Hyposmotic agents

Another low-volume PEG preparation requires the addition of a commercially available electrolyte solution in the form of a sports drink to PEG-3350 (PEG-SD). It should be emphasized that the combination of a sports drink and PEG-3350 is hyposmotic, is not FDA approved for colonoscopy preparation, and is not equivalent to FDAapproved low-volume 2-L isosmotic PEG-ELS preparations. However, low-volume 2-L PEG-SD (using over-the-counter generic or name brand PEG-3350) is widely used and is often administered with adjuncts such as bisacodyl. Studies that have compared full-volume 4-L PEG-ELS with low-volume 2-L PEG-SD combined with bisacodyl have demonstrated mixed results.80 One study suggested that there may be a lower adenoma detection rate with the low-volume 2-L PEG-SD/bisacodyl preparation compared with a 4-L PEG-ELS preparation due to differences in bowel preparation quality.81 A 4-armed study compared 4-L PEG-ELS administered the evening before, split-dose 4-L PEG-ELS, low-volume 2-L PEG-SD administered the evening before, and split-dose low-volume 2-L PEG-SD. This study found that both split-dose regimens were superior to the evening dose-only regimens with no significant preparation quality differences between the 4-L PEG-ELS and the PEG-SD preparations. Other studies comparing a 4-L PEG-ELS preparation with a low-volume 2-L PEG-SD preparation have found no differences in bowel preparation quality.

The safety of PEG-SD combined with bisacodyl has not been well reported to date. It remains unclear whether the addition of bisacodyl is beneficial and whether its use may increase side effects without improving the quality of the preparation. Although there are theoretical concerns regarding mixing PEG-3350 with Crystal Light or Gatorade due to the potential of unabsorbed carbohydrates to be metabolized into explosive gases, no such adverse events have been reported to date. There have been rare reports of hyponatremia. In studies that evaluated the metabolic effects of the PEG-SD preparation compared with a standard PEG-ELS regimen, there were no clinically significant electrolyte changes from baseline due to the bowel preparation. However, a recent study compared the effects of PEG-SD (n Z 180) with an FDA-approved low-volume 2-L PEG-ELS (n Z 184) on serum electrolytes and found that changes from baseline in serum Na, K, and Cl were significantly greater with PEG-SD.87 The incidence of hyponatremia, the primary endpoint of the study, with PEG-SD was nearly twice that with the low-volume 2-L PEG-ELS (3.9% vs 2.2%, odds ratio 1.82, 95% confidence interval, 0.45-8.62), although this difference was not statistically significantly different. Preparation completion and overall colonic cleansing (per the Aronchick Scale) were similar between the groups.

Hyperosmotic agents

Oral sodium sulfate. Oral sodium sulfate (OSS) preparations have not been associated with significant fluid and electrolyte shifts, likely because sulfate is a poorly absorbed anion. One study that compared this preparation with low-volume 2-L PEG-ELS with ascorbic acid found OSS to be noninferior. In a multicenter study of 136 patients receiving OSS versus 4-L of SF-PEG-ELS, patients who ingested the OSS had less bloating, more successful preparation administration, and more frequent achievement of an excellent preparation (71.4% vs 34.3%, P Z .01). There are limited data available on the safety of OSS, although no serious adverse effects have been reported to date. In one report, patients receiving the entire OSS preparation in 1 day did report slightly increased GI events and higher vomiting scores compared with 4-L PEG-ELS; however, this was not seen in the split-dose regimen.

Rex et al90 recently reported the results of a multicenter study that compared split-dose OSS with split-dose sodium picosulfate/magnesium citrate. Among 338 patients randomized to receive either preparation, OSS resulted in a higher rate of successful (excellent or good) preparation (94.7% vs 85.7%; P Z .006) and more excellent preparations (54% vs 26%; P! .001) compared with sodium picosulfate/magnesium citrate. Both preparations were well tolerated, and there was no difference in treatmentemergent adverse events between the 2 preparations

Magnesium citrate. Magnesium citrate is a saline solution laxative containing magnesium cations that acts osmotically and also stimulates the release of cholecystokinin, resulting in intraluminal accumulation of fluid and electrolytes promoting small intestinal and possibly colonic transit. Magnesium citrate is not FDA approved as a colonoscopy preparation, and there are limited data evaluating its effectiveness as a stand-alone colonoscopy preparation. One study that compared magnesium citrate with an aqueous sodium phosphate preparation found the magnesium citrate preparation to be superior.91 Magnesium is excreted via the kidneys, and this preparation should be avoided in patients with known kidney disease or the elderly. Magnesium toxicity can result in bradycardia, hypotension, nausea, and drowsiness. Serious adverse events including death have been reported.92,93 Because of the limited efficacy data and potential toxicity associated with this preparation, it is not recommended for routine colonoscopy preparation

Sodium phosphate. Aqueous sodium phosphate is a low-volume hyperosmotic solution that, due to serious adverse events, is no longer recommended, and the brand name version was voluntarily withdrawn from the market (although other brands are still available over the counter as laxatives). Patients with compromised renal function, dehydration, hypercalcemia, or hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have experienced phosphate nephropathy after use of oral sodium phosphate solutions. The effects seem to be primarily age and dose related, although phosphate nephropathy after sodium phosphate ingestion has been reported to occur in patients without underlying disease. Although usually asymptomatic, hyperphosphatemia is seen in as many as 40% of healthy patients completing sodium phosphate preparation and is especially significant in patients with renal failure. In addition, sodium phosphate has been shown to cause elevated blood urea nitrogen levels, increased plasma osmolality, hypocalcemia, hyponatremia, and seizures. Sodium phosphate can cause clinically important fluid and electrolyte shifts, especially in elderly patients or patients with bowel obstruction, small intestinal disorders, impaired gut motility, renal or liver disease, or congestive heart failure.100 Because of the risk of renal injury and electrolyte abnormalities, the FDA has issued a box warning for the prescription tablet form of sodium phosphate.