Journal of Pediatric Surgery 50 (2015) 581–585
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Evaluation of a water-soluble contrast agent for the conservative management of adhesive small bowel obstruction in pediatric patients Chee-Yew Lee a, Min-Hsuan Hung a,c, Lung-Huang Lin a,d,⁎, Der-Fang Chen b a
Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan Department of Surgery, Cathay General Hospital, Taipei, Taiwan Department of Pediatrics, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan d School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan b c
a r t i c l e
i n f o
Article history: Received 30 April 2014 Received in revised form 15 October 2014 Accepted 13 November 2014 Key words: Gastrografin® Water-soluble contrast agent Adhesive small bowel obstruction Children
a b s t r a c t Background/Purpose: The diagnostic and therapeutic benefits of a commercial water-soluble contrast agent (Gastrografin) in pediatric patients with adhesive small-bowel obstruction (ASBO) are controversial. The aim of this study was to assess the therapeutic value of Gastrografin in the management of ASBO in children after unsuccessful conservative treatment. Methods: Medical records from patients with uncomplicated ASBO managed at Cathay General Hospital, Taipei, Taiwan between January 1996 and December 2011 were retrospectively reviewed. All children ≤18 years of age with clinical evidence of ASBO were managed conservative treatment, unless there was suspicion of strangulation. Patients who did not improve after 48 hours of conservative treatment were administered Gastrografin. Results: Twenty-four patients with 33 episodes of ASBO were analyzed. Of those, there were 19 episodes of ASBO that failed to respond to the initial conservative management, and 16 (84%) responded well to Gastrografin administration thereby abrogating the need for surgical intervention. There were neither complications nor mortality that could be attributed to the use of Gastrografin. Conclusion: This preliminary study suggested that the use of a water-soluble contrast agent in ASBO is safe in children and useful for managing ASBO, particularly in reducing the need for surgery when conservative treatment fails. However, larger prospective studies would be needed to confirm these results. © 2015 Elsevier Inc. All rights reserved.
Every year, more than an estimated 300,000 patients undergo surgery to treat adhesion-induced small-bowel obstructions in the United States. Intra-abdominal adhesions related to prior abdominal surgery are the etiologic factor in up to 75% of cases of small-bowel obstruction [1]. In the past, there was a perception that children were less at risk of adhesions than adults; however, children also have a significant risk of adhesion and certain surgical procedures carry an appreciably high risk of readmission [2–4]. Van der Krabben et al. [5] reported bowel injuries in one-third of adult patients undergoing surgery for adhesive small-bowel obstruction (ASBO). Many studies have demonstrated the high risk of reoperation after adhesion, and surgery for ASBO results with greater morbidity and blood loss, is technically difficult, and can involve long operative times [6,7]. Published series have demonstrated that repeated surgery for ASBO increases the risks of readmission, the need for bowel resection, and complications [8]. ASBO is a significant health problem with major adverse effects on the quality of life and is a large burden on both healthcare and financial resources. The impact of admissions for ASBO, ⁎ Corresponding author at: Department of Pediatrics, Cathay General Hospital, No. 280, Section 4, Jen Ai Road, Taipei, 10630, Taiwan. Tel.: +886 2 27082121; fax: + 886 2 27074949. E-mail address: [email protected] (L.-H. Lin). http://dx.doi.org/10.1016/j.jpedsurg.2014.11.034 0022-3468/© 2015 Elsevier Inc. All rights reserved.
especially for those patients requiring surgical management, is considerable in terms of hospital resources [9]. Identifying conservative treatment modalities with a lower risk of morbidity and a reduction in the burden of both workload and costs would be advantageous. The outcomes of conservative treatment in children vary by age group. Akgur et al. [10] reported conservative treatment is feasible for childhood ASBO under special conditions, and Vijay et al. [11] advocated a conservative approach to ASBO in children. On the other hand, Al-Salem et al. [12] reported limitations in conservative management, and Eason et al. [13] suggested that ASBO is a distinct disease entity in children and identified increased age as a potential predictor of successful conservative management. The utilization of water-soluble contrast agents has revolutionized the nonoperative management of ASBO. Many studies have addressed the diagnostic and therapeutic benefits of using water-soluble contrast in ASBO, and the literature suggests that the hyperosmolarity of water-soluble contrast agent confers therapeutic benefits by activating movement of water into the small bowel lumen, decreasing edema of the small bowel wall, and enhancing smooth muscle contractility [14–20]. However, there are also studies with contrasting results, and data in pediatric populations are sparse [21–24]. The purpose of this study was to evaluate the possible use of the commercially available contrast agent diatrizoate meglumine and
