Enhanced recovery for colorectal surgery: Practical hints, results and future challenges

Abstract

Enhanced recovery after surgery (ERAS) protocols are now achieving worldwide diffusion in both university and district hospitals with special interest in colorectal surgery. The optimization of the patient’s preoperative clinical conditions, the careful intraoperative administration of fluids and drugs and the postoperative encouragement to resume the normal physiological functions as early as possible has produced results in a large amounts of studies. These approaches successfully challenged long-standing and well-established perioperative managements and finally achieved the status of gold standard treatments for the perioperative management of uncomplicated colorectal surgery. Even more important, it seems that the clinical improvement of the patient’s clinical management through ERAS protocols is now reaching his best outcomes (length of stay of 4-6 d after the operation) and therefore any further measures add little to the results already established (i.e., the adjunct of laparoscopic surgery to ERAS). Still dedicated meetings and courses around the world are exploring new aspects including the improvement the preoperative nutrition status to provide the energy necessary to face the surgical stress, the preoperative individuation of special requirements that could be properly addressed before the date of surgery and therefore would reduce the number of unnecessary days spent in hospital once fully recovered (i.e., rehabilitation, social discharges), and finally the development of an important web of out-of-hours direct access in order to individuate alarm symptoms in those patients at risk of complications that could prompt an early readmission.

INTRODUCTION

Enhanced recovery after surgery (ERAS) is a series of perioperative protocols that aim to improve the patient’s ability to face major operations and consequently ameliorate his postoperative recovery[1]. ERAS interventions focus on those key factors that usually keep patients in hospital and make them dependent on drugs and specialist assistance following uncomplicated surgery, namely the need for parenteral analgesia, the administration of intravenous fluids and confinement to bed[2]. Pillars of ERAS protocols cover all the perioperative phases by removing or decreasing the influence of such factors and promoting good habits that favour the recover of physiological functions. Therefore, they avoid mechanical bowel preparations (MBPs) and preoperative fasting before surgery and administer high carbohydrate meals until few hours from the operation; they limit the administration of fluids tailoring them to the real patient’s necessities during surgery; they encourage the resumption of an oral diet and early mobilization after surgery as well as they decrease the use of regular opioids using pain killers with less impact on the gut function[2-5].

Since their introduction ERAS protocols faced large resistances because they targeted diffuse and time-validated clinical practices[6]. These were mostly based on tradition, personal experiences, and surgical teaching that helped their historical perpetration. However, the growing amount of data available has showed now how such practices were not necessary or contributed to the adverse effects of the surgical trauma. As a result the most immediate and visible effect of ERAS introduction is a significant shortening of the length of stay (LOS) in hospital and therefore a better redistribution of the available resources. Nowadays ERAS is routine in large university hospitals and is also spreading to district general hospitals with special interests in colorectal operations[7].

PROTOCOLS

Preoperative period

Different ERAS protocols are available for colorectal surgery (Table 1). In most of them patients receive a preoperative functional assessment in order to target the eventual specific postoperative requirements and provide him with an adequate care organised for his necessities. Also, the preoperative visit would counsel the patients about the purposes and goals of the enhanced recovery addressing their expectations from the surgical recovery and reassuring them about the purposes of the early discharge. This should not be perceived as an economic necessity, but, when feasible and appropriate, is an integrated part of the treatment that avoids prolonged stays in wards where the risk of transmitted infections is significant.

Table 1.

