Gastrografin reduces the need for additional surgery in postoperative small bowel obstruction patients without long tube insertion: A meta‐analysis

Abstract Background Small bowel obstruction (SBO) is a well‐known major postoperative complication requiring immediate diagnosis and treatment to avoid additional invasive surgical procedures. Water‐soluble contrast medium is often given not only for diagnosis but also for treatment. Although numerous studies have investigated the significance of this treatment, no consensus has yet been established regarding its indications and efficacy. Objective To explore whether Gastrografin can reduce the need for additional surgery in patients with postoperative SBO (PSBO). Methods We carried out a comprehensive electronic search of the literature (Cochrane Library, MEDLINE, PubMed and the Web of Science) up to February 2017 to identify studies that had shown efficacy of Gastrografin in reducing the need for surgery in patients with PSBO. To integrate the individual effects of Gastrografin, a meta‐analysis was done using random‐effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I 2 statistics. Results Twelve studies involving a total of 1153 patients diagnosed as having PSBO were included in this meta‐analysis. Not all patients received long‐tube insertion. Among 580 patients who received Gastrografin, 100 (17.2%) underwent surgery, whereas among 573 patients who did not receive Gastrografin, 143 (25.0%) underwent surgery. Giving Gastrografin significantly reduced the need for surgery (RR, 0.66; 95% CI, 0.46‐0.95; P = 0.02; I 2 = 52%) in comparison with patients who did not receive Gastrografin. Conclusion Results of this meta‐analysis show that giving Gastrografin reduces the need for surgery in PSBO patients without long‐tube insertion.


| INTRODUC TI ON
Among several complications occurring after abdominal surgery, it is well known that small bowel obstruction (SBO) is one of the most important and common. 1 In order to reduce the incidence of postoperative SBO (PSBO), surgeons have explored a number of options for minimizing intra-abdominal adhesion. These have included active use of laparoscopic surgery instead of open surgery 2 and the use of adhesion barrier film to prevent adhesion between the small bowel and the abdominal wall. 3 However, PSBO still remains a serious problem. 4 There are two basic types of intervention for PSBO: conventional and surgical. Conventional intervention should be undertaken as a first choice before surgical intervention because of its low degree of invasiveness. 5 Among such interventions, giving water-soluble contrast medium (WSCM) through a nasogastric tube (NG tube) should be carried out after immediate decompression, because this type of medium is considered to be useful for not only diagnosis 6 but also for treatment of SBO through its osmic effect. 7 However, although several reports have demonstrated the usefulness of this treatment for PSBO, 8 its effects are still controversial. 8,9 In the present study, therefore, we carried out a meta-analysis to investigate whether giving Gastrografin (Bayer Healthcare, Loos, France), a WSCM, can reduce the need for surgery in PSBO patients without long-tube insertion.

| Inclusion and exclusion criteria
Inclusion criteria were as follows: (i) randomized controlled trials (RCT) or other comparative studies except those with a retrospective design. (ii) Studies that provided data suitable for evaluation of PSBO. (iii) Studies that provided data allowing calculation of the risk ratio (RR) or standardized incidence ratios with 95% confidence interval (CI). (iv) Studies that provided sample size and other appropriate data. (v) Articles had to be written in English. Exclusion criteria were: (i) Non-reporting of predefined outcomes for two groups, such as patients with or without Gastrografin, or inability to extract the number of outcome events from the published results. (ii) Urological, gynecological and pediatric surgery, or surgery involving animal models. (iii) Articles that were letters, comments, correspondences, editorials and reviews. (iv) Studies for which the published articles had considerable overlap between authors, centers and participants. (v) Studies using Urografin instead of Gastrografin.

| Study selection and data extraction
Full-text reviews were carried out independently by two of the authors (M.I. and N.S.) on the basis of the inclusion and exclusion criteria and PICO. Any disagreements were resolved by discussion and consensus. The same two authors also independently extracted the following information from each eligible article: first author's name, year of publication, nation in which the study was carried out, study design, number of patients with PSBO undergoing surgery, and sample size. If the necessary data could not be extracted from the publication, we contacted the original authors directly whenever possible.

| Data synthesis and statistical analysis
Review Manager (ver. 5.3) for Windows (downloaded from http:// ims.cochrane.org/revman/download) was used for this metaanalysis. Because there were 12 RCT, a random-effect model was used rather than a fixed-effect model. Dichotomous variables were analyzed by assessing the RR of surgery in PSBO patients treated with Gastrografin compared with those who were not treated with Gastrografin as a control group, along with the 95% CI. RR of less than 1 favored patients who were treated with Gastrografin.
Statistical heterogeneity was complemented with the I 2 statistic, which qualified the proportion of total variation across studies that was due to heterogeneity rather than to chance. Presence of publication bias was assessed by funnel plot. Forest plots were demonstrated in order by weight of each study. P value < 0.05 was considered to indicate statistical significance.
Ethical approval was not required because this was a metaanalysis of previously published literature.

| Study identification and eligibility
An electronic search yielded 234 articles, of which 105 were regarded as duplicate articles based on a title search. Among the remaining articles, 116 were excluded by title/abstract review on the basis of their selection criteria and PICO. The remaining 17 articles were screened by full-text review, after which 12 studies including a total of 1153 patients with PSBO were regarded as suitable for inclusion in the data synthesis. 9,[11][12][13][14][15][16][17][18][19][20][21] The selection process for exclusion is shown in Figure 1

| Characteristics of included studies
All of the 12 studies were RCT. Among them, two were designed as multicenter RCT. 10,18 Basic characteristics of the 12 included studies are shown in Table 1.

| Association between giving Gastrografin and surgery for PSBO
Data on surgery for PSBO were available for all 12 RCT.
With regard to the dose of Gastrografin given, 10 studies recommended 100 mL. Among them, one study recommended 60 mL Gastrografin for pediatric patients 21 and one study added 100 mL barium to 100 mL Gastrografin. 13 One study recommended 150 mL Gastrografin 17 and one study recommended 60 mL Gastrografin. 18 No Gastrografin-related complications (eg, fluid or electrolyte disturbance, aspiration pneumonia, or exacerbation of obstructive episodes) 11 were reported. In fact, previous studies have shown that complications, including allergic reactions, resulting from the use of Gastrografin are rare. 22 In all 12 RCT, Gastrografin was given through a NG tube. In one study, the timing of dosage was defined as after 2 hours of NG-tube aspiration; 9 in the other 11 studies, the timing of Gastrografin dosage by a NG tube was not clearly stated. Not all patients received long-tube insertion.
Indications for surgery after receiving Gastrografin are shown in Table 1. Patients who were and who were not given Gastrografin   Unlike the situation in most western countries, long-tube insertion is generally carried out in Japan to treat patients with PSBO. 27 Because only one small prospective RT of short versus long-tube insertion for adhesive SBO showed no significant therapeutic difference between the two as a conventional therapy, 28  It is obvious that a short tube cannot sufficiently reduce intrasmall bowel pressure because the tube tip is located in the stomach.

| D ISCUSS I ON
F I G U R E 2 Forest plot of the occurrence of surgery for patients with postoperative small bowel obstruction and funnel plot analysis of such patients using integrated data However, it is clear that a long tube can more effectively reduce intra-small bowel pressure because the tube tip is located in the dilated small bowel and can effectively aspirate the accumulated intestinal fluid. Furthermore, the balloon of the long tube is able to assist insertion of the tube to the far distal side of the small bowel, beyond the obstructed portion.
In fact, even if PSBO patients with a short NG tube receive WSCM, effect of the WSCM is diluted by accumulated intestinal fluid in the dilated small bowel. However, if PSBO patients receive WSCM by a long tube, the WSCM can work more effectively in the decompressed small bowel or near the obstructed portion.
Although a prospective RCT comparing short-tube versus longtube insertion would be required to adequately assess the effect of Gastrografin in PSBO patients, the results of this meta-analysis clearly demonstrate that giving Gastrografin reduces the need for surgery in PSBO patients without long-tube insertion.

ACK N OWLED G M ENT
The authors are grateful to Dr Akihisa Matsuda (Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan) for his useful advice and suggestions regarding meta-analysis.

CO N FLI C T S O F I NTE R E S T
Authors declare no conflicts of interest for this article.