-Original-

Association between Early Postoperative Sodium Change and Postoperative Delirium after General Anesthesia

Yuko Ikuma¹, Takuya Nishino², Yuki Genda^1,3, Toko Hirano¹, Makiko Yamamoto¹, Tomoki Mizuno¹, Natsuko Hyodo¹, Yuichi Tanaka¹, Masae Iwasaki¹, Hiroshi Mase^1,2 and Masashi Ishikawa¹

¹Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
²Department of Health Policy and Management, Nippon Medical School, Tokyo, Japan
³Department of Surgical Intensive Care, Nippon Medical School Hospital, Tokyo, Japan

Background: Postoperative delirium (POD) is a frequent neuropsychiatric complication after surgery under general anesthesia and is associated with adverse outcomes. Although perioperative dysnatremia has been linked to POD, most studies relied on static sodium measurements and failed to capture early postoperative dynamics. We investigated whether early postoperative sodium change is associated with late-onset POD.
Methods: This retrospective single-center cohort study included adults undergoing surgery under general anesthesia between July 2021 and December 2025. A Day-3 landmark design ensured temporal precedence between exposure and outcome. Perioperative sodium change (ΔNa) was defined as the difference between preoperative baseline sodium and the most recent sodium value within 48 hours after surgery and was categorized as decrease (≤-3 mmol/L), stable (-3 to +3 mmol/L), or increase (≥+3 mmol/L). Late-onset POD occurring on postoperative days 3 through 7 was identified using the Intensive Care Delirium Screening Checklist and antipsychotic prescriptions. Multivariable logistic regression and restricted cubic spline models were applied.
Results: Among 18,424 patients, both perioperative sodium increase and decrease were independently associated with higher odds of late-onset POD, as compared with stable sodium levels. Baseline preoperative sodium was not associated with POD. Spline analyses showed a U-shaped association between ΔNa and POD, with the lowest risk was near ΔNa = 0 mmol/L. Findings were consistent across sensitivity and subgroup analyses.
Conclusions: Early postoperative sodium fluctuations were associated with increased risk of late-onset POD. Monitoring of perioperative sodium trajectories may aid in stratifying early postoperative risk.

J Nippon Med Sch 2026; 93: 361-369

Keywords
postoperative delirium, serum sodium, anesthesia, perioperative period, landmark analysis

Correspondence to
Yuko Ikuma
k-yuko@nms.ac.jp

Received, April 20, 2026
Accepted, June 6, 2026