- Email: [email protected]
A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS Digestive and Liver Disease xxx (2020) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Alimentary Tract
A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis Michela Mineccia a,∗ , Francesca Menonna a , Paola Germani a , Valentina Gentile a , Paolo Massucco a , Rodolfo Rocca b , Alessandro Ferrero a a b
Department of Chirurgia Generale e Oncologica, Ospedale Mauriziano Umberto I, Torino, Italy Department of Gastroenterology, Ospedale Mauriziano Umberto I, Torino, Italy
a r t i c l e
i n f o
Article history: Received 11 September 2019 Accepted 15 January 2020 Available online xxx Keywords: Crohn disease surgery ERAS Length of stay Propensity score
a b s t r a c t Background: Enhanced Recovery After Surgery (ERAS) offers many benefits for patients with colorectal cancer. However, its application to patients with Crohn’s disease (CD) is questioned. Aim: The aim of this propensity-matched study was to validate the results of ERAS protocol on CD patients. Methods: Patients undergoing ileocolic resection for primary or relapsed CD from 2007 to 2018 were retrospectively analyzed and propensity-matched into two equal groups (ERAS vs standard of care). Demographic characteristics, length of stay, bowel function, oral intake, and perioperative morbidity were analyzed. Results: Ninety four out of 299 patients were selected for analysis. No significant difference was observed for age, gender, American Society of Anesthesiologists score, body mass index, previous surgery and therapy, operative time and laparoscopy. The median length of stay in ERAS and non-ERAS groups was 6 and 8 days (p < 0.001). Median postoperative days of first bowel movement and solid oral intake were day 1 and day 2 p < 0,001, and day 2 and day 4.5 p < 0,001 in ERAS and non-ERAS group, respectively. No statistically differences in other postoperative outcomes were shown. Conclusions: ERAS implementation showed decreased length of stay, faster bowel function restoration and earlier solid oral intake in patients who underwent laparoscopic or open ileocolic resection for primary or relapsing CD. © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Patients affected by Crohn Disease (CD) have an extensive disease which most of times involves the small bowel or the colon and are characterized by a systemic altered inflammatory response before surgery [1]. Patients with CD have been subjected, in most cases, to immunomodulating therapy, they might have intra-abdominal infections, and are often malnourished and anemic. Use of steroids, low albumin level, previous surgical operations and preoperative abdominal collections represent risk factors for complicated surgical outcome [2]. Patients with Inflammatory Bowel Disease (IBD) and in particular with CD could have postoperative prolonged ileus due to chronic inflammation of the intestinal wall; however, the literature that investigates the real causes and the incidence rate of postoperative ileus in patients with Crohn’s disease is, at the moment, not conclusive [3].
∗ Corresponding author. E-mail address: [email protected] (M. Mineccia).
Fast-track surgery or Enhanced Recovery After Surgery (ERAS) integrate various types of actions aimed to maintain physiological function and lightening postoperative hospital stay. The ERAS protocols implement a series of standardized steps aimed to reduce physiologic stress caused by surgery and to gain early discharge from the hospital. ERAS concerns the continuum of surgical care and includes processes such as patient education, multimodal analgesia, and early mobility. Implementation of ERAS involves the collaboration of a multidisciplinary team supporting the systematic coordination of processes. Many studies have shown that ERAS reduces postoperative Length of Stay (LOS) and may also reduce postoperative complications after surgery without worsening readmission or mortality rates [4–6]. However, the evidence on ERAS effectiveness in subgroup populations is limited by the historic use of homogenous patient samples. Despite patients with IBD have higher odds of adverse outcomes, including prolonged length of stay, serious morbidity, higher rate of readmission, and worse diet toleration [7], few studies have exam-
https://doi.org/10.1016/j.dld.2020.01.006 1590-8658/© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS
2
M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
ined the potential benefits of ERAS in this particular population [8,9]. We recently implemented the ERAS protocol in patients undergoing surgery for Ulcerative Colitis (UC) and CD. This is a single center propensity-matched study to validate the feasibility and short-term outcomes of ERAS protocol applied to patients with primary or relapsing ileocolic CD disease. 2. Materials and methods Patients with primary or recurrent CD who underwent ileocolic resection between May 2007 and December 2018 at the General and Oncologic Surgical Unit, were observed and data were collected from a prospectively maintained database. Our Surgical Unit has wide experience in surgery for Inflammatory Bowel Disease (IBD) and is well equipped to manage complex disease and complications. The ERAS protocol was implemented in our Institution since 2013 but has just recently extended to IBD patients. Data collection and analysis were performed according to the institutional guidelines and to the ethical standards of the Helsinki Declaration. The ERAS protocol is applied commonly for colorectal surgery and this paper is an observational study. Formal approval by the ethical Committee in our Country is not required for this kind of studies. Three Consultant Surgeons with experience of at least 10 cases per year in IBD surgery and laparoscopic surgery performed all operations (MM, PM, FB). Patients’ demographic (age, gender, BMI, ASA score, recurrent disease, years of disease, steroids or immunomodulating therapy within two months, malnutrition, nutritional support), intraoperative (operative time, laparoscopy) and postoperative factors (hospital stay, free oral intake, stool movements, postoperative complications, postoperative fistula, postoperative hemorrhage and 90 days readmission) were recorded [10]. From this cohort of patients, only those who underwent ileocolic resection were selected and analyzed. All the patients who underwent ileocecal or ileocolic resection received immunomodulating therapy (biological agents or thiopurine) or steroids before surgery. The therapy was stopped, whenever possible, at least one month before surgery; the therapy administrated within two months of surgery was recorded and analyzed. The primary endpoint was the length of stay. Secondary endpoints were time of postoperative solid oral intake, defined as tolerance of solid diet and the time of first bowel movement, defined as the first stool passage. Other endpoints were overall morbility (according to the Dindo-Clavien Classification [10]) and 90-day readmission. This paper has been worded in line with the STROCCS criteria [11]. 2.1. ERAS protocol Preoperative setting • avoidance of mechanical bowel preparation or premedication, • patients are invited to drink up to 2 h before surgery and to eat up to 6 h, • no preoperative midazolam is administered. Intraoperatively • the procedure is performed laparoscopically whenever possible, • an intraoperative fluid restriction regimen is applied (less than 10 ml/kg/h),
