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 toxicity effects should become a standard of care.
Chronic opioid toxicity should 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.