Opioid-induced Esophageal Dysfunction Research Articles

S3321 Opioid-Induced Esophageal Dysfunction Masquerading as Type I Achalasia

S3321 Opioid-Induced Esophageal Dysfunction Masquerading as Type I Achalasia

Peroral endoscopic myotomy and its use in non-achalasia disorders.

The aim of this review is to provide an overview of per-oral endoscopic myotomy (POEM) and its utilization in non-achalasia disorders of the esophagus. POEM, a relatively novel endoscopic technique, involves submucosal tunneling to access esophageal muscle layers, enabling selective myotomy and mitigating the consequences of motor disorders of the esophagus. POEM is an effective treatment modality for diffuse esophageal spasm providing resolution of chest pain and dysphagia in a majority of patients who have refractory symptoms despite medical therapy. The results of POEM are more equivocal compared to esophagogastric junction outflow obstruction (EGJOO). POEM in EGJOO has been shown to have a 93% clinical success rate in 6months. POEM appears to be more effective in motor disorders that affect the lower esophageal sphincter, such as EGJOO and opioid-induced esophageal dysfunction. While the current data for POEM in other entities such as DES and HE are positive, more supportive data are required to make POEM a consistent recommendation for patients.

Peroral endoscopic myotomy for spastic esophageal dysmotility among opioid users: a multicenter propensity score matching study

Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score≤3. A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n= 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P= .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P= .02). Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

S606 Opioid-Induced Esophageal Dysfunction in Current and Former Opioid Users

S606 Opioid-Induced Esophageal Dysfunction in Current and Former Opioid Users

Impact of opioids on esophageal motility

Opioids are well known to cause adverse effects on the gastrointestinal tract including nausea, vomiting, and constipation. Data regarding how opioids affect the esophagus are more limited. Opioid-induced esophageal dysfunction (OIED) is a clinical syndrome defined by chronic opioid use (≥3 months), esophageal symptoms (mainly dysphagia), and esophageal motility abnormalities diagnosed by manometry including achalasia type III, hypercontractile esophagus, distal esophageal spasm, and esophagogastric junction outflow obstruction. Up until now, the effect of opioids on esophageal motility assessed by the functional lumen imaging probe (FLIP) had not been described. In this issue of NGM, Patel et al. report that FLIP assessment in patients with esophageal symptoms showed that chronic opioid users have a significant increase in repetitive retrograde contractions, but no significant reduction in distensibility at the esophagogastric junction compared to non-users. Additionally, perceptive symptoms were higher, and quality of life metrics were lower in the chronic opioid users. This review article will discuss our current understanding of OIED and provide context for this latest study in chronic opioid users. Further investigation with larger prospective studies is needed to understand the pathophysiology, diagnosis, and management of OIED.

Diagnosis and Management of Opioid-Induced Esophageal Dysfunction

Diagnosis and Management of Opioid-Induced Esophageal Dysfunction

Incidence of opioid-induced esophageal dysfunction.

Retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction. A recent clinical entity known as opioid-induced esophageal dysfunction (OIED) has been postulated. There is no data from prospective studies assessing the incidence of opioid-induced effects on the esophagus. Evaluate the incidence of OIED during chronic opioid therapy. From February 2017 to August 2018, all patients seen in the Pain Unit of the hospital, who started opioid treatment for chronic non-neoplastic pain and who did not present esophageal symptoms previously, were included. The presence of esophageal symptoms was assessed using the Eckardt score after 3 months and 1 year since the start of the study. In February 2021, the clinical records of all included patients were reviewed to assess whether esophageal symptoms were present and whether opioid therapy was continued. In patients presenting with esophageal symptoms, an endoscopy was performed and, if normal, a high-resolution esophageal manometry was performed. For a confidence level of 95%, a 4% margin of error and an estimated prevalence of 4%, a sample size of 92 patients was calculated. 100 patients were included and followed while taking opioids, for a median of 31 months with a range between 4 and 48 months. Three women presented with dysphagia during the first 3 months of treatment, being diagnosed with esophagogastric junction outflow obstruction; type II and type III achalasia. The cumulative incidence of OIED was 3%; 95%-CI: 0-6%. Chronic opioid therapy in patients with chronic non-neoplastic pain is associated with symptomatic esophageal dysfunction.

