A study to evaluate the efficacy and safety of laxatives (Polyethylene glycol) vs placebo in paediatric foreign body ingestion: A randomized controlled trial

Background

Foreign body ingestion (FBI) is a prevalent and challenging paediatric emergency, particularly affecting children aged between six months to three years. The natural developmental tendency of young children to explore their environment through oral means places them at a heightened risk.[1] Unlike adults, paediatric FBI incidents are predominantly accidental, involving a spectrum of everyday items such as toys, coins, jewellery, batteries, and magnets.[2-3] The potential consequences of FBI in children are severe and can lead to complications like intestinal obstruction, bleeding, perforation, and peritonitis.[1-3] The types and locations of ingested foreign bodies vary based on the age, cultural background, and socioeconomic status of the children, adding complexity to the management of these cases.[3]

Despite the significant clinical implications and the frequency of paediatric FBI cases, the existing literature on the use of laxatives in this context is notably limited. Current evidence primarily relies on case reports, case series, and expert opinions, leaving a substantial gap in knowledge and practice.[2] The absence of robust evidence from well-designed randomized controlled trials (RCTs) hinders the development of clear guidelines and protocols for managing paediatric FBI, leaving healthcare professionals without a standardized approach.

To understand the complexities of the issue, we turn to existing studies that offer insights into the challenges faced in managing paediatric FBI. A retrospective study conducted by Khurshid Z et al at the Department of Paediatric Surgery, King Saud Medical City, Riyadh, sheds light on the prevalence of button batteries as the most common ingested foreign body among children (49%). The study reveals alarming complications, including jejunal perforation (12%) and oesophageal/gastric ulcers (10%). However, critical details regarding the specific type of foreign bodies subjected to oral lactulose and the outcomes of this intervention remain elusive.[4]

Similarly, a prospective study by Sayanthan B et al at the University of Jaffna, Sri Lanka, administered various laxatives—syrup lactulose, syrup liquid paraffin, syrup domperidone, and bisacodyl suppository—to all 55 children presenting with FBI. The study reported a high rate of spontaneous passage (90%) of foreign bodies, with minimal complications and a low endoscopic retrieval rate (8%). While the study provides valuable information on the overall success of laxatives in aiding passage, it lacks a comparative analysis of the effectiveness of each laxative and specific details on their impact.[5]

In another prospective observational study by Amini‐Ranjbar S at the Research Center for Healthcare Management, Kerman, Iran, laxatives, including lactulose and polyethylene glycol, were prescribed for the ingestion of batteries and heroin. The study reports a successful medical treatment rate of 68%. However, a notable gap exists in the data concerning the specific outcomes of laxative use in these cases, limiting our understanding of their effectiveness and safety.[6]

The current literature underscores the pressing need for a comprehensive and methodologically sound investigation into the role of laxatives in paediatric FBI. Our proposed study aims to address the current lacuna in knowledge and to enhance clinical outcomes, guide evidence-based practice, and ultimately contribute to the advancement of paediatric healthcare.
 

Significance/Rationale of this study

Paediatric FBI poses a considerable challenge in clinical practice, with endoscopic and surgical interventions being common approaches. However, the discrepancy between established guidelines (mandating endoscopic removal in 10-20% and surgical intervention in <1% of cases) [1,4] and observed intervention rates (ranging from 8% to 32% for endoscopy and 12-16% for surgery) [3,5,6] suggests a critical barrier in our understanding of optimal management strategies. This discrepancy underscores the need for innovative approaches to expedite the passage of ingested foreign bodies and reduce associated complications, especially in the context of the common tendency for children to swallow subsequent foreign bodies.[2] This study seeks to address this gap by exploring the potential of laxatives in expediting the passage of ingested foreign bodies in paediatric patients.

The central research question driving this investigation is: "Can the use of laxatives significantly enhance the natural passage of ingested foreign bodies in the paediatric population, reducing the risk of complications and the need for invasive interventions?" This question addresses the critical barrier in scientific knowledge regarding the optimal management of paediatric FBI. By evaluating the efficacy and safety of laxatives through well-designed randomized controlled trials (RCTs), we aim to provide robust evidence to guide clinical decision-making, thus improving the standard of care for paediatric FBI.

The lack of well-established evidence from RCTs on the use of laxatives in paediatric FBI creates a significant gap in scientific knowledge. [2] Our study aims to fill this void by systematically evaluating the outcomes associated with laxative interventions. The results will contribute to a deeper understanding of the potential benefits and risks, allowing for evidence-based recommendations that can reshape the existing paradigms in the management of paediatric FBI.

