Fast-track vs standard care in colorectal surgery: a meta-analysis update

Transcription

1 Int J Colorectal Dis (2009) 24: DOI /s REVIEW Fast-track vs standard care in colorectal surgery: a meta-analysis update Nikolaos Gouvas & Emile Tan & Alistair Windsor & Evaghelos Xynos & Paris P. Tekkis Accepted: 1 April 2009 /Published online: 5 May 2009 # Springer-Verlag 2009 Abstract Background Fast-track (FT) protocols accelerate patient's recovery and shorten hospital stay as a result of the optimization of the perioperative care they offer. The aim of this review is to examine the latest evidence for fasttrack protocols when compared with standard care in elective colorectal surgery involving segmental colonic and/or rectal resection. Materials and methods All randomized controlled trials and controlled clinical trials on FT colorectal surgery were reviewed systematically. The main end points were shortterm morbidity, length of primary postoperative hospital stay, length of total postoperative stay, readmission rate, and mortality. Quality assessment and data extraction were performed independently by two observers. Results Eleven studies were eligible for analysis (four randomized controlled trials (RCTs) and seven controlled clinical trials (CCT)), including 1,021 patients. Primary hospital stay (weighted mean difference 2.35 days, 95% confidence interval (CI) 3.24 to 1.46 days, P< ) and total hospital stay (weighted mean difference 2.46 days, 95% CI 3.43 to 1.48 days, P< ) were significantly lower for FT programs. Morbidity was N. Gouvas : E. Tan : P. P. Tekkis (*) Department of Biosurgery and Surgical Technology, Imperial College, St. Mary s Hospital, 10th Floor, QEQM, Praed Street, London W2 1NY, UK p.tekkis@imperial.ac.uk N. Gouvas : E. Xynos Medical School, University of Crete, Heraklion, Greece A. Windsor Department of Colorectal Surgery, University College Hospital, London, UK also lower in the FT group. Readmission rates were not significantly different. No increase in mortality was found. Conclusions FT protocols show high-level evidence on reducing primary and total hospital stay without compromising patients' safety offering lower morbidity and the same readmission rates. Enhanced recovery programs should become a mainstay of elective colorectal surgery. Keywords Fast-track protocols. Enhanced recovery programs. Meta-analysis. Colorectal surgery Introduction Patients undergoing colorectal surgery, where resection of bowel is involved, can have a complication rate of between 15% and 20% [1 3]. Such complications can prolong postoperative hospital stay by 6 to 10 days [4]. The financial burden imposed on health care systems due to prolonged hospital stay after colorectal surgery can be significant. In an effort to reduce the length of hospital stay after colorectal surgery, Kehlet et al. [5] were the first to describe in detail a specific protocol called fast-track or enhanced recovery after surgery protocol which had the potential to reduce hospital stay to a mean of 4 days, largely as a result of better understanding of postoperative physiology and advances in the field of health care in the last decade. The aim is to attenuate the surgical stress response, accelerate recovery, decrease complications, minimize hospital stay, and ultimately reduce health costs without compromising patients' safety. Many protocols have been put forward by hospital groups which consist of varying individual preoperative, intraoperative, and postoperative fast-track elements such as preoperative counseling and feeding, no bowel preparation, perioperative high oxygen concentrations, active

2 1120 Int J Colorectal Dis (2009) 24: prevention of hypothermia, no routine use of nasogastric tubes and drains [6 14]. One of the elements adopted by almost all groups is minimally invasive surgery, especially in studies conducted in the last decade when laparoscopy became very popular because it was associated with less postoperative pain and reduced length of stay [15, 16]. Further research on colorectal fast-track protocols was encouraged by studies that demonstrated their potential positive effects in various other fields of elective surgery such as thoracic surgery [17, 18]. However, it is still controversial if colorectal multimodal rehabilitation programs offer substantial benefits to patients. The argument is that fast-track protocols increase complication and readmission rate sufficiently that overall they do not reduce health costs or total hospital stay. Additionally, complications