The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.

The Role of Imaging for GI Bleeding: ACG and SAR Consensus Recommendations.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.

Factors affecting Family Physician follow-up 30 days post-discharge from a Canadian Academic Emergency Department.

Close outpatient follow-up of patients discharged from the emergency department (ED) has been associated with improved antimicrobial stewardship, medication compliance, and decreased mortality. Despite these clear benefits, studies have shown most patients do not receive follow-up from specialists or Family Physicians (FP). While age, race and insurance status may be factors in Australia and the United States, there remains a paucity of Canadian studies investigating potential factors that influence follow-up. This retrospective cohort study aimed to elucidate factors associated with Family Physician follow up within 30 days at two urban, academic Family Medicine clinics. Our study included patients aged 18 or older who have an academic Family Physician and visited a London Health Sciences Centre ED between January 1, 2021 and June 1, 2021. A binary logistic regression was used to determine if a specific patient or provider factor was associated with follow-up. Of the 367 cases that met criteria, 220 (60%) patients received Family Physician follow-up within 30 days. Additionally, 51 patients (23%) received specialist follow-up within 30 days. A higher number of medications (OR 1.12 p=0.003) and a Family Physician appointment within the 90 days preceding the ED visit (OR 2.51, p<0.001) were significantly predictive of Family Physician follow-up. The use of a Family Physician referral form, documented discharge instructions, and increasing comorbidity (as documented by the Charlson Comorbidity Index) were not associated with a higher odds of follow-up. These data suggest that patients on numerous medications may require close follow-up for monitoring, dose adjustments, and reassessment. Additionally, those patients with recent Family Physician visits may have stronger relationships with their provider, increasing their likelihood of follow-up. Based on this study, there is insufficient evidence to suggest that documented discharge instructions nor the use of a FP referral form impact the rate of follow-up. Future work should focus on an optimal mechanism to ensure Family Physician follow-up, when required, in urban centres. The impact of mental health and substance use disorders on the rate of follow-up should also be evaluated.

Dual-Energy CT Evaluation of Gastrointestinal Bleeding.

Gastrointestinal (GI) bleeding is a potentially life-threatening condition accounting for more than 300 000 annual hospitalizations. Multidetector abdominopelvic CT angiography is commonly used in the evaluation of patients with GI bleeding. Given that many patients with severe overt GI bleeding are unlikely to tolerate bowel preparation, and inpatient colonoscopy is frequently limited by suboptimal preparation obscuring mucosal visibility, CT angiography is recommended as a first-line diagnostic test in patients with severe hematochezia to localize a source of bleeding. Assessment of these patients with conventional single-energy CT systems typically requires the performance of a noncontrast series followed by imaging during multiple postcontrast phases. Dual-energy CT (DECT) offers several potential advantages for performing these examinations. DECT may eliminate the need for a noncontrast acquisition by allowing the creation of virtual noncontrast (VNC) images from contrast-enhanced data, affording significant radiation dose reduction while maintaining diagnostic accuracy. VNC images can help radiologists to differentiate active bleeding, hyperattenuating enteric contents, hematomas, and enhancing masses. Additional postprocessing techniques such as low-kiloelectron voltage virtual monoenergetic images, iodine maps, and iodine overlay images can increase the conspicuity of contrast material extravasation and improve the visibility of subtle causes of GI bleeding, thereby increasing diagnostic confidence and assisting with problem solving. GI bleeding can also be diagnosed with routine single-phase DECT scans by constructing VNC images and iodine maps. Radiologists should also be aware of the potential pitfalls and limitations of DECT. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Management of Patients With Acute Lower Gastrointestinal Bleeding: An Updated ACG Guideline.

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospitalization in the United States and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality. These revised guidelines implement the Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the use of risk stratification tools, thresholds for red blood cell transfusion, reversal agents for patients on anticoagulants, diagnostic testing including colonoscopy and computed tomography angiography (CTA), endoscopic therapeutic options, and management of antithrombotic medications after hospital discharge. Important changes since the previous iteration of this guideline include recommendations for the use of risk stratification tools to identify patients with LGIB at low risk of a hospital-based intervention, the role for reversal agents in patients with life-threatening LGIB on vitamin K antagonists and direct oral anticoagulants, the increasing role for CTA in patients with severe LGIB, and the management of patients who have a positive CTA. We recommend that most patients requiring inpatient colonoscopy undergo a nonurgent colonoscopy because performing an urgent colonoscopy within 24 hours of presentation has not been shown to improve important clinical outcomes such as rebleeding. Finally, we provide updated recommendations regarding resumption of antiplatelet and anticoagulant medications after cessation of LGIB.

