Skip to main content
PLOS ONE logoLink to PLOS ONE
. 2020 May 8;15(5):e0232857. doi: 10.1371/journal.pone.0232857

A retrospective observational study of enhanced recovery after surgery in older patients undergoing elective colorectal surgery

Katleen Fagard 1,*, Albert Wolthuis 2, Marleen Verhaegen 3, Johan Flamaing 1,4, Mieke Deschodt 4,5
Editor: Yan Li6
PMCID: PMC7209103  PMID: 32384120

Abstract

Background

Enhanced recovery programs (ERPs) in colorectal surgery have demonstrated beneficial effects on postoperative complications, return of bowel function, length of stay, and costs, without increasing readmissions or mortality. However, ERPs were not specifically designed for older patients and feasibility in older patients has been questioned.

Aim

The aim of this study was to assess ERP adherence and outcomes in older patients and to identify risk factors for postoperative complications and prolonged length of stay.

Method

Retrospective analysis of consecutive patients (≥70 years) undergoing elective colorectal resection in a tertiary referral hospital in 2017.

Results

Ninety-six patients were included. Adherence rates were above 80% in 18 of 21 ERP interventions considered. The lowest adherence rates were noted for preoperative carbohydrate loading and cessation of intravenous fluids. Postoperative complications (Clavien-Dindo ≥2) and prolonged postoperative length of stay (>75th percentile) were observed in 39.6% and 26.3%, respectively. Median length of stay was 7 days. The 30-day mortality, readmission and reoperation rates were 2.1%, 12.6% and 8.3%, respectively. Multivariable analysis indicated that polypharmacy and site of surgery were independent risk factors for postoperative complications, while higher age, American Society of Anesthesiologists class and preoperative radiotherapy were independent risk factors for prolonged postoperative length of stay.

Conclusion

ERP adherence in older patients undergoing colorectal resection is high and ERP is therefore considered feasible. Postoperative complications and prolonged postoperative length of stay are common, so at risk patients should be targeted with tailored geriatric interventions.

Introduction

Population growth, demographic ageing and advances in surgical and anesthetic techniques have caused a marked increase in the demand for surgical procedures in older persons [13]. As ageing is associated with a decrease in physiologic reserve and higher rates of comorbidity, many older patients are more susceptible to adverse postoperative outcomes, such as medical and surgical complications, prolonged hospital stay, loss of independence in activities of daily living, and need for institutionalization. This presents organizational and socio-economic challenges to our health care system [36].

Surgical teams have developed and implemented multidisciplinary care programs, known as Fast Track Surgery, Enhanced Recovery Programs (ERPs) or Enhanced Recovery After Surgery (ERAS®) programs, resulting in improved patient outcomes and reduced lengths of stay (LOS) [7, 8]. ERPs include evidence-based changes in traditional care, such as pre-admission counselling, avoidance of mechanical bowel preparation, shortened fasting, a carbohydrate drink two hours before surgery, avoidance of fluid overload, minimal invasive surgery, avoidance or early removal of drains and catheters, opioid-sparing multimodal analgesia, early feeding and mobilization. A recent meta-analysis has demonstrated that ERPs in colorectal surgery are associated with a significant reduction in LOS, postoperative complications, total cost of hospital stay, as well as earlier return of gastro-intestinal function, without increasing 30-day readmission or mortality rates [9]. However, ERPs were not specifically designed for frail older patients and data from these programs in older patients are scarce [1012]. It might be necessary to adapt ERPs for older patients with multi-morbidity, functional, cognitive or psychosocial problems.

The objectives of the present study were to assess ERP adherence and outcomes in older patients undergoing colorectal resection, and to identify risk factors for postoperative complications and prolonged LOS.

Materials and methods

Study design and setting

Single-center retrospective observational cohort study. The study was conducted in the University Hospitals Leuven. Patients were selected from a database with planned operations in 2017. Data were collected from the patients’ electronic medical records. The medical ethics committee of the University Hospitals Leuven approved the study (S61709).

Sample

Patients aged 70 years and over who underwent elective colorectal resections in an ERP were eligible for inclusion. Patients undergoing emergency surgery, hyperthermic intraperitoneal chemotherapy, adhesiolysis, stoma closure or transit repair, rectopexy or prolapse surgery, transanal procedures, proctological operations or local stoma procedures were excluded.

Enhanced recovery program

The standard ERP for colorectal surgical patients at the time of the study is detailed in S1 Table. The program was applied to all adult patients, irrespective of age. ERP components are divided in 20 intervention categories, based on the ERAS® guidelines (2012) that were valid at that time [13, 14].

Variables and measurements

Demographic variables

The following demographic data were collected: age, gender, and living situation: at home, assisted living facility, nursing home.

Clinical baseline variables

Preoperative baseline characteristics retrieved from the electronic medical records were: the Flemish version of the Triage Risk Screening Tool (fTRST) [15], number of medications, nutritional risk score (NRS-2002) initial screening items [16], Charlson Comorbidity Index (CCI) [17], age adjusted CCI (ACCI) [18], height, weight, cancer or benign diagnosis, and preoperative treatment for cancer with chemo- or radiotherapy.

The fTRST screens older patients for their risk of hospitalization associated functional decline, recurrent hospital admissions or nursing home admission by scoring the following risk factors: living alone, cognitive impairment, impaired mobility, polypharmacy (≥5 medications) and hospitalization within 3 months. Patients scoring ≥2 on the fTRST are at increased risk [15]. The NRS-2002 was developed to detect undernutrition in the hospital setting and includes the following items: Body Mass Index (BMI) <20.5, weight loss within the last 3 months, reduced dietary intake in the last week, severely ill. A patient scoring positive on at least one these risk factors in combination with planned major abdominal surgery is undernourished or at risk of undernutrition [16]. Both are routinely scored by the nursing team on admission to our hospital. The CCI as well as the ACCI were calculated based upon the comorbidities encountered in the medical records. The ACCI adds 3 points to the CCI for age 70–79, and 4 points for age ≥80 [18]. Height and weight were used to calculate the BMI. BMI results were classified using the World Health Organization criteria: underweight <18.5 kg/m2, adequate 18.5–24.9 kg/m2, overweight 25–29.9 kg/m2 or obese ≥30 kg/m2 [19].

Surgery-related variables

The following surgery-related variables were collected: American Society of Anesthesiologists (ASA) class [20], type of surgery (ileocecal resection or right colectomy or left colectomy, sigmoid resection or Hartmann, rectal surgery, total or proctocolectomy), site of surgery (colon, rectum), surgical approach (laparoscopic, open or converted), stoma creation, other surgical procedures (resection of structures other than those mentioned in ‘type of surgery’).