of fast-track patients are recognized relatively late with possibly significant consequences. Last but not least, there has been limited clarifying data which imply a reduced cost for bowel resection after the implementation of such enhanced recovery protocols [19]. In an effort to clarify the role of fast-track protocols in colorectal surgery, Wind et al. [20] conducted a metaanalysis of six studies (three RCTs and three CCTs) with a total of 512 patients which showed a reduction in primary hospital stay and morbidity for patients in fast-track programs after elective colorectal surgery. The authors however conclude that data are still limited and that there is need of more randomized studies for safe conclusions to be drawn [20]. The aim of this meta-analysis is to examine the latest evidence for fast-track protocols when compared with standard care (SC) in elective colorectal surgery involving segmental colonic and/or rectal resection. Data extraction Two reviewers (ET and NG) independently extracted the following from each study: first author, year of publication, study population characteristics, study design, inclusion and exclusion criteria, matching criteria, number of subjects enrolled in each type of care, and male-to-female ratio. Inclusion criteria To be included in the analysis, studies had to: (1) compare a perioperative fast-track protocol with standard care in patients undergoing elective segmental colonic, rectal, or colorectal resection for either malignant or benign disease; (2) report at least one of the outcome measures mentioned below; and (3) clearly document the multimodal fast-track program implemented. When two studies were reported by the same institution and/or authors, they were included only if there was no overlap between the results of the studies. Otherwise, the larger higher-quality studies were included in the analysis. Exclusion criteria Studies were excluded from the analysis if: (1) the outcomes of interest were not clearly reported for the two different kinds of perioperative care; (2) it was impossible to extrapolate or calculate the necessary data from the published results; and (3) there was considerable overlap between authors, centers, or patient cohorts evaluated in the published literature. Materials and methods Study selection A MEDLINE, Embase, Ovid, and Cochrane database search was performed on all studies between 1995 and 2008 comparing fast-track protocols with traditional care in elective colorectal surgery involving segmental colonic, rectal, or colorectal resection. The following Mesh search headings were used: fast-track protocols, enhanced recovery, multimodal rehabilitation, traditional care, standard care, colorectal surgery, colorectal resection, comparative study, randomized study, and treatment outcome. The related article function from PubMed was used to broaden the search, and all abstracts, studies, and citations scanned were reviewed. No language restrictions were made. The latest date for this search was July 17, Outcomes of interest The following outcomes were used to compare the fasttrack group with the standard care group after elective segmental colonic, rectal, or colorectal resection for either malignant or benign disease: 1. Short-term morbidity including anastomotic leak, complications other than anastomotic leak, and general postoperative complications (bowel obstruction/ stricture, prolonged ileus, abscess formation, wound infection, urogenital infection, and pulmonary embolism). Results are presented as percentages 2. Length of primary postoperative hospital stay expressed as days in the hospital after surgery 3. Length of total postoperative stay expressed as total days spent in the hospital including possible readmissions 4. Readmission rate expressed as percentage 5. Mortality expressed as percentage

3 Int J Colorectal Dis (2009) 24: All the above outcomes were measured for a follow-up period of 30 days. Statistical analysis The meta-analysis was performed in line with recommendations from the Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines. Odds ratio (OR) was used as the summary statistic to perform statistical analysis of dichotomous variables, and the weighted mean difference (WMD) was used to analyze continuous variables, such as postoperative hospital stay. Both were reported with 95% confidence intervals (CI). Odds ratios represent the odds of an adverse event occurring in the fasttrack group compared with the standard care group, and WMDs summarize the differences between