Is End Tidal CO2 Level Elevation During Upper Endoscopy With CO2 Gas Insufflation Physiologically Significant
Phase: NA
Conditions: Endoscopy
Sponsor: University of Nebraska

Title: Is end tidal CO2 level elevation during upper 
endoscopy with CO2 gas insufflation 
physiologically significant? 
 
 
 
 
 
 
NCT Number: NCT04541667 
 
 
 
 
 
 
 
Document Date: 6/3/2021 

Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 1 of 32
Biomedical
SECTION I
Therapeutic/Non-Therapeutic  
Does your research involve a drug, medical device, technique or other intervention or
strategy (including means like diet, cognitive therapy, behavioral therapy, exercise) to
diagnose, treat or prevent a particular condition or disease: "THERAPEUTIC
RESEARCH"?
Yes
1. Title of Protocol:  
Is end tidal CO2 level elevation during upper endoscopy with CO2 gas insufflation
physiologically significant?
2. Responsible Personnel:  
A. Principal Investigator (PI):
Dike, Chinenye R - Pediatrics Gastroenterology - 402-955-5150 - chinenye.dike@unmc.edu
- alt #: 402-955-5710 - degree: MBBS - address: CHMC-IHE 8200 Dodge Street, IHE6 (Zip
2155) - phone: 402-955-5150
B. Secondary Investigator (SI):
Huang Pacheco, Andrew Steve S - Pediatrics Gastroenterology - 402-955-5700 -
a.huangpacheco@unmc.edu - alt #: 612-800-1627 - degree: MD - address: CHMC-IHE
8200 Dodge Street, IHE6 (Zip 2155) - phone: 402-955-5700
Shukry, Mohanad - Anesthesiology - 402-955-4385 - mohanad.shukry@unmc.edu - alt #:
402-955-8581 - degree: MD/NE - address: BTH 2017 UNMC Midtown (68114-4455) -
phone: 402-955-4385
C. Participating Personnel:
Choudhry, Ojasvini C - Pediatrics Gastroenterology - 402-955-5700 -
ojasvini.choudhry@unmc.edu - alt #: 402-305-5484 - degree: MBBS - address: CHMC-IHE
8200 Dodge Street, IHE6 (Zip 2155) - phone: 402-955-5700
Freestone, David J - Pediatrics Gastroenterology - 402-955-5718 -
david.freestone@unmc.edu - alt #: 801-309-0615 - degree: DO - address: CHMC-IHE 8200
Dodge Street, IHE6 (Zip 2155) - phone: 402-955-5718
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Institutional Review Board (IRB)
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Kusek, Mark Edward - Pediatrics Gastroenterology - 402-955-5712 - mkusek@unmc.edu -
alt #: 402-955-5712 - degree: MD - address: CHMC-IHE 8200 Dodge Street, IHE6 (Zip
2155) - phone: 402-955-5712
Lyden, Elizabeth Ruby - COPH Biostatistics - 402-559-6061 - elyden@unmc.edu - alt #:
402-559-6061 - degree: MS - address: MCPH 3046 UNMC Midtown (Zip 4375) - phone:
9-6061
Quiros, Ruben E - Pediatrics Gastroenterology - 402-559-8968 - rquiros@unmc.edu - alt #:
402-955-5400 - degree: MD - address: UT1 5135 UNMC Midtown (Zip 2161) - phone:
9-8968
D. Lead Coordinator:
Roberts, Evan Michael - Child Health Research Institute - 402-836-9742 -
evan.roberts@unmc.edu - alt #: 402-547-1954 - degree: MBA, BS - address: CHMC-IHW
8200 Dodge Street, IHW5 (Zip 5456) - phone: 402-836-9742
E. Coordinator(s):
Abraham, Kym L - CHRI Administration - 402-559-2977 - kabraham@unmc.edu - alt #:
402-559-2977 - degree: RN, BSN - address: CHMC-IHW 8200 Dodge Street, IHW5 (Zip
5456) - phone: 9-2977
Hoover, Denise M - CHRI Administration - 402-559-0686 - dmhoover@unmc.edu - alt #:
402-559-0686 - degree: BS - address: CHMC-IHW 8200 Dodge Street, IHW5 (Zip 5456) -
phone: 9-0686
F. Data/Administrative Personnel:
Fischer, Laura Jean - CHRI Administration - 402-836-9762 - laura.fischer@unmc.edu - alt #:
-- - degree: MPH - address: CHMC-IHW 8200 Dodge Street, IHW5 (Zip 5456) - phone:
402-836-9731
Servais, Ashley Nicole - CHRI Administration - 402-559-2511 - ashley.servais@unmc.edu -
alt #: 402-559-2511 - degree: MPH - address: CHMC-IHW 8200 Dodge Street, IHW5 (Zip
5456) - phone: 9-2511
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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
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No
C. Does UNMC, TNMC, CHMC or UNO serve as the lead site with responsibility for data
and/or safety monitoring?
