Enhanced Recovery After Surgery (ERAS) is an evidence-based paradigm shift in perioperative care, proven to lower both recovery time and postoperative complication rates. The role of ERAS in several surgical disciplines was reviewed. In colo- rectal surgery, ERAS protocol is currently well established as the best care. In gastric surgery, 2014 saw an establishment of ERAS protocol for gastrectomies with resulting meta-analysis showing ERAS effectiveness. ERAS has also been shown to be beneficial in liver surgery with many centers starting implementation. The advantages of ERAS in pancreatic surgery have been strongly established, but there is still a need for large-scale, multicenter randomized trials. Barriers to implementation were analyzed, with recent studies concluding that successful implementation requires a multidisciplinary team, a willingness to change and a clear understanding of the protocol. Additionally, the difficulty in accomplishing necessary compliance to all protocol items calls for new implementation strategies. ERAS success in different patient populations was analyzed, and it was found that in the elderly population, ERAS shortened the length of hospitalization and did not lead to a higher risk of postoperative complications or readmissions. ERAS utilization in the emergency setting is possible and effective; however, certain changes to the protocol may need to be adapted. Therefore, further research is needed. There remains insufficient evidence on whether ERAS actually improves patients’ course in the long term. However, since most centers started to implement ERAS protocol less than 5 years ago, more data are expected. Keywords Enhanced recovery after surgery · Perioperative care · Laparoscopy · Complications · Length of stay Introduction patient care in surgical wards to one that standardizes it based on published evidence . Inspired by Danish Pro- Enhanced Recovery After Surgery (ERAS) is an evidence- fessor of surgery Henrik Kehlet, ERAS protocol questioned based multimodal perioperative protocol focused on stress traditional perioperative care including: prolonged fasting, reduction and the promotion of a return to function . mobility limitations, mechanical bowel preparation, routine ERAS has been proven to lower both recovery time and use of drains, and the slow return to eating normally post- postoperative complication rates while being cost-effective operatively . Kehlet theorized that the avoidance of such at the same time [2, 3]. It fundamentally shifts the traditional perioperative doctrine shortens the length of hospitalization by reducing the metabolic stress, fluid overload, and insu- lin resistance placed on the body . Professors Kenneth * Michał Pędziwiatr Fearon and Olle Ljungqvist added postulates to the ERAS email@example.com protocol, developing the ERAS study group in 2001 and the 2nd Department of General Surgery, Jagiellonian University ERAS Society in 2010. The international ERAS study group Medical College, Kopernika 21, 31-501 Krakow, Poland consisted of surgeons and anesthesiologists who reviewed Centre for Research, Training and Innovation in Surgery literature and evidence of the most optimal perioperative (CERTAIN Surgery), Krakow, Poland care . They created an ERAS protocol of 20 items along Carol Davila University of Medicine and Pharmacy, Sector 1, with a database to support the implementation of these prin- Strada Dionisie Lupu 37, 030167 Bucharest, Romania ciples. The protocol divided the perioperative period, into Department of Medical Education, Jagiellonian University pre-, intra-, and postoperative time periods based on the Medical College, św. Łazarza 16, 31-530 Krakow, Poland Vol.:(0123456789) 1 3 95 Page 2 of 8 Medical Oncology (2018) 35:95 aggregation of marginal gains theory. This theory identi- in prolonged recovery and increased morbidity. The larger fies, divides, and adapts each step taken through the entire the operation, the greater the graded response of resistance. perioperative patient journey to facilitate the efficient and Despite the developing hyperglycemia, a reduction of mus- safe progress from preoperative assessment to discharge cle and fat glucose uptake occurs. The loss of lean body and rehabilitation . 2010 saw the establishment of the mass coupled with the reduced glucose uptake and storage ERAS Society with the goal of an international network of in muscle leads to reduced muscle function. This impairs regional and national expert centers that facilitated ERAS mobilization. Further, noninsulin-sensitive cells increase protocol utilization . Currently, there is growing evidence their glucose uptake. This increase can lead to several post- that ERAS is beneficial in many other disciplines including operative complications, such as infections and cardiovas- colorectal, gastric, pancreatic, esophageal bariatric as well cular problems . as in non-gastrointestinal specialties [7–10]. Beginning with preoperative counseling, clear informa- This care focuses on counseling preoperatively, optimiz- tion to patients before surgery decreases anxiety, facilitates ing nutrition, standardizing analgesia without opioid use, postoperative recovery and pain control, and increases care minimizing electrolyte and fluid imbalance, using the most plan adherence, allowing for earlier recovery and discharge minimally invasive approaches, and promoting early ambu- . ERAS