Immunoinflammatory Regulation of Esketamine in Septic Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: 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.
|
| No Intervention: 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). |
Outcome Measures
Primary Outcome Measures
- 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 (48 h) [48 hours after study inclusion]
IL-6, TNF-α, IL-2, IL-4, IL-10, IL-17A, and 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
- 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
- ICU length of stay [up to 8 weeks]
Length of stay in the ICU
Secondary Outcome Measures
- Serum concentration of atrial natriuretic peptide (ANP) (0 h) [0 hour after study inclusion]
ANP is secreted primarily by atrial cardiomyocytes
- Serum concentration of atrial natriuretic peptide (ANP) (48h) [48 hours after study inclusion]
ANP is secreted primarily by atrial cardiomyocytes
- Serum concentration of atrial natriuretic peptide (ANP) (72h) [72 hours after study inclusion]
ANP is secreted primarily by atrial cardiomyocytes
- Acute physiology and chronic health evaluation (APACHE) Ⅱ score [0 hour after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
- Acute physiology and chronic health evaluation (APACHE) Ⅱ score [24 hours after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
- Acute physiology and chronic health evaluation (APACHE) Ⅱ score [48 hours after study inclusion]
0-67, higher scores correspond to more severe disease and a higher risk of death
- 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
- Sequential organ failure assessment (SOFA) score [0 hour after study inclusion]
0-43, higher scores correspond to more severe sepsis
- Sequential organ failure assessment (SOFA) score [24 hours after study inclusion]
0-43, higher scores correspond to more severe sepsis
- Sequential organ failure assessment (SOFA) score [48 hours after study inclusion]
0-43, higher scores correspond to more severe sepsis
- 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
- Total hospital length of stay [Through study completion, an average of 2 year]
Total length of hospital stay
- Infection complications [Through study completion, an average of 2 year]
Pulmonary infection, urinary tract infection, bloodstream infections, etc
- In-hospital mortality [Through study completion, an average of 2 year]
Mortality rates for the entire period of hospitalization
- 90-day readmission rate [Through study completion, an average of 2 year]
Percentage of readmission to hospital within 90 days of study inclusion
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 years old ≤ age ≤60 years old;
-
SOFA score ≥2;
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Mechanical ventilation should be required for at least 24 hours when included in the study;
-
Informed consent is obtained.
Exclusion Criteria:
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Age < 18 years old or ≥ 60 years old;
-
Previous solid organ or bone marrow transplantation;
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Autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.), or hematologic malignancies (leukemia and lymphoma, etc.);
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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);
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Unstable angina pectoris or myocardial infarction in the past six months;
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Acute brain injury (traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, acute intracranial hemorrhage, acute intracranial infection, etc.);
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Poorly controlled hypertension and congestive heart failure;
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Increased intraocular or intracranial pressure;
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Chronic kidney disease, received continuous renal replacement therapy in the past 30 days, or acute renal failure requiring CRRT;
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Severe chronic liver disease (Child-Pugh class B or C);
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Alcohol dependence, mental illness or severe cognitive impairment;
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Pregnancy or lactation;
-
Informed consent is not obtained.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | China | 430022 |
| 2 | Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | China | 430022 |
Sponsors and Collaborators
- Wuhan Union Hospital, China
Investigators
- Principal Investigator: Shiying Yuan, PhD, MD, Wuhan Union Hospital, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- YSY202001