No
D. Does this study involve any international sites where the PI will either; 1) conduct 2)
supervise or 3) receive / ship HBM or data to / from UNMC?
No
8. Principal Investigator Assurance
The PI understands and accepts the following obligations to protect the rights
and welfare of research subjects in this study:  
I certify that:
I have carefully reviewed this application and all supporting documents. I have
determined that the application is accurate, complete and ready for submission
to the IRB.
I, and all listed research personnel, have the necessary qualifications, expertise,
and hospital credentials to conduct this study in a manner which fully protects
the rights and welfare of research subjects.
There are, or will be, adequate resources and facilities to safely initiate, carry
out and complete this research at the study sites specified in Section I.7. This
includes sufficient staff, funding, space, record keeping capability, and
resources necessary to address adverse events and any unanticipated
problems involving risk to the subject or others. If the necessary resources
become unavailable I will promptly notify the IRB.
All listed research personnel, including external investigators, will be given a
copy of the final IRB approved application and any other relevant study-related
documents in accordance with their defined responsibilities.
All listed research personnel, including external investigators, will be notified
promptly of any changes in protocol, in accordance with their defined
responsibilities.
Research personnel, including data and administrative personnel who have
access to protected health information (PHI) or subject identifiers will have
adequate training in confidentiality and protection of PHI.
The minimum amount of protected health information (PHI) or other identifiers
necessary will be used and disclosed to conduct this research study (if
applicable). I will implement reasonable safeguards to protect the PHI/identifiers
at all times.
I and all other personnel listed in Section I.3A-E of the IRB Application have
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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
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disclosed all potential financial conflicts of interest as required and are in full
compliance with the UNMC Conflict of Interest Policy #8010 and HRPP Policy. I
further certify that all potential financial conflicts of interest are appropriately
managed in order to ensure protection of the rights and welfare of subjects.
I recognize that:
As the PI it is my responsibility to ensure that this research and the actions of
all research personnel involved in conducting the study will comply fully with
the IRB-approved protocol (including all amendments), all applicable federal
regulations, state laws, and HRPP policies.
It is my responsibility to ensure that valid informed consent/assent will be
obtained, as appropriate, from all research subjects or their legally authorized
representative(LARs).
I will:
Ensure that all research personnel involved in the process of consent/assent
are properly trained and are fully aware of their responsibilities relative to the
obtainment of informed consent/assent according to federal regulations, state
laws, and HRPP policies.
Promptly inform the IRB of internal adverse events, as well as any unanticipated
problems involving risk to the subjects or to others, as required within the time
frame defined by HRPP policies. I will analyze each internal adverse
event/reported problem to determine if it impacts the risk-benefit relationship of
the study, the safety of the subjects, or informed consent.
Analyze each MedWatch/safety report to determine if it impacts the risk/benefit
relationship of the study, the safety of the subjects, or informed consent.
Promptly submit external adverse event reports in accordance with HRPP
policies.
Promptly inform the IRB if I become aware of 1) any complaints from research
subjects, LARs, or others about research participation, 2) violations of federal
regulations or state law, 3) violations of the HIPAA Rule, or 4) violations of
HRPP policies.
Promptly inform the IRB of the results of external audits performed by
sponsors, Contract Review Organizations (CROs), cooperative groups, FDA, or
other external groups.
