MATERIALS AND METHODS

The study was a randomized, controlled, single-center evaluation of patients undergoing elective colonoscopy. Written informed consent was obtained from all participants before attending the study. Our institutional review board did not require an additional consent form for this study because the study was performed as part of a performance improvement project and all preparations were accepted bowel cleansing regimens already being used at our institution. The investigators had no ties to any of the pharmaceutical manufacturers of the products used in the study.

Between October 2003, and May 2004, 170 adult patients who were referred to our clinic for colonoscopic examination were assigned into three groups at the time when they scheduled. They were told to use either oral sodium phosphate (group 1), or polyethylene glycol (group 2), or senna (group 3). Bodyweight and arterial blood pressures were measured. Blood samples were also drawn for the determination of blood urea nitrogen, creatinine, and electrolytes (sodium, potassium, chloride, calcium, phosphorus, and magnesium).

Exclusion criteria were determined as follows: established renal failure (serum creatinine > 2.0 mg/dL), pregnancy, partial or complete intestinal obstruction, symptomatic congestive heart failure, myocardial infarction within the last 3 months, emergency colonoscopy, known drug allergies, acute exacerbation of inflammatory bowel disease, and presence of ascites.

Before the cleaning procedure, one of each of the forms below containing information about the preparation was handed out to all patients.

Group 1 (sodium phosphate)

Following a regular breakfast on the day before the colonoscopy, an ample amount of clear liquids without particles will be consumed. At 17:00 h, 45 mL sodium phosphate solution (Fleet Fosfo-Soda^®; Kozmed, Turkey) monobasic sodium phosphate, 2.4 g and dibasic sodium phosphate solution,

0.9 g/5 mL) will be mixed with clear fluid or juice and will be consumed, followed by an intake of approximately 300 mL water. At 20:00 h, another 45 mL of the same solution will be consumed in a similar way. Large quantities of fluids will be taken and nothing should be taken by the oral route after midnight.

Group 2 (polyethylene glycol)

Following a regular breakfast on the day before colonoscopy, no solid food will be consumed, and clear, particle-free liquids will be taken until midnight. After 16:00 h, 4 L polyethylene glycol lavage solution (Golytely^®; SSM, Turkey; 59.1 g/ L polyethylene glycol, 40 mM/L sodium sulfate, 10 mM/L potassium chloride, 25 mM/L sodium chloride and 20 mM/L sodium bicarbonate) will be totally consumed at approximately 1–2 L per hour. Nothing should be taken by the oral route after midnight.

Group 3 (senna)

Solid foods will not be taken during the 2 days prior to colonoscopy, and large amounts of particle-free clear liquids will be consumed. During these 2 days, a total of four senna compounds, each of 75 mL (75 mL X-M solution purgative^®; Yenisehir, Turkey; 150 mg Sennosid A + B calcium) will be taken. On the night before the colonoscopy, nothing should be taken by the oral route after midnight.

On the day of colonoscopy, the following information was recorded for each patient: sex, age, education, occupation, marital status, admission type (inpatient or outpatient), presence of any systemic illness, present medication(s), whether any difficulties were encountered during ingestion of the agent, history of previous colon cleansing, and occurrence of symptoms such as nausea, vomiting, discomfort, fatigue, fullness, anal irritation, abdominal cramps, and inability to sleep. The final question was the willingness to repeat the assigned preparation, or knowing that there are other preparations on the market, whether they would prefer another at the time of the next colonoscopy. Afterwards, the patients were weighed, and their arterial blood pressures were measured. A peripheral venous cannula was inserted, and blood was sampled for biochemistry immediately before colonoscopy.

The patients on the examination table were given both 50 mg pethidine hydrochloride (Aldolan^® ampule; Liba, Turkey; 100 mg/2 mL), and 2.5–5 mg midazolam (Dormicum^® ampule; Roche, Turkey; 15 mg/3 mL) prior to the procedure. Fujinon EC-300MS^®, and EC-300MR^® colonoscopes (Fujinon Inc, Tokyo, Japan) were used for all examinations. All of the colonoscopies were performed between 9:00 h and 12:00 h. Adequacy of cleansing was evaluated by endoscopists, who were blinded to the bowel preparation, as clean (completely clean or presence of scarce amounts of clear fluid), suboptimal (ample amount of clear or turbid fluid, scarce amount of semisolid feces that can be removed by washing or aspiration), and dirty (presence of feces that cannot be removed by washing or aspiration).

Statistical analysis was made by SPSS 10.0 for Windows (SPSS, SPSS Inc, Chicago, USA; trading package program. Depending on the quality of the data present for statistical analysis, Student t-test, Kendall’s tau b-test, analysis of variance, and regression analysis were used. P-values less than

0.05 and 0.01 were considered significant, and highly significant, respectively.

RESULTS

A total of 170 colonoscopies were conducted. Of the 170 patients, 42.3% were men and 57.6% were women. Their

DISCUSSION

Today, colonoscopy is the standard procedure in colonic examination. The success of colonic examination depends on the quality of bowel preparation. The ideal cleansing method for colonoscopy must provide the following conditions: (i) fecal content of the colon must be safely evacuated; (ii) appearance and histology of the colonic mucosa should not be affected; (iii) it should require a relatively short period of time to consume the preparation and empty the colon; (iv) it should be comfortable for the patient; (v) it should not result in important shifts in the fluid and electrolyte balance of the patients.⁵

Table 3. Comparison of mean arterial blood pressure, weight and biochemical data of patients undergoing colonoscopy

Group 1 (n = 61) Group 2 (n = 36) Group 3 (n = 73) P-value Before After Before After Before After Before/After Between groups

Table 4. Comparison of the efficacy of bowel preparations in patients undergoing colonoscopy

Mean ABP (mmHg) 99.5 ± 15.9 90.2 ± 13.6 104 ± 18.4 96.2 ± 18 100 ± 16.8 93.9 ± 17 0.0001 NS Weight (kg) 70.7 ± 14.8 68.9 ± 14.8 74.3 ± 14.5 73.3 ± 14.5 71.8 ± 13.1 69.7 ± 12.6 0.0001 NS BUN (8–22 mg/dL) 16 ± 6.3 14.8 ± 5.9 15.5 ± 4.8 12.2 ± 4.4 14.5 ± 4.3 11.3 ± 3.6 0.0001 NS Creatinine (0.7–1.4 mg/dL) 0.9 ± 0.2 0.9 ± 0.31 0.9 ± 0.1 0.9 ± 0.1 0.9 ± 0.2 0.9 ± 0.2 NS NS Sodium (135–146 mmol/L) 141.2 ± 2.5 142.6 ± 2.3 142.2 ± 2.3 141.1 ± 2.8 140.6 ± 2.6 139.4 ± 2.9 NS 0.0001 Potassium (3.5–5.1 mmol/L) 4.5 ± 0.5 3.94 ± 0.5 4.5 ± 0.4 4.4 ± 0.7 4.3 ± 0.3 4.3 ± 0.9 0.0001 0.003 Chloride (95–107 mmol/L) 103 ± 0.9 103.1 ± 3.4 102 ± 3.2 102 ± 3.1 102.6 ± 3.2 101.5 ± 3.8 0.001 0.032 Calcium (8.5–10.5 g/dL) 9.3 ± 0.5 8.8 ± 0.4 9.5 ± 0.5 9.4 ± 0.4 9.2 ± 0.4 9.4 ± 0.5 0.002 0.0001 Inorg. Phosphorus (2.7–4.5 mg/dL) 3.5 ± 0.7 5.2 ± 1.6 3.5 ± 0.5 3.5 ± 0.6 3.4 ± 0.5 3.8 ± 0.8 0.0001 0.0001 Magnesium (0.7–1.0 mmol/L) 0.85 ± 0.01 0.83 ± 0.01 0.84 ± 0.01 0.84 ± 0.11 0.85 ± 0.01 0.85 ± 0.11 NS NS

Values are mean ± SD. Values in parentheses are normal ranges. ABP, arterial blood pressure; BUN, blood urea nitrogen; NS, not significant.

Group 1 Group 2 Group 3 Total n = 61 n = 36 n = 73 n = 170

Clean 32 (52.4) 17 (47.2) 46 (63.0) 95 (55.8) Suboptimal 23 (37.7) 16 (44.4) 14 (19.1) 53 (31.1) Dirty 6 (9.8) 3 (8.3) 13 (17.8) 22 (12.9)

Values in parentheses are percentages.

During the last decade, polyethylene glycol and sodium phosphate solutions, primarily because of their ability to cleanse the colon rapidly, have largely replaced the traditional 2-day preparation consisting of clear liquid diet, laxatives and enemas. Direct head-to-head trials between these two regimens suggest that they are equally efficacious. A recent meta-analysis of all randomized controlled trials comparing the two preparations concludes that sodium phosphate is as effective as polyethylene glycol.²⁰

In the present study, patients who required colonoscopy underwent bowel preparation with three different methods, and these methods were compared. There was no difference between the groups when difficulties encountered that related to the use of the drug were considered. In our study method, preference analysis demonstrated that senna was the least preferred method. Vanner et al.⁶ reported that 37 patients who previously had bowel preparation with polyethylene glycol but received sodium phosphate solution during their latest preparation completed the latter procedure more easily, and 90% of those patients had less discomfort with sodium phosphate solution. Present studies mostly compare sodium phosphate and polyethylene glycol lavage solutions.^{6–8,11–13,18,21–28} These studies report that sodium phosphate preparations are tolerated either equally as¹¹ or better than polyethylene glycol solutions.^{6–8,12,13,18,21–26}

Analysis of the complaints related to the procedure revealed nausea as the most frequent symptom. Crampy abdominal pain was most frequently observed with senna solution. The medical literature lacks sufficient numbers of trials comparing sodium phosphate and senna. While a number of comparison studies made with sodium phosphate and polyethylene glycol do not demonstrate any differences with respect to complaints,^{6,8,11,12,22,26} some have found significant differences, such as abdominal distension and pain.^13,25 Kolts et al.⁷ in their study comparing sodium phosphate, polyethylene glycol and castor oil, also found no significant differences between the complaints.

