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Contents: Gynecologic Surgery: Original Research

Effect of an Enhanced Recovery After Surgery Program on Opioid Use and Patient-Reported Outcomes

Meyer, Larissa A. MD, MPH; Lasala, Javier MD; Iniesta, Maria D. MD, PhD; Nick, Alpa M. MD; Munsell, Mark F. MS; Shi, Qiuling PhD; Wang, Xin Shelley MD; Cain, Katherine E. PharmD; Lu, Karen H. MD; Ramirez, Pedro T. MD

Author Information
doi: 10.1097/AOG.0000000000002735

Surgical care reflects a significant component of national health care utilization and expenditures, with an estimated 8.4 million discharges associated with a surgical procedure and a cost estimate of greater than $157 billion.1 Enhanced recovery after surgery (ERAS) is a multidisciplinary, multimodal approach to perioperative care that aims to reduce the effects of surgical stress and to avoid traditional aspects of perioperative care that have documented harm.2 Recent data suggest wide variation and overprescription of opioids after elective surgery.3 Rates of new persistent opioid use after surgical procedures are estimated at 6%.4 Implementation of evidence-based clinical guidelines for pain management is an important component of prevention of substance use disorders involving prescription drugs.5

Kehlet,6 an early pioneer, developed an ERAS protocol in 2001. Subsequently, ERAS has continued to evolve with guidelines for multiple surgical disciplines, including the recently published guidelines for gynecologic surgery.2,7,8 Although prior studies involving ERAS have demonstrated improvements in traditional metrics, they have not captured crucial outcomes such as symptom burden and functional recovery from a patient's perspective. With the growing focus on patient-centered care, patient-reported outcomes are increasingly important in comparative effectiveness research.9–11 Patient-reported symptom monitoring during routine cancer care has been associated with improvements in survival and has the potential to improve postsurgical outcomes.12,13 Our objective was to compare perioperative outcomes with a focus on intraoperative and postoperative opioid consumption as well as patient-reported symptom burden and functional recovery in women undergoing surgery before and after implementation of an ERAS program.


Our previous practice and current ERAS program have been previously described.14 Our ERAS program included interventions that can be categorized into preoperative, intraoperative, and postoperative phases.14 These include but are not limited to preoperative medical optimization of chronic disease; nutritional counseling; allowing oral intake of clear fluids up to 2 hours before induction of anesthesia; carbohydrate loading; avoidance of mechanical bowel preparation; preoperative, intraoperative, and postoperative euvolemia through goal-directed fluid therapy; intraoperative and postoperative opioid-sparing multimodal analgesia; restrictive use of surgical drains; and an emphasis on early ambulation and feeding.

Cohort 1 includes all consecutive patients who underwent open elective gynecologic surgery on our ERAS pathway between November 6, 2014, and October 26, 2016. Cohort 2 is a subset of patients from Cohort 1 who consented to participate in a separate research protocol to collect patient-reported outcomes and symptom burden in the perioperative period. To minimize bias from changes in practice over time, patients who underwent open surgery in the 6 months before the start of our ERAS program (May–October 2014) and participated in the collection of patient-reported outcomes served as historical controls. To be included in cohort 2 or the historical control group, patients had to have at minimum a preoperative baseline patient-reported outcomes assessment in addition to assessments on the first and second postoperative days.

Clinical and demographic information collected from the medical record included age, body mass index (BMI, calculated as weight (kg)/[height (m)]2), ethnicity, race, tumor type (primary or recurrent disease and designation as malignant, benign, tumor of uncertain malignant potential) as well as indication for surgery. Ovarian, fallopian tube, and primary peritoneal cancer were combined into one primary disease site given their clinical similarity. Other sites were designated as cervix, uterine (nonsarcoma), and uterine sarcoma. American Society of Anesthesiologists classification of physical health15 and Charlson Comorbidity Index16 were used to assess comorbidities. The current malignancy was not included in the calculation of the Charlson Comorbidity Index to more accurately reflect precancer comorbid conditions. For participants with ovarian, fallopian tube, or primary peritoneal cancer, a surgical complexity score17 was assigned.

