Enhanced Recovery Program in Laparoscopic Colorectal Surgery: an Observational Controlled Trial
Condition: Colorectal Surgery; Recovery of Function
Study type: Observational

Summary: 
      Background: A few randomized clinical trials and meta-analysis provide evidence for enhanced
      recovery programs (ERPs) in colorectal surgery. Most of the evidence, however, relies on
      non-randomized controlled studies that have control groups being either historical or
      operated on at different facilities. The aim of this study was to compare a prospective
      series of patients undergoing elective colorectal surgery according to ERPs, with a coeval
      retrospective series of patients undergoing elective colorectal surgery in a different ward
      at the same hospital.

      The primary outcome was hospital length of stay, which was used as a proxy of functional
      recovery. Secondary outcomes included: postoperative complications, readmission rate,
      mortality, and adherence to the protocol.

      Materials and Methods: A prospective series of consecutive patients (N = 100) undergoing
      elective colorectal resection completing a standardized ERP in 2013-2015 (ERP Group) will be
      compared to patients (N = 100) operated at the same institution in the same period with a
      traditional perioperative care protocol (Non-ERP group). Despite different surgeons and ward
      nurses, the two groups shared the same anaesthesiologists and were located in separate wards.
      The exclusion criteria were: >80 years old, ASA score of IV, a stage IV TNM, and diagnosis of
      inflammatory bowel disease.
    

Detailed description: 
      1. Introduction

           One of the most important achievements in modern surgery is the implementation in
           perioperative care of Enhanced Recovery Programs (ERPs), pioneered by Henrik Kehlet in
           the mid-1990s [1]. ERP is an evidence-based perioperative care approach, involving a
           multidisciplinary team work including surgeons, anaesthesiologists, dieticians, and
           nurses, which aim to reduce the surgical stress and metabolic responses as well as organ
           dysfunction, thus leading to a faster recovery after surgery [2].

           Such a team works with a multimodal approach to perioperative care, sharing all the
           endpoints of management throughout the perioperative phases, and acting in close
           relationship with the patient along his/her "journey in hospital". In other words, each
           perioperative phase comprises several core items based on solid scientific evidence that
           are delivered by different professionals in different parts of the hospital [2].

           A few randomized clinical trials and meta-analysis provide evidence in the literature
           for the benefits of ERPs in colorectal surgery [3-6]. Most non-randomized controlled
           studies have compared patients undergoing colorectal enhanced recovery surgery with
           controls being either historical groups or patients operated on at different hospitals
           [7-9].

           In a previous investigation, the investigators showed the benefits of implementing an
           ERP in elective colorectal surgery by comparing a prospective series of 100 patients
           operated on receiving enhanced recovery care (ERP group), with a retrospective cohort of
           100 patients operated on by the same professionals at the same institution before the
           introduction of the ERP (Pre-ERP group) [10].

           The present study aims to investigate the differences between a prospective series of
           patients undergoing elective colorectal surgery following an ERP and a retrospective
           cohort of patients operated on with traditional perioperative care in the same period by
           a different team of surgeons and hospitalized in a different ward of the same hospital.

        2. Materials and Methods

      The study was designed as a prospective cohort with retrospective coeval control. A
      prospective series of 100 consecutive patients undergoing elective colorectal surgery
      completing a standardized ERP protocol at the S. Anna University Hospital in Ferrara (Italy)
      in 2013-2015 (ERP group), was compared to a retrospective series of 100 consecutive patients
      operated at the same hospital, in the same period of time, but with a traditional
      perioperative care protocol (Non-ERP group). Despite different surgeons and ward nurses, the
      two groups of patients shared the same anaesthesiologists and were located in two separate
      wards.

      In 2012 the enhanced recovery team was assembled, the ERP protocol was built up, according to
      the fast-track protocol proposed by Kehlet and Wilmore [11], and periodical audits were then
      performed. Eligible for this study were all patients between 18 and 80 years old scheduled
      for elective colorectal resection. Exclusion criteria in both study groups were: age > 80
      years old, American Society of Anaesthesia (ASA) score IV, TNM stage IV, and diagnosis of
      inflammatory bowel disease. Discharging criteria were also the same for both groups: 1) free
      oral diet, 2) complete intestinal function recovery (passage of flatus and stool), 3) dynamic
      pain control (Numerical Rate Scale - NRS ≤ 3) by oral analgesia, 4) independent walking, 5)
      no signs of infection [10].

      The study protocol was approved by the local Ethics Committee (Ethical Committee for Human
      Subject Research study number 52-2011), it complies with the Declaration of Helsinki, and all
      patients provided written informed consent The primary outcome of this study was the length
      of stay (LoS) in the hospital, adopted as a proxy of functional recovery. Secondary outcomes
      were: postoperative complications, readmission rate, mortality, and adherence to the
      protocol.