The study’s approach incorporates cutting-edge techniques in designing and conducting RCTs, ensuring scientific rigor and the reliability of the results. The technical capabilities involved in this research, from participant inclusion to nuanced data collection, will not only contribute to the robustness of the study but also set a precedent for the application of advanced methodologies in investigating clinical questions.

From a programmatic and clinical standpoint, this study addresses a critical gap in the current approach to paediatric FBI. By exploring an alternative, less invasive method of managing ingested foreign bodies, the study has the potential to influence clinical practices, reducing the reliance on endoscopic or surgical interventions. This shift could not only improve patient outcomes but also potentially alleviate the burden on healthcare systems by minimizing the need for resource-intensive procedures.

The relevance of this study extends to the local, national, and international context. Locally, the findings could directly impact the practices of healthcare providers dealing with paediatric FBI. Nationally, evidence-based recommendations from this study could contribute to the development or revision of guidelines, shaping the standard of care across various healthcare settings. Internationally, the study has the potential to influence practices and guidelines, fostering a global shift towards more effective and less invasive approaches to paediatric FBI.

Experimental plan/approach

A randomized controlled trial would be conducted in the Department of Paediatric Surgery, Bangalore Medical College and Research Institute, Bengaluru, India.

Study design: Randomized controlled trial with double blinding

Study period: March 2024 to February 2026

Sample size:

Formula: N₂= [k(s₁²+s₂²)](Z_1-α/2 + Z_1-β)²/D²

·     From our previous study on 65 children with FBI, mean time for spontaneous passage was 137 hrs with a standard deviation of 124 hrs. 

·     To calculate sample size, an arbitrary mean time to spontaneous passage of FBI in laxative group would be considered as 89 hours with a standard deviation of 70 hours. Hence, the mean difference would be 48 hours. The power of the study would be kept at 80% and confidence interval of 95%.

·    N= 67

·   Dropout rate = 10% = 7

·   Hence the sample size is 74 in each arm and a total sample size: 148

Inclusion Criteria:

All children aged 1 year to 18 years of age presenting with ingestion of foreign body to the Department of Paediatric Surgery, Bangalore Medical College and Research Institute.

Exclusion Criteria:

Children with features of intestinal obstruction or perforation peritonitis.

Children with oesophageal foreign body, multiple magnets, magnet and a metal, corrosive or biologically active foreign body, radiolucent foreign body, or impacted foreign body.

Children with history of gastrointestinal pathology or gastrointestinal surgery.

The children with foreign body aspiration, incomplete data, or lost to follow-up.

Methodology:

A randomized controlled trial with double blinding will be conducted in the Department of Paediatric Surgery. The children, aged 1 year to 18 years, presenting with ingestion of foreign body to the Department of Paediatric Surgery, Bangalore Medical College and Research Institute between June 2024 and May 2026 will be included in the study. 

Upon obtaining approval and clearance from the institutional ethics committee, the patients fulfilling the inclusion criteria will be enrolled for the study after obtaining informed consent from parents/guardian. An additional Written Assent form would be obtained from children between 7 and 18 years.

The data will be collected in a standardized proforma. The proforma will include demographic parameters (age, gender, and weight), details of FBI (date, time, type, number, size, and shape of the foreign body), symptoms, stooling pattern, h/o constipation, duration of symptoms, clinical findings, and relevant investigations.

Participants will be randomized to receive either oral polyethylene glycol (PEG) or placebo until the foreign body is passed or up to a maximum of 7 days, whichever comes first. The participants will be treated on outpatient basis. They would be admitted only if they need intervention such as endoscopy or surgery or in case of any adverse event. Polyethylene glycol is chosen as the laxative because it is widely available, inexpensive, safe, effective, and is the first line drug of choice in managing constipation as recommended by Consensus Practice Guidelines of Indian Society of Paediatric Gastroenterology, Hepatology and Nutrition and Paediatric Gastroenterology Chapter of Indian Academy of Paediatrics, ESPGHAN and NASPGHAN. [10,11] PEG will be administered at a dose of 1g/kg/day in two divided doses.[10] The PEG syrup used would have a concentration of 52.5g/100ml. Hence, a dose of 1ml/kg/dose (maximum 13g/dose i.e., 25ml) twice daily will provide 1g/kg/day of PEG. The placebo being used would contain Aspartame (an artificial sweetener) at a concentration of 100mg/100ml. Hence, a dose of 1ml/kg/dose (maximum 25mg/dose i.e., 25ml) twice daily would provide 2mg/kg/day which is 5% of allowable daily intake (40mg/kg/day) as per WHO. [12] The randomization sequence will be generated by a computerized system and concealed using sealed opaque envelopes. The study drugs will be identical in appearance and taste and will be dispensed by a pharmacist who is not involved in the study.

