Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic

Key Points Question Can video capsule endoscopy be safely used as an alternative to standard endoscopic procedures for the initial evaluation of gastrointestinal bleeding during the COVID-19 pandemic? Findings In this cohort study of 146 patients (74 with COVID-19), active bleeding was more frequently identified with video capsule endoscopy as the first strategy (59.5%) compared with conventional endoscopic evaluation (25.0%). The number of invasive procedures was significantly decreased with video capsule endoscopy without increased risk of rebleeding or compromising safety. Meaning The results of this study suggest that video capsule endoscopy can serve as a safe alternative to the standard endoscopic evaluation of gastrointestinal bleeding because it reduces the number of invasive procedures, personnel involved, and use of personal protective equipment.


Introduction
SARS-CoV-2, a single-stranded enveloped RNA virus, is responsible for the COVID-19 pandemic. 1 SARS-CoV-2, found in the gastric, duodenal, and rectal epithelia of infected patients, 2 can be transmitted via aerosols, droplets, and physical contact. 3,4 Esophagogastroduodenoscopy (EGD) and colonoscopy, routinely used in the evaluation of gastrointestinal (GI) disorders, are both known to produce aerosols, thus potentially exposing endoscopy personnel to SARS-CoV-2. 4 However, although many elective GI procedures can be deferred or canceled during surges of the pandemic, 5 the evaluation of acute GI bleeding is often urgent and as such cannot be deferred. Current guidelines recommend early EGD 6 and/or colonoscopy 7 within 24 hours as the first-line diagnostic and therapeutic modalities for acute GI bleeding.
More recently, several studies have suggested a role for video capsule endoscopy (VCE) in the management of acute GI bleeding. 8-10 Video capsule endoscopy is a minimally invasive tool that does not require sedation or GI manipulation and can visualize the upper, middle, and lower GI tract 8 without generating aerosols. Reports suggest that VCE is more effective than conventional endoscopy in detecting the site of active bleeding in many patients 9 and hence serves as a valuable tool in guiding further diagnostic and therapeutic interventions if needed. These changes in protocol, prioritizing early VCE as a first-line diagnostic procedure, have been shown to be safe 9,10 and well tolerated. In this study, we sought to examine the use of VCE for the initial evaluation of suspected GI bleeding in patients with suspected or established COVID-19 as a first-line tool to help minimize patient and personnel exposure to SARS-CoV-2, limit unnecessary contacts, save personal protective equipment (PPE), and avoid invasive and unnecessary procedures.

Methods Design
We designed a multicenter retrospective cohort study aimed at assessing the comparative use of VCE as a triaging tool as an alternative to standard of care (SOC) for evaluation of GI bleeding. The study was conducted at UMass Memorial Medical Center and Louisiana State University Health Sciences Center and approved by the institutional review boards at both institutions. Study personnel (S.H., M.H., L.S., M.P., and A.F.) collected data via review of medical records and completed data entry into a standardized secure online database, Research Electronic Data Capture (REDCap), 11 which was hosted at UMass Memorial Medical Center. Demographic, clinical, and outcome data were collected and analyzed. The institutional review boards for each facility granted a waiver of informed consent for the patients receiving SOC, because this was retrospective data collection. The patients undergoing VCE were regarded as receiving SOC and were not required to provide consent for the study; rather, only routine informed consent for procedures was required by the institutional review boards. The waiver also covered retrospective data collection for the VCE cohort. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
The video capsule group included 74 patients with COVID-19 admitted between March 15 to June 15, 2020, who underwent VCE as the first-line diagnostic modality for evaluation of GI bleeding.
A total of 72 historical controls were identified from January 1 to 31, 2020, a period before the known spread of the COVID-19 pandemic in the US; these patients had undergone SOC. Inclusion criteria for patients in both groups required that they be consecutive, hemodynamically stable adults (age >18 years) with suspected GI bleeding as evidenced by the presence of melena, hematochezia, hematemesis, and/or severe anemia. Patients who developed signs and symptoms of GI bleeding during their hospitalization for other indications were also included. Exclusion criteria for VCE included dysphagia, gastroparesis, previous intestinal surgery, abdominal radiotherapy, and the presence of an implantable cardiac device. Patients were followed up for 30 days after their episode of GI bleeding for assessments of rebleeding and mortality.

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Use of Video Capsule Endoscopy to Assess Acute GI Bleeding During COVID-19 Invasive procedures included EGD, colonoscopy, enteroscopy, conventional angiography, and surgery. Diagnostic procedures were defined as any of the abovementioned invasive procedures and computed tomographic angiography and VCE, which we defined as minimally invasive. An upper source of bleeding was defined to be within the reach of an EGD, a middle source as a small intestinal bleed beyond the second portion of the duodenum, and a lower source as a colonic source of bleeding. A presumptive source was defined as any lesions or blood typically associated with a bleeding source with or without signs of active bleeding or stigmata of bleeding.
Both centers used the PillCam SB 3 and RAPID software, version 8.00 or higher (both Medtronic). Patients fasted for 6 to 8 hours before capsule ingestion per standard protocol. Patients then swallowed the capsule with 118 to 237 mL of water. No purgative bowel preparation was used.
The real-time viewer was used immediately after ingestion to check for blood in the stomach and again within a few hours to check for bleeding in the small intestine. If bleeding was noted, the study was truncated, data were downloaded from the recorder, and a video created on a workstation was reviewed to determine the exact source of bleeding. If no blood was seen on the initial review, the capsule was allowed to record for up to 12 hours before download and review.
The primary end point of the study was detection of active bleeding or stigmata of recent hemorrhage. Secondary end points included the number of patients undergoing invasive procedures, number of additional procedures needed for evaluation, rates of rebleeding and rehospitalization, transfusion requirements, and rates of mortality.
To perform VCE, we assumed 1 staff member, albeit for a brief encounter, aided the patient in swallowing the video capsule and later collected and cleaned the equipment. For EGD, colonoscopy, and enteroscopy, we assumed 4 staff members were present during the procedure, which included the endoscopist, endoscopy nurse, endoscopy technologist, and anesthesia staff. We assumed no trainee involvement and no additional preprocedure and postprocedure staff for this estimate.