      All complications were recorded until 30 days after surgery, as well as mortality and
      hospital readmission. To evaluate adherence to the protocol, all ERP items were prospectively
      collected, recorded and checked by an independent observer using a detailed care program for
      each postoperative day. The grading of complications was defined according to a validated
      classification [12].

      Data were collected prospectively for patients in the ERP group and retrieved from a
      prospectively maintained database for those in the Non-ERP group.

      Surgery was preferably performed by laparoscopy, but alternative approaches were allowed and
      discussed with patients. A converted laparoscopy was defined as an unplanned extension of the
      surgical incision (either a median or a transverse suprapubic incision). All operations were
      performed by surgeons experienced in colorectal surgery and advanced laparoscopy (CVF, GA).

      2.1 ERP Group Patients received extensive preoperative counselling about protocol items, all
      phases of perioperative care, and discharge criteria, along with an illustrated booklet
      conceived by the multidisciplinary team. The patients were motivated to adhere to protocol
      items by members of the team throughout the preoperative and postoperative phases and were
      informed about the daily objectives to be achieved. Incentive spirometers were provided
      preoperatively and patients were instructed for perioperative breathing exercises.

      A normal meal was allowed on the day before surgery; a carbohydrate loaded drink was
      prescribed in the evening (100 grams of maltodextrin in 800 ml liquid drink) and at least two
      hours (50 grams of maltodextrin in 400 ml liquid drink) before surgery. No patient was
      prescribed mechanical bowel preparation.

      The nasogastric tube (NGT) and bladder catheter were removed at the end of the procedure and
      within the second postoperative day [13], respectively, whereas abdominal drains were
      selectively used.

      Postoperative pain control was achieved with thoracic epidural analgesia within the first
      three postoperative days and with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) or
      paracetamol thereafter. Resumption of liquid and solid diets and discontinuation of
      intravenous fluids were all achieved within the first and the second postoperative day.
      Patients were out of bed on postoperative day one and encouraged by nurses to deambulate
      according to a predefined schedule.

      The anaesthetic protocol was standardized as previously described elsewhere [10]. In brief, a
      blended anaesthesia was performed with short-acting anaesthetic agents and mid-thoracic
      epidural intraoperative analgesia. Attention was put on maintaining normothermia with forced
      air warming devices during surgical procedures and a multimodal approach to prevent
      PostOperative Nausea and Vomiting (PONV) was pursued. Intravenous fluid overload was avoided.

      2.2 Non-ERP Group Patients were treated according to traditional perioperative care
      principles in use at the institution. Specifically, on the day before surgery patients fasted
      from midnight, received no carbohydrate loaded drink, and performed a mechanical bowel
      preparation.

      An opioid-based anaesthesia with or without thoracic epidural was used, while postoperative
      pain control was achieved by intravenous opioids, thoracic epidural or NSAIDs.

      The NGT was removed at the restoration of intestinal activity when oral feeding was resumed,
      while the abdominal drain was removed at bowel movements.

      No predefined schedule was followed for patients' mobilization and the bladder catheter was
      removed at full mobilization and after discontinuation of intravenous fluids.

      Patients received no daily goal assignments or specific preoperative counselling.

      In order to determine in between groups perioperative care differences, an independent
      observer reviewed the medical charts of all patients to evaluate the adherence to the 21
      protocol items.

      2.3 Statistical Analysis Clinical parameters were expressed as median (interquartile range -
      IQR 25-75) and mean ± standard deviation according to distribution assessed by Shapiro-Wilk
      test. Categorical data were presented as numbers. Clinical and pathological variables were
      analysed with Chi-square, t-student, and Mann-Whitney tests as appropriate. The Kaplan-Meier
      test method and Log-Rank test were used to compare duration of surgical operation, time to
      functional recovery and hospital LoS between groups. A P value of less than 0.05 was
      considered statistically significant. Statistical analysis was performed with IBM SPSS
      Statistics for Windows, Version 24.0 (IBM Corp. Armonk, NY: IBM Corp.).
    

Intervention name(s): Enhanced Recovery Program (ERP)
Intervention type(s): Other
Intervention description(s): An evidence-based perioperative care approach, involving a multidisciplinary team work including surgeons, anaesthesiologists, dieticians, and nurses, which aim to reduce the surgical stress and metabolic responses as well as organ dysfunction, thus leading to a faster recovery after surgery
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients undergoing elective colorectal resection at the S. Anna University Hospital in
        Ferrara (Italy) between 2013-2015 (ERP group vs Non-ERP group)
      
Keywords: Laparoscopy; Enhanced Recovery After Surgery; Colorectal Neoplasms