Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS^®) Society Recommendations: 2018

Starting from our previous guidelines in colon [9] and rectal [10] surgery published in 2013 the first and last author identified topics for inclusion. International authors known for their expertise in each item, respectively, and in overall perioperative care were invited to participate in the work. All invited authors accepted participation and received instructions for the literature search. PubMed, Embase and Cochrane databases were used to identify relevant contributions from January 2012 (end date for the search in the previously published guidelines [9]) and October 2017. Keywords included “colon”, “rectum”, “enhanced recovery”, “ERAS” and “fast track”. Meta-analyses randomised controlled trials (RCTs) and prospective/retrospective cohort studies were considered for each perioperative item. The individual authors screened titles and abstracts in order to identify relevant articles. The first and last author then repeated this procedure.

The Cochrane checklist [11] was used to assess methodological quality of the included studies. Quality of evidence and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Quoting from the GRADE statement [12‐14], the recommendations are given as follows:

One or two authors covered the evidence base for each item. The quality of evidence for each item was then reviewed and crosschecked by several other authors in the author list.

The evidence and recommendations for ERAS items are presented in four different headings: preadmission, preoperative, intraoperative and postoperative and are numbered in the order they are to be used in clinical practice. A summary figure (Figs. 1, 2, 3, 4) shows an overview of the quality of evidence and grade of recommendation for each phase of the perioperative course. Table 1 shows all the ERAS items.

See Fig. 1.

Comprehensive preoperative counselling has several important goals. First, as patients fear the unknown, proper and complete information may reduce anaesthesia- and surgery-related anxiety and subsequent pain [15‐19]. Secondly, the patient’s preparedness, satisfaction and overall surgical experience may be improved considerably by detailed, procedure-specific and patient-centred information giving sessions [20‐22]. As a consequence of this psychological support, a positive impact of preoperative information on LOS and postoperative outcomes has been reported in an RCT and a Cochrane analysis [23, 24]. Modern education strategies including multimedia or virtual reality experiences may be considered [15, 25]. Patients and relatives/carers should meet with a multidisciplinary team comprising a surgeon, anaesthesiologist and most importantly a nurse or allied health professional, all whom have a role in guiding the patient through the surgery-related experience before admission to the hospital [26].

There are several examples of preoperative risk assessment scores proposed in the literature [27‐30] but due to the low level of evidence of these scores, their use is limited. For instance, while it is generally believed that a multidisciplinary team should evaluate patients with a high risk of cardiac disease undergoing major surgery, the level of evidence for this intervention is very low [29]. While nutritional assessment and intervention seem to be useful for the high-risk malnourished patients, there is only one prospective study available [28]. For more general preoperative risk assessment tools, prospective data showing any effect on outcomes are lacking [27]. Most commonly tools describe control of systemic diseases such as optimisation of heart disease, lung disease, kidney disease, hypertension, diabetes, correction of derangements such as anaemia and malnutrition, and cessation of excessive alcohol use and smoking. This section refers to the latter two aspects, which are mainly under the control of the patient.

Patients who smoke have an increased risk of intra- and postoperative complications [31]. There are many methods of achieving smoking cessation in different subsets of patients, utilising pharmacologic versus behavioural therapy. In the preoperative setting, there are several meta-analyses [32‐34] of preoperative smoking cessation, evaluating types of intervention and postoperative complications. In the preoperative setting, intense counselling and nicotine replacement therapy are most likely to be effective [33]. Although the optimal preoperative intervention, duration and intensity are unknown, 4–8 weeks of abstinence appear necessary to reduce respiratory and wound-healing complications [32, 34]. Even at the level of these meta-analyses, it is unclear whether short-term (< 4 weeks) smoking cessation reduces the risk of postoperative respiratory complications.

Observational studies suggest that alcohol abuse increases postoperative morbidity [35, 36]. A systematic review and meta-analysis identified thirteen observational studies and five RCTs [37] and showed that consumption of more than two units (equal to a total of 50 ml spirits 40%, 150 ml wine 13%, 500 ml 4% beer or alcopop (a ready-mixed drink containing alcohol) of alcohol per day increases the rate of postoperative infections, but not mortality. In the same paper [37], a separate meta-analysis of the RCTs also confirmed that interventions to reduce alcohol intake reduce infections but not mortality. The impact on patients with lesser alcohol intake is unknown. Preoperative abstinence of 4 weeks is recommended [37]. Another review [38] found only two RCTs evaluating the effect of intensive alcohol cessation interventions (69 patients). Intensive preoperative alcohol cessation interventions, including pharmacological strategies for prophylaxis of relapse and withdrawal symptoms, may reduce postoperative complication rates significantly. No effect was found on mortality rates and LOS [38].

General preoperative medical assessment and optimisation is intuitively important, but for specified risk assessment tools, the evidence of their clinical accuracy remains low.

Smoking increases the risk of postoperative complications. Smoking should cease preoperatively for at least 4 weeks to reduce respiratory and wound-healing complications; shorter periods may still yield lesser benefits. Intense counselling and nicotine replacement therapy are most likely to be effective. Although meta-analyses show the impact of alcohol abuse on postoperative outcomes, only 2 small RCTs show a benefit of alcohol cessation on outcomes.

Poor preoperative physical status has been shown to be a risk factor for serious postoperative complications and prolonged disability [39]. The preoperative period may provide an opportunity to increase the physiologic reserve in the anticipation of surgery with the intention to improve outcomes and accelerate recovery. Therefore, preoperative optimisation or “prehabilitation” can be a compelling strategy to address modifiable risk factors that impact cancer treatment outcomes [40].

Prehabilitation is defined as “A process in the continuum of care that occurs between the time of diagnosis and the beginning of acute treatment (surgery, chemotherapy, radiotherapy) and includes physical, nutritional and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments” [41]. The initial introduction of prehabilitation programmes using intense exercise showed poor compliance and modest changes in postoperative functional capacity [42]. A follow-up RCT using multimodal structured prehabilitation protocols, which included aerobic and resistance exercises together with protein supplementation and relaxation strategies, demonstrated a positive impact on preoperative physiologic reserve with sustained levels of functional capacity after surgery [43]. In this study, more than 80% of patients who received the multimodal prehabilitation programme returned to baseline values of functional walking capacity by 8 weeks. In contrast, only 40% of patients who did not receive prehabilitation returned to baseline values. With regard to postoperative complications, one RCT demonstrated a 51% reduction in postoperative medical complications using a 4-week prehabilitation programme, thus showing an association between increase in preoperative aerobic capacity and reduction in complications [44].

Prehabilitation shows promising results in recovery of functional capacity and may reduce complications after colorectal surgery. Patients who are less fit may be more likely to benefit. Further research is required before considering this as a mandatory item in an ERAS protocol.

Preoperative malnutrition has been associated with increased postoperative morbidity and mortality as well as poor oncologic outcomes in surgery for gastrointestinal cancer [45‐48]. Preoperative nutritional assessment to detect overt or subtle malnutrition offers the opportunity to improve nutritional status and correct specific deficits [28]. There is no consensus on how to assess preoperative nutritional status accurately [49]. However, nutritional risk determined using the Nutritional Risk Screening score (NRS 2002) has been associated with increased risk of complications [50]. Preoperative serum albumin concentration has been suggested to be a risk factor of morbidity and mortality in two large studies [51, 52] and may be considered part of the preoperative nutritional assessment [53]. Several more comprehensive assessment tools both subjective and objectives have been proposed. Poor scores on the Subjective Global Assessment (SGA), the Patient Generated Subjective Global Assessment (PG-SGA) and the Malnutrition Universal Screening Tool (MUST) have been associated with both morbidity and mortality after major abdominal surgery and have been considered to be the reference standard for nutritional screening [54‐58].

The risk of complications is increased in patients with unintentional weight loss of 5–10% or more [59], and patients with higher nutritional risk benefit from preoperative nutritional treatment [28]. For malnourished patients, oral nutritional supplementation (or additional parenteral nutrition when indicated) has the best effect if started 7–10 days preoperatively and is associated with a reduction in the prevalence of infectious complications and anastomotic leaks [60].

Preoperative routine nutritional assessment offers the opportunity to correct malnutrition and should be offered. Preoperatively, patients at risk of malnutrition should receive nutritional treatment preferably using the oral route for a period of at least 7–10 days.

The World Health Organisation definition of anaemia is a haemoglobin (Hb) concentration of < 130 g/L for men and < 120 g/L for women but recently it has been proposed that women should be considered anaemic if Hb < 130 g/L as most attain this figure if not iron deficient [61, 62]. Twenty-five percentage of women with subnormal Hb (120 g/L) are iron deficient [63]. This has significant implications for the potential to restore haemoglobin rapidly through haemopoiesis after blood loss. Anaemia is common in patients presenting for surgery. In a large study with data reported from all surgical specialties showed a prevalence of 31.1% in men and 26.5% in women [64]. Patients scheduled for surgery may have many factors causing anaemia: acute or chronic blood loss; vitamin B12 or folate deficiency; anaemia of chronic disease related or unrelated to their reason for surgery, or a combination of these [63]. All causes of anaemia should be investigated appropriately and corrected. Most patients presenting for colorectal surgery will have iron deficiency because of blood loss or chronic inflammation [62].