the two groups with respect to continuous variables, accounting for sample size. Statistical algorithms were used to calculate the standard deviations (SD) for studies that presented continuous data as means and range values, thus standardizing all continuous data for analysis. OR>1 favored the fast-track group, and the point estimate of the OR was considered to be statistically significant at the P<0.05 level if the 95% CI did not include the value one. The quality of case control studies was assessed by use of the Newcastle-Ottawa Scale. The quality of the randomized controlled studies was assessed by using the instrument developed by Jadad et al. [21] assessing randomized clinical trials. The quality of the studies was evaluated by two assessors (ET and NG) by examining three factors: patient selection, comparability of the study groups, and assessment of outcome. Case control studies achieving seven or more stars (maximum 11) were considered to be of higher quality. Randomized controlled studies achieving three or more stars (maximum five) were considered to be of higher quality. Three strategies were used to quantitatively assess heterogeneity. First, graphic exploration with funnel plots was used to evaluate publication bias. Second, data were reanalyzed by using both random-effect and fixed-effect models. Third, sensitivity analysis was undertaken by using the following subgroups: randomized studies and case control studies. Analysis was conducted by use of Review Manager version (The Cochrane\ Collaboration, Software Update, Oxford, UK). Results Eligible studies By using the search key words listed above, 52 publications were identified. Thirty-eight studies were excluded after title and abstract review. These included 14 noncomparative studies, one comparing fast-track vs standard care for laparoscopy, three letters, seven reviews, and 13 nonrelated studies. The remaining 14 studies were investigated in detail in full (Fig. 1) [6 8, 10, 13, 14, 22 29]. Examination of the references of these studies did not provide any further studies for evaluation. Of these 14 studies, three studies were excluded because of overlap of authors, institutions, and possibly patient cohorts; therefore, the larger higher-quality studies were included. A total of 11 studies [6, 8, 10, 13, 14, 22, 23, 25, 27 29] published from 1998 until 2007 fulfilled the selection criteria and were included in this meta-analysis. Analysis was performed on a total of 1,021 patients who were divided into two groups as follows: an FT group with 526 patients and an SC group with 495 patients. The study characteristics, patient demographic details, selection criteria, matching, discharge policy, and fast-track elements applied in each study are shown in Table 1. There were four randomized controlled trials [6, 8, 10, 13] and seven nonrandomized case control studies [14, 22, 23, 25, 27 29]. Most of the studies had a rather limited sample size because they were single-centered studies and possibly their power to identify important differences in outcomes such as patient satisfaction, quality-of-life scores, and pain scores could be questioned. The highest-quality randomized controlled study reported that randomization was done by a random number generator [13]; the other three reported the sealed envelope method [6, 8, 10]. As it is easily understandable by the nature of the enhanced recovery protocols, blinding of patients and nursing and medical staff was not possible in any of the studies. Furthermore, discharge criteria for the two groups were not clearly described in all studies. Follow-up was conducted for 30 days for each study except one that followed-up patients for days [13]. Losses to follow-up were not reported. Fast-track elements In the fast-track group, a total of 17 individual fast-track elements, applied on the group's patients, could be identified in the literature (Table 2). To be included in the meta-analysis, a study should have no less than four fasttrack elements because fewer fast-track elements could be part of modern standard care. A mean of 8.5 fast-track elements were applied in these ten studies ranging from four to 14. The most popular ones were preoperative counseling, epidural analgesia, no routine use of nasogastric tubes, enforced postoperative mobilization, and enforced postoperative oral feeding. On the other hand, preoperative feeding, synbiotics, no bowel preparation, no premedication, active prevention of hypothermia, and no use of drains were not reported that often.

