Results
From 1594 studies identified from the original search, 97 were reviewed as full text articles. Of these, 36 comprising 23[ 37 , 40 , 45 - 65 ] randomised controlled trials and 13 observational studies[ 29 , 66 - 77 ] were eligible for inclusion (Figure 1 ). The risk of bias of the randomised controlled trials included in this study was moderate (Table 1 ).
Risk of bias of studies included
NA: Not applicable (observational study); +: Low risk of bias; -: High risk of bias; (1): Allocation concealment utilized identification number of patient (odd or even); (2): Not blinded.
PRISMA diagram showing identification of relevant studies from initial search, PRISMA: Preferred reporting Items for systematic reviews and meta-analyses.
Overall, 21568 patients were included in the meta-analysis, of whom 6166 had no bowel preparation of any sort, 2739 had a solitary rectal enema and 12663 underwent full MBP as per local policy. Of these, 6277 patients were included in randomised controlled trials and 15291 in observational studies. Demographic details are summarised in Table 2 and of details of interventions (bowel preparation and perioperative antibiotics) in Table 3 .
Baseline patient demographics for all studies included
FAP: Familial adenomatous polyposis; IBD: Inflammatory bowel disease; MBP: Mechanical bowel preparation; RCT: Randomised controlled trial.
Nature of the bowel preparation used in studies included in the meta-analysis
MBP: Mechanical bowel preparation; PEG: Polyethylene glycol.
All studies except one[ 75 ] included data on the primary outcome measure of this meta-analysis, the incidence of anastomotic leak (Figure 2 ). When MBP was compared with no MBP (including no preparation at all and those who underwent a single rectal enema), there was no difference in the incidence of anastomotic leak (OR = 0.90, 95%CI: 0.74 to 1.10, P = 0.32). When MBP vs absolutely no MBP was analysed[ 29 , 40 , 46 , 48 - 50 , 52 , 54 - 65 , 68 , 70 , 71 , 73 ], this made no difference to anastomotic leak rates (OR 0.94, 95% CI 0.70 to 1.25, P = 0.67), nor when MBP was compared with a single rectal enema[ 37 , 45 , 47 , 51 , 53 , 66 , 67 , 69 , 72 , 74 , 76 , 77 ] (OR = 0.92, 95%CI: 0.70 to 1.20, P = 0.52).
Forest plot comparing overall anastomotic leak rate for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). A Mantel-Haenszel random effects model was used to perform the meta-analysis and odds ratios are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
When randomised controlled trials alone were included in the analysis[ 37 , 40 , 45 - 65 ] (Supplementary figure 1A), the use of MBP vs no MBP did not affect the incidence of anastomotic leak (OR = 1.02, 95%CI: 0.75 to 1.40, P = 0.90), nor when MBP vs absolutely no MBP[ 40 , 46 , 48 - 50 , 52 , 54 - 65 ] or MBP vs single rectal enema[ 37 , 45 , 47 , 51 , 53 ]were considered. When observational studies alone were analysed[ 66 - 73 , 76 , 77 ] (Supplementary figure 1B), the use of MBP vs no MBP did significantly affect the incidence of anastomotic leak (OR = 0.76, 95%CI: 0.63 to 0.91, P = 0.003), although this was not significant when MBP vs single rectal enema[ 66 , 67 , 69 , 72 , 74 , 76 , 77 ] and MBP vs absolutely no MBP[ 29 , 68 , 70 , 71 , 73 ] were considered separately.
Data on the incidence of SSI were presented in a total of 19780 patients in 32 studies[ 29 , 37 , 40 , 45 - 61 , 64 - 70 , 72 - 75 , 77 ] (Figure 3 ). There was no difference in the incidence of SSI in those who did vs those who did not undergo MBP (OR = 0.99, 95%CI: 0.80 to 1.24, P = 0.96), nor in those who had MBP vs those receiving a single rectal enema[ 37 , 45 , 47 , 51 , 53 , 66 , 67 , 69 , 72 , 74 , 77 ] (OR = 1.00, 95%CI: 0.57 to 1.76, P = 1.00) or those who had MBP vs those receiving absolutely no preparation[ 29 , 40 , 46 , 48 - 50 , 52 , 54 - 61 , 64 , 65 , 68 , 70 , 73 , 75 ] (OR = 0.98, 95%CI: 0.78 to 1.24, P = 0.87).