Anaemia—Risks of Complications & Mortality

Anaemia may be a risk factor for all complications and mortality [64, 65]. However, the administration of blood products peri-operatively may also increase complications and have a long-term impact on survival in patients with colorectal cancer [66]. One retrospective series of 23,388 patients undergoing colorectal surgery showed that 7.9% of patients received blood transfusions. Statistically, there was no increase in superficial or deep wound infection but there was an increase in organ space surgical site infection and septic shock [67]. In elective orthopaedic surgery, transfusion of blood products increased 4-year mortality by 10% [65]. In liver resection for metastatic colorectal cancer blood transfusion is an independent risk for poor short and long-term outcomes [68, 69]. It is therefore essential to optimise the patient’s Hb concentration preoperatively. The time frame to do this will vary according to the indication and urgency for surgery and how rapidly blood loss is occurring.

Significant perioperative blood loss can lead to the question of whether to transfuse blood products. The American Society of Anaesthesiologists recommend that a minimum Hb concentration of 60–100 g/L is maintained through the perioperative period individualised to a patient depending on their comorbidities and type of surgery [70]. Patients with, cardiac, renal and pulmonary problems are at higher risk as haemoglobin declines acutely and in these groups a target Hb of > 80 g/L may be better to avoid complications.

In anaemia of chronic disease, such as that encountered in inflammatory bowel disease, the iron regulatory protein hepcidin is activated in response to inflammation. It inhibits absorption of iron from the gastrointestinal tract and reduces bioavailability of iron stores for red cell production in the marrow, making oral iron therapy not very effective. Intravenous iron infusions can overcome this problem in some instances [63].

Oral iron is cheap and administered easily but may be tolerated poorly. Absorption of iron may be better by using lower doses between the range of 40–60 mg per day or alternate day with 80–100 mg [63]. Many colorectal surgical patients will either not respond to oral iron due to chronic illness or because of ongoing blood loss. Intravenous iron infusion may be worth considering in this group and is discussed below.

There are now several different iron infusions available in clinical practice with a low serious adverse reaction rate of 38 incidents per million episodes of administration [71]. Acute reactions are normally mediated via complement activation due to nanoparticles rather than an IgE-mediated response [72]. Timing of and the number of infusions depends on the urgency of surgery; 1–1.5 g usually restores iron stores back to normal and can be given in single or divided doses. One study reports a mean Hb increase of 8 g/L over 8 days following IV ferric carboxymaltose 15 mg/kg, max 1000 mg, given as a single dose over 15 min [73]. A reticulocytosis occurs at 3–5 days after administration. The addition of erythropoietin is not recommended. Timing of infusions and effectiveness in different colorectal populations has still to be determined by large-scale studies although the preoperative target of 130 g/L should be pursued. Serum ferritin concentration < 30 μg/L is the most sensitive and specific test used for the identification of absolute iron deficiency. However, in the presence of inflammation (C-reactive protein > 5 mg/L) and/or transferrin saturation < 20%, a serum ferritin concentration < 100 μg/L is indicative of iron deficiency [62].

Anaemia is common in patients presenting for colorectal surgery and increases all cause morbidity. Attempts to correct it should be made prior to surgery. Newer preparations of intravenous iron have a low risk of adverse reactions and are more effective than oral iron at restoring haemoglobin concentrations in both iron deficiency anaemia and anaemia of chronic disease. Blood transfusion has long-term effects and should be avoided if possible.

See Fig. 2.

The prevention of postoperative nausea and vomiting (PONV) is fundamental for patients undergoing colorectal surgery. PONV when severe may result in dehydration, delayed return of adequate nutrition intake, or may require the placement of a nasogastric tube, increase intravenous fluid administration postoperatively, prolong hospital stay, and increase healthcare costs.

PONV affects 30% (vomiting) to 50% (nausea) of all surgical patients and up to 80% of patients who are at high risk for developing these complications [74]. It is also a leading cause of patient dissatisfaction [75]. The aetiology of postoperative nausea and vomiting is multifactorial and is generally divided into patient-related, anaesthesia-related and surgery-related factors [76]. Female gender, those with a past history of PONV or motion sickness and non-smokers, are at particular risk [77]. Volatile anaesthetic gases, nitrous oxide (both of which can be mitigated in part by the use of total intravenous anaesthesia (TIVA) with propofol) and the liberal use of opioids increase the risk significantly [78]. The type and duration of surgery and the gastrointestinal pathology are also important. While opioid use cannot necessarily be avoided, analgesia is best provided by opioid-sparing multimodal techniques. Some studies suggest that carbohydrate loading may also reduce PONV [79].

Several scoring systems have been described for the prediction of PONV, with simpler ones appearing to provide better discrimination [80]. The most commonly used are the Koivuranta score and Apfel’s simplification of this score. These scores are useful when combined with specific therapeutic interventions, especially in high-risk patients [81, 82]. An alternative strategy employed in many practices but not yet studied may be to administer antiemetic prophylaxis (between one and three medications) to all patients who are having inhalational anaesthesia, opiates or major abdominal surgery. This approach is gaining popularity among anaesthetists given that the cost and side-effect profiles of commonly used antiemetic drugs are small [83].

There are several classes of first-line antiemetic drugs, including dopamine (D2) antagonists (e.g. droperidol), serotonin (5HT3) antagonists (e.g. ondansetron) and corticosteroids (e.g. dexamethasone). In one study of 5199 patients, when these classes of drugs were given individually, they were demonstrated to contribute a relative risk reduction of about 25% [84], while multimodal administration of antiemetic drugs reducing PONV even further [85]. If rescue PONV treatment is required, a different class of antiemetic should be administered than the one administered for prophylaxis [74]. For dexamethasone, the dose administered may vary, but a recent meta-analysis with 6696 patients showed that a 4–5 mg dose had clinical effects similar to the 8–10 mg dose [86]. The use of dexamethasone for open or laparoscopic bowel surgery was further confirmed in the recently published Dexamathasone Reduces Emesis After Major Gastrointestinal Surgery (DREAMS) Trial in which 1350 patients were studied. A single 8 mg dose of dexamethasone reduced PONV at 24 h and reduced the need for rescue antiemetics for up to 72 h, without an increase in adverse events [87]. However, the immunosuppressive effects of dexamethasone on long-term oncological survival are still unknown. Other, second-line drugs, such as antihistamines (e.g. promethazine), anticholinergics (e.g. scopolamine) and other D2 antagonists such as metoclopramide may also be used, but their use may be limited by common side effects such as sedation, dry mouth, blurred vision and dyskinesia.

More recently, the use of preoperative administration of gabapentin and pregabalin has been examined for a range of operations. Recent meta-analyses confirm that both drugs significantly reduce nausea and vomiting, although there is a significantly increased risk of visual disturbance (pregabalin) [88] and sedation (gabapentin and pregabalin) [89]. A neurokinin-1 (NK1) receptor antagonist (e.g. aprepitant) may be used in high-risk patients, although it has not been shown to be superior to ondansetron in PONV prevention [90].

In addition, the use of prophylactic analgesia such as intravenous paracetamol (acetaminophen) (i.e. before the onset of pain) in a meta-analysis of 2364 patients reduced the incidence of nausea and correlated with the reduction in pain [91]. There is also some evidence for the use of alternative therapies to reduce PONV, which include music therapy, aromatherapy, acupuncture, hypnosis and relaxation techniques [92]. Finally, there are also reports of a small beneficial effect of high-inspired oxygen concentration on reducing the incidence of nausea [93], although one meta-analysis show no benefit of the treatment [94].

A multimodal approach to PONV prophylaxis should be considered in all patients and incorporated into ERAS protocols. Patients with 1–2 risk factors should ideally receive a two-drug combination prophylaxis using first-line antiemetics. Patients with ≥ 2 risk factors undergoing colorectal surgery should receive 2–3 antiemetics. If nausea and or vomiting still occur, despite prophylaxis, salvage therapy should be provided using a multimodal approach using different classes of drugs from those used for prophylaxis.

Psychological distress (pre- and postoperative anxiety) may increase perioperative analgesic requirements [95] and postoperative complication rates [96]. Given that high levels of anxiety occur days prior to hospital admission, and only in a minority of patients peaks on the day of surgery, it is imperative that anxiolytic strategies are employed that exceed the mere administration of anxiolytic-sedatives (benzodiazepines) in the immediate preoperative period. Effective communication strategies, including attending a preoperative educational session (‘Surgery School’) with information for patients on the intent of ERAS pathways, can successfully reduce patient anxiety and improve their perioperative experience [18].

The adverse side effects of drugs, such as benzodiazepines, opioids or beta-blockers, can limit their use as anxiolytic pre-anaesthetic medications [97]. In particular, benzodiazepines, even after single-dose administration, may cause psychomotor and cognitive impairment and exhibit sedative effects. The American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication (PIM) use in older patient populations (aged 65 years and older) [98] provide a strong recommendation, with moderate quality of evidence, that due to their increased sensitivity to all benzodiazepines and due to their decreased metabolism of long-acting agents, that benzodiazepines should be avoided in older patients where possible to offset the risk of cognitive impairment, delirium and falls. While there are data against the use of pre-medication especially in the elderly, studies from day surgery report minimal impact on time to discharge, less nausea and headaches with the use of lower doses of benzodiazepines. However, there remains a risk of impaired motor function in higher doses [99, 100].

Given the disadvantages of benzodiazepines, alternate anxiolytics should be explored when pre-anaesthetic medication is needed. A meta-analysis, with high-grade quality of evidence, reported that melatonin (tablets or sublingually) provided effective preoperative anxiolysis with few side effects compared with placebo; with low-grade quality of evidence that melatonin is equally effective to midazolam and that melatonin may also provide postoperative anxiolysis [101].

