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E.R.A.S. pathway in colorectal surgery in elderly: Our experience: A retrospective cohort study
Accepted Manuscript E.R.A.S. pathway in colorectal surgery in elderly: Our experience Basilio Pirrera, MD, Andrea Lucchi, MD FACS, Carlo Gabbianelli, MD, Vincenzo Alagna, MD, Giacomo Martorelli, MD, Pierluigi Berti, MD, Ilaria Panzini, Elisabetta Fabbri, Gianluca Garulli, MD. PII:
S1743-9191(17)30395-3
DOI:
10.1016/j.ijsu.2017.05.013
Reference:
IJSU 3803
To appear in:
International Journal of Surgery
Received Date: 15 February 2017 Revised Date:
29 April 2017
Accepted Date: 2 May 2017
Please cite this article as: Pirrera B, Lucchi A, Gabbianelli C, Alagna V, Martorelli G, Berti P, Panzini I, Fabbri E, Garulli G, E.R.A.S. pathway in colorectal surgery in elderly: Our experience, International Journal of Surgery (2017), doi: 10.1016/j.ijsu.2017.05.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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E.R.A.S. pathway in colorectal surgery in elderly: our experience. Basilio Pirrera MD*, Andrea Lucchi MD FACS, Carlo Gabbianelli MD, Vincenzo Alagna MD, Giacomo Martorelli MD, Pierluigi Berti MD, Ilaria Panzini**, Elisabetta Fabbri**, Gianluca Garulli MD.
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General, Thoracic and Minimally Invasive Surgery, Ceccarini Hospital, Riccione, Italy * Corresponding Author ** Research Unit AUSL Romagna
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Acknowledgments Ilaria Panzini, Elisabetta Fabbri for analysis and interpretation of data and Cristopher Muscat for the review.
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Abstract
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Aim: Numerous geriatric patients develop colorectal disease. Elderly patients are often considered high-risk surgical candidates. Enhanced recovery after surgery (E.R.A.S.) has been proven to be beneficial for patients.. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger patients.
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Method: In the period between January 2010 to December 2015 a total of 589 patients underwent elective colorectal surgical interventions treated within the E.R.A.S pathway : 211 patients younger than 65 years, 175 patients aged from 66 years to 75 years, and 203 patients older than 75 years. End point of interest were postoperative complications, 90-day mortality, length of hospital stay and readmission within 30 days.
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Results: Significant differences between the three groups were observed for comorbidities (p:0.001); in particular older patients had significantly more diabetes, renal, cardiac, and respiratory diseases, ASA (p<0.001), presence of malignancy (p<0.001). However there were not differences between the groups in surgical procedures (p=0.095), operative time (p=0.823), anastomotic leakage (p=0.960), hospital stay (p=0.081), readmission rate (p=0.904), 90-days mortality (p=0.183) and morbidity (p=0.973) in accordance with Clavien-Dindo classification. Multivariate logistic regression analysis showed that advanced age in E.R.A.S. pathway is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality.
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Conclusion: There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75 years compared with younger patients. Old age does not represent a contraindication to the implementation of the E.R.A.S protocol in patients that underwent colorectal surgery. What does this paper add to the existing literature?
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In the literature there are not many studies that address the impact of older age in the treatment of colorectal disease in an ERAS program. The aging of the population raises new questions in the management of the colorectal surgery in the elderly. ERAS pathway has been proven to be beneficial for patients, which results in a reduction of postoperative morbidity. Compared to what is reported in the literature this study confirms that ERAS program in colorectal surgery can be applied in older patients with no significant difference in morbidity, 90-day mortality, length of stay or readmission rate compared with younger. Keywords: Colorectal surgery, elderly, E.R.A.S, surgical outcomes Introduction In Western countries, the percentage of elderly people in the general population is steadily increasing. [1,2] Older patients are a highly heterogeneous population with considerable differences in general state of health (biological age), often with numerous coexisting diseases. For these reasons a definition of “Old Patient” is difficult. Enhanced recovery after surgery (ERAS.) pathway has been proven to be beneficial for patients and should now be considered as standard of care in colorectal surgery [3,4]. The purpose of the ERAS pathway is to reduce postoperative stress and it
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allows for lower complication rates and shortened length of hospital stay at reduced costs [5,6]. However, a question remains about its applicability to the elderly population: ERAS pathway requires active participation and may be perceived as quite aggressive by older patients. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger.
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Methods The present study is a case-control retrospective evaluation. We analyzed 589 consecutive colectomies performed from January 2010 to December 2015. All consecutive patients were treated within the ERAS pathway. Data collected included patient demographics, relevant clinical characteristics, operative details and post-operative outcomes. Data from all the patients was prospectively recorded in a dedicated data base with a follow up of 90 days. There is not a worldwide accepted definition of “aged patients”. Population aging is a question of primary interest in our society. World Health Organization suggested 65-years old as a cut off to define “old patients”. In Italy , life expectancy is 79,4 and 84,5 years respectively for males and females. In addition, the peak of incidence of colorectal cancer is between the seventh and eighth decade of life, with an ever greater increase among the octogenarians. For these reasons we have adopted three comparison groups: 211 patients younger than 65 years (Group 1), 175 patients aged from 66 years to 75 years ( Group 2), and 203 older than 75 years (Group 3).
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Protocol The ERAS protocol was reported in Table 1: normal diet until 8 h before surgery; glucose load 2 h before surgery; Thrombo-prophylaxis ; antibiotic prophylaxis; continuous thoracic epidural opiatesparing anaesthesia exclusively for left colectomy; prevention of hypothermia and fluid overload; minimally invasive colonic surgery; no drainage; early removal of NGT and urinary catheter just after the procedure; early oral feeding (chewing gum from when the patient is awake, water after 12 h and light diet on POD 1) and mobilization (2 h on day of surgery, 6 h on POD 1 and 2 h of walk around the ward on POD 2); regular pain control with opiate-sparing multimodal analgesia; fluid restriction to 1500 ml/die on POD 0. The discharge criteria were reported in Table 2.