• patients receive, in the operating room, an intrathecal analgesia in the sitting position with opioid injection (100 g of hydromorphone). Postoperatively • the nasogastric tube is removed after the end of the operation before the awakening of the patient and the urinary catheter is removed the morning after, • the patient is mobilized early (2 h after surgery), • fluids intake is stimulated on the same day of surgery [5,6], • postoperative analgesia is administrated intravenously even 4−6 h with paracetamol, • pain assessment is done by nurses each 8 h, as part of their routinely clinical cares, using VAS (Visual Analogue Scale). Discharge criteria are: an acceptable pain control with oral analgesics, passage of first stool, adequate solid food intake and mobilization. 2.2. Surgical technique 2.2.1. Laparoscopic technique Laparoscopic ileocecal resection was performed with a standardized technique. Umbilical open access is done and two trocars are placed in the left iliac fossa and left upper quadrant. Trendelenburg tilt with the left-side down position is then adopted. After disease assessment, the right colon is completely mobilized, including the hepatic flexure. A short incision is performed in the right iliac fossa. The ileocecal or ileocolonic (in recurrent cases) resection and the mesentery division are performed extracorporeally, guided by intra-operative ultrasonography of the bowel. An endsewn ileo-colic anastomosis is then performed. The entire small bowel is carefully checked to exclude skip lesions. No drainage is left. 2.2.2. Open technique The same steps are performed by an open approach that usually is median laparotomy from the supraumbilical region to the pubis. 2.3. Statistical analysis Categorical variables are expressed as absolute numbers and percentages. Continuous variables are exposed as mean ± SD if normally distributed or as median and interquartile range (IQR) if not. Kolmogorov–Smirnov test was used to assess normality distribution. To identify all significant predictors of hospital stay and to calculate the variation of the estimated effect size for each predictor, multivariate Poisson regression was performed. All significative factors were used to eliminate confounding from the observed variables between the two study groups by propensity score analysis as to avoid bias related to the ERAS patient’s selection as much as possible; still, we recognize the possible existence of other unknown factors playing a role in the selection, that we are not able to account for due to lack of measurements. Linear propensity score values were used in a logistic regression analysis for risk-adjusted data. Values were used to perform a match using the nearest-neighbor method and 1-to-1 ratio, with substitution, within a specific caliper width of 0.2 SD of the logit of the estimated propensity score, beginning from cases with the largest propensity score. Covariance analysis and sensitivity analysis were then calculated with Rosenbaum test for Wilcoxon Signed-Rank p-value. We recognize that the relatively moderate sample size could represent a possible weakness of the study, especially using a propensity based method: nevertheless, we performed the same analysis with 2:1
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
3
Table 1 Baseline characteristics and surgical aspects of the study population.
Number of patients (%) Median age Gender, females (%) Median body mass index, (IQR) ASA score, (%) I II III IV Recurrent disease (%) Laparoscopy, (%) Median operative time, (IQR) Thiopurine (%) Mesalamine (%) Anti TNF blockers (%) Steroids (%) Septic (%) Malnutrition (%) Nutritional support (%) Course of disease (years), median
ERAS
N-ERAS
Overall
p
47 (15,7%) 35 (27,5–47) 28 (60%) 22 (19,96–24,96)
252 (84,3%) 42 (28,5–53) 129 (51%) 21 (19–23,2)
299 41 (28–52,5) 157 (52,5%) 21.3 (19–23)
0,06 0,36 0,12
8 (17%) 34 (72,3%) 5 (10,64%) 0 (0%) 17(36,2%) 37 (78,7%) 135 (110–161.5) 17 (36,2%) 24 (51,1%) 16 (34%) 23 (49%) 1 (2,1%) 4 (8,5%) 6 (12,8%) 6 (1,5–10)
1 (0,4%) 160 (63,5%) 90 (36%) 1 (0,4%) 108(43%) 157 (62,3%) 160 (130–195) 72 (26,9%) 109 (43,3) 43 (17,1%) 87 (35%) 5 (5,6%) 64 (25,4%) 81 (32,1%) 7 (3–14)
9 (3%) 194 (64,8%) 95 (31,8%) 1 (0,3%) 125(42%) 194 (64,9%) 155 (120–195) 89 (29,7%) 133 (44,5%) 59 (19,7%) 110 (37%) 15 (5%) 68 (22,7%) 87 (29%) 7 (3–13,5)
<0,001 0,32 0,0012 0,04 0,38 0,046 0,0089 0,41 0.41 0,013 0,086 0,53 0,019 0,012 0,25
In bold p significant values.
Table 2 Operative and post operative results of unmatched patients. ERAS (47)
N-ERAS (252)
Overall (299)
p
Median lengh of hospital stay (IQR) Days of free oral intake, median Days of first stool, median
6 (5–8,5) 2 (1–3,5) 1 (1–2)
9 (7–15) 5 (4–6) 2 (2–3)
9 (7–13) 4 (3–6) 2 (1–3)
<0,001 <0,001 <0,001
Post-operative complications, (%) Clavien–Dindo ≥ IIIb, (%) Post-operative fistula, (%) Post-operative hemorrhage, (%) 90-day readmission, (%)
1 (2,1%) 0 (0%) 1 (2,1%) 2 (4,3%)
18 (7,1%) 4 (1,6%) 13 (5,2%) 13 (5,2%)
19 (6,4%) 4 (1,3%) 14 (4,7%) 15 (5%)
0,46 0,86 0,6 0,9
In bold p significant values.
ratio and the results were almost exactly the same. Statistical analysis was performed using SPSS Statistics statistical software (version 20.0; SPSS Inc., Chicago, IL, USA), except for propensity score that was made using R Package (R Core Team 2014, R Foundation for Statistical Computing, Vienna AT).
Laparoscopic procedures and operative time did not differ between the two groups. No mortality occurred in the two groups. Serious postoperative complications (expressed with Clavien Dindo Classification ≥ IIIb, postoperative fistula, and hemorrage) and 90-day readmissions were lower in the ERAS group even if statistical significance was not reached (Table 4).
