What information is available on use of water-soluble contrast agents for uncomplicated adhesive small bowel obstruction?
Background
Acute small bowel obstruction is a frequent cause of emergency surgery and has a 90-day mortality rate of 13%.1-3 Small bowel obstruction is most commonly due to adhesions after abdominal surgery, and adhesive small bowel obstructions (ASBO) result in approximately 300,000 hospital admissions in North America. Patients typically experience abdominal pain, vomiting, and constipation.1 Most cases of ASBO resolve without surgery; however, predicting which cases will require surgery is challenging.1,3 Undiluted water-soluble contrast agents (WSCA) are used in order to help predict whether surgery is required in patients with ASBO.3 Gastrografin (sodium diatrizoate and meglumine diatrizoate) is the water-soluble contrast agent most used.4 With an osmolarity of 2150 mOsm/L, it shifts water from the small bowel wall into the lumen, decreases edema, and improves muscle contractility. Passage of WSCA into the colon, as determined by serial plain radiography, can predict whether surgery is required or whether ASBO will resolve with conservative management.
Guidelines
The World Society of Emergency Surgery working group on ASBO published an evidence-based guideline on diagnosis and management of ASBO in 2017 (Bologna guideline).5 In patients with ASBO, non-operative methods are preferred unless the patient has signs of peritonitis, strangulation, or bowel ischemia. Non-operative management consists of fasting and decompression using a nasogastric tube or long intestinal tube. The guideline states that non-operative management can be continued safely for 72 hours. The guideline recognizes the usefulness of WSCA in the diagnosis of ASBO for predicting the need for surgery and for reducing hospital stay. The guideline considers administration of WSCA as part of the optimal diagnostic work-up. Patients who do not need immediate surgery should receive a follow-up abdominal X-ray after 24 hours to check whether the contrast has reached the colon. If so, this is indicative of resolution of the bowel obstruction. However, if the WSCA has not reached the colon after 24 hours, it is “highly indicative of failure of non-operative management.” The guideline also acknowledges that, in addition to acting as a diagnostic agent, some experts suggest that WSCA works therapeutically to reduce the need for surgery.
Previously, the Eastern Association for the Surgery of Trauma (EAST) practice management guideline published in 2012 recommended that WSCA be considered for patients who do not improve after 48 hours of non-operative management.6
Literature Review
Consistent with treatment guidelines, multiple meta-analyses have found WSCA to be highly sensitive and specific for predicting resolution of uncomplicated ASBO.4,7,8 However, meta-analyses have found conflicting results regarding the ability of WSCA to reduce the need for surgery. The following section summarizes results from meta-analyses that evaluate the diagnostic and therapeutic use of WSCA for ASBO (Table). Most studies used Gastrografin; however, an agent available outside the United States (Urografin) was used in some studies.
Diagnostic Accuracy
While multiple meta-analyses have found WSCA to be a highly sensitive and specific for predicting resolution of ASBO, the optimal timing of abdominal X-rays after WSCA administration is not clear.4,7,8 A 2016 meta-analysis by Ceresoli et al found that, when accuracy was assessed by timing of abdominal X-rays (2 to 6 hours, 8 to 12 hours, and 24 to 36 hours), diagnostic accuracy improved if X-rays were taken after 8 to 12 hours or 24 to 36 hours compared to 2 to 6 hours.8 In prior meta-analyses, differences in diagnostic accuracy between different times were not observed, although the authors of previous meta-analyses noted a numerically lower number of false negative events in patients with abdominal X-rays at 24 hours compared to < 8 hours.4,7
Therapeutic Use
Need for surgery
Whether WSCA acts therapeutically to reduce the need for surgery is a controversial topic, and meta-analyses have found conflicting results. A 2019 meta-analysis by Koh et al found that WSCA did not reduce the need for surgery, consistent with the original meta-analysis by Abbas et al in 2007.2,4 However, meta-analyses by Ishizuka et al (2018), Ceresoli et al (2016) and Branco et al (2010) found that use of WSCA reduced the need for surgery.7-9
Length of hospital stay