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Patients All patients were scheduled for laparoscopic approach primarily and were operated on by the same surgical group. The aim of surgery in all cases was curative resection. The exclusion criteria were emergency surgery and palliative procedure. The primary objective of the present study was to evaluate postoperative morbidity and readmission after colorectal resection in an ERAS protocol in older patients compared to younger, with a secondary endpoint to compare the incidence of mortality in relation to age. Postoperative complications were classified according to the Dindo– Clavien classification. [7] Grade I includes minor complications that do not require any intervention and that can be treated with routine medications like antipyretics, analgesics, diuretics, or physiotherapy. Grade II includes conditions that require major pharmacological intervention, like respiratory infections, ascites, blood transfusions, and asymptomatic pulmonary embolism. Grade III includes any complication requiring a surgical, endoscopic, or radiological intervention, like a respiratory infection requiring bronchoscopy, a pleural effusion requiring drainage, ascites or an abdominal collection requiring percutaneous drainage, and reoperation for abdominal collection, bleeding, or other reasons. Grade IV includes patients with life-threatening complications requiring Intensive Care Unit, and grade V includes death in the postoperative period. Mortality was evaluated at 90 days. The data were entered into a Microsoft Access database (Microsoft Corp., Redmond, WA).
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Surgical techniques
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Both laparoscopic right and left colectomy in colon cancer were approached following a standardized method: primary vascular approach (ileocolic vessels, right colic vessels when present, right branch of middle colic vessels for right colectomy; inferior mesenteric vein and artery for left colectomy); mobilization of the specimen along the avascular planes between the mesocolon and the Gerota’s fascia, according to the principles of complete mesocolic excision and central vascular ligation; transection of the distal and proximal side of the specimen with linear staplers; totally laparoscopic intra-corporeal, iso-peristaltic, side to side anastomosis for right colectomy, and laparoscopic Knight–Griffen anastomosis for left colectomy with intra-corporeal section of the mesocolon. Laparoscopic anterior rectum resection was approached following a standardized method: primary vascular approach (inferior mesenteric vein and artery ), mobilization of the left colon along the avascular planes between the mesocolon and the Gerota’s fascia and of the splenic flexure, central vascular ligation with nerve sparing, TME and transection of the distal side of the specimen with linear staplers, laparoscopic Knight–Griffen anastomosis.
Result
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Statistical Method Data processing was done with the Stata Intercooled 9.2 (2006) statistical program. Twodimensional frequency distributions (cross tables) were compared with the Pearson chi-squared test. Continuous variables were evaluated using t-student test. Logistic backward stepwise regression was used in order to indentify the covariate influencing the postoperative morbidity, readmission and mortality. A p value less than or equal to 0.05 was considered significant and results are reported as OR with 95% confidence intervals.
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The patients were divided into three groups according to the age at the time of surgery: 211 patients younger than 65 years (Group 1), 175 patients aged from 66 years to 75 years ( Group 2), and 203 older than 75 years (Group 3). The gender distribution was not significantly different among the three groups (P = 0.219). Overall comorbidities rate differed among the three groups (P < 0.001), in particular Arterial hypertension was present in 29.4 % of patients in Group 1, compared with 52.0%in Group 2 and 74.9 % in Group 3 (P < 0.001). Even Myocardial infarction history and Cardiac Arrhythmia were more frequent in patients older 75 years old compared with younger ( P < 0.001). Diabetes rate was more frequent in patients older 75 years old compared with younger ( P = 0.006) as well as Chronic Renal Insufficiency (P = 0.030); however COPD rate was not significantly different among the three groups ( P = 0.285); consequently ASA classification differed significantly (P < 0.001) between the groups. The presence of malignancy differed significantly among the three group (P < 0.001), in particular it was more frequent in Group 3 ( 89.7% of patients) compared with 83.4% of patients in group 2 and 70.1% of patients in Group 1. Preoperative characteristics of patients in the study cohort are listed in Table 3. Disease localization ( colon vs. rectum) was not significantly different among the three groups ( P = 0.166) as well as surgical procedure (P = 0.095); in particular the resections with primary anastomosis rate was 95.3 % in Group 1 compared with 91.4 % in Group 2 88.7 and 88.7 %% in Group 3. The operative time was not significantly longer in older patients (166 min in Group 1 vs. 170 min in Group 2 and 167 min in Group 3, P = 0.823) with an estimated intraoperative blood loss of 78 ± 30
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Discussion
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cc for Group 1 vs. 81 ± 35 cc in Group 2 and 85 ± 38 cc in Group 3 ( P = 0.854). Surgical characteristics of the study population in relation to age are listed in Table 4. The overall postoperative complication rate was not significantly different among the three groups ( P = 0.739); in particular there was not differences in severe postoperative complications rate (grade 3-4), according to Clavien-Dindo classification among the three groups ( Group 1 = 8.1 % of patients , Group 2 = 8.5% of patients and Group 3 = 9.4 % of patients, P = 0.973). More specifically as regard to medical complications, no differences in Cardiac ( P = 0.480) , Respiratory ( P = 0.092), Thromboembolic ( P = 0.115) and Urinary complications rate ( P = 0.068) were found between the 3 groups. Postoperative ileus occurred in 6.6 % of patients in Group 1 vs. 8.0 % of patients in group 2 and 7.9 % of patients in Group 3 with no significant statistically differences ( P = 0.846). Regarding to surgical complication , anastomotic leakage occurred in a 3.8 % of patients in Group 1 vs 4.0 % of patients in Group 2 and 3.4% of patient in Group 3 with no statistical differences (P = 0.960), just as Wound infection rate ( P = 0.846). Hospital stay was not significantly different among the three groups ( P = 0.081). Readmission rate was 4.7 % in Group 1 vs. 4.6 % in Group 2 and 4.9 % in Group 3 with no statistical differences ( P = 0.904) as well as reoperation in readmission rate ( P = 0.955). No differences were observed in anastomotic leakage rate in readmission among the three groups ( P = 0.892) even in the readmission bowel obstruction ( P= 0.645) and bleeding rates (P = 0.990). The 90-day mortality rate was higher in elderly patients but not statistical different between three groups ( P = 0.183). Postoperative characteristics of the study population in relation to age are listed in Table 5. The logistical regression analysis identified the parameters in Tables 6-7-8 as significant predictive factors for morbidity, readmission and 90-day mortality after colorectal surgery in ERAS pathway. Older age was not an independent risk factor for a complicated postoperative outcome 30-day readmission and 90-day mortality.
