For several decades fast-track and enhanced-recovery (ER) surgical protocols have been described, mainly by European centers.1 More recently, the concept of ER has been integrated into surgical practice in North America, resulting in a paradigm shift in perioperative care. ER is a multimodality approach to patient care that is implemented by a multidisciplinary team. The driving principle behind these evidence-based care pathways is that by reducing stress associated with surgery, patients are able to recover more rapidly and completely, thereby minimizing complications and delays in further treatment.1,2 As ER has been incorporated into more surgical specialties, data are rapidly accumulating that demonstrate the benefits of ER protocols on patient outcomes. These benefits include reduced postoperative complications and inpatient length of stay (LOS).3,4,5,6,7,–8 As personalized care and precision medicine have become increasingly importantly concepts, studies examining more patient-centric, long-term outcomes reflecting functional recovery also are being reported.9,10,–11

Despite this revolution in perioperative care, much of the ER literature focuses on the impact of ER on patients undergoing nononcologic procedures.6,8,12 When oncologic patients are described, they often have early-stage disease amenable to less invasive surgical intervention.13,14 Because colorectal surgeons were amongst the earliest to incorporate ER into their practice, the largest amount of oncologic data on ER exists in this patient cohort. However, the majority of oncologic specialties are underrepresented in the ER literature.15,16,17,–18 To address this knowledge gap, we assessed the impact of ER implementation on patient outcomes across multiple oncologic surgical specialties at a large, comprehensive cancer center.

Methods

Defining Enhanced-Recovery Protocols

ER protocol implementation began in 2012 with a phased roll-out performed across disease sites and surgical specialties over a 3-year period. Surgical specialties included in the analyses were Colorectal, Gynecology, Hepatobiliary, Thoracic, and Urology. Each service area program was formed around a multidisciplinary team that included surgery, anesthesia, nursing, pharmacy, nutrition, rehabilitation services, and informatics support. Provider education regarding the core components of ER was supplemented by presentations at regularly scheduled CME meetings, surgical service orientations, and other didactics. For the purpose of this study, ER protocol compliance was defined as patient care that included preoperative patient education on ER and use of both pre- and postoperative ordersets in the institutional electronic medical record that incorporated the four pillars of ER: multimodal opioid-sparing analgesia, goal-directed fluid therapy, early feeding, and early ambulation.1,2,19

Patient education was performed by providers and nursing staff at preoperative clinic visits. Patients received education on both the indicated operation and on ER principles and goals, with the objectives of reducing anxiety by transparently sharing plans of care and setting patient expectations regarding their perioperative experiences.2,19 For opioid-sparing, multimodal analgesia, although each service had latitude to select the exact components, all used some combination of regional anesthetic options (e.g., epidural and transverse abdominus plane [TAP] blocks) with acetaminophen, nonsteroidal anti-inflammatories, and nonnarcotic neuromodulators. Goal-directed fluid therapy, performed both intraoperatively and postoperatively, involved titrating the amount of fluid being administered based on hemodynamic indices, low maintenance fluid rates, early discontinuance with per oral intake, and data-driven bolus strategies.19,20 Early feeding was built into order sets, begun in most cases on postoperative day 0, and programmatically advanced to regular diet. Early ambulation was likewise hard-wired into order sets and initiated in most cases on the day of surgery.21,22,23,24,25,26,27,–28

National Surgical Quality Improvement Program Analysis

This study was approved by the University of Texas MD Anderson Cancer Center institutional review board and performed in compliance with the National Surgical Quality Improvement Program (NSQIP) data use agreement. For the entire duration of the study, the center participated in the Essentials data collection model, capturing approximately 14% of the surgical volume across all specialties. Patient data were obtained from the institutional American College of Surgeons (ACS)-NSQIP database from January 2011 to December 2016 for the following surgical specialties: Colorectal, Gynecology, Hepatobiliary, Thoracic, and Urology. Both open and minimally invasive surgical cases were included in the analyses, but all outpatient and emergent cases were excluded. For patients undergoing surgeries involving more than one surgical team, the operation was classified by the primary team’s specialty. The date of ER protocol initiation was determined for each specialty, and the cases from each specialty were subsequently divided into two cohorts: those treated on ER versus TP protocols.

