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Enhanced Recovery After Surgery in Gynecologic Oncology Surgery


Enhanced Recovery After Surgery (ERAS) is a multimodal perioperative care pathway to improve functional rehabilitation after a surgical procedure, reducing the patient’s stress response in reaction to the operation and postoperative catabolism. The concept was first introduced by Kehlet, who suggested that a focus on early postoperative rehabilitation and nutrition, use of regional analgesia, and avoidance of recovery-limiting procedures (e.g., liberal use of intravenous [IV] fluids, placement of a urinary bladder catheter and drains) might lead to accelerated recovery and reduced postoperative morbidity and costs. In terms of costs, the use of ERAS has resulted in a mean savings of $2245 (€1651) per patient. The program includes a set of elements that are evidence-based modifications of traditional perioperative patient care, but it is a true change of paradigm in the care of surgical patients. The number of ERAS elements varies, but approximately 20 items are included in most programs. In 2010 the ERAS Society was officially founded. Since then, several sets of guidelines have been published to expand ERAS programs in different specialties, and so far such implementations have demonstrated the efficacy of ERAS in postoperative recovery. The main goals of ERAS programs described to date are to reduce the length of hospital stay after a surgical procedure and to “speed” patients’ return to normal daily activities without increasing complications, readmission rates, or cost. To achieve these goals, ERAS programs focus primarily on reduction of perioperative stress, achievement of satisfactory pain control, resumption of normal gastrointestinal function, and early mobilization. The Royal College of Obstetricians and Gynaecologists has suggested that ERAS programs offer safe, high-quality perioperative care and should become standard practice for all women undergoing elective gynecologic surgical procedures.

The aim of this chapter is to describe what an ERAS program is, with gynecologic oncology as the main focus of the discussion. For this purpose, the evidence that has been published so far in gynecologic oncology is outlined; every component of an ERAS pathway is described; and a focus summary of the recommendations based on the ERAS Society Gynecologic Oncology guidelines, Part I and Part II, is provided.

ERAS in Gynecologic Oncology

Data on the incorporation of ERAS programs in gynecologic oncology are limited. In 2006, one of the first publications that evaluated accelerated recovery in gynecologic oncology was published by Marx and co-workers, who evaluated 72 patients undergoing laparotomy for ovarian cancer. Patients were divided into two groups according to whether they received “traditional” care or underwent “multimodal rehabilitation” (no bowel preparation, prophylactic postoperative nausea and vomiting [PONV] medication, early mobilization, early removal of drains and urinary catheter, early oral intake, opioid-restrictive analgesia, and routine use of laxatives). The authors reported that the median postoperative stay was reduced from 6 days in group 1 (mean, 7.3 days) to 5 days in group 2 (mean, 5.4 days) ( P < .05). There were no differences in complication rates ( P < .01), and the readmission rates were higher in the traditional care group ( P < .05). In another study, Chase and co-workers retrospectively evaluated 880 gynecologic patients who underwent laparotomy (48% had a final pathologic assessment consistent with malignancies) with an ERAS program (called in the study “postoperative clinical pathway”). The most common cancer was endometrial (66%). Forty percent of the procedures performed were categorized as radical and/or staging procedures. The ERAS program consisted of preoperative counseling; no fluid overload in the intraoperative and postoperative settings; early mobilization; early removal of drains, lines, and urinary catheters; early oral intake; and opioid-sparing analgesia. The median length of hospital stay was 2 days (range, 0–52 days). The readmission rate was 5% (44/880), no reoperations were reported, and 7% (59/880) of patients had a complication (most commonly ileus). The complication rates were comparable or decreased when compared with those of other studies in the literature. The authors concluded that these clinical pathways reduced the length of hospital stay without increasing morbidity or mortality after laparotomy for suspected gynecologic malignancy.

