Immunoinflammatory Regulation of Esketamine in Septic Patients

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Esketamine hydrochloride
  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.

Первичные конечные точки

• Serum concentration of inflammatory cytokines (0 h) [Срок оценки: 0 hour after study inclusion]
• Serum concentration of inflammatory cytokines (48 h) [Срок оценки: 48 hours after study inclusion]
• Serum concentration of inflammatory cytokines (72 h) [Срок оценки: 72 hours after study inclusion]
• Absolute number of lymphocyte subsets in the peripheral blood (0 h) [Срок оценки: 0 hour after study inclusion]
• Absolute number of lymphocyte subsets in the peripheral blood (48 h) [Срок оценки: 48 hours after study inclusion]
• Absolute number of lymphocyte subsets in the peripheral blood (72 h) [Срок оценки: 72 hours after study inclusion]
• ICU length of stay [Срок оценки: up to 8 weeks]

Вторичные конечные точки (12)

• Serum concentration of atrial natriuretic peptide (ANP) (0 h) [Срок оценки: 0 hour after study inclusion]
• Serum concentration of atrial natriuretic peptide (ANP) (48h) [Срок оценки: 48 hours after study inclusion]
• Serum concentration of atrial natriuretic peptide (ANP) (72h) [Срок оценки: 72 hours after study inclusion]
• Acute physiology and chronic health evaluation (APACHE) Ⅱ score [Срок оценки: 0 hour after study inclusion]
• Acute physiology and chronic health evaluation (APACHE) Ⅱ score [Срок оценки: 24 hours after study inclusion]
• Acute physiology and chronic health evaluation (APACHE) Ⅱ score [Срок оценки: 48 hours after study inclusion]
• Acute physiology and chronic health evaluation (APACHE) Ⅱ score [Срок оценки: 72 hours after study inclusion]
• Sequential organ failure assessment (SOFA) score [Срок оценки: 0 hour after study inclusion]
• Sequential organ failure assessment (SOFA) score [Срок оценки: 24 hours after study inclusion]
• Sequential organ failure assessment (SOFA) score [Срок оценки: 48 hours after study inclusion]
• Sequential organ failure assessment (SOFA) score [Срок оценки: 72 hours after study inclusion]
• Mechanical ventilation time after inclusion [Срок оценки: Up to 8 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong Uni — Ухань
• Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong Uni — Ухань

Идентификаторы

NCT: NCT04843982 · YSY202001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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