Clinical Application of Enhanced Recovery After Surgery in Perioperative Period of Laparoscopic Colorectal Cancer Surgery

Abstract

Objective:

To investigate the clinical application value of enhanced recovery after surgery (ERAS) combined with the laparoscopic technique in the radical resection of colorectal cancer.

Methods:

A total of 200 patients undergoing laparoscopic radical surgery for colorectal cancer from June 2014 to June 2017 were selected and randomly divided into ERAS group (n = 100) and conventional (CON) group (n = 100). The ERAS group adopted enhanced recovery approach after surgery for perioperative treatment, while the CON group adopted a CON approach. The operation time, blood loss, first exhaust time, first defecation time, extubation time, complication rate (incision infection, pneumonia, gastric retention, anastomotic leakage, intestinal obstruction, etc.), scores of visual analog scale (VAS) 1, 3, and 7 days after surgery, and nutritional status (albumin, total protein) 1, 3, and 7 days after surgery were compared and analyzed.

Results:

Compared with the CON group, the ERAS group had significantly shorter first exhaust time, first defecation time, and extubation time (all P < .05). The incidence of overall complications in the ERAS group was less than those in the CON group (P < .05); and albumin and total protein were significantly higher in the ERAS group than in the CON group (both P < .05).

Conclusions:

ERAS combined with laparoscopic techniques for the treatment of colorectal cancer is a safe and feasible practice. It not only promoted the recovery of gastrointestinal function but also improved the perioperative nutritional status of patients.

Introduction

The concept of enhanced recovery after surgery (ERAS) was first proposed by Henrik Kehlet, a surgeon at the University of Copenhagen, Denmark in 1997.¹ In China, academician Li applied it in clinical practice in 2006 and achieved remarkable results.² ERAS is a concept of strengthening postoperative rehabilitation. It is based on evidence-based care methods and designs in medicine to reduce the impact of surgical stress and to enable patient's faster recovery.³ It reduces the psychological and physiological traumatic stress response, reduces complications, shortens hospital stay, and reduces the risk of readmission and mortality.

In recent years, the concept of ERAS has been gradually applied to various specialties such as orthopedics, cardiothoracic surgery, obstetrics, gynecology, and anesthesia and has achieved good results in all these fields.^4,5 It is also increasingly applied in general surgery, such as slow postoperative recovery caused by gastrointestinal dysfunction, pain, nausea and vomiting, intestinal obstruction, brake, cognitive dysfunction, and other problems in patients undergoing colorectal surgery. Although no single drug therapy, diagnosis, and treatment techniques can completely eliminate the problem of slow postoperative recovery, multi-channel methods can be used to regulate surgical stress response.^6,7 The clinical application of ERAS is in the process of continuous development, especially those concerning the requirements of Chinese hospitals and patients are gradually being formulated.⁸

Therefore, combined the actual situation of our hospital and that in China about ERAS guidelines, the general surgery department of Ninghai First Hospital carried out research on the effect of ERAS on laparoscopic radical resection of colorectal cancer, to develop the clinical application of the concept of ERAS under the multidisciplinary comprehensive diagnosis and treatment model.

Patients and Methods

Patients

From June 2014 to June 2017, 200 patients from Ninghai First Hospital with selective laparoscopic radical resection of colorectal cancer were enrolled and randomly divided into the ERAS group (n = 100) and the conventional (CON) group (n = 100). The ERAS group adopted enhanced recovery approach after surgery for perioperative treatment, while the CON group adopted a CON approach. Informed consent was signed by all patients and the study was approved by the Ethics Committee of Ninghai First Hospital.

Inclusion criteria

Patients aged 55–65 years old, with the preoperative diagnosis of colorectal malignant tumors by fiberoptic electron colonoscopy and histopathology, and undergoing elective laparoscopic radical resection of colorectal cancer. The inclusion criteria were not limited by gender.

Exclusion criteria

Pathologically confirmed benign colorectal tumor, emergency surgery, conversion from laparoscopy to open surgery, open surgery, and palliative surgery. Surgical contraindications included severe heart, liver, and lung disease, distant metastatic carcinoma of the organs and infiltration of adjacent organs.

Perioperative preparation of ERAS

Preoperative education

The preoperative issues were communicated to the patients in ERAS group through face-to-face communication, written notice, or multimedia. Preoperative education includes anesthesia and surgical procedure, encouragement of early postoperative feeding and activity, promotion of pain management and respiratory therapy, presetting discharge criteria, and notification of follow-up and readmission pathway. The education continues through the entire process of the perioperative period until the patient is discharged. The CON group was given a general preoperative presurgery education.

Preoperative bowel preparation

The ERAS group did not require regular bowel preparation. The preoperative bowel preparations in the CON group included mechanical bowel preparation and oral administration of antibacterials to clear the intestinal bacteria.