protocol suggests against the previously stand- lation and feeding . See Fig. 1 for overview of ERAS ard mechanical bowel preparation (MBP), which has been items. proven to result in dehydration, along with fluid and elec- trolyte imbalances. MBP was meant to rid the large bowel of solid feces and lower the bacterial content; however, this How does ERAS work? practice in fact liquefies the feces which increases the risk of surgical spilling and does not reduce the number of bac- The body physiologically responds to stress in a catabolic terial organisms in the bowel . Preoperative fasting has manner. The central nervous system mediates this, resulting been a part of traditional surgery protocol to avoid pulmo- in the production of various stress hormones and inflam- nary aspiration; however, no evidence supports this. Pre- matory mediators . More importantly, insulin resistance operative fasting instead exacerbates the already increased develops. Unlike traditional care, ERAS aims to attenu- metabolic stress found postoperatively . A metabolically ate the development of insulin resistance, a key element fed state for surgery can be achieved by the ingestion of a Fig. 1 Key components of ERAS protocol Active Patient Involvement Pre-operative Intra-operativePost-operative Pre-admission education Active warming Early oral nutrition Early discharge planning Opioid-sparing technique Early ambulation Reduced fasting duration Surgical techniques Early catheter removal Avoidance of prophylactic Carbohydrate loading Use of chewing gum NG tubes & drains No/selective bowel prep Defined discharge criteria Venous thromboembolism Goal directed peri-operative fluid management prophylaxis Antibiotic prophylaxis Pain & nausea management Pre-warming Audit of compliance & outcomes Whole Team Involvement 1 3 Medical Oncology (2018) 35:95 Page 3 of 8 95 clear carbohydrate-rich beverage before midnight and 2–3 h mobilization . To reduce the risk of ileus, strategies before surgery. This reduces preoperative thirst, hunger, include epidural analgesia in open surgery, avoidance of opi- anxiety, and postoperative insulin resistance . The ana- oids and fluid overload, and oral laxatives usage early after bolic state that carbohydrate loading produces in the patient surgery. Discharge should occur as soon as the patient has causes less postoperative nitrogen and protein losses and a solid food diet, bowel movements, orally controlled pain, better maintenance of mass and muscle strength . sufficient mobility for self-care, and no complications requir - Meta-analyses have shown that low molecular weight ing hospital care . What is probably the most important heparin (LMWH) is equally as effective as low-dose subcu- in ERAS—its aim is not to discharge a patient from hospital taneous unfractionated heparin in reducing the occurrence as soon as possible. It rather aims to prepare him for early of deep vein thrombosis, pulmonary embolism, and overall discharge by making him fully capable of going home. mortality in patients. LMWH is preferable because of its once a day dosing and lower risk of heparin-induced throm- bocytopenia . Research shows the preemptive control ERAS in different surgical disciplines of possible anaerobic and aerobic infections using prophy- lactic antibiotics is effective [ 14]. Studies support the fact The use of ERAS has been most extensively studied in colo- that preservation of normal body temperature reduces wound rectal surgery. A multicenter randomized LAFA trial, the infections, cardiac complications, bleeding, and transfusion paramount Dutch study, compared four groups of patients requirements. This can be accomplished by forced air heat- undergoing open/laparoscopic surgery with/without ERAS ing of the upper body, intravenous fluids given with extend- . It was shown that a combination of ERAS and lapa- ing heating to 2 h before and after surgery for additional roscopy was associated with significant improvements in benefits . Traditional surgery protocol often included postoperative recovery. Next RCTs and several subsequent the dosing of IV fluids that outweighed the losses during meta-analyses clearly showed that the introduction of ERAS surgery. By delaying the return of normal gastrointestinal to colorectal surgery decreased postoperative morbidity functioning, impairing wound and anastomosis healing, by 40–50% (mainly non-surgical) and shortened LOS by and affecting tissue oxygenation, such regimes increased 2–3 days [17–19]. Therefore, Greco et al. concluded that hospital stay. Evidence suggests that limiting postoperative new RCTs were not required to compare ERAS with the IV sodium-rich fluid administration by stopping IV infu- standard of care in colorectal surgery. Rather, it is apparent sions and beginning early oral fluids, even on the first day from current evidence that new policies are needed to help postoperatively, can reduce hospital stay and postoperative implement ERAS protocol worldwide . Moreover, it has complications such as ileus . been demonstrated that a combination of ERAS and lapa- According to patient experiences, postoperative nausea roscopy helps eliminate some well-established risk factors and vomiting is more stressful than pain. The risk factors for prolonged LOS and complications [20, 21]. Importantly, for these symptoms include female gender, non-smokers, ERAS can be successfully implemented