Incidence of opioid-induced esophageal dysfunction

Retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction. A recent clinical entity known as opioid-induced esophageal dysfunction (OIED) has been postulated. There is no data from prospective studies assessing the incidence of opioid-induced effects on the esophagus. Evaluate the incidence of OIED during chronic opioid therapy. From February 2017 to August 2018, all patients seen in the Pain Unit of the hospital, who started opioid treatment for chronic non-neoplastic pain and who did not present esophageal symptoms previously, were included. The presence of esophageal symptoms was assessed using the Eckardt score after 3 months and 1 year since the start of the study. In February 2021, the clinical records of all included patients were reviewed to assess whether esophageal symptoms were present and whether opioid therapy was continued. In patients presenting with esophageal symptoms, an endoscopy was performed and, if normal, a high-resolution esophageal manometry was performed. For a confidence level of 95%, a 4% margin of error and an estimated prevalence of 4%, a sample size of 92 patients was calculated. 100 patients were included and followed while taking opioids, for a median of 31 months with a range between 4 and 48 months. Three women presented with dysphagia during the first 3 months of treatment, being diagnosed with esophagogastric junction outflow obstruction; type II and type III achalasia. The cumulative incidence of OIED was 3%; 95%-CI: 0–6%. Chronic opioid therapy in patients with chronic non-neoplastic pain is associated with symptomatic esophageal dysfunction. Estudios retrospectivos han sugerido que el uso crónico de opiáceos puede causar disfunción esofágica. Se ha postulado una entidad clínica reciente denominada disfunción esofágica inducida por opioides (DEIO). No existen estudios prospectivos que evalúen la incidencia de esta entidad. Evaluar la incidencia de DEIO durante el tratamiento crónico con opiáceos. Desde febrero de 2017 hasta agosto de 2018, se incluyeron todos los pacientes atendidos en la Unidad del Dolor de nuestro hospital, que iniciaron opiáceos por dolor crónico no neoplásico sin síntomas esofágicos previos. La clínica esofágica se valoró mediante la escala de Eckardt a los tres meses y al año. En febrero de 2021, se revisaron las historias clínicas de todos los pacientes para evaluar la presencia de clínica esofágica y si continuaban con opiáceos. En los pacientes con síntomas esofágicos, se realizó una gastroscopia y, si era normal, una manometría esofágica de alta resolución. Para un nivel de confianza del 95%, una precisión del 4% y una prevalencia estimada del 4%, se calculó un tamaño muestral de 92 pacientes. Se incluyeron 100 pacientes que fueron seguidos mientras tomaban opiáceos, con una mediana de 31 meses y un rango entre 4 y 48 meses. Tres mujeres presentaron un trastorno motor esofágico durante el seguimiento (obstrucción funcional de la unión esofagogástrica; acalasia tipo II y tipo III). La incidencia acumulada fue del 3%; IC 95%: 0-6%. El tratamiento crónico con opiáceos en pacientes con dolor crónico no neoplásico se asocia a disfunción esofágica sintomática.

Opioid-Induced Esophageal Dysmotility (OIED) - A Case Report.

Recent studies have shown that chronic opioid use is associated with an increased risk of symptomatic esophageal motility disorders. Opioid-induced esophageal dysfunction (OIED) is most often identified in patients taking high doses of opioids. This condition is associated with poorer treatment outcomes than primary motility disorders and management of these cases is further complicated by the presence of chronic pain, opioid addiction, and physical and psychological comorbidity.We present the case of a 68-year-old Caucasian woman with OIED, induced by the chronic intake of low-dose Fentanyl and Tramadol prescribed to treat severe back pain. The clinical course highlights the sometimes difficult diagnosis and management of this recently recognized condition.

Prevalence and impact of opioid use in patients undergoing peroral endoscopic myotomy

Chronic narcotic use may cause opioid-induced esophageal dysfunction and associated type III achalasia, hypercontractile esophagus (HE), diffuse esophageal spasm (DES), and esophagogastric junction outflow obstruction (EGJOO). The frequency of opioid use and its impact on peroral endoscopic myotomy (POEM) in these patients is unknown. Consecutive patients between April 2017 and September 2021 who underwent POEM for type III achalasia, EGJOO, DES, or HE with≥6 months follow-up were identified. Baseline evaluation was done with EGD, esophageal high-resolution manometry (HRM), and functional lumen impedance planimetry (FLIP) of the esophagogastric junction (EGJ). Eckardt scores (ESs) were calculated at baseline and follow-up at 6 to 12 months after POEM for opioid users and nonusers. Clinical response was defined as ES≤3, EGJ distensibility index >2.8mm2/mm Hg, maximum EGJ diameter >14mm, and integrated relaxation pressure (IRP)<15mm Hg. Opioid use before baseline HRM was assessed. One hundred twenty-six patients underwent POEM, and 89 had≥6 months of follow-up. Daily opioid use was present in 18 of 89 patients (20%). Baseline demographics, FLIP metrics, IRP, distribution of motility disorders, and POEM characteristics were similar between both groups. At 6 to 12 months after POEM, clinical response and frequency of GERD, esophagitis, and proton pump inhibitor use were similar between opioid users and nonusers. Heartburn was more frequent in the opioid group (82.4% vs 38.6%, P= .002). In this single-center study of 89 patients with type III achalasia, EGJOO, DES, or HE treated with POEM, daily opioid use was present in 20%. Response to POEM and post-POEM GERD were similar between opioid users and nonusers. (Clinical trial registration number: NCT02770859.).

ASSOCIATION BETWEEN OPIOID USE AND OUTPATIENT VISITS FOR DYSPHAGIA: AN ANALYSIS OF THE NATIONAL AMBULATORY MEDICAL CARE SURVEY IN 2008-2018.

Opioids-induced esophageal dysfunction has been described with characteristic manometric patterns, but the population burden of dysphagia attributable to opioid use remains unclear. National Ambulatory Medical Care Survey (NAMCS) from 2008-2018 was used to assess the relationship between opioid use and outpatient visits for dysphagia. After controlling for potential confounders there were no significant difference in ambulatory visits for dysphagia between opioid users and non-users (adjusted odds ratio=0.98, confidence interval: 0.59-1.65). No correlation between opioid use and ambulatory visits for dysphagia was found in a nationwide sample. Opioid-related manometric changes may be clinically relevant only in a small proportion of patients.

The Impact of Medications on Esophageal Motility

The purpose of this review is to highlight the impact of common medications on esophageal motility. Esophageal motility is mediated through a complex network of neural innervation. Opioids lead to excitatory esophageal motor abnormalities termed opioid-induced esophageal dysfunction or OIED. Prokinetics have mixed effects on esophageal motility. Nitrates and calcium channel blockers relax esophageal smooth muscle, but they are limited clinically due to side effects. Sildenafil also relaxes smooth muscle, but it is costly. Peppermint oil may reduce distal esophageal spasm. Anticholinergics, selective serotonin reuptake inhibitors, estrogen, and cannabis need further study to evaluate their effects on esophageal motility.

Non-Acid Fluid Exposure and Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) accounts for the large majority of esophageal cancer cases worldwide. In this review, we examine the potential role of non-acidic fluid (NAF) exposure in ESCC carcinogenesis. Esophageal NAF consists of a mixture of salivary, esophageal, gastric, and duodenal fluids, containing inflammatory constituents such as digestive enzymes and bile acids that induce DNA damage, as well as known carcinogens such as acetaldehyde and N-nitrosamines. Exposure to NAF can occur in the setting of increased non-acid reflux, decreased gastric acidity, and decreased esophageal fluid clearance. Non-acid reflux has been associated with ESCC in small observational studies, and in animal models bile reflux can promote the development of ESCC. Associations have been found between increased ESCC risk and atrophic gastritis, a history of partial gastrectomy, and proton pump inhibitor use, all of which raise the pH of refluxate. Additionally, a minimally or non-acidic gastric environment contains an altered microbiome that can increase the production of acetaldehyde and N-nitrosamines. Esophageal motility disorders such as achalasia and opioid-induced esophageal dysfunction result in increased stasis and exposure to these potentially proinflammatory constituents of NAF. NAF may promote the development of ESCC via multiple mechanisms and is an understudied area of research.

Opioid-induced esophageal dysfunction - Prevalence and manometric findings.

prescription opioid use is on the rise. There has been an increasing recognition that chronic opioid consumption can result in esophageal motility disorders, and this association has been named opioid-induced esophageal dysfunction (OIED). to analyze the prevalence of chronic opioid consumption in patients referred for esophageal motility testing in a European center; to describe the clinical characteristics and the association of opioid consumption with esophageal motility disorders. a retrospective, descriptive study in patients who had undergone an HRM in a single center. The clinical history in the electronic medical records was reviewed. the prevalence of opioid prescription in patients referred to our institution was 10.1 %, and 4.8 % of them were chronic active opioid users. There was a 32 % prevalence of OIED. Comparing chronic active opioid users (CAOU) with OIED and CAOU patients without OIED, there was a higher prevalence of males (43.8 % vs 8.8 %; p-value = 0.007). Converting the different opioid medications to morphine milligram equivalent daily dose (MMED), CAOU patients with OIED had a higher MMED than CAOU patients without OIED (125.2 ± 31.3 vs 33.4 ± 5.7 MME; p = 0.041). Dysphagia was the most common indication for performing an HRM in 60.0 % of CAOU patients. Furthermore, dysphagia was more frequent in CAOU patients with OIED (87.5 % vs 47.0 %; p = 0.019). chronic opioid users with OIED complained mostly of dysphagia. There was an association of male sex and a higher dose of opioids in CAOU patients with esophageal motility disorders.

Same-day opioid administration in opiate naïve patients is not associated with opioid-induced esophageal dysfunction (OIED).