Pre-anaesthetic medication can also be employed as part of the ERAS strategy to achieve multimodal, opioid-sparing analgesia to decrease opioid-related adverse effects (e.g. nausea, vomiting, sedation, ileus and respiratory depression) and to expedite recovery after surgery. Pre-anaesthetic medication may therefore include a combination of paracetamol, a NSAID and a gabapentinoid (such as gabapentin and pregabalin, originally used for the treatment of chronic neuropathic pain). Paracetamol, NSAIDS and gabapentinoids administered as oral formulations prior to surgery are very cost-effective. All should be age and dose adjusted. It is important that the timing of dosing should achieve an optimal pharmacodynamic effect that coincides with the onset of surgery to ensure a maximal multi-modal opioid-sparing effect.

Gabapentinoids are only available in an oral form and are increasingly used as oral pre-anaesthetic medications for their opioid-sparing effects. Meta-analyses indicate that a single dose of gabapentin or pregabalin, administered preoperatively, associates with decreased postoperative pain and opioid consumption; however, these benefits are offset by increased postoperative sedation, dizziness and visual disturbances [102, 103]. All doses of pregabalin (≤ 75, 100–150 and 300 mg) resulted in an opioid sparing at 24 h after surgery. Importantly, there were no significant differences in acute pain outcomes between single preoperative dosing regimens and those including additional doses repeated after surgery [103]. To limit the adverse effects, including synergistic effects with opioids, sedation, dizziness and peripheral oedema, gabapentinoid dosing should be limited to a single and lowest preoperative dose, unless indicated for postoperative neuropathic pain. In elderly patients and patients with renal dysfunction the dose of these agents should be adjusted accordingly and be used with further caution.

Preoperative education can reduce patient anxiety to an acceptable level without the need for anxiolytic medication. Pharmacologic anxiolysis with long- or short-acting sedative medication (especially benzodiazepines and especially in the elderly) should be avoided if possible before surgery. Opioid-sparing multimodal re-anaesthetic medication can be used with a combination of acetaminophen, NSAIDS and [70] gabapentanoids. All should be dose adjusted according to age and renal function. Gabapentinoids should preferably be limited to a single lowest dose to avoid sedative side effects.

A Cochrane review published in 2014 underpinned the mandatory use of oral or intravenous antibiotic prophylaxis before colorectal surgery with a consecutive reduction of surgical site infections (SSI) from 39 to 13% [104]. Standard oral or intravenous antibiotics covering aerobic and anaerobic bacteria was the preferred option, with current preference for a cephalosporin in combination with metronidazole. Intravenous antibiotic prophylaxis should be administered within 60 min before incision. No benefit was shown for repeated administration [104, 105]. These conclusions are made on studies where patients are treated with bowel preparation.

Addition of oral antibiotic decontamination to preoperative intravenous antibiotics is an ongoing controversy. The additional benefits of administering oral antibiotics, which are usually given 18–24 h before surgery, are attributed to its possible local effects of inhibiting opportunistic pathogens in the colonic lumen before opening the colon, however, with a potential pitfall to disturb the gastrointestinal microbiota. The addition of oral antibiotics to intravenous administration in patients with bowel preparation was shown to reduce the risk for surgical site infections when compared with intravenous coverage alone [RR 0.56 (0.43, 0.74]) or oral alone [RR 0.56 (0.40–0.76)] [104]. These results were confirmed in a recent meta-analysis [106] where SSI was significantly reduced in patients who received oral and systemic antibiotics and mechanical bowel preparation compared with patients who received systemic antibiotics alone with mechanical bowel preparation. Similarly, retrospective registry data from the USA suggested largely reduced SSI rates in patients having both, mechanical bowel preparation in combination with oral antibiotics alone [107]. However, oral antibiotic decontamination alone in patients with no bowel preparation has not been studied and any potential effect remains unknown. Also, it remains unknown if the triple combination of intravenous antibiotics, oral decontamination and bowel preparation is superior to only intravenous prophylaxis and bowel without preparation.

For skin decontamination, a randomised trial in colorectal surgery and a recent meta-analysis of 13 RTCs (6997 patients) suggested lower incidence of SSI after preoperative antisepsis using chlorhexidine [108, 109]. In contrast, available evidence does not support the practice of preoperative antiseptic shower or adhesive drapes [110, 111]. Lastly, routine hair removal before surgery does not reduce SSI rates, but should be preferably performed—if deemed necessary—by use of clippers rather than razors immediately before surgery [112].

In previous ERAS guidelines in colon [9] and rectum [10] surgery, given the universal use of systemic antibiotic prophylaxis, the recommendation has been to avoid the use of mechanical bowel preparation (MBP) in colonic surgery but that it may be advantageous in rectal surgery. The rationale behind this is to avoid preoperative dehydration, electrolyte disturbance and discomfort with no clinical gain for the patient [113].

The role of MPB alone has been evaluated in a meta-analysis of 36 studies comparing adult patients receiving MBP versus with those receiving no MBP [114]. A total of 21,568 patients undergoing elective colorectal surgery were included from 23 RCTs and 13 observational studies. When all studies were considered, MBP versus no MBP was not associated with any significant difference in anastomotic leak rates (OR 0.90, 95% CI 0.74 to 1.10), surgical site infection (OR 0.99, 95% CI 0.80 to 1.24), intra-abdominal collection (OR 0.86, 95% CI 0.63 to 1.17), mortality (OR 0.85, 95% CI 0.57 to 1.27), reoperation (OR 0.91, 95% CI 0.75 to 1.12) or hospital LOS (overall mean difference 0.11 days, 95% CI − 0.51 to 0.73), when compared with no MBP, nor when evidence from RCTs only were analysed. A sub-analysis of MBP versus absolutely no preparation or a single rectal enema similarly revealed no differences in clinical outcomes. Still, in rectal surgery, a diverting stoma is often used and this may be a reason for MBP or an enema to avoid stools remaining in the diverted colon.

Recently the avoidance of MBP has been questioned mainly because of data from retrospective cohort and large database studies from the USA, indicating that the combination of oral antibiotic preparation together with systemic antibiotics and MBP reduces morbidity after colorectal surgery compared with MBP and systemic antibiotics alone [115], but also compared with patients who received no bowel preparation but systemic antibiotics alone [116]. These findings are also supported by a meta-analysis of 1769 patients in randomised trials [106]. Much of these new data have been derived from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP^®) targeted colectomy database, with a likely degree of cross-reporting of patient populations. A recent meta-analysis of 23 randomised controlled trials and 8 cohort studies [117] including a total of 63,432 patients undergoing elective colorectal surgery demonstrated that systemic antibiotic used alone was associated with a significant reduction in surgical site infection versus oral antibiotics alone [Odds Ratio (OR) 1.82, 95% CI 1.28 to 2.59], although the combination of oral and systemic antibiotics was superior to oral antibiotics alone (OR 0.44, 95% CI 0.33 to 0.58). The addition of oral antibiotic preparation to MBP in the setting of systemic antibiotics significantly reduced the incidence of surgical site infection (RR 0.48, 95% CI 0.44 to 0.52). However, when studies comparing oral antibiotic preparation and systemic antibiotic versus MBP and systemic antibiotic were compared, no significant difference was seen in the incidence of surgical site infection (RR 0.94, 95% CI 0.73 to 1.20).

The largest observational study to date arising from the ACS NSQIP database [118] included 40,446 patients, with 13,219 (32.7%), 13,935 (34.5%), and 1572 (3.9%) in the no-preparation, mechanical bowel preparation alone, and oral antibiotic preparation alone groups, respectively, and 11,720 (29.0%) in the combined preparation group. Conditional logistic regression following patient matching, oral antibiotic preparation alone was protective of surgical site infection (OR, 0.63; 95% CI, 0.45–0.87), anastomotic leak (OR, 0.60; 95% CI, 0.34–0.97), ileus (OR, 0.79; 95% CI, 0.59–0.98) and major morbidity (OR, 0.73; 95% CI, 0.55–0.96), but not mortality (OR, 0.32; 95% CI, 0.08–1.18). Combined oral antibiotics and MBP conveyed no benefit in any major outcome over oral antibiotics alone in this study. However, to date no RCTs have been performed to support this observation, and as such, further high-quality evidence is necessary to inform the debate.

It is imperative that the patient should reach the anaesthetic room in as close a state to euvolaemia as possible and any preoperative fluid and electrolyte excesses or deficits must be corrected. Pre-existing comorbidities must be taken into account when assessing fluid status. Avoidance of prolonged preoperative fasting, provision of clear liquids (including carbohydrate drinks) for up to 2 h prior to the induction of anaesthesia and avoidance of mechanical bowel preparation help reduce the incidence of preoperative fluid and electrolyte deficits and substantially reduced intraoperative fluid requirements. However, when mechanical bowel preparation is indicated, patients may lose up to 2 L of total body water as a consequence [113], and fluid and electrolyte derangements may occur even if patients are permitted oral fluids. Hence, some of these patients may require appropriate intravenous fluid therapy to compensate for these deficits and improve outcome [119].

Several RCTs have demonstrated that non-alcoholic clear fluids can be safely given up to 2 h, and a light meal up to 6 h, before elective procedures requiring general anaesthesia, regional anaesthesia or procedural sedation and analgesia in children and adults [120‐122].

