Effects of Esketamine Combined With Propofol for Sedation on Systemic Inflammation and Immune Function in Septic Patients in the ICU: a Single-center, Non-blind, Prospective Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Serum concentration of inflammatory cytokines (0 h)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
esketamine plus propofol
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.
干预措施: Esketamine hydrochloride (Drug)
结局指标
主要结局
Serum concentration of inflammatory cytokines (0 h)
时间窗: 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)
时间窗: 72 hours after study inclusion
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ
ICU length of stay
时间窗: up to 8 weeks
Length of stay in the ICU
Absolute number of lymphocyte subsets in the peripheral blood (0 h)
时间窗: 0 hour after study inclusion
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
Serum concentration of inflammatory cytokines (48 h)
时间窗: 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)
时间窗: 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)
时间窗: 72 hours after study inclusion
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells
次要结局
- Acute physiology and chronic health evaluation (APACHE) Ⅱ score(72 hours after study inclusion)
- Serum concentration of atrial natriuretic peptide (ANP) (48h)(48 hours after study inclusion)
- Infection complications(Through study completion, an average of 2 year)
- Serum concentration of atrial natriuretic peptide (ANP) (0 h)(0 hour after study inclusion)
- Total hospital length of stay(Through study completion, an average of 2 year)
- In-hospital mortality(Through study completion, an average of 2 year)
- CCL1 expression in alveolar macrophages (0 h)(0 hour after study inclusion)
- CCL1 expression in alveolar macrophages (24 h)(24 hours after study inclusion)
- expression of WNT pathway proteins in alveolar macrophages (24 h)(24 hours after study inclusion)
- Serum concentration of atrial natriuretic peptide (ANP) (72h)(72 hours after study inclusion)
- Sequential organ failure assessment (SOFA) score(72 hours after study inclusion)
- Mechanical ventilation time after inclusion(Up to 8 weeks)
- 90-day readmission rate(Through study completion, an average of 2 year)
- CCL1 expression in alveolar macrophages (72 h)(72 hours after study inclusion)
- expression of WNT pathway proteins in alveolar macrophages (0 h)(0 hour after study inclusion)
- expression of WNT pathway proteins in alveolar macrophages (72 h)(72 hours after study inclusion)