Papaverine: Papaverine will be administered intravenously as 30 mg infused over 10 minutes, followed by continuous infusion at 2-5 mg/hour. The maintenance infusion rate may be adjusted according to the patient's hemodynamic status, mean arterial pressure, heart rate, vasopressor requirement, PiCCO-derived variables, and adverse events. Dose reduction, temporary interruption, or discontinuation of papaverine is permitted for safety reasons, including clinically significant hypotension, rapidly increasing vasopressor requirement, new-onset or worsening arrhythmia, myocardial ischemia, severe liver function abnormality, or any other clinically significant adverse event judged by the treating physician or investigator.
Study summary
This is a prospective, multicenter, single-arm, open-label, pilot physiological study designed to evaluate the effects of intravenous papaverine on sublingual microcirculation and the vascular waterfall phenomenon in adult patients with septic shock.
Eligible patients will have septic shock according to Sepsis-3 criteria, require norepinephrine support after adequate fluid resuscitation, and have PiCCO-based hemodynamic monitoring available before papaverine administration. Papaverine will be administered as an intravenous infusion of 30 mg over 10 minutes, followed by a continuous infusion of 2-5 mg/hour. Sublingual microcirculatory variables, vascular-waterfall-related indices, PiCCO-derived hemodynamic variables, macrocirculatory parameters, tissue perfusion variables, vasopressor dose, and safety outcomes will be assessed before and after papaverine administration.
The study aims to explore whether papaverine can improve microvascular perfusion and reduce microcirculatory flow impairment in septic shock, and to provide preliminary physiological and safety data for future controlled trials.
Eligibility
Sex
ALL
Min age
18 Years
Max age
85 Years
Healthy volunteers
No
Inclusion Criteria:
* Age 18-85 years.
* Septic shock according to Sepsis-3 criteria, defined as suspected or documented infection requiring vasopressors 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 in the ICU.
* Receiving continuous norepinephrine infusion at enrollment.
* Receiving invasive mechanical ventilation at enrollment, allowing assessment of vascular waterfall-related hemodynamic variables.
* PiCCO-based hemodynamic monitoring, invasive arterial pressure monitoring, and central venous access available before papaverine administration.
* 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 primarily caused by non-septic etiologies, including cardiogenic, hypovolemic, obstructive, hemorrhagic, or anaphylactic shock.
* Expected death or planned withdrawal of life-sustaining treatment within 24 hours.
* Known allergy or hypersensitivity to papaverine.
* Severe hemodynamic instability judged unsuitable for papaverine by the treating physician, including refractory hypotension or rapidly escalating vasopressor requirement.
* Clinically significant arrhythmia, high-grade atrioventricular block, acute coronary syndrome, or active myocardial ischemia before enrollment.
* Severe hepatic dysfunction judged by the investigator to substantially increase the risk of papaverine-related adverse effects.
* Conditions preventing reliable sublingual microcirculatory assessment, including major oral or sublingual lesions, active oral bleeding, inability to access the sublingual area, or poor baseline image quality.
* Pregnancy or lactation.
* Participation in another interventional clinical trial that may affect study outcomes or safety.
Primary outcome measure(s)
Change From Baseline in Sublingual Microvascular Flow Index — Baseline, 3 hours, and 6 hours after initiation of papaverine 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 each post-papaverine time point.
Change From Baseline in Pcc-Pmsf Gradient — Baseline, 3 hours, and 6 hours after initiation of papaverine 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 each post-papaverine time point.
Trial sites (2)
Facility
City
Region
Status
The First Affiliated Hospital of Bengbu Medical University
Bengbu
Anhui
The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)
Wuhu
Anhui
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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