Preoperative administration of oral carbohydrates (complex CHO-maltodextrin, 12.5%, 285 mOsm/kg, 800 ml in the evening before surgery and 400 ml 2–3 h before induction of anaesthesia) has been shown to attenuate the catabolic response induced by overnight fasting and surgery [123]. CHO in RCTs has been shown to improve preoperative well-being, reduce postoperative insulin resistance, decrease protein breakdown and better maintain lean body mass and muscle strength, as well as beneficial cardiac effects. In a recent large RCT in 880 patients undergoing elective major abdominal surgery, oral CHO administration resulted in lower insulin requirements and less hyperglycaemia (> 180 mg/dl) compared with placebo [124]. Another recent RCT in coronary artery bypass patients, reported that CHO significantly reduced myocardial injury [125].

Faster surgical recovery and better postoperative well-being from CHO still remains controversial, while few data so far support an effect on postoperative morbidity or mortality from this treatment. In a recent Cochrane Review, 27 trials involving 1976 participants were included [126]. Trials were performed in Europe, China, Brazil, Canada and New Zealand and involved patients undergoing elective minor and major abdominal surgery, orthopaedic surgery, cardiac surgery and thyroidectomy. Overall, the administration of preoperative carbohydrate was associated with a small reduction in hospital stay (MD − 0.30 days, 95% CI − 0.56 to − 0.04) compared with the placebo or fasting group. Patients undergoing major abdominal surgery had a greater absolute decrease in LOS (MD − 1.66 days, 95% CI − 2.97 to − 0.34). However, the heterogeneity observed in average LOS, and the variation in study quality makes the interpretation of these results difficult.

Based on two trials including 86 participants, preoperative carbohydrate treatment was also, in this review, associated with shortened time to passage of flatus when compared with placebo or fasting, as well as increased postoperative peripheral insulin sensitivity.

Oral fluids including CHOs may not be administered safely in patients with documented delayed gastric emptying or gastrointestinal motility disorders as well as in patients undergoing emergency surgery. Although gastric emptying has been reported previously to be normal in obese patients [127], diabetics when given with their normal diabetic medication [128], and elderly patients with acute hip fracture [129], studies are still too small and incomplete to allow routine to recommendation of this intervention in such patients. However, both obese and diabetic patients have been increasingly included in recent studies of CHO [130] and no issues with regard to safety have been reported.

See Fig. 3.

The avoidance of benzodiazepines and use of short-acting general anaesthetic agents in an opioid-sparing ERAS Pathway allow rapid awakening with minimal residual effects. Propofol for induction of anaesthesia, combined with short-acting opioids such as fentanyl, alfentanil, sufentanil or remifentanil infusions, if opioids are required, minimises residual effects at the end of anaesthesia. There are no strong data to support the recommendation of either anaesthetic gases or total intravenous anaesthesia (TIVA) using propofol infusions to maintain anaesthesia. The use of propofol TIVA may reduce PONV in certain patients and there are data from a large retrospective study suggesting a beneficial effect of propofol on cancer outcomes, but no definitive recommendation can be made for this currently [131]. In intubated patients under general anaesthesia, using short-acting inhalational agents such as sevoflurane or desflurane in oxygen-enriched air is standard practice around much of the world [132]. Nitrous oxide is normally avoided due to its delaying effects on the bowel although the increased risk of PONV can be markedly reduced with standard PONV prophylaxis [133].

Cerebral Function Monitoring using bi-spectral index (BIS) and maintaining a target between 40 and 60 can reduce the risk of awareness in high-risk patients [134]. The use of BIS or newer burst suppression monitoring to avoid overdose of anaesthesia in the elderly may have a role in reducing the risk of postoperative delirium and postoperative cognitive dysfunction in this patient population [135].

Laparoscopic and robotic surgery requires insufflation of the peritoneum to create space for operating. High intra-abdominal pressure can worsen cardiac function, impede ventilation and reduce renal blood flow [136]. There is some evidence in certain patients suggesting that maintaining muscle relaxation of the abdominal muscles (a term called ‘deep block’) may allow operating at lower pressure while maintaining intra-abdominal space for surgery [137]. Reducing the intra-abdominal pressure below 10–12 mmHg may result in a reduction in the physiological effects of pneumoperitoneum leading to a reduction in aortic afterload, improvement in renal blood flow and lower peak airway ventilator pressures [138].

There is evidence to support that cumulative dosing of intermediate muscle relaxants increases the risk of postoperative pulmonary complications [139]. Neuromuscular monitoring should be a standard of care with acceleromyography (objective monitoring) being more accurate than basic peripheral nerve stimulators. Reversal of neuromuscular block to a train-of-four (TOF) ratio of 90% is important to avoid residual paralysis and risk of postoperative pulmonary complications [140]. Sugammadex reverses rocuronium and vecuronium rapidly and predictably by encapsulating the molecules responsible for paralysis. Neostigmine is an alternative option for reversal due to its anticholinergic effect. If correctly dosed, sugammadex reduces the risk of residual neuromuscular block [141].

The aim of intravenous fluid therapy is to maintain intravascular volume, cardiac output and tissue perfusion while avoiding salt and water overload. Most patients require crystalloids at a rate of 1–4 ml/kg/h to maintain homoeostasis [142]. However, some patients require volume therapy where goal-directed boluses of intravenous solutions (usually a colloid) aimed at maintaining central normovolaemia by utilising changes in stroke volume measured by a minimally invasive cardiac output monitor to optimise the patients on their individual Frank–Starling curve [143, 144]. Fluids are administered to treat objective evidence of hypovolaemia, and consequently improve intravascular volume and circulatory flow [145]. Although the earlier studies on goal-directed fluid therapy (GDFT) showed a significant improvement in outcome in terms of reduction in complications, shorter duration of ileus and reduced LOS, more recent studies performed within the context of enhanced recovery programmes showed no difference in outcome [146‐148]. Using this concept of GDFT in the setting or conventional care versus enhanced recovery protocols, a recent meta-analysis that included 23 studies with 2099 patients has generated interesting results [149]. Overall, GDFT was associated with a significant reduction in morbidity, LOS, intensive care LOS and time to passage of faeces. However, no difference was seen in mortality, return of flatus or risk of paralytic ileus. If patients were managed within enhanced recovery pathways, the only significant reductions were in intensive care LOS and time to passage of faeces. If managed in a traditional care setting, a significant reduction was seen in both overall morbidity and total hospital LOS. Hence, within ERAS programmes, it may not be necessary to offer all patients GDFT, and this should be reserved, after risk stratification, for high-risk patients or for patients undergoing high-risk procedures [142]. Arterial hypotension should be treated with vasopressors when administering intravenous fluid boluses fails to improve the stroke volume significantly (stroke volume > 10%) [150, 151]. Inotropes should be considered in patients with reduced contractility (cardiac index < 2.5 L/min) to achieve adequate oxygen delivery [151].

The importance of maintaining normothermia in patients (a temperature of 36 °C or over) undergoing major surgery including colorectal surgery is well recognised [152]. Both general anaesthesia and neuroaxial anaesthesia affect thermoregulation by impairing vasoconstriction and shivering, causing temperature redistribution from the core to the periphery, leading to heat loss in excess of heat production [153]. Even mild inadvertent perioperative hypothermia (IPH) has been associated with adverse effects: in a meta-analysis with a median temperature of 35.6 °C, blood loss was increased by 16% and blood transfusion rate by 22% [154]. Other effects may include vasoconstriction, increased afterload, myocardial ischaemia and cardiac arrhythmias, reduction in splanchnic blood flow and reduced drug biotransformation. The problems extend well into the postoperative period too, where there may be shivering with a concomitant increase in oxygen consumption, a prolonged stay in the post-anaesthetic care unit (PACU), an increase in rates of infection and a prolonged hospital stay. Patients at higher risk of IPH or its sequalae include ASA 2-5, preoperative hypothermia, those undergoing combined regional and general anaesthesia, major surgery and those at risk of cardiovascular complications [155].

Accurate measurement of temperature is fundamental. Core temperature measurements are best carried out directly (or using a direct estimate) rather than using indirect estimate. Various methods are used such as nasopharyngeal measurement (with the probe inserted 10–20 cm) [153]. More recently the zero heat-flux (deep forehead) thermometry is also recommended [155] and has been the subject of a separate recent review, with over 500 patients from 7 studies confirming its reliability [156]. There are many methods described to conserve body temperature, including warming and humidification of anaesthetic gases, warming IV and irrigation fluids and forced air warming blankets and devices. In addition, the ambient temperature should be at least 21 °C while the patient is exposed prior to active warming starting [155].

While heat loss in laparoscopic surgery is reduced when compared with open surgery, hypothermia may still occur due to cold, dry carbon dioxide used for insufflation. A recent meta-analysis analysed 13 studies and demonstrated that the use of warmed and humidified CO2 was associated with a significant increase in intraoperative core temperature (mean change 0.3 °C) [157]. However, a Cochrane review looked at 22 studies with 1428 participants, and while confirming the above preservation of temperature and demonstrating a reduced post-anaesthesia care unit (PACU) stay, commented that the data were heterogeneous and when low risk of bias studies only were included, the PACU stay was not significantly reduced. Overall there was no improvement in patient outcome, reduction in lens fogging, etc., and thus its use was not supported [158].

Another area to minimise IPH is the use of prewarming. Recent reviews supported this with significantly higher temperatures perioperatively [159, 160] unless this would delay emergency surgery, although the practicalities of this may not be easy to overcome.