In our study, a decrease in arterial blood pressure was noted following bowel preparation. Huynh et al.²⁹ determined a decrease in intravascular volume in 40% of hospitalized, and in 10% of outpatient, individuals following a 5-h sodium phosphate application. Vanner et al.⁶ have not shown any clinically significant change in intravascular volume in a comparative study where sodium phosphate and polyethylene glycol were compared. Although there was no difference in the supine blood pressure between the three groups of patients in the current study, we did not evaluate orthostatic changes in blood pressure. However,Afridi et al.¹² observed that orthostatic hypotension was seen more fre

COMPARISON OF BOWEL CLEANSING METHODS

quently in patients who were prepared with polyethylene glycol.

Our study found that bodyweight dropped in each patient group. However, the magnitude of this weight loss was not significantly different between the groups. Other studies have also demonstrated a similar decline within the groups following the procedure, but not between groups.^6,13,17,22

Although the analysis of the biochemical parameters in the sodium phosphate group showed that serum sodium and inorganic phosphorus increased, and potassium and calcium decreased significantly, no symptoms were associated with these variations. Despite the electrolyte fluctuations, no significant safety concerns have been raised when the recommended dose of 90 mL is used as directed in appropriately selected patients. Most studies performed with sodium phosphate and polyethylene glycol have demonstrated substance-related alterations in the levels of blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, inorganic phophorus, and magnesium.^{6,7,11–13,22,23,28–30} Only rarely have these changes resulted in clinical findings in healthy individuals.^31–33 However, as the use of oral sodium phosphate has increased, there have been a growing number of case reports of serious adverse events. Most have been the result of inappropriate dosing, but these reports also suggest that sodium phosphate has a lower therapeutic index compared with polyethylene glycol solution, which was found to be safer in patients with comorbid conditions.³⁴ Therefore, it is important to note that oral phosphate solutions should be used with caution in patients with congestive heart failure, ascites, or renal insufficiency.

When the efficacy of cleansing was compared, we did not find any significant difference between the groups. Studies made with sodium phosphate and polyethylene glycol lavage solutions have given conflicting data. While some studies report that sodium phosphate solution offers more effective cleansing than polyethylene glycol,^6,7,12,13 others state that both agents are equally effective.^{8,11,13,18,21–25} Polyethylene glycol was found to be more effective in cleansing than sodium phosphate in one study.²⁶ In their meta-analysis of eight studies, Hsu and Imperiale²⁰ found that sodium phosphate was better in three studies, and was equal to the others in the reing five. The use of concentrated senna extract in combination with polyethylene glycol solution has also been evaluated. Ziegenhagen et al.³⁵ randomly assigned 120 patients to senna preparation or placebo a day before proceeding ingestion of polyethylene glycol solution. Satisfactory clean colon was observed in 90% of patients receiving senna, compared with 57% in the placebo group. Finally, Hookey et al.³⁶ made an analysis of 28 studies related to the use of sodium phosphate in the preparation of the colon prior to colonoscopy, and showed the compound to be safe in adults when appropriate dosages were used.

When assessing the efficacy of a colon-cleansing regimen, along with patient compliance and effectiveness, cost must also be considered. In this study, sodium phosphate and senna were found to be significantly less expensive than oral glycol-based lavage solutions. In our country, the price of a polyethylene glycol solution is $12.30 USD, compared with $4.1/90 mL for sodium phosphate, and $3.8/300 mL for senna, approximately an $8 cost differential. Similarly, a meta-analysis of the studies comparing the use of polyethylene glycol and sodium phosphate shows that sodium phosphate is more economical.²⁰

In conclusion, when sodium phosphate, polyethylene glycol and senna solutions were compared with respect to their efficacies in bowel preparation, safety in healthy individuals, ease of application, and low frequency of side-effects, there were no significant differences. However, due to the better tolerance, requirement of a shorter period of time for effective preparation, and economical benefits, we feel that oral sodium phosphate is a superior rapid colonic cleansing agent, and would recommend it as the agent of choice for most patients.

ACKNOWLEDGMENTS

The authors thank nursing staff for data collection and management, Dr H. U. Aydin, and Dr B. Kucukemre for their valuable help, and Dr C. Korkut for his statistical support.

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