Adherence

Adherence to 21 ERP interventions was derived from the electronic medical records and reported as the percentage of patients that adhered to the intervention. The interventions considered were: 1) Preadmission education by ERP nurse, 2) No mechanical bowel preparation in colonic surgery, 3) Carbohydrate loading 3 hours prior to surgery, 4) No sedative or anxiolytic premedication, 5) Thromboprophylaxis with low molecular weight heparin, 6) Antimicrobial prophylaxis, 7) Postoperative nausea and vomiting (PONV) prophylaxis administered in patients with ≥1 risk factor on the Apfel Score [21, 22], 8) Planned laparoscopic operation, 9) No nasogastric tube after reversal of anesthesia, 10) Prevention of intraoperative hypothermia, 11) Cessation of intravenous fluids by postoperative day (POD) 3, provided removal of PCEA or patient controlled intravenous analgesia (PCIA), 12) No abdominal drain in colonic surgery, 13) Removal of urinary catheter on POD 1 in laparoscopic colonic surgery and on POD 3 in open colonic surgery, provided PCEA removal, 14) Patient controlled epidural analgesia (PCEA) activated before first incision in open surgery, provided patient without long-term anticoagulant therapy, 15) Oral food on POD 1, 16) Oral food on POD 2, 17) Oral food on POD 3, 18) Glucose day profile in patients with diabetes, 19) Out of bed on POD 1, 20) Out of bed on POD 2, 21) Out of bed on POD 3.

Outcome variables

The primary endpoints of this study were the occurrence of Clavien-Dindo grade 2 and above in-hospital postoperative complications and prolonged postoperative LOS, i.e. LOS exceeding the 75th percentile.

The secondary outcome variables included: In-hospital complications that occurred during or after surgery and their severity grading according to the Clavien-Dindo classification [23, 24], the Comprehensive Complication Index [25], mortality within the first 30 postoperative days, postoperative LOS, 30-day readmission rate, unplanned reoperation within the first 30 postoperative days. Postoperative LOS was defined as the number of postoperative days spent in the hospital until discharge or until transfer to a rehabilitation unit. The 30-day readmission rate was defined as the number of patients with unplanned readmissions to the hospital within 30 days of discharge due to a complication of the primary operation.

Data analysis

Continuous variables were reported as medians with interquartile ranges (IQR). Categorical variables were reported as numbers and percentages. The demographic, baseline and surgery-related variables were studied as predictors for the primary outcomes in univariable analysis. Dichotomous variables were compared using Chi-squared or Fisher’s exact tests. Nominal variables were compared using Chi-squared tests. Ordinal and non-normally distributed continuous variables were compared using Mann-Whitney U tests. To determine independent predictors for our primary outcomes, all variables were entered in a multivariable forward logistic regression model. P-values, Odds Ratios (OR), and 95% confidence intervals (CI) are reported. All tests were 2-tailed, assuming a 5% significance level. All analyses were performed using SPSS version 20.0 (SPSS Inc., Chicago, IL).

Results

Description of the sample

Ninety-six patients were included in the study (Fig 1). Their median age was 77 (IQR 73–82) years, and 50% were female (Table 1). The majority (92.7%) lived at home before admission. fTRST scoring was positive in 49% of the patients: 26% was living alone, 4.2% had cognitive impairment, 24% had impaired mobility, 62.5% took 5 or more medications, and 40.6% had been hospitalized in the last 3 months. The NRS-2002 identified 33 patients (34.4%) with undernutrition or risk for undernutrition. Median BMI was 25.3 kg/m2 (IQR 23.0–28.7). Fifty-eight patients (60.4%) had at least two chronic diseases in the CCI list and 31 patients (32.3%) scored above the median CCI score of 3. Forty-seven patients (49.0%) had ACCI scores above the median of 6. A majority of patients (68.7%) were classified in ASA class 3 or 4. One quarter of the patients underwent surgery for benign disease; the remaining patients had colorectal cancer. The majority of operations were planned laparoscopically: 82.0% of colonic operations (50/61) and 88.6% (31/35) of rectal operations. In 10.0% of colonic operations (5/50) and 16.1% of rectal operations (5/31) the laparoscopic procedure was converted to open surgery. The reasons for conversion were obesity (n = 2), extensive adhesions (n = 5), extensive malignancy (n = 2), and difficult splenic flexure mobilisation (n = 1).

Fig 1. Flowchart of the study recruitment.

Fig 1

HIPEC: hyperthermic intraperitoneal chemotherapy; TAE: transanal excision; TAMIS: transanal minimally invasive surgery.

Table 1. Baseline characteristics of the total study sample and in relation to the primary outcomes (univariable analysis).

