# Association between end-tidal sevoflurane concentration and postoperative cognitive dysfunction and pain sensitivity in elderly patients under general anesthesia

**Authors:** Yunyun Zhou, Han Zheng, Zhengyu Li, Jiaxuan Wang, Xue Zhang, Lifen Zheng, Hong Luo, Heng Yang

PMC · DOI: 10.3389/fnagi.2026.1761052 · Frontiers in Aging Neuroscience · 2026-02-16

## TL;DR

Higher sevoflurane concentration during surgery in elderly patients is linked to better cognitive recovery and less postoperative pain, possibly due to changes in brain and pain markers.

## Contribution

This study identifies a link between sevoflurane concentration and reduced postoperative cognitive dysfunction and pain sensitivity in elderly patients.

## Key findings

- Higher sevoflurane concentration was associated with lower incidence of postoperative cognitive dysfunction and better cognitive scores.
- Elevated sevoflurane reduced pain sensitivity measures and altered levels of neurological and pain-related biomarkers.
- Multivariate analysis showed higher sevoflurane concentration and preoperative NGF levels were protective factors against cognitive dysfunction.

## Abstract

To analyze the association between end-tidal sevoflurane concentration and postoperative cognitive dysfunction (POCD) and pain sensitivity in elderly patients under general anesthesia.

A total of 121 elderly patients undergoing abdominal surgery were enrolled and divided into a low-concentration group (0.8–1.2 MAC, n = 61) and a high-concentration group (1.5–2.0 MAC, n = 60). End-tidal sevoflurane concentration, recovery parameters, Mini-Mental State Examination (MMSE) scores, POCD incidence, pain sensitivity (PSQ score, mechanical hypersensitivity areas and thresholds), and serum levels of neurological markers (NSE, ApoJ, NGF) and pain mediators (PGE2, 5-HT) were compared between groups. Pearson correlation and multivariate logistic regression were used to assess associations and influencing factors for POCD.

The high-concentration group had longer recovery times but a lower incidence of POCD (10.00% vs. 24.59%) and higher MMSE scores on postoperative days 1 and 3 (P < 0.05). Pain sensitivity measures were reduced in the high-concentration group on postoperative day 1, with lower PSQ scores, smaller mechanical hypersensitivity areas, and higher mechanical thresholds (P < 0.05). Compared to the low-concentration group, the high-concentration group exhibited significantly lower postoperative levels of NSE, ApoJ, PGE2, and 5-HT, and higher NGF levels (P < 0.05). End-tidal sevoflurane concentration positively correlated with MMSE scores, mechanical thresholds, and NGF levels, and negatively correlated with pain sensitivity measures, NSE, ApoJ, PGE2, and 5-HT (P < 0.05). Multivariate analysis identified age and preoperative elevations of NSE, ApoJ, PGE2, and 5-HT as risk factors for POCD, while higher sevoflurane concentration and preoperative NGF levels were protective factors (P < 0.05).

Higher end-tidal sevoflurane concentration is associated with improved postoperative cognitive function and reduced pain sensitivity in elderly patients, likely mediated by the modulation of neurological and pain-related biomarkers, serving as a protective factor against POCD.

## Linked entities

- **Proteins:** ENO2 (enolase 2), CLU (clusterin), NGF (nerve growth factor), ptges2.L (prostaglandin E synthase 2 L homeolog), 5-HT1B (5-hydroxytryptamine (serotonin) receptor 1B)
- **Chemicals:** sevoflurane (PubChem CID 5206)

## Full-text entities

- **Genes:** BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CLU (clusterin) [NCBI Gene 1191] {aka AAG4, APO-J, APOJ, CLI, CLU1, CLU2}
- **Diseases:** multiple organ failure (MESH:D009102), hemorrhage (MESH:D006470), cerebral hypoxia (MESH:D002534), hypoxia (MESH:D000860), ischemia (MESH:D007511), Pain (MESH:D010146), ASA III (MESH:D056807), visual or auditory impairment (MESH:D014786), alcohol abuse (MESH:D000437), HL (MESH:C538324), trauma (MESH:D014947), inflammation (MESH:D007249), hepatic or renal insufficiency (MESH:D048550), POCD (MESH:D000079690), neuroinflammation (MESH:D000090862), neuronal atrophy (MESH:D001284), impair (MESH:D060825), neuropsychiatric function (MESH:D001523), substance abuse (MESH:D019966), neurotoxic (MESH:D020258), diabetes (MESH:D003920), Postoperative pain (MESH:D010149), postoperative (MESH:D019106), hypersensitivity (MESH:D004342), neuronal damage (MESH:D009410), neuropathic pain (MESH:D009437), cognitive dysfunction (MESH:D003072), neurological impairment (MESH:D009422), hyperalgesia (MESH:D006930), hypertension (MESH:D006973), Neurological Damage (MESH:D020196)
- **Chemicals:** PGE2 (MESH:D015232), ASA (MESH:D001241), remifentanil (MESH:D000077208), propofol (MESH:D015742), midazolam (MESH:D008874), oxygen (MESH:D010100), cisatracurium (MESH:C101584), cortisol (MESH:D006854), carbon dioxide (MESH:D002245), 5-HT (MESH:D012701), Sevoflurane (MESH:D000077149), alcohol (MESH:D000438), benzodiazepines (MESH:D001569), tropisetron (MESH:D000077526), ketamine (-), sufentanil (MESH:D017409)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

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## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950744/full.md

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Source: https://tomesphere.com/paper/PMC12950744