evidence-based care improvement processes for surgical patients, which are designed to decrease the impact the anticipated negative physiological cascades following surgery. Aim To perform a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the impact of ERAS protocols on outcomes following bariatric surgery compared to standard care (SC). Methods A systematic review was performed in accordance with PRISMA guidelines. Meta-analysis was performed using Review Manager version 5.4 Results Six RCTs including 740 patients were included. The mean age was 40.2 years, and mean body mass index was 44.1 kg/m2. Overall, 54.1% underwent Roux-en-Y gastric bypass surgery (400/740) and 45.9% sleeve gastrectomy (340/700). Overall, patients randomised to ERAS programmes had a significant reduction in nausea and vomiting (odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19–0.95, P = 0.040), intraoperative time (mean difference (MD): 5.40, 95% CI: 3.05–7.77, P < 0.001), time to mobilisation (MD: − 7.78, 95% CI: − 5.46 to − 2.10, P < 0.001), intensive care unit stay (ICUS) (MD: 0.70, 95% CI: 0.13–1.27, P = 0.020), total hospital stay (THS) (MD: − 0.42, 95% CI: − 0.69 to − 0.16, P = 0.002), and functional hospital stay (FHS) (MD: − 0.60, 95% CI: − 0.98 to − 0.22, P = 0.002) compared to those who received SC. Conclusion ERAS programmes reduce postoperative nausea and vomiting, intraoperative time, time to mobilisation, ICUS, THS, and FHS compared to those who received SC. Accordingly, ERAS should be implemented, where feasible, for patients indicated to undergo bariatric surgery. Trial registration International Prospective Register of Systematic Reviews (PROSPERO – CRD42023434492. Graphical Abstract


Introduction
In the western world, the incidence of obesity has increased nearly twofold over the past four decades [1], generating perceptions that the prevalence has reached 'epidemic proportions' [2].Furthermore, it is now estimated that 70% of the adult population are now considered to live with overweight or obesity [1,3,4].Medical therapies, such as glucagon-like peptide-1 receptor agonists, have demonstrated promise in achieving substantial weight loss in patients with obesity [5], as well as significant cardiovascular improvements; however, the response to medication is variable and a significant group of patients do not tolerate the medication due to side effects [6].The results are impressive, albeit short term, and the treatment is likely required long term for maintenance of effect.Surgical treatment of obesity remains the most effective and durable option for both significant weight loss and control or prevention of metabolic diseases such as type 2 diabetes mellitus (T2DM) [7,8] and prevention of a range of malignancies [9,10].Moreover, patients who undergo bariatric surgery have significant improvements in their all-cause mortality rates and overall life expectancy compared to those who do not undergo surgery [11].Accordingly, the pragmatism of using bariatric surgery to improve and optimise patient health has come into vogue, which has subsequently been reciprocated in the dramatic increase in the number of such procedures being performed across Europe and the USA in recent years [12,13].
Postoperative outcomes following bariatric surgery have improved significantly in recent times [14].This is likely due to widespread adoption of minimally invasive approaches [15,16], the centralisation of bariatric surgery to specialised bariatric units [17], and the overall increase in patient volume which has translated into enhanced clinical outcomes [15].Notwithstanding these advances in surgical care, the risk of mortality following bariatric surgery is far from negligible [18], in particular in cases who are considered to be 'high risk' through comorbidity or poor physiological reserve [19].Enhanced recovery after surgery (ERAS) protocols are an evidence-based care improvement process for surgical patients which have been designed to negate the impact of the anticipated physiological and immunological cascade patients are subject to following major surgery [20].ERAS protocols have been associated with reduced post-operative complications, inpatient hospitalisation duration, and hospital costs [20,21].Following the robust implementation and success of ERAS protocols in other surgical specialities (including thoracic [22], urological [23], and colorectal surgeries [24]), ERAS protocols have now been incorporated into the management paradigm for patients undergoing bariatric surgery, with results from observational and randomised clinical trial (RCT) data suggesting there may be benefit in postoperative outcomes expected following effective ERAS implementation [25][26][27][28].Consequently, the ERAS Society published recommended preadmission, pre-, intra-, and post-operative ERAS guidelines in 2021 to encourage implementation and adoption of these protocols for perspective patients due to undergo bariatric surgery [29].
While previous meta-analyses have been performed and demonstrate the positive effect of ERAS protocols on outcomes following bariatric surgery [30][31][32], these studies are limited due to a reliance upon observational and retrospective data to decipher the potential benefit of ERAS implementation.Therefore, a meta-analysis consisting solely of RCTs is necessary to determine the value of ERAS protocols on patients undergoing bariatric surgery.Accordingly, the aim of this study was to perform a systematic review and meta-analysis of RCTs to evaluate the impact of ERAS protocols on patient outcomes following bariatric surgery.

