The Impact of Difficult Biliary Cannulation on Post-ERCP Pancreatitis: A Secondary Analysis of the Stent versus Indomethacin Trial Dataset.

BACKGROUND AND AIMS: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors. METHODS: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk. RESULTS: In all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages. CONCLUSIONS: DBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages.

TC-325 Superiority in Malignant Gastrointestinal Bleeding: An Individual Patient Data Meta-Analysis of Randomized Trials.

INTRODUCTION: The efficacy of topical hemostatic agents, recommended for peptic ulcer bleeding, remains poorly characterized in malignant gastrointestinal bleeding (GIB). METHODS: We performed an individual patient data meta-analysis assessing the efficacy of topical hemostatic agents in malignant GIB. The literature was searched using OVID MEDLINE, EMBASE, and ISI Web of Science databases (database inception to November 2023). Only randomized controlled trials (RCTs) comparing topical hemostatic agents with conventional endoscopic modalities in malignant GIB were included. Original RCT patient-level data were obtained. Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. Quality of the evidence was evaluated using the revised Cochrane risk-of-bias tool and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation approach. The primary outcome was immediate hemostasis; secondary outcomes were 30-day rebleeding and the composite measure of further bleeding (persistent bleeding or 30-day rebleeding). Other outcomes were all-cause mortality, adverse events, and need for additional nonendoscopic treatment. Odds ratios (ORs) from endpoint comparisons were pooled using logistic regression models. RESULTS: Overall, 985 citations were identified; 3 RCTs (n = 160 patients) were included with all assessing TC-325 (Hemospray). TC-325 achieved immediate hemostasis more often than conventional endoscopic modalities (OR 46.6, 95% confidence interval [CI] 5.89-369.1) (low-level certainty). Thirty-day rebleeding (OR 0.28, 95% CI 0.11-0.70) and further bleeding (OR 0.11, 95% CI 0.05-0.26) were both significantly lower with TC-325 (very-low-level certainty). All-cause mortality and need for additional nonendoscopic treatment did not differ between groups. No adverse events were reported. Subgroup analysis confirmed TC-325 superiority in patients with upper GIB. DISCUSSION: TC-325 seems superior to conventional endoscopic therapy in managing patients with malignant GIB. TC-325 results in improvements in immediate hemostasis, 30-day rebleeding, and further bleeding, based on very low-to-low certainties of evidence.

Submucosal injection fluid and tattoo agents.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are minimally invasive endoscopic techniques, developed for the removal of benign and early malignant lesions throughout the GI tract. Submucosal injection of a marking agent can help to identify lesions during surgery. Endoscopic resection frequently involves "lifting" of the lesions by injection of a substance within the submucosal space to create a cushion for safe resection. This review summarizes the current techniques and agents available for endoscopic marking and lifting of GI tract lesions. METHODS: The MEDLINE database was searched through April 2023 for relevant articles related to the lifting and marking aspect of EMR by using key words such as "endoscopy" or "endoscopic" combined with "marking," "tattoo," and "lifting." The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS: This technology review describes the techniques for endoscopic tattoo placement and submucosal lifting, along with currently available agents, safety, and costs. CONCLUSIONS: Endoscopists performing EMR and ESD have several choices in submucosal injection materials for lifting and marking agents for tattoos. These may be commercially prepared agents or off-the-shelf materials with or without additives to facilitate visualization. A thorough understanding of the indications, techniques, properties of various agents, costs, and adverse events is necessary in choosing the appropriate materials and technique to optimize lesion resection in EMR and ESD.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Development and validation of a practical clinical risk prediction model for post-endoscopic retrograde cholangiopancreatography pancreatitis.