Statistical Analysis
Patient characteristics are described as means (SDs) or as percentages. Continuous variables were analyzed using t test and binary variables were analyzed using χ 2 or Fisher exact tests. Multivariate logistic and linear regression estimated adjusted odds ratios (ORs) or differences of means for primary and secondary outcomes. As a secondary analysis, the primary and secondary outcomes were compared in propensity score-matched patients. Key variables with a standardized difference in absolute value greater than 0.15 were considered for matching. Propensity scores were estimated using a logistic regression model for the COVID-19 vs SOC cohorts that included age, sex, race/ ethnicity, Glasgow-Blatchford score, cirrhosis, and kidney failure. One-to-one matching within center using a caliper of 0.15 maximized the sample size (n = 54 per arm) while balancing the key characteristics (eTable 2 in the Supplement). For the primary outcome of active bleeding, secondary analyses included a multivariable-adjusted OR (COVID-19 vs SOC) in the population on common support of the propensity score, and in the matched population adjusted for characteristics with standardized difference greater than 0.15 in absolute values. Sample size was based on data from 2 randomized clinical trials. 8, 12 With 70 patients per group, there would be greater than 80% power for differences in rates of active bleeding detection of 25% or for ORs of 3.0 or greater. The significance threshold was α = .05; all tests were 2 sided where appropriate. Unpaired t test, Fisher exact test, logistic regression, and linear regression assumed independent samples. Statistical analysis was conducted with Stata, version 16.1 (StataCorp LLC).

Results
The study included a total of 146 patients, with 74 patients in the COVID- 19   The P values for active bleeding and presumed source of bleeding were analyzed using the Fisher exact test (categorical variables). The other P values were analyzed using the t test (continuous variables). b Adjusted for sex; age; race; Glasgow-Blatchford score; use of nonsteroidal anti-inflammatory drugs, aspirin, warfarin, and direct oral anticoagulants; no anticoagulation; cirrhosis; kidney failure; and presenting symptoms. overall population or the matched population (Table 2). There was no mortality attributed to GI bleeding in either group.

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The matched population, but not the overall population, showed a significant difference in localization of bleeding (  Table 2). This calculation was associated with an estimated 30% reduction in the overall use of PPE.

Discussion
In this cohort study, we noted that the initial use of VCE as an alternative to the traditional, more invasive diagnostic evaluation of GI bleeding with EGD and/or colonoscopy appeared to be safe during the COVID-19 pandemic. When used early, VCE as the first strategy was associated with improved localization of active bleeding and reduced the number of urgent invasive endoscopic evaluations without increasing the risk of complications. In addition, VCE as the first strategy was associated with reduced staff use, and thereby reduced risk of exposure to endoscopic aerosols and conserved PPE.
Using VCE as a triaging tool before endoscopic evaluation is a new frontier in the management of GI bleeding described in recent randomized clinical trials. 9,12 The data presented herein are consistent with an earlier observation in nonhematemesis GI bleeding that showed improved localization of the anatomic source of bleeding in 64% of patients in the VCE group compared with 31% in the SOC group. 9 Previous data have shown that patients can be risk stratified using a combination of VCE data and clinical parameters and safely discharged if there is no evidence of active, ongoing bleeding. Therefore, in this setting, VCE serves as a triaging tool for endoscopic localization and to help determine the need for further invasive endoscopic intervention, because clinical history alone can be imprecise in localization and VCE provides additional clinical information beyond nasogastric tube aspiration 13  Video capsule endoscopy has the disadvantage of being a passive device that cannot be manipulated after ingestion, but this is a small disadvantage because the goal is not necessarily to reach an exact diagnosis, but rather to risk stratify and triage patients who may benefit from additional therapeutic interventions. Furthermore, VCE is currently a purely diagnostic test that does not offer therapeutic options-a disadvantage compared with EGD and colonoscopy. However, it has been shown that many patients do not need therapeutic interventions and can be spared from these invasive procedures, at least in the acute setting. 12 Our findings herein are consistent with those reported in a randomized clinical trial in which active bleeding was detected more than twice as frequently by VCE than SOC and 80% of patients 12 reporting hematemesis could safely be discharged for subsequent outpatient evaluation.
Although a full cost analysis was outside the scope of this study, it is reasonable to estimate that there would be a potential associated reduction in expenses by decreased use of procedures and PPE. In a previous cost analysis of the use of early VCE in nonhematemesis GI bleeding, Jawaid and colleagues 32 found no significant difference in total direct costs between patients who underwent early VCE compared with SOC. However, the costs were more efficiently distributed in the VCE group toward detection and treatment of bleeding, whereas in the SOC group, costs were incurred without obtaining a definitive diagnosis. Furthermore, Jawaid and colleagues projected that a more aggressive, albeit safe, discharge strategy could result in a 50% reduction in length of stay in the VCE vs SOC group (0.88 vs 1.63 days), with an associated decrease in direct costs attributed to less patient time spent in the hospital and less time occupying a bed. These potential savings are likely to be expanded in the COVID-19 era, owing to the costs of PPE and additional costs incurred for added hospital stays due to testing requirements (COVID-19 testing) before many endoscopic procedures requiring sedation.