Methods
This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [33].Ethical approval was not required from the local institutional review board due to this study using data from previously published resources.All authors contributed to formulating the study protocol, and it was then registered with the International Prospective Register of Systematic Reviews (PROSPERO -CRD42023434492).

Population, Intervention, Comparison, Outcome (PICO) Tool
Applying the PICO framework [34], the clinical research question the authors wished to address was as follows: Population -Any patients indicated to undergo bariatric surgery in a randomised clinical trial setting.
Intervention -Any patients who were randomised to undergo ERAS.
Comparison -Any patients who were randomised to standard care (SC).

Search Strategy
An electronic search was performed of the PubMed, EMBASE and Cochrane (CENTRAL) databases on the 12th May 2023 for relevant RCTs which would be suitable for inclusion in this study.The search was performed of all fields under the following headings: (enhanced recovery after surgery) and (bariatric surgery) which were linked by the Boolean operator, 'AND'.Included studies were limited to those published in the English language and of prospective randomised design.Studies were not restricted based on year of publication.For retrieved studies, their titles were initially screened, before the abstracts and full texts which were deemed appropriate were reviewed.

Inclusion and Exclusion Criteria
Studies were considered for inclusion in the current study if they met the following inclusion criteria: (1) studies had to be prospective RCTs which randomised adult patients aged 18 years or older indicated to undergo bariatric surgery to ERAS or SC protocols; (2) studies had to include surgical outcomes following ERAS and SC.Studies were excluded from this study if they failed to meet the above inclusion criteria.

Definitions
-Intensive care unit stay -time measured in hours from the end of the surgery until discharge criteria from the ICU were met.-Functional hospital stay -time measured in hours from the end of the surgery until discharge criteria had been met, as described by Geubells et al. [28].-Total hospital stay -time measured in hours from the end of the surgery until actual time of discharge from hospital, as described by Geubells et al. [28].-Overall complications -all complications, as measured using the Clavien-Dindo classification for surgical complications [35] -Major complications -complications of grade ≥ 3, as measured using the Clavien-Dindo classification for surgical complications [35] -Postoperative pain -measured using the visual analogue scale [36] Data Extraction and Quality Assessment The literature search was performed by two independent reviewers (M.G.D and N.E.D.) using a predesigned search strategy.Duplicate studies were manually removed.Each reviewer then reviewed the titles, abstracts, and/or full texts of the retrieved manuscripts to ensure all inclusion criteria was met, before extracting the following data: (1) first author name, (2) year of publication, (3) study design (including intervention and control), ( 4) country of research facility, (5) number of patients indicated to undergo bariatric surgery, ( 6) number of patients randomised to ERAS and SC protocols, and (7) surgical data (as outlined in the PICO framework).Risk of bias and methodological assessment of included studies was undertaken using the Risk of Bias 2.0 assessment for RCTs.

Statistical Analysis
Descriptive statistics were used to determine the associations between ERAS and SC with surgical outcomes (Fisher's exact test, †) [37].Thereafter, outcomes for patients randomised to ERAS and SC were expressed as dichotomous or continuous outcomes, reported as odds ratios (ORs) with their corresponding 95% confidence intervals (CIs), following estimation using the Mantel-Haenszel method.
Either fixed or random effects models were applied on the basis of whether significant heterogeneity (I 2 > 50%) existed between studies included in the analysis.All tests of significance were two-tailed with P < 0.05 indicating statistical significance.Descriptive statistics were performed using the Statistical Package for Social Sciences (SPSS) version 26 (International Business Machines Corporation, Armonk, New York).Meta-analysis was performed using Review Manager (RevMan), Version 5.4 (Nordic Cochrane Centre, Copenhagen, Denmark).

Literature Search and Study Characteristics
The systematic search strategy identified a total of 502 studies, of which 182 duplicate studies were manually removed.The remaining 320 studies were screened for relevance, after which 10 had their full texts reviewed.In total, 6 RCTs met the eligibility criteria and were included in this systematic review and meta-analysis (Fig. 1).Of the 6 RCTs included in this analysis, all studies reported outcomes in relation to patients indicated to undergo bariatric surgery and who were randomised to ERAS or SC pathways (100.0%,6/6).Publication dates of included studies ranged from 2013 to 2022.Study data, inclusion criteria, and risk of bias assessments for the 6 included RCTs are in Table 1.Breakdown of the components of each ERAS protocol from each included RCT is outlined in Table 2.