4 1122 Int J Colorectal Dis (2009) 24: Fig. 1 Forest plot of pooled data on primary hospital stay (SD standard deviation, CI confidence interval, RCT randomized controlled study) Overall meta-analysis Data on the outcomes of interest from the included studies with regard to primary postoperative hospital stay, total postoperative hospital stay, morbidity, and readmission rates are shown in Table 3. Primary hospital stay Nine out of 11 included studies reported on primary hospital stay [6, 8, 10, 13, 14, 22, 23, 28, 29]. Eight of them documented a clear advantage of the FT group over standard care. Only Delaney et al. [8] did not show a significant difference. Meta-analysis of the data showed a significantly lower primary hospital stay for the FT group in comparison with the SC group (weighted mean difference 2.35 days, 95% CI 3.24 to 1.46 days, P< ). The difference remained significant even when subgroup analysis of the RCTs and the non-rcts was conducted (Fig. 1). Total hospital stay Five out of ten studies reported on total hospital stay. All studies showed a clear significant difference favoring the FT group. After pooling all the data, total hospital stay was significantly shorter in the FT group compared to the SC group (weighted mean difference 2.46 days, 95% CI 3.43 to 1.48 days, P< ). Individual subgroup analysis of the RCTs and of the non-rcts gave the same result (Fig. 2). Morbidity Nine out of ten included studies reported on morbidity rates. For the FT group, morbidity rates ranged from 4% to 47%. The SC group displayed morbidity rates which ranged between 8% and 75%. Only Basse et al. [7] demonstrated a significant difference in morbidity rates favoring the FT group. All other studies showed a trend favoring mainly the FT group but the difference was not statistically significant.

5 Int J Colorectal Dis (2009) 24: Table 1 Characteristics of included studies Author Year Design Blind (y/n) Number of patients Match Inclusion criteria Exclusion criteria Discharge policy Number of FT elements Age (years) Quality rating FT Conventional Gatt 2005 RCT N , FT 67 *** Con 67 Delaney 2003 RCT N , 2, 4, 8 1, , 5 4 FT (50.6) ** Con (41.9) Anderson 2003 RCT N , 8 1, 2 Unclear 1, FT 64 *** Con 68 Khoo 2007 RCT N , 2, 4, 8 1 5, 9, 23, , 10 7 FT 69.3 *** Con 73.0 Bradshaw 1998 CCT N , 2, 6, 8 1 5, 7, FT 63 ******* Con 60 Stephen 2003 CCT N , 6 8 1, 3, , 8 7 FT (62) ********* Con (69) Raue 2004 CCT N , 3, 4, 6, 8, , 3, 21, FT 63 ********* Con 65 Basse 2004 CCT N , 2, 6, 8, , 17, FT 72 ********** Con 74 Wichmann 2007 CCT N , 2, 6, , 28, FT (59.7) ******* Con (61.1) Kariv 2007 CCT N , 2, , FT (38.8) ******* Con (39.1) Polle 2007 CCT N , 2, 3, 5, 8, 9 14 FT (49) ********** Con (47) Age: numbers are expressed as median (mean). Match: 1=age, 2=sex ratio, 3=body mass index, 4=ASA score, 5=POSSUM score, 6=malignant disease, 7=stoma formation, 8=operations performed, 9=concomitant disease. Inclusion criteria: 1=elective colorectal surgery, 2=living independently at home, 3=cancer, 4=diverticular disease, 5=reoperation, 6=comorbidity, 7=pelvic surgery, 8=intestinal or rectal resection, 9=colonic resection, 10=elective laparoscopic sigmoidectomy, 11=laparotomy with total proctocolectomy with IPAA or completion proctectomy with IPAA after subtotal colectomy or redo operation. Exclusion criteria: 1=failure to obtain consent, 2=age<18, 3=pregnancy, 4=intolerance to probiotics and/or prebiotics, 5=contraindication to optimization strategies, 6=contraindication to early postoperative discharge, 7=medication that may independently prolong hospital stay, 8=advanced malignancy, 9=palliative surgery, 10= emergency surgery, 11=failure to perform colonic or rectal resection, 12=ASA IV or V, 13=chronic pain, 14=drug alcohol dependence, 15=other diseases influencing independently outcomes, 16=radiation therapy, 17=stoma, 18=low anterior resection or rectal extirpation, 19=loop ileostomy closure, 20=ventral hernia repair without bowel resection, 21=conventional resection, 22= conversion to formal midline laparotomy, 23=preexisting clinical depression, 24=concomitant operation of other specialty, 25=pouch repair transanally, 26=laparoscopic pouch repair, 27= immunological dysfunction, 28=drug addiction, 29=cardiac or pulmonary insufficiency. Discharge policy: 1=three light meals per day, 2=safe mobilization, 3=oral medication, 4=toleration of oral nutrition, 5=gastrointestinal function restored, 6=normal body temperature, 7=no major complications, 8=toleration of liquid diet, 9=discharge on postoperative day3 according to patient s wish, 10=self-caring, 11=discharge on postoperative day2, 12=discharge on postoperative day5 or 6. Quality scoring: max number of stars (*) five for RCTs and 11 for other studies RCT randomized control trial, CCT clinical control trial, FT fast track

