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Enhanced Recovery After Surgery (ERAS) in Gynecologic Oncology

February 27, 2023 - read ≈ 26 min

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Authors

Jason Silberman, MD

Kevin M. Elias, MD

Content

Introduction

Enhanced Recovery After Surgery (ERAS) pathways were developed as a tool to optimize the body’s response to the altered physiological state induced by intraoperative stress. Specifically, the catabolic state experienced during surgery leads to alterations in cardiac, respiratory, and gastrointestinal function, while also affecting tissue metabolic function.[1] As a result of these physiologic changes, patients undergoing surgical intervention are at risk for delayed recovery, as well as post-operative morbidity and mortality.  

Prior to the introduction of ERAS, traditional perioperative management strategies provoked marked disturbances in homeostasis secondary to routine pre-operative bowel regimen, fasting prior to surgery, liberal use of intravenous fluids and postoperative narcotics. These practices, routed in nineteenth century surgical dogma, only further exacerbate the catabolic and deleterious physiological state induced by surgery. The ERAS pathway was first described in the colorectal literature with aims of targeting recovery through data driven interventions addressing pre-, peri-, and post-operative care.[2]

These pathways have been adapted to gynecology and gynecologic oncology with the same demonstrated efficacy and success. The purpose of this chapter is to outline the components of a standardized ERAS pathway, discuss improved outcomes associated with ERAS implementation, and provide useful information for implementing an ERAS protocol in clinical practice.

Preoperative ERAS Optimization

Preoperative optimization and planning

Preoperative optimization includes both optimization of a patient’s health status prior to surgery combined with preoperative counseling to educate the patient about ERAS principles and set expectations regarding recovery. Complete preoperative risk assessments should include an evaluation of tobacco and alcohol use, screening for nutritional deficiency and frailty, and laboratory investigations for diabetes and anemia.

Smoking has been demonstrated to be associated with a high risk of anesthesia complications, as well postoperative complications associated with poor wound healing and infection. However, the benefits of smoking cessation can be observed within four weeks of cessation. Therefore, every effort should be taken to encourage smoking cessation prior to surgery, when feasible.[3]

Alcohol use is associated with impaired function of multiple physiologic processes, including cardiac and liver function, as well as the body’s immune and clotting response to surgical stress. Even moderate alcohol use can also increase anesthetic requirements during surgery.

Data suggests that patients who consume 3-4 drinks per day may experience up to 50% higher complication rates compared to patients who drink between 0-2 drinks daily. For those who drink more than 5 drinks per day, the complication rates increase by 200-400%.[4]

A Cochrane Review including a small number of studies discovered that preoperative counseling and intervention aimed at complete alcohol cessation for at least four weeks prior to surgery can reduce the number of postoperative complications, though there is minimal effect on postoperative mortality and length of stay.[5]

The presence of anemia at the time of surgery is associated with increased risk for the need of blood transfusions either during or following surgery. Studies have demonstrated that patients who received perioperative blood transfusions have an increased risk for post-operative morbidity and mortality as well as an increased length of stay. Identification of anemia during pre-operative visits allows for an evaluation of the cause for the anemia, as well providing an opportunity to try to correct the underlying cause. Treatment of anemia in the preoperative period may offset the risks associated with anemia and transfusion at the time of surgery.[6,7]

If iron deficiency is identified, newer parenteral iron therapy can replenish iron stores with one or two outpatient infusions.

The office evaluation should include screening for nutritional deficiency and frailty.  Any patient with unexplained weight loss, reports of decreased oral intake, or signs of malabsorption (either frequent nausea / vomiting or diarrhea) is at risk for protein calorie malnutrition. Even 5-7 days of oral protein supplementation has been shown to reduce the risk of surgical site infection and improve recovery. Similarly, a simple frailty assessment can be performed by assessing grip strength, endurance (e.g. the 6-minute walk test, meaning the distance an individual can walk in 6 minutes), and balance (the “get up and go test,” wherein a patient is asked to rise from a chair walk across the room and return to their seat).[8–10]

Safety for discharge home should also be determined by asking whether the patient is able to independently carry out basic activities of daily living (preparing meals, shopping, dressing, and bathing). Patients with marked nutritional deficiency or frailty may benefit from a modest delay in surgery to complete prehabilitation prior to the hospital stay.[11] Similarly, patients undergoing neoadjuvant chemotherapy are optimal candidates for prehabilitation programs.[12]