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An increasing number of elderly patients is subjected to colorectal surgery. In particular colorectal carcinoma has a peak of incidence in the seventh and eight decade of life.[2,8] The present study compared young (less than 65 years) to old (more than 65 years) patients, all undergoing elective colorectal surgical interventions. Elderly patients are often considered high-risk surgical candidates. In the literature, several studies reported that overall comorbidity rate in patient older 70 years varied from 50 % to 85 %, in particular hypertension, coronary heart disease and pulmonary disease rates [9,10]. In the present study we reported an overall comorbidities rate of 81.3 % in patients older 75 years compared to 58.9% in patients aged from 66 years to 75 years and 35.5 % of in patients younger than 65 years. In particular cardiovascular risk factor (Arterial Hypertension, Myocardial infarction history, Cardiac arrhythmia history) differed significantly between the three groups ( p < 0.001). Historically, it has been suggested that elderly patients do not fare well after colorectal surgery with high rates of postoperative mortality e morbidity [11]. Several recent studies have addressed the use of enhanced recovery protocol in the elderly population in colorectal surgery and they suggest similar benefit for older patients regarding rate of complications and length of hospital stay [12-17]. Comparing younger and older patients, Baek SJ. et al. [13] did not found any difference in postoperative outcome between patients below and above 70 years following an enhanced recovery protocol. In a systematic review, Bagnall et al. [14] summarizing data from 16 studies including a total of 5965 patients, has evaluated and confirmed the safety of an ERAS in the elderly population by finding similar prevalence in morbidity and mortality compared to a younger
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population, with slightly longer hospital stays. Only two studies demonstrated a higher mortality among elderly patients [16,18]. In this review overall complications were higher in the elderly patients in four cohort studies [16,18-20] , but not in five studies [13,21-24]. In particular no difference was observed in the rate of postoperative pulmonary complications in any ERAS studies between younger or older patients. In our study we reported an overall complication rate of 21.2 % in older patients compared to 21.1% and 18.5 % of patients aged from 66 years to 75 years and younger than 65 years respectively with no significant difference. In particular, we reported a severe complication rate ( grade III and IV) of 9.4 % in older patients comparable to that reported in the existing literature. In a recent study Slieker J [25] et al. reported an high rate of non surgical postoperative complications in patients older 70 years; in our study we reported no differences in both surgical and non surgical complication rate between the groups, in particular no differences were observed in postoperative cardiovascular and Thromboembolic complications rates in older patients as well as pulmonary complications rate, which would suggest that there is no increased risk of aspiration pneumonitis in elderly patients following early resumption of oral feeding. In the present study no differences for surgical specific postoperative complications were seen between the aged groups, in particular we reported a postoperative ileus rate of 7.9% in Group 3 compared with a 8% and 6.6 % in Group 2 and in Group 1 respectively; no differences were found about wound infection rate and anastomotic leakage rates about three groups with a primary anastomosis rate of 88.7% in older groups. In literature, many studies found longer length of stay in elderly patients [16,19,.24,25], but in our series no differences were found about length of hospital stay between the Groups. The rate of readmission after discharge in elderly was not different in respect of younger patients; same as reoperation in readmission rate; this is in accordance to other reports in literature [16-18,21-23]. Anastomotic leakage rate in readmission was no different among the groups ( P = 0.892) and occurred in 1% of patients older than 75 years compared with a 0.6% and 0.9% in Group 2 and Group 1 respectively. In our opinion the low rate of readmission for anastomotic insufficiency is due to compliance of the discharge criteria in early diagnose of surgical complications. In a multivariate Cox regression analysis older age was not an independent predictive factor of morbidity, readmission and 90-day mortality; instead CRI and arterial hypertension were predictive of morbidity as well as Diabetes and Chronic Renal Insufficiency were strongly predictive of 90-day mortality. Therefore, old age as such does not represent a contraindication to the E.R.A.S pathway in colorectal surgery, but considering the fragility of the elderly patients and their high risk profile, the surgical management of older patient requires, therefore, the identification and correction of disorders of the cardiovascular system, the respiratory system, liver function, renal function, nutritional status and electrolyte balance [26,27]. The main limitations of our study is that it is a retrospective study and that data on compliance with the ERAS protocol of the three comparison groups were not provided. However, all data were prospectively collected; all patient undergoing surgery were included in the pathway and all patients in the database were analyzed. Conclusion
In conclusion this study shows that the ERAS pathway in colorectal surgery can be applied in older patients. There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75's compared with younger. Consequently enhanced recovery after colorectal surgery seems to be safe and feasible in the elderly.
Disclosures The authors declare no conflict of interest or any financial support to disclose.
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Table 1. E.R.A.S. protocol
E.R.A.S.
Intraoperative
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Day of surgery
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POD 3-4 POD 3-6 POD 7 POD 30 POD 90
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POD 1
POD 2
Counseling Informed consent No bowel preparation Glucose load 2 h before Antibiotic prophylaxis Thrombus prophylaxis Prevention of hypothermia Prevention of fluid overload Minimally invasive surgery Removal of NGT at the end of procedure Sit for > 1h Chewing gum Sips of water < 1 L Tea an Jam at dinner Removal of urinary catheter Sit in chair for > 4h Ward ambulation for > 400 m Semifluid diet > 1 L Liberal ward ambulation Soft diet Discharged Daily telephone contact Outpatient control Outpatient control End of follow-up
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Time Preoperative
POD post-operative day
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Table 2. Discharge criteria for E.R.A.S
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Parameter 1. Patient with no or minimal complaints 2. No fever 3. Flatus passage
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4. No tachycardia (pulse rate[100 bpm)
6. No complaint with a soft diet 7. Normal or decreasing WBC count
WBC white blood cells
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5. No abdominal tenderness
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Table 3 Preoperative characteristics of patients.
