Surgical site infection (SSI) is a major burden for patients undergoing elective colorectal surgery. It adds significantly to the cost of health care, and administration of preoperative bowel preparation has been proposed to reduce the incidence of SSI. The role of mechanical bowel preparation (MBP) with polyethylene glycol or sodium phosphate has been studied in randomized controlled trials (RCTs), with perceived benefits including ease of manipulation of the bowel, reduced spillage and resultant contamination, reduced luminal pressure, and lesser bacterial load. However, a recent meta-analysis1 of 36 RCTs and cohort studies, and an earlier one2 of 14 RCTs found that that the administration of MBP did not impact upon postoperative morbidity or mortality. This, in combination with high rates of patient dissatisfaction and fluid and electrolyte disturbances, has led to the conclusion that MBP should not be prescribed routinely. This is reflected in Guidelines from the Enhanced Recovery After Surgery Society,3,4 the National Institute of Health and Care Excellence,5 and the American Society for Enhanced Recovery,6 all of which suggest that MBP should not be administered routinely. However, although the American Society for Enhanced Recovery guidelines suggest that MBP should not be given in isolation, they recommend routine use of an isosmotic bowel preparation and combined oral antibiotic prior to elective colorectal surgery.6
The use of oral antibiotic (OAB) prophylaxis, in the form of nonabsorbable luminal antibiotics, was first proposed in 1971 by Rosenberg et al7 in a RCT of 150 patients undergoing large bowel surgery receiving MBP alone, or MBP in combination with phthalylsulphathiazole or phthalylsulphathiazole and neomycin. The combination of MBP+OAB was associated with a significant reduction in SSI (23% vs. 40%), anastomotic leak rates (24% vs. 52%), and sepsis rates (37.3% vs. 64.4%).6 Although several studies provided evidence for the role of oral antibiotics in elective colorectal surgery, the regimens included large volume preparations,8–10 prolonged preoperative hospital admission, and in the setting of prolonged preoperative starvation protocols, dehydration, and electrolyte disturbances were commonplace.11,12 Decreased compliance and inconsistent bowel cleansing resulted in a reduced intervention effect and, this, combined with reduced preoperative admission times, resulted in the practice of combined MBP+OAB dwindling in favor of more restrictive MBP regimens alone. However, recently there has been resurgent interest in the use of OAB in colorectal surgery,13,14 particularly in light of a large number of retrospective cohort and database studies, many of which originated from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted colectomy database.15–20 Evidence for the role of OAB has been summarized in several narrative reviews21,22 as well as meta-analyses,23–25 which have supported a reduction in SSI associated with combined MBP, OAB, and parenteral antibiotics over MBP and parenteral antibiotics alone. However, the most recent of these studies have been flawed in their inclusion of multiple studies based on the NSQIP database which have large degrees of cross-over of the same study population and have mostly focused upon SSI alone rather than other postoperative outcomes. In addition, recent studies18,26 have suggested that OAB alone may provide equivalent prophylaxis in terms of SSI and anastomotic leak rates when compared with a combined regimen of MBP+OAB.
The aims of this meta-analysis of RCTs and observational cohort studies in patients undergoing elective colorectal surgery were to:
- Compare the impact of OAB with or without MBP in elective colorectal surgery in terms of SSI, anastomotic leak, 30-day mortality, overall morbidity, development of ileus, reoperations, and Clostridium difficile infection.
- Compare evidence derived from RCTs and cohort studies.
- Compare the role of administration of OAB with and without MBP in the setting of laparoscopic versus open surgery.