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diatrizoate sodium solution USP (Gastrografin) in the management protocol of ASBO in children after unsuccessful conservative treatment. 2. Methods A retrospective review of medical records was performed to identify patients between 1 and 18 years of age who were admitted to the Pediatric Department of Cathay General Hospital with a primary diagnosis of ASBO between January 1996 and December 2011. The diagnosis of ASBO was made on the basis of historical, clinical, and radiological findings (e.g. history of abdominal surgery, bilious vomiting, failure to pass flatus or stool, abdominal distention, air-fluid level, and dilation of the small bowel loop on radiography). Patients with a known history of either allergy or hypersensitivity to contrast agents, inflammatory bowel disease, documented intra-abdominal malignancy, and intestinal obstruction within the first 4 weeks of a recent abdominal operation were excluded from participation in the study. Children under 1 year of age who are more prone to choking, and patients with tracheoesophageal fistulas were excluded to ensure safety of using Gastrografin. The initial work-up for all patients consisted of a complete physical examination with an emphasis on signs of bowel strangulation and peritonitis. The laboratory work-up included complete blood count, serum electrolytes, and C-reactive protein; and abdominal radiography was also performed. Surgery was performed immediately if the patient presented with signs of either strangulation or peritonitis (e.g., fever, tachycardia, leukocytosis). The remaining patients were managed conservatively over the subsequent 48 hours. The rationale for this timeframe was based on the results of a study by Choi et al. [14], which showed that patients with contrast observed in the colon within 24 hours were all treated successfully without surgery. Surgery was required in 96% of patients in whom contrast failed to reach the colon within 24 hours. It was safe to give Gastrografin even after the failure of conservative treatment. Complete resolution of bowel obstruction occurred a mean of 41 hours after administration of Gastrografin. It was usually at least 2 days later that solid food was allowed in our practice. We considered 48 hours of conservative treatment to be adequate. Patients were then followed up every year to monitor for obstruction recurrences. The contrast agent (diatrizoate meglumine and diatrizoate sodium solution, Gastrografin, Bayer Pharma, Spain) [25] is indicated for radiographic examination of segments of the gastrointestinal tract (esophagus, stomach, proximal small intestine, and colon). The preparation is particularly indicated when a more viscous agent such as barium sulfate, which is not water-soluble, is not feasible or is potentially dangerous. In this study, as per the package label, the contrast agent was applied to patients who failed to respond to conservative management as an intermediate step before surgical intervention. Contrast agent administration was preceded by infusion of intravenous Ringer’s solution bolus to guard against dehydration caused by the hygroscopic effect of the contrast medium. Gastrografin was given according to the age of the patient after dilution with equal volume of Ringer’s solution. The prepared mixture was given through the nasogastric tube (kept closed for 3 h and was then reopened).The conservative treatment protocol included nil per os (NPO), nasogastric tube decompression, laxative suppositories, enema, prokinetic agents (e.g. drugs that enhance gastrointestinal motility by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm), and adequate rehydration with isotonic fluid. When either the clinical or radiographic signs improved within 48 hours, the nasogastric tube was removed and oral feeding was initiated. Patients that developed signs of either bowel strangulation or peritonitis at any time during the conservative period underwent surgical interventions. In the patients with no improvement after 48 hours, Gastrografin and a mixture of sodium amidotrizoate and meglumine amidotrizoate were administered via the nasogastric tube. Patients b 10 years received 30–50 mL (diluted with twice its volume of water)
and other patients were administered 100 mL. All patients were carefully monitored, and any disturbances in water and electrolyte balances were corrected prior to using Gastrografin, since this agent produces a hyperosmotic effect. Potential complications related to the use of watersoluble contrast agent, such as aspiration pneumonia, renal failure, and anaphylaxis were carefully assessed. Other possible complications (e.g., bowel strangulation and resection, intra-abdominal abscess, fistula, sepsis, shock, thromboembolic events, and mortality) were also analyzed. Serial plain abdominal radiographs were obtained from 4 hours to ≥24 hours (based on the radiographs) after Gastrografin administration. Management was considered successful when the contrast was visualized in the cecum and a clinical improvement was noted. Once successful management was achieved, the nasogastric tube was removed and feeding was initiated. If the contrast agent failed to reach the cecum, complete obstruction was diagnosed and patients were scheduled for surgical intervention. The Ethics Review Board of the authors’ institute approved the study protocol. Because this study represents an analysis of secondary data, no informed consent was necessary. 3. Results Twenty-four patients (14 boys, 10 girls; range of patient age, 2–17 years) were admitted with a total of 33 episodes of ASBO that occurred between January 1996 and December 2011 (Table 1). Eight patients with nine episodes of ASBO underwent surgery immediately after initial resuscitation. The remaining 24 episodes of uncomplicated ASBO were managed conservatively for 48 hours under close monitoring. One episode of ASBO deteriorated clinically, had signs of strangulation during conservative management, and that patient immediately underwent surgery. Four episodes in three patients resolved within the 48-hour period of conservative management. In the remaining 19 episodes, conservative management failed and the patients received the contrast agent. In those 19 episodes, 16 episodes (84%) resolved clinically with radiological improvement (i.e., evidence of passage of the contrast to the cecum). The contrast agent failed to reach the cecum in the remaining 3 of 19 episodes (16%). Those patients were regarded as complete obstruction, eventually requiring an operation as no improvement was noted (Fig. 1). Of 8 surgically treated primary episodes, 3 episodes (38%) of recurrent ASBO developed. The recurrence rate after