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Abstract
Objectives This survey assessed the implementation of enhanced recovery after surgery (ERAS) for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on ERAS pathways in ovarian cancer, because high-level evidence for such interventions is lacking.
Methods In July 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, and the Association for Gynecologic Oncology Austria (AGO Austria) (n = 100). The survey covered all aspects of an ERAS pathway including surgery, nursing, and anesthesia. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report.
Results The overall response rate was 62%. Only a third of the centers in Italy and Austria follow a written ERAS protocol compared with 60% of the Scandinavian centers. Only a minority of centers have completely abandoned bowel preparation, with the highest proportion in Scandinavia (36%). Two hours of fasting for fluids before surgery is routinely practiced in Scandinavia and Austria (67–57%, respectively), but not in Italy (5%). Carbohydrate loading is routinely administered only in Scandinavia (67%). Peritoneal drainage is used by 22% routinely and by 61% in cases of bowel resection/lymphadenectomy/peritonectomy. Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia and Austria, but not in Italy.
Conclusions The degree of implementation of ERAS protocols varies across and within cooperative groups. The centralization of ovarian cancer care seems to facilitate standardization of peri-operative protocols. Currently, the high heterogeneity in patterns of care may challenge an international approach to a clinical trial.
- enhanced recovery
- fasttrack
- ovarian cancer
- perioperative care
- survey
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The implementation of enhanced recovery after surgery (ERAS) protocols varies across and within European cooperative groups.
Centralization of ovarian cancer care facilitates standardization of peri-operative protocols.
The heterogeneity in patterns of care may challenge an international approach to a clinical trial.
Introduction
Enhanced recovery after surgery (ERAS) protocols in colorectal surgery have resulted in shorter length of stay, fewer complications, fewer re-admissions,1 2 and reduced costs.3 Despite these benefits, uptake outside clinical studies has been slow, piecemeal, and challenged by the poor adherence to established protocols.4 5
Recently, international ERAS Society guidelines for peri-operative care in surgery for gynecological cancer were published.6 7 Only a few randomized trials have been conducted,8 9 and full ERAS protocols have mainly been explored in observational studies that included a broad range of interventions and surgical procedures. Conclusions regarding the efficacy of these protocols have been further based on the comparison with historical controls10 and are therefore highly susceptible to bias. Despite efforts to test single interventions, such as early feeding, in a randomized controlled trial design,11–17 the majority of the guideline recommendations only have a low or moderate level of evidence.6 7 There have been a growing number of reports from single centers that have also successfully implemented an ERAS protocol for patients undergoing cytoreductive surgery for ovarian cancer.18 However, there remains a lack of procedure-specific data on the peri-operative management of patients with advanced ovarian cancer. A recently reported randomized controlled trial had major limitations: only a few ERAS components were implemented in the intervention arm, compliance was not reported, and only a minority of patients underwent complex procedures.8 9
Common challenges in the management of ovarian cancer patients are poor nutritional status, fluid shifts, extensive surgery, and the risk of post-operative morbidity.19 The implementation of ERAS protocols in the care of these patients seems promising, since these patients potentially benefit most from enhanced recovery program. However, this requires a multidisciplinary team approach and resource-intensive implementation. Recent reports confirmed a wide variation of practice exists, and only a minority of ERAS interventions are held as the standard of care.20–23 Knowledge of the current patterns of care is crucial in order to achieve a multinational collaboration that improves peri-operative care. Our survey aimed to assess current pre-operative, intra-operative, and post-operative care in patients with advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. We aimed to understand to what extent the surgical, nursing and anesthesiologic aspects of ERAS principles have been implemented.
We hypothesized that there is currently no consistent standard of peri-operative care for patients undergoing surgery for ovarian cancer across Europe. Furthermore, we expected centers would show high heterogeneity in their uptake of ERAS principles. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report.
Methods
In June 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, as well as the Association for Gynecologic Oncology (AGO) Austria (n=100).
The survey invitation was sent to the directors of the gynecology oncology services at each center. It was left to their discretion whether to complete the survey themselves or delegate this to a colleague representing the unit’s practice. For Scandinavia, the lead surgeon for ovarian cancer surgery at each center was identified a priori and the invitation was sent directly to him/her.