The PubMed, Google Scholar, MEDLINE, and the Cochrane Library databases were searched to identify studies evaluating the effect of OAB in adults undergoing elective colorectal surgery published between January 1, 1981 and May 30, 2018. This date restriction was imposed as recommendations that parenteral antibiotics should be administered routinely for prophylaxis against SSI in colorectal surgery were made in 198127 and it was felt that all studies considering the role of oral antibiotic prophylaxis should include parenteral antibiotic prophylaxis, to reflect current perioperative care. The search terms used were: (oral antibiotic OR oral antibacterial) AND (colon OR rectal OR colorectal) AND surgery. The bibliographies of all studies which met the inclusion criteria, and previous systematic reviews and meta-analyses on the subject were reviewed to ensure study inclusion was as complete as possible. Non-English-language papers were translated for inclusion. The meta-analysis was conducted in accordance with the PRISMA statement.28
Selection of Articles
Articles were screened for suitability on the basis of title and abstract by 2 independent researchers (K.E.R. and H.J.-E.). Studies were eligible for inclusion if they examined the role of OAB preparation with or without MBP, compared with either MBP alone, OAB alone, or no preparation in adult patients due to undergo elective colorectal surgery, with at least 1 relevant clinical outcome reported. The type of colorectal surgery performed in terms of type of resection or laparoscopic versus open, the presence or absence of rectal enema administration, or the indication for surgery were not discriminants. Studies were excluded if they did not consider any relevant clinical outcomes, included emergency procedures, or duplicated study populations from other included studies. From the large number of ACS NSQIP studies published15–20,26,29–40 (Supplementary Table 1, http://links.lww.com/SLA/B542), only the largest study by Midura et al31 was included to avoid the risk of duplication of patient populations within the analysis. Similarly, 3 publications41–43 originated from the Michigan Surgical Quality Collaborative Colectomy Best Practices Project. When these were reviewed, 2 studies41,42 considered the same comparison of preparations (MBP+OAB vs no preparation), and as such only the more comprehensive study including a larger number of clinical outcomes was included.41 The third study from the Michigan Surgical Quality Collaborative database43 examined a different preparation combination, thus this was included in the meta-analysis. Finally, the national Veterans Affairs Surgical Quality Improvement Program was the basis for 2 studies44,45 on the same regimen comparison, thus only the largest study was included within the meta-analysis.45 One study46 included a small proportion of patients undergoing emergency colorectal resection within the cohort (311 of a total population of 2240), so any outcomes that included this study were analyzed both with and without it included to discern any difference in results.
Data were extracted by 2 independent researchers (K.E.R. and H.J.-E.) and any discrepancies were resolved by a senior author (D.N.L.). The primary outcome measure was SSI, with secondary outcome measures including anastomotic leak, 30-day mortality, overall morbidity, development of ileus, reoperation, and Clostridium difficile infection. Data were also collected on patient demographics (age, sex), surgical variables (type of resection, open vs. laparoscopic, underlying disease necessitating resection), and details of the preparation used, in terms of parenteral and oral antibiotics as well as MBP. Several studies stated that MBP was not used in patients with obstructing masses, which is mirrored in standard clinical practice, thus these papers were included in the meta-analysis.
The risk of bias was assessed for the RCTs included using the Cochrane Collaboration tool within the RevMan software47 which considers random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and selective reporting (reporting bias).
Data were entered into RevMan 5.3 software.47 Dichotomous variables were calculated as risk ratios (RR) with a 95% confidence interval using the Mantel–Haenszel random effects model. From this, forest plots were derived, with a P value of less than 0.05 on 2-tailed testing representing a statistically significant difference. Data from RCTs and cohort studies were included separately within each forest plot, with a summative analysis of all the evidence performed in addition. Inconsistency and heterogeneity between studies were estimated using the I2 statistic;48 ≤25% represented low heterogeneity, 25% to 50% represented moderate, and >50% high heterogeneity.
The protocol for this meta-analysis was registered with the PROSPERO database (www.crd.york.ac.uk/prospero)—registration number CRD42018098950.
