Anisodamine hydrobromide reduces 28-day mortality in septic shock: a randomized controlled.

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.