Already in 1984, Bessey et al. demonstrated the causality relation between stress hormones and systemic response by testing infusion of catecholamines and cortisol in healthy volunteers [13]. The authors observed that this artificial endocrine imbalance induced a systemic stress response, similar to what it is observed after low to intermediate injuries. Nowadays, it has been clarified that surgery induces a complex cascade resulting in inflammatory response, immune suppression, altered metabolism with hypercatabolism which lead to impaired wound healing and multi-organ failure [14]. The mediators of this endocrine-metabolic stress response are cytokines, arachidonic acid, nitric oxide and free oxygen radicals [15]. While the mechanisms mentioned above have been extensively studied, to date, no single intervention has been shown to eliminate postoperative morbidity and mortality. Thus, multimodal combined interventions may lead to a reduction of the undesirable effects of surgery with improved recovery and consequently reduced postoperative morbidity and overall costs.
5.3 Development of ERAS
Considering that the immediate challenge to improving the quality of surgical care is not discovering new knowledge, but rather to integrate what we already know [16], the concept “fast track” was introduced in the 1990 [17]. It was demonstrated that by applying evidence-based perioperative principles to patients undergoing open colonic surgery, the post-operative complication rate was halved and length of hospital stay was brought down to 2–3 days [18]. The initial items were complemented over the years by a multitude of perioperative measures with proven or probable impact on the surgical stress response. The current protocol consists of over 20 elements (Table 5.1). This multimodal perioperative care pathway was first propagated and further developed in northern Europe and Great Britain. In order to standardized practice and draw recommendation, the ERAS study group was created in 2001 and soon discovered that there were a variety of traditions in use in different units. There was also a great discrepancy between the actual practices and what was already known to be best practice, based on the literature [19]. This prompted the group to examine the process of change from tradition to best-practice.
ERAS represents a paradigm shift in perioperative care in two ways. First, it re-examines traditional practices, replacing them with evidence-based best practices when necessary. Second, it is comprehensive in its scope, covering all areas of the patient’s journey through the surgical process.
Since its creation, the ERAS Society has published recommendations for the use of ERAS protocols in colonic [20], rectal [21] and pancreatic surgery [3]. Several randomized controlled trials have been undertaken and included in two meta-analysis which demonstrate the significant and reproducible benefits of applying ERAS protocols to colorectal patients [22, 23].
5.4 ERAS Pathways Applied to Rectal Surgery
As already emphasized, standardization of perioperative care relying mostly on evidence-based measures reduces complications by 50 % and hospital stay by 2.5 days [23]. Moreover, ERAS programs have proven highly cost-effective [24]. The ERAS study group initially published comprehensive guidelines which did not differentiate between colon and rectal surgery, although there are important differences between the respective procedures and patient collectives [20, 25]. Later, dedicated recommendations were agreed on for “rectal/pelvic surgery” [21].
At first sight, rectal guidelines are very similar to those for colon surgery (Table 5.2). Obviously, these are general measures to reduce surgical stress response and prevention of postoperative ileus, such as optimized fluid management, no pre-operative sedation, carbohydrate loading, early mobilization and early oral intake. However, distinct differences have been underlined that could also be extrapolated for other pelvic surgeries mentioned in this chapter. Examples include dedicated pre-operative counseling for potential ostomy carriers, bowel preparation for low resections, acceptance of intrapelvic drains and prolonged urinary drainage. However, many items remain subject to debate, since no definitive evidence exists. This is especially true for perioperative pain management. Indeed, epidural analgesia—the backbone of opioid-sparing strategies—is questioned more and more in laparoscopic but also in open surgeries. Emerging alternatives include intrathecal analgesia, regional blocks and IV lidocaine [26]. Another open debate is the management of intra- and early postoperative fluids. While two randomized studies showed little benefit of sophisticated Doppler-guided fluid regimes [27, 28], the situation might be very different for major rectal, urological and gynecological procedures with longer duration and higher fluid shifts. In any event, the current protocols will be continuously developed and adapted according to the current evidence in order to keep ERAS as dynamic as possible and not to fall in “new dogmas”!