From the 520 studies identified in the initial search, 40 studies31,41,43,45,46,49–83 on 69,517 participants were included (Supplementary Figure 1, http://links.lww.com/SLA/B542). Of these 28 were RCTs with 6437 participants49–53,55–59,61–67,69–73,75,76,78–80,83 and 12 were cohort (case control) studies with 63,080 participants.31,41,43,45,46,54,60,68,74,77,81,82 The risk of bias in the RCTs included was variable, with poor levels of documentation particularly surrounding randomization methods, allocation concealment, and blinding in the earlier studies (Table 1). Six studies57,58,62,64–66 administered different parenteral antibiotic regimens depending upon whether the patient was receiving MBP+OAB or MBP alone, which may provide significant source of bias in terms of SSI prevention. In addition, 1 study73 included 2 differing parenteral antibiotic regimens, both in combination with MBP, versus OAB, MBP and parenteral antibiotics. As both of the parenteral antibiotic regimens were considered eligible for inclusion, these were grouped together to form the MBP alone group. In terms of oral antibiotics, 2 studies administered OAB preparation only on the day of surgery; one64 gave ciprofloxacin 1 g 1 hour preoperatively and the other74 ciprofloxacin 750 mg 1 to 3 hour preoperatively. A subgroup of another study51 received only 1 dose of OAB the day before surgery, with the remainder receiving 3 doses. These 3 studies may, therefore, have an attenuated the intervention effect from the OAB administered.
Two studies53,55 focused on surgery using laparoscopic techniques, 21 on open surgery alone,46,50,52,57,58,61,62,64–74,76,78,80 with 9 studies41,43,49,54,60,75,77,81,82 mixing both open and laparoscopic techniques and the remaining 8 studies not providing this information.31,45,51,56,59,63,79,83 The most recent publication31 included patients undergoing robotic surgery. The indication for surgery was colorectal cancer in 8 studies,46,54,55,59,61,75,78,81 inflammatory bowel disease in 2,67,80 with the remaining including a mixture of benign and malignant pathologies. Patient demographics and surgical variables as well as the details of MBP, OAB, and parenteral antibiotics administered are detailed in Table 2 .
Surgical Site Infection (SSI)
MBP+OAB Versus MBP
The comparison between MBP+OAB versus MBP alone was performed in 35 studies; 26 RCTs49–53,55–59,61–67,69,70,72,73,75,76,78–80 and 9 cohort studies31,43,45,54,60,68,74,77,81 with a total of 47,610 patients. When all studies were considered (Fig. 1), the combination of MBP+OAB was associated with a significant reduction in SSI versus MBP alone (RR 0.51, 95% CI 0.46–0.56, P < 0.00001, I2 = 13%). The results remained consistent when just RCT studies were examined (5378 patients; RR 0.57, 95% CI 0.48–0.68, P < 0.00001, I2 = 12%), as well as cohort studies (42,232 patients; RR 0.48, 95% CI 0.44–0.51, P < 0.00001, I2 = 0%).
MBP+OAB Versus OAB
The analysis of MBP+OAB versus OAB alone was considered by 4 studies; 2 RCTs71,83 and 2 cohort studies31,45 including 23,483 patients (Fig. 2). Overall, the combination of MBP+OAB was not associated with any difference in the incidence of SSI versus OAB alone (RR 0.98, 95% CI 0.64–1.50, P = 0.92), with high heterogeneity (I2 = 77%). When RCTs alone were considered, again no difference was seen (RR 1.36, 95% CI 0.78–2.35, P = 0.28, I2 = 0%), as with cohort studies (RR 0.83, 95% CI 0.48–1.43, P = 0.51, I2 = 90%).
MBP+OAB Versus No Preparation
No RCTs considered the comparison between combined MBP+OAB and no preparation, with evidence arising from just 4 cohort studies (36,642 patients).31,41,45,46 The combination of MBP+OAB was associated with a significant reduction in SSI (RR 0.54, 95% CI 0.43–0.68, P < 0.00001, I2 = 82%) when compared with no preparation.
OAB Alone Versus No Preparation
No RCTs focused upon the comparison between OAB alone versus no preparation, with evidence arising from 16,390 patients included in 2 cohort studies.31,45 OAB alone reduced the incidence of SSI versus no preparation (RR 0.56, 95% CI 0.38–0.83, P = 0.004, I2 = 81%).
OAB Versus MBP
Two studies31,45 considered the incidence of SSI with OAB alone versus MBP alone, with OAB associated with a reduction in SSI rates. However, this did not reach statistical significance (RR 0.57, 95% CI 0.31–1.05, P = 0.07, I2 = 93%).
