The goal of this clinical trial is to investigate whether methylene blue injection can safely and effectively improve the survival rate of patients with severe septic shock, shorten the duration of norepinephrine use, reduce the dosage of vasopressors, promptly correct hemodynamics, and improve tissue perfusion and organ function impairment.
Researchers will compare methylene blue to a placebo (a look-alike substance that contains no drug) to see if methylene blue works to treat severe septic shock. Participants will: Administer a loading dose of 2.5 mg/kg via micro-pump over 15 minutes, followed by a maintenance infusion at a rate of 0.25 mg/kg/hour for 12 hours or until norepinephrine has been continuously discontinued for 4 hours, whichever comes first. If norepinephrine needs to be increased to 0.25 μg/kg/min before the 12-hour period ends, continue using methylene blue until the 12-hour infusion is completed. Primary Study Endpoint \- 28-day all-cause mortality rate starting from the diagnosis of septic shock. Secondary Study Endpoints * Time from the start to the discontinuation of norepinephrine after the diagnosis of septic shock. * Total dose of norepinephrine used (from enrollment to 72 hours). * Number of days without norepinephrine within 28 days. * Duration of mechanical ventilation. * Rate of CRRT (Continuous Renal Replacement Therapy). * Length of ICU stay. * Total hospital stay. Record the following indicators before methylene blue intervention and at 24 hours, 72 hours, and 5 days after the intervention: * Highest serum lactate level. * Lowest mean arterial pressure. * Alanine aminotransferase (ALT). * Total bilirubin. * Creatinine. * Oxygenation index (P/F ratio). * Creatine kinase-MB (CK-MB). * Troponin I (TNI). * Systemic vascular resistance index (SVRI).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
488
In addition to standard treatment, patients will receive methylene blue intervention. The method is as follows: a loading dose of 2.5 mg/kg administered via micro-pump over 15 minutes, followed by a continuous infusion at a rate of 0.25 mg/kg/hour for 12 hours or until norepinephrine has been continuously discontinued for 4 hours, whichever comes first. If norepinephrine needs to be increased to 0.1 μg/kg/min before the 12-hour period ends, continue using methylene blue until the 12-hour infusion is completed.
In addition to standard treatment, patients will receive a placebo control with normal saline, administered for the same duration as the intervention group.
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITING28-day survival rate of enrolled patients
Our primary endpoint is the 28-day survival rate of enrolled patients: All enrolled patients will be followed from the time of randomization until 28 days post-enrollment, recording the survival status on the 28th day after enrollment. If a patient dies within 28 days post-enrollment, the number of survival days will be recorded. Note: 1. Cases where the family requests discharge to home for end-of-life care and the patient subsequently dies will be counted as death cases. 2. Cases where the family requests discharge for non-medical reasons such as financial constraints and no further treatment is sought will be counted as dropout cases.
Time frame: 28-day
The duration and dosage of norepinephrine use
The duration of norepinephrine use：The time from the start of norepinephrine (NE) administration after sepsis diagnosis until its discontinuation. The definition of discontinuation: NE must be stopped for ≥2 hours; if NE is stopped for \<2 hours, it is not considered discontinued. If NE is re-administered after being stopped for more than 2 hours, it is still considered discontinued. The dosage of norepinephrine use：the total dose of NE used within 72 hours after the patient is enrolled in the study.
Time frame: 28-day
The duration of mechanical ventilation
The number of days without mechanical ventilation within 28 days post-enrollment. Note: Only full days without mechanical ventilation can be counted as one day.
Time frame: 28-day
The duration of ICU stay
ICU length of stay: the number of days in the ICU starting from the time of patient enrollment in the study. Note: Some patients may have multiple ICU admissions; only the ICU stay duration after the current enrollment is recorded.
Time frame: 28-day
The duration of overall hospital stay
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The duration of overall hospital stay: the total number of days hospitalized starting from the time of patient enrollment in the study. Note: Days hospitalized prior to enrollment are not included.
Time frame: 28-day
The safety of methylene blue injection
We will record the complications due to the use of methylene blue, such as hemolysis: We will determine the presence of hemolysis by daily monitoring of urine color, red blood cells, hemoglobin count in complete blood count, and bilirubin levels in liver function tests. If the patient's urine turns dark brown (similar to soy sauce), accompanied by a decrease in hemoglobin and red blood cell count and a simultaneous increase in bilirubin, hemolysis will be considered.
Time frame: 28-day