Association between opioid usage and rectal dysfunction in constipation: A cross‐sectional study of 2754 patients

Abstract

BackgroundOpioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated.MethodsCross‐sectional (hypothesis‐generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004‐2016) for investigation of functional constipation (defined by “derived” Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub‐classified as prescriptions for mild‐moderate or moderate‐severe pain.Key ResultsA total of 2354 patients (85.5%) were classified as non‐opioid users, 162 (5.9%) as opioid users for mild‐moderate pain, and 238 (8.6%) for moderate‐severe pain. Opioids for moderate‐severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%‐CI 2.3‐3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%‐CI 1.23‐2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%‐CI 1.28‐2.34]; P < .001), and delayed whole‐gut transit (odds ratio 1.68 [95%‐CI 1.19‐2.37]; P = .003). Differences in anorectal variables between opioid users for mild‐moderate pain and non‐opioid users were not statistically significant. Hierarchical opioid use (non vs mild‐moderate vs moderate‐severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole‐gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%).Conclusions and InferencesOpioid use is over‐represented in patients referred for investigation of constipation. Opioids for moderate‐severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.

Rectal hyposensitivity: a common pathophysiological finding in patients with constipation and associated hypermobile Ehlers–Danlos syndrome

“…Recently, anorectal physiological studies have suggested that opioid usage is associated with rectal hyposensitivity in patients with refractory constipation. 20 Opioid analgesics are often prescribed in hEDS/HSD patients due to the presence of chronic pain. 27 Indeed, in the current study, a greater proportion of hEDS/ HSD patients were using opioids compared to controls at the time of lower GI physiological testing.…”

“…There is a known association between opioid usage and rectal hyposensitivity. 20 Despite the adjustment, hEDS/HSD patients were still more likely to be diagnosed with rectal hyposensitivity (ORadj 2.77 [1.45-5.34]; p = 0.002).…”

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation

“…153 However, in the majority of patients with chronic constipation, it remains unclear whether RH is a primary pathology leading to increasing severity of symptoms, whether chronic constipation itself results in the development of RH, or if indeed RH is an epiphenomenon. 113,154 With regard to pathophysiology of RH in CC, this is considered to be either due to dysfunction of the afferent pathway ("primary" RH), as a result of altered rectal wall biomechanics (ie, increased capacity or hypercompliance ("secondary" RH: see Figure 5), or both. 155 Symptomatically, RH is associated with "no urge constipation" 156,157 and is more common in individuals meeting the Rome IV criteria for F I G U R E 5 Rectal pressure-volume relationships determined through use of the electromechanical barostat (phasic isobaric distension protocol) in constipated patients with rectal hyposensitivity (RH) to balloon distension, constipated patients with normal rectal sensation (NS), and healthy volunteers (HV).…”

“…The Rome IV criteria define OIC as a change in bowel habit or defecatory patterns, in comparison with normal following initiation, alteration, or an escalation in opioid therapy, see Table 1 20 . Two recent cross‐sectional studies comparing symptoms and results of diagnostic testing in constipated patients either currently taking or not taking opioids have shown that opioid use is associated with increased symptom severity, diminution in quality of life, and a greater incidence of rectal hyposensitivity, functional EDs/dyssynergic defecation, and delayed whole‐gut transit 112,113 …”

“…In others, behavioral inattention to defecation (ie, voluntary withdrawal of attention from rectal sensations and/or habitual suppression of the desire to defecate) is a likely factor 153 . However, in the majority of patients with chronic constipation, it remains unclear whether RH is a primary pathology leading to increasing severity of symptoms, whether chronic constipation itself results in the development of RH, or if indeed RH is an epiphenomenon 113,154 …”