All patients
(n = 96)
CD < 2 POCs
(n = 58)
CD ≥ 2 POCs
(n = 38)
P-value LOS ≤ P751
(n = 70)
LOS > P751
(n = 25)
P-value
Age, median (IQR) 77 (73–82) 76 (72–81) 80.5 (73.8–84) 0.035 76 (72–81) 80 (75–84) 0.011
Gender, n (%)
 Male 48 (50.0) 29 (50.0) 19 (50.0) 1.000 34 (48.6) 13 (52.0) 0.769
 Female 48 (50.0) 29 (50.0) 19 (50.0) 36 (51.4) 12 (48.0)
Living situation, n (%)
 at home 89 (92.7) 55 (94.8) 34 (89.5) 0.556 66 (94.3) 22 (88.0) 0.272
 assisted living facility 3 (3.1) 1 (1.7) 2 (5.3) 1 (1.4) 2 (8.0)
 nursing home 4 (4.2) 2 (3.4) 2 (5.3) 3 (4.3) 1 (4.0)
fTRST-score ≥ 2, n (%) 47 (49.0) 24 (41.4) 23 (60.5) 0.066 28 (40.0) 18 (72.0) 0.006
 fTRST: living alone, n (%) 25 (26.0) 13 (22.4) 12 (31.6) 0.317 17 (24.3) 7 (28.0) 0.714
 fTRST: cognitive impairment, n (%) 4 (4.2) 1 (1.7) 3 (7.9) 0.297 3 (4.3) 1 (4.0) 1.000
 fTRST: impaired mobility, n (%) 23 (24.0) 12 (20.7) 11 (28.9) 0.654 11 (15.7) 11 (44.0) 0.004
 fTRST: polypharmacy2, n (%) 60 (62.5) 31 (53.4) 29 (76.3) 0.024 40 (57.1) 20 (80.0) 0.042
 fTRST: recent hospitalisation3, n (%) 39 (40.6) 23 (39.7) 16 (42.1) 0.811 26 (37.1) 12 (48.0) 0.342
Number of medications, median (IQR) 6 (4–8) 5 (3–8) 7 (4.75–8) 0.040 5 (3–8) 6 (5–8) 0.243
Nutrition risk4, n (%
 1 screening item positive 27 (28.1) 14 (24.1) 13 (34.2) 0.472 17 (24.3) 9 (36.0) 0.538
 2 screening items positive 5 (5.2) 3 (5.2) 2 (5.3) 4 (5.7) 1 (4.0)
 3 screening items positive 1 (1.0) 1 (1.7) 0 (0.0) 1 (1.4) 0 (0)
CCI, median (IQR) 3 (2–4) 3 (2–4) 3 (2–5) 0.077 3 (2–4) 3 (2–4) 0.378
ACCI, median (IQR) 6 (5–7.75) 6 (5–7) 7 (6–9) 0.007 6 (5–7) 7 (6–8) 0.101
BMI5, n (%)
 18.5–24.9 (normal) 41 (42.7) 28 (48.3) 13 (34.2) 0.078 30 (42.9) 11 (44.0) 0.956
 25–29.9 (overweight) 38 (39.6) 23 (39.7) 15 (39.5) 28 (40.0) 9 (36.0)
 ≥ 30 (obese) 17 (17.7) 7 (12.1) 10 (26.3) 12 (17.1) 5 (20.0)
ASA class, n (%)
 ASA 1 2 (2.1) 1 (1.7) 1 (2.6) 0.045 0 (0.0) 1 (4.0) 0.009
 ASA 2 28 (29.2) 22 (37.9) 6 (15.8) 27 (38.6) 1 (4.0)
 ASA 3 56 (58.3) 30 (51.7) 26 (68.4) 37 (52.9) 19 (76.0)
 ASA 4 10 (10.4) 5 (8.6) 5 (13.2) 6 (8.6) 4 (16.0)
Type of surgery, n (%)
 Ileocecal, right or left hemicolectomy 38 (39.6) 24 (41.4) 14 (36.8) 0.427 29 (41.4) 8 (32.0) 0.207
 Sigmoid, Hartmann 21 (21.9) 15 (25.9) 6 (15.8) 17 (24.3) 4 (16.0)
 Rectal 34 (35.4) 17 (29.3) 17 (44.7) 21 (30.0) 13 (52.0)
 Total colectomy or proctocolectomy 3 (3.1) 2 (3.4) 1 (2.6) 3 (4.3) 0 (0)
Site of surgery, n (%)
 Colon or total 61 (63.5) 41 (70.7) 20 (52.6) 0.072 48 (68.6) 12 (48.0) 0.067
 Rectum 35 (36.5) 17 (29.3) 18 (47.4) 22 (31.4) 13 (52.0)
Surgical approach, n (%)
 Laparoscopic 71 (74.0) 46 (79.3) 25 (65.8) 0.140 56 (80.0) 14 (56.0) 0.019
 Open or converted 25 (26.0) 12 (20.7) 13 (34.2) 14 (20.0) 11 (44.0)
Stoma6, n (%) 33 (34.4) 16 (27.6) 17 (44.7) 0.084 19 (27.1) 14 (56.0) 0.009
Other surgical procedures, n (%) 16 (16.7) 8 (13.8) 8 (21.1) 0.351 9 (12.9) 7 (28.0) 0.118
Cancer, n (%) 72 (75.0) 40 (69.0) 32 (84.2) 0.092 50 (71.4) 21 (84.0) 0.214
Preoperative chemotherapy, n (%) 11 (11.5) 6 (10.3) 5 (13.2) 0.748 5 (7.1) 6 (24.0) 0.034
Preoperative radiotherapy, n (%) 13 (13.5) 6 (10.3) 7 (18.4) 0.258 5 (7.1) 8 (32.0) 0.004

ACCI: Age Adjusted Charlson Comorbidity Index; ASA: American Society of Anesthesiologists; BMI: Body Mass Index; CCI: Charlson Comorbidity Index; CD: Clavien-Dindo severity grade; fTRST: Flemish version of the Triage Risk Screening Tool; IQR: interquartile range; LOS: (postoperative) length of stay; n: number; POCs: postoperative complications;

175th percentile = 10.75 days (only patients discharged alive were considered);

2≥5 medications;

3hospitalised in the last 3 months;

4Nutrition Risk Screening according to the NRS-2002;

5none with BMI <18.5 = underweight;

6colo- or ileostomy

Adherence to the ERP

Table 2 summarizes 21 ERP interventions with their level of adherence. The majority of interventions had high adherence rates ranging between 80.0 and 100%. Lower adherence rates were noted for urinary catheter removal (77.5%), for carbohydrate loading (69.8%), and for cessation of intravenous fluids by POD 3 (54.7%). There was no significant difference in carbohydrate loading in patients with or without diabetes: 65.0% of patients with diabetes versus 71.1% of patients without diabetes (p = 0.595). In the subgroup of patients without complications needing medical or surgical treatment (Clavien-Dindo <2) the adherence rate for cessation of intravenous fluids was 63.8% and the protocol for urinary catheter removal was applied in 87.7%. The median POD of urinary catheter removal was 1 (IQR 1–3) in patients with Clavien-Dindo <2 postoperative complications and 3 (IQR 1–6.75) in patients with Clavien-Dindo ≥2 postoperative complications. The need for urinary catheter (re)placement was low: 5/92 patients (5.4%). The overall (mean) adherence for the 21 measured interventions was 87.9% (SD ±10.8).

Table 2. Adherence to the ERP.

ERP component Assessment of adherence Result
n (%)
n patients
1 Preadmission counselling ERP consultation 83 (86.5) 96
2 Preoperative optimization n.a. n.a. 96
3 Preoperative bowel preparation No mechanical bowel preparation in colonic surgery 60 (98.4) 611
4 Preoperative fasting n.a. n.a. 96
Carbohydrate loading Yes 67 (69.8) 96
5 Pre-anesthetic medication No sedative or anxiolytic premedication 88 (91.7) 96
6 Thromboprophylaxis Yes 95 (99.0) 96
7 Antimicrobial prophylaxis Yes 96 (100) 96
8 Standard anesthesia protocol n.a.
9 PONV prophylaxis In patients with PONV risk ≥ 20% 89 (94.7) 942
10 Laparoscopy and modifications of surgical access Planned laparoscopic operation 81 (84.4) 96
11 Nasogastric tubes No NGT after reversal of anesthesia 92 (95.8) 96
12 Preventing intraoperative hypothermia Yes 84 (87.5) 96
13 Perioperative fluid management Stop intravenous fluids ≤ POD 3 (provided removal of PCEA/PCIA)
  • All patients

  • CD < 2 POCs*


52 (54.7)
37 (63.8)*

953
58
14 Drain peritoneal cavity No abdominal drain in colonic surgery 50 (82.0) 611
15 Urinary catheter Removal urinary catheter per protocol: laparoscopic colon POD 1, open colon or rectum POD 3 (only after PCEA removal)
  • All patients