MBP+OAB Versus MBP
Rates of anastomotic leak in those receiving combined MBP+OAB versus MBP alone were compared in 22 studies (Fig. 3); 17 RCTs49–53,55,56,58,61,63,64,66,69,70,75,76,78 and 5 cohort studies.31,68,74,77,81 Only 2 RCTs49,52 included data regarding the management of the anastomotic leak, with none of the 124 patients receiving combined MBP+OAB requiring return to theater for anastomotic leakage compared with 2 of 127 patients receiving MBP alone. Overall, the combination of MBP+OAB was associated with a significant reduction in anastomotic leak rates (RR 0.62, 95% CI 0.55–0.70, P < 0.00001, I2 = 0%), and when evidence from cohort studies alone was considered (RR 0.45, 95% CI 0.25–0.80, P = 0.007, I2 = 22%), but no significant difference was seen when RCTs were analyzed (RR 0.69, 95% CI 0.43–1.11, P = 0.13, I2 = 0%). Six studies51,53,55,68,77,81 included data on the use of a diverting stoma, with 133 patients of 1028 in the combined MBP+OAB group and 99 patients of 862 in the MBP alone group undergoing a protective stoma formation.
MBP+OAB Versus OAB
The combination of MBP+OAB versus OAB alone was considered by 3 studies; 2 RCTs71,83 and 1 cohort study,31 with no difference observed in anastomotic leak rates when all studies (RR 0.79, 95% CI 0.59–1.05, P = 0.11, I2 = 0%), or just RCTs (RR 1.39, 95% CI 0.47–4.10, P = 0.55, I2 = 0%) were considered (Supplementary Figure 2, http://links.lww.com/SLA/B542). No data were available on return to theater rates related to anastomotic leaks.
MBP+OAB Versus No Preparation
The comparison between MBP+OAB versus no preparation in terms of anastomotic leak was considered by just 2 cohort studies,31,46 with combined MBP+OAB being associated with a significant reduction in anastomotic leak rates (RR 0.52, 95% CI 0.45–0.59, P < 0.00001, I2 = 0%). No data were available on return to theater rates secondary to anastomotic leaks or diverting stoma rates.
The comparison of anastomotic leak rates between OAB alone versus no preparation and OAB versus MBP was each only considered by 1 cohort study,31 and as such meta-analysis was not feasible.
MBP+OAB Versus MBP
Seventeen studies (35,633 patients) examined 30-day mortality rates between those receiving MBP+OAB versus MBP alone; 14 RCTs49,50,52,55,58,59,62,64–66,70,72,76,79 and 3 cohort studies31,68,74 (Fig. 4). Overall, the combination of MBP+OAB was associated with a significant reduction in 30-day mortality versus MBP alone (RR 0.58, 95% CI 0.44–0.76, P < 0.0001, I2 = 0%). This was also the case when evidence arising from cohort studies alone was considered (RR 0.56, 95% CI 0.42–0.76, P = 0.0002, I2 = 0%), but not when RCTs alone were examined (RR 0.66, 95% CI 0.35–1.25, P = 0.20, I2 = 0%).
MBP+OAB Versus OAB
Three studies (2 RCTs71,83 and 1 cohort study31) including 19,360 patients considered 30-day mortality in those receiving MBP+OAB versus OAB alone (Supplementary Figure 3, http://links.lww.com/SLA/B542), with the combination being associated with a significant reduction in 30-day mortality in all studies (RR 0.58, 95% CI 0.34–0.97, P = 0.04, I2 = 0%). However, no difference was observed in RCTs (RR 1.02, 95% CI 0.30–3.50, P = 0.97, I2 = 0%).
MBP+OAB Versus No Preparation
Just 2 cohort studies31,46 including 29,350 patients considered the impact of MBP+OAB versus no preparation on 30-day mortality. The combination of MBP+OAB was associated with a significant reduction in 30-day mortality (RR 0.36, 95% CI 0.17–0.76, P = 0.008, I2 = 46%).
