Introduction
Sodium phosphate (NaP) is a key component of the standard bowel preparation regimen
for colon capsule endoscopy (CCE, PillCom® COLON2 Capsule Endoscopy: Medtronic, Minneapolis, MN, USA), particularly to cause
excretion of the capsule endoscope while the battery is still functioning. Previous
reports have demonstrated that other laxatives including polyethylene glycol and magnesium
citrate were not effective for excreting the capsule endoscope [1]
[2]
[3]. However, the use of NaP is limited due to the possibility of causing severe adverse
events, e. g. acute phosphate nephropathy, acute renal failure, hypertension, or mineral
imbalance [4]
[5]. The U.S. Food and Drug Administration issued a warning to restrict its purchase
without a prescription in 2008. In Japan, administration of NaP for hypertensive patients
64 years or older has been contraindicated since February 2012. Therefore, an alternative
to NaP is needed to perform CCE safely with a high completion rate.
According to the latest report investigating the performance of CCE compared with
CT colonography [6], Gastrografin (the water-soluble iodinated radiopaque oral contrast medium) was
first used for the CCE regimen, because Gastrografin is generally used as part of
the CT colonography regimen for “fecal tagging” [7]. In our experience, a CCE regimen using Gastrografin without NaP, achieved a very
high capsule excretion rate. The gastrointestinal transit time as well as the colon
transit time with this bowel preparation regimen were comparable to that of CCE regimens
using a NaP booster. In this paper, we report the results of a pilot study using Gastrografin
as a booster in the bowel preparation regimen for CCE.
Patients and methods
From June 2014 to November 2014, 29 patients in two tertiary care hospitals (Aizu
Medical Center and Otaru Ekiseikai General Hospital) underwent CCE, covered by the
national health insurance system of Japan. To be eligible for insurance payment for
colon capsule endoscopy, the patient must meet standardized indications for colon
screening as well as one of the following conditions including: a previously incomplete
colonoscopy, a previous laparotomy, or being unable to undergo colonoscopy due to
some organic abnormality.
Patient demographic data is shown in [Table 1]. The median age was 64 years and eight patients were older than 75 years. Most patients
(79 %) were female. All had a history of laparotomy and/or previously incomplete colonoscopy.
Patients with a history of bowel resection were not included. Sixteen patients (55 %)
underwent the procedure to evaluate a positive fecal immunochemical test.
Table 1
Patient demographic data.
|
All patients, n (%)
|
|
29 (100)
|
|
Age, years
|
Mean
|
64.1
|
|
Median
|
64
|
|
Range
|
42 – 91
|
|
Gender, n (%)
|
Female
|
23 (79)
|
|
Male
|
6 (21)
|
|
Previous laparotomy, n (%)
|
Yes
|
19 (66)
|
|
Previous incomplete colonoscopy, n (%)
|
Yes
|
16 (55)
|
|
Indication for colonoscopy, n (%)
|
Positive fecal immunochemical test
|
16 (55)
|
|
Post-polypectomy
|
6 (21)
|
|
Change in bowel habits
|
4 (14)
|
|
Hematochezia
|
2 (7)
|
|
Anemia
|
1 (3)
|
Details of the CCE regimen are shown in [Table 2]. Bowel preparation started from breakfast on the day before examination. Patients
had low residue meals at breakfast and lunch, and drank 1 L of polyethylene glycol
(PEG) plus ascorbic acid with 0.5 L of water in the evening, and 10 mL of sodium picosulfate
hydrate at bedtime. On the morning of the examination, patients again drank 1 L of
PEG plus ascorbic acid with 0.5 L of water. After capsule ingestion, 50 mL of Gastrografin
diluted with 0.9 L of magnesium citrate was administered to facilitate capsule excretion.
Gastrografin with magnesium citrate was given again after 1 hour. If the capsule was
not expelled within 4 hours of ingestion, 50 mL of Gastrografin with water (by mouth)
and/or a bisacodyl suppository were added. The capsule excretion rate within the duration
of battery life, gastrointestinal transit time, colon transit time, bowel cleansing,
and yield of colon polyp identification were measured. Bowel cleansing was rated on
a four-point scale (poor, fair, good, excellent) to describe the preparation of the
colon at the time of the capsule endoscopy [8]
[9].
Table 2
Bowel preparation regimen.
|
Day
|
Hour
|
Action
|
|
Day before exam
|
All day
|
Low-residue diet
|
|
Evening
|
Moviprep 1 L + water 0.5 L
|
|
Bedtime
|
Laxoberon 10 mL + water 0.2 L
|
|
Day of exam
|
07:00
|
Moviprep 1 L + water 0.5 L
|
|
09:30
|
Capsule ingestion
|
|
|
+ 0.1 % domperidone syrup 30 mL (30 mg)
|
|
|
+ mosapride 10 mg
|
|
10:30
|
Magcorol P isotonic solution 0.9 L
|
|
|
+ mosapride 10 mg
|
|
|
+ Gastrografin 50 mL
|
|
11:30
|
Magcorol P isotonic solution 0.9 L
|
|
|
+ Gastrografin 50 mL
|
|
12:30
|
Suppository (bisacodyl 10 mg)
|
Moviprep: polyethylene glycol + ascorbic acid; Laxoberon: sodium picosulfate hydrate;
Magcorol P: magnesium citrate; Gastrografin: diatrizoate meglumine and diatrizoate
sodium.
Results
The capsule excretion rate was 97 % (28 /29). The one patient who did not expel the
capsule within the duration of battery life was a 51-year-old man with severe diverticular
disease of the sigmoid colon. Gastrointestinal transit time, colon transit time, bowel
cleansing, and yield of colon polyps are shown in [Table 3]. Median colon transit time was 165 minutes and rapid transit ( < 40 minutes) through
the colon occurred in one patient (3.4 %, 1/29). Bowel cleansing was adequate (excellent/good)
in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. All patients followed
our regimen and diluted Gastrografin was well tolerated by all of them. No adverse
events occurred in this pilot study.
Table 3
Patient outcomes.
|
Capsule excretion rate within the life of the battery, n (%)
|
|
28 (97)
|
|
Gastrointestinal transit time, min
|
Median
|
281.5
|
|
Range
|
105 – 641
|
|
Colon transit time, min
|
Median
|
165
|
|
Range
|
25 – 565
|
|
Bowel cleansing, n (%)
|
Excellent
|
11 (38)
|
|
Good
|
15 (52)
|
|
Fair
|
3 (10)
|
|
Poor
|
0 (0)
|
|
Polyp yield, n (%)
|
None[1]
|
14 (48)
|
|
6 – 10 mm
|
7 (24)
|
|
≥ 11 mm
|
8 (28)
|
1 Includes polyps ≤ 5 mm.
Discussion
In our CCE regimen without NaP, but using Gastrografin instead, the capsule excretion
rate, gastrointestinal transit time, colon transit time, and bowel cleansing were
equivalent to previous reports using NaP as a booster [6]
[10]
[11]. Bowel cleansing was adequate in most patients, allowing a high polyp detection
rate. These results indicate that Gastrografin is an alternative to NaP for CCE bowel
preparation.
Gastrografin, known generically as diatrizoate meglumine and diatrizoate sodium, was
developed as a water-soluble iodinated radiopaque oral contrast medium in 1960, and
is still used in radiographic examinations because of its unique characteristics.
According to the manufacturer’s information [http://www.bayerhealthcare.at/de/produkte/g-l/gastrografin/index.php],
the osmolality of Gastrografin is nine times as high as that of blood plasma although
the osmolality of NaP could be more than 30 times higher in preliminary calculations.
Therefore, Gastrografin can work as a hyperosmotic laxative. While NaP is likely to
increase the serum level of inorganic phosphate due to high phosphate level, most
of the Gastrografin is not absorbed from the intestinal tract into the circulation.
Overall, ≤ 2 % of Gastrografin is excreted into the urine without being metabolized.
These characteristics suggest that an electrolyte imbalance is less frequently caused
by oral/anal administration of Gastrografin. Gastrografin is a safe hyperosmotic laxative,
and is a booster suitable for patients at increased risk. In this pilot study, including
eight patients older than 75 years, no adverse events occurred.
The latest clinical trial [12] conducted in the United States used a sulfate solution (SUPREP; Braintree Laboratories)
as a booster for colon capsule endoscopy. In this large clinical trial, the median
colon transit time was 75 minutes and occasionally the capsule passed through the
colon within 40 minutes. Subsequently, approximately 10 % (77/772) of subjects were
excluded from the final analysis, based on the combination of poor preparation and
rapid transit after enrollment. Because the sulfate solution is poorly absorbed, the
osmotic effect of unabsorbed sulfate anions and associated cations causes water to
be retained within the intestine, thus expelling the capsule in a short time. In the
present study using Gastrografin as a booster, the median colon transit time (165
minutes) was longer than that in the clinical trial using a sulfate solution. Gastrografin
booster may provide sufficient observation time for the colon. Indeed, the polyp (≥ 6 mm)
detection rate was comparably high (52 %) in the present study.
There are acknowledged limitations to this study. This is a pilot study before a clinical
trial, which limits the generalizability of the results. In addition, the present
study was conducted in highly selected patients with a history of laparotomy and/or
previously incomplete colonoscopy, possibly limiting the ability to generalize these
results to other patient groups. We acknowledge that the polyp detection with CCE
has not been verified by follow-up colonoscopy, which could alter the results of the
yield of colon polyps. Despite these limitations, we believe that consideration of
Gastrografin as an alternative booster is of interest.
In conclusion, the use of Gastrografin in the CCE bowel preparation regimen is promising.
Other modifications to the protocol may influence the high capsule excretion rate.
A clinical trial is warranted to compare regimens with and without Gastrografin.