Background: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) can lead to significant morbidity and mortality. We aimed to develop an accurate post-ERCP pancreatitis risk prediction model using easily obtainable variables. Methods: Using prospective multi-center ERCP data, we performed logistic regression using stepwise selection on several patient-, procedure-, and endoscopist-related factors that were determined a priori. The final model was based on a combination of the Bayesian information criterion and Akaike's information criterion performance, balancing the inclusion of clinically relevant variables and model parsimony. All available data were used for model development, with subsequent internal validation performed on bootstrapped data using 10-fold cross-validation. Results: Data from 3021 ERCPs were used to inform models. There were 151 cases of post-ERCP pancreatitis (5.0% incidence). Variables included in the final model included female sex, pancreatic duct cannulation, native papilla status, pre-cut sphincterotomy, increasing cannulation time, presence of biliary stricture, patient age, and placement of a pancreatic duct stent. The final model was discriminating, with a receiver operating characteristic curve statistic of 0.79, and well-calibrated, with a predicted risk-to-observed risk ratio of 1.003. Conclusions: We successfully developed and internally validated a promising post-ERCP pancreatitis clinical prediction model using easily obtainable variables that are known at baseline or observed during the ERCP procedure. The model achieved an area under the curve of 0.79. External validation is planned as additional data becomes available.

Cholangioscopy-guided tunneling and coaxial stenting of a large choledocholithiasis: a novel approach to mechanical lithotripsy.

Video 1Cholangioscopy-guided tunneling and coaxial stenting of a large choledocholithiasis: a novel approach to mechanical lithotripsy. Fluoroscopy image of initial ERCP shows large filling defect (blue circle) and guidewire passing toward the common hepatic duct (black arrow).

ERF54 regulates cold tolerance in Rosa multiflora through DREB/COR signalling pathways.

Ethylene-responsive factors (ERFs) participate in a wide range of physiological and biological processes. However, many of the functions of ERFs in cold stress responses remain unclear. We, therefore, characterised the cold responses of RmERF54 in Rosa multiflora, a rose-related cold-tolerant species. Overexpression of RmERF54, which is a nuclear transcription factor, increases the cold resistance of transgenic tobacco and rose somatic embryos. In contrast, virus-induced gene silencing (VIGS) of RmERF54 increased cold susceptibility of R. multiflora. The overexpression of RmERF54 resulted in extensive transcriptional reprogramming of stress response and antioxidant enzyme systems. Of these, the levels of transcripts encoding the PODP7 peroxidase and the cold-related COR47 protein showed the largest increases in the somatic embryos with ectopic expression of RmERF54. RmERF54 binds to the promoters of the RmPODP7 and RmCOR47 genes and activates expression. RmERF54-overexpressing lines had higher antioxidant enzyme activities and considerably lower levels of reactive oxygen species. Opposite effects on these parameters were observed in the VIGS plants. RmERF54 was identified as a target of Dehydration-Responsive-Element-Binding factor (RmDREB1E). Taken together, provide new information concerning the molecular mechanisms by which RmERF54 regulates cold tolerance.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Post-ERCP cholecystitis: Incidence, characteristics, and outcomes from a prospective multicenter biliary endoscopy registry.

BACKGROUND AND AIMS: The incidence, risk factors, and outcomes of post-ERCP cholecystitis are poorly described. We aimed to describe cases of post-ERCP cholecystitis from a prospective multicenter registry with protocolized 30-day follow-up. METHODS: Patient- and procedure-related data from 7 centers were obtained. The primary outcome was post-ERCP cholecystitis, defined according to a Delphi-based criteria and causal attribution system. Risk factors and outcomes were described for all cases. RESULTS: Seventeen cases of post-ERCP cholecystitis were identified among 4428 patients with gallbladders undergoing ERCP between 2018 and 2023 (incidence, 0.38%; 95% confidence interval, 0.20-0.57). In ERCPs with covered metal stenting, 7 of 467 resulted in cholecystitis (incidence, 1.50%; 95% confidence interval, 0.40-2.60). Patients had symptoms at a median of 5 days (interquartile range, 5) after ERCP. Management strategies included cholecystectomy, percutaneous cholecystostomy, and endoscopic stent removal/exchange. CONCLUSIONS: Estimates of post-ERCP cholecystitis incidence can inform discussions around procedural risk.

