New long-term opioid use after lung cancer surgery associated with 40% higher risk of death within the next 2 years

New long-term use of opioids for pain relief after lung cancer surgery is associated with a 40% increased risk of death from any cause within the next 2 years, according to a study published online in the journal Regional anesthesia & pain medicine.

Male gender, older age, chemotherapy, anxiety and insomnia are among the factors associated with new long-term use (6 or more months), the results show.

Lung cancer is the leading cause of cancer deaths worldwide with nearly 2.3 million diagnoses and 1.8 million deaths in 2020. New persistent postoperative pain was reported in up to 12% of patients.

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

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

Doctors in South Korea must enter details about their patients’ diagnoses, procedures and prescription medications in order to receive reimbursement from the government. The database also contains personal background information, including age, gender and household income, for each registrant and the date of his or her death.

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

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

Approximately 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 of them.

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

Long-term new opioid use was associated with an increased risk of death from any cause within 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 from any cause within the next 2 years.

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

Certain factors were associated with a higher likelihood of becoming a new long-term user: older age, male gender, certain surgical procedures, particularly thoracotomy with an incision between the ribs, longer hospital stays, a higher degree of disability, chemotherapy treatment, and preoperative anxiety and insomnia.

This is an observational study and therefore cannot determine a cause. And the researchers stress that they couldn’t determine lung health before the surgery, important lifestyle habits like smoking and drinking, or tumor stage, all of which may have influenced the results.

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

In addition, they point out, “This is the first study to identify the association between new long-term opioid use and poorer long-term survival outcomes after lung cancer surgery using real-world data based on a national registry.”