Anisodamine hydrobromide was associated with a lower 28-day death rate when added to standard treatment for septic shock, according to a randomized trial of 296 adults at one hospital. Forty-two of 148 patients in the anisodamine group died, or 28.4%, compared with 62 of 148, or 41.9%, in the group given standard therapy alone.
In the fully adjusted analysis, the hazard ratio was 0.64, with a 95% confidence interval of 0.43 to 0.95 and P = 0.028. A hazard ratio compares the rate at which events occur in two groups over time; this estimate favored the patients who received anisodamine.
How the trial was run
The prospective, parallel-group trial was carried out at one center between November 2018 and April 2020. Of 340 patients assessed for eligibility, 44 were excluded and 296 were randomized, with 148 assigned to each group.
Patients were allocated in a 1:1 ratio using a computer-generated sequence and concealed envelope allocation. Treating physicians were unblinded, while outcome assessors and data analysts were blinded.
The researchers planned to enroll 340 patients, or 170 per group. That calculation assumed 50% mortality in the control group and 31% mortality with anisodamine, an expected hazard ratio of 0.62, a two-sided alpha of 0.05 and 80% power. In the end, 296 patients were enrolled.
Every patient received standard sepsis bundle therapy. The intervention group also received anisodamine at 1.2 to 4.0 mg/kg/day intravenously until mean arterial pressure was at least 65 mmHg and lactate was no more than 2 mmol/L, followed by 20 to 40 mg twice daily for 7 to 14 days.
The primary outcome was all-cause mortality by day 28. Secondary measures included changes in lactate and its clearance, SOFA score trajectories, seven-day mortality and adverse events. Survival was assessed using Kaplan-Meier curves and log-rank tests, followed by four progressively adjusted Cox models.
Why the mechanism remains unsettled
The researchers also asked whether lactate and lactate clearance might mediate the result, meaning explain part of the link between treatment and survival. Lactate clearance was higher in the anisodamine group, and improving clearance trajectories were more common, but the trajectory classes were not significantly associated with 28-day mortality, with P = 0.53.
The mortality comparison and the proposed pathway are therefore separate findings. The trial reported a difference between treatment groups and a related change in lactate, but it did not establish that the lactate change caused the survival difference. The mediation results are pathway estimates, not definitive proof of a causal mechanism.
The mortality result also needs to be read in light of the study design. Treating physicians knew which treatment patients received, while outcome assessors and data analysts were blinded. The trial was conducted at a single center, so its findings are not automatically generalizable to other hospitals.
One further qualification is the sample size. The trial was planned for 340 patients but enrolled 296. The results therefore come from a smaller group than the researchers had planned, which is another reason to treat the size of the effect cautiously.
Taken together, the findings support a narrower conclusion: among the adults enrolled at this center, adding the reported anisodamine regimen to standard therapy was associated with lower 28-day mortality. The study does not establish that lactate clearance caused the difference, or that the result will hold in other settings.
Paper data and sources
Original title: Anisodamine hydrobromide reduces 28-day mortality in septic shock: a randomized controlled
Authors: Yang X, Peng H, Pan T et al.
Journal/Repository: Frontiers in pharmacology
Status: Peer-reviewed
First online: 2026-10-07
DOI: Not available
Original paper · Full text