Leaks
Four RCTs reported leak rates.Overall, there was a leak rate of 1.5% (6/392).There was no significant difference observed in the leak rate for ERAS patients compared to those who received SC (ERAS: 1.5% (3/196) vs. SC: 1.5% (3/196), P = 1.000, †) (Table 4).At meta-analysis, there was no significant difference observed in the leak rate for ERAS patients compared to those who received SC (OR: 0.97, 95% CI: 0.19-4.93,P = 0.970) (Fig. 2C).Geubbels et al. were the only study reporting on intra-operative leak testing to assess anastomotic or staple line integrity, where methylene blue dye was used [28].None of the included studies reported post-operative contrast swallow assessments.

Surgical Site Infection
Pimenta et al. were the only RCT that reported SSI rates.

Intraoperative Time
Three RCTs reported intraoperative time for patients subject to ERAS and SC protocols.At meta-analysis, there was significant increased observed in the intraoperative time for SC patients compared to ERAS (MD: 5.40, 95% CI: 3.05-7.77,P < 0.001) (Fig. 3B).

Postoperative Pain
Four RCTs reported postoperative pain using the visual analogue scale (VAS).At meta-analysis, there was a non-significant difference observed in postoperative pain

Time to Mobilisation
Two RCTs reported time to mobilisation for patients subject to ERAS and SC protocols.At meta-analysis, there was significant reduction in time to mobilisation for ERAS patients compared to SC (MD: − 3.78, 95% CI: − 5.46 to − 2.10, < 0.001) (Fig. 3D).

Total Hospital Stay
Five RCTs reported outcomes in relation to THS.At metaanalysis, there was a significant reduction in THS for ERAS patients compared to those who received SC (MD: − 0.42, 95% CI: − 0.69 to − 0.16, P = 0.002) (Fig. 4A).

Functional Hospital Stay
Three RCTs reported outcomes in relation to FHS.At metaanalysis, there was a significant reduction in FHS for ERAS patients compared to those who received SC (MD: − 0.60, 95% CI: − 0.98 to − 0.22, P = 0.002) (Fig. 4B).

Mortality Rates
Four of the included RCTs reported mortality rates.No patients died during these studies (0.0%, 0/740).

