New, long-term use of opioids after lung cancer surgery was linked to a 40% increased risk of death from any cause within the following 2 years, according to findings published by Oh et al in the journal Regional Anesthesia & Pain Medicine.

Persistent postoperative pain has been reported in up to 12% of patients who undergo lung cancer surgery. The researchers, therefore, wanted to know what proportion of patients become opioid users for the first time following surgery, whether particular factors are associated with long-term use, and if this is associated with any harmful effects within the subsequent 2 years.

Study Details

The research team, all based at Seoul National University Bundang Hospital in Seongnam, Korea, 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 retrieved from the National Health Insurance Service database. Doctors in South Korea must enter details of their patients’ diagnoses, procedures, and prescription drugs in order to be reimbursed for treatment costs by the government. The database also contains background personal information, including the age, sex, and household income of all registrants and the date of their death.

Codeine, dihydrocodeine, and tramadol were categorized as less potent opioids; all other opioids—such as fentanyl, morphine, oxycodone, hydromorphone, and methadone—were categorized as potent opioids.

The researchers took account of other underlying conditions/disabilities, the surgery type and whether it was a repeat or first-time procedure, where it was performed, and whether the patient was discharged home or to long-term care.

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

Findings on Opioid Use 

Six months after surgery, 3,325 patients (just over 6%) who had been newly prescribed opioids were still taking them: 859 (1.6%) were on potent drugs and 2,466 (4.5%) were on less potent drugs.

Nearly 18% (574 of 3,325) of long-term opioid users died compared with 9.5% (4,738 of 51,184) of those not taking opioids. Compared with those not taking opioids, new, long-term users of these drugs were 40% more likely to die within the next 2 years of any cause. When stratified by potency, those taking less potent opioids were still 22% more likely to die, and those taking more potent opioids were 92% more likely to die.

The findings showed that certain factors may be associated with a greater likelihood of becoming a new, long-term user after 6 months or more of taking opioids: older age, male sex, particular surgical procedures (especially thoracotomy), longer length of hospital stay, a greater degree of disability, chemotherapy treatment, and preoperative anxiety and insomnia.

This is an observational study, and as such, it can’t establish cause. The researchers highlighted that they weren’t able to ascertain lung health before surgery, important lifestyle behaviors such as smoking and drinking, or tumor stage, all of which may have influenced the findings. But previously published research indicates that opioids may help promote tumor growth and inhibit cancer cell death, while also suppressing the immune system.

“This is the first study to identify the association of new, long-term opioid use with poorer long-term survival outcomes after lung cancer surgery using real-world data based on a national registration database,” the researchers highlighted.

Disclosure: For full disclosures of the study authors, visit rapm.bmj.com.