Gerardi and co-workers evaluated an ERAS pathway in gynecologic oncology patients who underwent a rectosigmoid colectomy as part of their surgical treatment for advanced ovarian and primary peritoneal cancers. A total of 64 patients were included in the study and were divided into two groups: those who received ERAS perioperative care (group A; n = 19 patients) and a control group (group B; n = 45 patients). The ERAS elements included in this study were (1) early removal of drains, lines, and urinary catheters and (2) early oral intake. Although the median time to flatus was equivalent between groups, median time to tolerance of regular diet was significantly shorter in the clinical pathway group (ERAS) than in the conventional treatment group (3 vs. 6 days, respectively; P = .013). Patients in group A had a median length of stay (LOS) of 7 days, compared with 10 days for patients in group B ( P = .014). The median total hospital cost of postoperative care for patients in group A was $19,700, compared with a median total cost of $25,110 for patients in group B, with a median reduction in hospital cost of $5410 per patient with implementation of the clinical pathway. There was no difference in the 30-day readmission rate (group A, 21%; group B, 33%; P = .379).

Carter reported a review of a total of 389 patients who underwent laparotomy for a suspected or confirmed preoperative cancer diagnosis. The study included the majority of the 22 ERAS elements (preoperative counseling; minimization of fasting period; no bowel preparation; multimodal analgesia; no fluid overload; no routine drains; early mobilization; early removal of drains, lines, and urinary catheters; early oral feeding; balanced multimodal opioid-restrictive regimen; and routine use of laxatives). A total of 227 (58%) had cancer (51% ovarian, 39% endometrial, and 9% cervical). The surgical procedures were deemed to be complex in 348 patients (89%), with lymph node sampling or dissection performed in 68 of them (17%). The median length of hospital stay was 3 days, with a readmission rate of 4% and a reoperation rate of 0.5%. Twenty-eight percent of the patients were discharged on postoperative day 2. There were no differences in LOS according to the type of cancer or even if the final pathology report confirmed benign disease. In addition, the study evaluated the impact of program experience and the appointment of a clinical nurse consultant. The authors found that increasing program experience was associated with an improvement in the percentage of patients discharged on day 2 from 10% in the first year to 36% in the fifth year of the program.

A previously published study on ERAS in gynecologic oncology, by Kalogera and co-workers, was a retrospective comparison between an ERAS program and conventional care in women undergoing major abdominal surgical procedures for gynecologic malignancies or vaginal reconstructive procedures for pelvic organ prolapse. A total of 241 women in the ERAS group (81 cytoreductive, 84 staging, and 76 vaginal surgeries) were compared with 235 women in the conventional care group. In that study, postoperative nausea (55.6% vs. 38.5%, P = .031) and vomiting (17.3% vs. 2.6%, P = .002) were more frequent in the ERAS group than in the control group. The authors attributed these results to the fact that 40% of patients in the case group had undergone a large bowel resection. Despite this increase in nausea and vomiting, women in the case group had a return of bowel function 1 day earlier than the control group ( P = .001), and the rate of postoperative ileus was no different between groups. Eighty-seven percent of patients rated their satisfaction with nausea and vomiting control as excellent or very good, suggesting that early feeding overall is well tolerated. Women in the ERAS group had a median time to return of bowel function 1 day less than the time in the control group ( P < .001) without differences in postoperative ileus. Median length of hospital stay was 4 days less in the ERAS group than in the control group (8.7 ± 7.6 days vs. 11.9 ± 11.9 days, P < .001). Almost half (46.1%) of the patients in the ERAS group were discharged the day after the operation, compared with only 6.5% of women in the control group. The rates of readmission and postoperative complications were no different between the groups. The ERAS program was associated with a 30-day cost savings of more than $7600 per patient (18.8% reduction). In addition, 95% of patients in the ERAS group rated their care as excellent or very good (patient satisfaction surveys were not available in the control group). The authors concluded that implementation of an ERAS program was associated with acceptable pain management, reduced LOS with stable readmission and mortality rates, adequate patient satisfaction, and substantial cost reductions.