Age 66-75 years Group 2: 175 pz
Age ≥76 years Group 3: 203 pz
Age (years)* Male Sex Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes COPD CRI
56 119 (56.4%) 75 (35.5%) 62 (29.4%) 9 (4.3%) 3 (1.4%) 10 (4.7%) 23 (10.9%) 7 (3.3%)
69 96 (54.9%) 103 (58.9%) 91 (52.0%) 11 (6.3%) 8 (4.6%) 22 (12.6%) 27 (15.4%) 17 (9.7%)
80 98 (48.3%) 165 (81.3%) 152 (74.9%) 33 (16.3%) 21 (10.3%) 27 (13.3%) 32 (15.8%) 17 (8.4%)
Asa score 1 2 3 Malignancy
61 (28.9%) 138 (65.4%) 12 (5.7%) 148 (70.1%)
16 (9.1%) 131 (74.9%) 28 (16,0%) 146 (83.4%)
8 (9.4%) 108 (53.2%) 87 (42.9%) 182 (89.7%)
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Age ≤ 65 years Group 1: 211 pz
P value
0.219 < 0.001 < 0.001 < 0.001 < 0.001 0.006 0.285 0.030 < 0.001
< 0.001
Values in parentheses are percentages unless indicated otherwise; *values are median. COPD, chronic obstructive pulmonary disease. MI history, Myocardial infarction history. CRI Chronic Renal Insufficency. ASA, American Society of Anesthesiologists score.
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Table 4 Surgical characteristics of population. Age 66-75 years Group 2: 175 pz
Age ≥76 years Group 3: 203 pz
172 (81.5%) 39 (18.5%)
149 (85.1%) 26 (14.9%)
179 (88.2) 24 (11.8%)
201 (95.3%) 10 (4.7%) 166 (40-395) 78 ± 30
160 (91.4%) 15 (8.6%) 170 (65-350) 81 ± 35
P value
0.166
0.095
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Disease localization Colon Rectum Surgical Procedures Resection + anastomosis Resection + stoma Duration of procedures (min)* Estimated blood-loss
Age ≤ 65 years Group 1: 211 pz
180 (88.7%) 21 (10.3%) 167 (75-405) 85 ± 38
0.823 0.854
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Values in parentheses are percentages unless indicated otherwise ; *values are median (range).
Table 5 Postoperative characteristics of the study population Age ≤ 65 years Group 1: 211 pz
P value
37 (21.1%)
43 (21.2%)
172 (81.5%) 22 (10.4%) 17 (8.1%)
138 (79.3%) 22 (12.2%) 15 (8.5%)
160 (78.7%) 24 (11.9%) 19 (9.4%)
8 (3.8%) 14 (6.6%)
7 (4.0%) 14 (8.0%)
7 (3.4%) 17 (8.4%)
0.960 0.846
14 (6.6%) 1 (0.5%) 6 (2.8%) 8 (3.8%) 0 3.89 ± 3.00 0 10 (4.7%) 2 (0.9%) 1 (0.4%) 6 (2.8%) 1 (0.4%) 5 (2.4%)
14 (8.0%) 1 (0.6%) 12 (6.9%) 14 (8.0%) 3 (1.7%) 4.67 ± 4.48 1 (0.6%) 8 (4.6%) 1 (0.6%) 1 (0.6%) 3 (1.7%) 3 (1.7%) 2 (1.2 %)
16 (7.9%) 3 (1.5%) 15 (7.4%) 19 (9.4%) 1 (0.5%) 4.74 ± 5.05 3 (1.5%) 10 (4.9%) 2 (1.0%) 1 (0.5%) 4 (1.9%) 3 (1.5%) 7 (3.4%)
0.846 0.480 0.092 0.068 0.115 0.081 0.183 0.904 0.892 0.990 0.645 0.478 0.340
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Age ≥76 years Group 3: 203 pz
39 (18.5%)
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Postoperative complications (Clavien-Dindo classification) 0 1-2 3-4 Surgical complications Anastomotic leakage Wound infection Medical complications Postoperative ileus Cardiac Respiratory Urinary Thromboembolic Hospital stay* 90-day Mortality Readmission Anastomotic leakage Bleeding SBO ** Other *** Reoperation in readmission
Age 66-75 years Group 2: 175 pz
0.739 0.973
Values in parentheses are percentages unless indicated otherwise ; *values are mean and Standard Deviation (SD), SBO ** small bowel obstruction, Other *** are fever, urinary infection, cholecysitiss and acute pancreatitis
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Table 6 Factors significantly influencing morbidity after colorectal surgery in E.R.A.S. pathway (logistic regression model)
Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
NS NS NS NS < 0.001 NS NS NS < 0.001
OR (95%CI)
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P value
2.093 (1.34-3.25)
3.711 (1.90-7.23)
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Parameter
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MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
Table 7. Factors significantly influencing 90-day mortality after colorectal surgery in E.R.A.S. pathway (logistic regression model) P value
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Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
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Parameter
NS NS NS NS NS NS NS 0.010 0.027
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MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
OR (95%CI)
22.59 (2.1-243.1) 12.402 (1.33-115.2)
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Table 8. Factors significantly influencing readmission after colorectal surgery in E.R.A.S. pathway (logistic regression model) Parameter
P value
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NS NS NS NS 0.048 NS NS NS NS
2.657 (1.01-7.01)
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Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
OR (95%CI)
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MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
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Highlights •
Influence of ERAS program on surgical outcome after elderly.
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Comparing three groups: patients younger than 65 years, patients aged from 66 years to 75 years, and older than 75 years.
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Old age is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality in ERAS program.
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Old age not represent a contraindication to the implementation of the E.R.A.S protocol in patients underwent colorectal surgery.