3. Results 4. Discussion A total of 369 patients underwent surgery for CD during the study period. From this group we considered 299 patients undergoing ileocolonic resections (47 ERAS vs 252 non-ERAS). The compliance with the ERAS protocol was around 95% for each items, in particular regarding avoidance of drainage ad early fluid intake in day 0. Three patients failed in early mobilization because of pain and dizziness. Baseline demographic characteristics of the study population are compared in Table 1. At the analysis, through Poisson regression, factors influencing the outcome were sex, BMI, ASA = III, age, course of disease, laparoscopy, previous therapy with anti TNF blockers, malnutrition, preoperative nutritional support, and sepsis (see Supplementary table) (Table 2). Ninety four procedures were propensity-matched on the basis of the belonging to ERAS protocol. After propensity score matching, the obtained two groups showed no significant differences in regard to patients characteristics (see Table 3). The median length of stay was significantly shorter in the ERAS group (6 vs 8 days, p = <0.001) (Table 4). Days (median) of first stool movement and of free feeding were significantly lower in the ERAS group (1 vs 2 days p < 0.001, and 2 vs 4.5 p < 0,001, respectively) (Table 4).
The adoption of ERAS protocols has improved in last decades for colorectal neoplasms and diverticular disease. As a consequence, perioperative management of patient submitted for colorectal surgery has gained quality due to laparoscopy and Enhanced Recovery Protocols [12]. In the last three years, in our Department, the application of ERAS protocol has become the gold standard also for IBD. In our study, ERAS reduced LOS and gave better outcome with early stool movement and early return to free feeding for patients operated for CD. The findings of this study confirm some recent reports concerning the benefit of ERAS protocols applied to CD patients. Surprisingly, before 2013, there has just been one paper addressing the feasibility of fast track protocols in patients with CD undergoing open approach [8]. Moreover, a single case-matched study showed an improvement in surgical outcome and a significantly faster recovery for patients with primary ileocecal CD undergoing laparoscopic resection with ERAS protocol [13]. A recent paper from Zhu et al. [9] concludes that laparoscopic approach within an ERAS perioperative care program is a safe and effective treatment combination for CD patients requiring ileocecal resection. This ran-
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS
4
M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
Table 3 Baseline characteristics and surgical aspects of matched subgroups selected by propensity score analysis. ERAS
N-ERAS
Overall
p
Number of patients (%) Median age, (IQR) Gender, females (%) Median body mass index, (IQR)
47(50%) 35 (27,5–47) 28 (60%) 22 (19,96–24,96)
47 (50%) 35 (29–44) 31 (66%) 21,6 (19,7–24,7)
94 35(27–45) 59 (63%) 21,8 (19,8–24,9)
0,78 0,67 0,4
ASA score, (%) I II III IV Recurrent disease (%) Laparoscopy, (%) Median Operative time, (IQR) Thiopurines (%) Mesalamine (%) Anti TNF blockers (%) Steroids (%) Septic (%) Malnutrition (%) Nutritional Support (%) Course of disease (years), median
8 (17%) 34 (72,3%) 5 (10,6%) 0 (0%) 17 (36,2%) 37 (78,7%) 135 (110–161,5) 17 (36,2%) 24 (51,1%) 16 (34%) 23 (49%) 1 (2,1%) 4 (8,4%) 6 (12,8%) 6 (1,5–10)
0 (0%) 43 (91,4%) 4 (8,5%) 0 (0%) 17 (36,2%) 39 (83%) 150 (126–201,5) 22 (46,8%) 18 (38.3) 15 (31,9%) 20 (43%) 2 (4,3%) 6 (12,8%) 8 (17%) 7 (2–11,5)
8 (9%) 77 (81,9%) 9 (9,6%) 0 (0%) 34 (36,2%) 76 (80,1%) 149,5 (120–188,8) 39 (41,5%) 42 (44,7%) 31 (33%) 43 (46%) 3 (3,2%) 10 (10,6%) 14 (14,9%) 7 (2–10,5)
<0,001 0,03 1 NA 1 0,79 0,15 0,4 0.3 1 0,68 1 0.74 0.78 0.24
In bold p significant values.
Table 4 Operative and post-operative results of matched subgroups selected by propensity score analysis.
Median lengh of hospital stay (IQR) Days of free oral intake, median Days of first stool, median Post-operative complications Clavien–Dindo ≥ IIIb, (%) Post-operative fistula, (%) Post-operative hemorrhage, (%) 90-day readmission, (%)
ERAS
N-ERAS
Overall
p
6 (5–8,5) 2 (1–3,5) 1 (1–2)
8 (7–10) 4,5 (3–6,5) 2 (2–3)
7 (6–10) 3 (1–4,5) 2 (1–2)
<0,001 <0,001 <0,001
1 (2,1%) 0 (0%) 1 (2,1%) 2 (4,3%)
2 (4,3%) 1 (2,1%) 1 (2,1%) 2 (4,3%)
3 (6,4%) 1 (1%) 2 (2,1%) 4 (4,3%)
0,56 1 1 1
In bold p significant values.