Comparison of 30-day mortality between those receiving OAB versus no preparation and OAB versus MBP included just a single cohort study,31 thus meta-analysis was not conducted.
Only studies comparing MBP+OAB versus MBP alone were considered in terms of overall morbidity rates due to a paucity of data available for all other comparisons. When all 6 studies31,61,62,66,68,76 (32,568 patients) were compared, the combination of MBP+OAB was associated a significant reduction in overall morbidity (RR 0.67, 95% CI 0.63–0.71, P < 0.00001, I2 = 0%), as well as when evidence from cohort studies alone31,68 was considered (RR 0.67, 95% CI 0.63–0.71, P < 0.00001, I2 = 0%). However, with RCTs alone,61,62,66,76 there was no difference in overall morbidity between preparation methods (RR 0.71, 95% CI 0.41–1.24, P = 0.23, I2 = 9%).
Development of Ileus
MBP+OAB Versus MBP
Five studies31,43,51,53,54 were included in the comparison of MBP+OAB versus MBP; 2 RCTs51,53 (879 patients) and 3 cohort studies (33,119 patients).31,43,54 Only 1 study43 provided a definition of ileus, with the other 4 studies31,43,53,54 not providing a definition. Overall, the combination of MBP+OAB was associated a significant reduction in the incidence of postoperative ileus (RR 0.72, 95% CI 0.52–0.98, P = 0.04, I2 = 36%). However, no difference was seen when just RCTs were considered (RR 0.62, 95% CI 0.14–2.67, P = 0.52, I2 = 50%) or cohort studies alone (RR 0.68, 95% CI 0.45–1.03, P = 0.07, I2 = 53%).
MBP+OAB Versus OAB
Three studies31,71,83 were included in the comparison between MBP+OAB versus OAB; 2 RCTs71,83 and 1 cohort study.31 None of these studies provided a definition for ileus. Overall, the combination of MBP+OAB was associated with a significant reduction in the incidence of postoperative ileus (RR 0.83, 95% CI 0.73–0.95, P = 0.008, I2 = 0%), mostly determined by the large single cohort study.31 However, no difference was seen when RCTs were considered (RR 1.25, 95% CI 0.68–2.33, P = 0.47, I2 = 0%).
MBP+OAB Versus No Preparation
No RCTs considered the comparison between MBP+OAB versus no preparation, with evidence arising from 2 cohort studies only.31,41 Only 1 study41 provided a definition of ileus. This demonstrated that the combination of MBP+OAB was associated with a significant reduction in ileus (RR 0.72, 95% CI 0.68–0.77, P < 0.00001, I2 = 0%).
The comparison in reoperation rates between OAB alone versus no preparation and OAB versus MBP were each only considered by 1 cohort study,31 thus meta-analysis was not performed.
Insufficient data were available for any of the planned analyses on reoperation rates, with 2 studies including data comparing MBP+OAB versus MBP (1 RCT49 and 1 cohort study31), and just 2 studies comparing MBP+OAB versus OAB alone (again 1 RCT71 and 1 cohort study).31 Thus, no meta-analysis was performed. The comparisons of reoperation rates between MBP+OAB versus no preparation, OAB alone versus no preparation and OAB versus MBP were each only considered by 1 cohort study,31 and as such meta-analysis was not performed. However, the largest cohort study31 showed a significant reduction (P < 0.001) in reoperation rates with combined MBP+OAB (3.2%) compared with OAB alone (4.7%), MBP alone (4.2%), and no preparation (4.5%).
Clostridium difficile Infection
MBP+OAB Versus MBP
Data on Clostridium difficile infection were sufficient only for the comparison between MBP+OAB versus MBP alone, with data from 14 studies, including 10 RCTs53,55,61,62,65,67,69,75,78,80 and 4 cohort studies.43,54,68,82 No difference in C difficile infection rates were seen when all evidence was considered (RR 0.94, 95% CI 0.55–1.61, P = 0.81, I2 = 37%), nor when just RCT studies or cohort studies alone were analyzed (RR 0.79, 95% CI 0.21–2.96, P = 0.72, I2 = 10% and RR 0.97, 95% CI 0.54–1.75, P = 0.92, I2 = 64%, respectively).