Variable collection was performed by Surgical Clinical Reviewers trained in the analysis of medical records and audited by the ACS. Demographic and clinical information, operative details, and 30-day outcomes were included in the analyses. Age, American Society of Anesthesiologists (ASA) classification, preoperative functional status (defined as independent if assistance from another person for any activities of daily living was not required vs. dependent if some or total assistance was required), and preoperative comorbidities were compared between patients treated on ER and TP protocols.29 Wound class, operative time, and hospital length of stay (LOS) were assessed. Postoperative complications, as defined by the NSQIP Participant Use Data File, were compared between ER and TP cohorts and included wound infection, pneumonia, pulmonary embolism, urinary tract infection, renal failure, myocardial infarction, cardiac arrest, stroke, sepsis, and unplanned return to the operating room. A severe complication was defined per prior publications as having one or more of the following: organ space infection, wound dehiscence, pneumonia, unplanned intubation, acute renal failure, myocardial infarction, sepsis, septic shock, or unplanned return to the operating room.10 Thirty-day readmission and mortality rates also were compared. Mortalities that occurred during a continuous postoperative admission lasting longer than 30 days were included. Before implementation, throughout the study period, and after implementation, NSQIP patient outcomes reports were shared with each team and associated frontline providers. Likewise, individual teams internally reported their general and specialty-specific outcomes from existing department-level databases.

Analysis of High Magnitude Surgeries

A subanalysis was performed to assess the effects of implementation of ER protocols on patients undergoing high-magnitude surgery. Case magnitude was determined by primary CPT RVU, and cases with RVU >30 were considered high magnitude. All variables included in the complete ER versus TP cohort analyses also were assessed in this subanalysis.

Statistics

Statistical analyses were performed using JMP Pro software program (Version 12, SAS institute Inc., Cary, NC). Univariate analyses were performed using Chi square or Fisher’s exact test for categorical variables and the Mann–Whitney U test for continuous variables. Continuous variables are reported as median values and interquartile ranges. A two-tailed univariate p < 0.05 was considered significant.

Results

Study Population Demographics and Clinical Profile

A total of 2747 patients entered into the institutional NSQIP database between January 2011 and December 2016 were included in the analyses (Supplementary Fig. 1). Median age at the time of surgery was 60 years (interquartile range [IQR] 51-68 years), 1,548 (56%) were female, and the mean ASA score was 3. Fourteen percent of cases were performed laparoscopically, and the remainder were performed via an open surgical approach. Preoperative comorbidities are detailed in Table 1: 360 patients (13%) had diabetes, 1208 (44%) medication-controlled hypertension, and 82 (3%) required chronic steroids. Also, 365 patients (13%) were documented smokers within the 12 months before surgery, although the overall rates of COPD and dyspnea were low. With regard to their oncologic diagnoses, 1335 (48%) received preoperative chemotherapy within 30 days of surgery, and 495 (18%) received preoperative radiation within 90 days of surgery. At the time of surgery, 746 (27%) of patients had disseminated cancer and 72 (3%) reported loss of > 10% of their body weight during the 6 months before surgery.

Table 1 Clinical characteristics, based on recovery protocol
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A total of 1252 (46%) patients were treated on ER protocols. Compared with patients treated on TP protocols, patients on ER protocols had similar median age (60 vs. 60 years, p = 0.742) and rates of ASA ≥ 3 classification (88% vs. 87%, p = 0.270). Although patients treated using ER protocols had slightly lower rates of medication-controlled hypertension (42% vs. 46%, p = 0.027) and disseminated cancer (24% vs. 30%, p = 0.001), they were more likely to have undergone preoperative treatment with chemotherapy (51% vs. 47%, p = 0.014) and radiation (20% vs. 16%, p = 0.004).