  • CD < 2 POCs*


69 (77.5)
50 (87.7)*

893,4,5
57
16 Ileus prevention n.a. n.a. 96
17 Multimodal opioid sparing postop analgesia8 PCEA in patients without coagulation disorders for whom open surgery was planned 8 (88.9) 96
18 Early nutrition Oral food POD 1 79 (84.9) 937
Oral food POD 2 83 (89.2) 933,7
Oral food POD 3 82 (90.1) 913,7
19 Postoperative glycemic control Glucose day profile in patients with diabetes 19 (95.0) 208
20 Early mobilization Out of bed POD 1 78 (83.9) 937
Out of bed POD 2 87 (93.6) 933,7
Out of bed POD 3 90 (98.9) 913,7
Overall adherence, mean (± SD) 87.9% (± 10.8)

CD: Clavien-Dindo severity grade; ERP: enhanced recovery program; n: number; n.a.: adherence was not assessed; NGT: nasogastric tube; PCEA: patient controlled epidural analgesia; PCIA: patient controlled intravenous analgesia; POCs: postoperative complications; POD: postoperative day; PONV: postoperative nausea and vomiting; SD: standard deviation; excluded from the analysis:

1rectal surgery (n = 35),

2missing data (n = 2),

3deceased patient (n = 1),

4no urinary catheter (n = 3),

5permanent catheter (n = 3),

6open surgery planned (n = 15) in patients with coagulation disorders (n = 6),

7ICU admission on the POD considered,

8no diabetes (n = 76); 8all patients received paracetamol, restrictive use of NSAIDs due to age and comorbidities;

*this subgroup is not included in the calculation of the overall adherence

Outcome data

The median postoperative LOS was 7 days (IQR 5–10.8). Sixty-one patients (63.5%) had in-hospital postoperative complications, of whom 38 (39.6%) Clavien-Dindo ≥2 and 13 (13.5%) Clavien-Dindo ≥3 (Table 3). The median Comprehensive Complication Index was 8.7 (IQR 0–24.2). Details on individual postoperative complications can be found in S2 Table. Classification into specific disease categories showed the following in-hospital complication rates: ileus or gastroparesis with nasogastric tube placement 13.5%, urinary tract infection 9.3%, urinary retention 8.3%, medically treated confusion 5.2%, cardiac arrhythmia 5.2%, heart failure treated with diuretics 3.1%, pneumonia 3.1%, catheter-related bloodstream infection 2.1%, myocardial infarction 1%. None of the patients had deep venous thrombosis or pulmonary embolism. At 30 days post-surgery two patients (2.1%) had died and 12 patients were readmitted (12.6%). Eight patients (8.3%) had unplanned reoperations within 30 days of the initial operation. Six of them had an anastomotic leak.

Table 3. Primary and secondary outcomes.

n = 96
Postoperative length of stay, median (IQR) 7 (5–10.75)
In-hospital postoperative complications, n (%)
  • Clavien-Dindo grade 1

  • Clavien-Dindo grade 2

  • Clavien-Dindo grade 3

  • Clavien-Dindo grade 4

  • Clavien-Dindo grade 5


23 (24.0)
25 (26.0)
4 (4.2)
8 (8.3)
1 (1.0)
30-day mortality rate, n (%) 2 (2.1)
30-day readmission rate1, n (%) 12 (12.6)
30-day (unplanned) reoperation rate, n (%) 8 (8.3)

IQR: interquartile range; n: number;

1n = 95, only patients discharged alive were considered

Risk factors for postoperative complications and for prolonged hospital stay

All baseline characteristics (n = 23) were analyzed as risk factors in relation to the primary outcomes in univariable analysis (Table 1). Age, polypharmacy, ACCI, and ASA class were found to be significantly associated with Clavien-Dindo ≥2 complications. Polypharmacy was an independent risk factor in the forward logistic regression analysis (OR 3.4, 95% CI 1.3–8.9, p = 0.013), together with the site of surgery (OR 2.7, 95% CI 1.1–6.8, p = 0.032). Age, fTRST, impaired mobility, polypharmacy, ASA class, surgical approach, creation of a stoma, preoperative chemotherapy and preoperative radiotherapy were significantly associated with prolonged postoperative LOS (Table 1). Age (OR 1.1, 95% CI 1.0–1.2, p = 0.020), ASA class (OR 2.7, 95% CI 1.1–6.7, p = 0.031) and preoperative radiotherapy (OR 10.6, 95% CI 2.6–44.3, p = 0.001) remained as independent risk factors in forward logistic regression analysis.

Discussion

This retrospective study analyzed ERP adherence, outcomes, and risk factors for postoperative complications and prolonged postoperative LOS in older patients undergoing colorectal surgery in an ERP. Despite a high overall adherence rate to the ERP in our study, postoperative adverse events in our older patient population were common. In-hospital postoperative complications graded as Clavien-Dindo ≥2 were present in every two out of five patients. Site of surgery and polypharmacy were independent predictors of ≥ grade 2 postoperative complications, while age, ASA class and preoperative radiotherapy were independent predictors of LOS >75th percentile.

Compared with two multicenter studies in adult patients undergoing colorectal cancer resections, the mean adherence rate of 87.9% to the ERP in our study is considered as high. Van Zelm et al. observed adherence rates above 80% for only 8 of 43 considered interventions, while in the study by the ERAS Compliance Group the mean adherence to 13 interventions was 76.6% [26, 27]. The lowest adherence rates in our study were found for preoperative carbohydrate loading and for timely removal of intravenous lines or urinary catheters. A possible explanation for omitting the carbohydrate drink could be that surgeries may take place earlier than scheduled and logistic reasons might play a role. Having diabetes did not significantly affect carbohydrate loading. This is consistent with the ERAS® guideline that allows carbohydrate loading if given along with diabetes medication. Thirty-six percent of patients without postoperative complications needing treatment (Clavien-Dindo grades 0 and 1) and without PCEA or PCIA still had an intravenous line by POD 3. This could have been due to the presence of electrolyte disturbances, insufficient fluid intake or excessive fluid losses, but these factors were not considered during the data collection. Moreover, a short enquiry on the ward learned that nurses are reluctant to remove catheters and intravenous lines, despite being encouraged to do so, because they anticipate reinsertion later on.