domized study considers a little cohort of patients from western country (16 per arm) who underwent laparoscopic ileocecal resection for primary disease. Other authors, instead, showed a prolonged postoperative stay after surgery for CD when an ERAS protocol was implemented but such result could be justified by the degree of the disease, the type of resection performed, or other pre-existing patient conditions. This is why patients with CD should gain a better performance status before surgery and prehabilitation and postoperative management has to be optimized [14]. Ban et al. have analyzed the effect of diagnosis on the outcome of ERAS protocols. Patients with IBD (if compared with those with cancer or diverticular disease) had higher odds of adverse outcomes and always took them longer to achieve postoperative pain control and to tolerate a diet. IBD was identified as an independent predictor of adverse outcomes including unplanned reoperation and postoperative ventilator dependency [7]. Another paper emphasizes that preoperative steroid use, hypoalbuminemia, systemic inflammatory response syndrome (SIRS) status and postoperative intra-abdominal sepsis could represent an independent risk factors for prolonged ileus in IBD patients [15]. All these papers underline that patients affected by IBD and particularly by CD are prone to postoperative adverse events, including difficulty in pain control, delayed return of bowel function and prolonged ileus, probably also due to the chronic use of opioid [16]. The bad results showed by these Authors can be explained with the inclusion of both CD and Ulcerative Colitis in the study population and patients with UC are not always young, mostly if affected by “long-standing disease” with the onset of neoplasia. Further-
more, any kind of operation are considered (partial colectomy, total colectomy, ileocolic resection, ileostomy or colostomy) and it could bring sample variability. This is the reason why we selected a standardized surgical procedure (laparoscopic or open) in order to highlight the effective role of the ERAS management and to further reduce possible bias. Patients with ileocecal or ileocolic localization of CD (if relapse) were chosen. The propensity score was used, thereby balancing the treatment and control groups. A possible explanation for our good results is that patients affected by CD are mostly young and have often active lifestyles. Such patients have demonstrated a great adherence to the ERAS preoperative program wishing to gain a rapid recovery in order to achieve a quick return to work and social activities. As part of this management education program, it is also important to involve patients’ caregivers who can play a substantial role when the patient is discharged from the hospital. The preoperative education is crucial and consists of a detailed list of information by a team of surgeon, anesthesiologist, gastroenterologist, dietician, caregiver and stoma therapist if necessary. All those instructions are not limited to the surgical procedure but also include other important and practical aspects as preparation for surgery, timing and type of diet intake, pain management, and modalities and timing of mobilization. During such preoperative counseling young patients have proven to be interested and motivated with the desire to succeed. The avoidance of drains and nasogastric tube placement plays another substantial role in the success of ERAS program. Surgery for CD, especially if performed for relapse, could be more complex and shows a higher risk of bleeding and leakage due to the thickness
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
of inflamed mesentery and to the presence residue disease in the bowel wall. And so, even in those cases, the drain is not left because it couldn’t be completely fitted to the protocol guidelines. Limitations of this study are represented by bias inherent its retrospective design. Firstly, there is a risk for lead time bias because the study observes a period of 10 years and the ERAS protocol was implemented only in the last part of this time interval. The Propensity score was used in order to balance the ERAS and the control groups redistributing significant covariates. The risk remains that variables we have not been able to identify may play a determinant role. The exclusion of patients represents a limitation of this kind of study, but there is no difference between matched and unmatched records. Moreover, in the multivariate analysis adjusting for the same covariates in the original sample, results are similar compared to the matched analysis. Lastly, this paper shows the results of a single institution, and shouldn’t be considered as a representative sample and the small sample size gives the study less power. Confirmation from other studies is therefore necessary. 5. Conclusion This propensity score matched study showed a significantly shorter hospital stay, earlier stool movement and return to free oral intake for patients with primary or relapse ileocolic CD undergoing laparoscopic or open surgery, enrolled in ERAS protocol. It validates the ERAS protocol for a subgroup of patients with a complex disease, such as CD, and shows that effective perioperative care joined to an experienced surgical team may hesitate in further improvements of surgical outcomes for CD patients. Conflict of interest None declared. Ethical approval The ERAS protocol is applied routinely for colorectal surgery and this paper is an observation study. A formal approval by ethical Committee in our Country is not required for this kind of studies
5
References [1] de Buck van Overstraeten A, Van Hoef S, Vermeire S, et al. Postoperative inflammatory response in Crohn’s patients: a comparative study. J Crohns Colitis 2015;9:1127–31. [2] Grass F, Pache B, Martin D, et al. Feasibility of early postoperative mobilisation after colorectal surgery: a retrospective cohort study. Int J Surg 2018;56:161–6. [3] Murphy MM, Tevis SE, Kennedy GD. Independent risk factors for prolonged postoperative ileus development. J Surg Res 2016;201:279–85. [4] Ljungqvist O, Scott M, Fearon KC. Enhanced recovery after surgery: a review. JAMA Surg 2017;152:292–8. [5] Grant MC, Yang D, Wu CL, et al. Impact of enhanced recovery after surgery and fast track surgery pathways on healthcare-associated infections: results from a systematic review and meta-analysis. Ann Surg 2017;265:68–79. [6] Varadhan KK, Neal KR, Dejong CHC, et al. The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr 2010;29:434–40. [7] Ban KA, Berian JR, Liu JB, et al. Effect of diagnosis on outcomes in the setting of enhanced recovery protocols. Dis Colon Rectum 2018;61:847–53. [8] Andersen J, Kehlet H. Fast track open ileo-colic resections for Crohn’s disease. Colorectal Dis 2005;7:394–7. [9] Zhu Y, Xiang J, Liu W, et al. Laparoscopy combined with enhanced recovery pathway in ileocecal resection for Crohn’s disease: a randomized study. Gastroenterol Res Pract 2018;2018, 9648674. [10] Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. [11] Agha RA, Borrelli MR, Vella-Baldacchino M, et al. The STROCSS statement: strengthening the reporting of cohort studies in surgery. Int J Surg 2017;46:198–202. [12] Delaney CP, Brady K, Woconish D, et al. Towards optimizing perioperative colorectal care: outcomes for 1,000 consecutive laparoscopic colon procedures using enhanced recovery pathways. Am J Surg 2012;203:353–6. [13] Spinelli A, Bazzi P, Sacchi M, et al. Short-term outcomes of laparoscopy combined with enhanced recovery pathway after ileocecal resection for Crohn’s disease: a case-matched analysis. J Gastrointest Surg 2013;17:126–32, discussion p.132. [14] Enriquez-Navascues JM, Elorza G, Placer C, et al. «Fast track» and intestinal surgery for Crohn’s disease: factors associated with prolonged hospital stay. Cir Esp 2016;94:531–6. [15] Dai X, Ge X, Yang J, et al. Increased incidence of prolonged ileus after colectomy for inflammatory bowel diseases under ERAS protocol: a cohort analysis. J Surg Res 2017;212:86–93. [16] Cross RK, Wilson KT, Binion DG. Narcotic use in patients with Crohn’s disease. Am J Gastroenterol 2005;100:2225–9.
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.dld.2020.01. 006.
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
ARTICLE IN PRESS Digestive and Liver Disease xxx (2020) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Alimentary Tract
A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis Michela Mineccia a,∗ , Francesca Menonna a , Paola Germani a , Valentina Gentile a , Paolo Massucco a , Rodolfo Rocca b , Alessandro Ferrero a a b
Department of Chirurgia Generale e Oncologica, Ospedale Mauriziano Umberto I, Torino, Italy Department of Gastroenterology, Ospedale Mauriziano Umberto I, Torino, Italy
a r t i c l e
i n f o
Article history: Received 11 September 2019 Accepted 15 January 2020 Available online xxx Keywords: Crohn disease surgery ERAS Length of stay Propensity score
a b s t r a c t Background: Enhanced Recovery After Surgery (ERAS) offers many benefits for patients with colorectal cancer. However, its application to patients with Crohn’s disease (CD) is questioned. Aim: The aim of this propensity-matched study was to validate the results of ERAS protocol on CD patients. Methods: Patients undergoing ileocolic resection for primary or relapsed CD from 2007 to 2018 were retrospectively analyzed and propensity-matched into two equal groups (ERAS vs standard of care). Demographic characteristics, length of stay, bowel function, oral intake, and perioperative morbidity were analyzed. Results: Ninety four out of 299 patients were selected for analysis. No significant difference was observed for age, gender, American Society of Anesthesiologists score, body mass index, previous surgery and therapy, operative time and laparoscopy. The median length of stay in ERAS and non-ERAS groups was 6 and 8 days (p < 0.001). Median postoperative days of first bowel movement and solid oral intake were day 1 and day 2 p < 0,001, and day 2 and day 4.5 p < 0,001 in ERAS and non-ERAS group, respectively. No statistically differences in other postoperative outcomes were shown. Conclusions: ERAS implementation showed decreased length of stay, faster bowel function restoration and earlier solid oral intake in patients who underwent laparoscopic or open ileocolic resection for primary or relapsing CD. © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Patients affected by Crohn Disease (CD) have an extensive disease which most of times involves the small bowel or the colon and are characterized by a systemic altered inflammatory response before surgery [1]. Patients with CD have been subjected, in most cases, to immunomodulating therapy, they might have intra-abdominal infections, and are often malnourished and anemic. Use of steroids, low albumin level, previous surgical operations and preoperative abdominal collections represent risk factors for complicated surgical outcome [2]. Patients with Inflammatory Bowel Disease (IBD) and in particular with CD could have postoperative prolonged ileus due to chronic inflammation of the intestinal wall; however, the literature that investigates the real causes and the incidence rate of postoperative ileus in patients with Crohn’s disease is, at the moment, not conclusive [3].
∗ Corresponding author. E-mail address: [email protected] (M. Mineccia).
Fast-track surgery or Enhanced Recovery After Surgery (ERAS) integrate various types of actions aimed to maintain physiological function and lightening postoperative hospital stay. The ERAS protocols implement a series of standardized steps aimed to reduce physiologic stress caused by surgery and to gain early discharge from the hospital. ERAS concerns the continuum of surgical care and includes processes such as patient education, multimodal analgesia, and early mobility. Implementation of ERAS involves the collaboration of a multidisciplinary team supporting the systematic coordination of processes. Many studies have shown that ERAS reduces postoperative Length of Stay (LOS) and may also reduce postoperative complications after surgery without worsening readmission or mortality rates [4–6]. However, the evidence on ERAS effectiveness in subgroup populations is limited by the historic use of homogenous patient samples. Despite patients with IBD have higher odds of adverse outcomes, including prolonged length of stay, serious morbidity, higher rate of readmission, and worse diet toleration [7], few studies have exam-
https://doi.org/10.1016/j.dld.2020.01.006 1590-8658/© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS
2
M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
ined the potential benefits of ERAS in this particular population [8,9]. We recently implemented the ERAS protocol in patients undergoing surgery for Ulcerative Colitis (UC) and CD. This is a single center propensity-matched study to validate the feasibility and short-term outcomes of ERAS protocol applied to patients with primary or relapsing ileocolic CD disease. 2. Materials and methods Patients with primary or recurrent CD who underwent ileocolic resection between May 2007 and December 2018 at the General and Oncologic Surgical Unit, were observed and data were collected from a prospectively maintained database. Our Surgical Unit has wide experience in surgery for Inflammatory Bowel Disease (IBD) and is well equipped to manage complex disease and complications. The ERAS protocol was implemented in our Institution since 2013 but has just recently extended to IBD patients. Data collection and analysis were performed according to the institutional guidelines and to the ethical standards of the Helsinki Declaration. The ERAS protocol is applied commonly for colorectal surgery and this paper is an observational study. Formal approval by the ethical Committee in our Country is not required for this kind of studies. Three Consultant Surgeons with experience of at least 10 cases per year in IBD surgery and laparoscopic surgery performed all operations (MM, PM, FB). Patients’ demographic (age, gender, BMI, ASA score, recurrent disease, years of disease, steroids or immunomodulating therapy within two months, malnutrition, nutritional support), intraoperative (operative time, laparoscopy) and postoperative factors (hospital stay, free oral intake, stool movements, postoperative complications, postoperative fistula, postoperative hemorrhage and 90 days readmission) were recorded [10]. From this cohort of patients, only those who underwent ileocolic resection were selected and analyzed. All the patients who underwent ileocecal or ileocolic resection received immunomodulating therapy (biological agents or thiopurine) or steroids before surgery. The therapy was stopped, whenever possible, at least one month before surgery; the therapy administrated within two months of surgery was recorded and analyzed. The primary endpoint was the length of stay. Secondary endpoints were time of postoperative solid oral intake, defined as tolerance of solid diet and the time of first bowel movement, defined as the first stool passage. Other endpoints were overall morbility (according to the Dindo-Clavien Classification [10]) and 90-day readmission. This paper has been worded in line with the STROCCS criteria [11]. 2.1. ERAS protocol Preoperative setting • avoidance of mechanical bowel preparation or premedication, • patients are invited to drink up to 2 h before surgery and to eat up to 6 h, • no preoperative midazolam is administered. Intraoperatively • the procedure is performed laparoscopically whenever possible, • an intraoperative fluid restriction regimen is applied (less than 10 ml/kg/h),