Preoperative fasting

The ERAS group fasted 6 h before surgery, and water and clear liquid food was banned 2 hours before surgery. The CON group water fasted 12 hours before surgery, and water was banned 6 hours before surgery.

Intraoperative warming

Temperature monitoring and heat preservation were carried out in the ERAS group, and no special heat preservation measures were taken in the CON group.

Liquid management

The ERAS group focused on the needs of the patients and avoided excessive fluid intake mainly as oral water supplementation to prevent gastrointestinal edema. In the CON group, glucose saline and amino acid were administered intravenously on the day of surgery, which was reasonably controlled according to the patient's physiological requirements, intake, and output.

Pain treatment

The ERAS group was given multimodal analgesia, including intraoperative local anesthesia with ropivacaine infiltration and 50 mg intramuscular injection of tramadol after surgery. The CON group was given an analgesic pump intravenously.

Postoperative activities

For the ERAS group, patients were encouraged to move out of bed. The patients in the CON group got out of bed at the time as patients' will.

Surgical methods

Laparoscopic colorectal cancer surgery⁹: Just before surgery, the patient's vital signs were monitored, and the venous access was established to perform general anesthesia. Disinfection and draping were carried out when the patient was in a supine position. The angle of the operation bed was adjusted to 30° and the foot-high horizontal position was taken. A suitable incision was selected, pneumoperitoneum was opened, and the intraabdominal pressure was maintained at 15 mmHg. The location of the lesion and lymph node metastasis were determined. The mesocolon was opened along the superior mesenteric vessels, and the ileocolic vessels, right colonic vessels, and middle colonic vessels were dissected, clipped, and then cut. Simultaneously, the lymph nodes of the vascular root were cleaned. The posterior peritoneum was cut from the fossa iliaca to the colonic liver area along the lateral side of the colon, and the ascending colon was freed from the posterior abdominal wall. The radices mesocili transversi was first separated, and the root of arteriae colica media and the mesocolon transversum were cut. Then, the tumor and mesocolon corresponding intestinal segment of the right hemicolon were resected. Finally, the ileum end and the transverse colon end were matched. The small incision was closed, pneumoperitoneum was reestablished, abdominal cavity was flushed, and drainage tube was placed.

Visual analog scale score for affected limb pain

Visual analog scale (VAS): The patient's score was estimated based on his or her pain level. The rating was done in a range of 0–10 points; 0 points: no pain; 1–3 points: slight, tolerable pain; 4–6 points: pain and affected sleep, tolerable; 7–10 points: gradually strong pain, unbearable.¹⁰

Detection methods for albumin and total protein

The fasting peripheral blood samples of the patients were collected and ethylene diamine tetraacetic acid was added to prevent coagulation. The samples were allowed to stand for 2 hours and were centrifuged at a high speed (2500 rpm for 10 minutes) at 4°C. The upper plasma layer was separated and collected. The optical density values of serum albumin and total protein were determined by the ELISA kit according to the manufacturer's instructions (albumin: MAB602 and total protein: MAB206; R&D, USA), and the albumin and total protein concentrations of the two groups were calculated according to the standard curves.

Observation indicators

Primary observation indicators were the first exhaust time, first defecation time, extubation time, complication rate (incision infection, pneumonia, gastric retention, anastomotic leakage, intestinal obstruction, etc.), VAS scores 1, 3, and 7 days after surgery, and nutritional status (albumin, total protein) 1, 3, and 7 days after surgery.

Secondary observation indicators were patient general data (gender, age, clinical stage of the tumor, underlying disease, etc.), operation time, and amount of blood loss.

Statistical methods

All data were processed using SPSS 13.0. Measurement data were expressed as the mean ± standard deviation, and two-sample independent t-test was used for comparison between groups. The count data were expressed as the number of cases/percentage, and the comparison between groups was performed using the chi-square test. When the theoretical frequency was >5, the Pearson chi-square test was used; when the theoretical frequency is <5 and >1, the continuous calibration chi-square test was used; when the theoretical frequency was <1, the Fisher test was used. When P < .05, the difference was considered statistically significant.

Results

General data

There was no significant difference in the ratio of male to female, average age, body mass index, American Society of Anesthesiologists grade, tumor location, the degree of differentiation, and clinical stage between the two groups (Table 1).

Table 1.

Comparison of General Data (Mean ± Standard Deviation)

	ERAS group (n = 100)	CON group (n = 100)	t/χ²	P
Male/female	65/35	68/32	0.202	.653
Average age (years)	56.2 ± 5.5	55.3 ± 5.3	1.178	.240
BMI (kg/m²)	22.47 ± 3.88	22.84 ± 3.42	−0.124	.867
ASA grade			0.121	.728
I	22	20
II	78	80
Tumor location			0.089	.765
Colon	33	35
Rectum	67	65
Degree of differentiation			0.290	.865
High	12	10
Middle	45	48
Low	43	42
TNM stage			2.909	.233
I	10	12
II	57	45
III	33	43

ASA, American Society of Anesthesiologists; BMI, body mass index; CON, conventional; ERAS, enhanced recovery after surgery; TNM, tumor, node, metastasis.

