Chronic pain and multiple long-term health conditions: what happens when they collide? With over half of individuals with multimorbidity experiencing chronic pain, clinicians are often faced with difficult choices about how to manage pain in this complex group. A recent systematic review published in the British Journal of Anaesthesia by Grant et al. (2025) offers critical insights into the risks associated with commonly prescribed painkillers: opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and gabapentinoids.

What is multimorbidity?

Multimorbidity refers to the presence of two or more long-term physical or mental health conditions in the same individual. This increasingly common phenomenon, especially in aging populations, is associated with:

• Reduced quality of life
• Increased healthcare utilization
• Higher mortality rates
• Challenges in clinical management due to polypharmacy and conflicting treatment guidelines

Chronic pain in multimorbidity

Pain is a frequent and often poorly managed symptom in people with multiple health conditions. Despite the high prevalence, clinical guidelines for chronic pain seldom provide recommendations for patients with multimorbidity. Similarly, multimorbid patients are underrepresented in clinical trials, leaving a significant evidence gap.

Opioids: effective but dangerous?

Among 16 studies examining opioid use:

• 12 showed evidence of harm
• Reported harms included:
  • Increased risk of opioid overdose
  • Higher mortality rates
  • Greater rates of hospital readmission
  • More frequent opioid-related adverse drug events (ORADEs)
  • Elevated risk of hip fractures and opioid abuse

Examples of findings:

• Opioid use in multimorbid patients with sepsis was linked to a sevenfold increase in mortality
• Older patients on opioids had longer hospital stays and more frequent 30-day readmissions
• Higher Charlson Comorbidity Index (CCI) scores correlated with increased risk of ORADEs

NSAIDs: double-edged relief

Among 11 NSAID-related studies:

• 6 showed evidence of harm
• Associated harms included:
  • Gastrointestinal bleeding
  • Acute kidney injury (AKI)
  • Increased mortality
  • Possible cardiovascular events

Key insights:

• Postoperative NSAID use increased the need for red blood cell transfusion
• NSAID exposure was linked with treatment-resistant depression in patients with co-occurring mental health conditions
• NSAID users with multiple comorbidities showed increased mortality risk following cardiovascular events

Gabapentinoids: a blind spot in research

Only one study addressed the use of gabapentinoids in multimorbid patients. It found:

• Associations with delirium and pneumonia
• No clear link to increased mortality

Clinical implications and recommendations

1. Assess multimorbidity using validated tools (e.g., Charlson Comorbidity Index).
   
2. Avoid opioids as a first-line option; explore non-pharmacologic therapies like CBT, physical therapy, or acupuncture.
   
3. Limit NSAID use, especially in patients with GI, renal, or cardiovascular conditions.
   
4. Start low and go slow with all analgesics.
   
5. Monitor closely for adverse events, especially during care transitions.
   
6. Avoid polypharmacy and unnecessary duplication of medications.
   
7. Discuss risks with patients and involve them in shared decision-making.
   

Conclusion

Managing pain in patients with multimorbidity demands a nuanced approach that balances benefits against significant risks. This landmark review calls for caution in prescribing, closer monitoring, and a renewed focus on research that includes the very patients most often seen in real-world settings.

Reference: Grant CH. Br J Anaesth. 2025;134:1717-1745.

For more information on multimorbidity and perioperative care recommendations, check out Anesthesia Updates on the NYSORA Anesthesia Assistant App. 

Get access to step-by-step management algorithms, the latest research, and peer-reviewed insights—all in one place. Download the app today and experience the future of anesthesia education and decision-making.

Here’s what MAIA Anesthesia Assistant recommends:

Should I avoid opioids, NSAIDs, and gabapentinoids in patients with multimorbidity?