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Anisodamine hydrobromide reduces 28-day mortality in septic shock: a randomized controlled
Xueting Yang1, Hongqiong Peng1, Tianmeng Pan2
1Emergency Intensive Care Unit, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Background:
This randomized controlled trial evaluated whether anisodamine hydrobromide reduces 28-day mortality in septic shock and whether this effect is mediated by lactate and lactate clearance.
Methods:
In this prospective randomized controlled trial, 296 patients with septic shock were randomly assigned to receive anisodamine hydrobromide plus standard therapy (n = 148) or standard therapy alone (n = 148). The primary outcome was 28-day all-cause mortality. Causal mediation analyses were performed to assess the mediating roles of lactate and lactate clearance rate at 24, 48, and 72 h.
Results:
Anisodamine significantly reduced 28-day mortality compared with control (hazard ratio 0.64, 95% confidence interval 0.43-0.95; P = 0.028). Causal mediation analysis revealed that lactate at 24 h (average causal mediation effect -0.0166, P = 0.042) and lactate clearance rate at 24 h (average causal mediation effect -0.0206, P = 0.016) significantly mediated the protective effect, explaining 14.1% and 17.3% of the total effect, respectively. Lactate at 72 h also showed significant mediation (P = 0.032), with a mediated proportion of 21.6%. Sensitivity analysis using complete cases confirmed the robustness of these findings (hazard ratio 0.60, 95% confidence interval 0.40-0.91; P = 0.014), with consistent mediation effects for lactate and lactate clearance at 24 h.
Conclusion:
Anisodamine hydrobromide significantly reduces 28-day mortality in patients with septic shock, with effects partially mediated by lactate and lactate clearance at 24 h. These findings support the integration of anisodamine into sepsis management protocols.