Opioid-induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear. Opioid naïve patients with high-resolution manometry (HRM) <480min following esophagogastroduodenoscopy (EGD) (opioid-HRM) and a control group with HRM <36h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl. One hundred and seventy-four patients were identified, with 83 (47.7%) opioid-HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78-435)min. Baseline clinical features and HRM indications were similar between opioid-HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid-HRM and controls (27.7% vs. 36.3%, p=0.23). Mean distal contractile integrity (DCI) was higher in opioid-HRM (1939.3±1318.9 vs. 1792.2±2062.3mmHg∙cm∙s, p=0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240min after EGD, >240min after EGD, ≥125 mcg of IV fentanyl, <125mcg IV fentanyl and controls. Same-day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration-dependent relationship with opioids in OIED are needed.

Opioid-induced esophageal dysfunction.

Chronic opioid use is common and can cause opioid-induced esophageal dysfunction (OIED). We will discuss the pathophysiology, diagnosis, and management of OIED. 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. 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.

Esophageal Dysphagia in the Elderly.

With a globally aging population, dysphagia is a growing health concern among elderly. Increasing reflux disease has contributed to an increased prevalence of dysphagia from peptic strictures and esophageal cancer. Dysphagia can lead to malnutrition and aspiration pneumonia, causing considerable morbidity and mortality. This review article focuses on recent advances in the approach and management of esophageal dysphagia. Endoscopic functional luminal imaging probe is a novel test that complements upper endoscopy, esophagram, and esophageal manometry for evaluation of esophageal dysphagia. Opioid induced esophageal dysfunction (OIED) is an emerging clinical entity that can mimic achalasia. Strictures refractory to dilation can be treated with intralesional steroid injections, electrosurgical incision, or esophageal stents. Peroral endoscopic myotomy (POEM) is gaining in popularity for treatment of achalasia and other spastic disorders of esophagus. Treatment of esophageal dysphagia may include proton pump inhibitors, endoscopic dilation, or surgery and requires a personalized approach based on risks and benefits. POEM is a valuable therapy for achalasia, but further studies are needed to evaluate its use, and other alternatives, for treatment of OIED and spastic esophageal disorders.

Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose.

Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

Implications of the Opioid Epidemic for the Clinical Gastroenterology Practice.

The opioid epidemic in the USA has led to a rise in opioid-related gastrointestinal (GI) side effects that are often difficult to diagnose and treat. The aim of this report is to discuss opioid pathophysiology, opioid-related GI side effects, clinical presentation, and diagnostic criteria and to review the current pharmacotherapy available. Opioid-related GI disorders are increasingly recognized and include, but are not limited to, opioid-induced esophageal dysfunction (OIED), gastroparesis, opioid-induced constipation (OIC), narcotic bowel syndrome (NBS), acute post-operative ileus, and anal sphincter dysfunction. Treatment of these conditions is challenging. OIC has the most available pharmacotherapy for treatment, including classical laxatives, peripherally acting μ-receptor antagonists (PAMORAs), novel therapies (lubiprostone, prucalopride- 5-HT agonist), and preventative therapies (PR oxycodone/naloxone). The gastrointestinal effects of opioid therapy are variable and often debilitating. While medical management for some opioid-related GI side effects exists, limiting or completely avoiding opioid use for chronic non-cancer pain will mitigate these effects most effectively.

Emerging Issues in Esophageal Motility Diseases

With the advances in technology and medical knowledge, new diseases are being identified and investigated. Esophageal motility disorders have been re-defined using high-resolution manometry and their pathogenesis are being better understood. The use of opioid analgesics is increasing worldwide, particularly in the United States, but their chronic use can cause opioid-induced esophageal dysfunction, which mimics spastic motor disorders, including achalasia type 3 or 2 and esophagogastric junction outflow obstruction. Eosinophilic esophagitis is identified by eosinophilic infiltration confirmed on a pathological examination. The condition is often associated with esophageal motility abnormalities. On the other hand, recent studies have suggested that muscle-predominant eosinophilic infiltration, eosinophilic esophageal myositis, might manifest as spastic motor disorders, including achalasia or jackhammer esophagus. Lymphocytic esophagitis is an unusual esophageal condition, which is confirmed by the increased number of lymphocytes in the esophageal epithelium. Although several reports have supported the existence of lymphocytic esophagitis, it is still unclear whether lymphocytic esophagitis is a distinct disease entity or another spectrum of other esophageal diseases, such as gastroesophageal reflux disease or eosinophilic esophagitis. This review presents evidence and reports on the emerging issues in esophageal motility disorders, including opioid-induced esophageal dysfunction, eosinophilic esophagitis with eosinophilic esophageal myositis, and lymphocytic esophagitis.