Pain in palliative care remains a challenging symptom to treat. Non-steroidal anti-inflammatory drugs (NSAIDs) have been around for decades, but used less and less over concerns about safety. Are these fears justified for an effective drug?
Key points
- NSAIDs are non-sedating, non-addictive and effective, but use has been declining over concerns about acute kidney injury and bleeding.
- This is the first study to rigorously assess those risks in a real-world palliative population.
- Serious harm was seen in only 2% of patients prescribed NSAIDs and none stopped the NSAID due to harm.
- NSAIDs may be safer than previously thought and may be an important and underutilised class of analgesic.
NSAIDs and current practice
There has been little doubt about the effectiveness of NSAIDs for a variety of types of pain and clinical settings for many decades.
NSAIDs are recommended for post-operative pain, musculoskeletal pain, and the first step of the WHO analgesia ladder for cancer-related pain. They are available over the counter in Australasia for patient self-administration for minor ailments.
In palliative care, they are particularly effective for cancer-related bone pain, non-malignant musculoskeletal pain, soft tissue invasion (particularly pleura) by tumours, and a variety of other pains.
However, use of NSAIDs has been falling since the 2000s due to concerns about safety. NSAIDs are associated with some serious harms including acute kidney injury and bleeding, Studies show it is concern over these serious drug reactions that cause clinicians not to prescribe NSAIDs.
Old drugs, new opportunities
More recently, a new generation of NSAIDs has emerged - the COX-2 selective ‘coxibs’. These are associated with less bleeding than traditional NSAIDs, but at the cost of increased risk of cardiovascular disease.
The increased cardiovascular risk is very small and takes some time to develop, whereas the reduction in bleeding is larger and the bleeding risk is increased from the first dose. As such, we argue in a recent study that coxibs are a more rationale choice in palliative care and provide a potentially safe new option.
Evaluating the risks of NSAIDs for patients receiving palliative care
Although adverse reactions are the main barrier to prescribing NSAIDs in palliative care, no studies until now have rigorously evaluated the risk of NSAIDs in palliative patients.
The IMPACCT Rapid Program investigates the real-world harms and benefits of a variety of palliative interventions. We conducted a Rapid series to assess the harms of NSAIDs prospectively, systematically, and rigorously in 92 real-world patients from 14 sites across Australia, Aotearoa New Zealand and the UK.
We found that in spite of clinician concerns, only 3% of patients had episodes of bleeding or acute kidney injury in the month after starting NSAIDs. Only 2% of patients suffered serious harm and none stopped their NSAID due to harm. In contrast, almost 90% of patients had benefit and 65% had benefit without any harm. Half of the patients received the newer COX-2 selective NSAIDs.
Importantly, this study included many patients with significant risk factors for acute kidney injury and bleeding. These patients would never have been included in a randomised trial, and the study results show that NSAIDs can be safe and effective even outside of the ‘perfectly selected’ patient populations.
Implications for practice
The study suggests that NSAIDs are safer in a real-world palliative care setting than previously thought. NSAIDs are cheap, non-addictive, non-sedating, and effective analgesics. They may be an underutilised tool in the analgesic arsenal. Safety data from this study may be exactly what is needed to allow clinicians in palliative care to fully utilise these important drugs.
Reference
McNeill R, Boland JW, Wilcock A, et al. Non-steroidal anti-inflammatory drugs for pain in hospice/palliative care: an international pharmacovigilance study. BMJ Support Palliat Care 2023; spcare-2022-004154.
Dr Richard McNeill is a palliative care physician and clinical pharmacologist in New Zealand. He is currently employed at Nurse Maude Hospice in Christchurch, and he is also a research fellow at the University of Otago. He is undertaking a masters in clinical informatics. Richard has an interest in research involving all aspects of pharmacotherapy in palliative care.