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colon surgery in
S1743-9191(17)30395-3
DOI:
10.1016/j.ijsu.2017.05.013
Reference:
IJSU 3803
To appear in:
International Journal of Surgery
Received Date: 15 February 2017 Revised Date:
29 April 2017
Accepted Date: 2 May 2017
Please cite this article as: Pirrera B, Lucchi A, Gabbianelli C, Alagna V, Martorelli G, Berti P, Panzini I, Fabbri E, Garulli G, E.R.A.S. pathway in colorectal surgery in elderly: Our experience, International Journal of Surgery (2017), doi: 10.1016/j.ijsu.2017.05.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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E.R.A.S. pathway in colorectal surgery in elderly: our experience. Basilio Pirrera MD*, Andrea Lucchi MD FACS, Carlo Gabbianelli MD, Vincenzo Alagna MD, Giacomo Martorelli MD, Pierluigi Berti MD, Ilaria Panzini**, Elisabetta Fabbri**, Gianluca Garulli MD.
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General, Thoracic and Minimally Invasive Surgery, Ceccarini Hospital, Riccione, Italy * Corresponding Author ** Research Unit AUSL Romagna
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Acknowledgments Ilaria Panzini, Elisabetta Fabbri for analysis and interpretation of data and Cristopher Muscat for the review.
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Abstract
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Aim: Numerous geriatric patients develop colorectal disease. Elderly patients are often considered high-risk surgical candidates. Enhanced recovery after surgery (E.R.A.S.) has been proven to be beneficial for patients.. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger patients.
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Method: In the period between January 2010 to December 2015 a total of 589 patients underwent elective colorectal surgical interventions treated within the E.R.A.S pathway : 211 patients younger than 65 years, 175 patients aged from 66 years to 75 years, and 203 patients older than 75 years. End point of interest were postoperative complications, 90-day mortality, length of hospital stay and readmission within 30 days.
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Results: Significant differences between the three groups were observed for comorbidities (p:0.001); in particular older patients had significantly more diabetes, renal, cardiac, and respiratory diseases, ASA (p<0.001), presence of malignancy (p<0.001). However there were not differences between the groups in surgical procedures (p=0.095), operative time (p=0.823), anastomotic leakage (p=0.960), hospital stay (p=0.081), readmission rate (p=0.904), 90-days mortality (p=0.183) and morbidity (p=0.973) in accordance with Clavien-Dindo classification. Multivariate logistic regression analysis showed that advanced age in E.R.A.S. pathway is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality.
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Conclusion: There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75 years compared with younger patients. Old age does not represent a contraindication to the implementation of the E.R.A.S protocol in patients that underwent colorectal surgery. What does this paper add to the existing literature?
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In the literature there are not many studies that address the impact of older age in the treatment of colorectal disease in an ERAS program. The aging of the population raises new questions in the management of the colorectal surgery in the elderly. ERAS pathway has been proven to be beneficial for patients, which results in a reduction of postoperative morbidity. Compared to what is reported in the literature this study confirms that ERAS program in colorectal surgery can be applied in older patients with no significant difference in morbidity, 90-day mortality, length of stay or readmission rate compared with younger. Keywords: Colorectal surgery, elderly, E.R.A.S, surgical outcomes Introduction In Western countries, the percentage of elderly people in the general population is steadily increasing. [1,2] Older patients are a highly heterogeneous population with considerable differences in general state of health (biological age), often with numerous coexisting diseases. For these reasons a definition of “Old Patient” is difficult. Enhanced recovery after surgery (ERAS.) pathway has been proven to be beneficial for patients and should now be considered as standard of care in colorectal surgery [3,4]. The purpose of the ERAS pathway is to reduce postoperative stress and it
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allows for lower complication rates and shortened length of hospital stay at reduced costs [5,6]. However, a question remains about its applicability to the elderly population: ERAS pathway requires active participation and may be perceived as quite aggressive by older patients. The aim of the study was to evaluate the results of an ERAS protocol in older patients that underwent colorectal surgery compared to younger.
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Methods The present study is a case-control retrospective evaluation. We analyzed 589 consecutive colectomies performed from January 2010 to December 2015. All consecutive patients were treated within the ERAS pathway. Data collected included patient demographics, relevant clinical characteristics, operative details and post-operative outcomes. Data from all the patients was prospectively recorded in a dedicated data base with a follow up of 90 days. There is not a worldwide accepted definition of “aged patients”. Population aging is a question of primary interest in our society. World Health Organization suggested 65-years old as a cut off to define “old patients”. In Italy , life expectancy is 79,4 and 84,5 years respectively for males and females. In addition, the peak of incidence of colorectal cancer is between the seventh and eighth decade of life, with an ever greater increase among the octogenarians. For these reasons we have adopted three comparison groups: 211 patients younger than 65 years (Group 1), 175 patients aged from 66 years to 75 years ( Group 2), and 203 older than 75 years (Group 3).
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Protocol The ERAS protocol was reported in Table 1: normal diet until 8 h before surgery; glucose load 2 h before surgery; Thrombo-prophylaxis ; antibiotic prophylaxis; continuous thoracic epidural opiatesparing anaesthesia exclusively for left colectomy; prevention of hypothermia and fluid overload; minimally invasive colonic surgery; no drainage; early removal of NGT and urinary catheter just after the procedure; early oral feeding (chewing gum from when the patient is awake, water after 12 h and light diet on POD 1) and mobilization (2 h on day of surgery, 6 h on POD 1 and 2 h of walk around the ward on POD 2); regular pain control with opiate-sparing multimodal analgesia; fluid restriction to 1500 ml/die on POD 0. The discharge criteria were reported in Table 2.