Not to be overlooked is the importance of preoperative counseling and education. During pre-operative visits, the provider should have a discussion with the patient about ERAS and its principles. Part of this discussion should include expectations for recovery both in the hospital and at home following surgery, as well as the anticipated length of stay following surgery. Managing these expectations reduces patient anxiety, improves patient satisfaction, and can ultimately facilitate early discharge from the hospital.[13,14]

Furthermore, providing written materials to patients regarding their surgical procedure and post-operative management has been demonstrated to lead to improved patient satisfaction, reduced length of stay, and decreased utilization of pain medications.[15]

Pre-operative Bowel Preparation & Fasting

Traditionally, patients have been counseled in the pre-operative period to cease eating and drinking at midnight the evening prior to surgery. Additionally, some patients had been counseled towards performing a pre-operative mechanical bowel preparation, with the thought that doing so would decrease the risk for wound infections or anastomotic leaks in the setting of bowel resections. Additionally, there was also a belief that mechanical bowel preparation may provide for improved visualization during laparoscopic surgeries.[16]

However, a Cochrane Review demonstrated that there was no difference in wound infections or anastomotic leakage rates between groups who underwent mechanical bowel preparation versus those who did not.[17] Similarly, an RCT investigating women undergoing laparoscopic hysterectomy demonstrated no difference in visualization based on the presence of pre-operative bowel preparation.[18]

The traditional recommendation for patients to abstain from food or drink beginning the eve prior to surgery may exacerbate the abnormal physiological state that surgery induces. Fasting depletes liver glycogen and stimulates insulin resistance while impairing glucose metabolism. The ERAS pathway attempts to reduce pre-operative starvation and induce a metabolically “fed-state” by having patients consume a complex carbohydrate drink prior to surgery. Clear fluids up until 2 hours prior to surgery has not been shown to increase complications associated with aspiration. As adequate hydration improves patient comfort, facilitates intravenous catheter placement, and reduces anesthesia-induced hypotension, patients should actively be encouraged to consume clear liquids until 2 hours prior surgery.

Furthermore, rather than the fasting recommendation beginning at midnight the night prior to surgery, the recommendation is for a 6 hour fast for solid food prior to induction of anesthesia. For patients with delayed gastric emptying, they should have at least 8 hours of fasting prior to induction of anesthesia.

Pre-operative Venous Thromboembolism Prophylaxis

Gynecologic oncology patients carry a substantial risk for development of venous thromboembolism (VTE). The lifetime risk for VTE in patients with gynecological cancers range anywhere from 3 – 38%, with data demonstrating the highest risk for patients with ovarian cancer.[19,20] For women undergoing oncological surgery, it has been shown that the risk of developing a DVT during the 12 weeks following surgery is 1 in 85 patients.[21]

Given the elevated risk for development of peri- and post-operative VTE, the ERAS recommendation is for all gynecologic oncology patients undergoing a major surgery lasting longer than 30 minutes should receive chemoprophylaxis with either low molecular weight heparin or unfractionated heparin administered prior to induction of anesthesia, as well as mechanical prophylaxis with sequential compression devices placed prior to induction of anesthesia.

The use of pre-operative DVT prophylaxis with heparin has reduced rates of post-operative DVT, as well as their associated morbidity and mortality. Furthermore, the administration of pre-operative anti-coagulation does not increase rates of bleeding complications during surgery.[22,23]

Intraoperative ERAS Optimization

Minimizing Infection Risk

Most gynecologic oncology surgeries involve a total hysterectomy, which is classified as a clean contaminated procedure. Antibiotic prophylaxis should be given within 60 minutes of skin incision to cover for skin and vaginal flora. For laparotomy without bowel resections or hysterectomy, generally, the recommendation is for administration of a first-generation cephalosporin.[16]

The dose should be increased in obese patients (BMI > 35 or >100kg), and doses should be repeated in prolonged cases or in cases with a heavy blood loss (>1,500 ml). If a hysterectomy is planned or the bowel is likely to be entered during a case, it is recommended to add a second antibiotic for anaerobic coverage.[24]

