Adequate distension and visualization of gastrointestinal lumen is essential during colonoscopy [1]. Traditionally room-air has been used for insufflation during all endoscopic procedures. Carbon dioxide (CO₂) insufflation during colonoscopy has been studied since 1950’s in adults [2]. The initial purpose of CO₂ use was to reduce the explosive potential with room-air use during electrocauterization for polypectomy. Subsequent studies showed that CO₂ causes less postprocedural abdominal pain, decreased time taken to reach cecum and cecal intubation rate [3] and increased patient satisfaction [4]. Beneficial effect of CO₂ has been attributed to its rapid diffusion across intestine which is 160 times more rapid than nitrogen (78% of room-air) and 13 times more rapid than oxygen (21% of room-air) resulting in reduced bowel distension following the procedure [5]. Concerns regarding the safety of using CO₂ were raised but despite elevations reported in end-tidal carbon dioxide (ET-CO₂) levels, no significant adverse respiratory compromise has been reported so far [6]. Numerous studies have shown the safety and efficacy of CO₂ insufflation as compared to room-air insufflation in adults during colonoscopy [7,8]. A few published reports in children compared CO₂ and room-air insufflation during colonoscopy, however, all are underpowered. The aim of our study was to find out whether CO₂ insufflation is safe and reduces the postprocedural pain and discomfort when compared with room-air insufflation in children undergoing colonoscopy.

The study was a prospective randomized controlled clinical trial. Children of age 6 years to 18 years who underwent colonoscopy in the department of Pediatric Gastroenterology at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India between March 2023 and July 2024 were recruited. Children with neurological abnormalities and unable to complete visual analogue scale (VAS), chronic lung diseases, previous colectomy, prior participation in the study were excluded from the study. Written informed consent was obtained from either parents before participation in the study. The study was approved by the Institutional ethical committee and the study was registered with the Clinical Trial Registry of India (CTRI/2023/03/050641).

A total 200 children were randomly assigned to insufflation of either room-air or CO₂ during colonoscopy (100 children in each arm). Study design (CONSORT [Consolidated Standards of Reporting Trials] flow chart) is shown in Fig. 1. Patient’s demographic data are shown in Table 1. The patient population consisted of 126 boys (62.4%) and 74 girls (36.6%), with a median (IQR) age of 12 (9–16) years. The most common indications for colonoscopy were; surveillance for inflammatory bowel disease. No significant differences were observed between the 2 groups with respect to baseline characteristics. Highlights of the results are shown in graphical abstract.

This prospective, randomized, single-blind study in children undergoing colonoscopy with conscious sedation showed statistically significant change between postprocedure pain in children insufflated with CO₂ versus room-air. On multivariate analysis, we found reduced rate of postprocedural pain with CO₂ insufflation. To our knowledge, this is the first pediatric study to show a significant relationship with increased time to reach the cecum with CO₂ as compared to room-air. Subsequently, we also did subgroup analysis to find the duration of the procedure which revealed significantly longer time to reach the cecum and total duration of the procedure with CO₂ insufflation when done by first year trainees as compared to more competent endoscopists. The possible explanation for the same could be because of rapid diffusion of CO₂ across the intestinal wall as compared to room-air causing early collapse and reduced visualization of the lumen. Various studies have reported the advantages of CO₂ use in colonoscopy in reducing the postprocedure pain but none had reported increased duration of the procedure with CO₂ insufflation during colonoscopy. Our study had demonstrated significant increase in duration of procedure with CO₂ especially in beginners’ hands. These findings may need to be considered especially in training institutes during initial colonoscopy training.

Previously, Bretthauer et al. [4], in a study of 230 adult patients reported that the use of CO₂ in patients who underwent flexible sigmoidoscopy was associated with decreased post procedural pain up to 6 hours after examination. In another study of 103 patients reported by the same group, CO₂ insufflation was associated with decreased postprocedure pain compared with room-air at 1, 3, and 6 hours after colonoscopy [6]. A meta-analysis performed on 21 randomized control trials comprising 3,607 adult patients concluded that CO₂ insufflation during colonoscopy in adults decreases postoperative pain over room-air insufflation [7]. In those studies, insufflation with CO₂ did not prolong the procedure or lengthen the time to reach the cecum and proved to be safe in all patients. In another study of 35 adult patients by Saito et al. [10] reported reduced patient pain postprocedure with CO₂ insufflation in potentially difficult cases when performed by less experienced colonoscopist. Other studies in adults have also demonstrated the significant differences in postprocedural pain between room-air and CO₂ [11-21].

Very few studies have investigated the effects of CO₂ insufflation in children. Homan et al. [22] in a study of 76 children, reported a significantly higher proportion of children were pain free after colonoscopy in the CO₂ group compared with the room-air group. In our study, we found that significant pain (VAS≥3) was more with room-air group as compared to CO₂ group. Thornhill et al. [23] in a study of 40 children reported no significant increase in ET-CO₂ between groups in the pediatric population and significantly high pain scores following room-air compared with those receiving CO₂ insufflation. Dike et al. [24] in a study of 178 children who underwent esophago gastro duodenoscopy [EGD] (n=88) and colonoscopy with or without EGD, reported sustained elevation in ET-CO₂ (>50 mmHg elevation for >5 minutes) in 2 of the children who underwent colonoscopy with CO₂ insufflation but no significant respiratory events occurred. Our findings revealed significantly high ET-CO₂ levels in CO₂ group as compared to room-air group but no clinical signs of other adverse events or impaired ventilation was observed during the procedure or postprocedure and CO₂ insufflation was well tolerated in all patients in our study. In addition, various studies reported the benefits of permissive or therapeutic hypercapnia in increasing tissue perfusion, reduce barotrauma, infection risk even in preterm babies [25-28]. Dharmaraj et al. [29] in a study of 100 children reported significant pain when duration of the procedure extend beyond 30 minutes in multivariate analysis. But our observation revealed no significant difference in pain with relation to the duration of the procedure.

Our study highlights the advantage of using CO₂ insufflation in reducing postprocedure pain and discomfort in children undergoing colonoscopy. Regarding the disadvantage of CO₂ insufflation, beginners might have technical difficulties in negotiation of the scope through the flexures, possibly related to the rapid diffusion of CO₂ across the intestinal wall causing luminal collapse. However, we observed that this difficulty has been seen only in the early learning phase. Additionally, the availability of CO₂ source is a matter of concern. Additional randomized controlled trials with CO₂ insufflation in children for procedures like upper gastrointestinal endoscopy, endoscopic retrograde cholangio pancreatography is a potential area of research.

The present study has some limitations. Firstly, we did not measure the volume of gas used for insufflation during colonoscopy. Another limitation was that level of CO₂ was not measured by performing arterial blood gases; however, this does not seem to be appropriate, given that the children would have to undergo multiple arterial punctures during and after the procedure. We could not do double blinding due to logistic reason (CO₂ cylinder and connections are easily visible to endoscopist).

In conclusions, the use of CO₂ insufflation during colonoscopy makes the procedure less painful. CO₂ insufflation was well tolerated by all study participants. Use of CO₂ also makes the procedure longer especially during the initial learning phase which might be considered during the colonoscopy training.