Clinical trial NCT03287687
Conditions: Endoscopy Insufflation
Sponsor: Warren Bishop
Start date: 2017-11-27; Completion date: 2019-04-09
Enrollment: 180 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Hypothesis:

Carbon dioxide gas use for endoscopic insufflation is safe and results in less abdominal distension and discomfort; it is equally effective as air in pediatric patients undergoing endoscopic procedures.

Aim 1:

Determine the occurrence and severity of abdominal discomfort and distension associated with endoscopic procedures at baseline, upon awakening from anesthesia, at discharge and at 4 hours after discharge in carbon dioxide group when compared to the air group.

Aim 2:

Determine if the expertise level of the endoscopist contributes to abdominal discomfort and distension following endoscopy, and whether this differs in the carbon dioxide group versus air group.

Aim 3:

Determine if carbon dioxide is as effective as air for insufflation.

Detailed description:
STUDY DESIGN: A Prospective, Randomized, Double-Blinded, Controlled Trial We intend to enroll 250 patients aged between 6 months and 21 years in a randomized, double-blind study comparing the use of air (our current routine) vs. carbon dioxide (CO2) for insufflation (inflation) of the gut during endoscopy. The primary endpoint will be abdominal girth and abdominal pain/discomfort after undergoing the endoscopy. Secondary endpoints will be indirect measures of CO2 absorption (respiratory rate and end-tidal CO2)throughout the procedure, determination whether the endoscopist's training level influences the primary endpoint,and determination if CO2 and air are equally effective for adequate intestinal visualization . Similar studies in adults have demonstrated safety and efficacy of CO2 in minimizing bloating and abdominal pain following endoscopy and show no difference in efficacy of insufflation. However, studies done to date in children have not been comprehensive in data gathering and analysis. We now have the capability to routinely use CO2 for insufflation in our new Stead Family Children's Hospital procedure unit, and wish to take this opportunity to fully document both efficacy and safety of CO2 insufflation in children undergoing our most common endoscopic procedures, including esophagogastroduodenoscopy (EGD, upper endoscopy,) colonoscopy, or combined upper endoscopy and colonoscopy. All patients in the study will be sedated by the anesthesia team using propofol as the primary agent. We will exclude patients who are judged to be at risk of respiratory compromise.

Informed consent will be obtained as always for the procedure itself; additional consent and/ assent (when appropriate) will be obtained for study participation. For patients or parents who opt out of the study; air will be used, as per our current routine, for insufflation. Those willing to participate in the study will be randomly assigned to either carbon dioxide or air for insufflation during their endoscopic procedure. Both the endoscopist and patient will be blinded to arm of study.

DATA COLLECTION: At baseline, routine vital signs (HR, BP, RR, oxygen saturation), end tidal CO2, and pain assessment (see below) will be documented. Abdominal girth, measured at the umbilicus, will be documented at baseline as well. The expertise level of the primary endoscopist will be noted; fellow (1st, 2nd, or 3rd year) or faculty will be recorded. A faculty gastroenterologist will be present for the entire procedure.

During the endoscopic procedure, again as per our usual routine, end-tidal CO2 will be continuously monitored and recorded in Epic by the anesthesia team. Other parameters that will be monitored and recorded continuously will include, HR, BP respiratory rate, and oxygen saturation. Based on published studies, we do not anticipate any evidence of detectable CO2 absorption during the procedure, but will be prepared to unblind the study and switch to air insufflation if any concern arises during the procedure. The duration and type of procedure will be noted for all patients.

At the end of the procedure, Heart rate (HR) , Blood pressure (BP), respiratory rate (RR), oxygen saturation, end tidal CO2, abdominal girth, and pain assessment will be documented again. "Breath to breath" analysis of the end tidal CO2 monitor tracing will be performed later, using recorded data, study by Dr. Timothy Starner (Pediatric pulmonologist). This will enable us to determine if there had been any evidence of an increased respiratory rate associated with increased CO2 absorption.

We will use the verbal scale : face, legs, activity, cry, consolability (FLACC) scale to assess pain upon arrival to recovery area. After awakening, abdominal discomfort will be assessed for children who are able to do so, and the assessment will be repeated at discharge from the facility. FLACC will be used for all children with appropriate developmental status, age 5 years and older for normal children. After discharge, the parents will complete an additional brief pain assessment at home at 4 hours after discharge. For those who had an abdominal girth increase of at least 10% from baseline, abdominal girth will be re-measured at home, at 4 hours after discharge.

We will use the non-verbal FLACC scale for children unable to verbally report pain using the visual scale.

Parents will report pain and abdominal girth data done at home by returning a pre-stamped postcard. Those who do not communicate this information will be called by a member of the research team for this information after five working days.

We hypothesize, based on adult and few pediatric studies, that post-procedure abdominal discomfort will be significantly decreased in the CO2 group, and that CO2 will be shown to be safe and effective for endoscopic insufflation.

Efficacy of insufflation will be assessed by the endoscopist immediately after the procedure using a 5-point Likert scale.

Arms: arm 1: In this arm of patients, air which is currently used as standard of care will be used for insufflation arm 2: in this arm of patients, carbon dioxide (CO2) will be used for insufflation during endoscopy
Interventions: intervention 1: Carbon dioxide (CO2) gas insufflation intervention 2: Air insufflation
Intervention descriptions: intervention 1: CO2 gas use for insufflation during endoscopy instead of air insufflation intervention 2: Air insufflation is the standard of practice (used in the control arm)

Protocol documents:
Prot_002.pdf: 
Cover page 
Title: Safety and Efficacy of CO2 for Endoscopy 
NCT 03287687 
1/1/2020 
 
 
Study Protocol: 
The current literature in pediatric endoscopy does not include evidence on effectiveness and 
safety of CO2 insufflation in procedures besides colonoscopy and does not include children in 
the younger age range. Esophagogastroduodenoscopy procedures (EGDs) are much more 
commonly performed procedures in children so it is important to assess these clinical scenarios 
before adopting CO2 insufflation as the main mode of practice.   
Our study aimed to address these knowledge gaps by enrolling younger children, including 
infants, and a wide variety of endoscopic procedures, including EGDs and percutaneous 
endoscopic gastrostomy (PEG) tube placement.  
 
Study Design 
This is a double-blinded, prospective, randomized study comparing CO2 and air for insufflation 
during endoscopic procedures in pediatric patients performed in the Pediatric Endoscopy Unit at 
the University of Iowa Children’s Hospital.  The study was approved by the Institutional Review 
Board (IRB) at the University of Iowa  
 
Subjects and Randomization 
Patients aged 6 months to 21 years undergoing diagnostic or therapeutic endoscopic procedures 
were offered participation.  These procedures included EGD, colonoscopy, PEG tube placement, 
and endoscopic PEG tube exchange.  Exclusion criteria included non-English-speaking families 
needing an interpreter and patients with significant chronic lung disease, such as 
bronchopulmonary dysplasia, severe asthma, or cystic fibrosis.  Consents and assents were 
obtained proper to enrollment. 
Both the patient and endoscopist were blinded to the arm of study. Randomization was done by 
the procedure suite nurse using a sealed envelope system. To maintain allocation concealment, 
the nurse set up the equipment to deliver CO2 or air then covered the relevant equipment settings 


to assure complete blinding of the endoscopist and others in the room. The equipment was 
adjusted to deliver CO2 or air at a similar flow rate. 
Data Collection 
Collected data included patient demographics (age, sex, growth parameters), procedure 
indication, patient’s overall health status based on the American Society of Anesthesiologists 
(ASA) classification, endoscopy-related characteristics (duration, trainee vs faculty endoscopist 
and complications) and anesthesia-related parameters (duration, medication dosing, and 
complications). Vital signs, including EtCO2, heart rate, respiratory rate, oxygen saturation, and 
blood pressure were monitored and automatically recorded continuously throughout the 
procedure, according to the anesthesia protocol. EtCO2 was monitored and continuously 
sampled by nasal prong or via capnography for intubated patients. 
 
Outcome Measures 
Patient discomfort was assessed using 3 scales: 
1. Face, Legs, Activity, Cry, and Ability to be Consoled (FLACC) behavioral assessment score 
2. Global Parent Perception of Pain (PPP) scale 
3. FACES scale; for neurodevelopmentally appropriate children 5 years and older. 
 
Pain 
FLACC at baseline, within 15 minutes of return to recovery area, when awake. FLACC scores 
categorized as no pain, mild pain, moderate to severe pain, very severe pain or worst pain ever 
PPP at baseline, when awake and 4 hours post discharge. PPP scores categorized as no pain, mild 
pain, moderate to severe pain, very severe pain or worst pain ever 
VAS at baseline, when awake and 4 hours post discharge. VAS scores categorized as no pain, 
mild pain, moderate to severe pain, very severe pain or worst pain ever 
Abdominal girth at baseline, after procedure, at discharge, and 4 hours post discharge 
 
Endoscopist assessment  
Perceived ease of inflation: easy or average, mild difficulty, very difficult 


Perceived patient discomfort: comfortable or average discomfort, above average discomfort 
Endoscopist guess of inflation gas 
 
Abdominal girth was measured by the same nurse at the level of the umbilicus before the 
procedure, immediately upon arrival in the recovery area after the procedure, and again just 
before discharge. Patients were sent home with a tape measure and a postage-prepaid response 
card on which they recorded the abdominal girth four hours after completion of the procedure. 
Parents were also asked to indicate if the patient had experienced belching, bloating or 
flatulence.   
 
Sedation for all procedures was provided by an anesthesia team lead by a pediatric 
anesthesiologist, who was also blinded to the study group allocation. For most patients, 
anesthesia consisting of a continuous propofol infusion without an advanced airway such as 
endotracheal intubation was used. When indicated, based on the patient and procedure 
characteristics, general anesthesia with endotracheal intubation was occasionally used. 
Data were entered into Redcap software. Adverse events defined as any undesired event 
occurring during endoscopy, and sedation-related complications such as hypoxia and aspiration 
were reported at regular intervals to the IRB during enrollment. 

SAP_003.pdf: 
Cover page 
Title: Safety and Efficacy of CO2 for Endoscopy 
NCT 03287687 
12/1/2017 
 
STATISTICAL ANALYSIS PLAN 
Cohort demographics were analyzed using descriptive statistics. Continuous variables were summarized 
using the mean, and standard deviation (SD) or median and interquartile range (IQR) and compared 
using the Student t-test for normally-distributed data and the Wilcoxon rank-sum test for data with 
skewed distribution. Categorical variables were summarized using counts and frequency as a percentage 
and compared using Chi-Square test or Fisher's exact test. A p-value <0.05 was considered statistically 
significant. Statistical analysis was performed with SAS 9 statistical software (SAS Institute, Cary, NC). 
Power calculation 
The number of subjects enrolled was based on other studies, with the assumption that up to 20% of 
patients in the air insufflation group would report some degree of abdominal pain after endoscopy. We 
estimated that the frequency of reported abdominal pain in the CO2 group would be one-fourth of that 
(5%) seen in the air group. To accomplish this, a minimum total of 150 subjects would be needed 
(significance level of 5%, power of 80%) so we aimed to recruit a total of 180 patients (enrollment ratio 
of 1).