PROSPECTIVE EVALUATION OF OPIOID WITHDRAWAL IN PATIENTS WITH SUSPECTED OPIOID-INDUCED ESOPHAGEAL DYSFUNCTION (OIED)

Background:
Opioid-induced esophageal dysfunction (OIED) is a recognized consequence of chronic opioid use, manifesting mainly as non-obstructive dysphagia and esophageal motility abnormalities documented in manometry studies including type III achalasia, hypercontractile esophagus, distal esophageal spasm, and esophagogastric junction outflow obstruction (EGJOO). Despite the clear association between opioids and esophageal abnormalities the effect of opioid cessation has not been assessed. The primary aim of our study was to evaluate the causal relationship between chronic opioid use and esophageal dysfunction in symptomatic patients.
Methods:
We performed a prospective multicenter study in patients referred for non-obstructive dysphagia that were on chronic opioid treatment (> 3 months). Patients with dysphagia on opioid treatment were evaluated, during the initial referral and then after 7 days without opioid use. In each visit, patients completed an Eckardt questionnaire and underwent a high-resolution esophageal manometry (HRM) following the Chicago 4.0 protocol.
Results:
22 patients (mean age 66 yo, 14 women, 8 men) were included. The opioids used were tramadol (n=17, 77%), fentanyl (n=5, 23%). %). All patients were referred for non-obstructive dysphagia (n=22). In the initial clinical evaluation under opioids, the patients had an Eckardt score of 8 points and after suspension, 2.5 points (p=0.002). In 19 (86%) patients also had abnormal esophageal motility in HRM. In the initial HRM, 19 (86.4%) patients met DEIO criteria; 5 (22.7%) patients with HD, 5 (22.7%) with EEH, 7 (31.8%) OFUEG and 2 (9 .1%) with achalasia type III. There were 3 patients without OEID. In the second evaluation, 7 days after opioid withdrawal, 10/19 (53%) had normal esophageal motility in the second HRM performed and 9 patients did not resolve the motility disorder after opioid withdrawal (p=0.002). Discontinuation of opioids was associated clinically was associated with improvement on dysphagia, 9 patients (64.3%) with an Eckardt questionnaire <3 (p=0.0047). In HRM there was a decrease in baseline lower esophageal sphincter pressure (41.6 mmHg with opioids vs 35.1 mmHg without, p=0.059) and a normalization of the relaxation pressure integral (IRP) (15.2 mmHg with opiates vs 10.9 mmHg without, p=0.002). Regarding esophageal peristalsis, 8 (36.4%) patients under treatment with opioids presented hypercontractile waves in the HRM that resolved in 50% after their withdrawal (p=0.045) and there was an improvement in the percentage of premature waves (14 .1% premature waves with opioids vs 4.5% premature waves without p=0.026).
Conclusions:
Discontinuation of opioids is associated with objective clinical and manometric improvement in up to 50% of patients. In patients with OIED, opioid withdrawal should be performed to assess responsiveness prior to considerer aggressive therapy.