Association of a routine dexmedetomidine-remifentanil anesthetic strategy with POD3 morning cortisol change in older patients undergoing radical esophagectomy

Abstract

Background Older patients undergoing radical esophagectomy may experience marked postoperative endocrine stress, inflammation, pain, and short-term cognitive decline. We evaluated whether a routine anesthetic strategy combining dexmedetomidine with remifentanil was associated with a smaller POD3 serum cortisol increase than remifentanil- or dexmedetomidine-based strategies alone. Methods This single-center retrospective cohort screened 426 consecutive patients aged ≥65 years who underwent elective radical esophagectomy from January 2023 to December 2025. Of these, 347 had verifiable pathway-based POD3 biomarker and POD7 MoCA data after predefined clinical, laboratory, and follow-up exclusions. The primary analysis used a prespecified balanced common-support analytic cohort drawn from the naturally occurring REM (continuous remifentanil without dexmedetomidine), DEX (dexmedetomidine with non-remifentanil opioid analgesia and without continuous remifentanil), and Dex-REM (both infusions) exposure strata (100 patients each). The primary endpoint was morning serum cortisol change from preoperative day 1 to postoperative day 3 (POD3). Results POD7 screening-based cognitive decline occurred in 51 patients in the balanced common-support cohort. Mean cortisol change was +164.0 nmol/L in REM, + 126.0 nmol/L in DEX, and +86.0 nmol/L in Dex-REM. After adjustment, Dex-REM was associated with lower cortisol change than REM (adjusted mean difference, -78.4 nmol/L; 95% CI, -103.2 to -53.6; p<0.001) and DEX (-39.6 nmol/L; 95% CI, -64.1 to -15.1; p=0.002). Dex-REM also showed lower 24-h VAS AUC than REM (adjusted mean difference, -5.8 point-hours; 95% CI, -9.3 to -2.3; FDR q=0.006), while POD7 MoCA-decline risk was numerically lower but imprecise (12.0% vs. 22.0%; adjusted risk ratio, 0.52; 95% CI, 0.26 to 1.05; p=0.071). Conclusions The real-world Dex-REM anesthetic pathway was associated with a smaller POD3 morning serum cortisol increase. This pathway-level association does not establish an agent-specific effect, pharmacologic synergy, or attenuation of the complete surgical-stress trajectory. Clinical and screening-based cognitive secondary outcomes were exploratory and require prospective multicenter confirmation before causal or neuroprotective conclusions are drawn.

The authors' abstract, as published at the source. Frontiers in Endocrinology, 2026 · DOI ↗