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

importancePostoperative 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.

objectiveTo assess the efficacy of huperzine A injection on improving early postoperative cognitive function in patients undergoing neurosurgical procedures under general anesthesia. DESIGN, SETTING, AND

participantsThis 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.

interventionIn 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 (AUC0-96h) 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.

resultsThe 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) AUC0-96h 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 AUC0-96h 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.