Overall postoperative complication rates and median postoperative LOS were quite high. In a review performed by our team that summarized outcomes of ERPs in older patients (≥ 65 years) after colorectal surgery, the median overall morbidity was 23.5% and the median postoperative LOS was 6 days [12]. Conducting this review showed that it is challenging to compare postoperative complications among studies, because in- and exclusion criteria differ and because complications are not defined or assessed in a uniform way. Many studies only assess a selection of complications or range complications by organ system. Post-hoc classification of postoperative complications in our study into specific disease categories (see Results section) showed acceptable rates of individual complications. Due to decreased physiologic reserves and impaired homeostasis in older patients, the occurrence of postoperative complications often leads to a cascade of events, for example pneumonia, successively leading to cardiac ischemia, heart failure, renal insufficiency, electrolyte disturbances, and ileus. In our study, complications induced by a prior adverse event or its treatment were considered as individual complications, as suggested by Clavien et al. in a qualitative study that was performed to clarify controversies about the application of the Comprehensive Complication Index [28]. We have not found any study reporting the Comprehensive Complication Index in older patients undergoing elective colorectal surgery to compare our results with. The median postoperative LOS in this study was 1 day longer than the median postoperative LOS in our review [12]. This might be explained by variations in in- and exclusion criteria between our study and some of the studies included in the review, e.g. some studies included colonic procedures only, laparoscopic procedures only, excluded patients with intensive care stay, with multi-organ resection. Proactively considering time to readiness for discharge (TRD) on a daily basis could trigger earlier discharge [29]. There was no formal registration of TRD at the time of this study in our electronic medical records, neither was there a registration of discharge destination. Prolonged LOS might also reflect outflow difficulties, such as limited institutional rehabilitation capacity and insufficient elderly care facilities in our region.

Preoperative risk prediction in older patients is another challenge. Our study identified site of surgery and polypharmacy as independent risk factors for postoperative complications. Higher age, ASA class and preoperative radiotherapy were independent risk factors of prolonged postoperative LOS. In line with data from an inpatient national database in the United States, increasing age was negatively associated with postoperative complications and prolonged postoperative LOS in univariable analysis [30]. Although age was not an independent risk factor for postoperative complications, this study does underline the fact that older persons need special attention in the perioperative period due to a high prevalence of multimorbidity (60.4%), polypharmacy (62.5%) and ASA ≥3 classifications (68.7%). The fTRST showed a trend to predict postoperative complications (p = 0.066) and was associated with prolonged postoperative LOS in univariable analysis (p = 0.006). A prospective study in emergency abdominal surgery observed an association between the fTRST (cut-off ≥2), postoperative complications and postoperative LOS [31].

The findings of this study should be interpreted within the context of its design. First, it concerns a single center study with a small sample, focusing on short-term clinical outcomes. The results should therefore be viewed as hypothesis-generating to conduct future studies. Second, all data were retrospectively collected from the electronic medical records and the adherence rates are therefore based on what has been registered. Strengths of this study are the detailed reporting of the applied ERP components and of all postoperative medical events that occurred. Another strength is the fact that ERP components were listed unambiguously and in accordance with the ERAS® guidelines, which facilitates comparison with future studies.

This study will serve as a baseline for a quality improvement project in our center, in which we will implement surgical-geriatric co-management in the abdominal surgery department, followed by a mixed-methods prospective observational study. Future studies should incorporate frailty screening and geriatric assessment into the patients’ baseline assessment to be able to report their biological age in addition to chronological age and should incorporate these assessments in risk prediction models. At risk patients should be targeted with individually tailored geriatric interventions to prevent or manage adverse outcomes.

Conclusions

This study shows that ERPs are feasible with good adherence in older persons undergoing colorectal surgery. ERPs should be implemented in this patient group without reservations. The advantage of optimizing ERP-implementation in the older patient group could be larger than in younger patients, given the non-negligible occurrence of adverse postoperative outcomes and of baseline risk factors for adverse outcomes in this patient population.

Supporting information

S1 Table. Standard ERP in the University Hospitals Leuven for colorectal surgical patients in 2017.

(DOCX)

S2 Table. Postoperative complications in detail.

(DOCX)

S1 Data

(XLSX)

Acknowledgments

The authors would like to thank Camille Goossens for her contribution to the data acquisition, Ingrid Van Dessel for critical appraisal of the data and Annouschka Laenen for providing statistical advice.