Forest plot comparing overall surgical site infection rates for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). A Mantel-Haenszel random effects model was used to perform the meta-analysis and odds ratios are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
When data obtained from 21 randomised controlled trials[ 37 , 40 , 43 , 45 - 61 , 64 , 65 ] alone with a total of 5971 patients were included (Supplementary figure 2A), the use of MBP vs no MBP did not impact upon the incidence of SSI (OR = 1.16, 95%CI: 0.96 to 1.39, P = 0.12), nor when MBP vs single rectal enema[ 37 , 45 , 47 , 51 , 53 ] or MBP vs absolutely no preparation[ 40 , 43 , 46 , 48 - 50 , 52 , 54 - 61 , 64 , 65 ] were considered. When just observational studies were included[ 29 , 66 - 70 , 72 - 75 , 77 ] (11 studies, 13809 patients; Supplementary figure 2B), patients who received MBP had a significantly reduced incidence of SSI than those who did not receive MBP (OR = 0.64, 95%CI: 0.55 to 0.75, P < 0.0001), with similar results seen in those who received MBP vs absolutely no MBP[ 29 , 68 , 70 , 73 , 75 ], although no difference was seen between those who received full MBP vs a single rectal enema[ 66 , 67 , 69 , 72 , 74 , 77 ].
A total of 29 studies[ 29 , 37 , 40 , 45 , 46 , 48 , 49 , 51 , 53 - 56 , 58 , 59 , 61 , 62 , 64 - 75 , 77 ] on 19327 patients included data on postoperative intra-abdominal collections (Figure 4 ). The administration of MBP vs no MBP did not impact upon the incidence of intra-abdominal collection (OR = 0.86, 95%CI: 0.63 to 1.17, P = 0.34), nor when full MBP vs single rectal enema[ 37 , 45 , 47 , 51 , 53 , 66 , 67 , 69 , 72 , 74 , 77 ] (OR = 0.83, 95%CI: 0.45 to 1.51, P = 0.54) or MBP vs absolutely no preparation at all were considered[ 29 , 40 , 46 , 48 - 50 , 52 , 54 - 61 , 64 , 65 , 68 , 70 , 73 , 75 ] (OR = 0.92, 95%CI: 0.62 to 1.34, P = 0.65).
Forest plot comparing overall intra-abdominal collection rates for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). A Mantel-Haenszel random effects model was used to perform the meta-analysis and odds ratios are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
When randomised controlled trials alone were considered[ 37 , 40 , 45 , 46 , 48 , 49 , 51 , 53 - 56 , 58 , 59 , 61 , 62 , 64 , 65 ] (Supplementary figure 3A), no differences were seen in the incidence of intra-abdominal collection between any of the groups (OR = 1.17, 95%CI: 0.66 to 2.10, P = 0.59). However, when observational studies were analysed[ 29 , 66 - 75 , 77 ] (Supplementary figure 3B), the incidence of intra-abdominal collection was significantly reduced in those who had MBP vs those who did not (OR = 0.67, 95%CI: 0.53 to 0.85, P = 0.0008). A significant reduction in the incidence of intra-abdominal collection was seen in the subgroup of patients who underwent MBP vs absolutely no preparation[ 29 , 68 , 70 , 71 , 73 , 75 ] (OR = 0.65, 95%CI: 0.54 to 0.78, P < 0.0001), however no difference was seen in those undergoing MBP vs a single rectal enema[ 66 , 67 , 69 , 72 , 74 , 77 ] (OR = 0.80, 95%CI: 0.34 to 1.88, P = 0.60).
Hospital length of stay (LOS) was reported in 20 studies[ 40 , 45 , 46 , 49 , 51 - 56 , 61 , 63 , 67 - 69 , 71 - 74 , 77 ] including 7381 patients (Figure 5 ), with the use of MBP vs not (including those who received a single rectal enema) resulting in no significant difference in hospital length of stay (overall mean difference 0.11 d, 95%CI: -0.51 to 0.73, P = 0.72). This was mirrored when just randomised controlled trials were examined[ 40 , 45 , 46 , 49 , 51 - 56 , 61 , 63 ] (Supplementary figure 4A; overall mean difference 0.22 d, 95%CI: -0.44 to 0.88, P = 0.52) and when just observational studies were included[ 67 - 69 , 71 - 74 , 77 ] (Supplementary figure 4B; overall mean difference -0.12 d, 95%CI: -1.48 to 1.25, P = 0.87).