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis.

BACKGROUND: The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis. METHODS: We searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models. RESULTS: Six observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02). CONCLUSIONS: Evidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

Restarting Warfarin vs Direct Oral Anticoagulants After Major Gastrointestinal Bleeding and Associated Outcomes in Atrial Fibrillation: A Cohort Study.

BACKGROUND & AIMS: Limited data exist on the management of anticoagulation after hospitalization for gastrointestinal bleeding (GIB) and the risks of recurrent GIB and thromboembolism in patients who are prescribed warfarin vs direct oral anticoagulants (DOACs). The purpose of this study was to assess the risk of recurrent GIB and thromboembolism with resumption of anticoagulation after GIB. METHODS: This was a retrospective analysis of adults with atrial fibrillation prescribed warfarin or DOACs and subsequently hospitalized for GIB. We used claims data from IBM MarketScan Databases from January 2008 through December 2017. Multivariable time-varying regression was used to determine the risks of recurrent GIB and thromboembolism within 6 months of the index hospitalization. RESULTS: There were 2991 patients hospitalized for GIB on anticoagulants (warfarin, n = 1872; rivaroxaban, n = 676; dabigatran, n = 293; and apixaban, n = 250). Of warfarin users, 46% (n = 869) resumed warfarin after discharge compared with 43% (n = 483) of DOAC users who resumed DOACs. In the regression analysis modeling time-varying coefficients for anticoagulant use, warfarin resumption was associated with an increased risk of recurrent GIB (hazard ratio [HR], 2.12; 95% CI, 1.43-3.14; P = .0002) compared with no anticoagulant resumption, whereas there was no association with DOAC resumption and recurrent bleeding (HR, 1.43; 95% CI, 0.81-2.52; P = .22). Rivaroxaban was the only individual DOAC that was associated with recurrent GIB (HR, 2.73; 95% CI, 1.43-5.20; P = .002). Both warfarin (HR, 0.61; 95% CI, 0.39-0.96; P = .033) and DOAC (HR, 0.52; 95% CI, 0.28-0.98; P = .044) resumption as a class was associated with a decreased risk of thromboembolism. CONCLUSIONS: Either warfarin or DOAC resumption after hospitalization for GIB was associated with a decreased risk of thromboembolism, whereas warfarin and rivaroxaban resumption were associated with an increased risk of recurrent GIB.

Digital Navigation Improves No-Show Rates and Bowel Preparation Quality for Patients Undergoing Colonoscopy: A Randomized Controlled Quality Improvement Study.

OBJECTIVES: Because of high historical no-show rates and poor bowel preparation quality in our unit, we sought to evaluate whether text message navigation for patients scheduled for colonoscopy would reduce no-show rates and improve bowel preparation quality compared with usual care. METHODS: We performed a randomized controlled quality improvement study from April to August 2019 in an urban academic endoscopy unit. All patients scheduled for colonoscopy were randomly assigned to a control group that received usual care (paper instructions/nursing precalls) or to the intervention group that received usual care plus the text message program [short message service (SMS)]. The program provided timed-release instructions on dietary modifications and bowel preparation before colonoscopy. The primary outcome was no-shows. Secondary outcomes were no-show/same-day cancellations, no-show/cancellations within 7 days of the procedure, and bowel preparation quality. RESULTS: A total of 1625 patients were randomized (SMS=833, control=792). No-show rates were significantly lower in the SMS group compared with the control group (8% vs. 14%; P<0.0001). Similar results were found for no-show/same-day cancellations (10% vs. 16%; P=0.0003), and no-show/cancellations within 7 days (18% vs. 26%; P=0.0008). There was no difference in adequate bowel preparation for all colonoscopies between the groups (89% vs. 87%; P=0.47). However, rates of adequate bowel preparation for screening/surveillance colonoscopies were significantly higher in SMS versus control groups (93% vs. 88%; P=0.04). CONCLUSIONS: Text message navigation for patients scheduled for colonoscopy improved the quality of colorectal cancer screening by decreasing no-show rates and increasing adequate bowel preparation rates in patients undergoing screening colonoscopy compared with usual care.

Comparative Efficacy and Rapidity of Action for Infliximab vs Ustekinumab in Biologic Naïve Crohn's Disease.