All the survey items were developed based on the ERAS gynecologic guidelines6 7 and on a pilot survey among gyne-oncologists in Australia/New Zealand.20 In particular, we asked about pre-operative counseling, use of bowel preparation and carbohydrate loading, pre-operative fasting routines, pre-medication, prophylaxis of thromboembolism, antibiotic prophylaxis, prevention of hypothermia, type of anesthesia, intra- and post-operative fluid management, post-operative nausea and vomiting prevention, use of drains, post-operative nutritional care, prevention of post-operative ileus, use of a urinary catheter, post-operative analgesia, and mobilization. The questionnaire is provided in full in the online supplementary appendix.
Supplemental material
Several reminder emails were sent between June and July 2017. All responses were collected centrally, and data were analyzed anonymously. Descriptive statistics were used.
As this was a quality improvement/program evaluation study with no risk to patients, ethics approval was not required.
Results
Overall response rate (RR) was 62% (62/100), including institutions in 52 cities across Europe. NSGO RR was 65% (15/23), RR for Italian centers was 63.5% (40/63), and RR for AGO Austria was 50% (7/14). The estimated number of patients treated with suspected advanced ovarian/tubal/peritoneal cancer per center is given in Table 1.
Distribution of patients with suspected advanced ovarian/tubal/peritoneal cancer treated with debulking surgery (upfront or interval) per unit per year participating in the survey
Pre-operative Care
Only 37% of all centers follow a written ERAS protocol (Figure 1). However, >50% of the units in these countries state that they counsel their patients pre-operatively based on ERAS principles (eg, pre-operative counseling with all team members about surgical and anesthetic procedures, early post-operative feeding, early mobilization, etc). The majority of centers in all the countries surveyed advise patients to stop hormonal replacement therapy before surgery (60%, 86%, and 77% in Scandinavia, Austria, and Italy, respectively) as well as oral contraception (40%, 100%, and 75% in Scandinavia, Austria, and Italy, respectively) (data about compliance to individual ERAS recommendations are given by country in Table 2). The investigation and correction of anemia before surgery is standard pre-operative care in the majority of centers (80%, 86%, and 95% in Scandinavia, Austria, and Italy, respectively).
Key components of perioperative surgical management.
Compliance with enhanced recovery after surgery (ERAS) recommendations in different countries: expected target effects, relative level of evidence, and recommendation grade. Critical issues (level of evidence moderate or high and compliance <50%) are listed in bold
Only a minority of centers have completely abandoned bowel preparation (Figure 1). Details on bowel preparation prescription are given in Table 3.
Prescription attitude and type of bowel preparation
The adherence to contemporary fasting guidelines, with fluids permitted until 2 hours before surgery, is depicted in Figure 1. Prolonged fluid fasting for ≥6 hours before surgery is still common practice in Italy (79.5%), but less frequent in Scandinavia and Austria (27% and 29%, respectively). Carbohydrate loading (a carbohydrate-rich drink given pre-operatively) is only inconsistently administered (Figure 1). The timing of carbohydrate loading also varies, with centers in Austria administering carbohydrate loading the evening before surgery only, while centers in Italy and Scandinavia use carbohydrate loading both in the evening and 2–4 hours before the induction of anesthesia.
All the centers surveyed prescribe thromboembolic prophylaxis with low molecular weight heparin. In Austria, 100% of centers start pre-operatively, as do 57% in Italy and 40% in Scandinavia. In addition to prolonged prophylaxis, the use of compressive stockings is the standard of care (Table 2). Pneumatic compressive devices are inconsistently used, ranging from 20% in Italy to 40% and 57% in Scandinavia and Austria, respectively.
For antibiotic prophylaxis, a cephalosporin alone is used most frequently, sometimes in combination with metronidazole. In Scandinavia and Austria, most reporting centers routinely use this combination (80% and 71%, respectively), while most Italian centers surveyed administer a second generation (57.5%) or first generation (40%) cephalosporin only, except for cases in which bowel resection is performed. Repeated intra-operative doses of antibiotics are commonly used for prolonged operations, obese patients, and in cases with severe blood loss (Scandinavia 67%, Austria 86%, Italy 80%).
Intraoperative Care
In all cooperative groups, only a minority of centers routinely use post-operative peritoneal drainages in advanced ovarian cancer patients (Scandinavia 14%, Austria 14%, Italy 26%) (Figure 1). The specific indications stated by participating centers are given in Figure 2. The same applies to nasogastric tubes, which are rarely routinely applied (Scandinavia 21%, Austria 14%, Italy 23%) (Figure 1). When applied, they are removed before the reversal of anesthesia (60% in Scandinavia) or on day 1 (100% Austria and 50% Italy).