Forest plot comparing overall hospital length of stay for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). An inverse-variance random effects model was used to perform the meta-analysis and mean differences are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
Mortality was reported in 25 studies[ 29 , 37 , 40 , 45 - 49 , 51 - 54 , 56 , 57 , 59 , 60 , 65 , 66 , 68 , 69 , 71 - 74 , 77 ] that included 16657 patients (Figure 6 ). The time point this outcome measure was measured was variable between studies, with the majority taken at 30 d[ 29 , 37 , 45 - 49 , 51 , 53 , 60 , 65 , 69 , 71 , 73 , 77 ], two taken at first outpatient clinic quoted to be approximately two weeks following hospital discharge[ 40 ] or four weeks following surgery[ 66 ], one at two months[ 56 ] and one at three months[ 52 ], with six papers not stating when mortality was taken from[ 54 , 57 , 59 , 68 , 72 , 74 ]. No difference was seen with the use of full MBP, single rectal enema or no preparation at all.
Forest plot comparing overall mortality rates for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). A Mantel-Haenszel random effects model was used to perform the meta-analysis and odds ratios are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
A similar result was seen, with no significant differences, when this comparison was made using only randomised controlled trials[ 37 , 40 , 45 - 49 , 51 - 54 , 56 , 57 , 59 , 60 , 65 ] (Supplementary figure 5A). However, in observational studies[ 29 , 66 , 68 , 69 , 71 - 74 , 77 ], MBP was associated with a significant reduction in mortality (OR = 0.50, 95%CI: 0.34 to 0.74, P = 0.0005) (Supplementary figure 5B). A significant reduction in the incidence of intra-abdominal collection was seen in the subgroup of patients in observational studies who underwent MBP vs absolutely no preparation[ 29 , 68 , 71 , 73 ] (OR = 0.42, 95%CI: 0.27 to 0.56, P < 0.0001). However, no difference was seen in those undergoing MBP vs a single rectal enema[ 66 , 69 , 72 , 74 , 77 ] (OR = 0.99, 95%CI: 0.41 to 2.41, P = 0.98).
A total of 20 studies on 16742 patients[ 29 , 40 , 46 , 49 , 51 - 57 , 59 , 65 , 68 , 69 , 71 , 72 , 74 , 76 , 77 ] examined the impact of MBP upon reoperation rates (Figure 7 ). Overall the use of MBP vs no MBP did not impact upon requirement for reoperation[ 29 , 40 , 46 , 49 , 51 - 57 , 59 , 65 , 68 , 69 , 71 , 72 , 74 , 76 , 77 ] (OR = 0.91, 95%CI: 0.75 to 1.12, P = 0.38), nor when MBP vs a single rectal enema[ 51 , 53 , 69 , 72 , 74 , 76 , 77 ] (OR = 0.82, 95%CI: 0.42 to 1.60, P = 0.56) or MBP vs absolutely no preparation[ 29 , 40 , 46 , 49 , 52 , 54 - 57 , 59 , 65 , 68 , 71 ] (OR = 0.85, 95%CI: 0.72 to 1.01, P = 0.06) were compared.
Forest plot comparing overall reoperation rates for patients receiving mechanical bowel preparation vs either a single rectal enema (top) or absolutely no preparation (bottom). A Mantel-Haenszel random effects model was used to perform the meta-analysis and odds ratios are quoted including 95% confidence intervals. MBP: Mechanical bowel preparation.
When only randomised controlled trials were examined[ 40 , 46 , 49 , 51 - 57 , 59 , 65 ] (Supplementary figure 6A), again no difference was seen by the use of MBP, a single rectal enema or absolutely no preparation. When observational studies were examined[ 29 , 68 , 69 , 71 , 72 , 74 , 76 , 77 ] (Supplementary figure 6B) overall MPB resulted in no significant reduction in the reoperation rate vs those who did not have bowel preparation but may have had a rectal enema (OR = 0.86, 95%CI: 0.64 to 1.15, P = 0.30), as well as when those who has a single rectal enema (OR = 0.82, 95%CI: 0.44 to 1.52, P = 0.52), however a significant difference was seen when MBP was compared with patients who received absolutely no preparation (OR = 0.78, 95%CI: 0.63 to 0.97, P = 0.02).
A total of 11 studies[ 39 , 45 , 46 , 50 , 56 , 57 , 59 , 71 , 75 - 77 ] included either only patients who were undergoing rectal or surgery, or outcome measures for the subgroup of patients who had undergone rectal surgery. Ten studies compared MBP with no MBP, with just one study comparing MBP with a single rectal enema[ 45 ]. All studies except one[ 77 ] included data on anastomotic leak rates, finding MBP not to be associated with any difference in incidence (OR = 0.86, 95%CI: 0.64 to 1.15, P = 0.30). Only seven studies[ 39 , 45 , 46 , 50 , 71 , 75 , 77 ] included data on SSI, which also demonstrated no significant difference (OR = 1.22, 95%CI: 0.82 to 1.81, P = 0.33). Intra-abdominal collection and mortality data were similarly only available for five[ 39 , 45 , 46 , 71 , 77 ] and four studies[ 39 , 45 , 46 , 71 ] respectively, neither of which were associated with the use of MBP (OR = 0.54, 95%CI: 0.21 to 1.38, P = 0.20; and OR = 0.73, 95%CI: 0.29 to 1.82, P = 0.50, respectively). The results in patients undergoing rectal surgery are summarized in Table 4 .
Effect of bowel preparation on outcome in patients undergoing rectal surgery
Data from[ 39 , 45 , 46 , 50 , 56 , 57 , 59 , 71 , 75 - 77 ]. MBP: Mechanical bowel preparation
Discussion
This meta-analysis of 23 randomised controlled trials and 13 observational studies has demonstrated that, overall, the use of MBP vs either absolutely no bowel preparation or a single rectal enema was not associated with a statistically significant difference in the incidence of anastomotic leak, SSI, intra-abdominal collection, mortality, reoperation or total hospital length of stay. When just randomised controlled trial evidence was analysed, there was, again, no significant difference by preparation method in any clinical outcome measure. Finally, when observational studies were analysed, the use of full preparation was associated overall with a reduced incidence of anastomotic leak, SSI, intra-abdominal collection and mortality rates, with these results mirrored in patients receiving MBP vs absolutely no preparation, but no significant differences in those receiving MBP vs a single rectal enema. When a separate subgroup of just rectal surgery was considered, MBP was not associated with a statistically significant difference in anastomotic leak rates, SSI, intra-abdominal collection or mortality, irrespective of whether patients not receiving MBP were given a single rectal enema.
This study represents the most comprehensive examination of the role of MBP prior to elective colorectal surgery to date. As part of the study plan, the decision was made to include observational studies as well as randomised controlled trials. However, in order to ensure that inclusion of studies of less rigorous methodology did not exert an undue bias, a predetermined analysis of studies of both methodologies was conducted. This revealed that the overall results and those from analysing just evidence from randomised controlled trials were much the same. However, when analysing evidence from observational studies, this resulted in a significant reduction in anastomotic leak, SSI, intra-abdominal collection and mortality rates. The reasons for this difference in results is not clear from this study, but it is possible that selection bias may exert a confounding effect upon the results, and as such the use of MBP in selected patients as determined by the physician in charge may be appropriate.
With the exception of hospital length of stay ( I 2 = 85%), overall study heterogeneity was low to moderate (0%-34%) for all clinical outcome measures, suggesting the studies to be relatively homogeneous. The risk of bias for the randomised controlled trials included in the meta-analysis (Table 1 ) was relatively low.
As the raw mean and standard deviation data were not available on the hospital LOS for all studies, despite several attempts at obtaining this directly from the authors, it was necessary to infer this from what was available (either median and range or interquartile range) using statistical techniques previously described[ 42 ]. This is a valid technique which has been well described previously, but this may exert some degree of bias upon the results of the meta-analysis.
There was poor documentation within the studies included regarding the side effects of MBP including the incidence of electrolyte disturbance, fluid depletion and requirement of resuscitation, and renal disturbance or failure, hence this was not included as an outcome within the meta-analysis.
Emerging evidence, much of which has been derived from the studies based upon NSQIP datasets have focused upon the combination between intraluminal antibiotics and MBP and have demonstrated a reduction in SSI rates. However, the data contained within the studies included within this meta-analysis has been scanty regarding the use of intraluminal antibiotics and as such it has not been possible to include this data within the meta-analysis. This may act as a potential confounder when considering the effect of MBP and clinical outcomes.
