Effects of Anisodamine on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock

This prospective, multicenter, single-arm, open-label interventional pilot study aims to evaluate the short-term physiological effects of intravenous anisodamine on sublingual microcirculation and vascular-waterfall parameters in adult patients with septic shock. Eligible patients will have septic shock according to Sepsis-3 criteria, will require norepinephrine support after adequate fluid resuscitation, and will be receiving invasive mechanical ventilation and PiCCO-based hemodynamic monitoring. After baseline assessment, participants will receive intravenous anisodamine according to the study protocol. Anisodamine will be administered as a loading dose of 0.5 mg/kg within 3 minutes, with a minimum dose of 20 mg and a maximum dose of 40 mg, followed by continuous infusion at 0.02-0.1 mg/kg/hour, with a maximum total daily dose of 200 mg. Sublingual microcirculatory variables, including microvascular flow index, perfused vessel density, proportion of perfused vessels, and heterogeneity index, as well as vascular-waterfall parameters, including estimated critical closing pressure, estimated mean systemic filling pressure, and the Pcc-Pmsf gradient, will be measured at baseline, 3 hours, and 6 hours after initiation of anisodamine. Systemic hemodynamic, perfusion, vasopressor, PiCCO-derived variables, and safety outcomes will also be collected. The primary objective is to characterize immediate changes in sublingual microcirculation and vascular-waterfall physiology after anisodamine administration and to provide preliminary data for future controlled studies.

Inclusion Criteria: * Age 18-85 years. * Diagnosis of septic shock according to Sepsis-3 criteria, defined as suspected or documented infection with vasopressor requirement to maintain mean arterial pressure ≥65 mmHg and serum lactate \>2 mmol/L after adequate fluid resuscitation. * Enrollment within 24 hours after diagnosis of septic shock or within 24 hours after ICU admission for septic shock. * Receiving invasive mechanical ventilation at the time of enrollment. * PiCCO catheter in place and PiCCO-based hemodynamic monitoring available before anisodamine initiation. * Continuous norepinephrine infusion at enrollment. * Adequate initial fluid resuscitation and hemodynamic optimization as judged by the treating physician, with volume status assessed by dynamic indices, echocardiography, or PiCCO-derived variables. * Ability to obtain sublingual microcirculatory images of acceptable quality at baseline. * Written informed consent obtained from the patient or legally authorized representative. Exclusion Criteria: * Shock mainly caused by non-septic etiologies, including cardiogenic, hypovolemic, obstructive, hemorrhagic, or anaphylactic shock. * Expected death or withdrawal of life-sustaining treatment within 24 hours. * Known contraindications to anisodamine or anticholinergic therapy, including glaucoma, acute phase of intracranial hemorrhage, elevated intracranial pressure, untreated bowel obstruction, or prostatic enlargement without urinary catheterization. * Known allergy or hypersensitivity to anisodamine or any component of the study drug. * Severe or uncontrolled arrhythmia before enrollment, including sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, uncontrolled supraventricular tachycardia, or atrial fibrillation/flutter with uncontrolled ventricular response. * Acute coronary syndrome, clinically significant myocardial ischemia, or cardiac arrest before enrollment during the current ICU stay. * Severe cardiac dysfunction judged unsuitable for anisodamine by the treating physician, including severe ventricular dysfunction, cardiogenic shock, or need for high-dose inotropic support. * Conditions interfering with sublingual microcirculatory assessment, including major oral or sublingual lesions, active oral bleeding, inability to access the sublingual area, or poor baseline image quality. * Immunocompromised status or agranulocytosis, including long-term immunosuppressive therapy, chemotherapy-associated severe neutropenia, or other severe immune suppression judged by the investigator. * Pregnancy, planned pregnancy, or lactation. * Participation in another interventional clinical trial that may affect study outcomes or safety. * Inability to obtain informed consent.