Types of enhanced recovery after surgery protocols adopted

Ref.	Preoperative	Intraoperative	Postop (first 24 h)	Day 1	Day 2	Day 3	Day 4	Additional comments
Kahokehr et al[8,9]	Nutritional supplementation	Thoracic epidural	All IV fluid stopped	Removal of urinary catheter	Removal of epidural			Early mobilization and physiotherapy
	NBM two hours preinduction	Short acting anaesthetics	Prophylactic antiemetics
	Carbohydrate loading	Intraoperative fluids: 1000 mL of crystalloid and 500 mL of colloid	Early oral feeding
	No bowel preparation	Prophylactic antiemetics at induction (Dexamethasone)	Nutritional supplementation
	Functional assessment and goal setting	No drains or NG tubes	No opioids
King et al[12-14]	Nutrition supplementation	Thoracic epidural	Free fluid	All IV fluid stopped	Removal of epidural Regular NSAIDS	Removal of urinary catheter for rectal resections		Aim for discharge on day 3 for colonic or day 5 for rectal resection
Blazeby et al[15]	Optimised pre-morbid health status	Intraoperative fluids: 2000 mL of crystalloid	Nutritional supplementation	Regular paracetamol	Morphine for breakthrough			Provision of hospital contact numbers, review on ward if problems within 2 wk
Faiz et al[16]	Functional assessment and goal setting	Minimal-access surgery	Patient sat out in chair	3 high-protein/high-calorie drink				Review in outpatient clinic on day 12
	Stoma nurse	Local anaesthetic infiltration to the largest wound		Normal diet offered
	Bowel preparation in left-sided resections	No drains or NG tubes		Patient sat out in chair
				Start walking
				Removal of urinary catheter for colonic resections
				Laxatives
Jottard et al[7]	Nutrition supplementation	Thoracic epidural	Free fluid	All IV fluid stopped				Use of anti-emetics
	Functional assessment and goal setting	Standard anesthetic protocol		Normal diet offered				Early mobilization
	No bowel preparation	Prevention of intraoperative hypothermia						Postoperative nutritional care
		No drains or NG tubes
Maessen et al[20,21]	Nutrition supplementation1	Thoracic epidural	Oral analgesia	All IV fluid stopped	Removal of epidural Removal of urinary catheter
Nygren et al[22]	Functional assessment and goal setting	Prevention of intraoperative hypothermia	Patient sat out in chair	Nutritional supplements > 400 mL
Hendry et al[23]	No bowel preparation	Transverse/curved incision	Nutritional supplements	Normal diet offered
			Free fluid > 800 mL	Patient sat out in chair
Soop et al[26]	Nutrition supplementation	Thoracic epidural	Prophylactic antiemetics	Regular paracetamol and NSAIDS	Patient sat out in chair	Patient sat out in chair	Epidural removed (at least)
				Patient sat out in chair
Raymond et al[28]	Nutrition supplementation Functional assessment and goal setting	Thoracic epidural						Early mobilization/resumption of diet
		Intra-operative targeted fluid management
		No NG tube
Turunen et al[10]	Functional assessment and goal setting	Thoracic epidural		Removal of urinary catheter				Early mobilization/resumption of diet
	Preoperative feeding	High-oxygen P						No routine opioids, regular paracetamol and NSAIDS
	Bowel preparation	Prevention of hypothermia						Fluid restriction
		No drains or NG tubes
Senagore et al[35]		No NG tube	PCA	Removal of urinary catheter
			Free fluids	Normal diet offered
				regular NSAIDs, gabapentin, hydroxycodone if needed
				No drains
Wennstrom et al[11]	Functional assessment and goal setting	Thoracic epidural	Free fluid		Epidural removed
	No bowel preparation	Short acting anaesthetics	Patient sat out in chair		Urinary catheter removal
	Preoperative oral hydration	No opioids
Mohn et al[18]	Nutrition supplementation	Thoracic epidural	Patient sat out in chair	Removal of urinary catheter Patient sat out in chair	Epidural removed			Regular laxatives twice daily
	Functional assessment and goal setting	Total intravenous anaesthesia		Normal diet offered
	Bowel preparation	Intra-operative targeted fluid management		Regular paracetamol and NSAIDs, opioids for breakthrough				Restricted postoperative intravenous fluids
		Prophylactic antiemetics
		Short midline incisions
		No drains or NG tubes
Teeuwen et al[17]	Nutrition supplementation	Thoracic epidural	Free fluids	Normal diet offered	Epidural removed
	Bowel preparation in left-sided resections	Transverse incisions except in Crohn's disease and rectal surgery	Nutritional supplements	Intravenous fluid administration	Urinary catheter removal
		Intra-operative targeted fluid management (hypotension treated with vasopressors)	Patient sat out in chair	Start walking	Regular Paracetamol NSAIDs, opioids for breakthrough
		Prophylactic antiemetics
		No drains or NG tubes
Ahmed et al[24,25]	Nutrition supplementation	High inspired oxygen	Free fluids	Start walking				Regular paracetamol NSAIDs, opioids for breakthrough
	Functional assessment and goal setting	Concentration	Soft diet offered
	No bowel preparation	Transverse incisions	Patient sat out in chair
		No drains or NG tubes
Kirdak et al[19]	Nutrition supplementation	Thoracic epidural	Start walking	NG tubes and urinary catheters removed (except pelvic dissection)	Removal urinary catheter (low pelvic operations) and drains	Epidural removed
	Bowel preparation	Pelvic drains with rectal dissections		Soft diet offered		Regular paracetamol
		Urinary, central venous, and nasogastric catheters were routinely used		Patient sat out in chair		Central venous catheters removed
				Start walking		Normal diet