conservative management followed by Gastrografin administration was 55%. Two recurrent episodes after primary surgical management were treated conservatively with Gastrografin (67%), and one was managed surgically (33%). One recurrent episode after primary conservative management with Gastrografin was eventually treated surgically (17%), and the remaining 5 recurrent episodes were managed conservatively either with or without the contrast agent (83%). One episode of ASBO (initially presenting with a duplication cyst) did not improve clinically despite the presence of contrast in the colon (Fig. 2). Gastrografin was then instilled into the colon and terminal ileum, and clinical improvement was subsequently noted with radiological improvement after 24 hours. Patients with an initial presentation of Hirschsprung’s disease had the highest recurrence rate of ASBO (Table 1). Two of the three patients had two episodes of recurrent ASBO, and one developed three episodes of recurrent ASBO. No significant complications were related to water-soluble contrast agent administration in this study. Only one patient with a previous history of appendectomy who underwent immediate laparotomy for enterolysis required segmental bowel resection. 4. Discussion In 19 episodes of uncomplicated ASBO, conservative management failed and the patients then received the contrast agent. Most of these
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Table 1 Demographic and initial presentation of patients with ASBO. Primary condition
Gender (Male:Female)
No. of patients
Adhesion episodes
Median (range) patient age (in years) at time of ASBO
Appendicitis Hirschsprung’s disease Intussusception Ventriculoperitoneal shunt Perforation of peptic ulcer Spontaneous intestinal perforation Gastroschisis Volvulus Jejunal atresia Duplication cyst Hiatal hernia Total
4:5 2:1 2:0 2:0 0:2 0:1 0:1 1:0 0:1 1:0 1:0 14:10
9 3 2 2 2 1 1 1 1 1 1 24
9 10 2 3 2 2 1 1 1 1 1 33
13 (4.2–16.8) 10.2 (3–14) 16.6 (16–17.1) 13 (13–16) 11 (11–11) 2.3 (2.3–2.4) 4 14 3 13.6 14.2
episodes (84%) then resolved clinically with radiological improvement, with a recurrence rate of 55%. Of 8 surgically treated primary episodes, recurrent ASBO developed in 38%. In addition, patients with an initial presentation of Hirschsprung’s disease had the highest ASBO recurrence rate. Adhesions are internal, fibrous, band-like scars occurring after injury to the peritoneum. Adhesions are the result of both biochemical and cellular responses attempting to repair the peritoneum. Although that process is generally beneficial, it can also have detrimental effects, including small bowel obstruction. The most common cause of adhesions is iatrogenic (i.e., secondary to previous abdominal operations). The data on postoperative adhesions in children are sparse, and most of what is known about adhesions has been extrapolated from studies in adults.
A recent large-cohort study of 1541 children that had intestinal surgery reported an adhesion rate of almost 10% at the operative site and approximately 5% elsewhere [3]. The risk of further readmission is highest in the first year and continues with time [2,3]. No consensus has been reached regarding the diagnosis and management of such patients, especially in children with ASBO. Furthermore, specific and updated guidelines are currently lacking. Surgical treatment of ASBO may lead to the additional formation of adhesions, possibly contributing to recurrent episodes of ASBO. The surgical treatment for ASBO is characterized by long operative times and the risk of severe complications, such as bowel injury and bleeding. Therefore, the safety and efficacy of water-soluble contrast use in ASBO was addressed, initially by Assalia et al. [26] in the 1990s. Gastrografin, most commonly mentioned in the literature, is an ionic, bitter-
Fig. 1. Schematic presentation for the management of adhesive small bowel obstruction (ASBO). One episode did not improve clinically despite contrast in the colon. Lower gastrointestinal series with a Gastrografin enema was performed and both the clinical and radiological conditions improved after 24 hours.
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Fig. 2. A: Abdominal radiograph obtained 12 hours after Gastrografin administration showing a dilated bowel loop with air-fluid level filled with Gastrografin. B: Abdominal radiograph obtained 24 hours after Gastrografin administration showing that the contrast had reached the descending colon (arrow). C: Gastrografin successfully passed through the terminal ileum resulting in clinical improvement after 24 hours.
flavored mixture of sodium amidotrizoate, meglumine amidotrizoate, and a wetting agent (polysorbate 80) [25]. It has an osmolarity of 1900 mOsm/L, which is approximately 6 times that of extracellular fluid. It promotes shifting of fluid into the bowel lumen and increases the pressure gradient across an obstructive site. The bowel contents are diluted and in the presence of the wetting agent, passage of bowel contents through a narrowed lumen is facilitated. This contrast agent also decreases edema of the bowel wall and enhances bowel motility. Many studies have been performed to evaluate the role of watersoluble contrast in the management of ASBO in adult patients. Fevang et al. [22] suggested that contrast agent does not contribute to the resolution of small bowel obstruction, but is of great diagnostic benefit in evaluating the indication for surgical intervention and the timing of surgery. Abbas et al. [19,20] confirmed that water-soluble contrast followed by abdominal radiography after at least 4 hours can accurately predict the likelihood of resolution of a small bowel obstruction, and that the appearance of a water-soluble contrast agent in the colon on an abdominal radiograph within 24 hours of administration predicted resolution of the obstruction with a pooled sensitivity of 97% and specificity of 96%. Branco et al. [27] also reported that the appearance