BACKGROUND & AIMS: Comparative effectiveness has become increasingly important to help position therapies for inflammatory bowel disease. We compared the efficacy and rapidity of onset of action of infliximab vs ustekinumab induction therapy for moderate to severe biologic-naïve Crohn's disease (CD) using patient-level data from randomized controlled trials. METHODS: This was a post hoc analysis of 2 large CD clinical trial programs that included data on 420 biologic-naïve CD patients. Differences in proportions of patients achieving week 6 clinical remission, clinical response, and normalization of calprotectin were compared. Multivariate logistic regression was used to adjust for confounders. Sensitivity analysis was conducted using propensity scores to create a cohort of matched participants with similar distribution of baseline covariates. RESULTS: At week 6, a comparable number of patients achieved clinical remission with infliximab compared with patients treated with ustekinumab (44.9% vs 37.9%; adjusted odds ratio [aOR], 1.22; 95% CI, 0.79-1.89). Similarly, at week 6 the clinical response rates were not significantly different (58.4% infliximab vs 54.9% ustekinumab; aOR, 1.25; 95% CI, 0.82-1.90). No significant difference was observed between treatment groups for achieving a week 6 fecal calprotectin level less than 250 mcg/L in those with increased values at baseline (42.3% infliximab vs 34.7% ustekinumab; aOR, 1.34; 95% CI, 0.79-2.28). Similar results were seen for all analyses performed within the propensity matched cohort. CONCLUSIONS: Based on this post hoc analysis, infliximab and ustekinumab appear to have similar efficacy and speed of onset in patients with CD who are biologic-naïve.

Deep Learning Computer-aided Polyp Detection Reduces Adenoma Miss Rate: A United States Multi-center Randomized Tandem Colonoscopy Study (CADeT-CS Trial).

BACKGROUND & AIMS: Artificial intelligence-based computer-aided polyp detection (CADe) systems are intended to address the issue of missed polyps during colonoscopy. The effect of CADe during screening and surveillance colonoscopy has not previously been studied in a United States (U.S.) population. METHODS: We conducted a prospective, multi-center, single-blind randomized tandem colonoscopy study to evaluate a deep-learning based CADe system (EndoScreener, Shanghai Wision AI, China). Patients were enrolled across 4 U.S. academic medical centers from 2019 through 2020. Patients presenting for colorectal cancer screening or surveillance were randomized to CADe colonoscopy first or high-definition white light (HDWL) colonoscopy first, followed immediately by the other procedure in tandem fashion by the same endoscopist. The primary outcome was adenoma miss rate (AMR), and secondary outcomes included sessile serrated lesion (SSL) miss rate and adenomas per colonoscopy (APC). RESULTS: A total of 232 patients entered the study, with 116 patients randomized to undergo CADe colonoscopy first and 116 patients randomized to undergo HDWL colonoscopy first. After the exclusion of 9 patients, the study cohort included 223 patients. AMR was lower in the CADe-first group compared with the HDWL-first group (20.12% [34/169] vs 31.25% [45/144]; odds ratio [OR], 1.8048; 95% confidence interval [CI], 1.0780-3.0217; P = .0247). SSL miss rate was lower in the CADe-first group (7.14% [1/14]) vs the HDWL-first group (42.11% [8/19]; P = .0482). First-pass APC was higher in the CADe-first group (1.19 [standard deviation (SD), 2.03] vs 0.90 [SD, 1.55]; P = .0323). First-pass ADR was 50.44% in the CADe-first group and 43.64 % in the HDWL-first group (P = .3091). CONCLUSION: In this U.S. multicenter tandem colonoscopy randomized controlled trial, we demonstrate a decrease in AMR and SSL miss rate and an increase in first-pass APC with the use of a CADe-system when compared with HDWL colonoscopy alone.

Impact of Early Video Capsule Endoscopy on Hospitalization and Post-hospitalization Outcomes: A Propensity Score-Matching Analysis.

