The Development of Enhanced Recovery After Surgery Across Surgical Specialties

Introduction

Enhanced Recovery After Surgery (hereafter, ERAS^®) is a multidisciplinary approach to the care of patients undergoing surgery that is fast approaching nearly two decades of evolution in practice. The history, scientific and economic rationale, physiologic underpinnings, and phase-specific components of ERAS have been the topic of several excellent reviews and are presented elsewhere in this issue. ¹ In brief, drawing on lessons from the “fast-track” concept applied to coronary bypass surgery in the 1990s, ERAS focuses on optimization of perioperative nutritional status and fluid balance, promotion of opioid-sparing analgesia, pharmacologic anti-inflammatory measures, and early postoperative enteral feeding in an effort to blunt the body's reaction to surgical stress. An example of ERAS measures in colorectal surgery is shown in Table 1.

The majority of data pertaining to outcomes with ERAS are derived from patients undergoing colorectal surgery. When implemented in an environment with resources available to ensure both compliance and ongoing process improvement, ERAS has been demonstrated to reduce both length of stay and complication rates without adversely affecting readmission rates and mortality in this population. As the data in patients undergoing colorectal resection continue to grow and mature, however, the study of patient outcomes following implementation of ERAS has extended to several other surgical subspecialties.

The goal of this article is to provide an overview of ERAS as it has been described across a spectrum of surgical fields, with particular attention to the degree of ERAS penetration as well as to the differences that may exist in applying ERAS protocols to a diverse array of operations. These data are summarized in Table 2. A discussion of the application of ERAS in liver and pancreas surgery has purposefully been omitted, as this is the topic of a separate article in this issue.

Colon and Rectal Surgery

No field of surgery has seen greater penetration nor yet as substantial a benefit from the implementation of ERAS compared with colon and rectal surgery. Before the emergence of data from studies of ERAS and the subsequent dissemination of this care paradigm, the average length of stay for a patient undergoing colorectal resection was greater than 6 days; postoperative rates of respiratory and cardiovascular complications (e.g., myocardial infarction and pulmonary embolism), paralytic ileus, and urinary tract and skin and soft tissue infections occurred in reported range of 15%–48%. ² Initial studies of opioid-sparing analgesia and early enteral feeding in small numbers of patients in the mid-1990s demonstrated an impressive reduction in overall length of stay to as few as 2 days.^3,4 These thought-provoking articles have since been followed by more than 50 publications, including retrospective series and prospective trials across multiple countries, systematic reviews, and meta-analyses, and consensus statements.

It is now well established that ERAS in colorectal resection has contributed to substantial reduction in length of stay (hereafter, LOS) and nonsurgical complication rates on the order of 50%. ¹ The field has recently seen the emergence of “ultra ERAS^®” protocols that suggest even greater benefit when minimally invasive approaches are used in carefully selected subsets of patients.^5,6 Toward a similar end, risk calculators are under development that may predict failure of ERAS-directed care in certain circumstances based a variety of perioperative data points, including patient characteristics, operative approaches, and postoperative developments. ⁷

The magnitude of the effects seen with ERAS implementation in colorectal resection was shown in several meta-analyses to vary considerably across published trials.^2,8–10 This finding was attributed to the nonuniform application of ERAS components and variations in both quality assessments and study design in many early studies of ERAS in colon and rectal surgery. For example, the use, duration, and failure rate of epidural analgesia, if and when employed, were highly variable, as was reporting on measures to restrict injudicious fluid administration, promote early urinary catheter removal, guide the extent of preoperative feeding, or prevent hypothermia.^2,8 These data drove subsequent investigators to assess patient outcomes after colorectal resection, while simultaneously capturing adherence to institutional ERAS protocols.^11–15 The relationship between effect size and closer adherence to ERAS is not surprising; at least one meta-analysis has demonstrated more consistent outcomes across studies when at least seven components of an ERAS protocol were implemented. ¹⁵ A summary of these components is provided in Table 1. Consensus statements have emerged that address these inconsistencies across trials, call attention to the need to avoid “suboptimal” ERAS implementations, and serve as guides in interrogating the clinical evidence of the effectiveness of ERAS.^16–19

It is important at this juncture to address a critical lesson from the application of ERAS to colorectal surgery: merely implementing an ERAS protocol should not be conflated with the long-term success of such a program. Adherence to ERAS protocols has been shown to require substantial institutional support, both in the form of dedicated staff as well as a commitment to process improvement and flexibility in the context of ongoing, evidence-based revisions that may be needed over time.^18,20 Although effective long-term execution may present challenges at both individual and institutional levels, it has become axiomatic in the field that closer adherence to an ERAS protocol is associated with maximization of its potential benefits.