In addition to administration of prophylactic antibiotics, skin preparation also reduces the amount of bacterial flora present on the skin prior to incision. Chlorhexidine-alcohol skin preparations have been demonstrated to be superior in reducing rates of surgical site infections when compared to povidone-iodine preparations. [25] The solution should be allowed to dry for 3 minutes after scrubbing to prevent risk for cautery injury.[16] In addition to abdominal cleansing, vaginal cleansing with either 4% chlorhexidine gluconate or povidone-iodine should be performed in cases of hysterectomy.[26]

In cases where it is deemed that hair removal is necessary for incision, electric clipping is preferred to shaving, and the removal of hair should take place immediately before the operation. To minimize skin breaks, patients should not shave the evening prior to the procedure.[26]

Anesthetic Medications

The type of anesthetic used during a surgical procedure can have a tremendous impact not only on the intraoperative hemodynamic profile of a patient, but also on a patient’s recovery from surgery and the anesthetic side effects they experience. Propofol provides a rapid onset, rapid recovery as well as an added benefit of reducing risk for post-operative nausea and vomiting (PONV).

In contrast, nitrous oxide can increase PONV, and should be avoided when possible. Multi-modal anesthesia can reduce or even eliminate volatile anesthetic exposure, and with it, the tendency of anesthetic gases to induce hypotension, nausea, and postoperative ileus. Total intravenous anesthesia can be accomplished with use of continuous target-controlled infusions of propofol in combination with other anesthetic agents including dexmedetomidine, ketamine and lidocaine.

Specifically, intravenous lidocaine in the perioperative period has been shown to reduce intraoperative anesthetic requirements, decrease postoperative pain scores as well as postoperative analgesic requirements, improve return of bowel function, and decrease length of stay in the hospital.[27]

At the end of the procedure, reversal agents should be given to maximally counteract the effects of intraoperative paralytics. Full reversal is associated with faster weaning of supplemental oxygen, reduced risks of hypoventilation, and faster time to ambulation.

Post-Operative Nausea and Vomiting

Both female gender as well as gynecologic surgery are proven risk factors for development for PONV, and therefore, attention must be given to interventions that can reduce the risk of PONV. These interventions include utilizing propofol infusions, avoiding nitrous oxide and volatile anesthetics, decreasing opioid use, and decreasing the dose of neostigmine.[24] Multi-modal PONV prophylaxis should be administered using at least 2 medications from different pharmacological classes. Unless specifically contraindicated, 4-8 mg of dexamethasone should comprise one of these agents. The use of a scopolamine patch has been shown to be effective when placed the evening prior to surgery or 2 hours prior to surgery.[28]

Hypothermia

As part of the altered physiological state associated with surgery, there is disruption in the normal thermoregulatory response. As a result, patients are at risk for developing hypothermia, which can affect drug metabolism, negatively affect coagulation and alter cardiopulmonary physiology. These changes have been shown to ultimately lead to increased bleeding, cardiac morbidity and increased rates of wound infection.[29]

Active warming techniques, including using warmed IV fluids, as well as forced-air warm blankets have been shown to be effective ways of preventing hypothermia and its negative consequences. Conversely, care should also be taken to monitor for hyperthermia which can also result in altered physiology and negative consequences.  Active warming should begin in the preoperative area and continue through the case and into the recovery room.

Intraoperative Fluid Balance

While the administration of intravenous fluids during surgery is imperative for maintaining hemodynamic stability and organ perfusion, the surgical and anesthesia teams should ensure judicious use of fluids to achieve euvolemia. Both hypo- and hypervolemia are associated with increased morbidity and mortality. Under-resuscitated patients are at risk for development of an acute kidney injury and surgical site infections along with a prolonged hospital stay.[24] Conversely, over-resuscitation has been shown to cause delayed return of bowel function, pulmonary edema, cardiac arrythmia, PONV and an increased length of stay in the hospital.

One of the methods that can be used to optimize intraoperative fluid administration is the use of stroke volume assessments for goal directed therapy, such as an esophageal doppler, transthoracic impedance monitor, or pulse wave contour monitoring devices. This monitoring can assess the patient’s response to fluid administration, in real time, and can also help guide the anesthesia team when to manage hypotension with vasopressors versus fluid boluses.