Laparoscopic Versus Open Procedures
Nineteen RCTs50,52,57,58,61–67,69,70,72–74,76,79,80 provided data on SSI rates in patients undergoing open elective colorectal procedures between patients receiving combined MBP+OAB versus MBP alone, and 2 RCTs53,55 provided data on laparoscopic procedures alone. The remaining studies included either both open and laparoscopic procedures which could not be separated for analysis or did not state the surgical approach. No other comparison between preparations was considered due to a paucity of data. The combination of MBP+OAB versus MBP alone was associated with a significant reduction in SSI rates in patients undergoing an open resection (RR 0.55, 95% CI 0.44–0.69, P < 0.00001, I2 = 5%); however, no significant difference was seen in patients undergoing a laparoscopic procedure (RR 0.74, 95% CI 0.43–1.29, P = 0.29, I2 = 50%), although it should be borne in mind that this evidence was based upon 2 studies (1090 patients).
When anastomotic leak rates were compared between MBP+OAB versus MBP alone, divided by open and laparoscopic procedures, data could be analyzed from 9 RCTs50,52,58,61,64,66,69,70,76 in the open group and 2 RCTs53,55 in the laparoscopic group. There was no significant difference in anastomotic leak rates in either the open or laparoscopic groups (RR 0.69, 95% CI 0.30–1.60, P = 0.39, I2 = 13% and RR 0.68, 95% CI 0.28–1.65, P = 0.39, I2 = 0%, respectively).
This meta-analysis has provided evidence to suggest that MBP+OAB should be given serious consideration in patients undergoing elective colorectal surgery to reduce the risk of SSI. In addition, it has shown that the combination of MBP+OAB is associated with significant reductions in anastomotic leak rates, 30-day mortality, overall morbidity, and the incidence of postoperative ileus, without increasing the risk of developing C difficile infection (Table 3). Its findings are in contradiction with previous meta-analyses1,2 that did not account for the role of luminal antibiotics and showed that MBP on its own was of no benefit when compared with no bowel preparation or rectal enemas alone.
However, as only 9.3% (6437 patients) of the 69,517 patients included were studied in the context of RCTs, the results must be interpreted with some caution. Hence, when evidence arising from RCTs alone was considered, the combination of MBP+OAB was associated with a significant reduction in SSI alone. The evidence for the combination of MBP+OAB to reduce SSI rates is, thus, strong. European data reporting the results of colorectal surgery in the context of Enhanced Recovery After Surgery protocols where mechanical bowel preparation is not used routinely, have shown SSI rates of >10%,84,85 whereas the US NSQIP studies have shown that SSI rates are approximately 3% with a combination of MBP+OAB, 6% with MBP alone and 7% with no preparation.31
When the combination of MBP+OAB was compared with OAB alone, a significant reduction in 30-day mortality and incidence of postoperative ileus was seen, but no difference was seen between the 2 preparations in RCTs alone. There are no RCTs focusing on the combinations of MBP+OAB versus no preparation, OAB alone versus no preparation or OAB alone versus MBP alone. However, evidence from cohort studies suggests that the combination of MBP+OAB versus no preparation is associated with a significant reduction in SSI, anastomotic leak, 30-day mortality, and postoperative ileus. For OAB versus no preparation, the only significant reduction was in SSI rates, and for OAB versus MBP there was no significant difference in any of the clinical outcome measures. When a planned subgroup analysis of patients undergoing open versus laparoscopic surgery was undertaken, the combination of MBP+OAB versus MBP alone was associated with a significant reduction in SSI rates in patients undergoing open procedures, but not in those undergoing laparoscopic procedures.