Use of peritoneal drainage in different countries.
Post-operative Care
Post-operative fluid administration varies both among and within cooperative groups. Oral intake of fluids drives the administration of intravenous fluids in most centers, but others report no specific guidelines about fluid management (Scandinavia 29%, Austria 14%, Italy 31%).
Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia (50% day 0, 43% day 1) and Austria (100% day 1), while there is no consistent practice in Italy (2.5% day 0, 38.5% day 1, 20% day 2). Some Italian institutions delay oral intake until the presence of bowel movements or flatus (18% and 8%, respectively).
Several ERAS interventions are meant to reduce the risk of post-operative ileus. The routine use of prophylactic laxatives is common in Scandinavia and Austria (46% and 43%, respectively) but not in Italy (13%) (Table 2). Chewing gum is used to prevent post-operative ileus in 100% of institutions in Austria, while it is not commonly used in Scandinavia (28.5%) or Italy (0%).
The early removal of the urinary catheter may facilitate early mobilization in ERAS protocols. Still, the timing of removal often seems to be dependent on whether epidurals are used. In Scandinavia, where regional anesthesia is used in 78% of the centers, the urinary catheter is mostly removed when the epidural is stopped (64%, typically day 3). In Austria, however, with 83% of the institutions using an epidural, the catheter is removed on day 1 in 71% and on day 2 in 14%. Data on epidural removal timing was not collected. In Italy the management of the urinary catheter is highly variable, and it is removed either on day 1 (36%), on day 2 (33%), upon flatus (15%), or in 15% depending on the type of surgery performed.
Most of these institutions lack a specific protocol for mobilization (Scandinavia 43%, Austria 100%, Italy 67%), but early mobilization is generally encouraged.
Discussion
This survey assessed the implementation of ERAS principles for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on enhanced recovery pathways in ovarian cancer, as high-level evidence for such interventions is lacking.
The implementation of ERAS protocols varied across cooperative groups. The highest degree of implementation was seen in Scandinavia, where more than half of the centers had a written procedure. To a large degree, they followed the main principles of shorter fasting times, avoidance of drains and nasogastric tubes, and early oral feeding. While Austrian and Italian centers also report the avoidance of drains and tubes, unnecessarily long fasting hours and reluctance to feed early post-operatively are still common, at least in Italy.
The observed difference in implementation may be due to the historical interest of Nordic countries in ERAS principles. This concept of a multimodal approach to improve recovery after surgery was developed in Denmark by Henrik Kehlet and his group.24 These colorectal surgeons were the first to describe a “stress-free” colonic resection for neoplastic disease by a combination of laparoscopically assisted surgery, epidural analgesia, and early oral nutrition and mobilization.25 The first ERAS study group was formed in 2001, and included surgeons from Sweden, Norway, and Denmark as well as the UK and the Netherlands. They further developed ERAS by initiating clinical studies and organizing educational symposia,20 leading up to the formal foundation of the ERAS Society.
In addition to this early interest in ERAS principles, the centralization of care for ovarian cancer surgery in Nordic countries may have facilitated the standardization of peri-operative protocols. This centralization in Scandinavia is underlined by the given volume of the participating centers (Table 1). Here, most institutions performed 60–100 debulking surgeries per year. By contrast, in Austria and Italy, most patients with suspected advanced disease are treated in institutions with ≤30–59 cases per year. The development and implementation of an ERAS protocol requires a multidisciplinary approach of dedicated staff members committed to an ongoing process of monitoring and auditing with the aim of constant improvement of care.20 The development of such teams may be easier at institutions with a high caseload and which focus on the management of these patients.
