Background. Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients. In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days. Results. Only 318 (20.6%) of the 1542 screened adults during the 1/17–10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N (n = 6) and P (n = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P = 1.0). No patient experienced opioid withdrawal. Conclusions. Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.
Variceal bleeding is one of the most feared complications in patients with liver cirrhosis. It continues to be a leading cause of death among patients with liver cirrhosis. Although its prognosis has improved over the last several decades, it still carries substantial mortality. Preventing variceal bleeding has been extensively studied and evaluated in several studies in the recent years and the comparison between the different modalities available to prevent variceal bleeding has been an area of discussion. Currently the two most widely used modalities to prevent variceal bleeding are pharmacologic (non-selective beta-blockers [NSBB]) and endoscopic (variceal band ligation [VBL]) which have replaced sclerotherapy in the recent years. In addition to NSBB and recent carvedilol, different other medications have been evaluated including isosorbide mononitrates, spironolactone and angiotensin blocking agents. Comparing the outcomes and adverse effects of these two modalities has been evaluated in different studies. Some studies have showed superiority of VBL until recently, when carvedilol has been included, however; overall mortality has been similar in most trials. Despite that, NSBB remain the first line treatment, as they are cheaper and relatively effective in preventing both esophageal and gastric bleeding. The following sections discuss the primary prevention of variceal bleeding with a focus on NSBB, carvedilol and VBL.
Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of gastrointestinal pathology may signify locally advanced disease from a surrounding organ that secondarily involves the gastrointestinal tract. These findings warrant further investigation prior to any intervention to ensure appropriate treatment.
A Schatzki ring is a submucosal, fibrotic thickening located at the gastroesophageal junction. Endoscopic treatment traditionally involves disruption of the ring. Many approaches have been described including bougies, balloons, biopsies, and diathermic monopolar incision. While all of these approaches are effective in the short-term, recurrence is common. The objective of our study was to evaluate the feasibility of complete excision of the ring using jumbo cold biopsy forceps. Our main outcome measurements were the feasibility, safety, and efficacy of complete obliteration of Schatzki rings using jumbo cold biopsy forceps. We designed an observational study using a standard protocol for patient management and data collection using a university hospital as our setting. We followed 10 patients with dysphagia due to a Schatzki's ring, six of whom had previously undergone bougienage or balloon dilation. Five patients were on maintenance therapy with a proton pump inhibitor and one with an H2 blocker. Complete endoscopic obliteration of the Schatzki rings with a cold jumbo biopsy forceps was achieved in all 10 patients requiring a mean of 9.8 biopsies (range 8-12). Omeprazole (20 mg twice daily) was prescribed after the procedure. All 10 patients demonstrated improvement in dysphagia after treatment, which persisted during a mean follow-up time of 379 days (range 63-496 days). There were no serious complications. The limitations of our study include lack of a control group, a small sample size, and being a single-institution study. We concluded that complete Schatzki ring obliteration with jumbo cold biopsy forceps is a safe, feasible, and effective endoscopic treatment.
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