• patients receive, in the operating room, an intrathecal analgesia in the sitting position with opioid injection (100 g of hydromorphone). Postoperatively • the nasogastric tube is removed after the end of the operation before the awakening of the patient and the urinary catheter is removed the morning after, • the patient is mobilized early (2 h after surgery), • fluids intake is stimulated on the same day of surgery [5,6], • postoperative analgesia is administrated intravenously even 4−6 h with paracetamol, • pain assessment is done by nurses each 8 h, as part of their routinely clinical cares, using VAS (Visual Analogue Scale). Discharge criteria are: an acceptable pain control with oral analgesics, passage of first stool, adequate solid food intake and mobilization. 2.2. Surgical technique 2.2.1. Laparoscopic technique Laparoscopic ileocecal resection was performed with a standardized technique. Umbilical open access is done and two trocars are placed in the left iliac fossa and left upper quadrant. Trendelenburg tilt with the left-side down position is then adopted. After disease assessment, the right colon is completely mobilized, including the hepatic flexure. A short incision is performed in the right iliac fossa. The ileocecal or ileocolonic (in recurrent cases) resection and the mesentery division are performed extracorporeally, guided by intra-operative ultrasonography of the bowel. An endsewn ileo-colic anastomosis is then performed. The entire small bowel is carefully checked to exclude skip lesions. No drainage is left. 2.2.2. Open technique The same steps are performed by an open approach that usually is median laparotomy from the supraumbilical region to the pubis. 2.3. Statistical analysis Categorical variables are expressed as absolute numbers and percentages. Continuous variables are exposed as mean ± SD if normally distributed or as median and interquartile range (IQR) if not. Kolmogorov–Smirnov test was used to assess normality distribution. To identify all significant predictors of hospital stay and to calculate the variation of the estimated effect size for each predictor, multivariate Poisson regression was performed. All significative factors were used to eliminate confounding from the observed variables between the two study groups by propensity score analysis as to avoid bias related to the ERAS patient’s selection as much as possible; still, we recognize the possible existence of other unknown factors playing a role in the selection, that we are not able to account for due to lack of measurements. Linear propensity score values were used in a logistic regression analysis for risk-adjusted data. Values were used to perform a match using the nearest-neighbor method and 1-to-1 ratio, with substitution, within a specific caliper width of 0.2 SD of the logit of the estimated propensity score, beginning from cases with the largest propensity score. Covariance analysis and sensitivity analysis were then calculated with Rosenbaum test for Wilcoxon Signed-Rank p-value. We recognize that the relatively moderate sample size could represent a possible weakness of the study, especially using a propensity based method: nevertheless, we performed the same analysis with 2:1
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
3
Table 1 Baseline characteristics and surgical aspects of the study population.
Number of patients (%) Median age Gender, females (%) Median body mass index, (IQR) ASA score, (%) I II III IV Recurrent disease (%) Laparoscopy, (%) Median operative time, (IQR) Thiopurine (%) Mesalamine (%) Anti TNF blockers (%) Steroids (%) Septic (%) Malnutrition (%) Nutritional support (%) Course of disease (years), median
ERAS
N-ERAS
Overall
p
47 (15,7%) 35 (27,5–47) 28 (60%) 22 (19,96–24,96)
252 (84,3%) 42 (28,5–53) 129 (51%) 21 (19–23,2)
299 41 (28–52,5) 157 (52,5%) 21.3 (19–23)
0,06 0,36 0,12
8 (17%) 34 (72,3%) 5 (10,64%) 0 (0%) 17(36,2%) 37 (78,7%) 135 (110–161.5) 17 (36,2%) 24 (51,1%) 16 (34%) 23 (49%) 1 (2,1%) 4 (8,5%) 6 (12,8%) 6 (1,5–10)
1 (0,4%) 160 (63,5%) 90 (36%) 1 (0,4%) 108(43%) 157 (62,3%) 160 (130–195) 72 (26,9%) 109 (43,3) 43 (17,1%) 87 (35%) 5 (5,6%) 64 (25,4%) 81 (32,1%) 7 (3–14)
9 (3%) 194 (64,8%) 95 (31,8%) 1 (0,3%) 125(42%) 194 (64,9%) 155 (120–195) 89 (29,7%) 133 (44,5%) 59 (19,7%) 110 (37%) 15 (5%) 68 (22,7%) 87 (29%) 7 (3–13,5)
<0,001 0,32 0,0012 0,04 0,38 0,046 0,0089 0,41 0.41 0,013 0,086 0,53 0,019 0,012 0,25
In bold p significant values.
Table 2 Operative and post operative results of unmatched patients. ERAS (47)
N-ERAS (252)
Overall (299)
p
Median lengh of hospital stay (IQR) Days of free oral intake, median Days of first stool, median
6 (5–8,5) 2 (1–3,5) 1 (1–2)
9 (7–15) 5 (4–6) 2 (2–3)
9 (7–13) 4 (3–6) 2 (1–3)
<0,001 <0,001 <0,001
Post-operative complications, (%) Clavien–Dindo ≥ IIIb, (%) Post-operative fistula, (%) Post-operative hemorrhage, (%) 90-day readmission, (%)
1 (2,1%) 0 (0%) 1 (2,1%) 2 (4,3%)
18 (7,1%) 4 (1,6%) 13 (5,2%) 13 (5,2%)
19 (6,4%) 4 (1,3%) 14 (4,7%) 15 (5%)
0,46 0,86 0,6 0,9
In bold p significant values.
ratio and the results were almost exactly the same. Statistical analysis was performed using SPSS Statistics statistical software (version 20.0; SPSS Inc., Chicago, IL, USA), except for propensity score that was made using R Package (R Core Team 2014, R Foundation for Statistical Computing, Vienna AT).
Laparoscopic procedures and operative time did not differ between the two groups. No mortality occurred in the two groups. Serious postoperative complications (expressed with Clavien Dindo Classification ≥ IIIb, postoperative fistula, and hemorrage) and 90-day readmissions were lower in the ERAS group even if statistical significance was not reached (Table 4).