The survey also illustrates that surgical principles are still subject to traditional beliefs. High-level evidence is available for antibiotic and thromboembolic prophylaxis, interventions with the highest adherence across all groups. However, shorter fasting hours and early feeding have also been proven to be safe and beneficial,6 7 but these aspects of peri-operative care are still not part of routine care in all institutions. The personal beliefs of the surgeon or anesthetist still seem to be rated higher than the available evidence, while a key part of ERAS implementation is breaking through the traditional beliefs of the surgeon, anesthetist, and nursing caregivers and to achieve cross-disciplinary collaboration. The implementation of ERAS protocols may therefore benefit from a multicentric approach, where a protocol is defined on the basis of available evidence and consensus. The involvement of the national and regional healthcare systems in these initiatives could facilitate this process. Among individual ERAS components, omission of bowel preparation, intravenous fluid management after surgery, use of carbohydrate loading, post-operative ileus prevention, and the early removal of the urinary catheter are interventions with a high degree of variation even in countries with a strong commitment to ERAS (Table 2). These specific recommendations are all based on a moderate or low level of evidence and often are not derived from studies in ovarian cancer patients. Surgeons may be uncertain about the generalizability of evidence derived from other surgical disciplines, because of the peculiarity of ovarian cancer surgery and the typical co-morbidities of patients with advanced ovarian cancer.10
Previous surveys about ERAS and gynecological patients have been reported from Canada,23 Germany,22 and ANZGOG (Australia/New Zealand).21 Only the latter focused specifically on advanced ovarian cancer patients. Results in Canada were characterized by a high level of variation between centers and the rather traditional patterns of care with high rates of routine bowel preparation and long pre-operative fasting for solids and fluids. Results were similar in Germany, but the survey was limited by the poor response rate of 22%. Bowel preparation was much less common in Australia and New Zealand; however, fasting time data were similar to data from Canada. Pooled data from our survey underline the widespread use of bowel preparation, as in the surveys from Canada and Germany. The prolonged pre-operative fasting for solids and fluids remains common and is in line with all previous surveys.
The omission of bowel preparation and short pre-operative fasting may in particular require multidisciplinary collaboration and consensus with colorectal surgeons and anesthetists. These aspects may therefore be difficult to implement. This underlines the necessity of a broad embedment of ERAS, involving all relevant disciplines.
The more consistent attitude towards the omission of drains and nasogastric tubes and early feeding reported from other surveys is in line with our findings, especially in Scandinavia. These aspects are more likely to be guided by the attending surgeon’s personal decision and are less dependent on multidisciplinary collaboration.
Our approach of assessing patterns of care with a survey has limitations. Institutions already engaged in ERAS protocols may have been more likely to respond to the survey and our results may be more representative of institutions with a general interest in ERAS. Data were self-reported and may not mirror real patterns of care. Therefore, our results may overestimate the degree of ERAS implementation in these European countries. Practice may vary between surgeons and the results may not entirely represent the unit’s practice. However, in Scandinavia, Italy and Austria, even in those units without an ERAS peri-operative protocol, peri-operative management is often detailed in specific institutional guidelines, shared by surgeons, anesthetists and nurses. These protocols help to standardize clinical practice in all patients and to reduce failures, even when different surgeons and nurses take care of the patients during their hospitalization. Responses to the survey at least should mirror to a large degree the current protocols in the centers represented here and not an individual approach. Still, we cannot rule out that some of the results reported here mirror individual, rather than centre-wide, practices. The assessment of anesthetic principles in an ERAS pathway was included as a survey topic, but these results were considered beyond the scope of this report.
Despite these limitations, this survey brings awareness to the implementation of standardized, evidence-based peri-operative care. It hopefully facilitates a process of evaluating existing standards, not only in the participating groups but also beyond them to the field at large. The fact that a growing number of ovarian cancer centers are gaining experience with an ERAS pathway may encourage an international discussion and consensus.
The currently high heterogeneity in patterns of care across, and even within, groups may challenge a multicenter, international approach to a clinical trial. Well-designed cohort studies and novel trial designs (platform trial, stepped wedge cluster randomized controlled trial) may be alternatives to randomized controlled trials of individual interventions. Education and research on implementation may further enhance the dissemination of available protocols. Efforts should be undertaken to coordinate the work of those institutions willing to revise their perioperative protocols, and cooperative trial groups could be a suitable platform to facilitate this process.
Acknowledgments
Thanks to ENYGO (European Network of Young Gynae Oncologists) for connecting us for this project. We also acknowledge the contribution of the 62 participating institutions. A special thanks to Roldano Fossati, Elena Biagioli, and Emanuele Negri from Mario Negri Institute in Milan and from MaNGO for the suggestions provided on how to conduct the survey in Italy.