Comparison of clinical indicators

There was no significant difference in the operation time and intraoperative blood loss between the ERAS group and the CON group (both P > .05), while the first exhaust time, first defecation time, and time to remove the drainage tube in the ERAS group were significantly shorter than in the CON group (all P < .05, Table 2).

Table 2.

Comparison of Clinical Indicators (Mean ± Standard Deviation)

	ERAS group (n = 100)	CON group (n = 100)	t	P
Operation time (minutes)	203.25 ± 45.28	212.49 ± 44.39	1.457	.147
Blood loss (mL)	172.43 ± 23.41	175.88 ± 21.48	1.086	.279
The first exhaust time (hours)	56.29 ± 12.39	67.29 ± 18.57	4.927	<.0001
The first defecation time (hours)	60.33 ± 17.29	69.38 ± 15.55	3.892	.0001
The time to remove the drainage tube (days)	7.23 ± 1.28	8.69 ± 1.66	6.965	<.0001

CON, conventional; ERAS, enhanced recovery after surgery.

Complications

The incidence of overall complications in the ERAS group was significantly lower than that in the CON group (P < .05), but there was no significant difference in the number of complications (all P > .05, Table 3) among both the groups.

Table 3.

Comparison of Complication

	ERAS group (n = 100)	CON group (n = 100)	χ²	P
Total number	12	25	5.604	.028
Incision infection	3	6	0.465	.495^*
Pneumonia	6	10	1.087	.435
Gastric retention	0	2		.497^#
Anastomotic leakage	3	6	0.465	.495^*
Intestinal obstruction	0	1		1.000

, by continuity correction.

, by Fisher test.

CON, conventional; ERAS, enhanced recovery after surgery.

VAS scores

There was no significant difference in VAS scores between the ERAS group and the CON group at 1, 3, and 7 days after surgery (all P > .05, Table 4; Fig. 1).

FIG. 1.

Comparison of VAS. 1d, 3d, and 7d showed 1, 3, and 7 days after surgery respectively. CON, conventional; ERAS, group of enhanced recovery after surgery; VAS, visual analog scale.

Table 4.

Comparison of Visual Analog Scale Score

	ERAS group (n = 100)	CON group (n = 100)	t	P
1 Day after surgery	5.67 ± 1.23	5.78 ± 1.03	0.686	.494
3 Days after surgery	3.48 ± 1.43	3.55 ± 1.35	0.356	.722
7 Days after surgery	2.48 ± 1.56	2.39 ± 1.29	0.444	.657

CON, conventional; ERAS, enhanced recovery after surgery.

Postoperative nutritional status

There was no significant difference between the two groups in terms of albumin and total protein levels on the 1st and 3rd day after surgery (all P > .05), but they were significantly higher in the ERAS group than in the CON group on the seventh day after surgery (both P < .05). The albumin levels in the two groups decreased significantly on the first and third days after surgery, and the differences were statistically significant (all P < .05, Table 5; Fig. 2).

FIG. 2.

Comparison of nutritional status. (A) Comparison of albumin in different time point. (B) Comparison of total protein in different time point. Before, 1d, 3d, and 7d showed before surgery, 1, 3, and 7 days after surgery respectively. *P < .05, ****P < .0001. ^#P < .05, compared with ERAS group before surgery; ^ΔP < .05, compared with CON group before surgery. CON, conventional; ERAS, group of enhanced recovery after surgery.

Table 5.

Comparison of Nutritional Status (Mean ± Standard Deviation)

	ERAS group (n = 100)	CON group (n = 100)	t	P
Albumin (g/dL)
Before surgery	41.49 ± 2.34	41.65 ± 2.76	0.442	.659
1 Day after surgery	32.18 ± 3.48^#	32.43 ± 3.21^Δ	0.528	.598
3 Days after surgery	33.47 ± 3.28^#	33.75 ± 3.41^Δ	0.592	.554
7 Days after surgery	36.65 ± 3.65	34.59 ± 2.47	4.674	<.0001
Total protein (g/dL)
Before surgery	69.32 ± 10.34	69.84 ± 11.43	0.337	.736
1 Day after surgery	68.67 ± 9.28	68.23 ± 9.33	0.334	.738
3 Days after surgery	70.26 ± 10.23	70.37 ± 9.98	0.077	.939
7 Days after surgery	74.34 ± 12.23	70.88 ± 10.32	2.162	.032

P < .05, compared with ERAS group before surgery.