Aspirin exposure and its association with metal stent patency in malignant distal biliary obstruction: a large international multicenter propensity score-matched study.

BACKGROUND AND AIMS: Stent dysfunction is common after ERCP with self-expandable metal stent (SEMS) insertion for malignant distal biliary obstruction (MDBO). Chronic aspirin (acetylsalicylic acid; ASA) exposure has been previously shown to potentially decrease this risk. We aim to further ascertain the protective effect of ASA and to identify other predictors of stent dysfunction. METHODS: This multicenter retrospective cohort study was conducted at 9 sites in Canada and 1 in the United States. Patients with MDBO who underwent ERCP with SEMS placement between January 2014 and December 2019 were included and divided into 2 cohorts: ASA exposed (ASA-E) and ASA unexposed (ASA-U). Propensity-score matching (PSM) was performed to limit selection bias. Matched variables were age, sex, tumor stage, and type of metal stent. The primary outcome was the hazard rate of stent dysfunction. A multivariable Cox proportional hazards model was used to identify independent predictors of stent dysfunction. RESULTS: Of 1396 patients assessed, after PSM 496 patients were analyzed (248 ASA-E and 248 ASA-U). ERCP with SEMS placement was associated with a high clinical success of 82.2% in ASA-E and 81.2% in ASA-U cohorts (P = .80). One hundred eighty-four patients had stent dysfunction with a mean stent patency time of 229.9 ± 306.2 days and 245.4 ± 241.4 days in ASA-E and ASA-U groups, respectively (P = .52). On multivariable analysis, ASA exposure did not protect against stent dysfunction (hazard ratio [HR], 1.25; 95% confidence interval [CI], .96-1.63). An etiology of pancreatic cancer (HR, 1.36; 95% CI, 1.15-1.61) predicted stent dysfunction, whereas cancer therapy was protective (HR, .73; 95% CI, .55-.96). Chronic ASA use was not associated with an increased risk for adverse events including bleeding, post-ERCP pancreatitis, and perforation. CONCLUSIONS: In this large, multicenter study using PSM, chronic exposure to ASA did not protect against stent dysfunction in MDBO. Instead, the analysis revealed that the etiology of pancreatic cancer was an independent predictor of stent dysfunction and cancer therapy was protective.

EUS-guided gastroenterostomy using a novel through-the-scope exchangeable dual-balloon enteroclysis catheter: a potentially secure and scalable approach.

Video 1Clinical case of dual-balloon through-the-scope exchangeable enteroclysis catheter-assisted EUS-guided gastroenterostomy.

EUS-guided gastroenterostomy vs. surgical gastrojejunostomy and enteral stenting for malignant gastric outlet obstruction: a meta-analysis.

Background and study aims Malignant gastric outlet obstruction (MGOO) is traditionally treated with surgical gastrojejunostomy (SGJ), which is effective but associated with high rates of morbidity, or endoscopic stenting (ES), which is less invasive but associated with significant risk of stent dysfunction and need for reintervention. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) provides a robust bypass without the invasiveness of surgery. Methods We performed a systematic review and meta-analysis comparing EUS-GE to SGJ and ES for MGOO. Electronic databases were searched from inception through February 2022. A meta-analysis was performed with results reported as odds ratios (ORs) with 95% confidence intervals (CIs) using random effects models. Primary outcomes included clinical success without recurrent GOO and adverse events (AEs). Results Sixteen studies involving 1541 patients were included. EUS-GE was associated with higher clinical success without recurrent GOO compared to ES or SGJ [OR 2.60, 95% CI1.58-4.28] and compared to ES alone [OR 5.08, 95% CI 3.42-7.55], but yielded no significant difference compared to SGJ alone [OR 1.94, 95% CI 0.97-3.88]. AE rates were significantly lower for EUS-GE compared to ES or SGJ grouped together [OR 0.34, 95% CI 0.20-0.58], or SGJ alone [OR 0.17, 95% CI 0.10-0.30] but were not significant different versus ES alone [OR 0.57, 95% CI 0.29-1.14]. Conclusions EUS-GE is the most successful approach to treating MGOO, exhibiting a lower risk of recurrent obstruction compared to ES, and fewer AEs compared to SGJ.

Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

EUS-guided biliary drainage in malignant distal biliary obstruction: An international survey to identify barriers of technology implementation.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) is a promising alternative to ERCP in malignant distal biliary obstruction (MDBO). Despite accumulating data, however, its application in clinical practice has been impeded by undefined barriers. This study aims to evaluate the practice of EUS-BD and its barriers. Methods: An online survey was generated using Google Forms. Six gastroenterology/endoscopy associations were contacted between July 2019 and November 2019. Survey questions measured participant characteristics, EUS-BD in different clinical scenarios, and potential barriers. The primary outcome was the uptake of EUS-BD as a first-line modality, without previous ERCP attempts, in patients with MDBO. Results: Overall, 115 respondents completed the survey (2.9% response rate). Respondents were from North America (39.2%), Asia (28.6%), Europe (20%), and other jurisdictions (12.2%). Regarding the uptake of EUS-BD as first-line treatment for MDBO, only 10.5% of respondents would consider EUS-BD as a first-line modality regularly. The main concerns were the lack of high-quality data, fear of adverse events, and limited access to EUS-BD dedicated devices. On multivariable analysis, lack of access to EUS-BD expertise was an independent predictor against the use of EUS-BD, odds ratio 0.16 (95% confidence interval, 0.04-0.65). In salvage situations following failed ERCP, most favored EUS-BD (40.9%) over percutaneous drainage (21.7%) in unresectable cancer. In borderline resectable or locally advanced disease, however, most favored the percutaneous approach due to fear of EUS-BD complicating future surgery. Conclusions: EUS-BD has not reached widespread clinical adoption. Identified barriers include lack of high-quality data, fear of adverse events, and lack of access to EUS-BD dedicated devices. Fear of complicating future surgery was also identified as a barrier in potentially resectable disease.

Baseline Cannabinoid Use Is Associated with Increased Sedation Requirements for Outpatient Endoscopy.

Background and Aims: Given the underlying properties of cannabinoids, we aimed to assess associations between cannabinoid use and sedation requirements for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods: A prospective cohort study was conducted at three endoscopy units. Adult outpatients undergoing EGD or colonoscopy with endoscopist-directed conscious sedation (EDCS) were given questionnaires on cannabinoid use and relevant parameters. Outcomes included intraprocedural midazolam, fentanyl, and diphenhydramine use, procedural tolerability, and adverse events. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) of outcomes. Results: A total of 419 patients were included. Baseline cannabinoid use was associated with high midazolam use, defined as ≥5 mg, during EGD (AOR 2.89, 95% confidence interval, CI: 1.19-7.50), but not during colonoscopy (AOR 0.89, 95% CI 0.41-1.91). Baseline cannabinoid use was associated with the administration of any diphenhydramine during EGD (AOR 3.04, 95% CI: 1.29-7.30) with a similar nonsignificant trend for colonoscopy (AOR 2.36, 95% CI: 0.81-7.04). Baseline cannabinoid use was associated with increased odds of requiring high total sedation, defined as any of midazolam ≥5 mg, fentanyl ≥100 mcg, or any diphenhydramine during EGD (AOR 3.72, 95% CI: 1.35-11.68). Cannabinoid use was not independently associated with fentanyl use, intraprocedural awareness, discomfort, or adverse events. Conclusions: Baseline cannabinoid use was associated with higher sedation use during endoscopy with EDCS, particularly with midazolam and diphenhydramine. Given increasingly widespread cannabinoid use, endoscopists should be equipped with optimal sedation strategies for this population. As part of the informed consent process, cannabis users should be counseled that they may require higher sedation doses to achieve the same effect.