Trial Information

A Randomized, Controlled Trial Comparing Air Insufflation, Water Immersion and Water Exchange During on Demand Sedation Colonoscopy in Diagnostic Patients

Introduction Water-aided methods for colonoscopy can be broadly subdivided into two major
categories.

Water Immersion (WI) is characterized by suction removal of the infused water predominantly
during the withdrawal phase of colonoscopy and Water Exchange (WE) is characterized by
suction removal of infused water predominantly during the insertion phase of colonoscopy.

Several studies showed that WE significantly reduces pain compared to WI and colonoscopy
with traditional air insufflation (AI), increases the number of unsedated procedures and
adenoma detection rate (ADR), in particular proximal ADR. The hypothesis that the WE method
may provide a strategy to improve prevention of colorectal cancer by enhancing detection of
adenomas in screening colonoscopy is intriguing. A comparison of AI, WI, and WE in a
well-designed and adequately powered RCT of average-risk screening patients undergoing
colonoscopy deserves to be considered. Such an RCT would help answer unresolved questions
and determine the future role of water-aided method for colonoscopy.

Method

Examinations will be allocated to Water Exchange, Water Immersion or Air Insufflation during
the insertion phase of colonoscopy based on a computer generated random list. Procedures
will be started by 6 board-certified endoscopists, three with experience in 8,000-10,000 and
three with experience in 2,000-5,000 colonoscopies with AI, 285 with WI and 890 with WE
overall.

High-resolution wide-angle variable-stiffness adult video colonoscopes (Olympus HD 180
series; Olympus Corp, Hamburg, Germany) will be used. Need to change to a smaller caliber
colonoscope will be considered ITT failure.

Patients will have a low volume split dose bowel preparation with 2L of polyethylene glycol
(PEG) solution or Sodium Picosulfate. Investigators will be blinded to the colon preparation
used. Before starting the procedure, a questionnaire recording demographic data, previous
abdominal surgery, co-morbidities and current medications will be administered by the
endoscopists. The patients, but not endoscopists and assisting nurses, will be blinded to
the method used. At discharge the patient will be asked to guess which method has been used.
If no more than half of the responses are correct, patients' blinding will be considered
adequate.

Colonoscopy will begin with the patients in the left lateral position, without
premedication. The withdrawal phase will be identical in all arms of the study using air
insufflation to obtain adequate distension of the colonic lumen for mucosal inspection,
biopsy and/or polypectomy.

Patients randomized to the water-aided colonoscopy group, during the insertion phase after
reaching the rectosigmoid junction, will have the colon irrigated with water at 37°C
maintained with a water bath. Infusions will be performed using flushing pumps (Olympus
OFP2, Olympus, Hamburg, Germany or Velocity irrigation pump, US Endoscopy, OH, USA). There
will be no restriction of the overall volume of water that can be infused to get adequate
lumen distention and reach the cecum. With the patient in the left lateral position water
infused into the colon at the rectal sigmoid junction flows into the descending colon. The
weight of the water in the left side of the colon straightens the sigmoid segment increasing
the ease of insertion and reducing the risk of loop formation. The air pump will be turned
off to avoid inadvertent insufflation.

Water Immersion will involve the infusion of water during the insertion phase of colonoscopy
mainly to open the colonic lumen and progress to the cecum immersed in the water environment
thus created, without attempting to clear the colon contents. Use of water as an adjunct to
air insufflation to facilitate insertion and removal of infused water predominantly during
withdrawal are characteristic features of WI. This traditional adjunct facilitates passage
through the sigmoid colon with severe diverticulosis, speeds arrival to the splenic flexure,
decreases colonic spasm, minimizes pain, and even enhances cecal intubation in previously
incomplete colonoscopies.

Residual air in the colon will not be removed. The infused water and residual feces will be
suctioned back only during withdrawal. Air insufflation will be allowed if the lumen cannot
be seen and the endoscopists judges unsafe to advance the colonoscope. It will last no more
than 10 seconds and will be recorded in the patient data sheet. If more than 3 episodes of
air insufflation will be recorded the procedure will be considered ITT failure.

Water Exchange will involve complete exclusion of air insufflation, removal of residual
colonic air and feces and of infused water predominantly during insertion to assist
identification of the lumen. WE minimizes loop formation and decreases discomfort. By
providing salvage cleansing during insertion, WE allows the colonoscopist to devote a
greater proportion of the withdrawal to inspection. WE will involve the infusion of a
sufficient amount of water to open the lumen of the colon to allow passage of the
instrument, thus rendering the colonic lumen a slit to progress with the colonoscope. If the
lumen does not open, the colonoscope will be slightly retracted and the infusion started
again. Part of the infused water will be constantly suctioned back exchanging clean for
dirty or hazy water. Suction of infused water will also be applied when colonoscope
insertion proceeds smoothly. Air pockets, when encountered, will be always aspirated to
collapse the lumen: the absence of air space forces the colonoscopist to use water to clear
residual feces and to find the way through the colon. Removal of the air also shortens the
colon and takes out all the sharp turns at the flexures and redundant segments, reducing the
risk of loop formation: water instillation does not elongate the colon as much as air
insufflation does. In a collapsed, airless colon turbulences created at the tip of the
instrument facilitate the removal by suction of residual feces adherent to the mucosa. This
provides salvage cleansing during the insertion phase. After cecal intubation as much
residual water as possible will be aspirated before beginning the withdrawal phase. During
withdrawal scarce amounts of water are left to aspirate, and residual water and feces will
be suctioned.

In the AI group, colonoscopy will be performed in the standard fashion, allowing for washing
as needed. In all groups abdominal compression and position change were applied as needed.

Cecal intubation will be defined as passage of the tip of the colonoscope to a point
proximal to the ileocecal valve with adequate visualization of the cecum and appendix
orifice. A stopwatch will be used to time the procedures. Cecal intubation time will be
defined as the time for passage of the colonoscope from the rectum to the cecum. The
withdrawal phase will last at least 6 minutes. Polyp resection will be done during
withdrawal in all groups. Time for polypectomy or biopsy will add to the total colonoscopy
time. Pathology reports of all polyps will be reviewed and recorded to evaluate adenoma
detection rate (ADR, defined as the proportion of subjects with at least one adenoma of any
size), the location, the total number of adenomas resected per subject(ARR), and the
percentage of subjects with advanced adenomas. The amount of water infused during insertion
and withdrawal, the number of position changes and any adverse outcome will be recorded.
Cardiopulmonary function will be monitored. Significant oxygen desaturation (<85% for >15
seconds) will be recorded. Vagal reaction will be defined as heart rate <60 beats per minute
accompanied by excessive sweating, nausea and/or vomiting.