in both colonic and history of motion sickness, and postoperative use of opioids. rectal resections providing similar outcomes and level of Individuals with at least 2 of these should be administered adherence to the protocol, even in patients with advanced either dexamethasone sodium phosphate prophylaxis at the cancer [22, 23]. The position of ERAS protocol in colorectal beginning or serotonin receptor antagonists at the end of surgery is nowadays well established as the best care and it the surgical procedure . Drainage should not be used is very unlikely that future trials will change this. after uncomplicated procedures, as it does not lower the While proposed for gastric surgeries, ERAS protocol imple- risk or severity of anastomotic leaks . The use of mini- mentation is still being studied [24–26]. In 2014, Yu et. al’s mally invasive surgical techniques has been shown to reduce meta-analysis of 400 patients showed that postoperative hospi- complications, speed recovery, and lower pain. Nasogastric tal stay, time to first flatus, and hospital costs were significantly decompression should be avoided due to the occurrence of reduced in patients who received ERAS perioperative care fever, atelectasis, and pneumonia . Complete avoidance . Additionally in 2014, an international committee within or at least removal of nasogastric tubes before the rever- the ERAS society assembled an evidence-based 25-item long sal of anesthesia is vital in reducing the risk of pneumonia protocol for those patients undergoing gastrectomies . while supporting the progression to intake of solids . A 2015 meta-analysis, including 7 RCTs and 524 patients, Long acting premedication, such as opioids, long acting showed that ERAS treatment was associated with shorter post- sedatives, and hypnotics, can prolong recovery by delaying operative hospitalization, less hospitalization expenditure, less mobilization and the resumption of a normal diet. An earlier pain, and better quality of life . Then in 2018, a subse- return to normal diet both supports mobilization, energy, quent meta-analysis similarly showed ERAS led to shortened and protein supply and reduces starvation-induced insulin time to first flatus, postoperative hospital stay, postoperative resistance. The early removal of urinary catheters supports CRP levels, and hospitalization fees. Due to the limitations 1 3 95 Page 4 of 8 Medical Oncology (2018) 35:95 of the study, however, further larger and multicenter studies Difficulties in ERAS implementation are warranted to validate the findings . In particular, the use of drains in gastric surgery, not in compliance with ERAS A large body of evidence demonstrates the success rates of protocol, had been debated in the past. However, a Cochrane ERAS protocol, showing decreased recovery times, short- review of total or subtotal gastrectomies performed between ened hospital stays, reduced hospitals costs, and increased 1996 and 2014, showed no evidence in support of drainage patient satisfaction. However, ERAS’s challenge to tradi- regarding morbidity-mortality, nor in the diagnosis or manage- tional surgical doctrine has led to slow implementation . ment of leakage . Lastly, early postoperative oral feeding Every member of the team must overcome the resistance as compared with traditional, or late, feeding is associated with to change and embrace ERAS protocol . Resistance to shorter hospital length of stay and is not associated with an change, however, is just one of the many barriers. Addition- increase in clinically relevant complications . ally, compliance to all protocol items is crucial and often ERAS has also been shown to be beneficial in liver sur - difficult to accomplish. One single center study proved that gery and its implementation has started in many centers . a 50–90% increase in the compliance rate decreased com- Some reports show that current practices in hepatic surgery plication rates by 20% and the length of stay by 4 days . already cover several items of the modern perioperative Similarly, another single center study demonstrated that a care protocols, as suggested in a 2014 study by Wong-Lun- compliance rate of at least 80% is needed to decrease the Hing et al . However, this needs further optimization, length of hospital stay, and, that this compliance rate takes standardization, and broader research. A step towards this approximately 6 months and the treatment of 30 patients to standardization was the publication of the ERAS Society successfully achieve . In 2015, The ERAS Compliance Recommendations in 2016 . Additionally, it is impor- Group showed in a large-scale study on over 1500 colorectal tant to note a growing number of recently published trials, cancer patients that increasing ERAS compliance correlates including randomized prospective studies, that confirm there with fewer complications . This trend was later con- is a place for ERAS in this surgical discipline. Although firmed by two studies observing patients undergoing laparo- mentioned trials do not have an overwhelming number of scopic surgery for colorectal cancer. The first study showed subjects (62 patients in Kapritsou et al. study ; 160 in that the decrease in both the rate of complications and length Qi et al. RCT ), they provide strong evidence of clinical of hospital stay was correlated with level of compliance to safety and efficacy, even in major