Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility

Background: There is no therapeutic intervention that reliably restores smooth muscle contractility for patients with ineffective esophageal motility (IEM). Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in healthy volunteers to produce a significant increase in peristaltic amplitude in the distal esophagus. Aim: To identify whether bethanechol improves smooth muscle contractility and bolus transit in patients with IEM. Methods: Seven patients diagnosed with severe IEM documented by combined multichannel intraluminal impedance and esophageal manometry were asked to participate. IEM was defined by using the new proposed criteria of greater than or equal to 50% saline swallows with contraction amplitude < 30 min Hg either 5 and/or 10 cm above the lower esophageal sphincter (LES). In the supine position, the patients were given 10 swallows of 5 mL of normal saline then 10 swallows of viscous solution, each 20 to 30 seconds apart. Patients were then given 50 mg oral bethanechol. After 20 and 40 minutes, 5 swallows of saline and viscous solution were repeated. Studies were then analyzed by an investigator blinded to the relationship of bethanechol administration to the swallows. The analysis included measurement of distal esophageal amplitude (DEA) or the mean amplitude at 5 and 10 cm above the LES. Results: The use of bethanechol significantly increased (P < 0.05) the esophageal contraction pressures at 5 and 10 cm above the LES. The DEA increased (P < 0.05) for liquid and viscous, 20 minutes after its administration. Forty minutes after bethanechol administration, DEA and also individual pressures at 5 and 10 cm above the LES were still increased (P < 0.05) for liquid, but only the DEA increased (P < 0.05) with viscous solution. There was also a significant increase in complete bolus transit for saline swallows, both 20 and 40 minutes (P = 0.03 and 0.01, respectively) after bethanechol. Conclusions: Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM.