Immunoinflammatory Regulation of Esketamine in Septic Patients
- Conditions
- ImmunosuppressionSepsisInflammatory ResponseEsketamine
- Interventions
- Registration Number
- NCT04843982
- Lead Sponsor
- Wuhan Union Hospital, China
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description esketamine plus propofol Esketamine hydrochloride 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.
- Primary Outcome Measures
Name Time Method ICU length of stay up to 8 weeks Length of stay in the ICU
Serum concentration of inflammatory cytokines (0 h) 0 hour after study inclusion Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-10, IL-17A, and interferon (IFN)-γ
Serum concentration of inflammatory cytokines (72 h) 72 hours after study inclusion IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Absolute number of lymphocyte subsets in the peripheral blood (0 h) 0 hour after study inclusion CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Serum concentration of inflammatory cytokines (48 h) 48 hours after study inclusion IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
Absolute number of lymphocyte subsets in the peripheral blood (48 h) 48 hours after study inclusion CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Absolute number of lymphocyte subsets in the peripheral blood (72 h) 72 hours after study inclusion CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
- Secondary Outcome Measures
Name Time Method Acute physiology and chronic health evaluation (APACHE) Ⅱ score 72 hours after study inclusion 0-67, higher scores correspond to more severe disease and a higher risk of death
Serum concentration of atrial natriuretic peptide (ANP) (48h) 48 hours after study inclusion ANP is secreted primarily by atrial cardiomyocytes
Infection complications Through study completion, an average of 2 year Pulmonary infection, urinary tract infection, bloodstream infections, etc
Serum concentration of atrial natriuretic peptide (ANP) (0 h) 0 hour after study inclusion ANP is secreted primarily by atrial cardiomyocytes
Total hospital length of stay Through study completion, an average of 2 year Total length of hospital stay
In-hospital mortality Through study completion, an average of 2 year Mortality rates for the entire period of hospitalization
CCL1 expression in alveolar macrophages (0 h) 0 hour after study inclusion CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
CCL1 expression in alveolar macrophages (24 h) 24 hours after study inclusion CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
expression of WNT pathway proteins in alveolar macrophages (24 h) 24 hours after study inclusion Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
Serum concentration of atrial natriuretic peptide (ANP) (72h) 72 hours after study inclusion ANP is secreted primarily by atrial cardiomyocytes
Sequential organ failure assessment (SOFA) score 72 hours after study inclusion 0-43, higher scores correspond to more severe sepsis
Mechanical ventilation time after inclusion Up to 8 weeks Patients requiring mechanical ventilation after study inclusion
90-day readmission rate Through study completion, an average of 2 year Percentage of readmission to hospital within 90 days of study inclusion
CCL1 expression in alveolar macrophages (72 h) 72 hours after study inclusion CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
expression of WNT pathway proteins in alveolar macrophages (0 h) 0 hour after study inclusion Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
expression of WNT pathway proteins in alveolar macrophages (72 h) 72 hours after study inclusion Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid
Trial Locations
- Locations (1)
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China