Minimally invasive surgery (MIS) for both colonic and rectal resection is well established and in many countries, it has become the standard of care. The extent to which it has replaced open surgery varies widely but in European countries where data collection is good such as Denmark (Danish colorectal cancer group 2016) and Holland [161] the reported proportion of colonic and rectal cancer surgery undertaken with minimally invasive techniques is as high as 90% with conversion rates of < 10%. Some countries have achieved this through centralisation of services and others such as the UK have undertaken formalised centrally funded training programmes aimed at safely introducing new technologies while avoiding a rise in complications related to the learning curve [162].

There have been several RCTs [163‐169] of laparoscopic versus open surgery for colorectal cancer, which generally reveal an advantage in favour of laparoscopy for recovery, LOS, blood loss and complications. There is variable evidence of an oncological advantage but no evidence of an oncological disadvantage. Improved survival after laparoscopic surgery has been demonstrated in two trials [168, 169] and a large national audit [170]. Cochrane reviews of the available data concerning short and long-term outcomes also support the results of the trials [171‐173]. There is no evidence of a difference in survival comparing laparoscopic and robotic surgery [174], but data on long-term survival in robotic surgery are still sparse.

There have been two more recent non-inferiority trials published [175, 176] of laparoscopic versus open surgery for rectal cancer that use similar methodologies and use a composite score of specimen quality as the primary outcome. Non-inferiority of laparoscopic approach was not established in either trial but no long-term oncological results are yet available.

For colonic resection, the options are predominantly standard laparoscopy with no evidence, introducing robotic technology adds any advantage but increases costs considerably [177]. Variations such as single-port surgery also offers little advantage over multiport or reduced port surgery but is practiced effectively by some clinicians who report better cosmesis and reduced postoperative pain [178] although the evidence for this is weak. In both colon and rectal surgery, hand-assisted laparoscopy has been of historical interest but is not necessary in modern surgery.

For rectal resection, robotic surgery and laparoscopy combined with a trans-anal approach to the rectum [179] have developed as alternatives to standard laparoscopy. Robotic surgery for rectal cancer has been subjected to a meta-analysis and a RCT. The meta-analysis [180] showed no significant difference in any outcomes measure compared with standard laparoscopy except conversion rate. An RCT showed no significant difference in the primary outcome measure of conversion and the trial has also confirmed higher cost and that robotic rectal resection was not cost-effective [181]. Several systematic reviews of the trans-anal approach to rectal cancer [182‐185] reveal no difference in specimen quality or anastomotic leak rates compared with laparoscopic and open surgery. A large prospective registry of cases has revealed anastomotic failure rates and specimen quality not dissimilar to databases of standard laparoscopy [186]. An RCT comparing the trans-anal with standard laparoscopic approach (COLOR III) has been initiated [187].

The focus on the different minimally invasive approaches is on improving the cancer-related outcomes, reducing the morbidity of pelvic surgery and reducing conversion rates. However, all have a similar capacity to reduce the trauma and immunological impact of surgery compared with an open approach. MIS is both an important enabling technology for many of the elements of ERAS and an independent predictor of good outcome [188]. It independently has the capacity to reduce complications, which is the ultimate goal of an ERAS programme. MIS enables reduced pain and opiate requirement, early mobilisation, less impact on fluid shifts and reduced ileus.

The relative influences of laparoscopy and enhanced recovery protocols have been compared in several trials [189‐191]. The LAFA study [191] was a multicentre RCT, which randomised patients to laparoscopic and open segmental colectomy and ‘fast track’ and ‘standard care’ within nine Dutch centres. The median hospital stay was 2 days shorter after laparoscopic resection and the best outcomes with the least impact on the immune system was in the group receiving both minimally invasive surgery and enhanced recovery protocol. Regression analysis showed that laparoscopic surgery was the only predictive factor to reduce hospital stay and morbidity. The EnRol trial [190] randomised between laparoscopic and open colorectal resection within an enhanced recovery protocol and measured physical fatigue at 1 month as its primary outcome. Median hospital stay was 2 days shorter after laparoscopic surgery. A meta-analysis of protocol-driven care and laparoscopic surgery for colorectal cancer concluded that the combination reduced colorectal cancer surgery complications, but not mortality [192].

The use of a drain in the pelvic cavity after rectal surgery or the peritoneal cavity after rectal or colonic surgery has historically been advocated to evacuate or prevent blood or serous collections and to prevent or detect anastomotic leakage.

In 2004, a Cochrane systematic review compared the safety and effectiveness of routine drainage after elective colorectal surgery. The primary outcome was clinically anastomotic leakage [193] and included 6 RCTs enrolling 1140 patients, but only 2 RCTs (191 patients) separated low rectal anastomoses. The authors could not find a significant difference in outcomes. In 2005, a meta-analysis of pelvic drains in rectal surgery [194] including three RCTs reported no effect on anastomotic leakage rate or overall outcome. A more recent systematic review and meta-analysis of 11 RCTs with 1803 patients concluded that pelvic and peritoneal drains did not decrease anastomotic leakage (clinical or radiological), mortality, wound infection, nor reoperation rates [195]. Lastly, a recently published RCT [196], including 469 patients, showed that the use of a pelvic drain after rectal surgery for rectal cancer conferred no benefit to the patient.

See Fig. 4.

Nasogastric tubes have been in use with the aim of reducing postoperative discomfort from gastric distention and vomiting. However, all recent data show that the routine use of a NG tube has no positive, but rather a series of negative effects.

A recent meta-analysis of RCTs including 1416 patients undergoing colorectal surgery showed that pharyngolaryngitis and respiratory infections occurred less frequently if postoperative nasogastric decompression was avoided but that vomiting was more common [197]. A Cochrane meta-analysis of 33 trials with > 5000 patients undergoing abdominal surgery confirmed significant differences by an earlier return of bowel function and a decrease in pulmonary complications if a nasogastric tube was avoided [198]. A Dutch study with > 2000 patients found that the use of nasogastric decompression after elective colonic surgery declined from 88 to 10% without increases in patient morbidity or mortality [199]. In an RCT, patients not receiving nasogastric tubes tolerated oral intake earlier suggesting that routine nasogastric decompression may unnecessarily delay important nutrition in the postoperative period [200, 201]. A meta-analysis comprising seven recent RCTs (587 patients) comparing the outcomes following early oral feeding versus traditional oral feeding with gastric decompression by tube found that early oral feeding reduced hospital LOS and total of postoperative complications significantly; there were no significant differences in anastomotic dehiscence, pneumonia, wound infections, rate of nasogastric tube reinsertion, vomiting or mortality [202].

The routine insertion of a nasogastric tube during elective colorectal surgery should be avoided except for evacuating air that may have entered the stomach during ventilation by the facial mask prior to endotracheal intubation. An orogastric tube will suffice for this purpose and is recommended in laparoscopic cases to prevent inadvertent gastric injury. If placed during surgery, nasogastric tubes should be removed before the reversal of anaesthesia. There is still a roll for inserting an NG tube in patients with postoperative ileus refractory to conservative management to decompress the stomach and reduce the risk of aspiration.

Postoperative analgesia resulting in adequate pain control is essential in enhanced recovery pathways in colorectal surgery [9, 10, 200, 203, 204]. Although colon and rectal surgery (open and laparoscopic) differ considerably regarding technique, surgical trauma and early outcome, opioid avoiding or sparing techniques in both types of surgery are associated with early mobilisation, fast return of bowel function, fewer complications and a reduction in LOS [9, 10, 200, 203, 204]. Therefore, the key is to avoid opioids and apply multimodal analgesia in combination with epidural analgesia (in open surgery) when indicated. In fact, this multimodal strategy should ideally be included in the intraoperative period already and be a continuum postoperatively [9, 10, 200, 204].

The benefit of using a multimodal approach to pain management is based on the concept that several multiple pain reducing mechanisms will improve pain control while avoiding the side effects of each drug. Paracetamol is a basic part of this strategy and can be administered easily [203]. NSAIDS are also vital and key opioid-sparing component in multimodal analgesia. However, there is still debate whether NSAIDs are associated with an increased incidence of anastomotic leakage, but literature shows inconclusive evidence to avoid NSAIDs in colorectal surgery patients other than the regular contraindications [4, 205]. COX 2 drugs that do not effect platelet aggregation can be used if surgeons are concerned for bleeding. Several studies investigated opioid-sparing techniques with systemic additives like lidocaine infusions, α2-agonists like dexmedetomidine, ketamine, magnesium sulphate, high dose steroids or gabapentinoids [9, 10, 200, 206‐210]. Lidocaine and dexmedetomidine infusions do appear to reduce postoperative pain in colorectal surgery compared with placebo [207, 209, 210]. However, there are limited studies that have systematically assessed the combination of these systemic additives on adverse events, outcomes and the analgesic effects compared with other techniques or in combination with epidural analgesia and TAP blocks (discussed item 18d) [200]. In both colon and rectal surgery, the use of other additives seems to have promising pain relieving potential, but needs to be investigated more extensively regarding efficacy and safety. However, multimodal analgesia is the backbone to reduce opioids in both open and laparoscopic colorectal surgery. Surgical site infiltration or more specific port-site local infiltration with local anaesthetics does appear to reduce postoperative pain compared with placebo, but limited data are available [211].

It is well established that epidural blockade with local anaesthetics, initiated before and continued during and after surgery, is a successful modality to minimise the neuro-endocrine and catabolic response to surgery [212]. As one result, insulin resistance, an expression of surgical stress, is attenuated [213]. Epidural blockade has also shown to minimise postoperative protein breakdown [214]. This effect is particularly useful when patients are fed in the immediate postoperative period as postoperative nitrogen balance is normalised and protein synthesis facilitated [215, 216]. Current data on metabolic effects have been mainly shown for open surgery and data for laparoscopic surgery are yet to be found.