Both the groups will receive standard care, which may include close monitoring, symptomatic management, or potential interventions such as endoscopy or surgery, if required.

The participants will undergo an abdominal radiograph at baseline to confirm the presence and location of the foreign body. Parents will be instructed to monitor the passage of the foreign body in stool. The gastric foreign body would be managed as per Figure-1.[6] The foreign bodies beyond stomach would be monitored and intervened by surgical approach in case of obstruction or perforation. In asymptomatic cases, serial x-rays are taken at 7days, 14 days, 28 days, and monthly till the spontaneous passage. The time to passage of the foreign body will be calculated as the difference between the time of ingestion and the confirmed time of passage. The time of passage will be confirmed by visual inspection of stool. In case the parents have missed noticing the foreign body in stool and the subsequent abdominal radiograph is negative, the time of passage would be documented as not known.

Throughout the study, participants and their caregivers will maintain a daily diary to record any symptoms, adverse events, medication use, dietary intake, bowel movements, and stool characteristics. If the child develops bowel movements more than 5 times a day, the dose of medication would be reduced to half. And if the child doesn’t pass stools even after 48 hours, the dose would be increased to 1.5times. The parents would be advised to bring the child back to us if the child develops abdominal distension, persisting vomiting, pain abdomen, or high-grade fever. The occurrence of abdominal distension, vomiting, nausea, abdominal pain, loose stools, or diaper rash would be considered as adverse events of PEG.

Surgical/Endoscopy procedure details, date and time of spontaneous passage, and complications would be recorded. The children will be followed up to spontaneous passage or up to six months post foreign body retrieval.

Statistical analysis:

IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp., will be used to perform the statistical analysis. The categorical variables will be expressed in number and percentage. The difference between the groups would be assessed using chi-square or Fischer’s exact test. The continuous variables will be expressed in mean ± standard deviation or median with interquartile range. The difference between the groups would be assessed using t-test or Mann-Whitney U test.

Measurable outcomes

The primary outcome measures of the study include the rate of spontaneous passage of foreign bodies, the need for invasive interventions (endoscopy, surgery), and the occurrence of adverse events associated with laxative use. These outcomes will be assessed by radiographic imaging, clinical examination, and medical records review. 

References:

1. Lee JH. Foreign Body Ingestion in Children. Clin Endosc. 2018;51(2):129-136. doi:10.5946/ce.2018.039.

2. Arana A, Hauser B, Hachimi-Idrissi S, Vandenplas Y. Management of ingested foreign bodies in childhood and review of the literature. Eur J Pediatr 2001;160:468–472.

Seo JK. Endoscopic management of gastrointestinal foreign bodies in children. Indian J Pediatr. 1999;66(1):S75–S80.

4. Alexander W, Kadish JA, Dunbar JS. Ingested foreign bodies in children. In: Kaufmann HJ, editor. Progress in pediatric radiology. 2nd ed. Chicago (IL): Yearbook Medical Publishers; 1969. pp. 256–285.

5. Panieri E, Bass DH. The management of ingested foreign bodies in children-a review of 663 cases. Eur J Emerg Med. 1995;2:83–87.

6. Kramer RE, Lerner DG, Lin T, Manfredi M, Shah M, Stephen TC, et al. Management of ingested foreign bodies in children: a clinical report of the NASPGHAN endoscopy committee. J Pediatr Gastroenterol Nutr. 2015;60:562-574.

7. Sayanthan B, Sanjaya A, Ganeshrajah A, Thiruvarangan S. A non-invasive novel approach for managing digestive tract foreign body ingestion in children. Karnataka Paediatr J 2022;37:19-23. 

8. Khurshid Z, Ali AE, Al-Hamidi SAA, Alnafisah TI. Foreign Body Ingestion in Children: A Hospital Based Experience in Riyadh. Acta Scientific Paediatrics 2019;2(10):13-19. 

9. Amini-Ranjbar S. Foreign body ingestion in Iranian children: A 4 years observational study. Russian Open Medical Journal 2012;1:0307.

10. Yachha SK, Srivastava A, Mohan N, Bharadia L, Sarma MS. Management of Childhood Functional Constipation: Consensus Practice Guidelines of Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition and Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics. Indian Pediatr. 2018:15;55(10):885-892. 

11. Tabbers MM, DiLorenzo C, Berger MY, Faure C, Langendam MW, Nurko S, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; North American Society for Pediatric Gastroenterology. Evaluation and treatment of functional constipation in infants and children: Evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58(2):258-274. 

12. Butchko HH, Kotsonis FN. Acceptable daily intake vs actual intake: the aspartame example. J Am Coll Nutr. 1991;10(3):258-266.