of water-soluble contrast in the colon within 4–24 hours after administration could accurately predict the resolution of ASBO with a sensitivity of 96% and specificity of 98%. Atahan et al. [28] concluded that conservative treatment was recommended for patients in which contrast medium is observed in the right colon within 8 hours following administration, regardless of the presence of obstruction signs. ASBO is a heterogeneous and dynamic disease process with multiple different clinical presentations, which affect whether conservative management is successful. A large retrospective review of 710 patients with ASBO reported that previously demonstrated benefits from clinical trials have not been replicated in a clinical setting [29]. Factors other than watersoluble contrast agent use and protocol nonadherence owing to initial diagnostic uncertainty may have influenced patient management. Haule et al. [30] conducted a study to compare the efficacy of Gastrografin (n = 25) with standard conservative management (n = 25) for treating ASBO. In the contrast agent group, 22 (88%) patients experienced relief of ASBO following the intervention, with only 3 (12%) requiring surgery. Sixteen (64%) of the patients in the conservative treatment group experienced relief of ASBO, and 9 (36%) required surgery. The difference in operative rates between the two groups was
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not statistically significance (P = 0.67). Average time to relief of obstruction was significantly shorter in the contrast agent group (72.52 h) compared to the conservative treatment group (117.75 h; P = 0.023). The average length of hospital stay was significantly shorter in the contrast agent group (5.62 days) compared with the conservative treatment group (10.88 days; P =0.04). The investigators concluded that the use of Gastrografin in ASBO patients helps to promote an earlier resolution of obstruction and also reduces the length of hospital stay compared with standard conservative management. However, the role of the contrast agent in reducing the rate of laparotomies remained inconclusive. Further pilot studies in children have recently been proposed to evaluate the role of Gastrografin in the management of ASBO. Abdelkader et al. [23] demonstrated that Gastrografin may play a valuable role in the management of ASBO, either in a diagnostic or therapeutic capacity, and successfully completed the conservative management of 8 of 12 young (aged 1–16) patients (66.6%). Further, a prospective study from Bonnard et al. [24] (8 children with ASBO and 16 controls) found that Gastrografin may be useful for managing ASBO, and that it was associated with a significantly lower risk of hospitalization for N 3 days. This preliminary study suggests that Gastrografin is effective in the management of ASBO in children after unsuccessful conservative treatment. Out of 19 episodes ASBO with failure of initial conservative management, 16 episodes (84%) responded well to administration of the contrast agent and were successfully treated nonsurgically. There were neither complications nor mortality that could be attributed to the use of Gastrografin. There are some limitations to this study with respect to the small sample size and absence of a control group. Although the recurrence rate was higher in the Gastrografin group compared to the surgical group (55% vs. 38%), the need for surgery for the recurrent episodes was much lower (17% vs. 33%). The patients with Hirschsprung’s disease had the highest recurrence rates of ASBO, although the etiology was unclear (whether or not it was related to antecedent procedures or the nature of the disease). Lower gastrointestinal series with contrast agent instillation is an option when no clinical improvement is observed after oral administration of the agent. However, careful selection of the patients with no improvement despite contrast in the colon is required to avoid further morbidity. Finally, it should be noted that some surgeons would intervene earlier than 48 hours and that our prolonged observation may have contributed to the resolution of ASBO in our patients. 5. Conclusion A commercially available water-soluble contrast agent had a beneficial role in the conservative management of children with ASBO. This small study suggests the use of that product may avoid unnecessary surgical procedures. However, we cannot rule out the contribution of a prolonged observation period to ASBO resolution in our patient group. Further randomized controlled trials are recommended to confirm the diagnostic and therapeutic effects as well as the safety of the product for use in children.
References [1] Catena F, Saverio SD, Kelly MD, et al. Bologna Guidelines for Diagnosis and Management of Adhesive Small Bowel Obstruction (ASBO): 2010 Evidence-Based Guidelines of the World Society of Emergency Surgery. World J Emerg Surg 2011;6:5.
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[2] Grant HW, Parker MC, Wilson MS, et al. Population-based analysis of the risk of adhesion-related readmissions after abdominal surgery in children. J Pediatr Surg 2006;41:1453–6. [3] Grant HW, Parker MC, Wilson MS, et al. Adhesions after abdominal surgery in children. J Pediatr Surg 2008;43:152–6. [4] Choudhry MS, Grant HW. Small bowel obstruction due to adhesions following neonatal laparotomy. Pediatr Surg Int 2006;22:729–32. [5] Van der Krabben AA, Dijkstra FR, Nieuwenhuijzen M, et al. Morbidity and mortality of inadvertent enterotomy during adhesiolysis. Br J Surg 2000;87:467–71. [6] Beck DE, Ferguson MA, Opelka FG, et al. Effect of previous surgery on abdominal operating time. Dis Colon Rectum 2000;43:1749–53. [7] Ellis H, Moran BJ, Thompson JN, et al. Adhesion-related hospital readmissions after abdominal and pelvic surgery: retrospective cohort study. Lancet 1999;353: 1476–80. [8] Fevang BT, Fevang J, Lie SA, et al. Long-term prognosis after operation for adhesive small bowel obstruction. Ann Surg 2004;240:193–201. [9] Menzies D, Parker M, Hoare R, et al. Small bowel obstruction due to postoperative adhesions: treatment patterns and associated costs in 110 hospital admissions. Ann R Coll Surg Engl 2001;180:40–6. [10] Akgür FM, Tanyel FC, Büyükpamukçu N, et al. Adhesive small bowel obstruction in children: the place and predictors of success for conservative treatment. J Pediatr Surg 1991;26:37–41. [11] Vijay K, Anindya C, Bhanu P, et al. Adhesive small bowel obstruction (ASBO) in children – role of conservative management. Med J Malaysia 2005;60:81–4. [12] Al-Salem AH, Oquaish M. Adhesive intestinal obstruction in infants and children: the place of conservative treatment. ISRN Surg 2011;2011:645104 [Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200142/. Accessed April 18, 2014]. [13] Eeson GA, Wales P, Murphy JJ. Adhesive small bowel obstruction in children: should we still operate? J Pediatr Surg 2010;45:969–74. [14] Choi HK, Chu KW, Law WL. Therapeutic value of Gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: a prospective randomized trial. Ann Surg 2002;236:1–6. [15] Biondo S, Pares D, Mora L, et al. Randomized clinical study of Gastrografin administration in patients with adhesive small bowel obstruction. Br J Surg 2003;90:542–6. [16] Choi HK, Law WL, Chu KW. Value of Gastrografin in adhesive small bowel obstruction after unsuccessful conservative treatment: a prospective evaluation. World J Gastroenterol 2005;11:3742–5. [17] Di Saverio S, Catena F, Ansaloni L, et al. Water-soluble contrast medium (gastrografin) value in adhesive small intestine obstruction (ASIO): a prospective, randomized, controlled, clinical trial. World J Surg 2008;32:2293–304. [18] Abbas S, Bisset IP, Parry BR. Meta-analysis of oral water-soluble contrast agent in the management of adhesive small bowel obstruction. Br J Surg 2007;94:404–11. [19] Abbas S, Bissett IP, Parry BR. Oral water soluble contrast for the management of adhesive small bowel obstruction. Cochrane Database Syst Rev 2007;18(3): CD004651. [20] Joyce WP, Delaney PV, Gorey TF, et al. The value of water-soluble contrast radiology in the management of acute small bowel obstruction. Ann R Coll Surg Engl 1992;74: 422–5. [21] Feigin E, Seror D, Szold A, et al. Water-soluble contrast material has no therapeutic effect on postoperative small-bowel obstruction: results of a prospective, randomized clinical trial. Am J Surg 1996;171:227–9. [22] Fevang BT, Jensen D, Fevang J, et al. Upper gastrointestinal contrast study in the management of small bowel obstruction: a prospective randomised study. Eur J Surg 2000;166:39–43. [23] Abdelkader H, Abdel-Latif M, El-Asmar K, et al. Gastrografin in the management of adhesive small bowel obstruction in children: a pilot study. Ann Pediatr Surg 2011;7(1):3–6. [24] Bonnard A, Kohaut J, Sieurin A, et al. Gastrografin for uncomplicated adhesive small bowel obstruction in children. Pediatr Surg Int 2011;27(12):1277–81. [25] Gastrografin [package insert]. Princeton, NJ: Bracco Diagnostics Inc; 2011. [26] Assalia A, Schein M, Kopelman D, et al. Therapeutic effect of oral Gastrografin in adhesive, partial small-bowel obstruction: a prospective randomized trial. Surgery 1994;115(4):433–7. [27] Branco BC, Barmparas G, Schnüriger B, et al. 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):470–8. [28] Atahan K, Aladağli I, Cökmez A, et al. Hyperosmolar water-soluble contrast medium in the management of adhesive small-intestine obstruction. J Int Med Res 2010; 38(6):2126–34. [29] Srinivasa S, Thakore N, Abbas S, et al. Impact of Gastrografin in clinical practice in the management of adhesive small bowel obstruction. Can J Surg 2011;54(2):123–7. [30] Haule C, Ongom PA, Kimuli T. Efficacy of gastrografin compared with standard conservative treatment in management of adhesive small bowel obstruction at Mulago National Referral Hospital. J Clin Trials 2013;3(4) [pii: 1000144].
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Evaluation of a water-soluble contrast agent for the conservative management of adhesive small bowel obstruction in pediatric patients Chee-Yew Lee a, Min-Hsuan Hung a,c, Lung-Huang Lin a,d,⁎, Der-Fang Chen b a
Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan Department of Surgery, Cathay General Hospital, Taipei, Taiwan Department of Pediatrics, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan d School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan b c
a r t i c l e
i n f o
Article history: Received 30 April 2014 Received in revised form 15 October 2014 Accepted 13 November 2014 Key words: Gastrografin® Water-soluble contrast agent Adhesive small bowel obstruction Children
a b s t r a c t Background/Purpose: The diagnostic and therapeutic benefits of a commercial water-soluble contrast agent (Gastrografin) in pediatric patients with adhesive small-bowel obstruction (ASBO) are controversial. The aim of this study was to assess the therapeutic value of Gastrografin in the management of ASBO in children after unsuccessful conservative treatment. Methods: Medical records from patients with uncomplicated ASBO managed at Cathay General Hospital, Taipei, Taiwan between January 1996 and December 2011 were retrospectively reviewed. All children ≤18 years of age with clinical evidence of ASBO were managed conservative treatment, unless there was suspicion of strangulation. Patients who did not improve after 48 hours of conservative treatment were administered Gastrografin. Results: Twenty-four patients with 33 episodes of ASBO were analyzed. Of those, there were 19 episodes of ASBO that failed to respond to the initial conservative management, and 16 (84%) responded well to Gastrografin administration thereby abrogating the need for surgical intervention. There were neither complications nor mortality that could be attributed to the use of Gastrografin. Conclusion: This preliminary study suggested that the use of a water-soluble contrast agent in ASBO is safe in children and useful for managing ASBO, particularly in reducing the need for surgery when conservative treatment fails. However, larger prospective studies would be needed to confirm these results. © 2015 Elsevier Inc. All rights reserved.