Gastric Resection

Fast-track programs that have incorporated a number of ERAS principles have been applied to patients undergoing elective total or partial gastrectomy for malignant disease in a number of both cohort and randomized studies. Key components of these protocols have been preoperative nutritional optimization with carbohydrate loading, avoidance of bowel preparation, balanced fluid administration, avoidance of routine use of nasogastric tubes, prevention of intraoperative hypothermia, and early feeding and mobilization. Most studies did not employ epidural catheters or stipulate opioid-sparing techniques for postoperative pain control, and the nature of preoperative counseling and the anesthetic protocols were either variable or not explicitly discussed. All studies to date have shown an improved LOS over conventional perioperative care by at least 2 days. ²¹ A small study has demonstrated an added benefit to LOS in combining minimally invasive approaches to gastrectomy with ERAS principles. ²² Only one study, however, has demonstrated a true reduction in postoperative complications. ²³

Despite this, a number of reports have improved time to flatus, inpatient quality of life scores, and reduction in serum biomarkers associated with inflammation in patients whose care involved ERAS components.^24–26 Interestingly, one study described higher rates of postoperative complications and readmissions in patients older than 75 undergoing open gastric resection compared to younger patients. ²⁶ Overall, the literature on gastric resection suggests that the adoption of ERAS principles in this field has yet to extend beyond a limited number of institutions in Asia. Until additional studies with more uniform protocols are available, ERAS-associated outcomes in gastrectomy remain limited to improvements in LOS and may be limited to subset of patients undergoing the procedure.

Surgery for Weight Loss

Several recent prospective studies in the field of bariatric surgery have demonstrated shortened LOS without compromising patient safety in this population, both in those undergoing Roux-en-Y gastric bypass and sleeve gastrectomy.^27,28 A recent systematic review and meta-analysis of five studies of ERAS implementation in bariatrics revealed a shorter overall stay with ERAS, although the authors acknowledged considerable heterogeneity of ERAS protocol components across trials. ²⁹ Preoperative carbohydrate loading and early oral feeding were the most common components followed. Overall, despite the improvement in LOS, no conclusions could be drawn regarding complication and readmission rates. A separate meta-analysis of 11 trials, all of which had at least four ERAS protocol elements, also reported shorter hospital stay, but was similarly unable to determine a benefit with regard to postoperative morbidity. ³⁰ Optimized anesthesia protocols, multimodal analgesia, and early postoperative mobilization were the most commonly instituted measures; avoidance of high intra-abdominal pressures during leak tests and optimized OR scheduling times were the least commonly adapted.

The heterogeneity in ERAS components across these studies may be, in part, related to their publication before the release of ERAS guidelines for bariatric surgery. ³¹ Nevertheless, it has been difficult to assign a relationship to the number of ERAS components instituted and extent of LOS reduction observed. Studies have suggested that institution of as few as four ERAS components may produce similar reductions in LOS than those seen when as many as 15 components have been implemented.^32,33 Moreover, similar to early studies with ERAS in colon and rectal surgery, few studies in bariatrics have reported a true compliance rate with ERAS. Additional investigations, including randomized controlled studies, will need to take the preceding guidelines into account as well as monitor ERAS compliance before a benefit beyond decreased LOS may be revealed with ERAS implementation in weight-loss surgery.

Hernia Repair

There has been limited application of ERAS-directed perioperative care to the repair of ventral hernias. Only three studies exist, the earliest of which demonstrated reduced LOS and earlier time to gastrointestinal function in a small series of 42 patients undergoing large open ventral hernia repair. ³⁴ The authors report utilizing strategies centered on multimodal pain control, including intraoperative transverses abdominis plane (TAP) blocks, and acceleration of intestinal recovery with early feeding and minimization of opioids. The use of alvimopan, an orally administered, peripherally restricted μ-opioid antagonist, was also a component of care in this study; this measure has not been described in later studies. Subsequent reports embraced the use of either TAP blocks or epidural catheters for opioid-sparing analgesia based on institutional experience and success rates with these methods.^35,36 A more extensive preoperative phase centered on weight-loss counseling, smoking cessation, and nutritional optimization was also instituted. Although the data are quite young and call for validation in larger studies, patients undergoing ventral hernia repair treated under an ERAS protocol appear to benefit from a shorter LOS, improved pain scores, earlier advancement and tolerance of postoperative diet, and no difference in postoperative complications or readmission rate.

