Immunoinflammatory Regulation of Esketamine in Septic Patients

Huazhong University of Science and Technology

Status and phase: Enrolling; Phase 4

Conditions: Esketamine; Inflammatory Response; Immunosuppression; Sepsis

Treatments: Drug: Esketamine hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT04843982

YSY202001

Details and patient eligibility

About

Studies have shown that excessive systemic inflammatory response and concomitant immunosuppression are the main cause of early death in patients with sepsis. Therefore, it is very important to reduce excessive inflammation and improve immunosuppression in the acute phase of sepsis. Clinical studies have shown that esketamine combined with propofol for sedation has been proven to be safe and effective for septic patients in the ICU due to its cardiovascular stability. Previous studies have demonstrated that esketamine has anti-inflammatory effects against depression and surgical stress. Our preliminary experimental studies have found that esketamine had strong anti-inflammatory effects in the acute phase of sepsis. However, it is not clear whether esketamine could reduce excessive inflammation and improve immunosuppression in septic patients primarily sedated with a continuous infusion of propofol.

This intervention study is to investigate whether three consecutive days of intravenous esketamine infusions via infusion pump (0.07 mg/kg/h) could reduce excessive inflammation and improve immunosuppression in septic patients requiring mechanical ventilation in the ICU under sedation primarily with propofol.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years old ≤ age ≤60 years old;
• SOFA score ≥2;
• Mechanical ventilation should be required for at least 24 hours when included in the study;
• Informed consent is obtained.

Exclusion criteria

• Age < 18 years old or ≥ 60 years old;
• Previous solid organ or bone marrow transplantation;
• Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), or hematologic malignancies (leukemia and lymphoma, etc.);
• Received radiotherapy or chemotherapy within the past 30 days, or received immunosuppressant drugs (tripterygium wilfordii, mycophenolate mofetil, cyclophosphamide, FK506, etc.), or continuous treatment with prednisolone more than 10 mg/day (or equivalent doses of the other hormones);
• Unstable angina pectoris or myocardial infarction in the past six months;
• Acute brain injury (traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage, acute intracranial infection, etc.);
• Poorly controlled hypertension and congestive heart failure;
• Increased intraocular or intracranial pressure;
• Chronic kidney disease, received continuous renal replacement therapy in the past 30 days, or acute renal failure requiring CRRT;
• Severe chronic liver disease (Child-Pugh class B or C);
• Alcohol dependence, mental illness or severe cognitive impairment;
• Pregnancy or lactation;
• Informed consent is not obtained.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

esketamine plus propofol

Experimental group

Description:

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2). After inclusion, septic patients will be received a single intravenous injection of esketamine (0.7 mg/kg), and then followed by an intravenous administration of esketamine (0.07 mg/kg/h) with an infusion pump for three consecutive days.

Treatment:

Drug: Esketamine hydrochloride

propofol

No Intervention group

Description:

After inclusion, patients are sedated primarily with propofol (0-3 mg/kg/h) using a microinfusion pump and adjusted according to the depth of sedation (Richmond Agitation Sedation Scale (RASS): 0 to -2).