Table 5.2
Summary of the main ERAS items and their modifications when applied to pelvic cancer surgery
ERAS items | Colonic surgery | Rectal surgery | Urology | Gynecology |
|---|---|---|---|---|
Preoperative counseling and education | Surgical details, hospital stay and discharge criteria in oral and written form; stoma education; patient’s expectations | Idem | Idem | Idem |
Oral mechanical bowel preparation | Can be safely omitted | Might be needed when diverting ileostomy is planned and for total mesorectal excision | Can be safely omitted | Can be safely omitted |
Preoperative carbohydrates loading | Should be administered to all non-diabetic patients | Idem | Idem | Idem |
Preoperative fasting | Clear fluids until 2 h, solids until 6 h before induction of anesthesia | Idem | Idem | Idem |
Epidural analgesia | Opioid-sparing thoracic epidural analgesia in open surgery, level T9–11, duration: 72 h | Idem | Idem | Idem |
Minimally invasive approach | At most feasible; in trial setting | Not recommended outside of a trial | Cystectomy: not recommended outside of a trial | Conflicting results |
Long term oncological results awaited | Prostatectomy: robotic approach seems beneficial | |||
Resection site drainage | Perianastomotic and/or pelvic drain can be omitted | Should not be used routinely | Cystectomy: no evidence for avoidance of drainage | No evidence for avoidance of drainage |
Prostatectomy: drain can be safely removed at day 1 | ||||
Perioperative fluid management | Goal-directed to optimize cardiac output and organ perfusion | Idem | Idem | Idem |
Nasogastric intubation | Not indicated postoperatively | Idem | Idem | Idem |
Urinary drainage | Transurethral bladder catheter for 1–2 days, independently of epidural anesthesia | Can be safely removed at day 1 if low risk of urinary retention | Cystectomy: optimal duration of ureteral stenting unknown | Can be safely removed at day 1 |
Prostatectomy: urethral catheter usually removed between day 5–10 | ||||
Prevention of postoperative ileus | Multimodal approach | Multimodal approach | Multimodal approach | Multimodal approach |
Gum chewing and oral magnesium | Gum chewing and oral magnesium | Gum chewing and oral magnesium | ||
Postoperative analgesia | Multimodal postoperative analgesia should include thoracic epidural analgesia | Idem | Idem | Idem |
Early mobilization | 2 h out of bed POD 0 | Idem | Idem | Idem |
6 h out of bed POD 1 | ||||
Early oral diet | Normal diet starting 4 h after surgery | Idem | Idem | Idem |
Audit | Routine audit of outcomes, cost-effectiveness, compliance and changes in protocol | Idem | Idem | Idem |
5.5 ERAS Pathways Applied to Gynecological Surgery
One cohort study investigated the effects of an adapted ERAS protocol in patients operated for ovarian cancer [4]. The protocol included avoidance of bowel preparation and nasogastric decompression combined with the use of epidural analgesia, PONV prophylaxis, laxatives, and early oral nutrition and ambulation. The ERAS protocol was applied to 69 patients, which were compared with 72 historical controls receiving standard care. ERAS patients showed a reduced hospital stay (5 vs. 6 days; P < 0.05)) and a reduced morbidity (2 vs. 14 %; (P < 0.01)). The readmission rate was not increased, thus clearly favoring an ERAS care.
As far as uterine cancer surgery is concern, different ERAS protocols have been investigated. One randomized study applied a modified ERAS protocol, including no use of sedatives for premedication, pre-emptive anti-emetic therapy, intravenous fluid restriction, analgesics based on non-opioids, early enteral nutrition and mobilization, and standard criteria for discharge, to 162 women undergoing hysterectomy. The type of anesthesia, general vs. spinal, did not significantly impact on the LOS. Bowel recovery time was shorter in the spinal anesthesia group, but vomiting was more frequent [29]. Intrathecally administered morphine combined with a low-dose mode of total intravenous anesthesia allows for a shorter LOS, when compared to patient-controlled analgesia, although no difference were shown with respect to morbidity [30]. Results concerning potential benefits of a minimally invasive approach are somehow conflicting [31–34].
5.6 ERAS Pathways Applied to Urology
Bladder Cancer
Despite standardization of the surgical technique, improved anesthesia protocols and perioperative care, radical cystectomy with bladder reconstruction is still considered as the most significant surgical challenge in urology [35]. Indeed, morbidity after open radical cystectomy with bilateral pelvic lymph node dissection and urinary diversion or bladder reconstruction mounts up to 30–64 % [36, 37]. Cystectomy patients may therefore be ideal candidates for an ERAS pathway as the potential for reduction of surgical stress and complications is very high.
However, ERAS guidelines issued from colonic surgery [25] might not be applied identically to bladder cancer patients as the surgical procedure itself differs widely (small bowel anastomosis, risk of renal insufficiency in obstructive bladder tumors, urine within the peritoneal cavity during and after surgery, both extra- and intraperitoneal access, longer operative time, increased risk of blood loss). Moreover, colorectal ERAS items such as urinary and abdominal drains might not be applicable to cystectomy patients. Nevertheless, modified ERAS protocols have been investigated and are described below.
Maffezzini et al. applied a modified ERAS protocol complying with 6 of the 22 classic ERAS items (no oral mechanical bowel preparation, epidural analgesia, antimicrobial prophylaxis, standard anesthetic protocol, preventing intraoperative hypothermia, early nasogastric tube removal) to 71 patients undergoing radical cystectomy. When compared to 40 historical retrospective patients, those in the study group showed a reduced mean time to normal diet (from 7 to 4 days) and a shorter LOS (from 22 to 15 days). Morbidity did not differ significantly between the two groups [38]. Another retrospective study compared 56 consecutive patients undergoing open radical cystectomy with standard perioperative care to 56 patients after implementation of an enhanced recovery program including 7 of 22 items (no bowel preparation, no preoperative fasting, epidural analgesia, PONV prophylaxis, early oral nutrition, early mobilization, early removal of abdominal drain) [10]. Morbidity and time to first bowel movement did not differ between the two groups. LOS was significantly reduced (from 17 to 13 days) in the enhanced recovery group. Pruthi et al. published their experience of enhance recovery programs after cystectomy [12]. Two-hundred and sixty-two retrospective patients were compared to the most recent consecutive 100 patients. The protocol included 9 of 22 ERAS items (preoperative information, deep vein thrombosis prophylaxis, antibiotics prophylaxis, early removal of nasogastric tube, early oral nutrition, early mobilization, prevention of PONV, prevention of ileus, postoperative analgesia). However, due to inconsistent protocol throughout time and methodological flaws, no comparison of these two cohorts is possible. Donat et al. combined early nasogastric tube removal with metoclopramide in 27 prospectively included patients undergoing cystectomy and compared them with 54 controls receiving no metoclopramide and in which nasogastric tube was removed only after return of normal bowel function. Complication rate and LOS was similar in both groups. The study group showed earlier return to normal bowel sounds and tolerance to liquid and solid food. By combining thoracic epidural analgesia, early nasogastric tube removal, early oral nutrition and mobilization in 15 prospective patients, Brodner et al. showed a reduction of the time to first defecation, with no difference with regards to morbidity or LOS when compared to 15 patients undergoing a standard care plan [39].
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