Trauma and Emergency Surgery

Few studies exist that speak on outcomes with ERAS in the care of the patient undergoing surgery for trauma or an acute indication (e.g., perforated diverticulitis or perforated ulcer disease). Limited data from small series have nonetheless demonstrated reductions in hospital LOS without negative influence on postoperative complications or 30-day readmission rates. Perhaps, not surprisingly, most data supporting these conclusions are derived from cohort studies comparing ERAS versus conventional care in the setting of urgent colectomy for obstructing colon cancer, lower gastrointestinal bleeding, or perforation.^37–40 In addition to a reduced LOS, one investigation has demonstrated a significant reduction in major complications when patients undergoing urgent colectomy were treated under an ERAS protocol, including acute kidney injury, sepsis, intra-abdominal collections, and small bowel obstruction. ³⁹ Epidural analgesia was not employed and no significant reduction in the use of nasogastric tubes, central lines, or surgical drains in the post-ERAS cohort was reported. Other studies have called attention to the difficulty in compliance with ERAS principles in the urgent versus elective setting, particularly with regard to such factors as preoperative counseling, epidural analgesia, or the use of preoperative carbohydrate drinks. ⁴⁰ Taken together, these findings suggest that, despite an “incomplete” application of ERAS to patients requiring urgent colectomy, improvements in patient outcomes may still be achieved in these often unpredictable circumstances.

In addition to urgent colectomy, the use of ERAS in the operative care of penetrating abdominal trauma and perforated ulcer disease has been described. A small prospective cohort study of operative management of penetrating abdominal trauma within an ERAS framework demonstrated a shortened LOS with no significant difference in postoperative complication rate when compared to non-ERAS care; similar to several of the aforementioned studies, the use of epidural analgesia, preoperative counseling, and nutritional optimization was eschewed, while early mobilization, early postoperative feeding, and early removal of nasogastric tubes and indwelling catheters were prioritized. ⁴¹ Separately, a small series of patients undergoing Graham patch repair of perforated peptic ulcer disease found that care under a modified ERAS paradigm resulted in a shorter LOS without an increase in postoperative complications. ⁴²

Thoracic Surgery

Esophageal surgery has seen a steady increase in published reports of the use of ERAS protocols since 2010. A recent systematic review and meta-analysis have provided a summary of interventions and outcomes in the field. ⁴³ ERAS in esophageal surgery has comprised anywhere from 8 to 16 total key components of care, and published protocols have been remarkably consistent in the use of multimodal, opioid-sparing analgesia (including thoracic epidural catheters), goal-directed fluid therapy, early feeding and mobilization, and protocol-driven practices for early discontinuation of chest tubes and urinary catheters. Preoperative counseling measures, practices to prevent hypothermia, optimize preoperative nutrition status, and minimize the use of nasogastric tubes, however, have been less protocol driven. Nevertheless, patients undergoing esophagectomy under an ERAS protocol appear to benefit from an improved LOS; surgical complication rates, mortality rates, and readmission rates have not been found to differ significantly compared to conventional perioperative care measures.

These findings are similar to those in other surgical disciplines, as are the limitations of the data. The majority of studies in esophageal resection compare outcomes with ERAS to historical controls; only one randomized control trial has been published. ⁴⁴ Measures for monitoring adherence to ERAS protocols within studies have not been described. Moreover, within individual studies and across several published series, data have been captured from a broad array of open and minimally invasive approaches to esophageal resection. In an attempt to address the confounding potential of varied techniques, a small single-center experience expressly limited to either Ivor-Lewis or McKeown esophagectomy has recently been published. ⁴⁵ With increasing measures to control these variables and monitor adherence to ERAS components, the contribution of ERAS to outcomes in this challenging patient population is likely to grow.

The “fast-track” concept in major lung resection, which was historically limited to chest tube management protocols and epidural analgesia, has been shown to reduce LOS without adversely affecting perioperative morbidity or readmission rate. ⁴⁶ More recent retrospective data from programs incorporating early feeding and early aggressive mobilization measures have demonstrated these measures to be both safe and associated with fewer postoperative pulmonary complications.^47,48

Improvements in care with programs implemented before the development of ERAS have contributed, in part, to slow implementation of formal ERAS programs in this field. Nevertheless, data from a small but well-curated single-institution study of ERAS implementation that adopted nearly every component of ERAS has demonstrated reduced LOS, increased patient satisfaction score and hospital cost-savings, and no effect on perioperative morbidity or mortality. ⁴⁹ Of particular interest is the observation that additional gains in patient outcomes remain to be achieved when ERAS is compared against a more traditional “fast-track” control group. These findings have been the subject of recent publications calling for additional controlled studies of ERAS implementations in lung resection.^50–52

Urologic Surgery

Among urologic procedures, ERAS has been most extensively studied in radical cystectomy. Although more recent investigations have focused on formal, multicomponent ERAS protocols, single interventions such as bowel preparation and goal-directed fluid therapy were the focus of older studies in this field. ⁵³ Two recent reviews of the literature on ERAS protocols in radical cystectomy have corroborated individual study findings of improved LOS, although results concerning postoperative complication and readmission rates are less consistent and are at best unchanged over conventional perioperative care.^54,55 Nearly all published ERAS protocols in radical cystectomy have adopted the use of epidural analgesia, balanced fluid administration, and prevention of intraoperative hypothermia; the use of bowel preparation and nasogastric tubes has been avoided.

