Abstract
BackgroundSeptic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown.MethodsIn a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing.ResultsOf the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6).ConclusionsThere is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit.Trial registration ClinicalTrials.gov (NCT02442440; Registered on 13 April 2015).
Highlights
Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction
Sepsis is defined as a severe endothelial dysfunction syndrome that develops in response to infections leading to reversible or irreversible injury to the microcirculation, which is responsible for multiple organ failure [11]
We further examined the effect of anisodamine on C-reactive protein (CRP) and found that starting from day 1, the treated group had lower CRP
Summary
Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. Given the high global burden of sepsis, great efforts have been made to improve its clinical outcomes. Sepsis-related mortality and morbidity are still unacceptably high as estimated from the global disease burden database [2], and exploring novel therapeutic agents is a top research priority for sepsis/septic shock [10]. The primary underlying pathophysiology of septic shock is microcirculatory dysfunction, which in turn leads to tissue hypoxia, organ dysfunction and even mortality. In this regard, sepsis is defined as a severe endothelial dysfunction syndrome that develops in response to infections leading to reversible or irreversible injury to the microcirculation, which is responsible for multiple organ failure [11]. We hypothesized that anisodamine was able to reduce hospital mortality for critically ill patients with septic shock
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