The studies contained predominantly mixed populations of colonic and rectal procedures, with inadequate documentation to differentiate results between the two, which may be particularly important in addressing the question regarding the use of a single rectal enema as bowel preparation. In addition, there was poor documentation regarding the nature of the anastomoses within the studies included, with a mixture of ileocolic, colon-colon and colorectal. The role of mechanical bowel preparation in various anastomosis types has not been well established. The majority of studies included a predominance of colonic procedures, with some focusing entirely on colonic rather than rectal surgery. Only a small subgroup analysis was available to analyse the impact of MBP in rectal surgery, from which it is very difficult to draw strong conclusions. Further studies are required to discern the importance of a pre-operative enema in this setting. Similarly, the level of documentation in studies regarding laparoscopic vs open surgery was not sufficient in terms of correlation with clinical outcome measures to be able to discern the importance of MBP in this setting. Only one recent observational study has focused entirely on laparoscopic procedures[ 74 ] which demonstrated no significant difference in the rates of intra-abdominal septic complications by the use of MBP, and prior to this evidence was purely based on several small studies[ 38 , 78 ].
The nature of the MBP used was inconsistent between studies, and this may introduce a further bias[ 79 ]. There was also poor documentation regarding antibiotic usage, particularly in the early studies. Much of the recent literature regarding preparation of the bowel has focused upon the use of oral luminal antibiotics in combination with MBP, with these studies suggesting a potential role for this therapy[ 26 , 27 ]. A recent meta-analysis on this topic has demonstrated a significant reduction in the risk of SSI in patients undergoing elective colorectal surgery given oral systemic antibiotics with MBP vs systemic antibiotics and MBP[ 80 ], thus representing a further weakness in the studies included in this meta-analysis.
A recently published meta-analysis[ 8 ] of 18 randomised controlled trials, 7 non-randomised comparative studies, and 6 single-group cohorts compared the use of oral MBP with or without an enema vs no oral MBP with or without an enema. This study found that MBP vs no MBP was associated with no difference in the rates of all-cause mortality (OR = 1.17, 95%CI: 0.67 to 2.67), anastomotic leakage (OR = 1.08, 95%CI: 0.79 to 1.63), SSI (OR = 1.19, 95%CI: 0.56 to 2.63) as well as wound infections, peritonitis or intra-abdominal abscess or reoperation. This study however found considerable variance in the estimation of treatment effects, possibly due to the large range of study methodology included, which may mask a treatment effect seen.
This topic has been reviewed by the Cochrane Collaboration[ 81 - 83 ], with the most recent review conducted in 2011[ 10 ]. This included a total of 18 randomised controlled trials in elective colorectal surgery (5805 patients), and demonstrated no statistically significant evidence to support the use of MBP in either low anterior resection, rectal or colonic surgery in terms of anastomotic leakage or wound infection.
A previous meta-analysis has examined the role of MBP prior to proctectomy[ 12 ] from eleven publications (1258 patients), although extractable data were only available in a limited number of studies for outcome measures other than anastomotic leakage rates. This study[ 12 ] found no beneficial effect from MBP prior to proctectomy with regards to anastomotic leakage (OR = 1.144, 95%CI: 0.767 to 1.708, P = 0.509), SSI (OR = 0.946, 95%CI: 0.597 to 1.498, P = 0.812), intra-abdominal collection (OR = 1.720, 95%CI: 0.527 to 5.615, P = 0.369) or postoperative mortality.
Worldwide, elective colorectal surgery is performed frequently. Current opinion regarding the use of MBP prior to this surgery is inconsistent[ 17 , 18 ], despite several previous meta-analyses which have suggested this is not useful in reducing postoperative complications[ 9 , 10 ]. The use of MBP is not without cost implications, including the preparation itself and in elderly and frail patients, MBP may also necessitate an additional stay in hospital prior to surgery due to the risk of dehydration and electrolyte disturbance which is associated with considerable additional healthcare costs. This meta-analysis further reinforces that MBP is not associated with any difference in postoperative complication rates, mortality of hospital length of stay, particularly in elective colonic surgery, and as such should not be administered routinely.
In conclusion, this study represents the most comprehensive meta-analysis to date on MBP in elective colorectal surgery. It has demonstrated that MBP vs a single rectal enema or no bowel preparation at all is not associated with a statistically significant difference in any of the clinical outcome measures studied. Given the risks of electrolyte disturbance and patient dissatisfaction, as well as potentially significant levels of dehydration and requirement for pre-admission prior to surgery, MBP should no longer be considered a standard of care prior to elective colorectal surgery.