CO2 Insufflation During Double Balloon Enteroscopy
Condition: Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire
      small bowel. In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel
      to secure good visualisation. All endoscopes used for GI endoscopy provide a gas insufflation
      unit. Currently, air is used for this purpose in more than 90% of centres throughout the
      world. The use of air, however, is far from ideal to use for insufflation in GI endoscopy.
      After GI endoscopy, significant amounts of air are usually retained in the bowel segment
      inspected (5). This air has to pass the GI tract and exit physiologically through the rectum.
      Thus, abdominal pain and discomfort during and after the examination due to the retention of
      air has been shown to be very common during and after endoscopic procedures (5-9).

      Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes,
      several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to
      result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in
      several randomised trials (6-9). In these studies, CO2 insufflation almost completely reduced
      procedure-related pain and discomfort.

      To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is
      a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are
      insufflated during the procedure, leading to significant distension of the small bowel during
      and after the examination.

      One of the main technical difficulties in DBE is the formation of small bowel loops and scarp
      angels during deep intubation of the endoscope. These loops and angels are the major
      restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced
      in air-distended bowel segments.

      The aim of the present study is to examine whether CO2 insufflation leads to a reduction of
      abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation
      facilities a deeper intubation of the endoscope and thus a more complete examination of the
      small bowel mucosa.

      The study is designed as a two-centre randomised controlled trial. Randomisation to the two
      treatment groups (CO2 or air insufflation) is performed on basis of the individual
      participant.
    

Detailed description: 
      Background The small bowel has been a large blind spot for gastrointestinal (GI) endoscopy
      as, until recently, the small bowel was not accessible with conventional endosocopes.

      Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire
      small bowel. The method was first described by Yamamoto et al. and May et al in 2001 and
      2003, respectively (1,2). Since then, DBE has spread to a rising number of centres around the
      world. Both endoscopic diagnosis (e.g. by biopsy) and treatment can be easily performed using
      DBE. The first larger series, recently published, demonstrate that DBE is feasible in scoping
      large parts of the small bowel, with total small intubation possible in about 30-40% of cases
      (3,4).

      In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel to secure good
      visualisation. All endoscopes used for GI endoscopy provide a gas insufflation unit. The gas
      is pumped on demand into the area examined by the endoscopist via a gas tube incorporated in
      the endoscope. Currently, air is used for this purpose in more than 90% of centres throughout
      the world. The use of air, however, is far from ideal to use for insufflation in GI
      endoscopy. After GI endoscopy, significant amounts of air are usually retained in the bowel
      segment inspected (5). This air has to pass the GI tract and exit physiologically through the
      rectum. Thus, abdominal pain and discomfort during and after the examination due to the
      retention of air has been shown to be very common during and after endoscopic procedures
      (5-9).

      Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes,
      several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to
      result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in
      several randomised trials (6-9). In these studies, CO2 insufflation almost completely reduced
      procedure-related pain and discomfort.

      To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is
      a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are
      insufflated during the procedure, leading to significant distension of the small bowel during
      and after the examination.

      One of the main technical difficulties in DBE is the formation of small bowel loops and scarp
      angels during deep intubation of the endoscope. These loops and angels are the major
      restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced
      in air-distended bowel segments.

      The aim of the present study is to examine whether CO2 insufflation leads to a reduction of
      abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation
      facilities a deeper intubation of the endoscope and thus a more complete examination of the
      small bowel mucosa.

      Hypothesis

        1. The use of CO2 in DBE leads to a reduction in abdominal pain for the patient when
           compared with the use of air.

        2. The use of CO2 in DBE leads to deeper intubation when compared to air insufflation.

      Methods Study design The study is designed as a two-centre randomised controlled trial. The
      participating centres are Rikshospitalet University Hospital, Oslo, Norway and University
      Hospital Muenster, Germany.

      Randomisation to the two treatment groups (CO2 or air insufflation) is performed on basis of
      the individual participant. Equally large groups are randomised, using block randomisation
      (blocks of six patients) for each of the participating centres. Randomisation (using SPSS
      statistical software package) is performed by an independent researcher, who is not part of
      the DBE team.

      Individuals eligible for inclusion are patients referred for DBE at the trial centres who do
      not fulfil one of the following exclusion criteria:

        -  Age under 16 years

        -  Inability to understand information for participation

        -  Refusal of participation

      All eligible individuals are informed about the nature of the study. All individuals provide
      written informed consent before entering the trial. Patients who do not wish to participate
      in the present trial are treated according to standard procedures (using air insufflation).

      All procedures are performed by experienced endoscopists. Both patients and endoscopists are
      blinded with regard to type of gas used for any particular patient.

      Sedation is performed according to current standards at the centres.

      Double-balloon procedure DBE is performed using the DBE endoscope system (Fujinon Inc,
      Japan), as described in the literature (1-4). The DBE endoscope consist of a 200-cm long
      video endoscope with an outer diameter of 8.5 mm and a flexible overtube with a length of 145
      cm and an outer diameter of 12 mm. Latex balloons are attached to both the endoscope and the
      overtube. These balloons are inflated and deflated during insertion, as described elsewhere
      in detail (1,2).

      Gas insufflation CO2 is insufflated using Fujinons equipment (or other, to be specified) Air
      is insufflated using the ordinary air inlet system of the endoscope rack. The air inlet
      button is hidden from the view of the endoscopist to prevent unblinding (technical details to
      be specified in cooperation with company).

      Evaluation of pain and discomfort A questionnaire is used to classify patient pain during and
      after the procedure. Visual analogue scales (100-mm) are used to quantify abdominal pain
      during the examination and at 1, 3, 6, and 24 hours after the procedure, as validated in
      recent studies (7,8). The questionnaire is given to every participant after the procedure, to
      be filled in the next day, and mailed back to the respective trial centre using prepaid
      envelopes.

      Evaluation of ERCP examination parameters All procedure parameters of interest (e.g.
      duration, depth of insertion, use of sedatives) are registered by the endoscopist immediately
      after the examination using the existing GI lab databases.

      Ethics The regional ethics committees of the participating centres will be asked for approval
      of the study protocol.

      Power analysis A 15% reduction in mean pain score on VAS is considered to be clinically
      important to detect. There are no studies available regarding this outcome in DBE. Therefore,
      pilot study will be performed with 20 included patients in every group (air/CO2). The results
      of the pilot study will estimate the standard deviation needed to calculate power and thus
      size of the study.

      Ownership Data are owned by the respective centres. Publication of the study results is
      planned in a peer-reviewed journal. Michael Bretthauer and Dirk Domagk will co-ordinate study
      design, data generation and analysis and a first manuscript draft. Michael Bretthauer and
      Dirk Domagk will be the first authors of the planned publication, the other members of the
      study groups will be co-authors.

      Budget All procedures in the present study are performed in ordinary patients, with ordinary
      staff and endoscopists. Therefore, no extra costs occur for personal. For the purpose of the
      present study, however, some technical equipment has to be purchased (to be specified).

      Financial funding is needed for meetings of the study group and prepaid envelopes.

      References

        1. Yamamoto, Sekine Y, Saito Y, et al. Total enteroscopy with a non-surgical steerable
           double-balloon method. Gatrointest Endosc 2001;53:216-20

        2. May A, Nachbar L, Wardak A, et al. Double-balloon enteroscopy: preliminary experience in
           patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy
           2003;35:985-91

        3. May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull enteroscopy) of the
           small bowel: feasibility and diagnostic and therapeutic yield in patients with suspected
           small bowel disease. Gastrointest Endoc 2005;62:62-70

        4. Ell C, May A, Nachbar L, et al. Push-and pull enteroscopy in the small bowel using the
           double-balloon technique: results of a prospective European multicenter study. Endoscopy
           2005;37:613-6

        5. Hussein AMJ. Carbon dioxide insufflation for more comfortable colonoscopy. Gastrointest
           Endosc 1984; 30:68-70

        6. Stevensen GW et al. Pain following colonoscopy: elimination with carbon dioxide.
           Gastrointet Endosc 1992;38:564-567

        7. Bretthauer M, Thiis-Evensen E, Hoff G, et al. A randomized controlled trial to assess
           the safety and efficacy of carbon dioxide insufflation in colonoscopy. Gut 2002;
           50:604-607

        8. Bretthauer M, Hoff G, Thiis-Evensen E, et al. Carbon dioxide insufflation reduces
           discomfort due to flexible sigmoidoscopy in colorectal cancer screening. Scand J
           Gastroenterol 2002, 37:1103-8

        9. Sumanac K, Zealley I, Fox B , et al. Minimizing postcolonoscopy abdominal pain by using
           CO2 insufflation: a prospective, randomized, double blind, controlled trial evaluating a
           new commercially available CO2 delivery system. Gastrointest Endosc 2002;56:190-4

      Information and consent Research study: Insuflation of carbon dioxide(CO2) in double balloon
      enteroscopy

      Dear patient

      You are hereby kindly invited to participate in a research study while undergoing your
      planned endoscopic investigation of the small bowel (DBE, double balloon enteroscopy)

      During this examination, it is common practice to insufflate gas into the small bowel to
      provide the examiner with an adequate view. At the vast majority of hospitals around the
      world, ordinary room air is used for insufflation. However, the insufflated air can produce
      pain and abdominal discomfort for patients during and in the hours after the examination.

      There is some evidence that the use of carbon dioxide gas (CO2) instead of air can reduce
      abdominal pain after examination. In this study, we would like to find out if this is true.

      Study participants will be divided by random into a group that receives CO2 during the DBE
      examination and one group that receives air.

      Both the endoscopist and you as a patient do not know which gas is being used. Only the
      endoscopy assistant knows the type of gas used during your examination. After the
      examination, you will receive a short questionnaire about any complaints or discomfort, which
      we would like to ask you to fill in at home and mail back to the hospital.

      If you decide not to participate in the study, your examination will be performed with the
      use of air insufflation (standard method).

      The present study has been approved by the ethics committee. All information will be treated
      strictly confidential and only for research purposes within this study. Participation is free
      of charge and not mandatory. You may decline your participation at any time.

      Yours sincerely

      Dr. med. Michael Bretthauer (tlf:)

      Written informed consent I hereby declare my participation in the abovementioned research
      study. I am aware of that participation is voluntary.

      Date Signature

      Vedlegg C

      Carbon dioxide versus air insufflation in double-balloon endoscopy

      "Patient questionnaire (Version 300606), Michael Bretthauer

      This questionnaire is to be filled in the day after the procedure and to be mailed back to
      the GI lab.

      Patient ID

        1. Was the examination any painful??

           Please score the degree of pain with a vertical dash on the scale below, between No pain
           (left margin) and very heavy pain (right margin).

           No pain Very heavy pain

        2. Did you have any abdominal pain or distension after the examination?

      Please score the degree of pain with a vertical dash on the scale below, between No pain
      (left margin) and very heavy pain (right margin).

      No pain Very heavy pain

      1 hour after the exam

      3 hours after the exam

      6 hours after the exam

      24 hours after the exam

      Please use the back of the questionnaire for any comments
    

Intervention name(s): Carbon dioxide
Intervention type(s): Device
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Diagnostic
Keywords: pain, endoscopy; Pain, endoscopy, randomised trial