Glucagon’s Role in Esophageal Foreign Body Impaction

Esophageal foreign body impaction (EFBI) occurs in approximately 13 per 100,000 patients admitted to the emergency room, with the most commonly implicated food being steak. Multiple medications have been evaluated to help resolve EFBI based on their mechanisms of action, including nifedipine, sublingual nitroglycerin, proteolytic enzymes, benzodiazepines, and glucagon.

The mechanism of action for glucagon involves decreasing the lower esophageal sphincter tone through smooth muscle relaxation, increasing peristalsis, and improving transit time, all with a ceiling dose effect at 1 mg. Because of this, glucagon has commonly been used in clinical practice to help with food impactions, sometimes with delay in endoscopic intervention to give the medication time to take effect.

A Cochrane Library meta-analysis was completed in 2020 to review conservative management of esophageal soft food bolus impaction, with a single article meeting inclusion criteria for history of acute soft food bolus ingestion, history suggestive of esophageal impaction, and incidence of disimpaction without the need for endoscopic intervention as well as exclusion criteria of sharp- or solid-object ingestion, such as bone or foreign objects like dentures or coins.¹

The study that met these criteria was a presumed double-blind, parallel-group, randomized controlled trial (RCT) conducted in 1995 by Tibbling et al. in Sweden involving 43 participants and looking at the effects of disimpaction in a placebo versus a diazepam and glucagon group. The study found no significant difference between the groups. Of note, the randomization, baseline patient characteristics, and dropout rates were not described, and it was not clear if the study was evaluated with intention to treat (ITT) versus per protocol (PP) analysis.

With the above study being the only presumed RCT involving glucagon for food disimpaction, the field was in need of further evaluation, especially given the extent of the clinical use of glucagon. In January 2024, de Benito Sanz et al. published a double-blind, multicenter RCT comparing glucagon to placebo in the resolution of alimentary esophageal impaction.²

The study was conducted at 4 centers from April 2020 to March 2023 and included patients ≥ 18 years of age with a clinical diagnosis of EFBI, profuse salivation, or oral intolerance after their last meal. Exclusion criteria included pregnancy, non-alimentary foreign body, administration of glucagon or carbonated drinks prior to randomization, known non-passable strictures during prior endoscopy, or manometrically diagnosed esophageal motility disorders.

When patients presented to the ER with the above, the ER provider had a joint assessment with the on-call endoscopist. Although the ER provider and ER staff were not masked, the endoscopist was. The 2 arms of the study involved a placebo IV saline versus 1mg IV glucagon and a mandatory gastroscopy within 30-120 minutes of glucagon administration regardless of clinical symptom resolution. This was followed by a follow-up phone call within 7-10 days for assessment of pain (scale from 0-10) and dysphagia graded in 4 categories (to nothing, solids, liquids, or aphagia). Each arm of the study included 70 patients for 80% power given the success rate of 35% of glucagon based on minimal studies as previously mentioned.

The primary endpoint was the proportion of resolved EFBI while secondary endpoints included the duration of endoscopic exam and extraction length with post hoc analysis of different esophageal diagnoses. Statistical analysis of the primary outcome was done using Z-test and both ITT and PP, and the secondary endpoints were analyzed with chi-squared analysis.

A total of 17 endoscopists were involved in this study with 72 patients in the intervention group and 68 in the placebo. Baseline characteristics were generally similar between the groups except for a greater incidence of known Schatzki rings in the placebo group (P = .03). EFBI resolved with glucagon in 23.6% (n = 17) of cases versus 20.6% (n = 14) of cases in the placebo group with ITT. In PP analysis, these numbers were 20.9% for the glucagon group and 21.5% in the placebo group.

Secondary endpoints for time required to resolve EFBI were about the same in the 2 groups, but the duration of upper endoscopy was slightly longer in the glucagon group by 1.5 minutes. Post hoc analysis of the benefit of glucagon depending on esophageal diagnoses did not show significance, but it is important to note that the n values were relatively small for these subgroups.

There was no significant difference in the predominant location of the EFBI (lower third of the esophagus), type of EFBI (beef and chicken), and successful removal maneuver (pulsion, roth net, polypectomy snare, foreign body forceps). Across both groups, 8 adverse events were described, including oropharyngeal discomfort, esophageal obstruction, urinary retention, salivary gland infection, COVID, and fever, with the most significant being a case of aspiration pneumonia in the control group in a 92-year-old patient.

The study has clear strengths in that it was a double-blind, multi-center RCT with multiple endoscopists and a short time to EGD. The study did not limit the type of endoscopic interventions, correlating with clinical practice. The secondary outcomes were also very reasonable as a benefit in endoscopic time independent of the primary outcome could have been supportive of the use of glucagon. However, given the thoroughness of this study and its results, glucagon does not seem to make a difference in EFBI resolution, time of endoscopy, or extraction length.

Future studies powered for the subgroup analysis of different esophageal diseases would be interesting to see for specific esophageal diseases and pathophysiologies that might have a greater response to glucagon.

References:

1. ^{Hardman J, Sharma N, Smith J, Nankivell P. Conservative management of oesophageal soft food bolus impaction. Cochrane Database of Systematic Reviews 2020, Issue 5. Art. No.: CD007352. doi:10.1002/14651858.CD007352.pub3.}
2. ^{de Benito Sanz M, Tejedor-Tejada J, Mangas-Sanjuan C, et al. on behalf of the GLUCAGON study group. Double-Blind Multicenter Randomized Clinical Trial Comparing Glucagon vs Placebo in the Resolution of Alimentary Esophageal Impaction. The American Journal of Gastroenterology 119(1):p 87-96, January 2024. doi:10.14309/ajg.0000000000002511}