New long-term opioid use linked to increased risk of death, study finds

New long-term use of opioids to ease pain after lung cancer surgery is linked to a 40% increased risk of death from any cause in the next 2 years, according to research published in line in the magazine Regional anesthesia and pain medicine.

Male gender, older age, chemo use, anxiety, and insomnia are among the factors associated with long-term re-use (6 months or more), according to the results.

Lung cancer is the leading cause of cancer death worldwide, with almost 2.3 million diagnoses and 1.8 million deaths in 2020. And new persistent postoperative pain has been reported in up to 12% patients.

The researchers therefore wanted to know what proportion of them become first-time opioid users after surgery, whether particular factors are associated with long-term use, and whether this is associated with harmful effects in next 2 years.

They included all adults diagnosed with lung cancer who had undergone surgery for their disease between 2011 and 2018 in South Korea, details of which were extracted from the National Health Insurance Service (NHIS) database.

Doctors in South Korea must enter details of their patients’ diagnoses, procedures and prescription medications in order to be reimbursed for treatment costs by the government. The database also contains basic personal information, including age, gender, and household income on each registrant and the date of their death.

Codeine, dihydrocodeine and tramadol have been classified as less potent opioids; all other opioids, such as fentanyl, morphine, oxycodone, hydromorphone, and methadone, have been classified as strong opioids.

Researchers considered other underlying conditions/disabilities, type of surgery and whether it was a repeat or initial procedure, where it was performed and whether the patient was discharged home or in long-term care.

Some 60,031 adults underwent lung cancer surgery during the study period, and after excluding those who died in hospital or within the first 6 months of discharge, the final analysis included 54,509.

Six months after surgery, 3325 patients (just over 6%) who had recently been prescribed opioids were still taking them: 859 (1.6%) were taking potent drugs and 2466 (4.5%) were taking less potent drugs.

New long-term opioid use was associated with an increased risk of death from any cause over the next 2 years; 17.5% (574/3325) of long-term opioid users died, compared to 9.5% (4738/51,184) of those not taking opioids.

Compared to those not taking opioids, new long-term users of these drugs were 40% more likely to die within the next 2 years from any cause.

When stratified by potency, those taking less potent opioids were still 22% more likely to die; those taking stronger opioids were 92% more likely to die.

Some factors were associated with a greater likelihood of becoming a new long-term user: older age, male gender, specific surgical procedures, including thoracotomy where a cut is made between the ribs, longer hospital stay, degree of higher disability, chemotherapy treatment, preoperative anxiety and insomnia.

This is an observational study, and as such cannot establish cause. And the researchers point out that they were unable to ascertain lung health before surgery, important lifestyle behaviors, such as smoking and alcohol, or tumor stage, which may all have influenced the results.

But previously published research indicates that opioids can help promote tumor growth and inhibit cancer cell death, while also suppressing the immune system they note.

And they point out: “This is the first study to identify the association of new long-term opioid use with poor long-term survival outcomes after lung cancer surgery using real-world data based on a national registration data.


Journal reference:

Schwenk, ES & Gupta, RK (2022) Mortality associated with long-term opioid use after lung cancer surgery: an infographic. Regional anesthesia and pain medicine.

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