Thoracic epidural analgesia (TEA) (T7-T10) remains the gold standard in patients undergoing open colorectal surgery. Several RCTs and meta-analysis have demonstrated superior analgesia compared with patients receiving systemic opioids [217, 218]. Supplementary analgesia is required in patients undergoing abdominal perineal resection, in which perineal pain (S1–S3 dermatomes) is not controlled by TEA. Lumbar epidural blockade is discouraged because of insufficient upper sensory block covering the surgical incision, lack of blockade of sympathetic fibres and risk of lower limb motor block and urinary retention [212].

The same analgesic benefits have not been demonstrated in patients undergoing laparoscopic colorectal surgery [219] and epidurals may even increase LOS in patients undergoing minimally invasive surgery. In fact, alternative co-analgesic techniques, such as intravenous lidocaine [210, 220‐222], spinal analgesia [223‐227], abdominal trunk blocks (ultrasound guided or under direct laparoscopic guidance), intraperitoneal local anaesthetic [228, 229] or continuous wound infusion of local anaesthetics [230‐232] have shown to provide adequate analgesia, similar to those obtained with TEA [233], but superior to those provided by systemic opioids alone. TEA might still be valuable in patients with chronic pain or in patients in whom the risk of conversion to laparotomy is high. The results of an RCT comparing TEA with intravenous lidocaine in patients undergoing laparoscopic colorectal surgery demonstrated that TEA might still be advantageous in the first 48 h after rectal surgery, as rectal extraction and anastomosis was performed through a 8–10 cm Pfannenstiel incision [234]. Awareness of the type of laparoscopic approach used can assist physicians to decide whether TEA can still be valuable in patients undergoing laparoscopic colorectal surgery.

A continuous epidural infusion of a mixture of local anaesthetic and lipophilic opioids provides better analgesia than local anaesthetic or opioids alone [217, 218, 235]. The addition of adjuvants such as clonidine [236, 237] or epinephrine (1.5–5 µg/ml) [238, 239] can also be added to improve segmental analgesia and reduce certain opioids side effects. A mixture containing local anaesthetic with epidural morphine instead of lipophilic opioids can provide better analgesia in patients with long midline incision. Because of its pre-emptive analgesic effect [240], TEA should be initiated before surgery and continued in the intraoperative and postoperative period, for 48–72 h. A disadvantage of the use of TEA is the primary epidural failure rates that continue to remain high in some reports (ranging between 22 and 32%). Additional methods to correctly identify the epidural space (i.e. epidural stimulation or wave form analysis) and increase the success rate of epidural blocks can be employed [241, 242]. Appropriate postoperative support such as a pain team is also important to troubleshoot analgesia issues related to TEA to improve efficacy.

Postoperative non-analgesic outcomes

Despite the results of the largest multicenter RCT assessing the impact of combining TEA with general anaesthesia on 30-day morbidity or mortality in high-risk patients after major open gastrointestinal surgery did not show any benefit [237], several subsequent meta-analyses have shown that TEA accelerates the recovery of bowel function after colorectal surgery [243‐245] and reduces the risk of respiratory [245, 246] and cardiovascular complications [245]. There is, however, a higher risk of postoperative arterial hypotension and urinary retention [245]. It must be also acknowledged that the positive impact of TEA on postoperative morbidity originates from studies in open surgery with no context of an ERAS program. A recent meta-analysis including 5 RCTs of patients undergoing laparoscopic colorectal surgery and all treated with an ERAS programme does not demonstrate the same benefits [247]. Some recent evidence also demonstrates that TEA has no impact [248] or even delays [219, 247, 249] hospital discharge in patients undergoing laparoscopic colorectal surgery. This delay might be due to a higher incidence of hypotension, urinary retention or motor blockade requiring additional postoperative care [219, 250]. The impact of TEA on colorectal cancer recurrence and metastasis [251, 252] remains to be investigated further, especially in the context of an ERAS program.

Spinal anaesthesia has a high efficacy and relatively low complication profile [253]. It has been used to facilitate ultra-rapid recovery after laparoscopic colorectal surgery by minimising opioid consumption within an ERAS protocol [226]. As compared with epidural anaesthesia, the patient can be mobilised sooner and is at less risk of hypotension and fluid overload that is a risk due to the sympathetic block induced by continuous thoracic epidural analgesia [219]. A combination of local anaesthetic such as bupivacaine 0.5% and long-acting opioid (such as diamorphine or morphine) is usually used with the total volume dosing in the range of < 2.0 ml to avoid high spinal block. In addition to the local anaesthetic effect, spinals have been shown to reduce the endocrine-metabolic stress response but only for the duration of action of the local anaesthetic where after it returns to levels of controls [223]. The addition of a long-acting opioid has the benefit of reducing morphine requirements postoperatively by up to sixfold with the ability to mobilise patients very soon after surgery once the motor block has worn off [225]. In another study, although early recovery was superior there was no benefit on LOS compared with intravenous morphine alone [227]. The main concern of using intrathecal opioids is that of delayed respiratory depression. Commonly used doses are at the lower end of clinical practice: 300–500 mcg of diamorphine or 100–150 µg of preservative free morphine. Similar monitoring should be used as if the patient was using a patient-controlled analgesia pump.

The use of lidocaine infusions to reduce opioid use and nausea in colorectal surgery is now well established [210]. Published dosing ranges from 1.5 to 3 mg/kg/h depending on the bolus given (0 to 1.5 mg/kg) [254, 255]. Plasma lidocaine concentrations achieved are similar to those when running an epidural infusion (approximately 1 μM). Toxicity is related to the plasma concentration and appears to be rare, but monitoring in the postoperative period is important [256]. Continuous ECG monitoring is advised and nurses should be aware of symptoms of local anaesthetic toxicity such as tinnitus, blurred vision, dizziness, tongue paraesthesia and perioral tingling.

The analgesia benefit is in both open surgery and laparoscopic colorectal surgery. This beneficial effect appears to last longer than the infusion itself. Studies have been inconsistent in the duration of use of the infusion with some stopping at the end of surgery while others continue between 12 and 24 h postoperatively [254‐256].

The incidence of postoperative ileus, which is a major cause of delayed hospital discharge in colorectal patients, is reduced in some studies. It is currently unclear whether this is due to the reduction in opiates or if there are other direct beneficial actions on the bowel or an anti-inflammatory effect [254].

The role of epidural analgesia within the setting of an enhanced recovery programme has been questioned, especially with regard to laparoscopic operations [219, 257]. Interest in local anaesthetic abdominal walls blocks, as a component of multimodal analgesia, has thus increased.

Transversus abdominis plane (TAP) blocks are the most widely studied. Since the initial description, in 2001 [258], as the classic landmark-based technique, multiple variations have been described, including 2-point, 4-point, ultrasound-guided and laparoscopic-visualised blocks. TAP blocks provide analgesic coverage to the anterior abdominal wall from T10 to L1 [259] and have been demonstrated to provide an opioid-sparing approach in colorectal surgery [260]. As TAP blocks only provide analgesia reliably below the umbilicus, subcostal and rectus blocks are adjuncts, which can cover the upper abdomen.

An early Cochrane review of transversus abdominis plane (TAP) blocks found 5 heterogeneous studies, no comparisons with other methods of analgesia, and limited evidence of reduced opioid use [261]. A review of studies up to early 2016 of peripheral nerve blocks again demonstrated a lack of data [211]. There have been more recent RCTs indicating the benefits of TAP blocks in abdominal surgery in multiple specialties including gynaecologic, general, bariatric and transplant surgery [262‐266] and also specifically in colorectal surgery with less opioid use, faster resumption of GI tract function and recovery [267, 268] although others have not shown benefits [269]. One major weakness with abdominal blocks is short duration. Conventional bupivacaine and ropivacaine used in traditional TAP blocks have a short half-life (usually 8–10 h) [270]. Various methods have been used to increase the duration of abdominal wall blocks including mixing standard local anaesthetics with dexamethasone [271], dextran [272] and use of infusion catheters [266]. Liposomal bupivacaine, initially approved for infiltration and not for nerve blocks, is currently approved for TAP blocks as the target is an anatomical musculofascial plane between the internal oblique and transversus abdominis muscles not a specific nerve [273].

Older data in traditional perioperative care showed that without thromboprophylaxis there was a 30% incidence of asymptomatic deep vein thrombosis (DVT) after colorectal surgery [274]. Recent reviews of risk factors (high-risk patients) include ulcerative colitis, advanced malignancy (Stage III + IV), hypercoaguable state, steroid use, advanced age and obesity [275].

All patients benefit from mechanical thromboprophylaxis achieved with compression stockings and/or intermittent pneumatic compression (ICP) during hospitalisation or until mobilised as proven measure to reduce the incidence of DVT after general surgery even in the absence of pharmacological treatment [OR 0.27 (0.20–0.38)] [276‐278].

Pharmacological thromboprophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin has been shown to reduce the incidence of symptomatic venous thromboembolism and also overall mortality with a very low risk of bleeding complications. A single administration of LMWH per day was as effective as twice-daily administration [279, 280]. A combination of ICP together with pharmacological prophylaxis decreased the incidence of pulmonary embolism (PE) and DVT when compared with a single modality at the expense of higher risk for bleeding complications when comparing to ICP alone [277].