Every year, more than an estimated 300,000 patients undergo surgery to treat adhesion-induced small-bowel obstructions in the United States. Intra-abdominal adhesions related to prior abdominal surgery are the etiologic factor in up to 75% of cases of small-bowel obstruction [1]. In the past, there was a perception that children were less at risk of adhesions than adults; however, children also have a significant risk of adhesion and certain surgical procedures carry an appreciably high risk of readmission [2–4]. Van der Krabben et al. [5] reported bowel injuries in one-third of adult patients undergoing surgery for adhesive small-bowel obstruction (ASBO). Many studies have demonstrated the high risk of reoperation after adhesion, and surgery for ASBO results with greater morbidity and blood loss, is technically difficult, and can involve long operative times [6,7]. Published series have demonstrated that repeated surgery for ASBO increases the risks of readmission, the need for bowel resection, and complications [8]. ASBO is a significant health problem with major adverse effects on the quality of life and is a large burden on both healthcare and financial resources. The impact of admissions for ASBO, ⁎ Corresponding author at: Department of Pediatrics, Cathay General Hospital, No. 280, Section 4, Jen Ai Road, Taipei, 10630, Taiwan. Tel.: +886 2 27082121; fax: + 886 2 27074949. E-mail address: [email protected] (L.-H. Lin). http://dx.doi.org/10.1016/j.jpedsurg.2014.11.034 0022-3468/© 2015 Elsevier Inc. All rights reserved.
especially for those patients requiring surgical management, is considerable in terms of hospital resources [9]. Identifying conservative treatment modalities with a lower risk of morbidity and a reduction in the burden of both workload and costs would be advantageous. The outcomes of conservative treatment in children vary by age group. Akgur et al. [10] reported conservative treatment is feasible for childhood ASBO under special conditions, and Vijay et al. [11] advocated a conservative approach to ASBO in children. On the other hand, Al-Salem et al. [12] reported limitations in conservative management, and Eason et al. [13] suggested that ASBO is a distinct disease entity in children and identified increased age as a potential predictor of successful conservative management. The utilization of water-soluble contrast agents has revolutionized the nonoperative management of ASBO. Many studies have addressed the diagnostic and therapeutic benefits of using water-soluble contrast in ASBO, and the literature suggests that the hyperosmolarity of water-soluble contrast agent confers therapeutic benefits by activating movement of water into the small bowel lumen, decreasing edema of the small bowel wall, and enhancing smooth muscle contractility [14–20]. However, there are also studies with contrasting results, and data in pediatric populations are sparse [21–24]. The purpose of this study was to evaluate the possible use of the commercially available contrast agent diatrizoate meglumine and
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diatrizoate sodium solution USP (Gastrografin) in the management protocol of ASBO in children after unsuccessful conservative treatment. 2. Methods A retrospective review of medical records was performed to identify patients between 1 and 18 years of age who were admitted to the Pediatric Department of Cathay General Hospital with a primary diagnosis of ASBO between January 1996 and December 2011. The diagnosis of ASBO was made on the basis of historical, clinical, and radiological findings (e.g. history of abdominal surgery, bilious vomiting, failure to pass flatus or stool, abdominal distention, air-fluid level, and dilation of the small bowel loop on radiography). Patients with a known history of either allergy or hypersensitivity to contrast agents, inflammatory bowel disease, documented intra-abdominal malignancy, and intestinal obstruction within the first 4 weeks of a recent abdominal operation were excluded from participation in the study. Children under 1 year of age who are more prone to choking, and patients with tracheoesophageal fistulas were excluded to ensure safety of using Gastrografin. The initial work-up for all patients consisted of a complete physical examination with an emphasis on signs of bowel strangulation and peritonitis. The laboratory work-up included complete blood count, serum electrolytes, and C-reactive protein; and abdominal radiography was also performed. Surgery was performed immediately if the patient presented with signs of either strangulation or peritonitis (e.g., fever, tachycardia, leukocytosis). The remaining patients were managed conservatively over the subsequent 48 hours. The rationale for this timeframe was based on the results of a study by Choi et al. [14], which showed that patients with contrast observed in the colon within 24 hours were all treated successfully without surgery. Surgery was required in 96% of patients in whom contrast failed to reach the colon within 24 hours. It was safe to give Gastrografin even after the failure of conservative treatment. Complete resolution of bowel obstruction occurred a mean of 41 hours after administration of Gastrografin. It was usually at least 2 days later that solid food was allowed in our practice. We considered 48 hours of conservative treatment to be adequate. Patients were then followed up every year to monitor for obstruction recurrences. The contrast agent (diatrizoate meglumine and diatrizoate sodium solution, Gastrografin, Bayer Pharma, Spain) [25] is indicated for radiographic examination of segments of the gastrointestinal tract (esophagus, stomach, proximal small intestine, and colon). The preparation is particularly indicated when a more viscous agent such as barium sulfate, which is not water-soluble, is not feasible or is potentially dangerous. In this study, as per the package label, the contrast agent was applied to patients who failed to respond to conservative management as an intermediate step before surgical intervention. Contrast agent administration was preceded by infusion of intravenous Ringer’s solution bolus to guard against dehydration caused by the hygroscopic effect of the contrast medium. Gastrografin was given according to the age of the patient after dilution with equal volume of Ringer’s solution. The prepared mixture was given through the nasogastric tube (kept closed for 3 h and was then reopened).The conservative treatment protocol included nil per os (NPO), nasogastric tube decompression, laxative suppositories, enema, prokinetic agents (e.g. drugs that enhance gastrointestinal motility by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm), and adequate rehydration with isotonic fluid. When either the clinical or radiographic signs improved within 48 hours, the nasogastric tube was removed and oral feeding was initiated. Patients that developed signs of either bowel strangulation or peritonitis at any time during the conservative period underwent surgical interventions. In the patients with no improvement after 48 hours, Gastrografin and a mixture of sodium amidotrizoate and meglumine amidotrizoate were administered via the nasogastric tube. Patients b 10 years received 30–50 mL (diluted with twice its volume of water)