Strengths and Weaknesses
The main weakness of this meta-analysis is the inclusion of both RCTs and cohort studies. While this lowers the overall quality of evidence, the decision to include cohort studies and large database studies was made as a large proportion of the recent evidence supporting the potential role of OAB or combined MBP+OAB has arisen from such studies. However, every analysis was conducted separately using evidence from RCT and cohort studies alone, as well as a summative analysis, to provide a more robust interpretation of the data.
The role of parenteral antibiotic prophylaxis is considered a standard of care in current practice, with evidence published in 198127 providing evidence for its benefit in terms of infection prevention and overall mortality and dictating that no further placebo or no intervention trials should be conducted. Definitive support was provided in a Cochrane Review86 demonstrating a significant reduction in SSI in patients receiving parenteral antibiotic prophylaxis versus those receiving no antibiotics or placebo (RR 0.34, 95% CI 0.28–0.41, P < 0.0001).
The practice of mechanical bowel preparation has changed significantly since the early 1980s. The regimen of Lazorthes et al62 included admission 3 days prior to surgery and administration of a low-residue diet and standard mechanical procedures such as enemas and magnesium sulphate purges. In contrast, more modern regimens are typically administered the day before surgery and are less invasive. This is particularly important in the setting of prolonged starvation protocols in vogue prior to the more modern ones, as they resulted in increased preoperative dehydration and electrolyte disturbances which are known to have adverse effects on postoperative complications. It should, however, be considered that each study level comparison between preparation types should have been exposed to the same level of bias, thus making the results more comparable. The OAB agent, dosing, and timing as well as the parenteral antibiotic details were also inconsistent between studies, with insufficient data from each differing combination to perform a meaningful analysis. Several included just 1 preoperative dose of OAB, or differing parenteral antibiotic regimens depending upon which preparation regimen the patient received which exerts a potential significant bias. In addition, because of limited data, we have been unable to discern conclusively whether the reduction in morbidity is a result of OAB on their own or in combination with MBP.
The definition of anastomotic leak was not stipulated for inclusion within this meta-analysis, with the data from each individual study included, irrespective of whether this was based upon clinical or radiological diagnosis of anastomotic leak. However, the definition of leak was consistent within individual studies, thus the data from each study were comparable, attenuating this potential weakness.
Interpretation of the Data in Context of Other Recent Studies
A recent meta-analysis25 included 23 RCTs and 8 cohort studies published between 1980 and 2015. However, multiple cohort studies arising from the NSQIP database were included within this study,25 and this probably represents multiple reporting of the same patient datasets. This study25 reported a significant reduction in SSI rates in patients included within cohort studies receiving MBP, OAB, and IV antibiotics versus those receiving MBP and IV antibiotics alone (RR 0.48, 95% CI 0.44–0.52, P = 0.00001, I2 = 45%). However, 4 of the 5 studies included within this analysis arose from the ACS NSQIP database. Bellows et al23 previously performed a meta-analysis on the role of oral nonabsorbable and intravenous antibiotics versus intravenous antibiotics alone in colorectal surgery, focusing on SSI. This study included 16 RCTs encompassing 2669 patients published between 1980 and 2011, with all studies including MBP within the protocol. This meta-analysis found that the combination of oral and IV antibiotics versus IV antibiotics alone was associated with a significant reduction in wound infection rates (RR 0.57, 95% CI 0.43–0.76, P = 0.0002, I2 = 19%), but no significant difference in anastomotic leak rates (RR 0.63, 95% CI 0.28–1.41, P = 0.3, I2 = 0%). The findings of the currently reported meta-analysis coincide with the results of these previous meta-analyses.
The present meta-analysis is the largest and most comprehensive to date examining the role of bowel preparation prior to colorectal surgery, and supports a potentially significant benefit for OAB preparation, either in combination with MBP or alone, in the prevention of postoperative complications. While evidence arising from large retrospective cohort and database studies suggests a strong positive benefit, these are tempered when evidence arising from RCTs alone is considered. However, the evidence presented would suggest a benefit from OAB preparation in terms of SSI, which represents a major source of morbidity and increased healthcare costs. Further high-quality evidence is required to differentiate between the benefits of combined MBP+OAB or OAB alone in this setting before more definitive recommendations can be made.
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