References
Footnotes
Collaborators Survey participants. From Scandinavia (NSGO): Maarit Anttila - Kuopio University Hospital; Charlotte H. Søgaard - Aarhus University Hospital; Sami Saarelainen - Tampere University Hospital; Berit Jul Mosgaard - Rigshospitalet Copenhagen; Elisabeth Berge Nilsen - Stavanger University Hospital; Johanna Hynninen - Turku University Hospital; Pernille Jensen - Odense University Hospital; Pernilla Dahm Kahler - Sahlgrensksa University Hospital Goteborg; Karin Stalberg - Uppsala University Hospital; Brynhildur Eyjolfsdottir - The Norwegian Radiumhospital, Oslo University Hospital; Paivi Pakarinen - Helsinki University Hospital; Elisabeth Araya - St Olavs Hospital HF Trondheim; Martin M Lindblad - Universitetssykehuset Nord-Norge Tromsø; Line Bjørge - Haukeland University Hospital Bergen; Preben Kjolhede - Linkoping University Hospital. From Austria (AGO Austria): Karl Tamussino - Medical University of Graz; Gerhard Bogner - PMU Salzburg; Manfred Mortl - Clinical Center Klagenfurt; Christian Marth - University Hospital Innsbruck; Alexander Reinthaller - Medical University of Vienna; Lukas Hefler - Ordensklinikum Linz; Paul Sevelda - General Hospital Hietzing Vienna. From Italy (MaNGO and other Italian institutions): Alessandro Buda - San Gerardo Hospital Monza; Giorgio Giorda - CRO Aviano (PN); Tiziano Maggino - Ospedale dell' Angelo Mestre (VE); Pierandrea De Iaco - Policlinico S.Orsola Bologna; Vincenzo Dario Mandato - IRCCS-ASMN Reggio Emilia; Annamaria Ferrero and Guido Menato - Mauriziano Hospital Torino; Comerci Giuseppe - S. Maria delle Croci Hospital Ravenna; Antonino Ditto - Fondazione IRCCS Istituto Tumori Milano; Enrico Breda - San Giovanni Calibita Hospital Roma; Stefano Prigione - Ospedale Civile Santi Antonio e Biagio Alessandria; Stella Capriglione and Roberto Angioli - University Campus Biomedico of Rome; Francesco Plotti - University Campus Biomedico of Rome; Gianluca Gregori - Città della Salute e della Scienza di Torino, S.Anna Hospital Torino; Francesca Falcone - National Cancer Instituite G. Pascale Foundation Napoli; Graziana Ronzino - Vito Fazzi Hospial Lecce; Chiara Cassani - Fondazione IRCCS Policlinico San Matteo Pavia; Dionyssios Katsaros - Città della Salute e della Scienza di Torino, S.Anna University Hospital Torino; Silvia Corso - Alessandro Manzoni Hosptal, Lecco; Giuseppe Vizzielli and Giovanni Scambia - Policlinico Gemelli Roma; Marco Camanni and Elena Delpiano - Gradenigo Humanitas Hospital Torino; Andrea Puppo - Regina Montis Regalis Hospital Mondovì (CN); Angiolo Gadducci - Azienda Ospedaliera Universitaria Pisana Pisa; Alberto Daniele and Eugenio Volpi - Ospedale Santa Croce e Carle Cuneo; Marocco Francesco and Riccardo Ponzone – Istituto di Candiolo IRCCS Candiolo (TO); Michele Peiretti - University Hosptal of Cagliari; Flavia Sorbi e Massimiliano Fambrini - Careggi University Hospital Firenze; Ilaria Pezzani - Treviso Hospital; Daniela Gatti - Manerbio Hospital (BS); Paolo Sala - Policlinico San Martino Genova; Paolo Zola - Città della Salute e della Scienza di Torino, S.Anna University Hospital Torino; Giuseppe Scibilia and Paolo Scollo - Cannizzaro Hospital Catania; Simona Frezzini - Istituto Oncologico Veneto Padova; Gennaro Cormio - Bari University Hospital; Manuel Maria Ianieri and Marcello Ceccaroni - Ospedale Sacro Cuore Don Calabria Negrar (VR); Gerardo Rosati - S. Carlo Hospital Potenza; Stefano Greggi - Istituto Nazionale Tumori di Napoli; Roberto Berretta - Parma University Hospital; Giovanni Aletti - European Institute of Oncology Milano; Ilaria Spagnoletti - Fatebenefratelli Hospital Benevento; Martina Ratti and Enrico Sartori - ASST Spedali Civili Di Brescia.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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