and other patients were administered 100 mL. All patients were carefully monitored, and any disturbances in water and electrolyte balances were corrected prior to using Gastrografin, since this agent produces a hyperosmotic effect. Potential complications related to the use of watersoluble contrast agent, such as aspiration pneumonia, renal failure, and anaphylaxis were carefully assessed. Other possible complications (e.g., bowel strangulation and resection, intra-abdominal abscess, fistula, sepsis, shock, thromboembolic events, and mortality) were also analyzed. Serial plain abdominal radiographs were obtained from 4 hours to ≥24 hours (based on the radiographs) after Gastrografin administration. Management was considered successful when the contrast was visualized in the cecum and a clinical improvement was noted. Once successful management was achieved, the nasogastric tube was removed and feeding was initiated. If the contrast agent failed to reach the cecum, complete obstruction was diagnosed and patients were scheduled for surgical intervention. The Ethics Review Board of the authors’ institute approved the study protocol. Because this study represents an analysis of secondary data, no informed consent was necessary. 3. Results Twenty-four patients (14 boys, 10 girls; range of patient age, 2–17 years) were admitted with a total of 33 episodes of ASBO that occurred between January 1996 and December 2011 (Table 1). Eight patients with nine episodes of ASBO underwent surgery immediately after initial resuscitation. The remaining 24 episodes of uncomplicated ASBO were managed conservatively for 48 hours under close monitoring. One episode of ASBO deteriorated clinically, had signs of strangulation during conservative management, and that patient immediately underwent surgery. Four episodes in three patients resolved within the 48-hour period of conservative management. In the remaining 19 episodes, conservative management failed and the patients received the contrast agent. In those 19 episodes, 16 episodes (84%) resolved clinically with radiological improvement (i.e., evidence of passage of the contrast to the cecum). The contrast agent failed to reach the cecum in the remaining 3 of 19 episodes (16%). Those patients were regarded as complete obstruction, eventually requiring an operation as no improvement was noted (Fig. 1). Of 8 surgically treated primary episodes, 3 episodes (38%) of recurrent ASBO developed. The recurrence rate after conservative management followed by Gastrografin administration was 55%. Two recurrent episodes after primary surgical management were treated conservatively with Gastrografin (67%), and one was managed surgically (33%). One recurrent episode after primary conservative management with Gastrografin was eventually treated surgically (17%), and the remaining 5 recurrent episodes were managed conservatively either with or without the contrast agent (83%). One episode of ASBO (initially presenting with a duplication cyst) did not improve clinically despite the presence of contrast in the colon (Fig. 2). Gastrografin was then instilled into the colon and terminal ileum, and clinical improvement was subsequently noted with radiological improvement after 24 hours. Patients with an initial presentation of Hirschsprung’s disease had the highest recurrence rate of ASBO (Table 1). Two of the three patients had two episodes of recurrent ASBO, and one developed three episodes of recurrent ASBO. No significant complications were related to water-soluble contrast agent administration in this study. Only one patient with a previous history of appendectomy who underwent immediate laparotomy for enterolysis required segmental bowel resection. 4. Discussion In 19 episodes of uncomplicated ASBO, conservative management failed and the patients then received the contrast agent. Most of these
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Table 1 Demographic and initial presentation of patients with ASBO. Primary condition
Gender (Male:Female)
No. of patients
Adhesion episodes
Median (range) patient age (in years) at time of ASBO
Appendicitis Hirschsprung’s disease Intussusception Ventriculoperitoneal shunt Perforation of peptic ulcer Spontaneous intestinal perforation Gastroschisis Volvulus Jejunal atresia Duplication cyst Hiatal hernia Total
4:5 2:1 2:0 2:0 0:2 0:1 0:1 1:0 0:1 1:0 1:0 14:10
9 3 2 2 2 1 1 1 1 1 1 24
9 10 2 3 2 2 1 1 1 1 1 33
13 (4.2–16.8) 10.2 (3–14) 16.6 (16–17.1) 13 (13–16) 11 (11–11) 2.3 (2.3–2.4) 4 14 3 13.6 14.2
episodes (84%) then resolved clinically with radiological improvement, with a recurrence rate of 55%. Of 8 surgically treated primary episodes, recurrent ASBO developed in 38%. In addition, patients with an initial presentation of Hirschsprung’s disease had the highest ASBO recurrence rate. Adhesions are internal, fibrous, band-like scars occurring after injury to the peritoneum. Adhesions are the result of both biochemical and cellular responses attempting to repair the peritoneum. Although that process is generally beneficial, it can also have detrimental effects, including small bowel obstruction. The most common cause of adhesions is iatrogenic (i.e., secondary to previous abdominal operations). The data on postoperative adhesions in children are sparse, and most of what is known about adhesions has been extrapolated from studies in adults.
A recent large-cohort study of 1541 children that had intestinal surgery reported an adhesion rate of almost 10% at the operative site and approximately 5% elsewhere [3]. The risk of further readmission is highest in the first year and continues with time [2,3]. No consensus has been reached regarding the diagnosis and management of such patients, especially in children with ASBO. Furthermore, specific and updated guidelines are currently lacking. Surgical treatment of ASBO may lead to the additional formation of adhesions, possibly contributing to recurrent episodes of ASBO. The surgical treatment for ASBO is characterized by long operative times and the risk of severe complications, such as bowel injury and bleeding. Therefore, the safety and efficacy of water-soluble contrast use in ASBO was addressed, initially by Assalia et al. [26] in the 1990s. Gastrografin, most commonly mentioned in the literature, is an ionic, bitter-
Fig. 1. Schematic presentation for the management of adhesive small bowel obstruction (ASBO). One episode did not improve clinically despite contrast in the colon. Lower gastrointestinal series with a Gastrografin enema was performed and both the clinical and radiological conditions improved after 24 hours.