6 1124 Int J Colorectal Dis (2009) 24: Table 2 Fast track elements included per study Preoperative Perioperative Postoperative Study Design Preoperative counseling Preoperative feeding Synbiotics No bowel preparation No premedication Fluid restriction Perioperative high O2 concentrations Active prevention of hypothermia Epidural analgesia Minimally invasive/ transverse incisions No routine use of NG tubes No use of drains Enforced postoperative mobilization Enforced postoperative oral feeding No systemic morphine use Standard laxatives Early removal of bladder catheter Gatt RCT Anderson RCT Delaney RCT Khoo RCT Kariv CCT Stephen CCT Bradshaw CCT Raue CCT Wichmann CCT Basse CCT Polle CCT RCT randomized controlled trial, CCT clinical control trial Table 3 Extracted data on outcomes of interest from all studies Number of patients PHS (days) Total HS (days) Morbidity (%) Mortality (%) Readmissions (%) Author Year Design FT Standard care FT Standard care FT Standard care FT Standard care FT Standard care FT Standard care Gatt M 2005 RCT (4.4) 9 (4.6) Bradshaw BG 1998 CCT (1.9) 6 (1.7) Stephen A 2003 CCT (1.5) 6.6 (3.3) 4.2 (2.8) 6.9 (4.1) Raue W 2004 CCT Delaney CP 2003 RCT (2.5) 5.8 (3) 5.4 (2.5) 7.1 (4.8) Anderson ADG 2003 RCT (1.8) 7 (2.1) Basse L 2004 CCT (15.25) 10 (16.5) 5.5 (24.5) 13 (40.5) Khoo CK 2007 RCT (8.5) 7 (14.75) 5 (8.5) 7 (14.75) Kariv Y 2007 CCT Polle S 2007 CCT (8.75) 6 (9.5) 4 (8.75) 6.5 (9.5) Wichmann W 2007 CCT (0.4) 9.7 (0.6) Numbers for continuous variables are expressed as mean (SD). Numbers for dichotomous variables are expressed as percentages FT fast track, PHS primary hospital stay, HS hospital stay, RCT randomized controlled study, CCT case control study

7 Int J Colorectal Dis (2009) 24: Fig. 2 Forest plot of pooled data on total hospital stay. (SD standard deviation, CI confidence interval, RCT randomized controlled study) After pooling the data on morbidity rates of all studies, the FT group demonstrated significantly less morbidity compared to the SC group. Subgroup analysis showed that the difference remained significant when RCTs and non-rcts were analyzed individually. Wind et al. [20] in their meta-analysis showed just a trend in the reduction of the morbidity rates of the FT group when RCTs were analyzed individually (Fig. 3). Readmission rates All included studies provided data on readmission of patients. The FT group demonstrated readmission rates ranging from 0% to 24%. On the other hand, the readmission rates of the SC group ranged between 0% and 20%. Meta-analysis of the pooled data from all included studies did not show any significant difference in readmission rates between the two groups. However, subgroup analysis of non-rcts revealed significantly lower readmission rates in the SC group. That was not the case when RCTs were analyzed separately (Fig. 4). Other clinical outcomes Nasogastric tube reinsertions Four studies reported on postoperative gut function by recording the needs for nasogastric tube reinsertion [8, 13, 22, 27]. Particularly, the study from Basse et al. [22] reports a rather big difference between the two groups favoring the FT group [FT group 2/130 (1.5%), SC group 21/130 (16%)]. Despite that fact, pooling of the available data did not reveal any significant difference between the two groups as far as the need for nasogastric tube reinsertion is concerned (Fig. 5). Lung function Three studies provided data on the postoperative function of the respiratory system by measuring different parameters [6, 10, 27]. Anderson et al. [6] measured the forced expiratory volume in 1 s at different time intervals and did not find any significant difference between the two groups. Gatt et al. [10] in their study show the very same thing. When pulmonary function was assessed by measuring the forced vital capacity, as done by Raue et al. [27], the FT group demonstrated significantly better results than the SC group. Pain scores, fatigue scores, and quality-of-life scores Data on pain, fatigue, and quality of life were impossible to analyze because of incompatibility. Measurements of each outcomeweredonebydifferentscoringsystemsinthedifferent studies. The majority of studies that provided data on these

