Jack A. Di Palma

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience

BACKGROUND & AIMS Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. METHODS We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. RESULTS A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was

A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy.

5.3 million. CONCLUSIONS EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit.

A Randomized, Multicenter Comparison of Polyethylene Glycol Laxative and Tegaserod in Treatment of Patients With Chronic Constipation

OBJECTIVES:We sought to evaluate a new, low-volume, oral sulfate solution as a bowel preparation for colonoscopy in adult patients.METHODS:The investigations were designed as two multicenter, single-blind, randomized, non-inferiority studies to show that the sulfate regimen would effect cleansing that is acceptable and equivalent to polyethylene glycol electrolyte solution with ascorbic acid (PEG-EA), and would be suitable for colonoscopy. One study evaluated same-day administration; the other compared the two study preparations given by split-dose administration in which the first portion was taken the evening before colonoscopy and the second portion on the morning of the procedure. The primary efficacy variable was based on bowel cleansing graded by an investigator who was unaware of the preparation method received.RESULTS:Study 1 randomized 408 outpatients scheduled for colonoscopy for routine indications, with 387 subjects taking the preparation. In all, 364 subjects were randomized and took the preparation in study 2. The demographics of the enrolled subjects were similar across both treatment groups in the two studies, including gender, race, and ethnic characteristics. The primary efficacy analysis supports the conclusion that the oral sulfate solution produces the same degree of cleansing as PEG-EA. Successful preparations were seen in 82.4% and 80.3% in study 1 and 97.2% and 95.6% in study 2 for the oral sulfate solution and the PEG-EA regimen, respectively. Although no difference in excellent preparations was seen in the 1-day preparation, split-dose administration resulted in more excellent preparations in the sulfate group than in the PEG-EA group (63.3 vs. 52.5%, P=0.043). Preparation-related symptoms of cramping, bloating, nausea, and vomiting were generally mild and infrequent. Sulfate subjects reported slightly increased gastrointestinal events and higher vomiting scores (P=0.009) in the 1-day preparation but not in the split-dose regimen. There were no other differences for adverse events or clinically significant laboratory findings, including no increased creatinine.CONCLUSIONS:The new 960 -ml oral sulfate solution is effective for colonoscopy cleansing and has an acceptable safety profile.

A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy.

OBJECTIVE: Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. This study was designed to compare the efficacy of each product over a 4-wk treatment period.METHODS: Study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information.RESULTS: A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P = 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P = 0.019) and had significantly greater improvement in constipation symptoms (P = 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events.CONCLUSIONS: While PEG laxative and tegaserod are safe for their intended use in chronic constipation, PEG had superior efficacy, caused fewer headaches, and produced greater improvement of constipation symptoms. Trial is registered at: http://www.clintrials.gov. Unique registration number: NCT00153140

Overnight efficacy of polyethylene glycol laxative

BACKGROUND Low-volume bowel preparations for colonoscopy improve tolerability. OBJECTIVE We compared the efficacy, tolerability, and safety of a new low-volume sulfate solution with a standard 4-L polyethylene glycol electrolyte lavage solution as bowel preparation for colonoscopy. DESIGN Multicenter, single-blind, randomized, noninferiority study. SETTING Five academic and community endoscopy centers in the United States. PATIENTS One hundred thirty-six outpatients undergoing colonoscopy. INTERVENTIONS Patients were randomized to receive 4 L sulfate-free electrolyte lavage solution (SF-ELS) given the night before colonoscopy versus 12 oz oral sulfate solution (OSS) given in equally divided doses the evening before and the morning of colonoscopy. MAIN OUTCOME MEASUREMENTS Successful (ie, good or excellent) bowel preparation. RESULTS Successful bowel preparation was more frequent with OSS than with SF-ELS (98.4% vs 89.6%; P = .04). Excellent preparation also was achieved more frequently with OSS (71.4% vs 34.3%; P < .001). Patients receiving OSS had less residual stool in the cecum and ascending colon and less residual fluid in the cecum and ascending, transverse, and descending colon compared with SF-ELS. The percentage of patients with GI side effects and adverse events was not significantly different between the 2 groups. LIMITATIONS The OSS was administered in split doses, whereas the SF-ELS was administered the evening before (which is its FDA-approved regimen). CONCLUSIONS Oral sulfate solution is promising as a safe low-volume preparation for colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00856843.).