¹These authors followed Kearon for the nutritional supplementation. NBM: Nihil by mouth; NG: Nasogastric; IV: Intravenous; NSAIDs: Non-steroidal antinflammatory drugs; PCA: Patient-controlled analgesia.

Various protocols evaluate the nutritional status of patients, and, when necessary, oral supplementation is administered. Patients are usually fed until two hours before induction to avoid unnecessary consumption of body nutrients[8-11]. Few studies specified the necessity of a carbohydrate loading to prepare the body to the surgical stress and this seems a promising field of research[8,9]. Most studies do not administer MBP but some of them still use it in case of high-risk anastomosis (i.e., left-sided colonic resections)[12-17]. Only few authors use MBP routinely nowadays[10,18,19].

Intraoperative period

The leading concept of ERAS for the intraoperative phase is to administer drugs and fluids to the minimum dose effectively required by the patient and the operation. The avoidance of excessive amounts of drugs during surgery prevents their postoperative side-effects and accelerates the recovery. In this view, some authors administer short-acting anaesthetics to tailor them to the ongoing surgical necessity and to stop them quickly when not required anymore[8,9,11]. Similarly, intraoperative fluids are carefully given ranging from 1000 mL crystalloids and 500 mL colloids[8,9] to a total of 2000 mL crystalloids[12-16]. Intraoperative hypothermia is always avoided (Table 1).

Another important concept is that the control of postoperative pain already starts with some simple but effective intraoperative measures. Thoracic epidural can easily control postoperative pain after the operation. The simple infiltration of local anesthetics in the largest wound at the end of surgery also contribute to a better pain control[12-16]. Finally, transverse or curved incisions should be preferred when feasible[20-23].

Postoperative period

In the postoperative period the general purpose of ERAS is to resume the normal physiological activities and to stop the artificial introduction of fluids and drugs as soon as tolerated by patients. In this view, the administration of intravenous fluids, already restricted during the operation, is definitely discontinued during the first postoperative hours in most studies[18]. Early oral feeding is started in the form of free fluids up to 800 mL[8,9,20-23], a soft diet[24,25], or oral nutritional supplementation (one high-protein/high-calorie drink)[12-16] along with regular antiemetics to prevent nausea[8,9,17,18]. To facilitate the resumption of bowel motility patients avoid regular opioids (still used for breakthrough pain), receive oral analgesia in the form of regular Paracetamol and non-steroidal antinflammatory drugs (with proton-pump inhibitors coverage)[26] and are encouraged to sit out in chair. Rarely patients are encouraged to start walking after the operation[19] although this target is usually achieved on the first postoperative day[24,25]. Nasogastric tubes or drains are avoided to facilitate mobilisation and feeding but few authors maintain them after pelvic surgery[19].

During the 1st postoperative day the diet is built up to a normal meal or three high-protein/high-calorie drinks[12-16], and some laxatives may be used to stimulate the bowel function[12-16]. The urinary catheter is removed in most colonic resections exception made for pelvic surgery where it can last until the 2nd or 3rd postoperative day[12-16,19]. On the second postoperative day the epidural is removed and by the 4th or 5th day patients are evaluated for discharge.

