Even moderate doses — as low as 31 to 60 MME per day — were linked to a measurable increase in risk of respiratory depression.
Additionally, the combination of opioids and gabapentinoids, such as gabapentin and pregabalin, was associated with a further increased risk in respiratory depression.
Fentanyl’s high potency and rapid brain uptake help explain why it suppresses breathing more abruptly than other opioids.
Oxycodone’s role in opioid‑related deaths in North America adds further weight to concerns about its respiratory effects.
The study also found that patients with COPD faced even greater risks, with fentanyl linked to a fourfold increase in respiratory depression in this group.
These results suggest people with chronic respiratory disease may be especially vulnerable to the effects of potent opioids.
Fatal overdoses associated with opioids, up to 80 per cent of which are unintentional, are most often caused by opioid‑induced respiratory depression, where breathing slows to life‑threatening levels.
Although all potent opioids act on the same receptor system, they differ in how they affect respiratory control.
First author, Mr Carlos Raul Ramirez, a research associate at the University of Manchester, said: “As part of our study we were also able to assess for the additional risk associated with other co-administered medications, such as gabapentinoids and benzodiazepines, which may be prescribed for pain, anxiety and sleep problems.
“The use of gabapentinoids with opioids in particular was associated with an increased risk of respiratory depression.”
Senior author Dr Meghna Jani, NIHR Advanced Fellow and Senior Clinical Lecturer at The University of Manchester said: “Opioids remain important medicines for managing severe acute pain. Our findings show that the risks are not the same across all opioid drugs or doses.
“A key strength of our study was our ability to use detailed hospital electronic health records to accurately capture when opioids were actually administered to patients, alongside routinely collected vital signs to identify changes in breathing.
Dr Jani, who is also a researcher within the Rheumatic and Musculoskeletal Diseases Theme at Manchester BRC added: “Understanding how different medicines and combinations affect respiratory safety can help clinicians and patients make more informed prescribing decisions together, as well increasing awareness of what dose thresholds require closer monitoring.”
- The paper Opioid-specific Risk of Respiratory Depression in Non-Cancer Pain: A Retrospective Cohort Study is available here DOI
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