A Cochrane review of perioperative ERAS programs for gynecologic cancer patients published in 2012 and subsequently updated in 2015 concluded that there was no evidence to support or refute the use of an ERAS program; however, the authors recognized that this was likely due to the lack of prospective randomized trials and went on to discuss the benefits shown in the nonrandomized studies.

In 2014, Nelson and co-workers published a comprehensive review of the literature regarding ERAS programs in gynecologic oncology. The authors analyzed seven reports and found significant improvements in patient satisfaction, LOS (up to 4 days), and cost (up to $7600 in savings per patient) in ERAS programs compared with historical controls. They also found that morbidity, mortality, and readmission rates were no different between groups. The subject of physician and patient acceptance of ERAS programs was also addressed in a recent publication. Hughes and colleagues published a survey that assessed the perceptions of care providers and patients on the relevance and importance of an ERAS program. In that study, preoperative and postoperative surveys were completed by patients who underwent major hepatic, colorectal, or esophagogastric procedures. A total of 109 patients and 57 care providers completed the preoperative survey. Freedom from nausea and pain at rest were the care components rated highest by both patients and care providers. Further data are needed pertaining to overall acceptance of ERAS programs and patient-reported outcomes.

A point of interest to surgeons is whether the benefits obtained from use of an ERAS program in gynecologic oncologic patients undergoing open surgical procedures would also be achieved in patients undergoing minimally invasive procedures. This question arises from the well-known premise that minimally invasive surgical procedures offer benefits in terms of shorter LOS and fewer complications compared with their open counterparts.

Chapman and co-workers performed a retrospective case-control study including 165 patients undergoing robotic or laparoscopic gynecologic oncology procedures. Fifty-five patients received care according to an ERAS program, and 110 were historical controls. The ERAS elements included in the study were carbohydrate loading, no bowel preparation, opioid-sparing pain medications, PONV medication, transverse abdominis plane (TAP) block (a peripheral nerve block designed to anesthetize the nerves supplying the anterior abdominal wall, T6–L1) or IV lidocaine, no fluid overload, ambulation and removal of urinary catheter 6 hours after operation, and early regular diet. ERAS patients were significantly more likely to be discharged on postoperative day 1 than patients in the control group (91% vs. 60%, respectively; P < .001). The median LOS for ERAS patients was 30 hours (interquartile range, 30–54 hours) compared with 34 hours (interquartile range, 27–32) for historical control patients ( P < .01). Hospital costs for patients were on average $1810 less than for historical control patients ($13,771 compared with $15,649; P = .01), representing a 12% decrease in overall cost. Opioid use decreased by 30% in the ERAS group compared with patients in the control group (31 vs. 44 mg of IV morphine equivalents, P < .01), and the authors also reported significantly lower mean postoperative pain scores (visual analog scale score 2.6 vs. 3.12 on postoperative day 1, P = .03). No ERAS patient required patient-controlled analgesia or received epidurals. Readmission rates did not differ between groups ( P = .53). No patients in either group required reoperation. In conclusion, the authors argued strongly in favor of instituting this low-cost, low-risk intervention as a standard part of perioperative care in patients undergoing minimally invasive procedures.

Elements of ERAS Program and Guidelines

The elements of a standard ERAS program and measures of compliance are presented here as outlined and followed by the Department of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center. The program’s core elements are divided into three groups: preoperative, intraoperative, and postoperative ( Fig. 3.1 ). It should be noted that all programs include all elements of ERAS, and there remains some debate in the literature and among ERAS teams as to which are the absolutely crucial elements for successful outcomes. Emphasis is given to the elements that are present in most studies and in the two sets of ERAS guidelines (Part I and Part II) published in 2016 by the ERAS Society ( Tables 3.1–3.3 ).

Fig. 3.1, Elements of Enhanced Recovery After Surgery pathway. PONV, postoperative nausea and vomiting.