The Dindo-Clavien grading system was used to characterize the 30-day complication rates.18 Specifically, we evaluated gastrointestinal (GI), genitourinary (GU), central nervous system (CNS), and hematologic complications within 30 days of the surgery date. Specifically, the number of patients with any postoperative complications within 30 days of surgery was identified and then categorized as either mild (grade 1–2), or severe (grade 3–4). A patient was characterized according to their highest grade postoperative complication of a given type (GI, GU, or CNS).

Study data were collected and managed using Research Electronic Data Capture electronic data capture tools19 hosted at MD Anderson as part of an institutionally approved quality improvement study (QI-6033).

Perioperative patient-reported symptom burden was collected on a separate institutional review board-approved protocol (BS99-094) where patients provided written informed consent. Women from the historical control group and cohort 2 were given the MD Anderson Symptom Inventory-Ovarian Cancer module, a 27-item validated tool plus two additional questions on diarrhea and heartburn.20 For the MD Anderson Symptom Inventory symptom components, individuals were asked to rank symptom severity during the previous 24 hours on a scale of 0–10 with 0 being “not present” and 10 being “as bad as you can imagine.” Interference was also assessed on a 0–10 scale with 0 being “did not interfere” and 10 being “interfered completely.”20 The MD Anderson Symptom Inventory-Ovarian Cancer was administered preoperatively, daily while hospitalized after surgery, on days 3 and 7 postdischarge, and weekly for 7 additional weeks postoperatively. The MD Anderson Symptom Inventory-Ovarian Cancer was administered on paper, by an interactive voice-recorded telephone system, or electronically by email link.

Pain medication data were collected on the day of surgery (postoperative day 0) and on the first 3 days after surgery. Patient-reported pain was assessed by the MD Anderson Symptom Inventory-Ovarian Cancer as described previously. Postanesthesia care unit pain scores were assessed using the 11-point pain scale (range 0–10).

Descriptive statistics were used to summarize the demographic and clinical characteristics. Categorical variables were compared between the pre-ERAS and ERAS groups with Fisher exact test. The Wilcoxon rank-sum test was used to compare medians between continuous variables. Opioid medication data were collected for the first 4 days of the hospitalization and converted into morphine equivalent daily doses. The patient cohorts were determined using convenience sampling. However, considering that the SD for pain at its worst is 2.5, utilizing the criteria of half a SD, the minimally important difference is 1.2 points on the MD Anderson Symptom Inventory. Thus, we would estimate that each group would need a minimum of 67 patients.21

Linear mixed-effects modeling was used to examine the longitudinal change of symptom burden from pain, fatigue, and symptom interference during hospitalization (from day of surgery to day 5 postsurgery). To control for other factors that might influence patient-reported outcomes, age, performance of cytoreductive surgery, cancer site, estimated blood loss, and surgical complexity score were included in all models. The Wilcoxon test was used to compare the pre-ERAS and ERAS groups with respect to the median time to return to mild or no symptom burden, defined as a score less than 4 at two consecutive assessments. Kaplan-Meier curves were used to illustrate the time to return to mild or no symptom burden for the two groups.

Compliance with the ERAS pathway was defined as adherence to the recommendations in the published guidelines.7,8 We estimated the percentage of patients compliant with each of the 20 components of the compliance measure with 95% exact binomial CIs, and we estimated the overall percentage of compliance with a 95% CI. All statistical analyses were performed using SAS 9.3 for Windows.