Avoidance of Tubes and Drains

Prophylactic nasogastric decompression after open abdominal surgery has not been shown to decrease the risk for wound dehiscence or bowel anastomotic leaks. In fact, placement of nasogastric tubes intraoperatively, for the purpose of gastric decompression postoperatively has demonstrated an increased incidence of pneumonia compared to avoidance of nasogastric tube placement.[30]

Abdominal, pelvic and/or peritoneal drains have traditionally been used to both detect and “conservatively” treat anastomotic leakages following bowel resections and re-anastomosis. However, these drains hinder mobilization and therefore inadvertently increase risk for development of a VTE. And furthermore, RCT data from the colorectal literature has demonstrated that the use of pelvic drains after a bowel resection does not, in fact, confer any benefit to the patient in terms of rates of and time to diagnosis of pelvic sepsis, as well as rates of reoperation.[31] Therefore, it is recommended that should intraabdominal drains need to be placed peri-operatively, they be removed as soon as possible.

Similarly, removal of urinary catheters within 24 hours of surgery facilitates ambulation and has been shown to decrease length of stay in the hospital by reducing urinary infection risk.[16]

Postoperative ERAS optimization

Activity

An important post-operative tenet of the ERAS pathway is early mobilization and ambulation. One of the main effects of early mobilization is to reduce VTE events in the post-operative period. However, there may be added benefits including a decrease in pulmonary complications such as atelectasis, less muscle atrophy, and decreased length of hospital stay.[32]

As discussed earlier, removal of unnecessary drains, including foley catheters, abdominal drains, or nasogastric tubes all may hinder early mobilization, and should therefore be removed as early as safely possible. Similarly, intravenous fluids should be stopped within 6-8 hours of surgery to allow free patient movement and avoid an excess fluid balance. Additionally, it’s imperative to provide multi-modal analgesia (See Analgesia, below) to limit reliance on systemic opiates that may also limit early mobilization.

Post-operative Venous Thromboembolism Prophylaxis

As discussed in the pre-operative VTE section, patients with gynecologic malignancies are at an elevated risk for development of VTE, and even more so following a major abdominal surgery. Therefore, the recommendation is for all post-operative patients to receive both mechanical VTE prophylaxis with pneumatic compression devices and/or compression stockings, as well as chemical VTE prophylaxis, with medications such as low-molecular-weight heparin. Furthermore, the ENOXACAN II trial demonstrated the added benefit, as well as safety, of extending chemical VTE prophylaxis for 28 days following abdominal surgery for cancer.[33]

It is generally not recommended to continue prophylaxis for 28 days following minimally invasive surgery, unless the patient has other high-risk features for development of VTE.[32]

Fluid Therapy, Post-Operative Nutrition, and Bowel Routine

Patients often require IV fluids in the post-operative period, as they recover from surgery and have limited oral intake. In general, balanced, iso-molar crystalloid solutions are preferred to 0.9% normal saline due to the risk of hyperchloremic acidosis and the negative effects of excess sodium administration.[32]

ERAS emphasizes that patients have early return of oral intake following surgery, with an administration of a solid diet as early as post-operative day 0, and certainly within 24h of surgery. Once a patient is tolerated oral intake of fluids, IV fluids should be discontinued, normally within 6-8 hours of surgery. Additionally, when available, patients should be provided oral nutritional supplements with high protein content (ideally up to 2g protein/kg/day), as this has been shown to provide benefits for post-operative healing and earlier hospital discharge.[32]

Attention should be paid to the patient’s bowel function after surgery, as return of bowel function is oftentimes the last milestone preventing discharge from the hospital. There are multiple factors that influence the development of post-operative ileus, including exposure to opioids, fluid balance, extent of disease and surgery complexity, receiving intraoperative blood transfusion, and development of post-operative complications.[34]

When studied, early feeding following gynecologic oncology surgery has demonstrated to lead to accelerated return of bowel function and reduced length of stay without an increase in post-operative complications. Interestingly, chewing gum orally, as well as coffee consumption are also recommended, as they have been shown to accelerate return of bowel function.[35] Gentle laxatives and fiber supplements post-operatively have also been shown to be effective at reducing the risk of developing an ileus.[32]

Maintenance of post-operative glycemic control is critical for recovery following gynecologic oncology surgery. Strict glucose control (less than 139 mg/dL) has been shown to reduce the rate of surgical site infections by 35% in women with diabetes mellitus.[36] However, there may be concern for precipitating hypoglycemia, and therefore, the general recommendation is to maintain a patient’s blood glucose level to less than 180 mg/dL.

