Immuninflammatorisk regulering av esketamin hos septiske pasienter
Effekter av esketamin kombinert med propofol for sedasjon på systemisk betennelse og immunfunksjon hos septiske pasienter på intensivavdelingen: en enkeltsenter, ikke-blind, prospektiv randomisert kontrollert studie
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.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Fase 4
Kontakter og plasseringer
Studiesteder
-
-
Hubei
-
Wuhan, Hubei, Kina, 430022
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
|
Ingen inngripen: 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). |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Serum concentration of inflammatory cytokines (0 h)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: up to 8 weeks
|
Length of stay in the ICU |
up to 8 weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Serum concentration of atrial natriuretic peptide (ANP) (0 h)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 72 hours after study inclusion
|
0-43, higher scores correspond to more severe sepsis |
72 hours after study inclusion
|
|
Mechanical ventilation time after inclusion
Tidsramme: Up to 8 weeks
|
Patients requiring mechanical ventilation after study inclusion |
Up to 8 weeks
|
|
Total hospital length of stay
Tidsramme: Through study completion, an average of 2 year
|
Total length of hospital stay |
Through study completion, an average of 2 year
|
|
Infection complications
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 72 hours after study inclusion
|
Wnt5a, FZD5, b-catenin, Lef1 expression in alveolar macrophages collected from bronchoalveolar lavage fluid |
72 hours after study inclusion
|
Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Shiying Yuan, PhD, MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- YSY202001
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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.
IPD-delingstidsramme
Six months after the paper was published
Tilgangskriterier for IPD-deling
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
IPD-deling Støtteinformasjonstype
- CSR
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