Not initiate any change in protocol without IRB approval except when it is
necessary to reduce or eliminate a risk to the subject, in which case the IRB will
be notified as soon as possible.
Promptly inform the IRB of any significant negative change in the risk/benefit
relationship of the research as originally presented in the protocol and
approved by the IRB.
Maintain all required research records on file and I recognize that
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Institutional Review Board (IRB)
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SECTION II
PROTOCOL ABSTRACT
1. Provide a brief (less than 2500 characters) abstract of the research protocol.
(2500 characters)
This summary should include: 1)) a brief description of the purpose of the study, 2)
eligibility criteria, 3) interventions and evaluations and 4) follow-up.
Luminal inflation is essential for adequate visualization and endoscope advancement during
endoscopy. Although air has previously been the standard gas used, CO2 is increasing
preferred in adult endoscopy centers, due to reports of decreased post-procedural
abdominal discomfort compared to air. Few published studies in children demonstrated
decreased abdominal discomfort with use of CO2, but safety concerns for its use in pediatric
endoscopy remain. During my fellowship, I conducted a randomized, double-blinded study
comparing the safety and efficacy of CO2 and air for all procedures. This study showed that
CO2 use for insufflation in pediatric upper endoscopy was associated with multiple transient
elevations in end-tidal CO2, in non-intubated patients. It is important to investigate whether
the observed elevations in end-tidal CO2 may be actually absorbed or just eructated.
Therefore, with this study we plan to: (I) compare the end tidal CO2 levels observed during
upper endoscopy in children managed with endotracheal intubation or laryngeal mask
airway using CO2 versus air and compare how these levels deviate from the pre-procedure
baseline levels. (ii) Observe whether there are particular pre-procedural risk factors that
predispose children to hypercapnia with CO2 use during upper endoscopy. (iii) Determine if
carbon dioxide gas use for insufflation results in significant changes in the minute
ventilation. This is a Double-blinded, prospective, randomized study of all pediatric patients
undergoing procedures involving upper endoscopy in the Childrens Hospital & Medical
Center. Children from 6 months to 19 years of age undergoing upper endoscopy related
procedures. Randomization will for intubated patients who require an advanced airway
(endotracheal intubation or laryngeal mask airway) 1:1 for air or CO2. Risks assessed
before the procedure will include past medical history, American Society of Anesthesiology
(ASA) classification. Vital signs will be recorded before the procedure, throughout the
procedure and after the procedure until fully awake. While in the procedure room, end-tidal
CO2 level and minute ventilation (tidal volume X RR) will be continuously recorded. Patients
and legal guardians who decline participation in the study and patients with chronic
respiratory disease (defined as severe asthma, bronchopulmonary dysplasia and CF related
pulmonary disease), cyanotic heart disease and ASA status >/= 3 will be excluded from the
study.
PURPOSE OF THE STUDY AND BACKGROUND
2. Purpose of the Study  
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What are the specific scientific objectives of the research?
(I) Compare the end tidal CO2 levels observed during upper endoscopy in children
managed with endotracheal intubation or laryngeal mask airway using CO2 versus air and
compare how these levels deviate from the pre-procedure baseline levels.
(ii) Observe whether there are particular pre-procedural risk factors that predispose children
to hypercapnia with CO2 use during upper endoscopy.
(iii) Determine if carbon dioxide gas use for insufflation results in significant changes in the
minute ventilation
3. Background and Rationale  
Describe the background of the study. Include a critical evaluation of existing
knowledge, and specifically identify the information gaps that the project is intended to
fill.
Luminal inflation is crucial for proper visualization and advancement of the endoscope
during endoscopy (2). Air has been the standard insufflation gas during endoscopy.
However, multiple adult studies have demonstrated decreased abdominal discomfort and
increased efficacy with carbon dioxide (CO2) use (3-9). Therefore, many adult endoscopy
centers now use carbon dioxide routinely for endoscopy insufflation. Only 3 pediatric studies
exist on the use of CO2 for colonoscopy (10-12). Two of these studies demonstrated that
CO2 use was associated with decreased abdominal discomfort after colonoscopy. During
my fellowship, we showed, through a recent survey of fellow trainees across North America,
that though air remains the predominant gas for insufflation during endoscopy in pediatrics,
CO2 is increasingly being used. We have also demonstrated through our study that CO2 use
during upper endoscopy in children is associated with significant elevations in end-tidal
CO2 levels. This finding is likely the result of eructated CO2 used during in upper endoscopy,
as most of the patients in our study did not have the airway isolated by intubation. It is also
possible that there is excessive direct absorption of CO2 from the upper GI tract. This study
has been written up and the manuscript is awaiting editorial decision. It has been presented
at a national conference (Digestive Disease Week, San Diego; May 2019). In a follow up
study, CO2 use during upper endoscopy was not associated with significant elevations in
transcutaneous CO2 level.
We hypothesize that transient elevations in end tidal CO2 level observed with CO2 use
during upper endoscopy is due to eructation of the instilled gas and will be eliminated by
protection of the airway. We also hypothesize that there will be no changes in minute
ventilation associated with CO2 use during upper endoscopy in patients who are intubated
(via endotracheal tube or laryngeal mask airway).
**Amendment- We will now enroll 19 year old's (Adults) into this study and also Spanish
Speaking subjects.
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Institutional Review Board (IRB)
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CHARACTERISTICS OF THE SUBJECT POPULATION
4. Accrual  
A. Is this study conducted solely at sites under the oversight of the UNMC IRB (e.g.
UNMC, Nebraska Medicine, CHMC, UNO)?
Yes
1. How many subjects will need to be consented (per group, as applicable) in order to
achieve the scientific objectives of the research?
230 subjects total ( 100 each group). This extra 30 subjects will allow for screen failures that
occur on the study for example change in plans from use of ETT or LMA to nasal cannula in
the procedure room after subjects may have been consented. They will not be randomized
and need to be replaced on the study.
2. What is the statistical or other justification for the total number of subjects described
above?
Sample sizes of 75 per group achieve 80% power to detect a difference of 2 mmHg
between the null hypothesis that both group mean EtCO2 measurement over the length of
the monitoring period are 37.2 mmHg and the alternative hypothesis that the mean of the
CO2 group is 39.2 with an estimated within group standard deviation of 4.3 mmHg and with
a significance level (alpha) of 0.05 using a two-sided two-sample t-test. To adjust for the
possibility of a 25% drop out rate 100 patients per group will be enrolled.
We have also allowed 30 extra subjects due to some screen failures we have had.
5. Gender of the Subjects  
A. Are there any enrollment restrictions based on gender?
No
6. Age Range of Subjects  
A. Will adults be enrolled ?
Yes
1. What is the age range of the adult subjects?
The adults in this study will be 19 years old.
2. What is the rationale for selecting this age range?
As we were enrolling subjects into this study we noticed we had several 19 year old subjects
still being seen by our GI Department. Therefore, they would qualify for the study. We did
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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 11 of 32
not want to exclude them from participating in the study. The research will be conducted in
children aged 6 months to 19 years to determine if end tidal CO2 remains persistently
elevated in intubated children undergoing upper endoscopy with CO2 insufflation and to
determine if there are changes in minute ventilation with CO2 use during upper endoscopy.
B. Will children (18 years of age or younger) be included in this research?
Yes
1. What is the justification for inclusion of children in this research?
The research will be conducted in children aged 6 months to 18 years to determine if end
tidal CO2 remains persistently elevated in intubated children undergoing upper endoscopy
with CO2 insufflation and to determine if there are changes in minute ventilation with CO2
use during upper endoscopy.
2. What is the age range for the child subjects, and what is the justification for
selecting this age range?
6 months to 18 years. The justification for this age range is that carbon dioxide is
increasingly used for insufflation in pediatric endoscopy. Though there is an increase in its
use, the deleterious effects of carbon dioxide insufflation and absorption in this age group
are not known. This highlights the importance on further studies in this age group to
determine if this elevated end tidal CO2 level can be avoided by intubation, if there are
changes in the minute ventilation with CO2 use and if it is physiologically significant and
should be used with caution.
3. Will this study enroll wards of the state?
No
7. Race and Ethnicity  
Are there any subject enrollment restrictions based upon race or ethnic origin?
No
8. Vulnerable Subjects  
A. Will prisoners be included in the research?
No
B. Select from the list all of the vulnerable populations that will specifically be recruited
to participate in this research.
Decisionally-impaired persons 
Critically ill patients 
Version 7 - PROTOCOL # 0632-19-FB
  Page 11 of 32

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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 14 of 32
No
METHODS AND PROCEDURES
12. Methods and Procedures Applied to Human Subjects  
A. Are there any evaluations or tests that will be performed for the purpose of
determining subject eligibility which would not be routinely conducted as part of
standard clinical care of the prospective subject?
No
B. Describe the research plan, including all procedures, interventions, evaluations and
tests.
This is a double blinded prospective randomized study of pediatric patients undergoing
procedures involving upper endoscopy in Childrens Hospital of Omaha.
Children from 6 months to 19 years of age who meet the inclusion criteria would be
approached for enrollment.
Consent will be obtained and signed by all legal guardians or parents
A verbal explanation of the study will be done to all children who are 7 years of age
and neuro developmentally appropriate up to age 12 and verbal assent will be
obtained by children who agree to participate in the study.
Children who are 13 years to 19 years of age will be required to sign the consent
form with their parents or legal guardians if they are willing to participate in the study.
Patients will be randomized 1:1 for air and CO2 using a card system by the
endoscopy room/procedure nurse.
The procedure room/ endoscopy room nurse will then randomize the patients as
described below:
The nurse will receive 4 envelopes.
Each envelope will contain 25 cards marked "Air" and 25 cards marked "CO2;
Therefore, there will be a total of 100 cards marked "Air" and 100 cards marked
"CO2" in all the 4 sets of envelopes
After it has been determined that the patient can be included in the study and the
consents have been signed; the procedure nurse will open the first envelope and
randomly pick either CO2 or Air. She will then set up the insufflation gas based on
the gas picked. She will cover the air and CO2 dispensing machine so that the
patient, anesthesiologist and endoscopist are all blinded to the type of insufflation
gas used during the procedure. She will complete randomization using the cards in
each set of envelope before moving to the next set. The endoscopy room/procedure
room nurse will keep a record of patients randomized into the air or CO2 group in a
locked cabinet. She will assign arbitrary letters or numbers to the gas used so that
the biostatistician who will perform the interim analysis will be blinded to the arm of
Version 7 - PROTOCOL # 0632-19-FB
  Page 14 of 32

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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 16 of 32
used so that the biostatistician who will perform the interim analysis will be blinded to the
arm of study as well.
We will perform an interim analysis after enrolling 100 patients (50 patients in the Air group
and 50 patients in the CO2 group)
D. Identify:
1. All procedures, interventions, evaluations and tests performed solely for research
purposes (eg, administration of an investigational drug or a new psychological
assessment instrument; randomization)
The consenting process for the study is only done for research purposes. Also, the only
other procedures that would be performed solely for research purposes is the randomization
of enrolled patients to air or CO2 gas for insufflation during the endoscopic procedure.
Although, air is the standard insufflation agent for endoscopy in pediatrics; many centers
now routinely use carbon dioxide given the vast data in adults showing decreased
abdominal discomfort and distension with carbon dioxide use.
In our center, we routinely use CO2 for colonoscopy and most endoscopists use air for
upper endoscopy.
2. All procedures, interventions, evaluations and tests performed for clinical indication
but more frequently than they would be if the subject was not participating in the
research (eg, extra blood tests; additional radiology exams)
There will be no extra blood tests or additional radiology exams
E. Describe briefly the statistical methods used to analyze the data (or reference the
appropriate section of the detailed protocol or grant).
Continuous data will be reported as means with standard deviations, or medians with
interquartile ranges depending if variable has normal or skewed distribution respectively.
Categorical variables will be described by percentages and proportions. Comparisons of
continuous data will be performed using the t-test or Wilcoxon signed-ranks test. Categorical
variables will be compared using the chisq test or Fishers exact test. A probability value
<.05 will be considered significant. Statistical analysis will be performed using SAS 9
statistical software (SAS Institute, Cary, NC) or Graph Pad Prism 7 for Windows (Graph pad
Software, San Diego, CA).
Descriptive statistics, including counts and %, means, SD, medians, will be used to
summarize patient characteristics, procedural, anesthesia and safety outcomes for the two
groups. Patient characteristics, Patient safety outcomes;(MV, EtCO2), procedural, and
anesthesia outcomes will be compared between the groups using the independent sample t-
test or Mann-Whitney test or Fishers exact test as appropriate to the data. Changes in these
safety outcome measurements across the monitoring period between the two groups using
a mixed effects model will be considered
Version 7 - PROTOCOL # 0632-19-FB
  Page 16 of 32

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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 21 of 32
audits and specify the audit frequency.
The principal investigator will conduct auditing of the data after every 50 subjects enrolled in
the study.
D. Describe the specific subject withdrawal criteria.
If any potential risks is observed during the procedure such as with evidence of respiratory
distress or other potential CO2 complications, the endoscopist will be unblinded; and CO2
will be turned off if it is being used and the subject will be withdrawn from the study.
E. Describe the stopping rules for the research (e.g., the specific criteria for halting or
early termination of the study).
The research will be terminated early if there are significant reports of adverse events
reported in an arm of the study. It will also be stopped early if significant results are reported
during the interim analysis after enrollment of the first half of the subjects are enrolled. .
F. Describe plans and resources available to promptly address any subject injury.
Physicians will be immediately available throughout the procedure and prior to discharge
from the procedure suite. They will also be available by phone 24/7/365.
19. Potential Benefits to the Subject  
Is there the prospect for direct benefit (eg, research on diagnosis or treatment of
disease)?
Yes
Describe potential benefits to the subjects that may reasonably be expected from
participation in the research, if any. If there are therapeutic and non-therapeutic
components of the research, address anticipated benefits to subjects that may
reasonably be expected from each of these components.
Patients randomized to the CO2 arm may benefit from less procedure pain when used
during colonoscopy as a few pediatric studies have shown these benefits with the use of
CO2 for colonoscopy.
20. Potential Benefits to Society  
Describe the potential benefits to society that may reasonably be expected to result
from this research.
Publishing this work may encourage the use of safe and best insufflation practices in all
children. If elevated end tidal CO2 levels persist despite protection of the airway, then CO2
use in children may be limited or restricted to only colonoscopy.
Version 7 - PROTOCOL # 0632-19-FB
  Page 21 of 32

Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
  Page 22 of 32
ALTERNATIVES TO PARTICIPATION
21. Alternatives to Participation  
1. Describe the likely care the subject would receive at this institution were he/she not
to participate in the research. If there are more than one reasonable courses of
treatment briefly describe.
There is currently no standard of care at this institution regarding use of "CO2" versus "air
"as the insufflation gas. The gas of choice to be used is usually at the discretion of the
endoscopist and the availability of carbon dioxide gas in the procedure room or OR.
2. Is the potential benefit of the research at least as good as the potential benefits of
the alternatives described above?
Yes
3. Are there any reasonably available alternatives outside this institution which would
have the potential for providing benefit to the subjects outside the research context?
No
4. Would any of the study procedures or courses of treatment in the protocol be
available to the subject if they elected not to participate?
Yes
a. Explain.
If the subject refuses to participate in the study and requests carbon dioxide gas use for
endoscopic insufflation based on the varst adult studies and limited pediatric studies; if
carbon dioxide gas is available and the endoscopist wishes to use it despite its limited data
on safety in children; it could be potentially offered to a subject who refuses to participate in
the study as there is no standard of care at CHMC for insufflation gas. On the other hand,
air is most readily available and if a subject requests air used for endoscopic insufflation,
this could be used. However, subject may not benefit from the potential benefits of
decreased post procedure pain associated with CO2 use reported in the few pediatric
studies that compared CO2 use to air in colonoscopy.
