Enhanced Recovery After Surgery: Which Components, If Any, Impact on The Systemic Inflammatory Response Following Colorectal Surgery?

Enhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery. The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015. Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6. Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioidminimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery. The present systematic review shows that, with the exception of rley, MB, ChB, Pa PhD, cMillan, PhD (Medicine 94(36):e1286) Abbreviations: CRP = C-reactive protein, EA = epidural analgesia, ERAS = Enhanced Recovery After Surgery, IL-6 = interleukin-6, LA = local anaesthetic, LMWH = low molecular weight heparin, MBP = mechanical bowel preparation, NSAID = non-steroidal anti-inflammatory drug, SIR = systemic inflammatory response, TAP = transversus abdominis plane, TNF = tumor necrosis factor. INTRODUCTION S urgery for colorectal disease is associated with variable short-term outcomes. Recent advances in perioperative care methods have attempted to improve these outcomes. The development and widespread application of enhanced recovery or fast track surgical protocols (ERAS), in combination with laparoscopic surgery, represent a paradigm shift in perioperative care. ERAS involves multimodal, protocol-driven perioperative care which proponents of have stated reduces the stress response to surgery. The trauma of surgery leads to well-understood metabolic, neuroendocrine, and immune responses, the aims of which are to promote physiological stability and wound healing. The cellular response to surgical injury is to activate neutrophils and macrophages of the innate immune system by the production of proinflammatory cytokines such as tumor necrosis factor (TNF) alpha, and the interleukins (ILs), for example, IL-1 and IL-6. Proinflammatory cytokines alter the levels of circulating acute phase proteins, for example, C-reactive protein (CRP), albumin, ferritin, transferrin, and fibrinogen, through their action on hepatocytes. Indeed, it has been reported that concentrations of circulating acute phase proteins and cytokines are associated with the magnitude of the stress response, that is, the systemic inflammatory response (SIR) to surgery. Furthermore, CRP and IL-6 have been reported to have the strongest association with the magnitude of the surgical injury, although CRP is perhaps the most clinically useful of these. Moreover, this knowledge forms the basis of an objective examination of the evidence for the impact of ERAS protocols and their components. Although it is recognized that laparoscopic surgery generates a reduced postoperative SIR following colorectal surgery, the impact of individual components of ERAS protocols, in terms of SIR, has not been examined in a systematic manner. The aim of the present review was to examine the ERAS protocols and their components bjective markers of the postoperative www.md-journal.com | 1 TABLE 1. Components of Enhanced Recovery After Surgery—ERAS Group Recommendations ERAS Component Recommendation Preoperative counselling Should receive oral and written information about admission, what to expect and their role in recovery Preoperative fasting and carbohydrate loading Fasting – 2 hours for liquids and 6 hours for solids. Patients should receive carbohydrate loading preoperatively Mechanical bowel preparation Patients should not routinely receive mechanical bowel preparation Thromboprophylaxis Patients should wear compression stockings, have intermittent pneumatic compression and pharmacological prophylaxis with LMWH Antibiotic prophylaxis Single-dose antibiotic prophylaxis 30–60 min prior to surgery Maintenance of intraoperative normothermia Intraoperative maintenance of normothermia with an upper body forced air warmer should be used routinely Goal-directed fluid therapy Balanced crystalloids preferred. Goal-directed fluid therapy should be considered on an individual basis Surgical incisions Midline or transverse laparotomy incision of minimal length should be used Laparoscopic surgery Laparoscopic surgery recommended if the appropriate expertise is available Avoidance of nasogastric tubes Should not be used routinely postoperatively Postoperative analgesia Thoracic epidural analgesia or spinal analgesia with local anaesthetic and opioids. Paracetamol and NSAIDs used following epidural withdrawal Prevention of postoperative ileus Mid thoracic epidural analgesia. Avoidance of fluid overload laparoscopic surgery (if available) Avoidance of peritoneal drains Not indicated routinely for resections above peritoneal reflection. Short term (<24 hrs) may be appropriate after low rectal resections Early removal of urinary catheter For colonic surgery, both suprapubic and urethral techniques are appropriate. Suprapubic catheter should be used for pelvic surgery Early postoperative enteral nutrition Patients should be encouraged to commence oral diet as early as possible after surgery Oral nutrition supplements should be given until normal diet has been resumed. Early mobilization Patients should be nursed in environment that encourages mobilization ERAS1⁄4Enhanced Recovery After Surgery, LMWH1⁄4 low-molecular weight heparin, NSAID1⁄4 nonsteroidal anti-inflammatory drugs. Watt et al Medicine Volume 94, Number 36, September 2015 METHODS Recent separate guidelines on ERAS recommendations following elective colonic and elective rectal/pelvic surgery have been published. The present systematic review focuses on the components reported in the ERAS Group consensus review in colorectal surgery. These recommendations for patients undergoing colorectal surgery are summarized in Table 1. A systematic literature search of the US National Library of Medicine (MEDLINE), the Excerpta Medica Database (EMBASE), PubMed, and the Cochrane Database of Systemic Reviews (CDSR) was made using the following search criteria: ‘‘ERAS component’’ AND (systemic inflammation OR SIR OR stress response OR C-reactive protein OR CRP OR IL-6) AND surgery. This was performed independently by the 2 lead authors and any conflicts that were encountered were discussed with the senior authors. Included data were from the inception of the searched databases until February 2015. From this search, abstracts of articles were analyzed for relevance and the bibliographies of relevant studies as well as the bibliography of the consensus review of perioperative care following colorectal surgery were hand-searched for any additional studies. Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or interleukin-6 (IL-6). Both prospective clinical trials and observational trials were included. The selection process is summarized in Figure 1. Using the aforementioned search strategy, relevant abstracts were 2 | www.md-journal.com obtained for each ERAS component. Articles were excluded if they were animal studies, not in the English language, were review articles, were not related to colorectal surgery or did not use either CRP or IL-6 as the marker of the SIR. Table 2 summarizes the included studies for each ERAS component and the marker of the SIR analyzed. Evidence relating to other outcomes of ERAS programmes such as length of stay or postoperative complications were obtained from the most recent Cochrane Reviews or meta-analyses on the specific topic. Metaanalysis of included studies was not performed because of significant heterogeneity among study methodology, populations, and outcomes measured. Subjective assessment of study validity was carried out by two authors independently (DW and SM) using the Cochrane Collaboration tool provided by Review Manager version 5.3 (RevMan 5.3, The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Any uncertainties were resolved by consensus following discussion with the senior authors (PH and DM). Both prospective clinical trials and observational trials were included. Ethical approval was not required for the present study as this was a systematic review of published data. RESULTS Assessment of Included Study Validity The validity of included studies is summarized in Figure 2. The present systematic review included 15 randomized Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. Studies identified by search strategy