Regulación inmunoinflamatoria de esketamina en pacientes sépticos
Efectos de la esketamina combinada con propofol para la sedación sobre la inflamación sistémica y la función inmunitaria en pacientes sépticos en la UCI: un ensayo controlado aleatorizado, prospectivo, no ciego, de un solo centro
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.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Tipo de estudio
Tipo de estudio
Inscripción (Actual)
Inscripción
Fase
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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Hubei
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Wuhan, Hubei, Porcelana, 430022
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Experimental: 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. |
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. |
|
Sin intervención: 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). |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Serum concentration of inflammatory cytokines (0 h)
Periodo de tiempo: 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 |
0 hour after study inclusion
|
|
Serum concentration of inflammatory cytokines (48 h)
Periodo de tiempo: 48 hours after study inclusion
|
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ |
48 hours after study inclusion
|
|
Serum concentration of inflammatory cytokines (72 h)
Periodo de tiempo: 72 hours after study inclusion
|
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IFN-γ |
72 hours after study inclusion
|
|
Absolute number of lymphocyte subsets in the peripheral blood (0 h)
Periodo de tiempo: 0 hour after study inclusion
|
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells |
0 hour after study inclusion
|
|
Absolute number of lymphocyte subsets in the peripheral blood (48 h)
Periodo de tiempo: 48 hours after study inclusion
|
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells |
48 hours after study inclusion
|
|
Absolute number of lymphocyte subsets in the peripheral blood (72 h)
Periodo de tiempo: 72 hours after study inclusion
|
CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(-) CD16(+) CD56(+) , and CD19(+) cells |
72 hours after study inclusion
|
|
ICU length of stay
Periodo de tiempo: up to 8 weeks
|
Length of stay in the ICU |
up to 8 weeks
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Serum concentration of atrial natriuretic peptide (ANP) (0 h)
Periodo de tiempo: 0 hour after study inclusion
|
ANP is secreted primarily by atrial cardiomyocytes |
0 hour after study inclusion
|
|
Serum concentration of atrial natriuretic peptide (ANP) (48h)
Periodo de tiempo: 48 hours after study inclusion
|
ANP is secreted primarily by atrial cardiomyocytes |
48 hours after study inclusion
|
|
Serum concentration of atrial natriuretic peptide (ANP) (72h)
Periodo de tiempo: 72 hours after study inclusion
|
ANP is secreted primarily by atrial cardiomyocytes |
72 hours after study inclusion
|
|
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Periodo de tiempo: 0 hour after study inclusion
|
0-67, higher scores correspond to more severe disease and a higher risk of death |
0 hour after study inclusion
|
|
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Periodo de tiempo: 24 hours after study inclusion
|
0-67, higher scores correspond to more severe disease and a higher risk of death |
24 hours after study inclusion
|
|
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Periodo de tiempo: 48 hours after study inclusion
|
0-67, higher scores correspond to more severe disease and a higher risk of death |
48 hours after study inclusion
|
|
Acute physiology and chronic health evaluation (APACHE) Ⅱ score
Periodo de tiempo: 72 hours after study inclusion
|
0-67, higher scores correspond to more severe disease and a higher risk of death |
72 hours after study inclusion
|
|
Sequential organ failure assessment (SOFA) score
Periodo de tiempo: 0 hour after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
0 hour after study inclusion
|
|
Sequential organ failure assessment (SOFA) score
Periodo de tiempo: 24 hours after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
24 hours after study inclusion
|
|
Sequential organ failure assessment (SOFA) score
Periodo de tiempo: 48 hours after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
48 hours after study inclusion
|
|
Sequential organ failure assessment (SOFA) score
Periodo de tiempo: 72 hours after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
72 hours after study inclusion
|
|
Mechanical ventilation time after inclusion
Periodo de tiempo: Up to 8 weeks
|
Patients requiring mechanical ventilation after study inclusion |
Up to 8 weeks
|
|
Total hospital length of stay
Periodo de tiempo: Through study completion, an average of 2 year
|
Total length of hospital stay |
Through study completion, an average of 2 year
|
|
Infection complications
Periodo de tiempo: Through study completion, an average of 2 year
|
Pulmonary infection, urinary tract infection, bloodstream infections, etc |
Through study completion, an average of 2 year
|
|
In-hospital mortality
Periodo de tiempo: Through study completion, an average of 2 year
|
Mortality rates for the entire period of hospitalization |
Through study completion, an average of 2 year
|
|
90-day readmission rate
Periodo de tiempo: Through study completion, an average of 2 year
|
Percentage of readmission to hospital within 90 days of study inclusion |
Through study completion, an average of 2 year
|
|
CCL1 expression in alveolar macrophages (0 h)
Periodo de tiempo: 0 hour after study inclusion
|
CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
0 hour after study inclusion
|
|
CCL1 expression in alveolar macrophages (24 h)
Periodo de tiempo: 24 hours after study inclusion
|
CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
24 hours after study inclusion
|
|
CCL1 expression in alveolar macrophages (72 h)
Periodo de tiempo: 72 hours after study inclusion
|
CCL1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
72 hours after study inclusion
|
|
expression of WNT pathway proteins in alveolar macrophages (0 h)
Periodo de tiempo: 0 hour after study inclusion
|
Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
0 hour after study inclusion
|
|
expression of WNT pathway proteins in alveolar macrophages (24 h)
Periodo de tiempo: 24 hours after study inclusion
|
Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
24 hours after study inclusion
|
|
expression of WNT pathway proteins in alveolar macrophages (72 h)
Periodo de tiempo: 72 hours after study inclusion
|
Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
72 hours after study inclusion
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Shiying Yuan, PhD, MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Actual)
Finalización primaria
Finalización del estudio (Actual)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- YSY202001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
After the completion of the study, the original data will be sent to the email address: zhjcheng1@163.com, and the password will be provided after the paper is published.
Marco de tiempo para compartir IPD
Six months after the paper was published
Criterios de acceso compartido de IPD
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Tipo de información de apoyo para compartir IPD
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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