Huperzine A associated with improved early postoperative cognitive function after neurosurgery under general anesthesia: a randomized clinical trial

Importance: Postoperative neurocognitive disorders (PNCD) are a group of complications following surgery and anesthesia. Huperzine A, an acetylcholine esterase (AChE) inhibitor used to treat cognitive disorders, is promising in improving the postoperative cognitive function. Objective: To assess the efficacy of huperzine A injection on improving early postoperative cognitive function in patients undergoing neurosurgical procedures under general anesthesia. Design, setting, and participants: This parallel-group, randomized trial was conducted at a neurosurgical department of a tertiary hospital in China from May, 2021 to February, 2023. Adult patients scheduled for selective neurosurgical operations requiring general anesthesia were recruited. Participants were randomized 1:1 to postoperative huperzine A injections or standard care without additional pharmacological intervention. Intervention: In the intervention group, 0.2 mg huperzine A was intramuscularly injected after tracheal extubation, and at 10:00 ± 2 h on the first, second and third postoperative days, respectively. Patients in the non-intervention group did not receive huperzine A injection after surgery. Main outcomes and measures: The evaluation was performed at 6 h ± 2 h, 24 h ± 2 h, 48 h ± 2 h, 72 h ± 2 h, 96 h ± 2 h after the first administration. The primary outcome was the area under the curve in 0 to 96 hours postoperatively (AUC 0-96h ) of the mini-mental state examination (MMSE; score range: 0-30, with the higher score indicating better cognitive function) in total score and score changes from baseline, which represented total “cognitive burden” over the critical first 96 postoperative hours. Results: The trial recruited 127 patients, of which 123 patients were included in the full analysis set (76 females [61.8%]; mean [SD] age, 59.6 [12.6] years). There were 58 patients in intervention group (40 females [69.0%]; mean [SD] age, 59.6 [11.9] years) and 65 in non-intervention group (36 females [55.4%]; mean [SD] age, 59.7 [13.2] years). Preoperative MMSE baseline were comparable between the two groups (intervention group: 28.5 [2.1]; non-intervention group: 28.0 [2.7], P = 0.608). Postoperatively, the intervention group demonstrated a significantly less decline in cognitive function, as measured by the mean (SD) AUC 0-96h of the MMSE total scores (2770.67 [150.67]) compared with non-intervention group (2651.34 [257.41]) (P = 0.010). Accordingly, the mean MMSE change from baseline in the AUC 0-96h was also significantly better in the intervention group (−2.67 [170.29]) than in the non-intervention group (−53.05 [164.04]) (P = 0.021). Conclusions and relevance: In adults undergoing neurosurgery with general anesthesia, postoperative administration of Huperzine A associated with significantly improved MMSE scores over the 96-hour postoperative period.