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Patients All patients were scheduled for laparoscopic approach primarily and were operated on by the same surgical group. The aim of surgery in all cases was curative resection. The exclusion criteria were emergency surgery and palliative procedure. The primary objective of the present study was to evaluate postoperative morbidity and readmission after colorectal resection in an ERAS protocol in older patients compared to younger, with a secondary endpoint to compare the incidence of mortality in relation to age. Postoperative complications were classified according to the Dindo– Clavien classification. [7] Grade I includes minor complications that do not require any intervention and that can be treated with routine medications like antipyretics, analgesics, diuretics, or physiotherapy. Grade II includes conditions that require major pharmacological intervention, like respiratory infections, ascites, blood transfusions, and asymptomatic pulmonary embolism. Grade III includes any complication requiring a surgical, endoscopic, or radiological intervention, like a respiratory infection requiring bronchoscopy, a pleural effusion requiring drainage, ascites or an abdominal collection requiring percutaneous drainage, and reoperation for abdominal collection, bleeding, or other reasons. Grade IV includes patients with life-threatening complications requiring Intensive Care Unit, and grade V includes death in the postoperative period. Mortality was evaluated at 90 days. The data were entered into a Microsoft Access database (Microsoft Corp., Redmond, WA).
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Surgical techniques
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Both laparoscopic right and left colectomy in colon cancer were approached following a standardized method: primary vascular approach (ileocolic vessels, right colic vessels when present, right branch of middle colic vessels for right colectomy; inferior mesenteric vein and artery for left colectomy); mobilization of the specimen along the avascular planes between the mesocolon and the Gerota’s fascia, according to the principles of complete mesocolic excision and central vascular ligation; transection of the distal and proximal side of the specimen with linear staplers; totally laparoscopic intra-corporeal, iso-peristaltic, side to side anastomosis for right colectomy, and laparoscopic Knight–Griffen anastomosis for left colectomy with intra-corporeal section of the mesocolon. Laparoscopic anterior rectum resection was approached following a standardized method: primary vascular approach (inferior mesenteric vein and artery ), mobilization of the left colon along the avascular planes between the mesocolon and the Gerota’s fascia and of the splenic flexure, central vascular ligation with nerve sparing, TME and transection of the distal side of the specimen with linear staplers, laparoscopic Knight–Griffen anastomosis.
Result
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Statistical Method Data processing was done with the Stata Intercooled 9.2 (2006) statistical program. Twodimensional frequency distributions (cross tables) were compared with the Pearson chi-squared test. Continuous variables were evaluated using t-student test. Logistic backward stepwise regression was used in order to indentify the covariate influencing the postoperative morbidity, readmission and mortality. A p value less than or equal to 0.05 was considered significant and results are reported as OR with 95% confidence intervals.
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The patients were divided into three groups according to the age at the time of surgery: 211 patients younger than 65 years (Group 1), 175 patients aged from 66 years to 75 years ( Group 2), and 203 older than 75 years (Group 3). The gender distribution was not significantly different among the three groups (P = 0.219). Overall comorbidities rate differed among the three groups (P < 0.001), in particular Arterial hypertension was present in 29.4 % of patients in Group 1, compared with 52.0%in Group 2 and 74.9 % in Group 3 (P < 0.001). Even Myocardial infarction history and Cardiac Arrhythmia were more frequent in patients older 75 years old compared with younger ( P < 0.001). Diabetes rate was more frequent in patients older 75 years old compared with younger ( P = 0.006) as well as Chronic Renal Insufficiency (P = 0.030); however COPD rate was not significantly different among the three groups ( P = 0.285); consequently ASA classification differed significantly (P < 0.001) between the groups. The presence of malignancy differed significantly among the three group (P < 0.001), in particular it was more frequent in Group 3 ( 89.7% of patients) compared with 83.4% of patients in group 2 and 70.1% of patients in Group 1. Preoperative characteristics of patients in the study cohort are listed in Table 3. Disease localization ( colon vs. rectum) was not significantly different among the three groups ( P = 0.166) as well as surgical procedure (P = 0.095); in particular the resections with primary anastomosis rate was 95.3 % in Group 1 compared with 91.4 % in Group 2 88.7 and 88.7 %% in Group 3. The operative time was not significantly longer in older patients (166 min in Group 1 vs. 170 min in Group 2 and 167 min in Group 3, P = 0.823) with an estimated intraoperative blood loss of 78 ± 30
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Discussion
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cc for Group 1 vs. 81 ± 35 cc in Group 2 and 85 ± 38 cc in Group 3 ( P = 0.854). Surgical characteristics of the study population in relation to age are listed in Table 4. The overall postoperative complication rate was not significantly different among the three groups ( P = 0.739); in particular there was not differences in severe postoperative complications rate (grade 3-4), according to Clavien-Dindo classification among the three groups ( Group 1 = 8.1 % of patients , Group 2 = 8.5% of patients and Group 3 = 9.4 % of patients, P = 0.973). More specifically as regard to medical complications, no differences in Cardiac ( P = 0.480) , Respiratory ( P = 0.092), Thromboembolic ( P = 0.115) and Urinary complications rate ( P = 0.068) were found between the 3 groups. Postoperative ileus occurred in 6.6 % of patients in Group 1 vs. 8.0 % of patients in group 2 and 7.9 % of patients in Group 3 with no significant statistically differences ( P = 0.846). Regarding to surgical complication , anastomotic leakage occurred in a 3.8 % of patients in Group 1 vs 4.0 % of patients in Group 2 and 3.4% of patient in Group 3 with no statistical differences (P = 0.960), just as Wound infection rate ( P = 0.846). Hospital stay was not significantly different among the three groups ( P = 0.081). Readmission rate was 4.7 % in Group 1 vs. 4.6 % in Group 2 and 4.9 % in Group 3 with no statistical differences ( P = 0.904) as well as reoperation in readmission rate ( P = 0.955). No differences were observed in anastomotic leakage rate in readmission among the three groups ( P = 0.892) even in the readmission bowel obstruction ( P= 0.645) and bleeding rates (P = 0.990). The 90-day mortality rate was higher in elderly patients but not statistical different between three groups ( P = 0.183). Postoperative characteristics of the study population in relation to age are listed in Table 5. The logistical regression analysis identified the parameters in Tables 6-7-8 as significant predictive factors for morbidity, readmission and 90-day mortality after colorectal surgery in ERAS pathway. Older age was not an independent risk factor for a complicated postoperative outcome 30-day readmission and 90-day mortality.