Lubiprostone neither decreases gastric and small-bowel transit time nor improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled study

OBJECTIVES:Clinical studies in constipated adult patients have shown that a 17- or 34-g daily dose of polyethylene glycol (PEG) 3350 (MiraLax) is safe and effective for the treatment of constipation, with the best efficacy seen in wk 2 of treatment. The purpose of this study was to determine an optimal dose of PEG to provide satisfactory relief of constipation within 24 h.METHODS:A total of 24 adult study subjects who met Rome II criteria for constipation were randomized in a double-blind, parallel pilot study to receive a single dose of placebo or PEG laxative at doses of 51, 68, or 85 g in 500 ml of flavored water. Over a 72-h period, subjects rated bowel movements (BM), completeness of evacuation, and satisfaction.RESULTS:The 68-g dose seemed to be most satisfactory. Five of six subjects had a BM within 24 h. The time to first BM was 14.8 h for 68 g versus 27.3 h for placebo (p = NS). The time to second BM was 19.2 h versus 47.2 h for 68 g and placebo, respectively (p = 0.003). Of the subjects receiving 68 g of PEG, 50% and 100% reported complete evacuation for the first and second BM, respectively. The average number of BMs in 24 h for placebo, 51 g, 68 g, and 84 g were 0.5, 2.2, 2.2, and 4.2, respectively (p = 0.004). There were no adverse reactions, and no patient reported incontinence or complained of cramps or diarrhea at any dose. There were no changes in measured electrolytes, calcium, glucose, BUN, creatinine, or serum osmolality.CONCLUSIONS:A 68-g dose of PEG laxative seems to provide safe and effective relief in constipated adults within a 24-h period.

Durability of the diagnosis of irritable bowel syndrome based on clinical criteria

BACKGROUND Lubiprostone, a selective activator of type 2 chloride channels, is approved for treatment of chronic idiopathic constipation and recently constipation-predominant irritable bowel syndrome. It has been suggested that lubiprostone has a prokinetic effect. OBJECTIVE This investigation was designed to evaluate lubiprostone as a preparation and propulsive agent for small-bowel capsule endoscopy. The PillCam Small Bowel capsule endoscopy system with the PillCam SB1 capsule and Rapid 5 software platform were used. DESIGN The study was designed as a double-blind, placebo-controlled trial. PATIENTS Forty healthy adults. MAIN OUTCOME MEASURES Gastric transit time (GTT), small-bowel transit time (SBTT), and adequacy of small-bowel cleansing preparation. INTERVENTIONS The study subjects received 24 mug lubiprostone or placebo 30 minutes before PillCam capsule ingestion. METHODS Capsule endoscopy studies were read by 2 independent investigators unaware of the study medication received, and differences in interpretation were resolved by consensus. Anatomical landmarks were identified, and GTT and SBTT were calculated. Overall preparation quality assessment of the proximal, mid, and distal small bowel was determined by using a 4-step scale. The percentage of visualized bowel was determined by review of 10-minute video segments at 1-hour intervals after the capsule passed through the pylorus. RESULTS In the lubiprostone group (n = 20), 2 subjects did not pass the capsule through the pylorus in the 8-hour battery life of the capsule. An additional 3 capsules did not pass into the colon. In the placebo group (n = 20), all capsules passed into the small bowel, but 1 did not pass into the colon. The subjects in whom the capsule did not pass into the small bowel were excluded from the small-bowel analysis. In the subjects in whom the capsule did reach the colon, the SBTT could not be calculated and they were excluded from SBTT analysis. The mean GTT in the lubiprostone group was 126 minutes and 43 minutes in the placebo group (P = .0095). The mean SBTT in the lubiprostone group was 188 minutes and 219 minutes in the placebo group (P = .130). The overall preparation assessment of the small bowel was not statistically significant between the 2 groups in the proximal, mid, or distal small bowel (proximal, P = .119; mid, P = .118; distal, P = .121). There was no significant difference in lubiprostone compared with placebo in the percentage of visualized small bowel. LIMITATIONS Some capsules did not leave the stomach or reach the cecum. CONCLUSION Lubiprostone produced a significant increase in GTT but did not result in a significant decrease in SBTT compared with placebo. The administration of lubiprostone before capsule ingestion did not result in improved overall preparation of the small bowel for capsule endoscopy or increase the percentage of visualized small bowel. (The trial was registered at www.clinicaltrials.gov, identifier NCT00746395.).

The Role of Capsule Endoscopy in Evaluating Inflammatory Bowel Disease

Our purpose was to evaluate the durability of the diagnosis of irritable bowel syndrome (IBS) based on clinical criteria. The study population consisted of a cohort of previously published study patients evaluated for IBS between 1989 and 1992, who met the International Congress of Gastroenterology criteria for IBS. Patients were reinterviewed for cardinal features of IBS, Rome I, Rome II, and Manning criteria 10–13 years after the initial diagnosis. During the observational follow-up period, there were 75 patients, 14 males and 61 females, with a mean age of 47.5 ± 11.3 years (SD; range, 20 to 75 years). Mean time of reinterview after initial diagnosis was 11.8 ± 0.9 years (range, 10 to 13 years). None of the 75 patients had an abdominal condition which could have been mistaken for IBS. Other abdominal conditions diagnosed during this period included diverticulitis (five), uterine fibromyoma (three), and gallbladder disease (three). Sixty-nine patients (92%) did not consider their symptoms as resolved. Thirty-five (46.7%) had repeat structural evaluation of the colon for similar symptoms without any new diagnoses made. Twenty-six (34.7%) and 32 (42.7%) presently meet the Rome II and Rome I criteria for IBS, respectively. Clinicians are advised to use clinical criteria for a specific and durable diagnosis of IBS.

Endemic fungal infections in inflammatory bowel disease associated with anti-TNF antibody therapy.

Capsule endoscopy is a relatively new technology available in the investigation of IBD. Its place in the algorithm of evaluating IBD is being refined. Capsule endoscopy has the ability to visualize the entire SB with very few complications. It is a sensitive test for the diagnosis of mucosal changes, but should be viewed as complementary to other radiologic evaluations, such as CTE and MRE. Capsule endoscopy is nonspecific and its findings have to be interpreted with caution and in the right clinical setting, because up to one fifth of normal individuals may have subtle changes in the small intestine. Care should also be taken to exclude NSAID use because it mimics findings seen in CD. Capsule endoscopy is an exciting technology that opened the possibility of the evaluation of the SB in the era of “deep remission.” It is best applied in patients with a high clinical suspicion for IBD after unremarkable colonoscopy with terminal ileal intubation and radiologic investigation.

How to choose the best preparation for colonoscopy.

Abstract:Patients with inflammatory bowel disease are susceptible to complications from pharmacologic treatment of their disease. Tumor necrosis factor (TNF)-&agr; inhibitors are being used increasingly in the treatment of inflammatory bowel disease and can be associated with adverse events, including common infections, and rarely the development of serious life-threatening opportunistic infections. TNF-&agr; inhibitors have the ability to prevent an effective patient granulomatous response, and this may be associated with an increased risk of developing mycobacterial and certain fungal infections, including histoplasmosis, blastomycosis, and coccidioidomycosis, endemic in several parts of the United States. The concern for invasive fungal infection was realized during clinical trials and further demonstrated after the marketing of TNF-&agr; inhibitors. Because of this awareness, the Food and Drug Administration developed an adverse event-reporting system to capture cases of infections associated with the use of TNF-&agr; inhibitors. These opportunistic fungi have a great degree of regional variability, and it has been very difficult to quantify the incidence of infection in patients treated with TNF-&agr; inhibitors. Currently, there are no formal guidelines regarding the use of TNF-&agr; inhibitors and these fungal infections. Considering that gastroenterologists have embraced the use TNF-&agr; inhibitors as a valuable armamentarium in the treatment of inflammatory bowel disease, they must be aware of therapy-related infectious complications, including appropriate diagnostic, therapeutic, and preventive strategies. In this article, we explore the association of these fungal entities in relation to the TNF-&agr; inhibitor therapy by considering information provided in the gastroenterology, infectious diseases, rheumatology, and transplant literature. Finally, we provide some recommendations on diagnosis and treatment.