The usefulness of extended thromboprophylaxis (ETP) for 28 days after colorectal surgery relies on data from traditional perioperative care. Based on a Cochrane meta-analysis of four RCTs [279], previous ERAS recommendations and other guidelines (NICE, NHMRC) recommended ETP (28 days) for patients having major cancer surgery in the abdomen or pelvis. However, with changes in surgical techniques from open to minimally invasive and advances towards less stress with modern anaesthesia, the extended prophylaxis regime has been questioned. A recent report indicates that only 8–27% of colorectal surgeons followed these traditional recommendations [281]. Furthermore, incidence of symptomatic VTE, DVT and PE after discharge is reported to be very low at 0.60–0.73%, 0.29–0.48% and 0.26–0.40%, respectively, in the three largest and recent cohort studies including 236,066 patients [275, 281]. Also, in non-cancer surgery, such as after hip replacement surgery, 90-day risk for VTE was indifferent for short thromboprophylaxis (1–6 days) as compared with standard (> 7 days) and extended (> 28 days) regimens [282]. So far, RCTs investigating the benefit or risks of ETP versus shorter prophylaxis show no reduction in symptomatic DVT, symptomatic pulmonary emboli or VTE-related death [281]. However, these studies are heavily underpowered and cannot answer this clinical question. The clinical value in that the same studies showed that subclinical thrombosis were several times more frequent with in-house short-term prophylaxis compared to 4 weeks is uncertain [281]. Given the reduction in stress using minimally invasive techniques and several other stress-reducing ERAS elements combined with the almost immediate mobilisation of the patients the relevance of older studies can be questioned and needs to be revisited. Lastly, no specific data are available supporting the use of ETP in low-risk ERAS patients.

However, given the seriousness of the complications, the risk factor spectrum for thrombosis among colorectal surgery patients and the lack of data showing no risk or a benefit from shorter or no prophylaxis, the recommendation needs to continue to rely on current old but available evidence.

Patients undergoing major colorectal surgery should have (I) mechanical thromboprophylaxis by well-fitting compression stockings and/or intermittent pneumatic compression until discharge and (II) receive pharmacological prophylaxis with LMWH once daily for 28 days after surgery.

Intravenous fluid therapy is usually not necessary after the day of operation for most patients undergoing colorectal surgery. Patients should be encouraged to drink when they are awake and free of nausea after the operation and an oral diet can usually be started within 4 h after surgery [202, 283]. If oral fluid intake is tolerated, intravenous fluid administration should be discontinued as soon as feasible, preferably at least by day 1 POD and should be restarted only if clinical indications exist. In such situations and in the absence of surgical losses, physiological maintenance fluids should be given, when indicated, at a rate of 25–30 ml/kg per day with no more than 70–100 mmol sodium/day, along with potassium supplements (up to 1 mmol/kg/day) [284]. As long as this volume is not exceeded, hyponatraemia is very unlikely to occur despite the provision of hypotonic solutions [285, 286]. Any ongoing losses (e.g. vomiting or high stoma losses) should be replaced on a like for like basis for what is being lost in addition to the maintenance requirement. After ensuring the patient is normovolaemic, hypotensive patients receiving epidural analgesia should be treated with vasopressors rather than indiscriminate fluid boluses [287, 288]. It is important that patients are maintained in as near a state to zero fluid balance as possible in the perioperative period, as both fluid deficits and overload (of as little as 2.5 L [289]) can cause adverse effects in the form of increased postoperative complications, prolonged hospital stay and higher costs due to increased resource utilisation [6, 290, 291].

There is considerable evidence from physiological studies that large volumes of intravenous 0.9% saline cause a hyperchloraemic acidosis, interstitial fluid overload, impairment of renal haemodynamics and a reduction in urinary water and sodium excretion as a result of a reduction in renal blood flow and glomerular filtration rate [292‐296].

Large observational, propensity-matched studies have suggested 0.9% saline, because of the high chloride content, may cause harm, especially to the kidney in patients undergoing surgery [297], critically ill patients [298] and those with the systemic inflammatory syndrome [299]. Another propensity-matched study has suggested that up to 22% of patients develop acute hyperchloraemia (> 110 mmol/L) in the postoperative period and that this is associated with an increased risk of 30-day mortality and longer LOS than those who do not develop hyperchloraemia [300]. However, as there are no large-scale RCTs yet comparing 0.9% saline with balanced crystalloids in a surgical population, the current evidence cannot be regarded as high. In addition, a recent meta-analysis that was limited by imprecision and studies of a small sample size has shown that for unselected critically ill or perioperative adult patients there was no benefit evidence of low versus high chloride solutions [301].

Oliguria in the adult is usually defined as urine output < 0.5 ml/kg/h, or < 500 ml in 24 h, in an adult. However, urine output and oliguria alone are not reliable indicators of hypovolaemia in the first 48 h after surgery as the postoperative metabolic response to stress leads to renal vasoconstriction and physiological salt and water retention [302]. Oliguria should be assessed carefully (fluid balance chart), and a thorough clinical examination performed before commencing intravenous fluid resuscitation for dehydration or hypovolaemia, as excess fluid administration has been associated with acute kidney injury [303, 304]. If the patient does not demonstrate clinical signs of hypovolaemia (e.g. tachycardia, hypotension, sweating, confusion and decreased capillary return), it is useful to average urine output out over 4 h. A conservative fluid regimen does not appear to increase the risk of postoperative oliguria or acute kidney injury [305‐308]. In addition, supplemental intravenous fluids or diuretics do not improve renal function or protect against acute kidney injury [304‐306, 309]. Indeed, allowing a lower urine output in the perioperative phase appears safe and results in significantly reduced administration of intravenous fluid [308].

Urinary drainage during and after colorectal surgery is used traditionally for two main reasons: prevention of urinary retention and monitoring of urine output. The duration of catheterisation is directly related to a risk of urinary tract infection (UTI) and may hinder postoperative mobilisation and should therefore be limited. In a RCT of catheter removal after major abdominal and thoracic surgery on day 1 (n = 105) versus day 4 (n = 110), the risk of UTI was markedly reduced with early removal (2 vs 14%) and the risk of retention was low in both groups (8 vs 2% single in–out catheterisation; 3 vs 0% 24-h catheterisation) [310]. A large observational study (n = 513) confirms low retention rates (14%) in patients undergoing colorectal surgery within an established ERAS protocol that included early catheter removal [311]. This study highlighted male gender and postoperative epidural analgesia as important independent predictors of retention. Thus, tailored removal of the bladder catheter can be guided by such risk factors.

The importance of closely monitoring the perioperative urine output to avoid oliguria has recently been challenged. In renal medicine, oliguria is defined as a daily urine output < 400 ml, or approximately < 0.2 ml/kg/h in average weight adults [312]. In the perioperative setting, oliguria is traditionally defined as a urine output < 0.5 ml/kg/h, and additional fluid is administered to reach above this target. There are no data to support this practice. A recent RCT demonstrated that fluid therapy guided by the lower target of 0.2 ml/kg/h during and after colorectal surgery is not only safe but also spares a significant volume of intravenous fluids compared with the standard target of 0.5 ml/kg/h [308]. An hourly measurement of urinary output is therefore by itself no longer an indication for bladder catheterisation.

Patients undergoing pelvic surgery appear to be at particular risk of postoperative urinary retention. A RCT performed in the 1990s found retention rates of 25% versus 10% when the transurethral catheter was removed on day 1 versus day 5 after proctectomy [313]. A more recent RCT of transurethral catheterisation for 1, 3 or 5 days after pelvic surgery (n = 118) supported a higher risk of retention with early removal (15, 5 and 10%, respectively) [314]. The 15–25% urinary retention rate associated with catheter removal on the first day after pelvic surgery suggests that delaying catheter removal in this group to 2 or 3 days is justified in this group.

Extended bladder catheterisation may be required in selected cases undergoing complex pelvic reconstructive surgery. A recent meta-analysis has confirmed that when the duration of postoperative catheterisation exceeds 5 days, a suprapubic tube or clean intermittent catheterisation are safer alternatives to the standard transurethral catheter [315].

Prolonged postoperative ileus is a major contributor to patient discomfort, delayed discharge and increased cost; hence, its prevention is a key objective of enhanced recovery protocols. Many of the core elements of these protocols, such as (1) limiting opioid administration through application of multimodal analgesia techniques (including use of mid-thoracic epidurals and peripheral nerve blocks), (2) use of minimally invasive surgery, (3) eliminating routine nasogastric tube placement, and (4) maintaining fluid balance including goal-directed fluid therapy, can limit the duration of postoperative ileus [9]. These elements are supported by high-quality evidence and are discussed elsewhere in these guidelines. This section focuses on additional interventions and pharmacological agents that specifically target ileus.

Peripherally acting µ-opioid receptor (PAM-OR) antagonists with limited ability to cross the blood–brain barrier include alvimopan, methylnaltrexone, naloxone and naloxegol. These agents can ameliorate opioid-induced bowel dysfunction without reversing analgesia through central µ-opioid receptor antagonism. Of these agents, alvimopan is the best studied in the context of limiting duration of postoperative ileus. This drug is currently approved by the US Food and Drug Administration (FDA) but not universally available, for the indication of accelerating upper and lower gastrointestinal recovery following partial large or small bowel resection with primary anastomosis. However, in a recently published systematic review of eight randomised, placebo-controlled, clinical trials evaluating of the efficacy of alvimopan in reducing duration of postoperative ileus following major abdominal surgery, six of these studies found a reduction with alvimopan administration, whereas two found no difference among study groups [316]. Each of these studies were graded as moderate or low in quality and tended to focus on patients undergoing open surgery. In addition, two randomised, placebo-controlled, clinical trial found no difference between methylnaltrexone and placebo in decreasing duration of postoperative ileus following segmental colectomy [317]. Conflicting data on efficacy, costs and concerns over cardiovascular complications, limit recommendation for routine use of these agents, particularly in the context of increasingly wide-spread application of opioid-sparing anaesthesia and analgesia techniques and of minimally invasive surgery.