RESULTS

LOS and readmission rates

Nine studies compared LOS between ERAS and conventional care (CC) in colorectal surgery[7,9,14,17,18,20,22,27,28] (Table 2). In all of them the LOS was reduced of about 54%-61% following ERAS protocols[14] and the ERAS median hospital stay was 4-6 d compared to 8-9 d following CC[7,9,17,20,27,28]. There was no evidence that the relative effect of ERAS on LOS varied according to the type of surgery (laparoscopic, laparoscopic converted, open)[14]. In one study ERAS reduced the LOS equally in both laparoscopic (from a median of 7 d to a median of 5 d) and open surgery (from a median of 9 d to a median of 7 d)[28]. However, there was no change or improvement in the time taken to return to full activity for either group[28].

Table 2.

Clinical characteristics of studies examined

Ref.	Type of study	Patients (n)	Sex (males%)	Age (yr)	Type of surgery	Approach	Length of stay (d)	Morbidity	Mortality	Readmission	Comments
King et al[14]	Prospective case series	60	31 (52)	72 ± 11		ERAS	5.8	11 (18%)	2 (3%)	7 (12%)	ERAS ↓ hospital stay
		86	45 (52)	70 ± 11		Conventional	10.7 (P < 0.001)	24 (28%)	6 (7%)	8 (9%)
Maessen et al[20]	Observational study	425	-	-	Resections above peritoneal reflection	ERAS	5 d	-	-	-	Delay in discharge was due to the development of major complications
Maessen et al[21]	Case series	121	67 (55)	66 ± 12	Resections above peritoneal reflection without stoma	ERAS	Discharge delay = 1 d	-	-	-	↓ in hospital stay may relate to changes in organization of care and not to a shorter recovery period
		52	22 (42)	64 ± 12	Resections above peritoneal reflection without stoma	Conventional	Discharge delay = 2 d
Jottard et al[7]	Prospective ERAS group matched with historical data	36	-	-		ERAS	6 (3-27)	-	-	-	ERAS was implemented in a district general hospital
		92	-	-		Conventional	9 (3-64)	-	-	-
Hendry et al[23]	Prospective case series	1035	498 (48.10)	59 (69-78)		ERAS	6 (4-8)	294 (28.40%)	17 (1.60%)	86 (8.60%)	Higher ASA, advanced age, sex (male) and rectal surgery associated with delayed mobilization, morbidity and prolonged stay
Mohn et al[18]	Prospective ERAS group matched with historical data	94	40 (43)	66		ERAS		29 (31%)	1 (1%)	14 (15%)	ERAS ↓ hospital stay
		153	68 (44.40)	71 (15-90)		Conventional	11 (5-108)	27 (18%)	1 (1%)	-
Nygren et al[22]	Prospective ERAS group matched with historical data	99	-	-		ERAS	-	18%1	-	15%1	ERAS ↓ time to resumption of oral diet, mobilization and passage of stool, improved lung function, ↓ morbidity and hospital stay but ↑ readmissions
		69	27	65 ± 2		Conventional	8.6 ± 0.6/7 for colonic resection	17 (37%) for colonic	0	2 (4%) for colonic
							12.7 ± 1.2/11 for rectal resection	12 (52%) for rectal resection		1 (4%) for rectal
Ahmed et al[24]	Retrospective case series	231	101 (44)	68 (56-76)	Elective open bowel resection	ERAS	6 (5-9)		-	-	Lower ASA grade, use of epidurals and avoidance of regular oral opiates are associated with an earlier discharge
Kahokehr[9]	Prospective case series	100	-	68 (31-92)		ERAS	4 (3-46)	-	-	-	Lower ASA score, transverse incision laparotomy and laparoscopy associated with earlier discharge
Teeuwen et al[17]	Prospective ERAS group matched with historical data	61	22 (36.1)	57 ± 17.6	elective open colonic or rectal resection	ERAS	6 (3- 50)	9 (14.8%)	0%	2 (3.3%)	ERAS ↓ morbidity and hospital stay
		122	-	-		Conventional	9 (3-138)	33.60%	1.60%	1.60%
Bryans et al[34]	Retrospective case series	20	-	-	Colorectal surgery with stoma (excluding abdominoperineal resection)	ERAS	mean = 7	-	-	-	ERAS ↓ hospital stay and ability to manage stoma
		20				Conventional	mean = 20
Kahokehr et al[8]	Prospective case series	74	-	-	Open right hemicolectomy	ERAS	Median (43-28)	-	-	-	No difference in morbidity or surgical recovery
		39			Laparoscopic right hemicolectomy	Conventional	5 (2-18)