5. Would the research intervention be available outside the context of research?
No
6. Are there any treatments that the subject would be denied as a consequence of
participating in research that he/she would have received had he/she not participated?
No
Version 7 - PROTOCOL # 0632-19-FB
  Page 22 of 32

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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
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29. Process of Informed Consent  
A. When will the prospective subject/parent(s)/guardian(s)/LAR be approached relative
to their/the subject's actual participation in the study?
Prospective subjects parents or legal guardians will be informed of the study at the time the
subject is seen in the clinic or in the inpatient setting or when the decision is being made to
schedule an endoscopic procedure. This is usually days or weeks to months prior to the
procedure or actual study date.
B. Where will informed consent be obtained, and how will the environment be
conducive to discussion and thoughtful consideration?
Consent procedures will be performed in a private room, either in the exam room in the
clinic or in the private inpatient room or a privater pre-procedure room . Parents and legal
guardians will be given the time to fully understand the study before the consent is obtained.
It is possible that we will let the families know our GI research coordinator will be following
up with them and give the names of the potential subjects to our research coordinator and
they will follow-up with the family and e-mail them the consent form so the family can review
the consent form in private at home. The research study coordinator would then follow-up
with the family to see if they would like to participate in the study or not.
C. Who will be involved in the process of consent and what are their responsibilities?
The principal investigator, some of the co-investigators (A.H. D.F.) and study coordinators
will be involved in the consenting process. The other responsible personnel may inform the
patients about the study but will not be involved in the consenting process.
D. How much time will be allotted to the process of consent?
When possible, we will discuss the study and obtain consent in the clinic prior to the day of
the procedure or in the inpatient setting. Otherwise, consent will be obtained before the
procedure; family members present will be included in the discussion. Duration of the
consenting process will vary from one family to the other depending on how long it takes to
answer all their questions. As much time that is needed will be allowed for the consenting
discussion and process.
E. How will the process of consent be structured for subjects who are likely to be more
vulnerable to coercion or undue influence?
All patients will have been seen by a member of our clinical team (Pediatric
Gastroenterology) in the clinic prior to the procedure or in the inpatient setting. Patients who
need a diagnostic or therapeutic endoscopy will be scheduled for the procedure. The need
for an endoscopic procedure will identify them to the research team as a candidate. In some
cases, the enrollment will happen in the clinic at the time the need for endoscopy is
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Institutional Review Board (IRB)
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identified, particularly when a research team member is seeing the patient. In other cases,
potential subjects will be identified by review of scheduled procedures on the day of the
procedure. Subjects who have not been offered participation in the study in the clinic will
then be approached in the procedure unit on the day of the procedure by a member of the
research team.
During enrollment, we will emphasize that we will provide the same quality of care
regardless of their participation, and that no stigma will be attached to them if they prefer not
to give consent.
We will involve all family members present during the consent process and will explain the
consent form in detail.
Prior to signing the consent, we will ask if they have any questions and if they have fully
understood the study.
We will discuss their options such as not participating if they choose.
We will also assess if a subject advocate is needed and should one be needed then one will
be appointed.
F. Will non-English speaking subjects be enrolled in this research?
Yes
Describe the plan to conduct the process of informed consent in the language of the
subject/parent(s)/guardian(s)/LAR
We have developed Spanish consents for this study. All of the subjects are appointed an
interpreter if Spanish speaking that the CARES RN works with to see the patient. The
Interpreter will also be utilized to approach the family and subject for this study. Dr. Huang is
fully fluent in Spanish so he will not use an interpreter. The study coordinator will ensure an
interpreter is utilized when Dr. Huang is not available.
G. How will it be determined that the subject/parent(s)/guardian(s)/LAR understood the
information presented?
At the end of the consenting process, subjects, parents and legal guardians will be asked a
series of questions at the appropriate grade level to ensure they full understand the study.
We will also ask them if they have any questions. The consent form will be only signed
when they have fully understood the study and voluntarily wish to participate in the study.
30. Documentation of Informed Consent and Assent  
Select who will obtain consent from the subject/parent(s)/LAR.
Choudhry, Ojasvini C
Dike, Chinenye Rebecca
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Institutional Review Board (IRB)
IRB PROTOCOL # 0632-19-FB
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1. Provide justification.
To protect the integrity of the research and the results; blinding will continue until statistical
analysis has been done before the arm of randomization will be unmasked. Individual
patients will not be informed. However, the results of the research will be presented in
scientific meetings and published. The results of this research will help guide our practice on
the safety of CO2use for insufflation during upper endoscopic related procedures in children.
RESOURCES
33. Describe the resources available to safely conduct this study at each study
sites specified in Section I.7.  
The availability of physicians (anesthesiologists and pediatric gastroenterologists) at CHMC
and most of the pediatric GI procedures are performed at CHMC makes it the ideal site to
safely and successfully conduct this study
LITERATURE REVIEW
34. References  
Provide a full listing of the key references cited in the background (Section II.3). The
references should clearly support the stated purpose of the study.
1 Steppan J, Hogue CW, Jr. Cerebral and tissue oximetry. Best Pract Res Clin Anaesthesiol
2014;28(4):429-39.
2 Lo SK, Fujii-Lau LL, Enestvedt BK, et al. The use of carbon dioxide in gastrointestinal
endoscopy. Gastrointest Endosc 2016;83(5):857-65.
3 Chen SW, Hui CK, Chang JJ, et al. Carbon dioxide insufflation during colonoscopy can
significantly decrease post-interventional abdominal discomfort in deeply sedated patients:
A prospective, randomized, double-blinded, controlled trial. J Gastroenterol Hepatol
2016;31(4):808-13.
4 Liu X, Liu D, Li J, et al. [Safety and efficacy of carbon dioxide insufflation during
colonoscopy]. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2009;34(8):825-9.
5 Lynch I, Hayes A, Buffum MD, et al. Insufflation using carbon dioxide versus room air
during colonoscopy: comparison of patient comfort, recovery time, and nursing resources.
Gastroenterol Nurs 2015;38(3):211-7.
6 Memon MA, Memon B, Yunus RM, et al. Carbon Dioxide Versus Air Insufflation for
Elective Colonoscopy: A Meta-Analysis and Systematic Review of Randomized Controlled
Trials. Surg Laparosc Endosc Percutan Tech 2016;26(2):102-16.
7 Riss S, Akan B, Mikola B, et al. CO2 insufflation during colonoscopy decreases post-
interventional pain in deeply sedated patients: a randomized controlled trial. Wien Klin
Wochenschr 2009;121(13-14):464-8.
8 Sajid MS, Caswell J, Bhatti MI, et al. Carbon dioxide insufflation vs conventional air
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Institutional Review Board (IRB)
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insufflation for colonoscopy: a systematic review and meta-analysis of published
randomized controlled trials. Colorectal Dis 2015;17(2):111-23.
9 Singh R, Neo EN, Nordeen N, et al. Carbon dioxide insufflation during colonoscopy in
deeply sedated patients. World J Gastroenterol 2012;18(25):3250-3.
10 Homan M, Mahkovic D, Orel R, et al. Randomized, double-blind trial of CO2 versus air
insufflation in children undergoing colonoscopy. Gastrointest Endosc 2016;83(5):993-7.
11 Kresz A, Mayer B, Zernickel M, et al. Carbon dioxide versus room air for colonoscopy in
deeply sedated pediatric patients: a randomized controlled trial. Endosc Int Open
2019;7(2):E290-e97.
12 Thornhill C, Navarro F, Alabd Alrazzak B, et al. Insufflation With Carbon Dioxide During
Pediatric Colonoscopy for Control of Postprocedure Pain. J Clin Gastroenterol 2017.
13 Eastwood GM, Tanaka A, Bellomo R Cerebral oxygenation in mechanically ventilated
early cardiac arrest survivors: The impact of hypercapnia. Resuscitation 2016;102(11-6.
14 Erdogan S, Oto A, Bosnak M Reliability of cerebral oximeter in non-invasive diagnosis
and follow-up of hypercapnia. Turk J Pediatr 2016;58(4):389-94.
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