3. Results 4. Discussion A total of 369 patients underwent surgery for CD during the study period. From this group we considered 299 patients undergoing ileocolonic resections (47 ERAS vs 252 non-ERAS). The compliance with the ERAS protocol was around 95% for each items, in particular regarding avoidance of drainage ad early fluid intake in day 0. Three patients failed in early mobilization because of pain and dizziness. Baseline demographic characteristics of the study population are compared in Table 1. At the analysis, through Poisson regression, factors influencing the outcome were sex, BMI, ASA = III, age, course of disease, laparoscopy, previous therapy with anti TNF blockers, malnutrition, preoperative nutritional support, and sepsis (see Supplementary table) (Table 2). Ninety four procedures were propensity-matched on the basis of the belonging to ERAS protocol. After propensity score matching, the obtained two groups showed no significant differences in regard to patients characteristics (see Table 3). The median length of stay was significantly shorter in the ERAS group (6 vs 8 days, p = <0.001) (Table 4). Days (median) of first stool movement and of free feeding were significantly lower in the ERAS group (1 vs 2 days p < 0.001, and 2 vs 4.5 p < 0,001, respectively) (Table 4).
The adoption of ERAS protocols has improved in last decades for colorectal neoplasms and diverticular disease. As a consequence, perioperative management of patient submitted for colorectal surgery has gained quality due to laparoscopy and Enhanced Recovery Protocols [12]. In the last three years, in our Department, the application of ERAS protocol has become the gold standard also for IBD. In our study, ERAS reduced LOS and gave better outcome with early stool movement and early return to free feeding for patients operated for CD. The findings of this study confirm some recent reports concerning the benefit of ERAS protocols applied to CD patients. Surprisingly, before 2013, there has just been one paper addressing the feasibility of fast track protocols in patients with CD undergoing open approach [8]. Moreover, a single case-matched study showed an improvement in surgical outcome and a significantly faster recovery for patients with primary ileocecal CD undergoing laparoscopic resection with ERAS protocol [13]. A recent paper from Zhu et al. [9] concludes that laparoscopic approach within an ERAS perioperative care program is a safe and effective treatment combination for CD patients requiring ileocecal resection. This ran-
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS
4
M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
Table 3 Baseline characteristics and surgical aspects of matched subgroups selected by propensity score analysis. ERAS
N-ERAS
Overall
p
Number of patients (%) Median age, (IQR) Gender, females (%) Median body mass index, (IQR)
47(50%) 35 (27,5–47) 28 (60%) 22 (19,96–24,96)
47 (50%) 35 (29–44) 31 (66%) 21,6 (19,7–24,7)
94 35(27–45) 59 (63%) 21,8 (19,8–24,9)
0,78 0,67 0,4
ASA score, (%) I II III IV Recurrent disease (%) Laparoscopy, (%) Median Operative time, (IQR) Thiopurines (%) Mesalamine (%) Anti TNF blockers (%) Steroids (%) Septic (%) Malnutrition (%) Nutritional Support (%) Course of disease (years), median
8 (17%) 34 (72,3%) 5 (10,6%) 0 (0%) 17 (36,2%) 37 (78,7%) 135 (110–161,5) 17 (36,2%) 24 (51,1%) 16 (34%) 23 (49%) 1 (2,1%) 4 (8,4%) 6 (12,8%) 6 (1,5–10)
0 (0%) 43 (91,4%) 4 (8,5%) 0 (0%) 17 (36,2%) 39 (83%) 150 (126–201,5) 22 (46,8%) 18 (38.3) 15 (31,9%) 20 (43%) 2 (4,3%) 6 (12,8%) 8 (17%) 7 (2–11,5)
8 (9%) 77 (81,9%) 9 (9,6%) 0 (0%) 34 (36,2%) 76 (80,1%) 149,5 (120–188,8) 39 (41,5%) 42 (44,7%) 31 (33%) 43 (46%) 3 (3,2%) 10 (10,6%) 14 (14,9%) 7 (2–10,5)
<0,001 0,03 1 NA 1 0,79 0,15 0,4 0.3 1 0,68 1 0.74 0.78 0.24
In bold p significant values.
Table 4 Operative and post-operative results of matched subgroups selected by propensity score analysis.
Median lengh of hospital stay (IQR) Days of free oral intake, median Days of first stool, median Post-operative complications Clavien–Dindo ≥ IIIb, (%) Post-operative fistula, (%) Post-operative hemorrhage, (%) 90-day readmission, (%)
ERAS
N-ERAS
Overall
p
6 (5–8,5) 2 (1–3,5) 1 (1–2)
8 (7–10) 4,5 (3–6,5) 2 (2–3)
7 (6–10) 3 (1–4,5) 2 (1–2)
<0,001 <0,001 <0,001
1 (2,1%) 0 (0%) 1 (2,1%) 2 (4,3%)
2 (4,3%) 1 (2,1%) 1 (2,1%) 2 (4,3%)
3 (6,4%) 1 (1%) 2 (2,1%) 4 (4,3%)
0,56 1 1 1
In bold p significant values.