INTRODUCTION: Video capsule endoscopy (VCE) has become the accepted evaluation of choice for patients with suspected small bowel bleeding. Our aim was to evaluate the impact of early as compared to delayed inpatient VCE on post-index hospitalization readmission rates. METHODS: We performed a retrospective study using medical claims from the IBM® Marketscan® Commercial Database from January 1, 2004, through September 30, 2018, including adult patients that underwent an inpatient VCE. Early VCE was defined as occurring on days 0, 1, or 2 of the index hospitalizations, whereas delayed VCE was performed on days 3-7. Propensity matching was performed to create an analytic cohort, and outcomes were assessed using logistic regression. RESULTS: Following propensity score matching, 607 patients undergoing early VCE were matched 1:1 with 607 patients undergoing delayed VCE. The median patient age was 65 (IQR: 56-78) years, and 560 (37.9%) of the included patients were female. The mean time to VCE was 1.6 (± 0.6) days for the early VCE group and 4.0 (± 1.2) days from admission for delayed VCE. In unadjusted comparisons, we found no significant difference between early VCE and delayed VCE with respect to 90-day all-cause readmission (18.6% vs. 17.0%, P = 0.5) or 90-day rebleeding risk (10.5% vs. 8.7%, P = 0.331). Patients undergoing an early VCE had a shorter hospital LOS and less total hospitalization charges. CONCLUSION: Early as compared to delayed inpatient VCE was associated with a reduction in index hospitalization resource utilization. No differences were found with respect to reductions in readmissions or rebleeding events.

Interventional treatments for chronic, axial or radicular, non-cancer, spinal pain: a protocol for a systematic review and network meta-analysis of randomised trials.

INTRODUCTION: Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain. METHODS: We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence. PROSPERO REGISTRATION NUMBER: CRD42020170667.

Effect of preoperative cannabis use on perioperative outcomes: a retrospective cohort study.

INTRODUCTION: The reported use of cannabis within surgical population is increasing. Cannabis use is potentially associated with increased harms and varied effects on pain control. These have important implications to perioperative care. METHODS: We conducted a retrospective cohort study comparing surgical patients reporting cannabis use preoperatively to control patients with no cannabis exposure, in a 1:2 ratio. To control for confounding, we used a propensity score-matched analysis to assess the adjusted association between cannabis use and study outcomes. Our primary outcome was a composite of (1) respiratory arrest or cardiac arrest, (2) intensive care admission, (3) stroke, (4) myocardial infarction and (5) mortality during this hospital stay. Secondarily, we assessed the effects on pain control, opioid usage, induction agent dose and nausea-vomiting. RESULTS: Between January 2018 and March 2019, we captured 1818 patients consisting of cannabis users (606) and controls (1212). For propensity score-matched analyses, 524 cannabis patients were compared with 1152 control patients. No difference in the incidence of composite outcome was observed (OR 1.06, 95% CI 0.23 to 3.98). Although a higher incidence of arrhythmias (2.7% vs 1.6%) and decreased incidence of nausea-vomiting needing treatment (9.6% vs 12.6%) was observed with cannabis users vs controls, results were not statistically significant. No significant differences were observed with other secondary outcomes. CONCLUSION: Our results do not demonstrate a convincing association between self-reported cannabis use and major surgical outcomes or pain management. Perioperative decisions should be made based on considerations of dose, duration, and indication.

Triage of General Gastrointestinal Endoscopic Procedures During the COVID-19 Pandemic: Results From a National Delphi Consensus Panel.

BACKGROUND AND AIMS: As the COVID-19 pandemic moves into the postpeak period, the focus has now shifted to resuming endoscopy services to meet the needs of patients who were deferred. By using a modified Delphi process, we sought to develop a structured framework to provide guidance regarding procedure indications and procedure time intervals. METHODS: A national panel of 14 expert gastroenterologists from throughout the US used a modified Delphi process, to achieve consensus regarding: (1) common indications for general endoscopy, (2) critical patient-important outcomes for endoscopy, (3) defining time-sensitive intervals, (4) assigning time-sensitive intervals to procedure indications. Two anonymous rounds of voting were allowed before attempts at consensus were abandoned. RESULTS: Expert panel reached consensus that procedures should be allocated to one of three timing categories: (1) time-sensitive emergent = scheduled within 1 week, (2) time-sensitive urgent = scheduled within 1-8 weeks, (3) nontime sensitive = defer to > 8 weeks and reassess timing then. The panel identified 62 common general endoscopy indications (33 for EGD, 21 for colonoscopy, 5 for sigmoidoscopy). Consensus was reached on patient-important outcomes for each procedure indication, and consensus regarding timing of the procedure indication was achieved for 74% of indications. Panelists also identified adequate personal-protective-equipment, rapid point-of-care testing, and staff training as critical preconditions before endoscopy services could be resumed. CONCLUSION: We used the validated Delphi methodology, while prioritized patient-important outcomes, to provide consensus recommendations regarding triaging a comprehensive list of general endoscopic procedures.

Anticoagulant Reversal in Gastrointestinal Bleeding: Review of Treatment Guidelines.

BACKGROUND: Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa). AIM: To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed. METHODS: This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data. RESULTS: GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio > 2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications. CONCLUSIONS: The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios.