Pre-operative pain: an unaddressed confounder in anaesthesia-related cognitive outcomes

Abstract

Li et al. [1] investigated whether regional anaesthesia confers long-term cognitive benefits over general anaesthesia in older patients having hip fracture surgery. The study includes several methodological strengths, such as a pragmatic design, stratification by baseline cognitive status and the use of validated tools like the Abbreviated Mental Test or Mini-Mental State Examination (MMSE) adapted for Chinese populations, all of which enhance its validity. In addition, the study included long-term follow-up. However, pre-operative pain was not included in peri-operative assessment. Moderate-to-severe acute/chronic pain is strongly associated with accelerated cognitive decline, particularly memory, attention and executive function [2]. Chronic pain, particularly multi-site pain, is associated with twice the dementia risk of pain-free individuals and is linked to accelerated hippocampal ageing and cognitive decline [3]. A cohort study conducted in a Chinese population found that individuals experiencing persistent musculoskeletal pain or multi-site pain had higher dementia risk scores and lower cognitive function scores over a 4-year follow-up period [4].

Differences in peri-operative analgesia between regional anaesthesia and general anaesthesia groups also may have introduced confounding. The severity of pre-operative pain, if not balanced, may influence both the selection of anaesthesia and postoperative cognitive outcomes, thereby potentially introducing bias into the results. For example, patients with severe pain might receive regional anaesthesia disproportionately for early analgesia, yet baseline pain levels were neither measured nor adjusted for. This oversight may confuse anaesthesia effects with pain-related cognitive changes, obscuring causal interpretations. Pre-operative pain is a potential confounder that warrants consideration. Failure to include this variable could result in heterogeneity in baseline cognitive status (due to pain-induced cognitive changes) and lead to either an under- or overestimation of the impact of anaesthesia on cognitive outcomes. Future studies should incorporate standardised pain metrics (e.g. NRS or VAS) and anatomical sites for all enrolled patients and include these as covariates in multivariate models to adjust for the influence of pain on cognitive assessment. Generalisability considerations include the female predominance in the cohort (74%) and low educational attainment, which align with hip fracture epidemiology but may limit extrapolation to populations with differing MMSE cultural adaptations or anaesthesia practices. Cognitive outcomes in this vulnerable population likely reflect multifactorial interactions among anaesthesia type, haemodynamic stability and pre-operative risk profiles – including unaddressed pain. Multimodal interventions targeting these factors remain critical for optimising cognitive health.