Data Availability

All relevant data are within the paper and supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Etzioni DA, Liu JH, Maggard MA, Ko CY. The aging population and its impact on the surgery workforce. Ann Surg. 2003;238(2):170–7. 10.1097/01.SLA.0000081085.98792.3d [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Etzioni DA, Beart RW Jr., Madoff RD, Ault GT. Impact of the aging population on the demand for colorectal procedures. Dis Colon Rectum. 2009;52(4):583–90; discussion 90–1. 10.1007/DCR.0b013e3181a1d183 [DOI] [PubMed] [Google Scholar]
  • 3.Partridge JS, Harari D, Dhesi JK. Frailty in the older surgical patient: a review. Age and ageing. 2012;41(2):142–7. 10.1093/ageing/afr182 [DOI] [PubMed] [Google Scholar]
  • 4.Griffiths R, Beech F, Brown A, Dhesi J, Foo I, Goodall J, et al. Peri-operative care of the elderly 2014: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia. 2014;69 Suppl 1:81–98. [DOI] [PubMed] [Google Scholar]
  • 5.Deschodt M, Claes V, Van Grootven B, Milisen K, Boland B, Flamaing J, et al. KCE report 245. 2015 [https://kce.fgov.be/sites/default/files/page_documents/KCE_245_geriatric_care_in_hospitals_Report.pdf.
  • 6.Rasmussen LS, Jorgensen CC, Kehlet H. Enhanced recovery programmes for the elderly. European journal of anaesthesiology. 2016;33(6):391–2. 10.1097/EJA.0000000000000452 [DOI] [PubMed] [Google Scholar]
  • 7.Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA surgery. 2017;152(3):292–8. 10.1001/jamasurg.2016.4952 [DOI] [PubMed] [Google Scholar]
  • 8.Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, et al. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS((R))) Society Recommendations: 2018. World journal of surgery. 2019;43(3):659–95. 10.1007/s00268-018-4844-y [DOI] [PubMed] [Google Scholar]
  • 9.Lau CS, Chamberlain RS. Enhanced Recovery After Surgery Programs Improve Patient Outcomes and Recovery: A Meta-analysis. World journal of surgery. 2017;41(4):899–913. 10.1007/s00268-016-3807-4 [DOI] [PubMed] [Google Scholar]
  • 10.Bagnall NM, Malietzis G, Kennedy RH, Athanasiou T, Faiz O, Darzi A. A systematic review of enhanced recovery care after colorectal surgery in elderly patients. Colorectal disease: the official journal of the Association of Coloproctology of Great Britain and Ireland. 2014;16(12):947–56. [DOI] [PubMed] [Google Scholar]
  • 11.Ljungqvist O, Hubner M. Enhanced recovery after surgery-ERAS-principles, practice and feasibility in the elderly. Aging Clin Exp Res. 2018;30(3):249–52. 10.1007/s40520-018-0905-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Fagard K, Wolthuis A, D’Hoore A, Verhaegen M, Tournoy J, Flamaing J, et al. A systematic review of the intervention components, adherence and outcomes of enhanced recovery programmes in older patients undergoing elective colorectal surgery. BMC geriatrics. 2019;19(1):157 10.1186/s12877-019-1158-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin D, Francis N, et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS(R)) Society recommendations. Clinical nutrition (Edinburgh, Scotland). 2012;31(6):783–800. [DOI] [PubMed] [Google Scholar]
  • 14.Nygren J, Thacker J, Carli F, Fearon KC, Norderval S, Lobo DN, et al. Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced Recovery After Surgery (ERAS(R)) Society recommendations. Clinical nutrition (Edinburgh, Scotland). 2012;31(6):801–16. [DOI] [PubMed] [Google Scholar]
  • 15.Braes T, Flamaing J, Sterckx W, Lipkens P, Sabbe M, de Rooij SE, et al. Predicting the risk of functional decline in older patients admitted to the hospital: a comparison of three screening instruments. Age and ageing. 2009;38(5):600–3. 10.1093/ageing/afp097 [DOI] [PubMed] [Google Scholar]
  • 16.Kondrup J, Allison SP, Elia M, Vellas B, Plauth M. ESPEN guidelines for nutrition screening 2002. Clinical nutrition (Edinburgh, Scotland). 2003;22(4):415–21. [DOI] [PubMed] [Google Scholar]
  • 17.Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. 10.1016/0021-9681(87)90171-8 [DOI] [PubMed] [Google Scholar]
  • 18.Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. Journal of clinical epidemiology. 1994;47(11):1245–51. 10.1016/0895-4356(94)90129-5 [DOI] [PubMed] [Google Scholar]
  • 19.WHO. Obesity: Preventing and Managing the Global Epidemic. Technical Report Series 894. 2004:9. [PubMed]
  • 20.Owens WD, Felts JA, Spitznagel EL Jr. ASA physical status classifications: a study of consistency of ratings. Anesthesiology. 1978;49(4):239–43. [DOI] [PubMed] [Google Scholar]
  • 21.Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999;91(3):693–700. [DOI] [PubMed] [Google Scholar]
  • 22.Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia and analgesia. 2014;118(1):85–113. 10.1213/ANE.0000000000000002 [DOI] [PubMed] [Google Scholar]
  • 23.Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. 10.1097/01.sla.0000133083.54934.ae [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, et al. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surgery today. 2016;46(6):668–85. 10.1007/s00595-015-1236-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258(1):1–7. 10.1097/SLA.0b013e318296c732 [DOI] [PubMed] [Google Scholar]
  • 26.van Zelm R, Coeckelberghs E, Sermeus W, De Buck van Overstraeten A, Weimann A, Seys D, et al. Variation in care for surgical patients with colorectal cancer: protocol adherence in 12 European hospitals. International journal of colorectal disease. 2017;32(10):1471–8. 10.1007/s00384-017-2863-z [DOI] [PubMed] [Google Scholar]
  • 27.The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection: Results From an International Registry. Ann Surg. 2015;261(6):1153–9. 10.1097/SLA.0000000000001029 [DOI] [PubMed] [Google Scholar]
  • 28.Clavien PA, Vetter D, Staiger RD, Slankamenac K, Mehra T, Graf R, et al. The Comprehensive Complication Index (CCI(R)): Added Value and Clinical Perspectives 3 Years "Down the Line". Ann Surg. 2017;265(6):1045–50. 10.1097/SLA.0000000000002132 [DOI] [PubMed] [Google Scholar]
  • 29.Fiore JF Jr., Bialocerkowski A, Browning L, Faragher IG, Denehy L. Criteria to determine readiness for hospital discharge following colorectal surgery: an international consensus using the Delphi technique. Dis Colon Rectum. 2012;55(4):416–23. 10.1097/DCR.0b013e318244a8f2 [DOI] [PubMed] [Google Scholar]
  • 30.Jafari MD, Jafari F, Halabi WJ, Nguyen VQ, Pigazzi A, Carmichael JC, et al. Colorectal Cancer Resections in the Aging US Population: A Trend Toward Decreasing Rates and Improved Outcomes. JAMA surgery. 2014;149(6):557–64. 10.1001/jamasurg.2013.4930 [DOI] [PubMed] [Google Scholar]
  • 31.Zattoni D, Montroni I, Saur NM, Garutti A, Bacchi Reggiani ML, Galetti C, et al. A Simple Screening Tool to Predict Outcomes in Older Adults Undergoing Emergency General Surgery. Journal of the American Geriatrics Society. 2019;67(2):309–16. 10.1111/jgs.15627 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Yan Li

19 Feb 2020

PONE-D-20-01592

A retrospective observational study of enhanced recovery after surgery in older patients undergoing elective colorectal surgery.

PLOS ONE

Dear Dr. Fagard,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Apr 04 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Yan Li

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Comments: This study retrospectively reported enhanced recovery programs (ERP) in elective colorectal surgery in older patients. It is a very interesting issue that was not answered in this population. 96 patients were included from a single center. ERP adherence in older patients is high and feasible. The postoperative complications and prolonged postoperative length of stay are acceptable.

Some questions are raised for adherence to 21 ERP interventions in this study:

2) no mechanical bowel preparation in colonic surgery (116 line): why mechanical bowel preparation not applied in these older patients? The incidence of anastomotic leak in this study is occurred in 6 out of 96 patients.

12) no abdominal drain in colonic surgery (123 line): If there are some remaining fluid or SSI in the abdomen/pelvis, how to handle these conditions without drains?

15) oral food on POD 1 (126 line): How many prophylactic stomas were created after colectomy? I wonder whether these 6 cases with anasto leak start oral food on POD 1.

Reviewer #2: Review for Plos One

ERAS in elderly patients over 70 YO

Authors make a retrospective single center observational study of patients over 70 years old, who underwent elective colorectal surgery following Enhanced Recovery Protocols (ERP).

The abstract is clear and well written. The abstract points to the existence of ERP, but also to its limitations for elderly patients. Therefore, the aims of the study link well to the background, and it is also well shown in the main manuscript.

The results of the abstract are also well briefly demonstrated, showing the good adherence of elderly patients to ERP, the complications with Clavien Dindo score and length of stay, which was long for an ERP. Finally, the multivariable analysis indicates the risk factors for complications and for prolonged length of stay.

The conclusions of the abstract are also clear and explain well the high adherence consequently the feasibility of ERP for elderly patients undergoing colorectal surgery.

The manuscript is also well written, with a comprehensive English.

The introduction of the manuscript is concise and goes directly to the point of ERP in elderly patients which is scarce in the literature and links well with the objectives of the study.

The materials and methods session is also well explained and divided. Figure one brings the flowchart of the study and exclusions which are also well pointed. However, figure 1 is not cited in the text, and I would consider citing in the sample subtitle after line 79.