Discussion
This systematic review and meta-analysis integrated data from six prospective, randomised studies which evaluated the impact of ERAS protocols on both peri-and postoperative clinical outcomes following bariatric surgery.Overall, 740 patients (vastly representative of real-world patients undergoing bariatric surgery) were included, and the results from this meta-analyses demonstrate favourable clinical outcomes for those who were randomised to ERAS protocols (compared to SC) when undergoing bariatric surgery.While these data support the results of previous reviews [30,32,38], this study provides novelty through combining the highest possible quality evidence to demonstrate the significant benefits which may be anticipated through robust ERAS adherence when performing bariatric surgery.Moreover, this review incorporates recent data from bariatric units from all over the world, providing a congruent message in support of using ERAS protocols as a strategy to improve outcomes, irrespective of cultural exposure, healthcare (in)equity, or the genetic composition of the local population in question.Thus, this data supports implementation of ERAS protocols for suitable candidate patients indicated to undergo bariatric surgery, where feasible.
As outlined, these results support the routine utility of ERAS protocols in primary bariatric surgery where feasible.This is due to a significant reduction being observed in the proportion of patients experiencing nausea and vomiting, coupled with significant reduction in intraoperative duration, time to mobilisation, ICUS, THS, and FHS, while not increasing complications or readmission rates as a consequence.In tandem, with reduced hospital and ICU stays, these results suggest positive implications for patient health, quality of life metrics, and clinical outcomes following bariatric surgery [39].Thus, these results demonstrate the potential cost effectiveness of using ERAS protocols in dayto-day clinical practice, albeit not directly demonstrated in the results of this rudimentary systematic review.In essence, reduced intra-operative time, ICUS, THS, and FHS will have positive implications on the cost-effectiveness of the provision of bariatric services are significant when attempting to optimise healthcare economies across the globe, particularly as we move towards 'fast track' and'23-h' hospital discharges following bariatric surgery [40,41].For example, several previous high-quality studies have illustrated the cost-effectiveness of ERAS in other surgical specialties, including those reporting outcomes following hepatobiliary [42], colorectal [24], and thoracic resections [22], which is secondary to an overall reduction in patient morbidity and hospital stay, when ERAS has been diligently implemented and adhered to [43,44].Furthermore, if such measures were adopted in the setting of high-volume bariatric-dedicated high dependency units, costs could theoretically be further extenuated through increased efficiency and experience in managing these patients post-operatively [45].Albeit this cost-effectiveness was not directly observed in the results in the current review, this shortcoming is most plausibly explained by a type II statistical error [46], which is due to results from just 1 RCT (where n = 78) being integrated and analysed for this outcomes measure.Therefore, it is plausible that ERAS following bariatric surgery has similar cost-effectiveness to that noted in other surgical specialties [22,24,42], as has been previously demonstrated in observational studies in bariatric surgery [47].
Traditionally, enhancing surgical outcomes focused primarily upon advancing technological innovations, the centralisation of specialised (complex or revisional) cases, and increasing the adoption of checklists to ensure the provision of consistently high-quality care [48][49][50].These timely changes have improved patient outcomes; however, providing benchmark care to the increasing numbers of people living with obesity creates several surgical and anaesthetic challenges, which must be combatted by pre-empting the physiological and immunogenic sequelae that follow surgical manipulation of the upper gastrointestinal tract.Importantly, the data explored in this meta-analysis of RCTs supports the pragmatism of implementing ERAS protocols in this unique and increasingly more common patient cohort, though the illustration of promise these simple adjustments have in further optimising patients prior to and during bariatric surgery.
Despite several strengths, the authors acknowledge that this study is subject to several unavoidable limitations.Firstly, as stands true for the majority of RCTs performed in the field of surgery, none of the included RCTs in this analysis were 'blinded'.The inability to blind surgeons to interventions leads to these RCTs to be classed as 'open label', making them subject to unintentional biases [51].Secondly, it is plausible that certain potential confounders (for example, patient age, patient comorbidities, surgeons experience) may influence the results of this study, and the authors also acknowledge the measurement of the severity of morbidities and clinical conditions triggering readmission are not measured in the current analysis.Thirdly, none of the included studies provided data surrounding patient reported perspectives in relation to ERAS protocols following bariatric surgery, thus limiting subjective insights this study provides into the impact of ERAS on the patient experience of bariatric surgery.Finally, while data was compiled from all available RCTs published on this topic, this meta-analysis relies on data from just 740 patients, limiting the robustness of results.Despite these limitations, this meta-analysis of RCTs provides comprehensive, high-quality analyses which support the of ERAS protocols to bariatric surgical practice, where feasible.
In conclusion, this systematic review and meta-analysis of RCT data demonstrates the clinical utility of ERAS protocols in reducing post-operative nausea and vomiting, time to ambulation, ICUS, FHS, and THS.Based on the results of this study, we advocate for the routine implementation of ERAS protocols to bariatric surgical units, where feasible.Thus, the next generation of prospective randomised clinical trials should focus on refining and adjusting our approach to ERAS following bariatric surgery, in order to further improve outcomes for patients undergoing bariatric surgery.
Funding Open Access funding provided by the IReL Consortium

Fig. 1
Fig. 1 PRISMA flowchart demonstrating the systematic search process

Fig. 2
Fig. 2 Forest plots for A overall complications, B major complications, C leaks, D bleeding, and E nausea and vomiting for comparison of enhanced recovery after surgery and standard care protocols following bariatric surgery

Fig. 3
Fig. 3 Forest plots for A reoperation rates, B intraoperative time, C postoperative pain using the visual analogue scale, D time to mobilisation, and E intensive care unit stay time for comparison of enhanced recovery after surgery and standard care protocols following bariatric surgery

Fig. 4
Fig. 4 Forest plots for A total hospital stay, B functional hospital stay, C 30-day readmission rates, and D hospitalisation costs for comparison of enhanced recovery after surgery and standard care protocols following bariatric surgery

Table 1
Study data from the 6 included prospective, randomised clinical trials ROB 2.0 risk of bias version 2.0 assessment, RCT randomised clinic trial, BMI body mass index, RYGBS Roux-en-y gastric bypass surgery, LSG laparoscopic sleeve gastrectomy, BJS British Journal of Surgery, USA United States of America, ASA American Society of Anesthesiologists, SORD Surgery for Obesity and Related Disorders

Table 2
Components of the enhanced recovery after surgery protocols for each randomised clinical trial included in this study NGT nasogastric tube, IAP intra-abdominal pressure, PPI proton pump inhibitors, H2 histamine-2, appt appointment

Table 3
Patient data from the 6 included prospective, randomised clinical trials

Table 4
Descriptive statistical analysis of outcomes for patients randomised to enhanced recovery after surgery and standard care protocols after bariatric surgery † denotes Fisher's exact test