8 1126 Int J Colorectal Dis (2009) 24: Fig. 3 Forest plot of pooled data on morbidity. (CI confidence interval, RCT randomized controlled study) outcomes did not demonstrate any significant difference between the two groups [6, 8, 10, 27]. One study, however [11], showed that patients in the fast-track group were significantly more able in activities of daily living and had significantly less fatigue than the conventional group at 14 days. Mortality and immune system function Seven studies reported on mortality rates [6, 10, 13, 14, 22, 25, 27], three of which gave zero mortality to both groups [14, 25, 27]. The FT group's mortality rate ranged from 0% to 5%. On the other hand, the SC group demonstrated a mortality rate between 0% and 9% (Table 3). Pooling of the data did not identify any significant difference between the two groups (data not shown). The only study that tried to assess the postoperative function of the immune system was the one by Wichmann et al. [29]. The authors measured various parameters of the immune system postoperatively including C-reactive protein (CRP), interleukin (IL)-6, T cells, T helper cells, and natural killer (NK) cells. CRP and IL-6 did not differ between the two groups, but all other parameters mentioned above were significantly better for the FT group. Discussion Fast-track protocols contribute to a quicker recovery of the patients after major colorectal surgery. Morbidity and primary and total hospital stay are significantly reduced. In addition to that, postoperative gut and immune system

9 Int J Colorectal Dis (2009) 24: Fig. 4 Forest plot of pooled data on readmission rates. (CI confidence interval, RCT randomized controlled study) function are significantly improved in comparison with standard care, as this is demonstrated by parameters like nasogastric tube reinsertions, T cells, T helper cells, and NK cell numbers. Readmission rates and objective assessment from patients concerning pain, fatigue, and quality of life were unchanged. Despite these encouraging results from a large number of studies, fast-track protocols are not adopted widely in daily clinical practice [30 32]. Wind et al. [20] in their previous systematic review attributed that to long-standing medical traditions and dogma which suggest, without strong evidence base, that patients should not eat or move right after a major abdominal procedure in general. Kehlet states that, even under ideal circumstances, there is great difficulty with the collaboration and the right communication among the different disciplines required to run the protocol [33]. The multidisciplinary teams, comprising surgeons, anesthesiologists, and nursing staff all require additional training and management in order to carry out respective fast-track roles. There must be significant emphasis on organization and structure before such a complex program can be implemented consistently. One of the most controversial matters about fast-track colorectal surgery is whether it is cost-effective or not. Fast-track protocols seem to cost less money and resources [25, 28], but this is not entirely true. All included studies that compared health costs between the two groups either assessed primary health costs or total

10 1128 Int J Colorectal Dis (2009) 24: Fig. 5 Forest plot of pooled data on nasogastric tube reinsertions. (CI confidence interval, RCT randomized controlled study) health costs including costs from possible readmissions. But these are not the only costs that should be taken into account. As it is well-known, the success of an enhanced recovery program depends on a committed, well-trained, and experienced multidisciplinary team often comprised by anesthesiologists, surgeons, dieticians, physiotherapists, and a very dedicated nursing group. The training of such a team costs a very large amount of money and resources and if the program should be implemented in daily practice, then every member of this team should always be present because it is an important ring in a chain which must never be broken. The above fact is extremely difficult to be achieved in daily practice and it is very well illustrated in the studies by Basse et al. and Delaney et al. [8, 22]. Another reason for not implementing a whole protocol is because many centers around the world have adopted and incorporated various features of an enhanced recovery program in their traditional care plans, such as no routine use of nasogastric tubes, early postoperative feeding, and mobilization, in an effort to modernize them. Another sound argument made against the extremely strict structure of fast-track protocols is that not all of the fast-track