Outcomes of Patients Treated using ER Versus TP Protocols

Compared with TP protocols, treatment using ER protocols was associated with decreased perioperative complications (Table 2). Specifically, patients on ER protocols were less likely to have complications (20% vs. 33%, p < 0.0001), including severe complications (7% vs. 10%, p = 0.010). The median hospital LOS was lower for patients on ER protocols (4 vs. 5 days, p < 0.0001). Despite the shorter LOS, unplanned 30-day readmission rates did not increase in the ER cohort (107 vs. 134 patients, 8.6% vs. 9.0%, p = 0.701). Lastly, while the 30-day mortality rates were low for both cohorts, a reduced mortality rate was observed amongst patients treated on ER protocols (0.2% vs. 0.6%, p = 0.245).

Table 2 Postoperative complications, based on recovery protocol
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Individual Specialty Outcomes of Patients treated on ER Versus TP Protocols

The previously described analyses also were performed on an individual basis for each of the surgical specialties included in the NSQIP database. These analyses demonstrated that many of the beneficial effects of ER protocol adoption observed for all cases were seen within each specialty. Although the exact factors that significantly improved with ER-protocol implementation differed for each specialty, these protocols uniformly resulted in decreased rates of complications (Fig. 1a), including severe complications. This included decreased rates of surgical site infections following ER protocol implementation for all specialties except thoracic surgery, for which no change in the already low rates of SSIs was observed (1.0% vs. 2.8%, p = 0.085). Patients across all specialties treated using ER protocols also had shorter median hospital LOS (Fig. 1b). Lastly, evaluation by the individual specialties of their patients’ average postoperative opioid use, measured as morphine-equivalent daily doses, demonstrated a 42–85% decrease in opioid use after ER protocol implementation.30 Although no data regarding patient-reported pain scores are collected within the NSQIP database, results of previously published studies utilizing ER protocols suggest that the lower observed opioid use was associated with improved patient-reported pain scores.31,32,–33

Fig. 1
figure 1

Specialty-specific outcomes based on recovery protocol. Comparison of a complication rates and b median hospital length of stay between patients managed on traditional versus enhanced recovery protocols

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Assessment of High Magnitude Case Outcomes

To further assess the effects of ER protocol implementation on patient outcomes and to better control for case complexity, a subanalysis was performed on those patients undergoing high-magnitude surgeries (primary CPT RVU >30); 1,022 cases (37%) satisfied this definition. High-magnitude cases by surgical subspecialty are shown in Supplementary Fig. 2. Within this cohort of patients, 371 (36%) were treated using ER protocols. Compared with patients on TP protocols, ER-protocol patients were less likely to have disseminated cancer at the time of surgery (19% vs. 36%, p < 0.0001) but were more likely to have undergone radiation (27% vs. 19%, p = 0.001). Median procedure duration was similar between the ER and TP cohorts (327 vs. 326 min, p = 0.466; Table 3).

Table 3 Clinical characteristics for high–magnitude casesa, based on recovery protocol
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Compared with patients undergoing surgeries of any magnitude, patients undergoing high-magnitude operations had increased rates of perioperative complications (41% of cases with RVU > 30 vs. 27% of all cases, p < 0.0001), longer median LOS (6 vs. 4 days, p < 0.0001), and higher readmission rates (13% vs. 9%, p = 0.0003). Despite this confirmation of increased case complexity, a beneficial effect of ER protocols was still observed, and many of the key findings from the analysis of the entire study population also held true for patients who underwent high-magnitude surgery. Specifically, patients undergoing more complex cancer surgery and on ER protocols were less likely than traditionally treated patients to have any complication (35% vs. 44%, p = 0.002). The median LOS for the ER protocol-treated cohort also was shorter (5 vs. 6 days, p < 0.0001), while no corresponding increase in 30-day readmissions was observed (14% vs. 12%, p = 0.348). No significant differences in the rates of severe complications or 30-day mortality were found in this subanalysis; however, both were trending in a confirmatory direction in the ER cohort (Table 4).

Table 4 Clinical characteristics for high-magnitude casesa, based on recovery protocol
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Discussion

This study found that the adoption of enhanced recovery protocols for the perioperative care of oncologic patients resulted in improved patient outcomes, including decreased rates of complications, reduced hospital LOS without a concomitant increase in readmission rates, and lower opioid utilization. These findings of ER protocol implementation at a large comprehensive cancer center mirror those reported in the ER literature for other surgical specialties.3,4,5,6,7,–8 To our knowledge, this is the largest study to date looking at multispecialty ER implementation within the setting of oncologic surgery, and so provides substantial evidence that ER protocols can be successfully utilized in the treatment of this complex patient population.