Numerous RCTs have evaluated the efficacy of postoperative gum chewing in reducing duration of postoperative ileus. A Cochrane review of this topic concluded that, while gum chewing may be associated with mild reductions in ileus duration, the evidence on this topic is largely limited to small, poor quality studies [318]; in particular, most studies lack appropriate blinding of patients and investigators [319]. Further, the benefits of gum chewing in the context of ERAS pathways have been unclear. Recently, a well-designed, large-scale multicentre RCT evaluating the effects of postoperative gum chewing in patients undergoing abdominal surgery and on ERAS pathways was reported [320]. Gum chewing had no impact on time to first postoperative flatus or bowel movement, on postoperative length of stay, or on incidence of postoperative complications. Thus, while gum chewing is associated with little, if any, harm in postoperative patients, currently available evidence does not support the efficacy of gum chewing in reducing duration of ileus in patients undergoing abdominal surgery on ERAS pathways. Accordingly, its routine inclusion as a component of ERAS care is not recommended.

Various other agents that have been tested for efficacy in reducing duration of postoperative ileus, including laxatives and coffee. In prospective controlled trials, reductions in various indices of postoperative ileus have been observed to occur with oral bisacodyl administration in patients undergoing colorectal surgery [321], with oral magnesium oxide administration in patients undergoing hysterectomy [322], with oral daikenchuto (a traditional Japanese herbal medicine) administration in patients undergoing gastrectomy [323], and with oral coffee administration in patients undergoing colorectal surgery [324]. Interestingly, another RCT revealed greater reductions in indices of postoperative ileus with de-caffeinated coffee administration than with caffeinated coffee in patients undergoing left-sided laparoscopic colectomy [325]. These studies have methodological limitations, and confirmatory studies are needed before routine application is recommended. Nevertheless, we recommend against withholding coffee from postoperative patients who tolerate oral liquids.

A hallmark of the physiological response to surgical trauma is insulin resistance, or so-called pseudodiabetes of injury, which persists for several weeks after elective surgery [326]. This leads to an osmotic shift of fluid into the vascular space and an increased availability of glucose for glucose-dependent tissues such as white blood cells and the brain. Although hyperglycaemia after surgery was reported in 1934, it was not until 2001 that negative consequences of perioperative hyperglycaemia were fully recognised, with the publication of a large RCT comparing permissive hyperglycaemia with strict glycaemic control by intensive insulin therapy [327]. Morbidity and mortality were decreased in the intervention group.

No further trials of strict glycaemic control in surgical patients have been reported, although a subgroup analysis of trauma patients in a multi-centre trial shows similar results [328]. Intensive insulin therapy can therefore not be recommended in routine colorectal surgery, but these trials do highlight the clinical risks posed by perioperative hyperglycaemia.

In elective surgery, there are opportunities to prevent insulin resistance from developing in the first place. Several interventions that blunt insulin resistance are part of the ERAS care pathway, including oral preoperative carbohydrate treatment, laparoscopic surgery and thoracic epidural analgesia. A recent large RCT showed that preoperative carbohydrates moderated postoperative glucose concentrations and reduced the need for insulin [124]. Two trials have shown that surgery within ERAS is associated with partial or complete attenuation of key stress responses. In the first, unchanged postoperative nitrogen losses, neutral nitrogen balance, minimal insulin resistance and preserved normoglycaemia during feeding were found after major open colorectal surgery [329]. A recent four-way randomised study of laparoscopic versus open surgery and ERAS versus traditional care assessed the independent effects of laparoscopic surgery and ERAS [191, 330]. ERAS was associated with a blunted stress mediator response, measured by growth hormone concentration changes. Nevertheless, observational studies have revealed that hyperglycaemia remains prevalent during the postoperative period, in particular in patients with an increased preoperative haemoglobin A1c [331]. The association to postoperative adverse outcomes appears to be the strongest in subjects without a diagnosis of diabetes [332].

It has been well established that any delay in the resumption of normal oral diet after major surgery is associated with increased rates of infectious complications and delayed recovery [333]. Early oral diet has been shown to be safe 4 h after surgery [3] in patients with a new non-diverted colorectal anastomosis. Some report that low residue diet, rather than clear liquid diet, after colorectal surgery is associated with less nausea, faster return of bowel function, and a shorter hospital stay without increasing postoperative morbidity when administered in association with prevention of postoperative ileus [334]. Spontaneous food intake rarely exceeds 1200–1500 kcal/day [331]. To reach energy and protein requirements, additional oral nutritional supplements have been shown to be useful [335].

Surgical stress can cause an acute depletion of arginine, which both impairs T cell function and wound healing [336]. This acute nutritional deficiency is potentially modifiable and has been the target of nutritional optimisation around the time of surgery. Therefore, supplementation of enteral feeds with immunomodulators such as l-arginine, l-glutamine, ω-3 fatty acids and nucleotides (immunonutrition) is thought to modify immune and inflammatory responses favourably and result in reduced postoperative infective complications and shorter LOS [337, 338]. The recent ESPEN guideline on perioperative nutrition presented an extensive review of multiple RCTs and meta-analysis and concluded that peri-or at least postoperative immunonutrition (arginine, omega 3 fatty acids and ribonucleotides) should be given to malnourished patients undergoing major cancer surgery [53]. A reduction in infectious complications was reported in favour of immunonutrition over standard ONS in two recent prospective RCTs within an ERAS protocol [339, 340].

Most patients can and should be offered food and ONS from the day of surgery. Perioperative immunonutrition in malnourished patients is beneficial in colorectal cancer surgery.

Postoperative resumption of oral intake: Moderate

Immunonutrition: Low

Postoperative resumption of oral intake: Strong

Immunonutrition: Strong (no harm)

Early mobilisation after abdominal surgery is widely regarded as an important component of perioperative care for enhanced recovery. Prolonged bed rest is associated with risk for developing pulmonary complications, decreased skeletal muscle strength, thromboembolic complications and insulin resistance [341‐343]. Early mobilisation has therefore been an integral component of enhanced recovery after surgery protocols. While there is strong evidence regarding the harmful effects of immobilisation, evidence is more limited regarding the benefit of dedicated interventions specifically designed to increase early mobilisation after surgery.

A recent systematic review of the effect of early mobilisation protocols on postoperative outcomes following abdominal and thoracic surgery evaluated a total of 8 studies [344] (including 3 RCTs and 1 prospective observational study) in abdominal surgery and 4 (including 3 RCTs and 1 retrospective observational study) in thoracic surgery. The specific outcomes of interest included postoperative complications, LOS, gastrointestinal function recovery, performance-based outcomes and patient-reported outcomes. While not all studies evaluated all outcomes, for each outcome, only one study could demonstrate a benefit for the intervention group.

The impact of early mobilisation in critically ill patients was recently demonstrated in an international multicentre randomised trial of goal-directed mobilisation versus usual care in intensive care unit patients [345]. The intervention arm included basic manoeuvres such as sitting and standing or stepping in place at the bedside. Compared with usual care, goal-directed early mobilisation was associated with a short duration of surgical intensive care unit stay and better functional mobility at discharge. Moreover, lack of early mobilisation after abdominal surgery has been associated with an up to 3.0 (95% confidence interval 1.2–8.0) fold increased in likelihood of developing a pulmonary complication [346]. Yet the applicability of these findings to patients who have few limitations for mobility following elective surgery is uncertain.

Early mobilisation is an essential component of multimodality strategies for enhanced recovery after surgery. A multivariate linear regression analysis of data collected during the LAFA trial supported the notion that mobilisation on postoperative days 1, 2 and 3 is a factor significantly associated with a successful outcome of ERAS [191]. However, despite the demonstrated effectiveness of the ERAS pathways, there remains considerable variation in the extent to which the different ERAS pathway interventions are implemented, including with respect to the implementation of early mobilisation [347, 348]. Although the degree of compliance to ERAS principles including early mobilisation has been associated with improved outcomes [203], a recently reported RCT comparing facilitated mobilisation during postoperative days 0–3 to a standard enhanced recovery programme increased out-of-bed activities but did not improve outcomes [349].

Finally, another important consideration is that failure of early mobilisation may be due to a variety of factors such as inadequate control of pain, continued intravenous intake of fluids, prolonged indwelling urinary catheter, patient motivation, and pre-existing comorbidities which are likely themselves associated with poorer outcomes, leading to question of whether the observed outcomes are associated with early mobilisation or are due to the underlying factors that lead to the inability to mobilise.

Taken together, the studies suggest that bedrest should be discouraged in favour of early mobilisation, but the allocation of additional resources to implement structured early mobilisation beyond integration into multimodal enhanced recovery protocols has not shown to be of benefit.

Early mobilisation through patient education and encouragement is an important component of enhanced recovery after surgery programmes; prolonged immobilisation is associated with a variety of adverse effects and patients should therefore be mobilised.