resections. ERAS protocol; there was no correlation to patient specific The advantages of ERAS in pancreatic surgery have been comorbidities or stage of cancer. The second study further strongly established through a number of research papers, supported the validity of this trend, when it demonstrated including both meta-analyses and guidelines; for example, a significant decrease in complication rates with increas- a study on ERAS care post pancreaticoduodenectomy was ing compliance (35.7% vs. 36.4% vs. 16.4%, p = 0.0024) as published in 2012 . Literature reviews agree that ERAS well as a decrease in the severity of complications that did may be introduced without compromising patients’ safety, occur [20, 48]. although there is still a need for large-scale, multicenter ran- This correlation between compliance and clinical out- domized trials [39, 40]. It seems one of the greatest concerns comes raises the issue on how to maximize patients’ adher- arises around minimally invasive pancreatic surgery because ence to the protocol. Some authors suggest auditing patient the evidence for its safety in cancer patients is still limited compliance weekly, potentially allowing for the implemen- [41, 42]. As with hepatic surgery, recent high-quality trials tation of any necessary changes to the protocol [5, 49]. It is have provided new evidence in regard to the implementa- also important to educate patients . With no doubt, the tion of ERAS in pancreatic surgery. For instance, results of early implementation period is the most inconsistent when it Takagi et al. RCT published in January 2018 showed not comes to ERAS compliance. According to Pędziwiatr et al. a only significantly lower rates of complications and readmis- multidisciplinary team needs at least 40 cases and 6 months sions, but also improved patients’ quality of life when treated to reach satisfactory level of adherence to the protocol . with ERAS . On the other hand, one has to bear in mind Still, reports from institutes that use ERAS in periopera- that pancreatic surgery is particularly prone to specific com- tive care are optimistic. Compliance rate is usually above plications such as delayed gastric emptying or pancreatic 60% and can be as high as over 90% [20, 51, 52]. Even in fistula formation which can severely affect both LOS and groups with lower compliance (< 70%), implementation of postoperative compliance with early enteral feeding. all ERAS items is beneficial and improves short-term out- comes . The question is whether a high level of compli- ance can be sustained in long-term observation. Roulin et al. found that over the 8-month study period, reasons for non- compliance are usually (in almost 80% of cases) medically 1 3 Medical Oncology (2018) 35:95 Page 5 of 8 95 justified and that they are mostly observed in the postopera- in younger and 74% (64–85%) in older patients. Adherence tive period . was 100% (83–100%) versus 100% (83–100%) for preop- In another study, all members of the ERAS multidisci- erative protocol, 80% (80–85%) versus 80% (75–100%) for plinary team from nurses to surgeons were interviewed to intra-operative protocol, and 72% (76–81%) versus 69% better understand the barriers and enablers of ERAS. When (52–81%) for postoperative protocol. No significant differ - asked what the largest hindrance is to successfully imple- ences were noted for any of the three phases, despite the menting ERAS, some responded institutional barriers, such older population having significantly more comorbidities, as a lack of nursing staff and financial resources. Another worse disability scores and more emergency procedures. group blamed the lack of communication and collaboration One difference in the studied groups was that urinary cathe- within the team . ters and nasogastric tubes were retained longer in the elderly Recent studies claim that the successful implementation population. However, no differences in urinary retention or of ERAS protocol requires a multidisciplinary team coupled postoperative ileus were observed . Kisialeuski et al. with a willingness to change and a clear understanding of further supported ERAS implementation in the elderly; how to utilize the protocol . In their study on the barriers the authors demonstrated again that even with higher ASA of ERAS utilization, Kahokehr et. al recommended that the grades, ERAS shortened the length of hospitalization and keys to successful implementation were developing a mul- did not lead to a higher risk of postoperative complications tidisciplinary team, distributing patient educational mate- or readmissions . Although there are relatively many rials, and modifying the postoperative ward into a patient studies in literature comparing younger patients with the friendly rehabilitation center. A prospective study on 425 elderly, there are discrepancies in the age cutoffs used in patients treated under ERAS guidelines in the Netherlands, these studies. For example, Wang et al. , Bagnall et al. Norway, Sweden, United Kingdom, and Denmark showed , and Kisialeuski et al. defined the cutoff as over 65 years that the lowest compliance rates occurred postoperatively. , Baek et al.  and Slieker et al.  defined the cutoff The author called for patients to complete their own daily as over 70 years old, and even further Verheijen et al defined logs and the reeducation of the members of the team to clar- the cutoff at 80 