Carbon dioxide is increasingly used in insufflation during colonoscopy in adult patients; however, air insufflation remains the primary practice among pediatric gastroenterologists. This systematic review and meta-analysis aims to evaluate insufflation using CO2 versus air in colonoscopies in pediatric patients.
Individualized search strategies were performed using MEDLINE, Cochrane Library, EMBASE, and LILACS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane working methodology. Randomized control trials (RCTs) were selected for the present meta-analysis. Pooled proportions were calculated for outcomes including procedure time and abdominal pain immediately and 24 hours post-procedure.
The initial search yielded 644 records, of which five RCTs with a total of 358 patients (CO2:
Based on this systematic review and meta-analysis of RCT data, CO2 insufflation reduced abdominal pain immediately following the procedure, while pain was similar at 24 hours post-procedure. These results suggest that CO2 is a preferred insufflation technique when performing colonoscopy in pediatric patients.
Over the last 30 years, gastrointestinal endoscopy in pediatric patients has been increasingly developed to improve its diagnostic and therapeutic utilities [
Since 1980, scientists have been investigating the impact of pain and pain relief among pediatric patients and the potential for negative physiological, emotional, and psychological ramifications [
To date, novel advancements have been made in the diagnostic and therapeutic areas of endoscopy, including visualization of the intestinal mucosa and insufflation [
This systematic review and meta-analysis was conducted following the guidelines of the Cochrane handbook for systematic reviews of interventions and information Elements (PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Aanalyses) [
The search strategy was carried out in the following electronic databases: MEDLINE, Cochrane Library, EMBASE, and LILACS from the start date to December 2020. Only RCTs were included, regardless of language and year of publication. The terminologies used for the search were the following in Medline: “(CO2 OR CO 2 OR carbon dioxide OR air OR insufflation / methods*) AND (colonoscopy OR colonoscopic) AND (pediatric OR pediatrics OR child OR preschool)”. For other databases, the following search “Carbon Dioxide AND Air AND Colonoscopy” was used.
RCTs using CO2 or air for colonoscopic insufflation in patients under 21 years old were included. Exclusion criteria were RCTs comprising patients with a history of cardiac health issues, acute pulmonary infections, chronic lung disease, oxygen-dependent pulmonary disease (such as bronchopulmonary dysplasia, severe asthma, or cystic fibrosis), mental disability, pregnancy, colon resection or stoma, known allergy to certain sedatives used during the procedure, inability to complete the visual analog scale or Wong-Baker Faces Scale, psychomotor impairment, or hemodynamic instability. Additionally, RCTs with patients undergoing colonic manometry were also excluded. Other exclusion criteria were case and series reports, editorial articles, and non-randomized studies (i.e., prospective or retrospective comparative studies). The outcomes measured in this study were the duration of the colonoscopy procedure, abdominal pain immediately after the procedure, and abdominal pain 24 hours after the procedure.
The information was collected from the selected clinical trials, contained in tables or graphs according to our results. Two independent investigators conducted the screening for eligibility with the criteria of inclusion and exclusion to our evaluation. Any disagreements were resolved by consensus or by consultation with a third reviewer. The data collected were type of study, patients by age, sex, total number, and indication of the examination.
For the analysis of the risk of bias of the selected studies, using the Cochrane guidelines we assessed the adequate risk of bias exclusively for RCTs (Rob-2, risk-of-bias tool for RCTs), with the latest version updated on August 22, 2019 [
To qualify the evidence, it was evaluated using GRADEproGDT software (Mc Master University, Ontario, Canada). through objective analysis, according to the results of our study. GRADEproGDT is a software used to grade the evidence from included studies according to the following guidelines: number of studies, study design, risk of bias, imprecision, indirect evidence, inconsistency and other considerations, summary of findings, and importance.
The rating of the evidence and the risk of bias were guided and analyzed according to our statistical staff.
Statistical analysis was performed using the Cochrane RevMan 5 version 5.4 software (Cochrane Collaboration, Oxford, UK) that was updated in May 2020. Continuous variables were calculated by mean difference (MD) and 95% confidence interval (CI) using a random effect with inverse variance while the risk of difference (RD) and 95% CI for dichotomous variables were calculated using the Mantel-Haenszel method with a fixed effects model.
Heterogeneity was calculated using the Higgins method (I²). The values <45% were considered as low heterogeneity, 46-75% as moderate heterogeneity, and >75% as high heterogeneity. For the analyses, the mean, standard deviation, and absolute numbers were considered. When we had no means or standard deviations, they were calculated using mathematical equations [
When we placed the terms of our search strategy in the selected databases, 644 studies were identified. After analysis and confirmation of all the databases, duplicate articles were discarded, which were verified by titles and abstract comprising 522 articles, of which 46 were subsequently selected for manual verification of the complete literature. After the analysis of complete articles, seven studies were selected, of which two were excluded because they were not randomized controlled studies. Finally, we included five RCTs [24–28] for analysis (
Five RCTs [24–28] were included and 358 patients were identified: 178 in the CO2 insufflation group and 180 in the air insufflation group. The characteristics of the individual studies are listed in
On assessment of the risk of bias, the studies by Dike et al. [
The estimated outcome of procedure time demonstrated low-quality evidence. Abdominal pain immediately post-procedure showed high quality of evidence, while that at 24 hours after the procedure showed low quality of evidence (
Four studies [24–26,28] in which 256 patients were included (CO2 insufflation group,
Three studies [25–27] with a total of 213 patients (CO2 insufflation group,
Three studies [
The role of colonoscopy in pediatric patients should include careful consideration of individual patient preference, be performed in a collaborative friendly environment, ensure the use of appropriate equipment, and be performed by a trained pediatric endoscopist [
We decided to conduct the first systematic review with meta-analysis comparing the benefits of CO2 versus ambient air insufflation during pediatric colonoscopy. In this study, we included five RCTs [24–28] with good quality and adequate methodological design, including 358 pediatric patients. Furthermore, it was found that there was no statistical difference in terms of colonoscopy time, demonstrating that the type of gas used during the procedure does not influence the duration of the procedure. Additionally, based on this meta-analysis, post-procedure pain was also analyzed and CO2 insufflation showed clinical advantage in terms of reducing immediate post-colonoscopy abdominal pain in children.
These results are similar to those of several previous meta-analyses analyzing CO2 and air insufflation use in endoscopic procedures in adult patients [
While not assessed in our meta-analysis, four studies specifically evaluated abdominal bloating [24–26,28], showing no significant difference in bloating with CO2 versus ambient air insufflation during pediatric colonoscopy. This result is divergent from those analyzing adult patients, who demonstrated objectively decreased abdominal bloating post-procedure [
This meta-analysis did not find a significant difference in abdominal pain 24 hours post-colonoscopy between groups. However, the included studies assessed pain through telephone calls and questioning of the family members, thereby increasing the risk of bias. Several meta-analyses from adult populations have demonstrated decreased patient discomfort with CO2 insufflation, and therefore its use has been recommended in the British and European endoscopy guidelines for colonoscopy in adults [35–37]. However, to date, pediatric endoscopy societies have not adopted CO2 insufflation into formalized guidelines, likely due to the low quality of evidence [
Although this meta-analysis only included RCTs, our study is not without limitations. First, some patients included in this study underwent same-session upper digestive endoscopy in some cases using ambient air or CO2 for insufflation, which may interfere with the quantity of gas within the gastrointestinal lumen as well as alter the procedure time depending on the technique used to perform the colonoscopy, according to an experienced endoscopist or pediatric gastroenterology fellows. Second, the study by Dike et al. [
In conclusion, CO2 insufflation significantly reduced the amount of post-procedure abdominal pain following colonoscopy. When compared to air insufflation for colonoscopy among a group of pediatric patients, immediate abdominal pain was decreased for patients undergoing CO2, with no change in procedure time or pain at 24 hours post-procedure. These findings suggest that CO2 insufflation should be the method of choice in pediatric colonoscopy.
Overall risk of bias.
GRADEpro. Supplementary file.
Funnel plot - Procedure time. MD, mean difference; SE, standard error
Funnel plot - Abdominal pain immediately post-procedure. RD, the risk of difference; SE, standard error.
Funnel plot - Abdominal pain at 24 hours post-procedure. RD, the risk of difference; SE, standard error
None.
Conceptualization: John Alexander Lata Guacho, Diogo Turiani Hourneaux de Moura, Igor Braga Ribeiro
Data curation: JALG, DTHM, IBR, Bruna Furia Buzetti Hourneaux de Moura, Megui Marilia Mansilla Gallegos, Thomas McCarty, Ricardo Katsuya Toma
Formal analysis: JALG, DTHM, IBR, TM
Methodology: JALG, DTHM, IBR, TM
Project administration: Eduardo Guimarães Hourneaux de Moura
Resources: EGHM
Software: EGHM
Supervision: DTHM, EGHM
Validation: DTHM, IBR, EGHM
Visualization: DTHM, IBR, EGHM
Writing-original draft: JALG, DTHM, IBR, MMMG
Writing-review and editing: JALG, IBR
Flow diagram of the analyzed studies.
Forest plot comparing the time of the colonoscopy procedure, using CO2 insufflation versus air insufflation in pediatric patients. CI, confidence interval; IV, instrumental variable; SD, standard deviation.
(A) Forest plot comparing abdominal pain immediately post-procedure using CO2 insufflation versus air insufflation in pediatric patients. (B) Forest plot comparing abdominal pain at 24 hours after the procedure, using CO2 insufflation versus air insufflation in pediatric patients. CI, confidence interva.
Characteristics of Included Studies
Study | Country | Study type | Blinding | Age (yr) | Population (n) | Participants (CO2/Air) | Sedation and analgesia | Indications for colonoscopy |
---|---|---|---|---|---|---|---|---|
Dike et al. (2020) [ |
USA | RCT | Double | 6 months to 21 | 69 | 33/36 | Propofol and general anesthesia administered by pediatric anesthesiologist. | Abdominal pain, diarrhea, hematochezia, feeding or growth concerns, other. |
Dharmarj et al. (2020) [ |
USA | RCT | Double | 8 – 21 | 100 | 48/52 | General anesthesia administered by pediatric anesthesiologist. Sevoflurane and propofol was used to obtain a level of deep sedation during the procedure. | Chronic abdominal pain and non-abdominal pain. |
Kresz et al. (2019) [ |
Germany | RCT | Double | 4 – 17 | 73 | 39/34 | Midazolam, propofol and narcotics (alfentanil, remifentanil, ketamine) were administered by an anesthesiologist to maintain deep sedation. | Inflammatory bowel disease (active disease, evaluation of therapy effectiveness), chronic abdominal pain, diarrhea, hematochezia and other. |
Thornhill et al. (2017) [ |
USA | RCT | Double | 5 – 18 | 40 | 20/20 | General anesthesia administered by pediatric anesthesiologist. | Abdominal pain, bleeding, diarrhea, surveillance for inflammatory bowel disease, anemia, weight loss and other. |
Homan et al. (2016) [ |
USA | RCT | Double | 7 – 18 | 76 | 38/38 | Midazolam, ketamine. | Chronic diarrhea, chronic abdominal pain, suspicion of inflammatory bowel disease, inflammatory bowel disease therapy effectiveness evaluation, hematochezia, rectal prolapse and malabsorption syndrome. |
RCT, randomized control trial.