¹Significant difference. ERAS: Enhanced recovery; ASA: American society of anesthesiologists score; QOL: Quality of life.

Significant predictors for longer discharges using ERAS protocols are the patient’s fitness for surgery [American society of anesthesiologists (ASA) score greater than 1][9,20,23,24], higher physiological and operative severity score for the enumeration of mortality and morbidity scores[20], the use of oral opiates in the post-operative period[24], age[20,23,24], rectal surgery[23], complex resections[20], the development of major complications[20] and the inability to discharge patients when they had reached functional recovery[20]. In fact, the increase in LOS with age might be attributed to delayed discharge related to difficulties in arranging social care (see below). Contrasting results were reported for the postoperative duration of epidurals [24,29] and the use of a transverse vs midline incision[9,24], sex[9,23].

The readmission rate after ERAS is 3%-15% and is similar to CC[14,17,23,24]. Only Nygren showed a significant higher readmission rates after ERAS (4% vs 15 %)[22].

Mortality and morbidity

Most studies found no significant differences in mortality rates between ERAS and CC which ranged between 1.6% and 2% [17,18,22,23,27]. The overall morbidity rate after ERAS is 18%-28% (anastomotic leak 2%-5%, reoperation rate 7.4%)[23,24] (Table 2). Morbidity rates were lower than those published for the same units before the introduction of an ERAS protocol (35%)[27]. However, contrasting results were reported by other articles. Some studies showed similar overall complication rates[14,17,22] for both colonic and rectal resections[22], others claimed lower morbidity rates after ERAS (14.8% vs 33.6%)[17], others higher rates with ERAS but only for minor complications (nausea, wound infection)[18]. Morbidity was predicted by ASA grade III–IV, male sex and rectal surgery[30], while low BMI or advanced age were not associated with it[23].

FUTURE CHALLENGES

Laparoscopic vs open resection on ERAS

Randomized trials involving the application of ERAS protocols to laparoscopic surgery showed conflicting results[12,31] (Table 3). A recent review of the published literature suggests that little additional benefit is added by laparoscopy to an already well-established ERAS program[32] especially in terms of postoperative quality of life[13], but a large multicentre study is still ongoing[33]. Patients who underwent laparoscopic surgery had a shorter LOS than those having open surgery (4-6 d for the laparoscopic group vs 6-10 d for the open group) for both colonic and rectal surgery[12,16]. Readmission rates also were lower after laparoscopic surgery (5.8% vs 22.0%)[16]. No significant differences were found in the overall morbidity (52% after laparoscopic vs 42% after open surgery) and major morbidity (15% after laparoscopic vs 26% after open surgery)[8,12,16] while contrasting results were reported for mortality rates: one study showed no significant differences[12] while another claimed higher mortality after open surgery[16]. Differently, Basse et al[31] did not reveal significant differences in LOS or morbidity between groups, but these authors excluded patients with rectal anastomoses (requiring a stoma) and those not living independently at home that required social setting for discharge. In fact, the social discharge is a problem that was also faced by Kahokehr and colleagues in their study (see below)[8].

Table 3.