elements are of equal importance. Laparoscopy, in particular, has been considered as the key element of success for the multimodal rehabilitation protocols. However, since 2005, studies have come to inconsistent conclusions on this matter, but no study could convincingly identify any significant differences in clinical outcomes between patients who had undergone open or laparoscopic colorectal surgery within an enhanced recovery program, indicating that laparoscopy might not have the great importance attributed to it [14, 34 36]. The study by Basse et al. [34] in particular performed a randomized controlled trial directly comparing open versus laparoscopic surgery with both groups undergoing multimodal enhanced recovery programs. Patients in both groups, despite having a mean age of 75 and having comparable comorbidities and ASA status, did not show a significant difference in either postoperative hospital stay or readmissions. The relation between fast-track colorectal surgery and laparoscopy remains uncertain, but in the future laparoscopy may become an essential part of fast-track surgery in the trend towards further reducing length of stay. In general, there are elements whose use in fast-track protocols is fully justified by very strong evidence, such as epidural analgesia, no bowel preparation, or no routine use of nasogastric tubes and there are others for which data are not so strongly supportive. In order for the above conclusions to be confirmed and for the relative value of each element to be

11 Int J Colorectal Dis (2009) 24: fully investigated, more randomized studies are needed to make all possible comparisons among open approach, laparoscopy, and fast-track protocols incorporating various elements and traditional care plans. Even if the use of fast-track elements in an FT protocol is widely accepted, the issue of compliance with the protocol is justifiably raised. To our knowledge, there is only one study which assesses the compliance of a fully implemented FT program by Polle et al. [14]. Interestingly, the authors report that a mean of 7.4 fast-track elements out of 13 were put to practice per patient. Despite the discouraging result, they also report that there had been almost no impact on the clinical outcomes of the accelerated recovery strategy, reduction in hospital stay, and no effect on overall morbidity or patients' satisfaction [14]. Surprisingly, in contrast to what was expected, compliance did not increase along with the experience of the team responsible for running the program. Low compliance according to the authors is attributed to bad collaboration of three different disciplines in daily clinical practice [14]. If such protocols are to be implemented in daily practice, low compliance with the protocol must be resolved. This can be achieved by conducting more studies to identify and analyze its possible causes. A major concern about fast-track surgery is possible higher readmission rates. After pooling the data provided on readmissions, no significant difference could be identified by the overall analysis or the analysis conducted on the subgroups of RCTs and non-rcts. The study by Kariv et al. [25] assumes that readmission rates are approximately the same in both groups and base their assumption on the same impact that readmissions have on total hospital stay, which in their study is raised by one day in both groups, not affecting in this way the statistically significant difference in total hospital stay. To minimize the possibility of higher readmission rates in the FT group, it must be realized that all fast-track protocols must have rigid and strict discharge criteria for their patients. Only by ensuring that FT patients leave the hospital in the same physical condition as the ones offered traditional care, one can be sure of acquiring accurate results regarding readmission rates. In order to achieve this, planned length of stay in patients on a fasttrack program need to be carefully considered. One study by Anderson et al. [37] in 2007 showed that when plans were made in a fast-track program to keep patients in hospital for 3 days rather than 2, with the same discharge criteria, there were significantly fewer readmissions as a result. This reduced the overall hospital stay including readmission days. As far as immediate postoperative morbidity is concerned, this meta-analysis demonstrates a clear-cut statistically significant difference between the two groups with the FT group having lower morbidity rates. In this case, the difference remains statistically