domized study considers a little cohort of patients from western country (16 per arm) who underwent laparoscopic ileocecal resection for primary disease. Other authors, instead, showed a prolonged postoperative stay after surgery for CD when an ERAS protocol was implemented but such result could be justified by the degree of the disease, the type of resection performed, or other pre-existing patient conditions. This is why patients with CD should gain a better performance status before surgery and prehabilitation and postoperative management has to be optimized [14]. Ban et al. have analyzed the effect of diagnosis on the outcome of ERAS protocols. Patients with IBD (if compared with those with cancer or diverticular disease) had higher odds of adverse outcomes and always took them longer to achieve postoperative pain control and to tolerate a diet. IBD was identified as an independent predictor of adverse outcomes including unplanned reoperation and postoperative ventilator dependency [7]. Another paper emphasizes that preoperative steroid use, hypoalbuminemia, systemic inflammatory response syndrome (SIRS) status and postoperative intra-abdominal sepsis could represent an independent risk factors for prolonged ileus in IBD patients [15]. All these papers underline that patients affected by IBD and particularly by CD are prone to postoperative adverse events, including difficulty in pain control, delayed return of bowel function and prolonged ileus, probably also due to the chronic use of opioid [16]. The bad results showed by these Authors can be explained with the inclusion of both CD and Ulcerative Colitis in the study population and patients with UC are not always young, mostly if affected by “long-standing disease” with the onset of neoplasia. Further-
more, any kind of operation are considered (partial colectomy, total colectomy, ileocolic resection, ileostomy or colostomy) and it could bring sample variability. This is the reason why we selected a standardized surgical procedure (laparoscopic or open) in order to highlight the effective role of the ERAS management and to further reduce possible bias. Patients with ileocecal or ileocolic localization of CD (if relapse) were chosen. The propensity score was used, thereby balancing the treatment and control groups. A possible explanation for our good results is that patients affected by CD are mostly young and have often active lifestyles. Such patients have demonstrated a great adherence to the ERAS preoperative program wishing to gain a rapid recovery in order to achieve a quick return to work and social activities. As part of this management education program, it is also important to involve patients’ caregivers who can play a substantial role when the patient is discharged from the hospital. The preoperative education is crucial and consists of a detailed list of information by a team of surgeon, anesthesiologist, gastroenterologist, dietician, caregiver and stoma therapist if necessary. All those instructions are not limited to the surgical procedure but also include other important and practical aspects as preparation for surgery, timing and type of diet intake, pain management, and modalities and timing of mobilization. During such preoperative counseling young patients have proven to be interested and motivated with the desire to succeed. The avoidance of drains and nasogastric tube placement plays another substantial role in the success of ERAS program. Surgery for CD, especially if performed for relapse, could be more complex and shows a higher risk of bleeding and leakage due to the thickness
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006
G Model YDLD-4261; No. of Pages 5
ARTICLE IN PRESS M. Mineccia et al. / Digestive and Liver Disease xxx (2020) xxx–xxx
of inflamed mesentery and to the presence residue disease in the bowel wall. And so, even in those cases, the drain is not left because it couldn’t be completely fitted to the protocol guidelines. Limitations of this study are represented by bias inherent its retrospective design. Firstly, there is a risk for lead time bias because the study observes a period of 10 years and the ERAS protocol was implemented only in the last part of this time interval. The Propensity score was used in order to balance the ERAS and the control groups redistributing significant covariates. The risk remains that variables we have not been able to identify may play a determinant role. The exclusion of patients represents a limitation of this kind of study, but there is no difference between matched and unmatched records. Moreover, in the multivariate analysis adjusting for the same covariates in the original sample, results are similar compared to the matched analysis. Lastly, this paper shows the results of a single institution, and shouldn’t be considered as a representative sample and the small sample size gives the study less power. Confirmation from other studies is therefore necessary. 5. Conclusion This propensity score matched study showed a significantly shorter hospital stay, earlier stool movement and return to free oral intake for patients with primary or relapse ileocolic CD undergoing laparoscopic or open surgery, enrolled in ERAS protocol. It validates the ERAS protocol for a subgroup of patients with a complex disease, such as CD, and shows that effective perioperative care joined to an experienced surgical team may hesitate in further improvements of surgical outcomes for CD patients. Conflict of interest None declared. Ethical approval The ERAS protocol is applied routinely for colorectal surgery and this paper is an observation study. A formal approval by ethical Committee in our Country is not required for this kind of studies
5
References [1] de Buck van Overstraeten A, Van Hoef S, Vermeire S, et al. Postoperative inflammatory response in Crohn’s patients: a comparative study. J Crohns Colitis 2015;9:1127–31. [2] Grass F, Pache B, Martin D, et al. Feasibility of early postoperative mobilisation after colorectal surgery: a retrospective cohort study. Int J Surg 2018;56:161–6. [3] Murphy MM, Tevis SE, Kennedy GD. Independent risk factors for prolonged postoperative ileus development. J Surg Res 2016;201:279–85. [4] Ljungqvist O, Scott M, Fearon KC. Enhanced recovery after surgery: a review. JAMA Surg 2017;152:292–8. [5] Grant MC, Yang D, Wu CL, et al. Impact of enhanced recovery after surgery and fast track surgery pathways on healthcare-associated infections: results from a systematic review and meta-analysis. Ann Surg 2017;265:68–79. [6] Varadhan KK, Neal KR, Dejong CHC, et al. The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr 2010;29:434–40. [7] Ban KA, Berian JR, Liu JB, et al. Effect of diagnosis on outcomes in the setting of enhanced recovery protocols. Dis Colon Rectum 2018;61:847–53. [8] Andersen J, Kehlet H. Fast track open ileo-colic resections for Crohn’s disease. Colorectal Dis 2005;7:394–7. [9] Zhu Y, Xiang J, Liu W, et al. Laparoscopy combined with enhanced recovery pathway in ileocecal resection for Crohn’s disease: a randomized study. Gastroenterol Res Pract 2018;2018, 9648674. [10] Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. [11] Agha RA, Borrelli MR, Vella-Baldacchino M, et al. The STROCSS statement: strengthening the reporting of cohort studies in surgery. Int J Surg 2017;46:198–202. [12] Delaney CP, Brady K, Woconish D, et al. Towards optimizing perioperative colorectal care: outcomes for 1,000 consecutive laparoscopic colon procedures using enhanced recovery pathways. Am J Surg 2012;203:353–6. [13] Spinelli A, Bazzi P, Sacchi M, et al. Short-term outcomes of laparoscopy combined with enhanced recovery pathway after ileocecal resection for Crohn’s disease: a case-matched analysis. J Gastrointest Surg 2013;17:126–32, discussion p.132. [14] Enriquez-Navascues JM, Elorza G, Placer C, et al. «Fast track» and intestinal surgery for Crohn’s disease: factors associated with prolonged hospital stay. Cir Esp 2016;94:531–6. [15] Dai X, Ge X, Yang J, et al. Increased incidence of prolonged ileus after colectomy for inflammatory bowel diseases under ERAS protocol: a cohort analysis. J Surg Res 2017;212:86–93. [16] Cross RK, Wilson KT, Binion DG. Narcotic use in patients with Crohn’s disease. Am J Gastroenterol 2005;100:2225–9.
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.dld.2020.01. 006.
Please cite this article in press as: Mineccia M, et al. A retrospective study on efficacy of the ERAS protocol in patients undergoing surgery for Crohn disease: A propensity score analysis. Dig Liver Dis (2020), https://doi.org/10.1016/j.dld.2020.01.006