Other colorectal studies involving enhanced recovery after surgery patients

Ref.	Type of study	Patients (n)	Approach	Comments
Soop et al[26]	RCT	9 vs 9	Complete or hypocaloric postoperative enteral nutrition on ERAS	Complete enteral nutritions was associated with minimal postop insulin resistance, hyperglycemia and nitrogen losses
King et al[12]	RCT	43 vs 19	Lap vs open resections on ERAS patients	Reduced hospital stay and with laparoscopic resections
King et al[13]	RCT	41 vs 19	Lap vs open resections on ERAS patients	Laparoscopic surgery achieves quicker return to daily activities
Kirdak et al[19]	RCT	14 vs 13	Preop. dexamethasone vs placebo on ERAS patients	Preoperative dexamethasone has no significant effects on the inflammatory response or outcomes
Turunen et al[10]	RCT	29 vs 29	Epidural anesthesia vs control for laparoscopic resection on ERAS	The epidural G. needed less oxycodone than the control G. Until 12 h postop. Epidural alleviated pain, reduced opioids requirements
Raymond et al[28]	Retrospective case series	179 vs 144	Lap vs open resections on ERAS patients	Laparoscopic surgery achieves quicker return to daily activities
Blazeby et al[15]	Prospective	20	Laparoscopic assisted and open	QOL evaluation. Patients liked quicker discharges, few were dissatisfied due to complications requiring readmissions
Senagore et al[35]	RCT	22 vs 21 vs 21	Standard vs lactated Ringer’s vs hetastarch-lactated Ringer’s periop fluid	Individualized intraoperative fluid management with crystalloid reduced overall fluid administration compared to colloid
Faiz et al[16]	Prospective non-randomized	191 vs 50	Lap vs open resections on ERAS patients	Laparoscopic has advantages over open approach also in ERAS patients
Wennstrom et al[11]	Prospective	32	ERAS	Postoperative survey on QOL following discharge: fatigue, nausea and bowel disturbances
Ahmed et al[25]	Case series	100 vs 95	ERAS audit protocols application vs ERAS clinical practice	Observance to ERAS protocol was lower outside clinical trials

RCT: Randomized controlled trial; ERAS: Enhanced recovery after surgery; QOL: Quality of life; Preop.: Preoperative; Postop.: Postoperative.

Functional recovery and delay in discharge

In the pre-ERAS era 90% of patients were not discharged on the day that criteria were fulfilled. Wound care and symptoms pointing towards an anastomotic leakage were the most important reasons for a medical appropriate delay of discharge[21]. With regards for the stoma independence, 60% of patients audited in the pre-ERAS era were taking more than 8 d to be deemed stoma-independent and only 15% were able in less than 5 d. Following the introduction of ERAS protocols the percentage of patients not discharged on the day that criteria were fulfilled decreased to 34%-87%[20,21], 75% of patients achieved stoma independence in 5 d or less and only 5% took 8 or more days - the figures completely reversed compared to the pre-ERAS era[34]. Results achieved represent a huge step forward especially considering that they simply reflect an optimization of the patients’ management and of the impact of surgery without the necessity to introduce any additional procedures into clinical practice. At the same time they also show us that 13%-66% of patients are still not discharged when deemed medically fit by one or two days[24]. Various authors feel that ERAS protocols ultimately optimized the patient’s medical fitness for discharge and that nowadays a further reduction of the LOS must relate to changes in the organization of care and not to shorter recovery periods. This could be obtained in example by evidencing those social factors that can delay the discharge and therefore organizing the available resources outside the hospitals well in advance the operation. In example, older patients leaving alone and likely requiring specialist assistance or short admissions to nursing homes or rehabilitative structures can be individuated during the preoperative counseling and necessary arrangements well planned before surgery.

When asked about their experience with the ERAS programs, most patients appreciated a planned short hospital stay because it was perceived that better recovery could be achieved in the home environment[15] (Table 3). However, some of them reported feeling vulnerable at home so shortly after major surgery and those who experienced complications were less satisfied with the process[15]. The first period at home is the most troublesome and the main problems perceived are fatigue, nausea and bowel disturbances (not pain)[11] (Table 3). In this view, it is necessary that ERAS programs are paralleled by the development of services aimed to provide direct contacts and accesses to healthcare resources that could reassure patients about their recovery when normal or quickly individuate suspicious symptoms that require readmissions[8,15]. A direct telephone contact is a simple measure that might alleviate the patient anxiety and maintain the continuity of care from health professionals[11].