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An increasing number of elderly patients is subjected to colorectal surgery. In particular colorectal carcinoma has a peak of incidence in the seventh and eight decade of life.[2,8] The present study compared young (less than 65 years) to old (more than 65 years) patients, all undergoing elective colorectal surgical interventions. Elderly patients are often considered high-risk surgical candidates. In the literature, several studies reported that overall comorbidity rate in patient older 70 years varied from 50 % to 85 %, in particular hypertension, coronary heart disease and pulmonary disease rates [9,10]. In the present study we reported an overall comorbidities rate of 81.3 % in patients older 75 years compared to 58.9% in patients aged from 66 years to 75 years and 35.5 % of in patients younger than 65 years. In particular cardiovascular risk factor (Arterial Hypertension, Myocardial infarction history, Cardiac arrhythmia history) differed significantly between the three groups ( p < 0.001). Historically, it has been suggested that elderly patients do not fare well after colorectal surgery with high rates of postoperative mortality e morbidity [11]. Several recent studies have addressed the use of enhanced recovery protocol in the elderly population in colorectal surgery and they suggest similar benefit for older patients regarding rate of complications and length of hospital stay [12-17]. Comparing younger and older patients, Baek SJ. et al. [13] did not found any difference in postoperative outcome between patients below and above 70 years following an enhanced recovery protocol. In a systematic review, Bagnall et al. [14] summarizing data from 16 studies including a total of 5965 patients, has evaluated and confirmed the safety of an ERAS in the elderly population by finding similar prevalence in morbidity and mortality compared to a younger
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population, with slightly longer hospital stays. Only two studies demonstrated a higher mortality among elderly patients [16,18]. In this review overall complications were higher in the elderly patients in four cohort studies [16,18-20] , but not in five studies [13,21-24]. In particular no difference was observed in the rate of postoperative pulmonary complications in any ERAS studies between younger or older patients. In our study we reported an overall complication rate of 21.2 % in older patients compared to 21.1% and 18.5 % of patients aged from 66 years to 75 years and younger than 65 years respectively with no significant difference. In particular, we reported a severe complication rate ( grade III and IV) of 9.4 % in older patients comparable to that reported in the existing literature. In a recent study Slieker J [25] et al. reported an high rate of non surgical postoperative complications in patients older 70 years; in our study we reported no differences in both surgical and non surgical complication rate between the groups, in particular no differences were observed in postoperative cardiovascular and Thromboembolic complications rates in older patients as well as pulmonary complications rate, which would suggest that there is no increased risk of aspiration pneumonitis in elderly patients following early resumption of oral feeding. In the present study no differences for surgical specific postoperative complications were seen between the aged groups, in particular we reported a postoperative ileus rate of 7.9% in Group 3 compared with a 8% and 6.6 % in Group 2 and in Group 1 respectively; no differences were found about wound infection rate and anastomotic leakage rates about three groups with a primary anastomosis rate of 88.7% in older groups. In literature, many studies found longer length of stay in elderly patients [16,19,.24,25], but in our series no differences were found about length of hospital stay between the Groups. The rate of readmission after discharge in elderly was not different in respect of younger patients; same as reoperation in readmission rate; this is in accordance to other reports in literature [16-18,21-23]. Anastomotic leakage rate in readmission was no different among the groups ( P = 0.892) and occurred in 1% of patients older than 75 years compared with a 0.6% and 0.9% in Group 2 and Group 1 respectively. In our opinion the low rate of readmission for anastomotic insufficiency is due to compliance of the discharge criteria in early diagnose of surgical complications. In a multivariate Cox regression analysis older age was not an independent predictive factor of morbidity, readmission and 90-day mortality; instead CRI and arterial hypertension were predictive of morbidity as well as Diabetes and Chronic Renal Insufficiency were strongly predictive of 90-day mortality. Therefore, old age as such does not represent a contraindication to the E.R.A.S pathway in colorectal surgery, but considering the fragility of the elderly patients and their high risk profile, the surgical management of older patient requires, therefore, the identification and correction of disorders of the cardiovascular system, the respiratory system, liver function, renal function, nutritional status and electrolyte balance [26,27]. The main limitations of our study is that it is a retrospective study and that data on compliance with the ERAS protocol of the three comparison groups were not provided. However, all data were prospectively collected; all patient undergoing surgery were included in the pathway and all patients in the database were analyzed. Conclusion
In conclusion this study shows that the ERAS pathway in colorectal surgery can be applied in older patients. There was no significant difference in morbidity, 90-day mortality, length of stay or readmission rate in patients aged over 75's compared with younger. Consequently enhanced recovery after colorectal surgery seems to be safe and feasible in the elderly.
Disclosures The authors declare no conflict of interest or any financial support to disclose.
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Table 1. E.R.A.S. protocol
E.R.A.S.
Intraoperative
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Day of surgery
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Counseling Informed consent No bowel preparation Glucose load 2 h before Antibiotic prophylaxis Thrombus prophylaxis Prevention of hypothermia Prevention of fluid overload Minimally invasive surgery Removal of NGT at the end of procedure Sit for > 1h Chewing gum Sips of water < 1 L Tea an Jam at dinner Removal of urinary catheter Sit in chair for > 4h Ward ambulation for > 400 m Semifluid diet > 1 L Liberal ward ambulation Soft diet Discharged Daily telephone contact Outpatient control Outpatient control End of follow-up
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Table 2. Discharge criteria for E.R.A.S
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Parameter 1. Patient with no or minimal complaints 2. No fever 3. Flatus passage
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4. No tachycardia (pulse rate[100 bpm)
6. No complaint with a soft diet 7. Normal or decreasing WBC count
WBC white blood cells
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Table 3 Preoperative characteristics of patients.
