Septic shock Tachycardia Hyperlactatemia Septic shock Methylene blue Dexmedetomidine Vasopressor Heart rate control Randomized controlled trial
Conditions
Interventions
Intravenous methylene blue infusion combined with dexmedetomidine titration for heart rate control in septic shock
,Standard septic shock management according to institutional practice including flui
Methylene blue plus dexmedetomidine,Usual care strategy
Sponsors
Ramathibodi Hospital, Faculty of Medicine, Mahidol University
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1 Age 18 years or older 2 Diagnosis of septic shock according to Sepsis 3 criteria defined as suspected or confirmed infection requirement of vasopressor therapy to maintain mean arterial pressure 65 mmHg or higher despite adequate fluid resuscitation and serum lactate level more than 2 mmol per liter 3 Receiving continuous infusion of norepinephrine at a dose 0 point 25 microgram per kilogram per minute or higher 4 Persistent tachycardia defined as heart rate more than 100 beats per minute despite initial resuscitation 5 Persistent hyperlactatemia defined as serum lactate level more than 2 mmol per liter after initial fluid resuscitation 6 Presence of indwelling arterial line for continuous hemodynamic monitoring presence of central venous line and presence of or planned initiation of cardiac output monitoring as part of advanced hemodynamic assessment 7 Provision of informed consent by patient or legally authorized representative
Exclusion criteria
Exclusion criteria: 1. Moribund state, irreversible multi-organ failure, as determined by the treating clinical team. 2. Pregnancy 3. Advanced-stage, incurable malignancy 4. Do Not Resuscitate (DNR) orders 5. Shock Due to Other Primary Causes: a. Shock primarily due to hypovolemia (e.g., concurrent uncontrolled hemorrhagic shock, major burns, or patients undergoing damage control surgery for trauma) b. Cardiogenic shock (e.g., acute myocardial infarction, severe valvular dysfunction as primary cause). c. Obstructive shock (e.g., massive pulmonary embolism, tension pneumothorax). 6. Anuria acute kidney injury (Anuria AKI) 7. Known or suspected Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency (based on patient's medical history or family history) 8. History of severe allergy to methylene blue, dexmedetomidine, phenothiazines, or any food dyes. 9. Concurrent use or intake within the last 4 weeks of Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Monoamine Oxidase Inhibitors (MAOIs), Tryptophan. 10. Inability or refusal to provide informed consent by the patient or their legally authorized representative
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite hemodynamic response 24 hours after randomization Proportion of patients achieving all criteria heart rate 90 beats per minute or less mean arterial pressure at least 65 mmHg and norepinephrine dose reduction at least 20 percent from baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Vasopressor free days Day 28 Count of days alive and free from any vasopressor infusion between randomization and day 28,28 day mortality Day 28 Proportion of patients who die from any cause within 28 days after randomizatio,Change in SOFA score baseline and 72 hrs Difference between total SOFA score at baseline and at 72 hours after randomization,Serum lactate clearance 24 hrs Percentage reduction in serum lactate level from baseline to 24 hours after randomization,ICU length of stay Day28 Number of days from ICU admission to ICU discharge during the index hospitalization,Heart rate change 48 hours Change in heart rate from baseline measured repeatedly during the first 48 hours after randomization,Time to vasopressor discontinuation Up to day 28 Time from randomization to complete discontinuation of all vasopressor infusions,Duration of mechanical ventilation At ICU discharge Total number of days requiring invasive mechanical ventilation during the index ICU stay,Hospital length of stay At hospital discharge Number of days from hospital admission to hospital discharge,Methemoglobinemia and safety Up to day 7 Incidence of methemoglobinemia maximum methemoglobin level urine discoloration and change in hemoglobin level after study drug administration | — |
Countries
Thailand
Contacts
Public ContactKittikorn Kittirukwarakorn
Ramathibodi Hospital Faculty of Medicine Mahidol University
Outcome results
None listed