years old . ify their individual roles as well as the multidisciplinary Postoperative complications and prolonged hospital protocol . An additional study of 107 patients treated stays remains a problem in emergency surgeries. For obvi- with ERAS guidelines in the Netherlands called for continu- ous reasons, not all ERAS items are possible to implement ous education to ensure compliance . Kisielewski et al. in the emergency setting (e.g., preoperative carbohydrate found that Polish surgeons followed several ERAS elements loading in mechanical bowel obstruction or limited feasi- such as antibiotic and antithrombotic prophylaxis, postopera- bility of minimally invasive surgery, needs for drains etc). tive oxygen therapy, and lack of nasogastric tubes. On the Lohsiriwat et al. investigated the feasibility of implementing other hand, several elements were not followed. Surgeons ERAS protocol in the setting of emergent colorectal surgery. were not willing to change their practice but were support- He compared the surgical outcomes of patients treated with ive of changes in anesthesiologist-dependent elements of ERAS protocol with those receiving conventional postopera- perioperative care that did not interfere with their own work, tive care in a matched case-control study. A reduction in hos- such as restrictive fluid therapy and the use of transversus pital stay, time to first flatus, and time to resume normal diet abdominis plane blocks . was found in those receiving ERAS based care, without an increase in 30-day readmission or postoperative complica- tions. He concluded that implementation of selected ERAS ERAS in specific patient populations items in the setting of emergency colorectal surgeries was feasible and effective. Limitations in this study included its Regarding the elderly population, a systematic review of small sample size and selective inclusion of low risk patients 16 studies including 5965 patients supported the safety of . Gonenc et al. demonstrated safe usage of ERAS guide- ERAS in the elderly, with similar prevalence of morbidity lines in certain gastrointestinal emergent surgeries. When and mortality compared to a younger population . Baek comparing 47 patients undergoing emergency surgery for et al. found no difference in postoperative results between perforated peptic ulcers, treatment with ERAS protocol patients below and above 70 years of age following enhanced effectively decreased the length of hospital stay [64 ]. Wisely recovery protocol . However, ERAS protocol requires et al. investigated the utilization of ERAS protocol in 370 active participation and adherence to it within the elderly patients undergoing emergent major abdominal surgery. The population had yet to be studied. A study of ERAS proto- ERAS patient group had significantly reduced presence of col adherence compared 513 patients: 311 patients in the catheters, drains, patient-controlled analgesia, urinary tract younger group and 202 in the older group . The overall infections, urinary retention, and chest infections. While adherence to ERAS protocol had a median of 78% (67–85%) the results supported ERAS implementation in emergency 1 3 95 Page 6 of 8 Medical Oncology (2018) 35:95 abdominal surgeries, only some of the ERAS guidelines sustaining a high level of compliance with ERAS items in were implemented and further research is needed . This the long term as well as the introduction of ERAS to emer- call for further trials was supported by Paduraru et. al’s sys- gency surgery. It shows clearly that changing surgical dog- tematic review of the successful implementation and surgi- mas is more difficult that one could assume. Therefore, new cal outcome of ERAS protocol for emergency surgeries. The implementation strategies are needed in order to increase the authors showed that the number of employed ERAS items popularity and utilization of this approach. ranged from 11 to 18 of the 20 recommended by the ERAS Society for elective procedures; patients treated within the Compliance with ethical standards guidelines had fewer postoperative complications, shorter Ethical approval This article does not contain any studies with human hospital stays, with equal or lower mortality rates in certain participants or animals performed by any of the authors. studies. It seems that ERAS utilization in emergency setting is possible and effective; however, certain changes to the Informed consent None. protocol may need to be adapted. Therefore, further research is needed to fully establish the role of ERAS in decreasing Open Access This article is distributed under the terms of the Crea- major morbidity and mortality . tive Commons Attribution 4.0 International License (http://creat iveco mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- tion, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the ERAS impact on long‑term outcomes Creative Commons license, and indicate if changes were made. There is still very little evidence on how ERAS implemen- tation benefits patients long term [5 ]. Reports have been published which suggest that enhanced recovery protocols References can increase long-term survival; however, these results are quite recent and need to be studied further . One of these 1. 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Medical Oncology – Springer Journals
Published: May 9, 2018
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