Efficacy and safety of anisodamine as adjuvant therapy in septic shock: a systematic review and meta-analysis

Background Some patients with septic shock still exhibit microcirculatory dysfunction and impaired tissue oxygen metabolism (macro–micro dissociation), even when macrohemodynamic targets are achieved. Anisodamine may improve patients’ symptoms through multiple mechanisms, including anti-inflammatory and immunomodulatory effects mediated by the cholinergic anti-inflammatory pathway and the relief of microvascular spasm; however, the quality of existing evidence is variable. This study aimed to systematically evaluate the efficacy and safety of anisodamine as adjuvant therapy for septic shock. Methods We systematically searched PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, CNKI, Wanfang Data, and the VIP database from inception to 1 June 2026. RCTs comparing anisodamine with control in septic shock were included. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was rated using the GRADE approach. Results A total of 14 RCTs (2 in English and 12 in Chinese) were included. Compared with control, anisodamine reduced 28-day mortality (6 studies; RR = 0.76; 95% CI, 0.62–0.93). Anisodamine also significantly increased mean arterial pressure (MD = 3.92; 95% CI, 1.85–5.98) and the systemic vascular resistance index (MD = 74.78; 95% CI, 17.59–131.97). Furthermore, anisodamine increased the Lactate clearance rate (MD = 16.27; 95% CI, 9.26–23.28), reduced serum Lactate (MD = −0.68; 95% CI, −1.10 to −0.26), and increased oxygen consumption (VO 2 ; MD = 23.10; 95% CI, 11.53–34.68) without increasing oxygen delivery (DO 2 ). Anisodamine also reduced the SOFA score (MD = −1.17; 95% CI, −1.95 to −0.39) and the APACHE-II score (MD = −1.50; 95% CI, −2.34 to −0.65), and shortened the duration of vasoactive agent use, ICU length of stay (LOS), and duration of mechanical ventilation, although the total hospital LOS was unchanged. Heart rate was similar between groups based on limited data. However, adverse events were under-reported across studies, and cardiac safety of anisodamine could not be reliably assessed from the available evidence. Conclusion Anisodamine as an adjuvant therapy for septic shock may reduce 28-day mortality and improve certain macrocirculatory hemodynamic parameters, tissue perfusion, oxygen metabolism, and organ function indicators. A microcirculatory mechanism is plausible but remains unproven, as no direct microcirculatory endpoint could be pooled. In addition, given that the included studies were mostly small-sample trials with substantial heterogeneity and limited certainty of evidence, large-sample, multicenter RCTs are needed (ideally focusing more on microcirculatory indicators) to further clarify the mechanism, optimal dose, timing, and appropriate treatment population.