Data analysis: seems ok to me, despite my experience in statistics is limited to the statistical methods applied. The methods look correct so far to me.

The results session is well fragmented to facilitate the understanding.

The conversion rates for were acceptable, but relatively high, specially for the rectal operations (16%). What were the criteria of conversion utilized in the study and how do the authors explain this conversion rates?

The adherence to ERP was quite high, congratulations. Although, is there any explanation for lower adherence rates for urinary catheter removal, carbohydrate loading and cassation of IV fluids?

I understand that patients age has an importance influence in postoperative outcomes and ERAS protocol applications, however in my understanding the mean LOS of 7 days seems to long for a fast track protocol despite the low complication rates. How do the authors explain these results? Also, analyzing the risk factors for prolonged LOS do the authors think they could represent an impairment on ERP and fast track protocols?

The discussion session is comprehensive and up-to-date. In line 241 why do authors cite (see results) instead of putting the reference of your previous publication? Also you try to answer the question I did before in the results about the LOS, however it was still not very clear for me? Specially after seeing the reference of your prior review.

I liked the criticism of the authors about your own production at the limitations of the study and when you say it “should be viewed as hypothesis-generating to conduct future studies”. Also, I liked the application this study will have for quality improvement in your center.

The conclusion of the manuscript is confused. I would follow the idea of the conclusion of the abstract. You don’t need to repeat some things you just wrote in the discussion, which are not conclusions.

Congratulations and good luck for the authors for this study and future ones.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Zixu Yuan

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 May 8;15(5):e0232857. doi: 10.1371/journal.pone.0232857.r002

Author response to Decision Letter 0


28 Mar 2020

Reviewers' comments:

Reviewer #1

1. No mechanical bowel preparation in colonic surgery (116 line): why mechanical bowel preparation not applied in these older patients? The incidence of anastomotic leak in this study is occurred in 6 out of 96 patients.

Response: We understand the reviewer’s concern. The ERAS guidelines 20121 (which were the guidelines applied in our hospital at the time of our study) recommend to avoid mechanical bowel preparation (MPB) in colonic surgery because it has no clinical advantages and can cause dehydration, electrolyte disturbances, discomfort for the patient, prolonged ileus, and spillage of residual bowel contents into the abdominal space during the operation (evidence level: high, recommendation grade: strong). The latest ERAS guidelines (2018)2 repeat the same recommendation and refer to a recent meta-analysis comparing adult patients receiving MBP with those receiving no MBP: no significant difference was found between the two groups in the rates of surgical site infections, anastomotic leaks, intra-abdominal collections, mortality, reoperation, length of stay. To clarify that ERP guidelines contain several interventions in contradiction with past common surgical practices, the following sentence was added to the introduction: ‘ERPs include evidence-based changes in traditional care, such as pre-admission counselling, avoidance of mechanical bowel preparation, shortened fasting, a carbohydrate drink two hours before surgery, avoidance of fluid overload, minimal invasive surgery, avoidance or early removal of drains and catheters, opioid-sparing multimodal analgesia, early feeding and mobilization.’

1. Gustafsson et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS(R)) Society recommendations. Clinical nutrition (Edinburgh, Scotland). 2012;31(6):783-800.

2. Gustafsson et al. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS(R)) Society Recommendations: 2018. World journal of surgery. 2019;43(3):659-95.

2. No abdominal drain in colonic surgery (123 line): If there are some remaining fluid or SSI in the abdomen/pelvis, how to handle these conditions without drains?

Response: The ERAS guidelines 2012 discourage the use of drains because there is no proven benefit on clinical or radiological anastomotic dehiscence, wound infection, re-operation, extra-abdominal complications or mortality. Peri-anastomotic drainage does not allow early detection of anastomotic leak, nor does it help to control anastomotic dehiscence (evidence level: high, recommendation grade: strong). The latest ERAS guidelines (2018) repeat the same recommendation and cite more recent studies to underline the recommendation. In our experience spontaneous resorption of remaining fluids occurs. Moreover, avoidance or early removal of catheters and drains facilitates early mobilisation, which is also part of the ERAS protocol.

3. Oral food on POD 1 (126 line): How many prophylactic stomas were created after colectomy? I wonder whether these 6 cases with anastomotic leak start oral food on POD 1.

Response: In our center no prophylactic stomas are created after elective colectomy. Five of six patients with anastomotic leak started oral food on POD 1. Their anastomotic leaks occurred on postoperative day 3, 9, 10, 12 and 17. The sixth patient was not eating on POD1 and had a reoperation for an anastomotic leak on POD 2. The rates of anastomotic leaks in our study (6.25%) might seem high. In studies with comparable in- and exclusion criteria we have found percentages between 0 and 9%.1-5 In some studies it was not clear if the complication was registered upon discharge or during follow-up. In our study in four patients an anastomotic leak occurred during hospitalisation, and two patients were readmitted for anastomotic leaks after discharge. The ERAS 2012 guidelines state that early oral feeding (versus nil by mouth) reduces the risk of infection and length of stay, and is not associated with an increased risk of anastomotic dehiscence. The risk of vomiting might increase, but therefore multi-modal anti-ileus and nausea and vomiting prophylaxis is recommended and part of the ERAS protocol. The ERAS 2018 guideline refers to a study that confirmed the safety of an early oral diet (4h after surgery) in patients with a new non-diverted colorectal anastomosis.

1. Gonzalez-Ayora et al. Enhanced recovery care after colorectal surgery

in elderly patients. Compliance and outcomes of a multicenter study from the

Spanish working group on ERAS. Int J Colorectal Dis. 2016 Sep;31(9):1625-31.

2. Braga et al. PeriOperative Italian Society Group. Enhanced recovery pathway in elderly

patients undergoing colorectal surgery: is there an effect of increasing ages?

Results from the perioperative Italian Society Registry. Updates Surg. 2018

Mar;70(1):7-13.

3. Tejedor et al. Short-term outcomes and benefits of ERAS program in elderly

patients undergoing colorectal surgery: a case-matched study compared to

conventional care. Int J Colorectal Dis. 2018 Sep;33(9):1251-1258.

4. Ostermann et al. Randomized Controlled Trial of Enhanced Recovery Program Dedicated to

Elderly Patients After Colorectal Surgery. Dis Colon Rectum. 2019

Sep;62(9):1105-1116.

5. Joris et al. Elderly patients over 70 years

benefit from enhanced recovery programme after colorectal surgery as much as

younger patients. J Visc Surg. 2020 Feb;157(1):23-31.

Reviewer #2

1. Figure one brings the flowchart of the study and exclusions which are also well pointed. However, figure 1 is not cited in the text, and I would consider citing in the sample subtitle after line 79.

Response: Figure 1 is referred to in the text: not in the materials and methods section but in the results section ‘description of the sample’ (figure 1 reports the results of the study recruitment).