Age 66-75 years Group 2: 175 pz
Age ≥76 years Group 3: 203 pz
Age (years)* Male Sex Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes COPD CRI
56 119 (56.4%) 75 (35.5%) 62 (29.4%) 9 (4.3%) 3 (1.4%) 10 (4.7%) 23 (10.9%) 7 (3.3%)
69 96 (54.9%) 103 (58.9%) 91 (52.0%) 11 (6.3%) 8 (4.6%) 22 (12.6%) 27 (15.4%) 17 (9.7%)
80 98 (48.3%) 165 (81.3%) 152 (74.9%) 33 (16.3%) 21 (10.3%) 27 (13.3%) 32 (15.8%) 17 (8.4%)
Asa score 1 2 3 Malignancy
61 (28.9%) 138 (65.4%) 12 (5.7%) 148 (70.1%)
16 (9.1%) 131 (74.9%) 28 (16,0%) 146 (83.4%)
8 (9.4%) 108 (53.2%) 87 (42.9%) 182 (89.7%)
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Age ≤ 65 years Group 1: 211 pz
P value
0.219 < 0.001 < 0.001 < 0.001 < 0.001 0.006 0.285 0.030 < 0.001
< 0.001
Values in parentheses are percentages unless indicated otherwise; *values are median. COPD, chronic obstructive pulmonary disease. MI history, Myocardial infarction history. CRI Chronic Renal Insufficency. ASA, American Society of Anesthesiologists score.
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Table 4 Surgical characteristics of population. Age 66-75 years Group 2: 175 pz
Age ≥76 years Group 3: 203 pz
172 (81.5%) 39 (18.5%)
149 (85.1%) 26 (14.9%)
179 (88.2) 24 (11.8%)
201 (95.3%) 10 (4.7%) 166 (40-395) 78 ± 30
160 (91.4%) 15 (8.6%) 170 (65-350) 81 ± 35
P value
0.166
0.095
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Disease localization Colon Rectum Surgical Procedures Resection + anastomosis Resection + stoma Duration of procedures (min)* Estimated blood-loss
Age ≤ 65 years Group 1: 211 pz
180 (88.7%) 21 (10.3%) 167 (75-405) 85 ± 38
0.823 0.854
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Values in parentheses are percentages unless indicated otherwise ; *values are median (range).
Table 5 Postoperative characteristics of the study population Age ≤ 65 years Group 1: 211 pz
P value
37 (21.1%)
43 (21.2%)
172 (81.5%) 22 (10.4%) 17 (8.1%)
138 (79.3%) 22 (12.2%) 15 (8.5%)
160 (78.7%) 24 (11.9%) 19 (9.4%)
8 (3.8%) 14 (6.6%)
7 (4.0%) 14 (8.0%)
7 (3.4%) 17 (8.4%)
0.960 0.846
14 (6.6%) 1 (0.5%) 6 (2.8%) 8 (3.8%) 0 3.89 ± 3.00 0 10 (4.7%) 2 (0.9%) 1 (0.4%) 6 (2.8%) 1 (0.4%) 5 (2.4%)
14 (8.0%) 1 (0.6%) 12 (6.9%) 14 (8.0%) 3 (1.7%) 4.67 ± 4.48 1 (0.6%) 8 (4.6%) 1 (0.6%) 1 (0.6%) 3 (1.7%) 3 (1.7%) 2 (1.2 %)
16 (7.9%) 3 (1.5%) 15 (7.4%) 19 (9.4%) 1 (0.5%) 4.74 ± 5.05 3 (1.5%) 10 (4.9%) 2 (1.0%) 1 (0.5%) 4 (1.9%) 3 (1.5%) 7 (3.4%)
0.846 0.480 0.092 0.068 0.115 0.081 0.183 0.904 0.892 0.990 0.645 0.478 0.340
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Age ≥76 years Group 3: 203 pz
39 (18.5%)
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Postoperative complications (Clavien-Dindo classification) 0 1-2 3-4 Surgical complications Anastomotic leakage Wound infection Medical complications Postoperative ileus Cardiac Respiratory Urinary Thromboembolic Hospital stay* 90-day Mortality Readmission Anastomotic leakage Bleeding SBO ** Other *** Reoperation in readmission
Age 66-75 years Group 2: 175 pz
0.739 0.973
Values in parentheses are percentages unless indicated otherwise ; *values are mean and Standard Deviation (SD), SBO ** small bowel obstruction, Other *** are fever, urinary infection, cholecysitiss and acute pancreatitis
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Table 6 Factors significantly influencing morbidity after colorectal surgery in E.R.A.S. pathway (logistic regression model)
Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
NS NS NS NS < 0.001 NS NS NS < 0.001
OR (95%CI)
RI PT
P value
2.093 (1.34-3.25)
3.711 (1.90-7.23)
SC
Parameter
M AN U
MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
Table 7. Factors significantly influencing 90-day mortality after colorectal surgery in E.R.A.S. pathway (logistic regression model) P value
EP
Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
TE D
Parameter
NS NS NS NS NS NS NS 0.010 0.027
AC C
MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
OR (95%CI)
22.59 (2.1-243.1) 12.402 (1.33-115.2)
ACCEPTED MANUSCRIPT
Table 8. Factors significantly influencing readmission after colorectal surgery in E.R.A.S. pathway (logistic regression model) Parameter
P value
RI PT
NS NS NS NS 0.048 NS NS NS NS
2.657 (1.01-7.01)
SC
Group age Presence of malignancy Asa score Comorbidities Arterial Hypertension MI History Cardiac arrhythmia Diabetes CRI
OR (95%CI)
AC C
EP
TE D
M AN U
MI history, Myocardial infarction history. CRI Chronic Renal Insufficiency.
ACCEPTED MANUSCRIPT
Highlights •
Influence of ERAS program on surgical outcome after elderly.
•
Comparing three groups: patients younger than 65 years, patients aged from 66 years to 75 years, and older than 75 years.
•
Old age is not a predictive factor of morbidity, readmission within 30 days and 90-day mortality in ERAS program.
•
Old age not represent a contraindication to the implementation of the E.R.A.S protocol in patients underwent colorectal surgery.
AC C
EP
TE D
M AN U
SC
RI PT
colon surgery in