A total of 533 patients (cohort 1) participated in the enhanced recovery pathway compared with 74 patients in the historical control (Table 1). The median age of both groups was 58 years (range 18–85 years). There was no difference between the two groups in terms of ethnicity, American Society of Anesthesiologists or Charlson Comorbidity Index score, BMI, tumor type, or indication for surgery. Additionally, there was no difference in receipt of prior chemotherapy or radiation or history of chronic opioid use. There were racial differences noted between the two groups (P=.04). In the ERAS group, there were more black women (11.2% vs 2.7%) and more Asian women (4.9% vs 1.4%). There were fewer white women in the ERAS group (79.9% vs 96%).

Table 1.
Table 1.:
Demographics, Clinical Characteristics, and Perioperative Outcomes
Table 1.-a
Table 1.-a:
Demographics, Clinical Characteristics, and Perioperative Outcomes

Cohort 2, the subset of patients on ERAS who participated in the collection of patient-reported outcomes (n=226), was compared with 67 historical controls (Appendix 1, available online at Similarly, there was no difference in ethnicity, American Society of Anesthesiologists or Charlson Comorbidity Index scores, tumor type, or indication for surgery. In the subgroup analysis with cohort 2, there were also no significant differences in history of prior chemotherapy or radiation or history of chronic opioid use. Similar to cohort 1, there were differences in race between the two groups with more black women in the ERAS group (13.3% vs 1.5%). There were fewer intraoperative complications in the ERAS group (3.1% vs 10.5%, P=.02) but no difference between the groups in GI, GU, CNS, or hematologic postoperative complications. Estimated blood loss was lower in the ERAS group (250 vs 350 cc, P=.04).

Median operating time for the all patients was 219 minutes with a median of 236 (range 98–575 minutes) for the historical controls and 216 minutes for the ERAS group (range 33–885 minutes, P=.02). Median estimated blood loss for the group was 250 mL with a median of 400 mL (range 40–5,250 mL) for the control group and 250 mL (range 5–5,500 mL) for the ERAS group (P=.01). The distribution of low, intermediate, or high surgical complexity scores did not differ between the ERAS and control groups. There was no significant differences between groups with respect to intraoperative complications.

There was a 25% reduction in median length of stay after surgery for patients in the ERAS pathway (3 vs 4 days, P<.001). There were no significant differences in overall, grade 1–2, or grade 3–4 GI, GU, CNS, or hematologic complications between the pre- and post-ERAS patient groups. Reoperation (P=.12), readmission (P=.86), and 30-day mortality (P=.99) rates were similar (Table 1).

Intraoperative and postoperative opioid use was significantly lower in the ERAS group (Table 2 for cohort 1; Appendix 2, available online at, for cohort 2). The median intraoperative morphine equivalent daily dose for the pre-ERAS group was 102.5 (range 0–544.5) compared with 62.5 (range 0–1,407.5), representing a 39% reduction (P<.001). The reduction in opioid intake was even greater postoperatively (Fig. 1A). There was an 83.8% reduction in median morphine equivalent daily dose on postoperative day 0 for the ERAS group (49.3 vs 8, P<.001). Median postanesthesia care unit pain scores were improved in the ERAS group (4 vs 6, P<.001). The decreased opioid requirement persisted with an 80.2% reduction on postoperative day 1 with median morphine equivalent daily dose (50.6 vs 10, P<.001), a 71.2% reduction on day 2 (26 vs 7.5, P<.001), and a 50% reduction on day 3 (15 vs 7.5, P=.003). Despite the overall 72% reduction in median daily morphine equivalent daily dose from postoperative day 0 to postoperative day 3 in the ERAS group, pain scores were not significantly higher in the ERAS group (P=.80) (Appendix 3, available online at Notably, 86 patients (16%) on the enhanced recovery pathway were opioid-free from the first to third postoperative day compared with none of the patients in the pre-ERAS cohort (P<.001).

Table 2.
Table 2.:
Opioid Use (Including Chronic Opioid Users)
Table 2.-a
Table 2.-a:
Opioid Use (Including Chronic Opioid Users)
Fig. 1.
Fig. 1.:
Morphine equivalent dose (postanesthesia care unit and inpatient unit). The median is shown as a bold horizontal bar across the waist of the box, the top of the box represents the third quartile of the distribution, and the bottom of the box represents the first quartile of the distribution. The notches on the box represent the 95% CI for the median. The whiskers for each box extend to 1.5×interquartile range above and below the box with a lower limit of 0. Outliers are represented by small circles beyond the whiskers. For aesthetic reasons, the extreme outliers beyond 250 are omitted from the figures. The width of a box is proportional to the sample size of the distribution represented by the box. Postoperative days 1 and 2, P<.001; postoperative day 3, P=.003.Meyer. Patient Outcomes in Enhanced Recovery. Obstet Gynecol 2018.

Longitudinal assessments of patient-reported outcomes were analyzed in the hospital (Fig. 2A–C) and after hospital discharge (Fig. 3A–C). After pain, fatigue is the most highly ranked symptom in the hospital and rises to the highest ranking symptom after hospital discharge. Fatigue during the hospital stay was significantly lower in the ERAS group (Fig. 2A; P=.01). After discharge from the hospital, patients on the enhanced recovery care pathway had a significantly shorter median return to no or mild fatigue, 10 days (95% CI 6.6–13.4 days) compared with 30 days (95% CI 7.6–52.4 days; P=.03; Fig. 3A).

Fig. 2.
Fig. 2.:
Longitudinal assessment of fatigue during the hospital stay (P=.01) (A), in-hospital interference with walking (P=.003) (B), and daily total interference composite score during the hospital stay (P=.008) (C). Line with bar represents mean and 95% CI. P values calculated from mixed-effect model. ERAS, enhanced recovery after surgery.Meyer. Patient Outcomes in Enhanced Recovery. Obstet Gynecol 2018.
Fig. 3.
Fig. 3.:
Time to recovery. A. Return to mild or none (less than 4) for fatigue level after discharge after surgery (P=.03). B. Return to mild or none (less than 4) for interference with walking after discharge after surgery (P=.003). C. Return to mild or none (less than 4) for composite total interference score after discharge after surgery (P=.02). ERAS, enhanced recovery after surgery.Meyer. Patient Outcomes in Enhanced Recovery. Obstet Gynecol 2018.

Self-reported interference with walking during hospitalization was significantly lower in the ERAS group with the greatest difference in the mean seen on postoperative day 1 (Fig. 2B; P=.003). Total interference score is a calculated composite endpoint of both physical and emotional interference and includes interference scores with work, activity, walking, enjoyment of life, mood, and relations with others. Mean total interference after surgery was also lower in the ERAS group during hospital (Fig. 2C; P=.008). After hospital discharge, patients in the ERAS group returned to no or mild (less than 4) interference with walking at a median of 5 days (95% CI 2.2–7.8 days) compared with 13 days (95% CI 4.5–21.5 days, P=.003) in the pre-ERAS group (Fig. 3B). Similar improvements were seen in total interference scores with the ERAS group reporting a median return to mild or no interference in 3 days (95% CI 0.54–5.4 days) compared with 13 days (95% CI 3.6–22.4 days, P=.02; Fig. 3C).

Compliance with ERAS protocol elements was based on the published guidelines.7,8 Details on compliance with any individual element can be seen in Table 3. Overall, 75.2% of patients were compliant with at least 70% of the elements. Only six patients (1.1%) were compliant with 50% or fewer of the elements. Although minimally invasive surgery is recommended in the guidelines when appropriate and surgical expertise is available, our group of patients included only those undergoing open gynecologic surgery, so compliance with use of minimally invasive surgery is by design nil in this study cohort.

Table 3.
Table 3.:
Percentage of Patients Compliant With Enhanced Recovery After Surgery Components


Implementation of a robust ERAS program requires a team approach with active involvement of surgeons, anesthesiologists, nurses, dieticians, and pharmacists along with active engagement of the patient and their nonclinical caregivers. Although there are inherent limitations when using historical controls, we did not believe a randomized trial of ERAS would be feasible because of the extensive culture and practice shifts that occur with successful implementation. Therefore, we implemented a multidisciplinary quality improvement initiative based on ERAS principles for all patients undergoing laparotomy for gynecologic indications. Initially, only patients undergoing open surgery were included with a plan to expand to patients undergoing minimally invasive surgery at a later date.

Implementation of ERAS programs coupled with a continuous performance audit represents an effective approach to embracing multidisciplinary changes aimed to improve the delivery of surgical care. We have demonstrated how implementation of an enhanced recovery program for patients undergoing open abdominal surgery for gynecologic indications can improve patient-reported outcomes and significantly decrease the rate of intraoperative and postoperative opioid consumption without compromising pain control. Increasing compliance with individual ERAS protocol elements has been associated with reductions in length of stay and other postoperative complications.22 We demonstrated a high level of compliance with the ERAS pathway, which decreased length of stay without increasing complications. A significant proportion of patients undergoing open surgery for gynecologic malignancies will require postoperative chemotherapy or radiation. Delays in initiating adjuvant therapy have been associated with decreased survival in multiple cancer types, including gynecologic cancers.23–25 In colorectal surgery, improvements in 5-year survival were documented in patients who had high levels of compliance with ERAS protocols.26 Therefore, improvements in postoperative recovery may be especially meaningful in an oncologic patient population.

Multiple studies across disease sites and procedures have demonstrated improvements to patients on enhanced recovery programs, including decreased length of stay, complications, cost27–30 as well as an association with improved survival.26,31 Although our findings such as 25% reduction in length of stay with no increase in complication or readmission rates are similar to other findings and contribute to the growing literature on the effects of ERAS programs, the unique contribution of our study lies in the demonstration of “enhanced recovery” from the patient perspective with improvement in patient-reported outcomes such as fatigue, walking, and total interference after surgery. The MD Anderson Symptom Inventory interference score has been validated as a measure of symptom-related functional impairment in patients with cancer after surgery.32 Interference with walking has been further described as a sensitive marker for functional recovery after surgery.33 We found significant improvements both in the hospital and faster return to mild or no symptoms after hospital discharge for both walking and total interference score, a composite score that includes interference with work, activity, walking, enjoyment of life, mood, and relations with others.

A possible contributing factor to the demonstrated “enhancement” in recovery may be the decrease in opioid use and the effect it had on patients' symptoms and functional recovery. In our patient population, we demonstrated a striking 72% reduction in median opioid intake in patients on our ERAS pathway without an increase in patient-reported pain scores. Additionally, 16% of our patients who underwent laparotomy on an ERAS pathway were opioid-free during their hospital stay from the day of surgery up to postoperative day 3. This reduction in opioid intake and its related side effects likely contributed to the improvements identified in symptom burden and functional recovery. The Surgeon General has named the opioid epidemic as a major public health concern.34 Data suggest that those who receive an opioid prescription after surgery are 44% more likely to become long-term opioid users.35 For certain individuals with opioid overuse disorder, opioid pain medications prescribed after surgery provided their first exposure that develops into addiction.36 Implementation of multimodal analgesia through our enhanced recovery program was associated with both statistically and clinically meaningful decreases in opioid use and aligns with guidelines for safe and effective postoperative pain management.37 The Center for Medical Technology Policy has called for an “order-of-magnitude” change in U.S. adoption of enhanced recovery programs to dramatically reduce preventable complications and deaths for future surgical patients.38 Our findings suggest that not only can an ERAS program be safe and effective in the immediate and extended postoperative period, but from a patient's point of view, physical and affective aspects of recovery are improved. The reduction in opioid use within an enhanced recovery pathway is also an important contribution to multipronged efforts aimed to address the growing opioid epidemic39 and improved symptoms and functional recovery after surgery.


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