2. The conversion rates were acceptable, but relatively high, especially for the rectal operations (16%). What were the criteria of conversion utilized in the study and how do the authors explain this conversion rates?

Response: Although the ERAS guidelines state that conversion rates (in colorectal cancer surgery) of less than 10% should be achievable, we do believe that the reported conversion rates in our study are acceptable. In a large database analysis (National Inpatient Sample database, United states)1 that included 337 732 laparoscopic colorectal resections (2009-2012), 48 265 procedures (14.3%) were converted to open surgery and a conversion of 31.2% was observed for proctectomy. In another analysis of the same database (2009-2010) by the same group2 Crohn's disease, prior abdominal surgery, proctectomy, malignant pathology, emergent surgery, obesity, and ulcerative colitis showed the highest conversion rates. In our study 10.0% of colonic operations and 16.1% of rectal operations were converted from laparoscopic to open surgery. The reasons for conversion were added in the results section: ‘The reasons for conversion were obesity (n=2), extensive adhesions (n=5), extensive malignancy (n=2), and difficult splenic flexure mobilisation (n=1).’

1. Moghadamyeghaneh et al. Outcomes of conversion of laparoscopic colorectal surgery to open surgery. JSLS. 2014;18(4):e2014.

2. Masoomi et al. Risk Factors for Conversion of Laparoscopic Colorectal Surgery to Open Surgery: Does Conversion Worsen Outcome? World J Surg 39, 1240–1247 (2015).

3. The adherence to ERP was quite high, congratulations. Although, is there any explanation for lower adherence rates for urinary catheter removal, carbohydrate loading and cassation of IV fluids?

Response: Thank you for this remark. We agree to provide further explanation in the discussion. The second paragraph of the discussion has been rewritten as follows (new parts in italics): ‘… The lowest adherence rates in our study were found for preoperative carbohydrate loading and for timely removal of intravenous lines and urinary catheters. A possible explanation for omitting the carbohydrate drink could be that surgeries may take place earlier than scheduled and logistic reasons might play a role. Having diabetes did not significantly affect carbohydrate loading. This is consistent with the ERAS® guideline that allows carbohydrate loading if given along with diabetes medication. Thirty-six percent of patients without postoperative complications needing treatment (Clavien-Dindo grades 0 and 1) and without PCEA or PCIA still had an intravenous line by POD 3. This could have been due to the presence of electrolyte disturbances, insufficient fluid intake or excessive fluid losses, but these factors were not considered during the data collection. Moreover, a short enquiry on the ward learned that nurses are reluctant to remove catheters and intravenous lines, despite being encouraged to do so, because they anticipate reinsertion later on.’

4. I understand that patients age has an importance influence in postoperative outcomes and ERAS protocol applications, however in my understanding the mean LOS of 7 days seems to long for a fast track protocol despite the low complication rates. How do the authors explain these results? In the discussion you try to answer the question I did before in the results about the LOS, however it was still not very clear for me? Specially after seeing the reference of your prior review.

Response: We appreciate this comment. The median postoperative LOS was 7 days in this study, compared to 6 days in the review.1 Apart from the explanations provided in the text, there may be some additional explanations. The patients included in this study (patients ≥ 70y) might have been somewhat older than the patients included in the review, which included patients ≥ 65y. Moreover, some of the included articles in the review had stricter inclusion criteria than this study, which might also explain a shorter median length of stay (e.g. colonic surgery only, laparoscopic surgery only, exclusion of patients with metastatic cancer / intensive care admission / multi-organ resection / cognitive impairment / ASA 4). These are assumptions that cannot be proven because the studies included in the review do not provide sufficient information to allow pooling and subanalyses of the results. We have added the following sentence to the discussion: ‘This might be explained by variations in in- and exclusion criteria between our study and some of the studies included in the review, e.g. some studies included colonic procedures only, laparoscopic procedures only, excluded patients with intensive care stay, with multi-organ resection. Prolonged LOS might also be due to outflow difficulties …’

1. Fagard et al. A systematic review of the intervention components, adherence and outcomes of enhanced recovery programmes in older patients undergoing elective colorectal surgery. BMC geriatrics. 2019;19(1):157.

5. Analyzing the risk factors for prolonged LOS do the authors think they could represent an impairment on ERP and fast track protocols?

Response: This question was not entirely clear to us, but we suppose the reviewer wants to know if reduced ERP adherence at individual patient level was a risk factor for prolonged LOS in our study. The response to this question is that we studied overall adherence. It was not our aim to study individual adherence per patient in relation our primary outcomes (complications ≥ grade 2 and prolonged LOS). We have found a review published in 20171 that tried to answer the question: They found that the most frequently identified predictor of prolonged LOS was reduced individual compliance with the ERAS protocol, both globally and with specific components such as delayed mobilisation and delayed resumption of oral intake. It is noteworthy that lower adherence in the postoperative period might reflect the development of complications. Therefore we think that lower adherence rates for early mobilisation and early feeding should not automatically be considered as an implementation failure, but could be due to unforeseen events.

2. Messenger et al. Factors predicting outcome from enhanced recovery programmes in laparoscopic colorectal surgery: a systematic review. Surg Endosc 31, 2050–2071 (2017).

6. The discussion session is comprehensive and up-to-date. In line 241 why do authors cite (see results) instead of putting the reference of your previous publication?

Response: We apologize for the confusion: ‘see results’ refers to the results section of the current manuscript and does not refer to our previous publication. This was clarified in the text: ‘Post-hoc classification of postoperative complications in our study into specific disease categories (see results section) showed acceptable rates of individual complications.’

7. The conclusion of the manuscript is confused. I would follow the idea of the conclusion of the abstract. You don’t need to repeat some things you just wrote in the discussion, which are not conclusions.

Response: We thank the reviewer for this constructive comment. The reviewer is right that the conclusion was broader than the findings of the study. To correct this, and in order to avoid repetition, the last two sentences of the conclusion have been removed.

Attachment

Submitted filename: Response to reviewers_11 03.docx

Decision Letter 1

Yan Li

23 Apr 2020

A retrospective observational study of enhanced recovery after surgery in older patients undergoing elective colorectal surgery.

PONE-D-20-01592R1

Dear Dr. Fagard,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Yan Li

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Yan Li

29 Apr 2020

PONE-D-20-01592R1

A retrospective observational study of enhanced recovery after surgery in older patients undergoing elective colorectal surgery.

Dear Dr. Fagard:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Yan Li

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Standard ERP in the University Hospitals Leuven for colorectal surgical patients in 2017.

    (DOCX)

    S2 Table. Postoperative complications in detail.

    (DOCX)

    S1 Data

    (XLSX)

    Attachment

    Submitted filename: Response to reviewers_11 03.docx

    Data Availability Statement

    All relevant data are within the paper and supporting information files.


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES