Guidelines for the Bowel preparation prior to colonoscopy
For evaluation of the colon, Colonoscopy is the current standard method. Diagnostic accuracy and therapeutic safety of colonoscopy depends on the quality of the colonic cleansing or preparation. The ideal preparation for colonoscopy would reliably empty the colon of all fecal material in a rapid fashion with no gross or histologic alteration of the colonic mucosa. The preparation would also not cause any patient discomfort or shifts in fluids or electrolytes and would be inexpensive. Unfortunately, none of the preparations currently available meet all of these requirements.
EVOLUTION OF BOWEL PREPARATIONS
From radiologic and surgical preparations preparation of Colonoscopy evolved. Early preparations used dietary limitations, cathartics, and enemas. Although these preparations cleansed the colon, uncomfortable for the patient, they were time consuming (48-72 hrs) and associated with fluid and electrolyte disturbances. A rapid preparation used high volume (7-12L) per oral gut lavage with saline/electrolyte solution. This was also associated with poor patient tolerance and severe fluid and electrolyte shifts. Chang et al. developed a method of pulsed rectal irrigation combined with magnesium citrate. These regimens and their utilization continue to evolve. In 1980, Davis et al. formulated polyethylene glycol (PEG), an osmotically balanced electrolyte lavage solution. The standard 4L dosing regimen given the day before the procedure was established as safe and effective. For colonoscopy, PEG quickly became the “gold standard”. However, poor compliance related to the salty taste, the smell from the sulfates, and the large volume of fluids required led to modifications of the PEG solutions and their dosing recommendations and reevaluations of other osmotic laxatives (e.g. sodium phosphate). More recent studies have focused on identifying the “ideal” preparation including such parameters as taste, electrolyte supplementation, the timing of doses, and the division of doses.
REGIMENS FOR COLONIC CLEANSING PRIOR TO COLONOSCOPY
Dosing: Dietary regimens characteristically incorporate clear liquids and low residue foods over 1-4 days. Regimens typically incorporate dietary changes, and oral cathartic and/or additional cathartic enemas. A cathartic such as magnesium citrate or senna extract is often used on the day prior to the procedure. Tap water enemas are administered on the morning of and occasionally on the evening prior to the procedure.
Dosing: Prior or the morning of the procedure, tap water or sodium phosphate enemas are administered on the evening. For colonic cleansing, they are usually administered in conjunction with dietary restrictions or cathartics. In patients with poor or incomplete cleansing, one or two sodium phosphate enemas are useful in washing out the distal colon. Enemas are useful in washing out the distal segment of bowel in patients with a proximal stoma or a defunctioned distal colon (e.g. Hartman’s).
High Volume Gut Lavage
Dosing: Per oral gut lavage with high volumes (7-12L) of saline solution or balanced electrolyte solutions with or without a nasogastric tube have been used for colonic preparation. Mannitol was used in early formulations but abandoned secondary to bacterial fermentation into hydrogen and methane gas, which can cause explosion when electrocautery is used.
Rectal Pulsed Irrigation
Per rectal pulsed irrigation in combination with per oral ingestion of 10 oz of magnesium citrate the night before the colonoscopy is another potential preparation. The patient is given a 30-minute infusion of short pulses of warm tap water via the rectum through a rectal tube immediately before the colonoscopy. Disadvantages to this regimen are that is it is time consuming and requires skilled nursing to administer, making it expensive to use.
PEG-ELS (Polyethylene Glycol-Electrolyte Lavage Solution)
PEG is a non-absorbable solution that should pass through the bowel without net absorption or secretion. Large volumes (4L) are still required to achieve a cathartic effect. Significant fluid and electrolyte shifts are therefore avoided.
Dosing: No solid food for at least two hours prior to ingestion of the solution 240 mL (8 oz.) every 10 minutes until rectal output is clear or 4 L are consumed. Dosage for nasogastric administration is 20-30mL/min (1.2-1.8L/hr).
SF-ELS (Sulfate Free-Electrolyte Lavage Solution)
PEG-based lavage solution without sodium sulphate was developed by Fordtran et al. In an attempt to improve the smell and taste of PEG solutions, the improved taste was due to a decrease in potassium concentration, increase in chloride concentration, as well as a complete absence of sodium sulfate. The removal of sodium sulfate results in a lower luminal sodium concentration. Therefore, the mechanism of action is dependent on the osmotic effects of PEG.