significant even in the subgroup of RCTs unlike the systematic review by Wind et al. [20] where they demonstrated only a trend in the same subgroup. This is partly explained by the better reaction of the cell-mediated immunity in the FT group [29]. Good clinical outcomes in general and low morbidity rates in the FT group in particular possibly are associated with better preserved cell-mediated immunity [29]. Some of the fast-track elements responsible for this preservation are decreased preoperative and postoperative fasting, carbohydrates, and no bowel preparation. The most controversial issue that preoccupies medical staff worldwide is the selection of patients to be included with safety in multimodal rehabilitation programs. Most of the studies recruit in their FT groups young patients in good physical condition and with no important comorbidities (ASA I II). The studies by Kariv et al. [25] and Delaney et al. [8] had patients whose mean age was considerably lower than others because of the predominance of patients with inflammatory bowel disease having colonic resection. Others such as Khoo et al. [13] didnot have an age limit but still required patients to walk more than 100 m unaided a surrogate marker for a lower ASA grade. Individually, these studies all still showed significant advantages with fast-track care pathways. Do old patients with accompanying severe comorbidities have a place in FT protocols? Recently, Hammer et al. [38] tried to directly implement an FT protocol into their hospital daily practice. They observed that morbidity and mortality rates remained the same or were lower compared to those before implementing an FT protocol. The study concludes that fast-track surgery is feasible in an unselected patient population scheduled for elective colon cancer resections without compromising quality and safety and the same conclusion is drawn by Maessen et al. [32]. The above conclusion seems a little bold and this is because even in well-designed studies fast-track surgery fails in a subgroup of patients. Kariv et al. [25] tried to determine possible factors that affect early discharge of their FT group's patients. The analysis of their data showed that three main factors were responsible for late discharge of FT patients and those were male gender, reoperations, and anastomotic complications. They did not assess FT patients' body mass index, which is an important factor responsible for the presence of postoperative complications (especially anastomotic leakage) in colorectal surgery. In conclusion, selection of patients is very controversial and more solid evidence is required to clarify the matter. In summary, the concept of fast-track protocols in colorectal surgery is becoming more and more appealing among doctors because there is solid evidence that reduces primary and total hospital stay without compromising

12 1130 Int J Colorectal Dis (2009) 24: patients' safety offering lower morbidity and the same readmission rates. However, there are many issues that need to be resolved in order for such strategies to be implemented into ordinary daily practice. To achieve that, many more randomized carefully designed studies need to be conducted to answer all the above-mentioned raised issues. Accelerated recovery protocols must be very rigid, must be followed very strictly, and constantly and incorporate evidence-based fasttrack elements and a well-specified discharge policy in order to achieve an earlier patient discharge. What current studies have shown is that fast-track care does not predispose to greater patient morbidity or mortality. With this in mind, well-constructed randomized studies, stratified into upper and lower gastrointestinal surgery, as well as anatomically specific planned surgery such as right or left colonic resections will be useful in further assessing its utility under different circumstances and scenarios. Conclusion Enhanced recovery programs have shown to be effective in reducing overall hospital stay without compromising patient safety or increasing morbidity. There is good evidence that fast-track programs should form the mainstay of elective colorectal surgery. References 1. Arenal JJ, Benito C, Concejo MP, Ortega E (1999) Colorectal resection and primary anastomosis in patients aged 70 and older: prospective study. Eur J Surg 165(6): Bokey EL, Chapuis PH, Fung C, Hughes WJ, Koorey SG, Brewer D, Newland RC (1995) Postoperative morbidity and mortality following resection of the colon and rectum for cancer. 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