A 2025 meta-analysis published in the British Journal of Anaesthesia reveals a concerning connection between how much pain a patient feels after surgery and their risk of experiencing cognitive issues. While pain after surgery is often considered temporary and manageable, this research suggests it may have deeper, longer-lasting effects on brain function.

This extensive systematic review, led by Maram Khaled and an international team of experts, analyzed data from 30 observational studies involving over 9,000 patients. The findings shed light on the association between acute postoperative pain and two key neurocognitive complications:

• Postoperative delirium (POD): a temporary but serious state of confusion
• Postoperative cognitive dysfunction (POCD): a longer-lasting decline in memory and thinking skills

The study focused exclusively on noncardiac surgeries, which are far more common than cardiac operations and affect a wide range of patient populations. 

Understanding POD and POCD

Before examining the study’s findings, it’s essential to understand the neurocognitive complications it investigated.

What is postoperative delirium (POD)?

• • An acute and fluctuating disturbance in awareness, attention, and cognition
  • Can emerge within hours or days after surgery
  • Often mistaken for dementia or depression

• Reported in 7% to 26% of patients after noncardiac surgery

What is postoperative cognitive dysfunction (POCD)?

• A more gradual and persistent decline in cognitive function
• Can affect memory, concentration, and executive functioning
• May last weeks to months, and sometimes up to a year
• Particularly prevalent in older adults and those undergoing major surgery
  

Key findings

• Every 1-point increase in pain intensity (on a 0–10 scale) was associated with a 26% higher risk of POD.
• This equates to an additional 42 cases of delirium per 1,000 patients for each pain level increase.
• A smaller subset of studies confirmed that pain measured before POD onset was still associated with increased risk, reinforcing the theory of pain as a predictive factor, not just a co-occurring symptom.
• The evidence linking pain to POCD was very uncertain, with inconsistent results and methodological variability.
• No studies examined the relationship between chronic postsurgical pain (CPSP) and POCD.

How pain may affect brain health

The review explored several biological mechanisms that could explain why pain might contribute to cognitive complications:

Inflammatory cascade

• Surgery and pain trigger systemic inflammation, which can lead to neuroinflammation.
• Neuroinflammation is a known contributor to delirium and other cognitive disorders.

Sensitization and stress

• Pain increases the release of neurotransmitters like glutamate, promoting central nervous system sensitization.
• Chronic pain may create a cycle of persistent stress and cognitive impairment.

Shared pathways

• Pain and cognition share neurobiological circuits, especially in the hippocampus and prefrontal cortex.
• Animal models show that untreated pain leads to hippocampal dysfunction, a key area involved in memory.

Integrating findings into practice

• Evaluate pain proactively: Use scales like the Numeric Rating Scale (0–10) or Visual Analogue Scale. Assess pain at rest and during movement.
• Prioritize multimodal analgesia: Combine opioids with non-opioid medications (e.g., acetaminophen, NSAIDs). Consider regional blocks or epidural analgesia where appropriate.
• Identify at-risk patients early: 
  • Age > 65
  • History of cognitive impairment
  • Undergoing major or prolonged surgery
• Monitor for signs of delirium: Use tools like the Confusion Assessment Method (CAM). Screen daily for fluctuating consciousness and orientation.
• Minimize unnecessary sedatives: Avoid medications like benzodiazepines unless absolutely necessary.

Final takeaway

Pain after surgery isn’t just an unpleasant side effect; it may be a warning sign of something deeper.

The 2025 systematic review by Khaled et al. underscores that higher levels of postoperative pain are consistently associated with higher risks of postoperative delirium after noncardiac surgery. While the evidence is still evolving, this study adds important weight to the need for early, effective, and individualized pain management.

For more information on this topic,  check out Anesthesia Updates on the NYSORA Anesthesia Assistant App. 

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