Table 3.1
Preoperative Components
Component Recommendation
Preoperative counseling Patients should routinely receive dedicated preoperative counseling
Preoperative optimization Smoking and alcohol consumption should be stopped 4 weeks before operation
No bowel preparation Routine oral bowel preparation is not recommended
Minimal preoperative fasting Clear fluids should be allowed up to 2 h and solids up to 6 h before induction of anesthesia
Carbohydrate loading Carbohydrate loading reduces postoperative insulin resistance and should be used routinely
No anxiolytic premedication Routine administration of sedatives to reduce anxiety preoperatively should be avoided
Thromboprophylaxis Heparin 5000 units subcutaneously on arrival in holding area
Antibiotic prophylaxis IV antibiotics (first-generation cephalosporin or amoxicillin–clavulanic acid) should be administered routinely within 60 minutes before skin incision (IV cefazolin 2 g or IV cefoxitin 2 g)
IV, Intravenous.

Table 3.2
Intraoperative Components
Component Recommendation
Short-acting anesthesia Short-acting anesthetic agents should be used to allow rapid awakening
Maintenance of normothermia Maintenance of normothermia with active warming devices should be used routinely
No drainage of the peritoneal cavity or nasogastric intubation Avoidance of routine drainage of the peritoneal cavity and nasogastric tube (NGT) placement
NGT inserted during a surgical procedure should be removed before reversal of anesthesia
Avoidance of salt and water overload Goal-directed fluid therapy (restrictive or liberal fluid regimens should be avoided)
Minimally invasive procedures Should be the selected approach when possible

Table 3.3
Postoperative Components
Component Recommendation
Postoperative nausea and vomiting (PONV) prophylaxis Patients should receive prophylaxis using a multimodal approach to PONV that includes more than two antiemetic agents
Nonopioid oral analgesia or multimodal analgesia Multimodal approach to analgesia (nonsteroidal antiinflammatory drugs [NSAIDs] or acetaminophen, gabapentin, and dexamethasone [unless contraindications exist])
Avoidance of salt and water overload Intravenous fluids discontinued on postoperative day 1; balanced crystalloid solutions are preferred to 0.9% normal saline
Early oral nutrition Regular diet within the first 24 h after gynecologic oncology surgical procedures
Removal of urinary catheter Urinary catheter should be removed within 24 h postoperatively
Early mobilization Early mobilization within 24 h of surgical procedure
Postoperative glucose control ERAS elements that reduce metabolic stress should be employed to reduce insulin resistance and the development of hyperglycemia
Glucose levels above 180–200 mg/dL should be treated with insulin infusions and regular blood glucose monitoring to avoid the risk of hypoglycemia
Audit of compliance and outcomes Audit of compliance should be done regularly

Preoperative Components

Preoperative Counseling

Preoperative counseling helps to set expectations about surgical and anesthetic procedures, fatigue, and pain and to diminish fear. Information should be given to patients not only on the details of the procedure but also on what the patient can expect during recovery. Most studies show that counseling provides beneficial effects with no evidence of harm.

  • It is recommended that patients routinely receive dedicated preoperative counseling.

Preoperative Optimization

It is generally accepted that preoperative medical optimization is necessary before surgical procedures. Use of tobacco and alcohol should be routinely assessed preoperatively because they increase postoperative morbidity and negatively influence recovery. Smoking and alcohol cessation at least 4 weeks before an operation is strongly recommended. Studies have shown that this intervention reduces postoperative complications. The presence of anemia and undiagnosed diabetes or hyperglycemia should be identified and corrected. For patients with gynecologic cancer, the risk of delaying a procedure in order to complete preoperative optimization must be considered.

  • Smoking and alcohol consumption (alcohol abusers) should be stopped 4 weeks before a surgical procedure.

  • Anemia should be actively identified, investigated, and corrected preoperatively.

Preoperative Mechanical Bowel Preparation

Mechanical bowel preparation (MBP) is not routinely recommended because it has been associated with patient distress, may cause dehydration, and is associated with prolonged ileus. A Cochrane review of 18 randomized clinical trials (5805 patients) found no statistically significant evidence that patients benefit from either bowel preparation or rectal enemas. There were no differences in infection rates in patients with and without bowel preparation (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.95–1.42), and the rate of anastomotic leak was 4.4% for patients with bowel preparation and 4.5% for those without (OR, 0.99; 95% CI, 0.74–1.31). In patients undergoing minimally invasive procedures, the routine use of MBP has not been shown to improve intraoperative visualization, bowel handling, or ease of performing the procedure.

A 2014 Cochrane review regarding antibiotic use in patients undergoing colorectal surgical procedures included 260 trials and 43,451 patients. The authors of that review concluded that there is high-quality evidence showing that antibiotics covering aerobic and anaerobic bacteria delivered orally or intravenously (or both) before elective colorectal surgical procedures can reduce the risk of postoperative surgical wound infection by as much as 75%. Also, the study revealed that there is no need for a second intraoperative dose or any postoperative doses when the antibiotic is being given for prophylaxis alone and that additional administration may increase the risk of resistant organisms and Clostridium difficile colitis. It appears that a combination of both routes of administration (oral and IV) results in the greatest decrease in risk of surgical site infection (SSI). Currently, the preponderance of the evidence regarding MBP favors avoiding the routine use of MBP.

One question that remains unanswered pertains to whether preoperative oral antibiotics (OAs) reduce SSI after bowel operations when MBP is not used. Two retrospective studies have addressed this subject. In the first study, Cannon and co-workers analyzed Veterans Affairs Surgical Quality Improvement Program preoperative risk and SSI outcome data linked to Veterans Affairs Surgical Care Improvement Project and Pharmacy Benefits Management Services data including 9940 patients. Colonic and rectal procedures were included. For the analysis, patients were categorized into four groups (MBP alone, MBP with preoperative OAs, no MBP and no OAs, and no MBP with OAs). The authors found that the use of OAs, with or without MBP, resulted in a significant decrease in SSI in comparison with no bowel preparation alone (9.0% vs. 18.1%, P < .0001). There was no significant difference in the SSI rates between those receiving OA alone and those receiving OA plus MBP (8.3% vs. 9.2%, P = .47). Those receiving no bowel preparation had SSI rates similar to those in patients who had MBP only (18.1% vs. 20%), regardless of OA use. In an adjusted analysis, the use of OA alone was associated with a 67% decrease in SSI rates (OR, 0.33; 95% CI, 0.21–0.50). The second study, published by Atkinson and co-workers, used the National Surgical Quality Improvement Program database. This study included 6399 patients who underwent elective segmental colectomy without MBP. The authors concluded that the incidence of SSI differed substantially between patients who had received OAs and those who had not (9.7% vs. 13.7%, P = .01). When confounding factors are controlled for, the use of preoperative OAs decreased the incidence of SSI rates (OR, 0.66; 95% CI, 0.48–0.90; P = .01).

  • Routine oral MBP is not recommended for gynecologic oncology patients, including those with a planned bowel resection.

OAs should be used before an operation when it is known in advance that the patient will undergo a bowel procedure. There is no need to use MBP. A combination of neomycin and metronidazole is a valid option. Neomycin is given at a dose of 500 mg orally at 9:00 p.m. and 11:00 p.m. the night before the operation, and metronidazole is also given at a dose of 500 mg orally at 9:00 p.m. and 11:00 p.m. the night before the procedure.

Preoperative Fasting and Carbohydrate Loading

Prolonged fasting is associated with insulin resistance, which in turn is associated with increased morbidity, mortality, and length of hospital stay. To attenuate these, diminished fasting and carbohydrate drinks are recommended for patients undergoing major abdominal surgical procedures. Scientific evidence has shown that intake of clear fluids until 2 hours before an operation does not increase gastric contents, reduce gastric fluid pH, or increase complication rates. Caution must be implemented in diabetic patients, particularly those with diabetic neuropathy, given that such patients may have delayed gastric emptying for solids, thereby possibly increasing their risk of regurgitation and aspiration. One must note that patients with uncomplicated type 2 diabetes mellitus have normal gastric emptying.

Carbohydrate loading before surgical procedures has been advocated to achieve a metabolically fed state, reducing postoperative insulin resistance. In a meta-analysis including 27 randomized controlled trials (RCTs) (1976 patients) evaluating the effects of preoperative carbohydrate treatment on patients undergoing elective procedures, the authors demonstrated a significant reduction in LOS among patients undergoing major open abdominal operations. Preoperative carbohydrate treatment was safe (no occurrence of drink-related complications) and was associated with reduced development of postoperative insulin resistance without an increase in postoperative complications. Aspiration pneumonitis was not reported. ERAS guidelines recommend 400 mL of a 12.5% carbohydrate–containing clear drink with a proven safety profile until 2 hours before anesthesia. Both laparoscopic and minor surgeries are associated with minimal development of insulin resistance and low complication rates, and an intervention such as preoperative carbohydrate loading would not be expected to improve clinical outcomes in this group of patients. Hence, in patients without conditions associated with delayed gastric emptying, the intake of clear fluids until 2 hours before the induction of anesthesia as well as a 6-hour fast for solid food is recommended.

  • Clear fluids should be allowed for up to 2 hours and solids for up to 6 hours before induction of anesthesia.

  • Carbohydrate loading should be considered because it reduces postoperative insulin resistance and increases overall patient satisfaction.

Preanesthetic Medication

Routine administration of long-acting sedatives to decrease anxiety within 12 hours of a surgical procedure should be avoided owing to the effects of these sedatives on immediate postoperative recovery. Among the most common effects are somnolence, sedation, confusion, dysarthria, ataxia, vertigo, and stomach discomfort. The use of short-acting anxiolytics for severe preoperative anxiety may be appropriate on a case-by-case basis. When patients are appropriately informed and prepared for an operation, they exhibit suitably low levels of stress before elective procedures.

  • Routine administration of sedatives to reduce anxiety preoperatively should be avoided.

Thromboembolism Prophylaxis

The risk of venous thromboembolic events (VTEs) among patients undergoing surgical procedures for cancer is twofold to threefold higher than in patients without cancer. Venous thromboembolism is a major risk in gynecologic oncology patients, with rates as high as 8% in endometrial cancer and 38% in ovarian cancer. All gynecologic oncology patients undergoing major surgical procedures (i.e., longer than 30 minutes) should receive VTE prophylaxis with either low-molecular-weight heparin (LMWH) or heparin. Prophylaxis should be commenced preoperatively, combined with mechanical methods, and continued postoperatively. Pneumatic compression stockings reduce the rate of VTE when compared with observation within the first 5 days postoperatively. Their efficacy is equivalent to that of heparin and improved when combined with heparin in gynecologic oncology patients. Combined oral hormonal contraception is a risk factor for postoperative thromboembolism. The risk of thromboembolism varies according to progesterone type. There is lower risk with levonorgestrel, norethisterone, and norgestimate. Women should be encouraged to use an alternative form of contraception preoperatively. Continued use of combined oral hormonal contraception is an indication for thromboprophylaxis.

With regard to long-term thromboprophylaxis, a large prospective cohort trial showed an increased rate of VTE within 30 days of operation in patients with cancer, and extended prophylaxis (28 days) is considered the standard of care in such patients. A Cochrane review of four RCTs examining extended prophylaxis showed a decrease in overall VTE (14.3% vs. 6.1%; P < .0005) and a decrease in symptomatic VTE (1.7% vs. 0.2%; P = .02). Extended prophylaxis in minimally invasive procedures is likely not necessary without other high-risk features (elevated body mass index [BMI], previous VTE, coagulopathy, decreased mobility).

  • Patients at risk of VTE should receive prophylaxis with either LMWH or heparin, commenced preoperatively, combined with mechanical methods.

  • Extended prophylaxis (28 days) should be given to patients after laparotomy for abdominal or pelvic malignancies.

  • Patients should discontinue oral contraception before surgical procedures and switch to another form.

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