Unlike other reported ER studies, this analysis looked at ER implementation across multiple surgical specialties. Overall, the findings for each specialty were similar to those for the entire cohort with regard to patient outcome improvement. Even if a significant improvement in an individual outcome was not seen, a trend in the improved direction was observed. An exception to this was the outcomes observed for the HPB group, which demonstrated equivalent patient outcomes following adoption of ER protocols. These findings were likely the result of smaller included case volume and later provider adoption of ER protocols. It should be noted that this group has previously published on their larger experience with implementation of ER protocols in liver surgery and demonstrated that these protocols resulted in improved patient outcomes.10,31,34

Perhaps more important than the effects seen following ER implementation for all cases were those seen amongst patients undergoing high-magnitude surgery. While it is challenging to amalgamate outcomes across multiple specialties, focusing on high-magnitude cases enabled analysis of a cohort of patients undergoing operations of more uniform complexity. This is reflected by the equivalent median procedure durations for patients undergoing high-magnitude surgery and treated on ER versus TP protocols (327 vs. 326 min, p = 0.466). That patients in the high magnitude cohort on ER protocols also were found to have improved outcomes, including decreased complications and reduced LOS, suggests the results of the analysis for all cases were not driven by a single specialty performing a large number of lower-complexity cases.

Because all surgical programs engage in continuous quality improvement at some level, one critique of this study is that it is possible that other simultaneous initiatives contributed to the observed improved patient outcomes. For example, the hepatobiliary and colorectal groups developed a quality improvement program around urinary tract infections that preceded ER implementation, and the gynecology group designed a perioperative bundle to reduce their rates of surgical site infections in parallel with their implementation. However, there were no ongoing system-wide improvements that could explain the consistency or magnitude of our cross-specialty findings, including the dramatic decrease in opioid utilization shared by all groups.

A second critique of the methodology may be the definition of ER protocol compliance. As previously discussed, the four pillars of ER protocols have been well described, and each pillar includes more than one patient intervention. Although specific interventions were not proscribed at an institutional level, each team designed ordersets and pathways that facilitated high compliance rates with multiple accepted individual elements. Several studies have shown that ER protocol compliance of ≥ 70% results in a demonstrable effect on patient outcomes.1,35,36 Regarding the adherence to guidelines in this study, preoperative education, preoperative carbohydrate loading (where indicated), and preoperative multimodal nonnarcotic oral analgesia were uniform. To facilitate consistent implementation and trainee education, electronically implemented ordersets (including the postoperative protocols and the analgesia plans) were utilized in more than 90% of ER pathway patients across all disciplines. Each of these ordersets was designed to include > 70% of recommended postoperative elements. Case audits demonstrated 60% to 100% compliance for each core component of the ER protocols (i.e., preoperative patient education and the four pillars of ER clinical care).

Lastly, the retrospective nature of this study makes it possible that other unmeasured confounding factors impacted our results. Although it is possible that confounding factors may have resulted in overestimation of the observed benefits of ER protocols, several elements of this study counter the potential for selection bias and support the conclusion that improvements in outcomes were attributable to ER protocol implementation. These include the NSQIP methodology, random case sampling, consistency of implementation within and across specialties, correlation with high-magnitude cases, and large patient numbers.

Conclusions

This analysis of a multispecialty enhanced recovery implementation at a large comprehensive cancer center demonstrates that not only is ER protocol implementation feasible for oncologic patients, but it is safe and effective in improving postoperative outcomes. This study provides evidence in support of ER utilization for a population of patients previously underrepresented in the ER literature. Considering the number of major oncologic operations performed annually across the world, wide-scale adoption of ER protocols is likely to improve the outcomes of many patients. As postoperative complications and delayed postoperative recovery is known to prevent return to adjuvant treatment for oncologic patients, future work should focus on defining the potential long-term oncologic benefits of ER protocols.9,16,37,38,–39