Anesthetic Effects of Spatial and Motor Abilities

Every year, more than 300 million patients undergo surgery worldwide, with the vast majority using some form of general anesthesia (1). Unfortunately, persistent cognitive impairment after surgery and anesthesia is a significant clinical problem, and elderly and newborn/infant patients are at the most risk of developing these impairments. These deficits, including difficulties with fine-motor coordination and impaired high-level cognitive functions, can increase patient morbidity, inconvenience and stress family members, and reduce patients’ quality-of-life (2).

Clinical studies have provided clues about the effects of anesthesia, but they are often limited in their ability to discriminate the effect of anesthesia from the physiological and psychological effects of surgery and often do not control for factors known to influence cognition, such as postoperative medications. Animal experiments allow anesthesia to be studied independently of surgery and permit greater experimental control (2). For instance, at the University of British Columbia, Butterfield et al. undertook a study to investigate whether general anesthesia alone leads to prolonged cognitive impairment in mice and whether age is a risk factor, using both a spatial memory (Barnes maze) and a psychomotor task (rotarod). Mice were anesthetized with isoflurane (a general anesthetic) for 30 min, while controls received 90% oxygen. They found that anesthesia, administered during the asymptotic period of maze learning, did not impair performance tested the following day (P > 0.05). Additionally, repeated anesthesia, 2–3 h after each session, also did not impair overall maze or rotarod performance in young or aged mice (P > 0.05). Spatial learning appeared to be facilitated by anesthesia (P < 0.01) for pooled results. Asymptotic performance—when learning had stabilized—remained unimpaired in both the maze and rotarod tasks. Essentially, they found that an age-related risk of anesthetic-induced impairment appears to be limited to the acquisition of a novel motor skill and that anesthesia alone does not lead to prolonged cognitive impairments in aged mice (2).

Although clinical studies have their limits, they can still provide vital information about any potential anesthetic effects on spatial and motor abilities. Particularly, studies on infants and the elderly are particularly salient, as these groups most often suffer from complications related to surgical operations (3). In 2009, a retrospective cohort study by Wilder et. al found that multiple rounds of anesthetic exposure, and in young children under 2–4 years of age, were associated with learning difficulty and academic underachievement during childhood and adolescence (4). However, another study in 2012 by Ing et al. reported that both single and multiple exposures to anesthesia were linked to language and abstract reasoning deficits (5). The discrepancy is likely due to the selection bias inherent to retrospective study design, different assessment parameters, and/or age at assessment (3). On the other hand, a clinical study by the Pediatric Anesthesia Neurodevelopment Assessment (PANDA) examined the effect of single general anesthetic exposure at young age on future neurocognitive performance. The trial did not observe significant decline in cognitive, behavioral and memory capacity in general anesthesia exposed subjects in comparison to their unexposed siblings, at 8–15 years of age (3).

Cognitive disturbance is commonly observed in elderly patients following surgery and general anesthesia and is predictive of short- and long-term outcomes. Alzheimer’s disease (AD) can be a potential, and serious, outcome of cognitive disturbance (3). In 2011, a meta-analysis on 15 case-control studies by Seitz et. al reported that GA exposure, single or cumulative, is not associated with higher risk of AD compared to no-surgery/anesthesia control or regional anesthesia (6). In contrast, a 2014 nationwide case-control study reported that subjects undergoing general anesthesia were at a higher risk of developing dementia when compared to the control group (3).

Essentially, it remains inconclusive whether or not anesthetics negatively affect spatial and motor abilities in both pediatric and geriatric patients. Both human and animal studies provide mixed evidence of an association between anesthesia exposure and later deficits in spatial and motor abilities. Further studies will be needed to determine whether general anesthetics alone lead to cognitive impairments.

References

1. Wiedbusch, V., LaTendresse, K., Avidan, M., Nelson, A., Phyle, M., Aljuni, R., Mashour, G. (2019). General Anesthesia Does Not Have Persistent Effects on Attention in Rodents. Frontiers in Behavioral Neuroscience, 13, 76. doi: 10.3389/fnbeh.2019.00076
2. Butterfield, N., Graf, P., Ries, C., MacLeod, B. (2004). The Effect of Repeated Isoflurane Anesthesia on Spatial and Psychomotor Performance in Young and Aged Mice. Anesthesia & Analgesia, 98(5), 1305-1311. doi: 10.1213/01.ANE.0000108484.91089.13
3. Wu, L., Zhao, H., Weng, H., & Ma, D. (2019). Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment. Journal of anesthesia, 33(2), 321–335. doi:10.1007/s00540-019-02623-7
4. Wilder, R. T., Flick, R. P., Sprung, J., Katusic, S. K., Barbaresi, W. J., Mickelson, C., … Warner, D. O. (2009). Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology, 110(4), 796–804. doi:10.1097/01.anes.0000344728.34332.5d
5. Ing, C., DiMaggio, C., Whitehouse, A., Hegarty, M., Brady, J., von Ungern-Sternberg, B., Davidson, A., Wood, A., Li, G., Sun, L. (2012). Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia. Pediatrics, 130(3), 476-485. doi: 10.1542/peds.2011-3822
6. Seitz, D. P., Shah, P. S., Herrmann, N., Beyene, J., & Siddiqui, N. (2011). Exposure to general anesthesia and risk of Alzheimer’s disease: a systematic review and meta-analysis. BMC geriatrics, 11, 83. doi:10.1186/1471-2318-11-83