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Fig. 2. A: Abdominal radiograph obtained 12 hours after Gastrografin administration showing a dilated bowel loop with air-fluid level filled with Gastrografin. B: Abdominal radiograph obtained 24 hours after Gastrografin administration showing that the contrast had reached the descending colon (arrow). C: Gastrografin successfully passed through the terminal ileum resulting in clinical improvement after 24 hours.
flavored mixture of sodium amidotrizoate, meglumine amidotrizoate, and a wetting agent (polysorbate 80) [25]. It has an osmolarity of 1900 mOsm/L, which is approximately 6 times that of extracellular fluid. It promotes shifting of fluid into the bowel lumen and increases the pressure gradient across an obstructive site. The bowel contents are diluted and in the presence of the wetting agent, passage of bowel contents through a narrowed lumen is facilitated. This contrast agent also decreases edema of the bowel wall and enhances bowel motility. Many studies have been performed to evaluate the role of watersoluble contrast in the management of ASBO in adult patients. Fevang et al. [22] suggested that contrast agent does not contribute to the resolution of small bowel obstruction, but is of great diagnostic benefit in evaluating the indication for surgical intervention and the timing of surgery. Abbas et al. [19,20] confirmed that water-soluble contrast followed by abdominal radiography after at least 4 hours can accurately predict the likelihood of resolution of a small bowel obstruction, and that the appearance of a water-soluble contrast agent in the colon on an abdominal radiograph within 24 hours of administration predicted resolution of the obstruction with a pooled sensitivity of 97% and specificity of 96%. Branco et al. [27] also reported that the appearance
of water-soluble contrast in the colon within 4–24 hours after administration could accurately predict the resolution of ASBO with a sensitivity of 96% and specificity of 98%. Atahan et al. [28] concluded that conservative treatment was recommended for patients in which contrast medium is observed in the right colon within 8 hours following administration, regardless of the presence of obstruction signs. ASBO is a heterogeneous and dynamic disease process with multiple different clinical presentations, which affect whether conservative management is successful. A large retrospective review of 710 patients with ASBO reported that previously demonstrated benefits from clinical trials have not been replicated in a clinical setting [29]. Factors other than watersoluble contrast agent use and protocol nonadherence owing to initial diagnostic uncertainty may have influenced patient management. Haule et al. [30] conducted a study to compare the efficacy of Gastrografin (n = 25) with standard conservative management (n = 25) for treating ASBO. In the contrast agent group, 22 (88%) patients experienced relief of ASBO following the intervention, with only 3 (12%) requiring surgery. Sixteen (64%) of the patients in the conservative treatment group experienced relief of ASBO, and 9 (36%) required surgery. The difference in operative rates between the two groups was
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not statistically significance (P = 0.67). Average time to relief of obstruction was significantly shorter in the contrast agent group (72.52 h) compared to the conservative treatment group (117.75 h; P = 0.023). The average length of hospital stay was significantly shorter in the contrast agent group (5.62 days) compared with the conservative treatment group (10.88 days; P =0.04). The investigators concluded that the use of Gastrografin in ASBO patients helps to promote an earlier resolution of obstruction and also reduces the length of hospital stay compared with standard conservative management. However, the role of the contrast agent in reducing the rate of laparotomies remained inconclusive. Further pilot studies in children have recently been proposed to evaluate the role of Gastrografin in the management of ASBO. Abdelkader et al. [23] demonstrated that Gastrografin may play a valuable role in the management of ASBO, either in a diagnostic or therapeutic capacity, and successfully completed the conservative management of 8 of 12 young (aged 1–16) patients (66.6%). Further, a prospective study from Bonnard et al. [24] (8 children with ASBO and 16 controls) found that Gastrografin may be useful for managing ASBO, and that it was associated with a significantly lower risk of hospitalization for N 3 days. This preliminary study suggests that Gastrografin is effective in the management of ASBO in children after unsuccessful conservative treatment. Out of 19 episodes ASBO with failure of initial conservative management, 16 episodes (84%) responded well to administration of the contrast agent and were successfully treated nonsurgically. There were neither complications nor mortality that could be attributed to the use of Gastrografin. There are some limitations to this study with respect to the small sample size and absence of a control group. Although the recurrence rate was higher in the Gastrografin group compared to the surgical group (55% vs. 38%), the need for surgery for the recurrent episodes was much lower (17% vs. 33%). The patients with Hirschsprung’s disease had the highest recurrence rates of ASBO, although the etiology was unclear (whether or not it was related to antecedent procedures or the nature of the disease). Lower gastrointestinal series with contrast agent instillation is an option when no clinical improvement is observed after oral administration of the agent. However, careful selection of the patients with no improvement despite contrast in the colon is required to avoid further morbidity. Finally, it should be noted that some surgeons would intervene earlier than 48 hours and that our prolonged observation may have contributed to the resolution of ASBO in our patients. 5. Conclusion A commercially available water-soluble contrast agent had a beneficial role in the conservative management of children with ASBO. This small study suggests the use of that product may avoid unnecessary surgical procedures. However, we cannot rule out the contribution of a prolonged observation period to ASBO resolution in our patient group. Further randomized controlled trials are recommended to confirm the diagnostic and therapeutic effects as well as the safety of the product for use in children.
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