Opioid-induced esophageal dysfunction

Abstract

Purpose of review Chronic opioid use is common and can cause opioid-induced esophageal dysfunction (OIED). We will discuss the pathophysiology, diagnosis, and management of OIED. Recent findings OIED is diagnosed based on symptoms, opioid use, and manometric evidence of distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or jackhammer esophagus. Chronic opioid use appears to interfere with inhibitory signals involved in control of esophageal motility, allowing for unchecked excitatory stimuli, and leading to spastic contractility and impaired esophagogastric junction relaxation. Patients may present with dysphagia and chest pain. OIED is significantly more prevalent in patients taking the stronger opioids oxycodone and hydrocodone compared with the weaker opioid tramadol. Based on 24-h morphine equivalent doses, patients with OIED take higher opioid doses than those without OIED. Impaired inhibitory signaling was recently demonstrated in a study showing reduced deglutitive inhibition during multiple rapid swallows in patients taking opioids. Summary OIED is frequent in chronic opioid users undergoing manometry for esophageal symptoms, especially at higher doses or with stronger opioids. OIED appears to be due to impaired inhibitory signals in the esophagus. Opioid cessation or dose reduction is recommended, but studies examining management of OIED are lacking.

The Impact of Medications on Esophageal Motility

“…Endogenous opioids including enkephalin, dynorphin, and β-endorphin control esophageal motility through µ, Ƙ, and δ G-protein coupled receptors. 6,7 Exogenous opioids used clinically are structurally distinct and selectively activate the µ opioid receptor leading to downstream pathways which inhibit voltage-gated calcium channels and increase transmembrane potassium current causing neural inhibition. 7 This neural inhibition blocks NO releasing inhibitory neurons resulting in increased LES tone, decreased LES relaxation, and high amplitude simultaneous contractions in the esophagus (Figure 1).…”

“…There is limited data to explain the pathophysiologic mechanisms of OIED, but the proposed mechanism is that chronic opioids interfere with inhibitory neural signaling leading to unregulated excitatory control in the esophagus. 6-9…”

“…The manometric classifications include distal esophageal spasm (DES), esophagogastric outflow obstruction (EGJOO), achalasia type III, and hypercontractile esophagus. 6-8,11 These classifications are seen in about 25% of chronic opioids users referred for high resolution manometry (HRM). Research suggests that OIED is associated with stronger opioids such as oxycodone and hydrocodone compared to tramadol, likely requires chronic opioid use, and has a dose-dependent effect with higher likelihood of OIED for patients taking higher morphine equivalent doses.…”

“…Retrospective studies suggest there is a dose dependent effect so potential reduction in dose, weaning to a weaker opioid, or complete opioid cessation may treat OIED; however, this needs to be confirmed in prospective studies. 6,8,13 Many questions remain on management of OIED. The overall prevalence of OIED needs to be further investigated in a general chronic opioid population rather than the symptomatic population referred for HRM.…”

“…Moreover, there are no prospective clinical trials to date to determine the effect of opioid dose reduction, cessation, or antagonism. 6,8…”