Prospective Evaluation of Oral Gastrografin^® in the Management of Postoperative Adhesive Small Bowel Obstruction

Abstract

Oral Gastrografin®, a hyperosmolar water-soluble contrast medium, may have a therapeutic effect in adhesive small bowel obstruction. However, findings are still conflicting, as some authors did not find a therapeutic advantage. So, this prospective, randomized, and clinical trial study was designed to determine the value of Gastrografin in adhesive small bowel obstruction. The primary end points were the evaluation of the operative rate reduction and shortening the hospital stay after the use of Gastrografin. A total of 84 patients were randomized into two groups: the control group received conventional treatment, whereas the study group received in addition of 100 mL Gastrografin meal. Patients were followed up within 4 days after admission, and clinical and radiological (if needed) improvements were evaluated. Although the results showed that Gastrografin can decrease the need for surgical management by 14.5 %, no statistically significant differences were observed between the two groups (P = 0.07). Nevertheless, the length of hospital stay revealed a significant reduction from 4.67 ± 1.18 days to 2.69 ± 1.02 days (P = 0.00). The use of Gastrografin in adhesive small bowel obstruction is safe and reduces the length of hospital stay. As a result, the cost of hospital bed occupancy is reduced. Hence, if there was no indication of emergency surgery, administration of oral Gastrografin as a nonoperative treatment in adhesive small bowel obstruction is also recommended.

Introduction

Intestinal obstruction is responsible for one of the most common emergencies in general surgery, and is also a major cause of morbidity and financial expenditure worldwide [1]. Adhesions have been well documented as the leading cause of intestinal obstruction, especially in the old patients with a history of previous abdominal surgery [2]. Between 49 % and 74 % of small bowel obstructions are caused by intra-abdominal adhesions [3]. Adhesive small bowel obstruction is one of the most common surgical causes for admission, and its treatment is still controversial. Emergency surgery is mandatory when strangulation or complete obstruction occurs [4]. Nonoperative conservative management is indicated in the case of partial obstruction [5]. The reported operative rate for adhesive small bowel obstruction ranges from 27 % to 42 % [6]. More than two-thirds of all small bowel obstructions were due to peritoneal adhesions [4]. Adhesive obstruction may occur at any time after surgery, about 20 % of the obstructions appeared more than 10 years after the initial abdominal operation [7].

Some surgeons suggest conservative management for up to 5 days provided that no obvious signs of intestinal strangulation are present [8]. On the other hand, it has been suggested that a delay in surgical intervention of more than 24 h increases complication rates and prolongs postoperative hospital stay [9].

The use of Gastrografin in the management of adhesive small bowel obstruction has been evaluated in the recent years. Gastrografin is a water-soluble contrast medium composed of sodium diatrizoate, meglumine amidotriozoate, and a wetting agent (polysorbate 80). It has an osmolarity of 1 900 mOsm/L, which is approximately six times that of extracellular fluid. So, Gastrografin may have a therapeutic effect in adhesive small bowel obstruction [10, 11]. However, this topic is still debated, because some authors did not find any therapeutic advantage [12, 13].

The present prospective study was undertaken to evaluate the therapeutic effect of Gastrografin in adhesive small bowel obstruction.

Patients and Methods

This prospective randomized clinical trial study included 84 patients with adhesive intestinal obstruction who were admitted to the Imam teaching hospital, affiliated to Mazandaran University of Medical Sciences, Sari, Iran. The diagnosis was based on a history of previous abdominal operation with clinical and radiologic picture of adhesive small bowel obstruction, without signs of strangulation. Supine and erect abdominal radiographs were taken and the maximal diameter of the small bowel was measured on admission. Radiological signs of adhesive intestinal obstruction were existence of multiple airs in small intestine, lack of gas in the colon, and small intestine with diameter more than 3 cm. The materials and methods of this study were decided based on previous studies [11, 13–15]. The randomization was obtained through table of random numbers. Both control and treatment groups were randomly divided into the two groups and there were not any significant differences in term of age, sex, previous surgery, etc. All patients met the inclusion and exclusion criteria before enrolling to the study.

Inclusion Criteria

Patients over 18 years of age, history of previous abdominal operation, clinical and radiological evidence of adhesive small bowel obstruction. Informed consent was obtained from all the patients. The patients were free to withdraw at anytime. We enrolled patients above 18 years of age. The cut off age was 18 years in all similar studies. It might because of evaluation these studies in adult patients. The patients under 18 years, who were already under the care of their own specialist pediatric surgeons, were excluded from this study. Because, they sometimes had congenital problems and their problems were relatively more complex. Therefore, it was better to refer the patients under 18 years to their own specialist pediatric surgeons for their considerations. We, therefore, excluded them from this study and we might carry out another study including patients less than 18 years of age.

Exclusion Criteria

Patients with age less than 18 years, large bowel obstruction, early postoperative obstruction (within 4 weeks), ileus, documented intra-abdominal malignancy, inflammatory bowel disease, history of abdominal irradiation, hyperthyroidism, any sensitivity to iodine, and all patients in whom the final diagnosis was not adhesive small bowel obstruction.

All patients were treated initially by stopping oral feeding, nasogastric tube (NGT) decompression, and intravenous fluid resuscitation. The randomization was obtained through table of random numbers. Patients were divided into two groups (conventional and Gastrografin) to evaluate the effect of Gastrografin on adhesive small bowel obstruction regarding the success of conservative treatment and the need for surgery. One hundred milliliters Gastrografin® (Meglumin compound, Meglumin amidotrizoate®, Darou Pakhsh Pharmaceutical Manufacturing Co. Tehran, Iran) were administered through nasogastric tube. If a manifestation of strangulation was detected at admission, laparotomy was done and such patients were excluded from the study. Gastrografin, 100 cc containing 37 mg iodine; once a day, and conventional treatment were given within 4 days after admission. However, treatment procedure was considered to be successful if any patient met the end point requirements. Otherwise, the patients who showed no progressive clinical and radiological improvement after 4 days, either in the group of patients who received Gastrografin or in the group solely managed by conservative treatment, underwent surgery. Parameters used to reach the end point of adhesive intestinal obstruction were clinical improvement (decreased pain, distension, passage of flatus and/or stool, normal intestinal sounds, stool in P/R examination and decreased amount of Ryle tube output) and radiological improvement. So, oral fluids were allowed and if tolerated, the amount was increased gradually, then semisolid, then solid diet.

Patients’ data included demographic data; number of previous surgeries, the length of hospital stay, and operative rate were recorded and analyzed in order to compare the two groups.

All data were coded and a Statistical Package for Social Sciences (version 13; SPSS Inc., Chicago, IL) was used for the statistical analysis. The results were presented as mean (±SD) for continuous variables and percentages for categorical variables. Differences in the proportions were tested with chi-square (χ²) test. Independent t test was used to test the difference between continuous variables. A P value of less than 0.05 was considered to be significant.

Results

Both conventional and Gastrografin groups did not differ significantly in age, sex, and number of previous surgeries, as shown in Table 1.

Table 1.

General characteristics of the two groups

	Control	Gastrografin	P
Male	23 (55 %)	27 (64 %)	0.432
Age (years)*	50.14 ± 15.36	53.17 ± 18.23	0.41
Number of previous surgeries	2.11	2.19	˃0.05

^*Values are mean ± SD (range)

In the conventional group, obstruction resolved in 76 % of control patients within 4 days. This percent was increased up to 90.5 % in patients who received Gastrografin. Also, surgical procedure was performed in 24 % of the control patients for whom conservative treatment failed at the end of fourth day. In contrast, surgery was required in 9.5 % of patients who received Gastrografin, but obstruction was not resolved at the end of fourth day. These findings show that Gastrografin decreased the need for surgical management by 14.5 %, but no statistically significant differences were observed (P = 0.07) (Table 2).

Table 2.

Outcome

	Control	Gastrografin	P
Successful conservative treatment	76 %	90.5 %	0.07
Surgical treatment	24 %	9.5 %	0.07
Hospital stay (days)*	4.67 ± 1.18	2.69 ± 1.02	0.00

^*Values are mean ± SD (range)

In addition, the length of hospital stay revealed a significant reduction from 4.67 ± 1.18 days to 2.69 ± 1.02 days for control and Gastrografin groups, respectively (P = 0.00).

No side effects or sensitivity to iodine were observed in patients who received Gastrografin.

Discussion

The most frequent cause of acute small bowel obstruction is postoperative adhesion. Numerous attempts have been made to prevent postoperative adhesion, but till now no method has proven to be completely effective [16]. In the absence of strangulation, initial trial of conservative treatment is given to most patients. Successful response to nonoperative treatment is reported to be 73–90 % [14]. A delay in surgical treatment may lead to an increased mortality rate, from 3 % to 5 % when the obstruction is simple to about 30 % when it is strangulated or when the bowel becomes necrotic or perforated [17].

The role of Gastrografin, the most widely used water soluble contrast medium in adhesive small bowel obstruction, has been assessed recently with regard to diagnostic and therapeutic value [15]. The precise mechanism of Gastrografin in the management of adhesive small bowel obstruction is not yet well known. Gastrografin, ionic bitter-flavored mixture of sodium diatrizoate and meglumine diatrizoate, having osmolarity of 1900 mOsm/L, approximately six times more than extracellular fluid, promotes shifting of fluids into the bowel lumen and increases the pressure gradient across obstructive sites. Furthermore, because Gastrografin dilutes the bowel content, it facilitates its passage and decreases edema of the intestine wall facilitating motility [10, 18, 19]. It is proposed that Gastrografin has therapeutic value because it reduces the operative rate and the length of hospital stay. However, findings are still conflicting, as some authors did not find a therapeutic advantage [15].

In a randomized controlled study performed by Assalia et al. [20], about 100 mL of Gastrografin was given on admission to patients in the study group. A significant reduction in the need for operative treatment in the study group was reported [20]. Also, Biondo et al. [13] noticed that oral Gastrografin reduced the operative rate by 35 % (11.4 % in the Gastrografin group vs. 17.4 % in the control group), increased the success of conservative treatment by 7 % (88.6 % in the Gastrografin group vs. 82.6 % in the control group), and significantly reduced hospital stay by 52 % (4.1 vs. 8.5 days) [13]. Di Saverio et al. [21] noticed that oral Gastrografin significantly reduced the operative rate (18.5 % in the Gastrografin group vs. 45 % in the control group), reduced hospital stay by 59.8 % (4.67 vs. 7.8 days), and shortened the time of resolution of obstruction (6.9 vs. 43 h) [21]. In spite of these studies, in the meta-analysis by Abbas et al., water-soluble contrast agent did not reduce the need for surgical intervention, but reduced the length of hospital stay for patients who did not require surgery compared with placebo [22, 23]. In a randomized study, no significant differences in the operative rate, incidence of bowel strangulation requiring resection, and readmission rate were found between the two groups. Instead the overall hospital stay was significantly shorter in the Gastrografin group (4.1 vs. 8.5 days) compared with control, as well as in both subgroups of patients who responded to conservative treatment or those surgically treated [13]. The results observed from our study totally confirmed the data obtained in this study. Nevertheless, Feigin et al. [12] denied the therapeutic effect of Gastrografin and did not find any advantage with regard to operative rate, resolution symptoms, and hospital stay.

In the current study, Gastrografin decreased the need for surgical management from 24 % to 9.5 % for patients in whom conservative treatment did not resolve obstruction after 4 days. This reduction was not statistically significant. So, the role of Gastrografin in the management of adhesive small bowel obstruction in terms of operative rate is not still clear and the results are controversial. On the one hand, in our study, Gastrografin reduced the need for surgical operation similar to previous studies by Biondo et al., Di Saverio et al., and Assalia et al.; on the other hand, conflicting result was observed in our study as there was not statistically significant reduction between Gastrografin and control groups. Although in our study Gastrografin could not statistically decrease the need for surgical procedures, it reduced the need for surgical management by 14.5 %. These controversial results may be related to the differences between two groups of patients in our study compared with the previous studies. Another reason could probably be the patients’ tendency to get surgery in order to reduce any possible side effects observed following adhesive small bowel obstruction in our university hospital.

Interesting results were observed in the length of hospital stay in patients who received Gastrografin compared with the control group. The length of hospital stay revealed a significant reduction by 57.6 % in Gastrografin group (P = 0.00). Our results confirm data obtained in other investigations, where Gastrografin significantly reduced hospital stay such as studies by Biondo et al. and Di Saverio et al. by 52 % and 59.8 %, respectively.

In our study, there was no complication or mortality that could be attributed to the use of Gastrografin. Adverse effects due to the use of Gastrografin in small bowel obstruction have rarely been reported. A potential complication of using Gastrografin in the presence of bowel obstruction is aspiration pneumonia. By the time that the contrast medium was administered, the stomach should be adequately decompressed through nasogastric tube and therefore the risk of aspiration pneumonia minimized. Another potential adverse effect of Gastrografin is that it may further dehydrate a patient with small bowel obstruction because of the shifting of fluid into the bowel lumen. The practice of giving Gastrografin at 48 h may also reduce the risk of this adverse phenomenon because the patients should have been adequately rehydrated prior to the administration of Gastrografin [11].

We conclude that the use of Gastrografin in adhesive small bowel obstruction is safe and reduces the length of hospital stay. As a result, the cost of hospital bed occupancy will be reduced. Also, the operation rate in these patients regarding to its difficulty due to the previous adhesions and risk of complications including gastrointestinal fistulas and unwanted enterotomy is been reduced. Hence, if there was no indication of emergency surgery, administration of oral Gastrografin as a nonoperative treatment in adhesive small bowel obstruction is also recommended.