Effects of Anisodamine on Sublingual Microcirculation and Vascular Waterfall Phenomenon in Patients With Septic Shock
Study Details
- Unmapped
- Drug: Anisodamine intravenous infusion
- 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.
- 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.
Protocol Summary
This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant can use. The study doctor will tell the participants more about this. In case the participants experience bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor. Female participants cannot take part if they are pregnant, breast-feeding or plan to get pregnant during the study period.