P < .05, compared with CON group before surgery.

CON, conventional; ERAS, enhanced recovery after surgery.

Discussion

The ERAS practices accelerate patient recovery by reduction of postoperative stress, rational management of pain, early recovery of diet, and early activity. According to some studies, the factors affecting the recovery of postoperative patients include pain caused by surgery, surgery-induced stress response such as organ dysfunction, postoperative nausea and vomiting, intestinal obstruction, restricted movement, various discomforts caused by drainage tubes, and nasogastric tubes or straps.¹¹ Corresponding intervention method was developed according to the stress source, and the best postoperative management plan was explored in practice.^12,13 According to the available literature, the existing ERAS measures include perioperative feeding, epidural analgesia, and minimally invasive surgery. These measures can modulate the stress response and promote insulin sensitivity, thereby attenuating protein breakdown.

The altered levels of hormones and various intrinsic inflammatory responses lead to surgical stress responses.^14,15 For instance, responses to decreased insulin sensitivity include a significant change in protein and glucose metabolism, increased endogenous hepatic glucose production, reduced peripheral glucose absorption, and increased protein breakdown.^16,17 The surgical stress can lead to inflammatory response and metabolic response. The inflammatory response results in an imbalance between proinflammatory and anti-inflammatory cytokines, while the metabolic response is manifested by increased catabolism, including increased albumin and total protein breakdown. This study found that the levels of albumin in both groups decreased significantly after surgery. Albumin and total protein levels were significantly increased on the seventh day after surgery in the ERAS group, which was also significantly higher than the levels in the control group. It is likely that ERAS promotes insulin sensitivity by modulating the stress response, thereby attenuating protein breakdown.¹⁸

Preoperative routine bowel preparation is a stress stimulator that can lead to dehydration and electrolyte imbalance, especially in elderly patients.¹⁹ Likewise, the meta-analysis showed that bowel preparation is not beneficial for patients undergoing colon surgery and may increase the risk of postoperative intestinal anastomosis fistula. Therefore, routine preoperative bowel preparation is not recommended for patients undergoing colorectal surgery. Preoperative bowel preparation is suitable for patients who require intraoperative colonoscopy or suffer from severe constipation, and can also promote postoperative gastrointestinal function recovery.²⁰ In ERAS group, no routine bowel preparation was performed before the operation, and the time of first defecation and exhaustion were significantly shortened after the operation. This indicates that the preoperative bowel preparation cannot accelerate the recovery of postoperative patients. It may be due to preoperative bowel preparation that leads to dehydration, electrolyte imbalance, and intestinal bacterial ectopic and bacterial disorders.

The nasogastric tube should not be routinely placed in colorectal surgery, to reduce the incidence of complications such as postoperative fever, atelectasis and pneumonia, and gastric retention.²¹ During intubation, if any gas enters, the gastric tube can be inserted into the stomach to discharge gas, but it should be removed before the patient wakes up. The placement of the drainage tube can cause pain in the wound and the surgical site, ultimately affecting the time of the patient's early bed activity, although the use of the abdominal drainage tube after colon anastomosis does not reduce the incidence of anastomotic leakage and other complications.²² The removal of the drainage tube as early as possible after the operation is beneficial to the early movement of the patient, thus avoiding complications such as infection at the site of incision, pneumonia, and gastric retention caused by prolonged bed rest. This study reveals that although the type of complications did not decrease, the incidence of overall complications in the ERAS group was significantly reduced.

Adequate postoperative analgesia can reduce stress and help patients recover faster. The postoperative analgesia model of ERAS advocates a multimodal analgesia regimen.²³ Zhu et al.²⁴ found that multimodal analgesia after surgery is more beneficial to alleviating pain after gastric cancer surgery. In this study, intraoperative local ropivacaine infiltration analgesia and postoperative intramuscular injection of 50 mg tramadol were given, and the CON analgesia used intravenous analgesia pump. Both groups of operations are beneficial for postoperative analgesia. The VAS scores of both groups were significantly lower, with no significant difference.

In this study, the clinical application of ERAS in the perioperative period of laparoscopic colorectal cancer operation was studied, although there are few reports already available in this field. However, in this research, the mechanism by which ERAS can improve the nutritional status of patients and accelerate the recovery of patients has not been studied. The mechanism of ERAS will be further explored in our future studies.

Conclusions

ERAS combined with laparoscopy is a safe and feasible practice for radical resection of colorectal cancer. It can not only promote the recovery of gastrointestinal function after the operation but also improve the nutritional status of patients during the perioperative period.

Footnotes

Acknowledgment

This work was supported by the Science and Technology Foundation of Ninghai County, China (Grant No. 201711H010034).

Disclosure Statement

No competing financial interests exist.

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