Evidence: SF-PEG is less salty, more palatable, and comparable to PEG in terms of effective colonic cleansing and overall patient tolerance.
Low Volume PEG/PEG-3350 (Polyethylene Glycol-3350) and Bisacodyl Delayed- Release Tablets
In an attempt to improve patient tolerance low volume PEG solutions were developed. In order to reduce the amount of volume of lavage solution required and reduce volume-related symptoms such as bloating and cramping while maintaining efficacy, bisacodyl and magnesium citrate are administered.
Dosing: Only clear liquids on the day of the preparation. Dosage is 4 bisacodyl delayed-release tablets (5mg) at noon. Wait for bowel movement or maximum of 6 hours. 240mL (8oz.) every 10 minutes until 2L are consumed.
Low Volume PEG-3350 and Bisacodyl Delayed- Release Tablets
An additional low-volume PEG 3350 without electrolytes with adjuncts such as bisacodyl has also been used.
Dosing: Clear liquids only the day of the preparation Dosage is 4 bisacodyl delayed-released tablets (5 mg) at noon, Wait for bowel movement for maximum of 6 hours. 240mL (8oz.) of clear liquid containing 1 capful of Miralax every 10 minutes until 2L are consumed.
Aqueous Sodium Phosphate
Aqueous NaP is a low-volume hyperosmotic solution which contains 48g (400mmol) of monobasic NaP and 18 g (130mmol) of dibasic NaP per 100 ml. The NaP osmotically draws plasma water into the bowel lumen to promote colonic cleansing. Significant fluid and electrolyte shifts can occur. Sodium phosphate must be diluted prior to drinking to prevent emesis and must be accompanied by significant oral fluid to prevent dehydration. Patients with compromised renal function, dehydration, hypercalcemia, or hypertension with the use of Angiotensin-converting Enzyme (ACE) Inhibitors, or Angiotensin receptor blockers (ARBs) have experienced phosphate nephropathy after use of oral sodium phosphate solutions. The effects seem to be age and dose related. Linden and Waye described the pharmacologic properties of NaP. The mean onset of bowel activity was 1.7 hours after the first dose and 0.7 hours after the second dose. The mean duration of action was 4.6 hours after the first dose and 2.9 hours after the second dose. Bowel activity ceased within 4 hours in 83% of patients and within 5 hours in 87%.
Dosing: Only clear liquids can be consumed on the day of preparation. Two doses of 30-45mL (2-3tbsp) of oral solution are given at least 10-12 hours apart. Each dose is taken with at least 8 oz of liquid followed by an additional minimum of at least 16 oz of liquid. The second dose must be taken at least 3 hours before the procedure.
Tablet Sodium Phosphate
The tablet form of sodium phosphate was designed to improve the taste and limit the volume of liquid required. The results of two large, identically designed, Phase III multi-center randomized investigator-blinded trials that compared tablet sodium phosphate with 4L PEG regimens were the basis for FDA approval in 2000. Each 2gm tablet contains 1500mg of active ingredients (monobasic and dibasic NaP) and 460 mg of microcrystalline cellulose as a tablet binder. The amount of active ingredient in this regimen is comparable to the standard aqueous NaP regimen. Microcrystalline cellulose is a non-absorbable inert polymer and is therefore insoluble in the gastrointestinal tract. The remnants of this polymer can be visualized during colonoscopy and may interfere with the examination of the bowel mucosa. Therefore, reduced amounts of microcrystalline cellulose may help visualize the colonic mucosa. In 2001, a laboratory study demonstrated the beneficial effects of ginger ale when administered with Visicoltablets. This study attempted to provide a scientific basis for the clinical observation that ginger ale facilitates the removal of microcrystalline cellulose from the colon after the administration of Visicolprior to colonoscopy.
Dosing: Dosage is 32-40 tablets; 20 tablets on the evening before the procedure and 12-20 tablets the day of the procedure (3-5 hours before). The 20 tablets are taken as 4 tablets every 15 minutes with 8oz of clear liquid. Note: Bisacodyl is prescribed by some physicians as an adjunct.
