Pharmacologic interrogation of patients with esophagogastric junction outflow obstruction using amyl nitrite

Abstract

Background The Chicago Classification of esophageal motility includes a group of patients who show evidence of esophagogastric junction outflow obstruction (EGJOO) as demonstrated by elevated integrated relaxation pressure (IRP) and preserved peristalsis. Our aim is to classify EGJOO patients based on response to amyl nitrite (AN) during high‐resolution manometry. Methods Patients were considered to have true EGJOO if elevated IRP during supine swallow persisted in the upright position and was associated with high intrabolus pressure. The EGJ response to AN was compared between patients with achalasia type 2 (A2) and normal esophageal motility. Based on the relaxation gain (deglutitive IRP—AN IRP) value that best discriminated these two groups (10 mm Hg), patients with true EGJOO were categorized as being in either the AN‐responsive (AN‐R) or AN‐unresponsive (AN‐U) subgroups. Key Results In the group of 49 patients with true EGJOO, the AN response classified 27 patients (IRP = 25 ± 10 mm Hg) with AN‐R and 22 patients (IRP = 20 ± 5 mm Hg) with AN‐U (P = 0.2). In AN‐R, AN produced a relaxation gain and rebound after‐contraction response at the EGJ comparable to A2 patients. AN‐U patients had an elevated IRP after AN and a relaxation gain similar to normal esophageal motility patients. AN‐U patients were obese and had higher prevalence of sleep apnea (P < 0.05). Conclusions Among patients with true EGJOO, only half have pharmacologic evidence of impaired LES relaxation. Pharmacologic interrogation of the EGJ is thus necessary to identify the subgroup of EGJOO patients who could be expected to benefit from LES ablative therapies.

Diagnostic differences in the pharmacologic response to cholecystokinin and amyl nitrite in patients with absent contractility vs type I Achalasia

“…The outcome data for ACH1 patients were queried, similar to our previous publications 8,11 . Laparoscopic myotomy and pneumatic dilation (>30 mm) were considered permanent LES‐ablative treatments.…”

“…The four second IRP was measured during the 10 seconds period of lowest EGJ pressure during AN‐induced relaxation. We defined the "relaxation gain" as the deglutitive IRP minus the AN‐induced relaxation IRP 11 . The subsequent 120 seconds window of analysis after termination of AN‐induced relaxation was considered the "recovery" phase.…”

“…The deglutitive IRP of the first dry swallow, and peak expiratory LES pressure during the recovery phase (excluding the 20 seconds postdeglutitive after contractions) were recorded. The "rebound contraction" was computed as the LES peak expiratory pressure during recovery minus LES nadir expiratory pressure during AN‐induced relaxation 11 …”

“…We have historically used AN and CCK to investigate the integrity of inhibitory pathway in patients with major esophageal motor disorders, such as achalasia 8‐11 . Amyl nitrite (AN) administration in typical achalasia patients results in LES relaxation beyond the deglutitive relaxation observed with wet swallows (ie, relaxation gain), typically followed by an exaggerated LES contractile response during the subsequent recovery period (ie, rebound contraction) 11 . During AN‐induced esophageal inhibition, residual EGJ pressure is considered unrelated to LES smooth muscle 11 .…”

“…Amyl nitrite (AN) administration in typical achalasia patients results in LES relaxation beyond the deglutitive relaxation observed with wet swallows (ie, relaxation gain), typically followed by an exaggerated LES contractile response during the subsequent recovery period (ie, rebound contraction) 11 . During AN‐induced esophageal inhibition, residual EGJ pressure is considered unrelated to LES smooth muscle 11 . Administration of cholecystokinin‐octapeptide (CCK) during HRM typically results in LES relaxation in healthy subjects 12 but causes a paradoxical LES contraction in achalasia patients 8,9 …”