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

NCT07657702 | Not Yet Recruiting

• 1 other identifier: 2026-ICU06
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock; Sepsis; Critical Illness

Keywords

anisodamine; anisodamine hydrobromide; septic shock; sublingual microcirculation; microvascular flow index; vascular waterfall; critical closing pressure; mean systemic filling pressure; Pcc; Pmsf; PiCCO; mechanical ventilation; arrhythmia

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Pcc-Pmsf Gradient

  The vascular-waterfall pressure gradient will be calculated as the difference between estimated critical closing pressure and estimated mean systemic filling pressure. The outcome is the change in Pcc-Pmsf from baseline to 3 and 6 hours after anisodamine initiation

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

• Change From Baseline in Sublingual Microvascular Flow Index

  Microvascular flow index will be assessed using sublingual microcirculatory imaging. Three to five sublingual video fields will be recorded at each time point, and MFI will be calculated according to standard microcirculatory scoring methods. The outcome is the change in MFI from baseline to 3 and 6 hours after anisodamine initiation.

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

Secondary Outcomes (15)

• Change From Baseline in Perfused Vessel Density

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

• Change From Baseline in Proportion of Perfused Vessels

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

• Change From Baseline in Microcirculatory Heterogeneity Index

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

• Change From Baseline in Estimated Critical Closing Pressure

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

• Change From Baseline in Estimated Mean Systemic Filling Pressure

  Baseline, 3 hours, and 6 hours after initiation of anisodamine

Study Arms (1)

Anisodamine arm

EXPERIMENTAL

Adult patients with septic shock receiving invasive mechanical ventilation, norepinephrine support, and PiCCO-based hemodynamic monitoring after initial resuscitation will receive intravenous anisodamine. Sublingual microcirculatory, vascular-waterfall, PiCCO-derived, macrocirculatory, perfusion, and safety variables will be assessed at baseline, 3 hours, and 6 hours after anisodamine initiation.

Drug: Anisodamine intravenous infusion

Interventions

Anisodamine intravenous infusion DRUG

Anisodamine will be administered as an intravenous 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 intravenous infusion at 0.02-0.1 mg/kg/hour. The maximum total daily dose will be 200 mg. The maintenance dose may be adjusted according to microcirculatory status, serum lactate level, capillary refill time, mean arterial pressure, heart rate, PiCCO-derived hemodynamic variables, vasopressor requirement, and adverse effects. Dose reduction, temporary interruption, or discontinuation is permitted for safety reasons, including clinically significant hypotension, excessive tachycardia, new-onset or worsening arrhythmia, prolonged QT interval, suspected myocardial ischemia, mental status changes, urinary retention, ileus, or other clinically significant adverse events. The actual dose, infusion duration, and reasons for dose adjustment or discontinuation will be recorded.

Also known as: Anisodamine hydrobromide, Ani HBr

Anisodamine arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Wannan Medical College: lead
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)

Wuhu, Anhui, 241000, China

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Critical Illness; Hemophilia B; Arrhythmias, Cardiac

Interventions

anisodamine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Disease Attributes; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Heart Diseases; Cardiovascular Diseases

Central Study Contacts

qiancheng xu

CONTACT

+86-18297529106; qianchengxu@wnmc.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All enrolled participants will receive intravenous anisodamine and undergo repeated physiological assessments before and after treatment.

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: June 18, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

CN (1)