The Research Question

1. The Research Question • What is the scope of clinically-relevant signs and symptoms of chronic opioid toxicity ? • What are the most common clinical approaches to the chronic opioid toxicity screening and management ?

2. What the Researchers Did • Ovid MEDLINE(R), EMBASE, PsychInfo, Cochrane and Google Scholar databases were searched. • Systematic and scoping reviews, and empirical studies regarding the most clinically relevant chronic opioid toxicity signs and symptoms in humans were grouped by organ systems and summarized narratively. • We reviewed toxic effects reversibility, screening and management relevant to clinical practice. • We was requested an Expert Commentary from the specialists with appropriate expertise.

3. What the Researchers Found • Chronic opioid toxicity manifests by the dysfunction of one or more organ systems, with some of these changes requiring a specific treatment, remaining partially or fully irreversible even after opioid therapy discontinuation. • Neuro-endocrine, immune, gastrointestinal, respiratory, cardiovascular, musculoskeletal systems, and the skin are all affected. • Examples of the irreversible chronic opioid toxicity effects include fractures, advanced neuroendocrine changes, addiction and death.

4. What This Means for Clinical Practice • The concept is important for clinicians to assure high quality patient care. • If a decision is made to proceed to long-term opioid therapy, the risks and benefits should be presented to the patient and an explicit consent to continue should be obtained. • The pre-therapy and during long-term opioid therapy screening for potential chronic opioid toxicityeffects should become a standard of care. • Chronic opioid toxicityshould be managed as soon as identified. • Regular attempts to taper to the minimal effective dose, choose a safer option or discontinue opioid therapy should be made.