ADJUNCTS TO COLONIC CLEANSING PRIOR TO COLONOSCOPY
There have been many attempts to improve the flavor of both PEG-electrolyte solutions and NaP solutions. As a result, PEG-electrolyte solutions are available in multiple flavors such as cherry, citrus-berry, lemon-lime, orange, and pineapple. In addition, the sulfate salts have been removed from HalfLytely and NuLytely, resulting in a less salty taste and avoidance of the “rotten egg” smell. Gatorade, Crystal Lite, and carbohydrate-electrolyte solutions have been used to improve palatability in both PEG and NaP solutions. Ginger Ale and water are used with NaP to improve the taste. However, improved flavor does not necessarily equate to improved tolerance. Special care must be taken to avoid altering the osmolarity of the preparation or adding substrates to the preparation which can metabolize into explosive gases or alter the amount of water and salts absorbed.\
Nasogastric/Orogastric Tube Administration of Colonic Preparations
Nasogastric tubes have been used to instill colonic preparations primarily PEG-electrolyte based solutions in both children and adults. In addition to the potential complications related to placement of the nasogastric tube, case reports have demonstrated the potential for severe life threatening complications such as aspiration.
Carbohydrate-electrolyte solutions have been used in combination with both PEG solutions and NaP to make the preparation more palatable and, in the latter, to avoid the severe electrolyte/fluid shifts. Combining PEG 3350 laxative powder (Miralax) and Gatoradehas been shown to improve the taste and tolerability of the preparation. E-Lytecombined with NaP was demonstrated to improve overall tolerability and reduce the degree of volume contraction, hypokalemia, and the need for intravenous rehydration. Although beneficial, the addition of these carbohydrate-based solutions is associated with a theoretical risk of cautery-induced explosion if these carbohydrates are metabolized by colonic bacteria into explosive gases.
Prior to the development of PEG, enemas were an essential component of colonic preparation. However, conclusive evidence has demonstrated that enemas do not improve the quality of bowel cleansing, yet significantly increase patient discomfort. Enemas may still play a role in the patient who presents for colonoscopy with a poor preparation.
Metaclopramide is a dopamine antagonist gastro-pro-kinetic that sensitizes tissues to the action of acetylcholine. This result in increased amplitude of gastric contraction, increased peristalsis of the duodenum and jejunum, and does not change colonic motility. Metaclopramide used as an adjunct with PEG has been shown to reduce nausea and bloating but not improve colonic cleansing. However, a second study did not reveal any advantage with regards to colonic cleansing or patient tolerance.
Simethicone is an anti-flatulent, anti-gas agent that has been used as an adjunct to colonoscopy preparations. The use of simethicone as an adjunct to PEG-electrolyte solution to eliminate foam formation after colonoscopy preparation and improve visualization during colonoscopy has been studied. Simethicone reduced foaming and improved tolerability and improved efficacy (i.e. reduction in residual stool at time of colonoscopy). However, the mechanism of action of simethicone was unclear. A subsequent study also showed a reduction in bubble formation seen during colonoscopy and an improvement in overall tolerability.
Bisacodyl is a poorly absorbed diphenylmethane that stimulates colonic peristalsis. Bisacodyl used as an adjunct with high volume balanced solution decreased the duration of whole gut irrigation although no significant difference in colon cleansing was identified. Bisacodyl, when used as an adjunct with PEG, has demonstrated no significant difference in the quality of the preparation or amount of residual colonic fluid during colonoscopy. Bisacodyl and magnesium citrate are used as adjuncts to PEG solutions and have allowed for less volume of PEG necessary for colonic cleansing. Afridi et al. studied bisacodyl as an adjunct with NaP given in split doses the evening before the procedure. This combined regimen was found to be equally effective and tolerable as standard 4L PEG. Anecdotally, bisacodyl has been used as an adjunct for aqueous and tablet NaP, although further studies are necessary.
Magnesium citrate is a hyper-osmotic saline laxative that increases intra-luminal volume resulting in increased intestinal motility. Magnesium also stimulates the release of cholecystokinin which causes intra-luminal accumulation of fluid and electrolytes and promotes small bowel and, possibly, colonic transit. Since magnesium is eliminated from the body solely by the kidneys, magnesium citrate should be used with extreme caution in patients with renal insufficiency or renal failure. Two studies by Sharma et al. utilized magnesium citrate as an adjunct to PEG. The addition of magnesium citrate allowed for less PEG solution (2L) to be used in order to achieve the same result. Thus, the 2L volume PEG regimen was significantly better tolerated by patients.
Senna laxatives contain anthraquinone derivatives (glycosides and sennosides) that are activated by colonic bacteria. The activated derivatives then have a direct effect on intestinal mucosa, increasing the rate of colonic motility, enhancing colonic transit, and inhibiting water and electrolyte secretion. Senna has been used as an adjunct to PEG regimens in a manner similar to that of bisacodyl. When used as an adjunct in combination with PEG, No differences were found between senna and bisacodyl. The adjunctive use of senna with PEG solutions has been demonstrated to improve the quality of bowel preparation and to reduce the amount of PEG-ELS required for effective bowel preparation.
In order to fix the efficacy of bowel preparation, one must locate the relatively subjective appearance of the prepared colonic mucosa to a relatively objective parameter. Towards that end, several colonic cleansing systems have been proposed. However, no single system seems ideal in all situations.
Prior to colonoscopy, the safety of the various bowel preparation protocols currently available for use is related to the safety profile of the base agent, either PEG or NaP, and whether used in solid or liquid formulation. Generally speaking, all of the preparations detailed in this document have been demonstrated safe for use in otherwise healthy individuals without significant comorbid conditions. Caution should be used in selecting a bowel preparation for patients with significant hepatic, renal, or cardiac dysfunction, and for those at the extremes of age.
Inadequate bowel preparation
Inadequate bowel preparation for colonoscopy can result in missed lesions, cancelled procedures, increased procedural time, and a potential increase in complication rates. One study examined the possible causes for poor preparations. Surprisingly, less than 20% of patients with an inadequate colonic preparation reported a failure to adequately follow preparation instructions. Independent predictors of an inadequate colon preparation included a later colonoscopy starting time, failure to follow preparation instructions, inpatient status, and a procedural indication of constipation, use of tri-cyclic antidepressants, male gender, and a history of cirrhosis, stroke, or dementia. Anecdotally, a poor preparation following a PEG preparation is usually liquid and more easily managed than a preparation following NaP that tends to be thick and tenaciously adhered to the mucosa. There is no published information on the management of the patient who has received a colonoscopy preparation that has been deemed inadequate. Regardless of the preparation selected, the patient and physician must be aware of potential financial obligations of a repeat colonoscopy and preparation. Specifically, the patient may be required to pay additional co-pay for each examination and the financial intermediary may deem one or both examinations unnecessary. In these instances, the patient may be responsible for payment in full for both examinations. Identify whether the patient has consumed the preparation as prescribed. If not, it would be reasonable to repeat the same preparation, although not within 24 hours using sodium phosphate (NaP) due to the risk of toxicity. If the patient has properly consumed the preparation, reasonable options include repeating the preparation with a longer interval of dietary restriction to clear liquids, switching to an alternate but equally effective preparation (if the patient received PEG, change to sodium phosphate or vice versa), adding another cathartic such as magnesium citrate, bisacodyl, or senna to the previous regimen, or double administration of the preparation over a two-day period (with the exception of NaP). Combining preparations, for example PEG solution and sodium phosphate solution, has also been described with some success.
Selection of Bowel Preparation Based on Co-morbidities
Elderly patients tend to have poorer preparations, although between PEG and NaP solutions, one study found no difference in the adequacy of the colonic preparation. They are at an increased risk for phosphate intoxication due to decreased kidney function, medication use, and systemic and gastrointestinal diseases. Administration of NaP causes a significant rise in serum phosphate, even in patients with normal creatinine clearance. Hypokalemia is more prevalent in frail patients. However, NaP preparations may be safe in selected healthy elderly patients.
Possible underlying inflammatory bowel disease
NaP preparations may cause mucosal abnormalities that mimic Crohn’s disease. However, the frequency of this problem is rare and may not mitigate against using NaP. This caveat is most important in the initial colonoscopic evaluation of patients with symptoms suspect for colitis.
One study showed that patients with diabetes have significantly poorer preparations with PEG solutions than non-diabetics, although there is no evidence that NaP preparations are superior in this group.
During pregnancy the need for colonoscopy is uncommon, therefore the safety and efficacy of colonoscopy in these individuals is not well studied. However, invasive procedures are justified when it is clear that by not doing so could expose the fetus and/or mother to harm. The safety of PEG electrolyte isotonic cathartic solutions has not been studied in pregnancy. PEG solutions are FDA Category C for use in pregnancy, as defined in the FDA Current Category for Drug Use in Pregnancy, wherein no adequate and well-controlled studies have been undertaken in pregnant women and a limited number of animal studies have shown an adverse effect. The common use of PEG solutions such as Miralaxto manage constipation associated with pregnancy supports its safety as a bowel preparation. Sodium phosphate preparations, which are FDA Category C, may cause fluid and electrolyte abnormalities and should be used with caution.
While there are no “national standards” per se for pediatric bowel preparations for colonoscopy, review of the literature documents the three most commonly used preparations. The least commonly used preparation is the administration of two pediatric Fleetsenemas and X-prep (for age). A more widely used preparation includes Miralaxat 1.25mg/kg/day for 4 days, the last day of which the child is maintained on clear liquids. This regimen is mild, well tolerated, and relatively simple to administer. The simplest preparation, both for the parents and the child, is the administration of a sugar-free clear liquid diet the day prior and then nil per os for 8 hours prior to the colonoscopy. This regimen is combined with Fleetsphosphosoda at a dosage of 1.5 tablespoons for children less than 15kg and 3 tablespoons for children 15kg or more, the afternoon and then again the evening prior to the colonoscopy. Each of these preparations is safe and will adequately prepare the child’s colon for colonoscopy (GRADE 1A).
Table 3 shows the cost of bowel preparation agents listed as average wholesale price (AWP) that is provided by the “Red Book” July 2005. As can be seen, the least expensive solution is oral sodium phosphate and the most expensive the tablet form of sodium phosphate. The various polyethylene glycol preparations are intermediate in cost. None of the bowel preparation agents has an associated CPT code that would allow for separate payment reimbursed by the patients’ insurance company or Medicare in an outpatient setting. In an inpatient setting, the reimbursement for these agents would be included in the DRG payment. Of note, patients’ compliance and adequacy of bowel preparation agents can affect the direct cost for colonoscopic examination. A cost analysis has shown that, imperfect bowel preparation could prolong the procedure time and increase the chance for aborted examination and repeat colonoscopy earlier than suggested or required by current practice standards. Therefore, imperfect bowel preparation led to a 12% increase in costs at a university hospital setting and a 22% increase at a public hospital setting. A meta-analysis performed on eight colonoscopist-blinded trials showed that the direct costs of colonoscopic examination (excluding the cost of bowel preparation agents) were $465 for NaP and $503 for PEG, assuming that the rates of re-examination secondary to incomplete bowel preparation for NaP and PEG were 3% and 8%, respectively. The results suggest that NaP is less costly than PEG with a more easily completed preparation.
For inspection of the colonic mucosa, Colonoscopy is the most commonly employed technique used. The safety and effectiveness of colonoscopy in identifying important colonic pathology is directly impacted by the quality of the bowel preparation done in anticipation of the procedure. Physicians favor preparations associated with the best patient compliance in order to achieve the best results. Patients favor preparations that are low in volume, palatable, have easy to complete regimens, and are either reimbursed by health insurance or are inexpensive. Both patients and physicians favor preparations that are safe to administer in light of existing comorbid conditions and those that will not interact with previously prescribed medications. Aqueous NaP solutions, NaP tablets, and PEG solutions, especially low volume solutions, are all accepted and well tolerated by the majority of patients undergoing bowel preparation for colonoscopy. Physicians are advised to select a preparation for each patient based on the safety profile of the agent, either NaP or PEG, in light of the overall health of the patient, their co-morbid conditions, and currently prescribed medications. In certain circumstances, such as bowel preparation in children and the elderly and renal insufficiency, it may be advisable to adhere to PEG-based solutions because of the risks of occult physiologic disturbances that may contraindicate the use of NaP-based regimens. A variety of other preparations, none of which seem as popular due to inferior efficacy and/or patient acceptance, remain available for use in other circumstances where bowel preparation is necessary. Many adjuncts to bowel preparation have been proposed but remain largely inefficacious and therefore cannot be recommended for routine use.