Most meta-analyses have found a reduced hospital length of stay in patients with ASBO who were administered WSCA. A 2019 meta-analysis by Koh et al found that WSCA reduced length of hospital stay modestly (-0.15 days [3.6 hours]), which the authors did not consider to be clinically significant.2 Two previous meta-analyses found that WSCA reduced the hospital length of stay by a clinically significant length of time, while a 2007 meta-analysis did not find a difference in hospital length of stay.4,7,8
Time to resolution of ASBO
Time to resolution of ASBO (often defined as time to pass first stool) was also significantly reduced by the meta-analysis conducted by Ceresoli et al (2016) but could not be evaluated by Branco et al (2010) and Abbas et al (2007) due to heterogeneity between studies.4,7,8
Differences between meta-analyses
The 2019 meta-analysis by Koh et al included different studies from previous meta-analyses, such as only including randomized controlled trials published after 2000, and including a recent randomized controlled trial not included in meta-analyses published after 2017.2,10 The 2017 study included a relatively large number of patients (N=242) and did not find Gastrografin to be beneficial for need for surgery, length of stay, or mortality, which may have influenced the findings of the meta-analysis by Koh et al.
Table. Meta-analyses evaluating WSCA for ASBO.2,4,7-9 Heading link
| Table. Meta-analyses evaluating WSCA for ASBO.2,4,7-9 | |||
|---|---|---|---|
| Citation | Design | Outcomes | Conclusion/ Limitations |
| Koh 20192 | MA of 9 RCTs (N=879 patients) evaluating WSCA (vs control or conservative management) for ASBO Gastrografin was used in 8 of 9 studies, Urografin was used in 1 of 9 studies | Primary Need for surgery was not significantly different between WSCA and controls (RR, 0.84; 95% CI, 0.533 to 1.339) Secondary Hospital LOS was reduced with WSCA (WMD, -0.15 days [3.6 h]; p<0.0001) Mortality was not significantly different between groups No AEs with WSCA were reported | WSCA did not provide a clinically significant improvement in outcomes The definition of time to resolution of ASBO differed between studies, so the authors did not pool this outcome Most studies were not double-blinded Variation in study protocols |
| Ishizuka 20189 | MA of 12 RCTs (N=1153 patients) evaluating WSCA (Gastrografin) for postoperative small bowel obstruction without long-tube insertion | Primary Surgery was conducted in 17.2% of patients who received Gastrografin and 25% of patients who did not (RR, 0.66; 95% CI, 0.46 to 0.95; I2=52%) Safety No Gastrografin-related complications were reported | Clinical efficacy endpoints other than surgery were not assessed Included studies for post-operative SBO, not ASBO specifically Most studies were not double-blinded Variation in study protocols |
| Ceresoli 20168 | MA of 12 prospective studies and RCTs (N=1216) evaluating the therapeutic role of WSCA (vs conservative management) and 13 studies (N=947) evaluating the diagnostic role of WSCA | Diagnostic accuracy of WSCA WSCA in the right colon 4 to 36 hours after administration in the plain abdominal X-ray had a sensitivity of 92%, specificity of 93%, PPV of 98%, NPV of 75%, LR+ of 12.78, and an LR- of 0.08 When accuracy was assessed by timing of abdominal X-rays (2 to 6 hours, 8 to 12 hours, and 24 to 36 hours), diagnostic accuracy improved if X-rays were taken after 8 to 12 hours or 24 to 36 hours compared to 2 to 6 hours Therapeutic role of WSCA Primary Need for surgery was reduced with WSCA compared to conservative management (OR, 0.55; 95% CI, 0.37 to 0.32; p=0.003). Secondary Time to resolution (passing of first stool) in patients who did not undergo surgery was reduced with WSCA (WMD, -28.25 hours; 95% CI, -40.13 to -16.37; p<0.00001) Hospital LOS was shorter with WSCA (WMD, -2.12 days; 95% CI, -2.63 to -1.60; p<0.00001) Overall LOS was shorter with WSCA compared to conservative treatment (WMD, -2.18 days; 95% CI, -2.61 to -1.74; p<0.00001) Risk of complications and mortality were not significantly different between groups | WSCA is safe for patients with ASBO and reduces the need for surgery, LOS, and time to resolution; diagnostic accuracy improves if abdominal X-rays are taken 8 hours after contrast administration Most studies were not double-blinded Variation in study protocols |
| Branco 20107 | MA of 9 RCTs (N=765) evaluating the therapeutic role of WSCA (vs conventional treatment) and 7 prospective observational studies and RCTs (N=508) evaluating the diagnostic role of WSCA In the therapeutic analysis, 8 studies used Gastrografin and 1 used Urografin | Diagnostic accuracy of WSCA WSCA in the colon 4 to 24 hours after administration had a sensitivity of 96%, specificity of 98%, PPV of 99%, NPV of 90%, LR+ of 40.14, and an LR- of 0.04 There were no differences in diagnostic accuracy based on timing of radiography of 4 to 8 hours compared to 24 hours Therapeutic role of WSCA Need for surgery was reduced with WSCA (20.8%) compared to conventional treatment (29.6%) (OR, 0.62; 95% CI, 0.44 to 0.88; p=0.007) Time to resolution of obstruction (passing of first stool) was faster with WSCA (WMD, -19.43 h; 95% CI, -22.71 to -16.15 h). However, a MA was not performed based on significant heterogeneity between studies (p<0.001) Hospital LOS was shorter with WSCA compared to conventional treatment (WMD, -1.87 days; 95% CI, -2.21 to -1.52 days; p<0.001) No reported complications were directly related to WSCA. Rates of complications and mortality were not different between groups | Data support the diagnostic and therapeutic role of WSCA for ASBO Most studies were not double-blinded Variation in study protocols |
| Abbas 20074 | MA of 6 prospective studies evaluating diagnostic accuracy and 6 prospective randomized studies evaluating therapeutic role of Gastrografin (vs placebo) for ASBO | Diagnostic accuracy of WSCA WSCA in the colon from 4 to 24 hours had a sensitivity of 97%, specificity of 96%, a LR+ of 25.1 and a LR- of 0.036. Therapeutic role of WSCA Primary Rate of resolution of SBO without surgery was not significantly different between groups (OR, 0.81; 95% CI, 0.54 to 1.21) Secondary Hospital LOS was shorter with WSCA compared to conventional treatment (WMD, -1.83 days; 95% CI, -2.21 to -1.45 days) Overall complication rates, small bowel strangulation, and mortality were not significantly different between Gastrografin compared to control Time to resolution (passing first bowel motion) and time from admission to operation could not be evaluated based on heterogeneity between studies | WSCA followed by abdominal X-ray can accurately predict resolution of SBO Gastrografin does not reduce need for surgery, but studies were not adequately powered for that outcome Hospital LOS was shorter with WSCA in patients who did not require surgery Most studies were not double-blinded Variation in study protocols |
| Abbreviations: AE=adverse event; ASBO=adhesive small bowel obstruction; CI=confidence interval; LOS=length of stay; LR+=positive likelihood ratio; LR-=negative likelihood ratio; MA=meta-analysis; NPV=negative predictive value; NS=non-significant; OR=odds ratio; PPV=positive predictive value; RCT=randomized controlled trials; RR=relative risk; SBO=small bowel obstruction; WMD=weighted mean difference; WSCA=water-soluble contrast agent. | |||
Administration
Protocols for administering WSCA vary. Doses of Gastrografin have ranged from 40 to 150 mL, while 100 mL undiluted Gastrografin is the most common dose used in clinical studies.2,3,8 Some experts recommend administering WSCA after 4 hours of gastric decompression and appropriate fluid resuscitation.3 Another study administered Gastrografin after 2 hours of nasogastric tube aspiration.9,10 The nasogastric tube should be clamped. The time to take abdominal X-rays has ranged in studies from 2 hours to 36 hours.8 The Bologna guideline recommends that a follow-up X-ray occur at 24 hours, while some experts recommend taking abdominal X-rays after 8 to 12 hours.3,5 The time to surgery has ranged from 48 hours to 5 days; the Bologna guideline states non-operative management can be continued safely for 72 hours.2,5
Safety
Gastrografin appears to be safe based on the results of meta-analyses.2,4,7-9 Gastrografin should not be used in patients with hypersensitivity or with hyperthyroidism due to its iodine component.11 Other risks include potential aspiration, intravasation if nasogastric tube is not appropriately placed, or pulmonary edema.4,11
Conclusion
The WSCA, Gastrografin, is a safe and effective agent for predicting whether surgery is required in patients with uncomplicated ASBO. Gastrografin reduces length of hospital stay in meta-analyses, but the effect of Gastrografin on need for surgery is unclear. When used for conservative management of uncomplicated ASBO, exact protocols for Gastrografin vary between studies; however, 100 mL undiluted Gastrografin is a common dose, and abdominal X-rays should be taken between 8 to 24 hours.
References
- Price TG. Bowel obstruction. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH, eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 9th ed. New York, NY: McGraw-Hill; 2020. http:accessmedicine.mhmedical.com/content.aspx?bookid=2353§ionid=204498674. Accessed December 18, 2019.
- Koh A, Adiamah A, Chowdhury A, Mohiuddin MK, Bharathan B. Therapeutic role of water-soluble contrast media in adhesive small bowel obstruction: a systematic review and meta-analysis [published online ahead of print August 13, 2019]. J Gastrointest Surg. doi: 10.1007/s11605-019-04341-7.
- Kostenbauer J, Truskett PG. Current management of adhesive small bowel obstruction. ANZ J Surg. 2018;88 (11):1117-1122.
- Abbas S, Bissett IP, Parry BR. Oral water soluble contrast for the management of adhesive small bowel obstruction. Cochrane Databse Syst Rev. 2007;3:CD004651.
- Ten Broek RPG, Krielen P, Di Saverio S, et al. Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the World Society Emergency Surgery 2017 working group. World J Emerg Surg. 2018;13:24.
- Maung AA, Johnson DC, Piper GL, et al; Eastern Association for the Surgery of Trauma. Evaluation and management of small-bowel obstruction: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg. 2012;73(5 Suppl 4):S362-S369.
- Branco BC, Barmparas G, Schnuriger B, Inaba K, Chan LS, Demetriades D. Systematic review and meta-analysis of the diagnostic and therapeutic role of water-soluble contrast agent in adhesive small bowel obstruction. Br J Surg. 2010;97(4):470-478.
- Ceresoli M, Coccolini F, Catena F, et al. Water-soluble contrast agent in adhesive small bowel obstruction: a systematic review and meta-analysis of diagnostic and therapeutic value. Am J Surg. 2016;211(6):1114-1125.
- Ishizuka M, Shibuya N, Takagi K, et al. Gastrografin reduces the need for additional surgery in postoperative small bowel obstruction patients without long tube insertion: a meta-analysis. Ann Gastroenterol Surg. 2018;3(2):187-194.
- Scotte M, Mauvais F, Bubenheim M, et al. Use of water-soluble contrast medium (gastrografin) does not decrease the need for operative intervention nor the duration of hospital stay in uncomplicated acute adhesive small bowel obstruction? A multicenter, randomized, clinical trial (Adhesive Small Bowel Obstruction Study) and systematic review. Surgery. 2017;161(5):1315-1325.
- Hill AG, Sammour T. Gastrografin for adhesive small bowel obstruction. UpToDate website. www.uptodate.com. Updated November 19, 2019. Accessed December 18, 2019.
Prepared by:
Patricia Hartke, PharmD, BCPS
Clinical Assistant Professor
College of Pharmacy
University of Illinois at Chicago
January 2020
The information presented is current as of December 11, 2019. This information is intended as an educational piece and should not be used as the sole source for clinical decision making.