Use of Tramadol vs Traditional Opioids and Adverse Outcomes in Patients with Inflammatory Bowel Disease: A Danish Nationwide Cohort Study

Abstract

Background Use of traditional opioids (TOs) for pain management has been associated with adverse outcomes among patients with inflammatory bowel diseases (IBDs). It is unknown if similar associations exist for tramadol, a partial opioid agonist and serotonin and norephinephrine reuptake inhibitor. We sought to compare adverse outcomes associated with tramadol vs TOs in an IBD population. Methods This nationwide cohort study included adults with IBD diagnosed from 1995 to 2021 in Denmark with subsequent prescriptions for tramadol or TOs. For each analgesic, 2 populations were assessed: initial users (first prescription) and persistent users (first 3 consecutive prescriptions within 365 days). Outcomes included infection, bowel obstruction/ileus, IBD surgery, and mortality within 90 days after the initial use index date (date of first prescription) and within 365 days after the persistent use index date (date of third prescription). Odds ratios adjusted for demographics, comorbidities, and IBD severity were calculated using multivariable logistic regression. Results We identified 37 377 initial users and 15 237 persistent users of tramadol or TOs. Initial users of tramadol had lower adjusted odds of infection (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.99), bowel obstruction/ileus (aOR, 0.74; 95% CI, 0.53-1.03), and mortality (aOR, 0.43; 95% CI, 0.35-0.55), and a higher adjusted odds of IBD-related surgery (aOR, 1.27; 95% CI, 1.02-1.60) vs initial users of TOs. Similar results were found for persistent users. Conclusions Tramadol was associated with lower odds of infection, bowel obstruction/ileus, and mortality vs TOs among patients with IBD. These associations may be impacted by residual confounding.

Tramadol protects enterocytes after cytokine storm

“…IBD is an autoimmune bowel disease characterized by chronic inflammation [4,11]. Opioids are recommended in the analgesic treatment protocols of patients exposed to IBD [11].…”

“…IBD is an autoimmune bowel disease characterized by chronic inflammation [4,11]. Opioids are recommended in the analgesic treatment protocols of patients exposed to IBD [11]. In a cohort study of IBD patients, lower rates of infection, intestinal obstruction or ileus, and mortality were reported with the use of tramadol [11].…”

“…Opioids are recommended in the analgesic treatment protocols of patients exposed to IBD [11]. In a cohort study of IBD patients, lower rates of infection, intestinal obstruction or ileus, and mortality were reported with the use of tramadol [11]. Application of TNF-α+IFN-ɣ proinflammatory cytokines to the IEC-6 cell line triggers inflammation [7,8].…”