Analgesia

Maintenance of adequate post-operative analgesia is a critical component in a patient’s recovery. Interventions related to analgesia begin in the pre-operative setting, as unless there is a contraindication, patients should receive both Tylenol and Celecoxib in the pre-operative area.[37]

As mentioned prior, administration of total IV anesthesia with propofol along with Ketamine, Lidocaine or Dexmedetomidine can help to improve post-operative analgesia. Unless contraindicated, patients should receive some form of IV, non-narcotic pain medication in the OR, prior to awaking from anesthesia. Examples of these medications include ketorolac, meloxicam or IV acetaminophen. When available, regional analgesia — such as transversus abdominis plane (TAP) blocks, epidural catheters, or infiltration of liposomal bupivacaine — can aid to reduce the need for post-operative narcotics.[24]

At minimum, the surgical team should liberally infiltrate the rectus sheath with bupivacaine with epinephrine within the safety profile of weight-based dosing.

During the post-operative period, it’s anticipated that patients may require opioids to control their pain. However, first line medications should be NSAIDs and acetaminophen, preferably in the form of standing Ketorolac (for 48 hours) or Meloxicam (for 24 hours) alongside standing acetaminophen. Following the 24-48 hours of initial NSAIDs, patients can be switched to ibuprofen.

In our practice, we prefer to manage breakthrough pain with oral Tramadol, rather than oral Oxycodone or Dilaudid, as it has a lower rate of pruritis and nausea and tends to be less sedating. However, in patients who are taking SSRI’s, Oxycodone is preferred due to the risk for serotonin syndrome with Tramadol. Opioid exposure can be minimized, however, by using 2.5 mg doses rather than the 5 mg dose whenever possible, especially in elderly patients.

Criteria for Discharge

Patients managed under the ERAS protocol should have set criterion for discharge from the hospital, including tolerance of a diet, adequate pain control on oral medications and ability to ambulate. Providers may differ on expectations for return of bowel function prior to discharge. As mentioned in the discussion of pre-operative counseling, it is imperative that expectations are set with the patient pre-operatively, to inform them that their recovery is going to extend into the home setting following surgery.

For this model to be effective, patients should receive detailed education materials, including printed information for both the patient and their caregiver, regarding expectations for recovery at home, as well as emergency contact information alongside guidelines for when to contact the surgical team. Providing this information is critical for decreasing post-operative emergency room visits and possible re-admissions.

Conclusion

The ERAS pathway is a comprehensive protocol addressing all phases of peri-operative care with the goal of optimizing patient recovery and outcomes. Importantly, the interventions and recommendations associated with ERAS are evidenced-based. In addition, data supporting the individual recommendations comprising ERAS, the entirety of the ERAS bundle has shown to be effective in improving patient outcomes, patient experiences, and reducing hospital costs. Randomized trials in gynecologic oncology comparing ERAS with standard perioperative care have demonstrated a shorter length of stay post-operatively, lower rate of complications, as well as decreased rate of readmission.[38,39]

Retrospective data has shown that ERAS can also be associated with a lower rate of ICU admissions, as well as decreased mortality.[40] The benefits of ERAS extend far beyond the peri-operative period, as a recent study examining the risk of VTE in ovarian cancer patients found that patients on an ERAS protocol have a dramatically lower cumulative incidence of VTE at 30 days, 6 months, and 1 year following diagnosis when compared to previously reported data.[41]

While ERAS is comprised of numerous components, some of which may be difficult to institute in areas with limited resources, there is utility in targeting specific ERAS components to facilitate compliance. For example, a retrospective study looking at compliance with 10 ERAS components, found that for open surgery, the use of 2 or more anti-emetics and as well as judicious post-operative fluid administration were most significantly associated with a reduced length of stay. For laparoscopic surgery, ambulation within 8 hours of surgery was found to be most strongly associated with a decreased length of stay.[42]

Instituting an ERAS program requires a multidisciplinary approach, including active involvement among the surgical anesthesia, and nursing teams, couple with support from medical nutrition, physical therapy, and pharmacy. In order to ensure the success of the program, an ERAS taskforce should meet consistently to review and troubleshoot any issues with implementation and/or compliance. Ultimately, established outcomes of interest should be audited regularly to determine the success of the program.

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