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Pharmacologic Challenge With Amyl Nitrite Distinguishes Between Structural Esophagogastric Junction and Functional Lower Esophageal Sphincter Abnormalities Causing Esophageal Outflow Obstruction in the Post-Operative Setting
Arash Babaei^*2, Jon Gould³, Syed I. Rahman¹, Reza Shaker², Benson T. Massey^2
1Medical College of Wisconsin, Milwaukee, WI; ²Division of Gastroenterology & Hepatology, The Medical College of Wisconsin, Milwaukee, WI; ³Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI

Background: Assessment of esophageal outflow resistance (EOR) in symptomatic postoperative patients poses a significant clinical challenge, as this could result from structural abnormalities, impaired lower esophageal sphincter (LES) relaxation, or a combination of factors. The current Chicago classification of esophageal motor disorders cannot reliably distinguish between these possibilities in postoperative patients. Administration of amyl nitrite (AN), a nitric oxide donor, during manometry profoundly inhibits the LES to allow discrimination of the different forms of EOR. The diagnostic yield of this approach in symptomatic post-operative patients is uncertain.
Aim: To assess the diagnostic value of NO donor challenge in postoperative patients with manometric findings consistent with EOR
Method: We identified all non-achalasia patients with a history of any bariatric surgery or esophogastric junction operative intervention who received inhaled AN during esophageal high-resolution manometry to evaluate possible EOR. We applied the latest iteration of Chicago Classification of esophageal motility v3.0 to classify these patients based only on their supine wet swallows. In a separate analysis we used EGJ relaxation response to AN to classify these patients into AN responsive (LES pressure fall > 8 mmHg more than deglutition nadir) and unresponsive subgroups.
Results: We identified 19 post-operative patients (14 fundoplication/5 bariatric surgery) who had AN challenge to assess EOR during high resolution manometry. Eight were identified as having an AN responsive form of EOR (Figure 1). Correlation of topographic phenotype based Chicago classification with response to AN is presented in Table 1. Only 1/5 patients with topographic phenotype of type II achalasia showed positive response to AN, and could be confirmed as idiopathic achalasia. 3/5 patients with type III achalasia phenotype and 4/10 EOR patients who showed some normal peristalsis were AN responsive patients suggestive of functional impaired LES relaxation. All of these patients were chronically taking high dose of opioid analgesic medications for chronic pain syndromes, and their total daily morphine equivalent dose was 69 + 71 mg.
Conclusions: In post-operative patients with manometric evidence of EOR, AN challenge indicates that the clinical problem is secondary to impaired LES relaxation rather than operative structural abnormalities nearly half the time. Most of these are manifestations of chronic opioid therapy. These patients cannot be identified with the topographic phenotype Chicago classification without additional pharmacologic testing.

Chicago Classification	Topographic Metric	Patients	Amyl Nitrite Response	Patients	Diagnosis
Achalasia Type II	IRP>15mmHg 100% Failed peristalsis Panesophageal pressurization	5	Yes	1	Idiopathic achalasia II
			No	4	Structural Esophageal Outflow Resistance
Achalasia Type III	IRP>15mmHg No normal peristalsis Premature spastic contraction	4	Yes	3	Functional Impaired LES Relaxation
			No	2	Structural Esophageal Outflow Resistance
Esophageal Outflow Resistance (EOR)	IRP>15mmHg Normal peristalsis present	10	Yes	4	Functional Impaired LES Relaxation
			No	5	Structural Esophageal Outflow Resistance

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