Brian W. Sipe

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 RESULTS A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified.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

Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases

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.

Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate

Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases

Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

Severe and severe/complicated Clostridium difficile infection (CDI) can result in ICU admission, sepsis, toxic megacolon and death. In this setting, colectomy is the standard of care but it is associated with a 50% mortality.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

Background:New treatments are needed as Clostridium difficile infection (CDI) is becoming increasingly formidable. Fecal microbiota transplantation (FMT) has a 90% success rate in the treatment of recurrent CDI. However, evidence regarding its safety, efficacy, and effect on disease activity in patients with inflammatory bowel disease (IBD) is lacking. Methods:This cohort study used data from 8 national and international academic centers. Patients with established IBD who underwent FMT for recurrent CDI were followed for a minimum of 3 months. The primary outcome was CDI recurrence at 3 months after FMT. The secondary outcomes were (1) IBD activity and severity at 3 months based on the judgment of the treating physician, endoscopic findings, and clinical disease activity scores; and (2) safety. Results:Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohns disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients. Serious adverse events included colectomy (1.4%), hospitalization for CDI (2.9%), hospitalization for IBD flare (2.9%), small bowel obstruction (1.4%), CMV colitis (1.4%), and pancreatitis (1.4%). Discussion:The overall CDI cure rates were high, with a large percentage of patients experiencing clinical improvement of their IBD after FMT. A minority of patients developed an IBD flare. No severe adverse events directly attributable to FMT were found in this largest reported series of recurrent or refractory CDI patients with concurrent IBD.

A low-residue diet improved patient satisfaction with split-dose oral sulfate solution without impairing colonic preparation

OBJECTIVES:Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10–20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure.METHODS:Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model.RESULTS:Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26–15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55–9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18–1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1–2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort.CONCLUSIONS:Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach

BACKGROUND Preprocedural dietary restrictions have been identified as a common reason potential candidates for colorectal cancer screening do not undergo colonoscopy as recommended. OBJECTIVE To study whether a low-residue diet impacts bowel preparation with oral sulfate solution. DESIGN Endoscopist blinded, prospective, randomized controlled trial. SETTING Community-based outpatient ambulatory surgical center. PATIENTS Patients scheduled for outpatient colonoscopy. INTERVENTIONS Subjects were randomized to ingest either a low-residue diet of specified foods for breakfast, lunch, and snack or a clear liquid diet the day before the colonoscopy. MAIN OUTCOME MEASUREMENTS The quality of the bowel preparation was assessed using the Boston Bowel Preparation Scale. Subject satisfaction with bowel preparation, diet, and severity of side effects was measured by a visual analog scale. RESULTS Two hundred thirty subjects were recruited (114 clear liquid and 116 low residue). Mean preparation scores were not statistically different in either their segmental scores or total score. Subjects in the low-residue arm reported significantly higher satisfaction with bowel preparation medication, diet, and entire preparation process. Observed rates of side effects were low, and there was no statistical difference between the two groups. The rate of procedural cancellation was significantly higher in the clear liquid group compared with the low-residue group (20% vs 9%, P = .03). LIMITATIONS Single-center study. CONCLUSIONS A low-residue diet did not impair the quality of bowel preparation achieved with split-dose oral sulfate solution but did improve patient satisfaction.

Stool Donor Body Mass Index Does Not Affect Recipient Weight After a Single Fecal Microbiota Transplantation for C. difficile Infection

ABSTRACT Severe and severe-complicated Clostridium difficile infection (CDI) is associated with high morbidity and mortality. Colectomy is standard of care; however, post-surgical mortality rates approach 50%. Case reports suggest fecal microbiota transplant (FMT) is a promising treatment of severe and severe-complicated disease but there is a paucity of data. Here, we present a single center experience with a novel sequential FMT protocol for patients refractory to maximal medical therapy. This approach consists of at least one FMT delivered via colonoscopy with criteria for repeat FMT and continued vancomycin therapy based on clinical response and pseudomembranes. Our cohort included 57 consecutive inpatients diagnosed with severe or severe-complicated CDI and treated with FMT. Overall, 91% (52/57) experienced clinical cure at 1 month with a 100% cure rate among severe CDI (n = 19) patients and an 87% cure rate for severe-complicated CDI (n = 33) patients. For the cohort, the survival rate was 94.7% at 1 month and 78.6% at 3 months. There were no serious adverse events related to FMT including no procedure-related complications or perforation. There was no difference in outcome between fresh or frozen fecal material. Sequential FMT for inpatients with severe or severe-complicated CDI is promising and may be preferred over colectomy in certain patients.

Letter: Faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection - Authors' reply

*Department of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada; OpenBiome, Somerville, Massachusetts; kDivision of Infectious Diseases, University of Calgary, Calgary, AB, Canada; Down25, Indianapolis, Indiana; Department of Biostatistics, Richard M. Fairbanks School of Public Health and School of Medicine, Indiana University, Indianapolis, Indiana; **Tufts Friedman School of Nutrition Science and Policy, Boston, Massachusetts; Brigham and Women’s Hospital, Boston, Massachusetts; and Harvard Medical School, Boston, Massachusetts

Propofol versus midazolam/meperidine for outpatient colonoscopy: Administration by nurses supervised by endoscopists

SIRS, We were delighted to read that Pecere et al. have successfully applied sequential faecal microbiota transplantation (FMT) in combination with fidaxomicin to cure severe and complicated Clostridium difficile infection (CDI). In our protocol developed for severe and complicated CDI, we used vancomycin because of institutional availability and cost considerations. We agree with Pecere et al. that fidaxomicin could be a superior alternative to vancomycin. A meta-analysis of two phase III trials comparing fidaxomicin and vancomycin in the treatment of CDI showed that fidaxomicin use was associated with a 37% decrease in persistent diarrhoea and early death within 12 days of treatment initiation. Further, a recent analysis concluded that fidaxomicin was cost-effective (incremental cost-effectiveness ratio of £16 529 per quality-adjusted life year) compared with vancomycin when used to treat severe CDI. It is not yet known whether fidaxomixin is more effective and less costly when used in combination with sequential FMT.