While no guidelines are yet in place, ERAS society recommendations for patients undergoing radical cystectomy have similarly argued against the use of bowel preparation and support early nasogastric tube removal and judicious fluid administration. ⁵³ Analysis of these particular measures in single-intervention studies revealed an association with reduced morbidity and shorter LOS. Larger studies with appropriate controls and stronger internal measures of protocol adherence may produce more consistent data, allowing meaningful conclusions concerning the use of enhanced recovery pathways and key outcomes in this group of patients

Gynecologic Surgery

ERAS has been applied in studies examining a variety of gynecologic surgeries for both benign and malignant indications. Observational studies of patients undergoing abdominal and vaginal hysterectomy have demonstrated reduced LOS and no significant difference in postoperative complication or readmissions with ERAS compared to either historical or matched controls.^56–59 Studies focusing on major abdominal surgeries for gynecologic cancers have also demonstrated a benefit in LOS over conventional care and suggested improved patient satisfaction scores, despite increases in reported incidences of postoperative nausea and vomiting in some series.^60–62

It is worth noting that these reports captured data from a broad spectrum of surgeries and operative approaches (abdominal, laparoscopic, and transvaginal). There has also been considerable variation in the use of standardized anesthesia protocols, perioperative regional analgesia, and opioid-sparing techniques; the most consistent ERAS components employed have been balanced fluid administration, early feeding, and early mobilization. As with the challenges faced by many surgical disciplines, the strength of findings related to ERAS in the gynecologic literature is undercut by a lack of randomized studies. ⁶³

To address the variability in ERAS components across studies, a standardized ERAS protocol was recently proposed. ⁶⁴ ERAS Society guidelines have also been published with recommendations for implementation in gynecologic surgery, although the authors acknowledge a dearth of high-quality evidence supporting individual components of the ERAS pathway in the gynecologic literature to date. ⁶⁵ Nevertheless, a recent study focusing on gynecologic surgery has examined ERAS adherence and assigned scores to select hospitals, demonstrating that efforts to more rigorously delineate ERAS benefits to these patients are well underway. ⁶⁶

Conclusion

As ERAS evolves, its dissemination into an array of surgical fields will continue. Data from studies examining the application of ERAS will grow, and calls for standardized practices and head-to-head comparisons in a randomized trial framework will increase. The outcomes described with ERAS will continue to be scrutinized, with an eye toward protocol adherence.

The concept of marginal gains in ERAS is certainly not new. Data from colorectal surgery have convincingly demonstrated that more uniform adherence to ERAS components offers the highest likelihood of positive outcomes. Efforts to standardize ERAS protocols and call attention to the need for quality control both in the literature and in the day-to-day individual and institutional execution of ERAS are commendable. Nevertheless, not all surgeries, and certainly not all patients, should be treated equal. An emerging body of research is identifying those patients and situations in which ERAS may not produce the outcomes intended as well as those in which the principles of ERAS can be pushed to an even greater degree.

As ERAS is applied to a greater number of fields, findings to date also seem to suggest that implementation of ERAS may not be a zero-sum game. In acute care surgery and major lung resection, for example, improved outcomes have been described with a fraction of the measures typically utilized in the care of patients undergoing colorectal resection. In contrast, elderly patients undergoing gastric resection were shown to have higher postoperative complications and readmission rates when ERAS principles were applied than their younger counterparts. More research will be needed to determine whether graded implementation of ERAS can be safely and reliably associated with improvements in surgical care across surgical disciplines.

The benefits of ERAS-driven perioperative care will doubtless expand. Thus far, the most commonly described benefit of ERAS application has been a reduced LOS. Although several studies in different fields have demonstrated that complication rates and readmission rates are decreased with ERAS as well, these data are most consistent in the colorectal literature. Few studies have looked at additional outcomes beyond inpatient quality-of-life scores and return of bowel function that may be of importance in furthering the dissemination of ERAS. Return to work or independent living, minimization of postdischarge narcotic requirements, time to initiation of adjuvant chemotherapy or radiation, and postdischarge quality of life are important outcomes that merit further study in trials of ERAS.

Despite the challenges implicit in measuring these outcomes and incorporating them into trial design, these results will no doubt realize the future promises of ERAS in optimizing care of the surgical patient.