Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 主要终点
- T cell subset T Helper 1
研究概览
简要总结
ICU patients always experience all kinds of pain, discomfort and sleep disturbance,especially the sepsis patients. Appropriate sedation and analgesia is must,the newest sepsis guideline strongly recommend that mechanically ventilated sepsis patients need sedation therapy.
Recent studies show than immune dysfunction dose have an important effect on the occurrence and development of sepsis. When the body suffer from the pathogenic microorganism attacking and sepsis, it activate the systemic inflammatory response (SIRS) and compensatory anti-inflammatory response syndrome (CARS). When it is out of balance between SIRS and CARS, the inflammatory response, immune paralysis or immune dysfunction occurs and the mixed anti-inflammatory response syndrome (MARS) exists, and then the multiple organ dysfunction. So, immune dysfunction is thought to be the key factors on the development of the sepsis. Some studies show that the sedation drug such as midazolam, propofol, dexmedetomidine could suppress the inflammatory response effectively and then modulate the immune function.
Several recent studies show that midazolam has the immunoregulation effect and trend of suppress the inflammatory response, but the result is controversy, the possibly reason is the different immune status. Now there is the guideline about the different immune status: the normal immune function means that the value of mHLA-DR is more than 15000 monoclonal antibody; moderate-sever immune suppression means that the value of mHLA-DR is in the range of 5000 and 15000 monoclonal antibody; the immune paralysis means that the value of mHLA-DR is less than 5000 monoclonal antibody.
The purpose of the study is to explore the effect of midazolam to inflammatory response and organ function at mechanically ventilated sepsis patients who have different immune status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Mechanically ventilated ICU patients, sedation is needed.
- •Sepsis patients.
- •Age 18-80 yrs
- •Anticipated sedation duration is more than 3 days.
- •Agreed to participate the study and assigned the informed consent. -
排除标准
- •Allergic to the Benzodiazepine.
- •Hepatic dysfunction(Child-Pugh is C level).
- •Participated other study.
- •Bad prognosis and possibly become the major reason of patients death, such as sever craniocerebral injury,cardiopulmonary resuscitation,advanced malignant tumor,etc.
- •History of immune system disease, immune treatment (including hormone ) or treatment that could affect immune function (including continuous renal replacement therapy,CRRT).
- •Alcoholic and drug abuse.
- •Tendency for major mental disease or treatment of anti psychotics.
- •Pregnant,lactation woman.
- •Unwilling to assign the informed consent or bad compliance. -
研究组 & 干预措施
Normal immune function
The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.
干预措施: blood sample collection (Other)
Normal immune function
The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.
干预措施: Sedation interruption (Procedure)
Normal immune function
The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.
干预措施: Midazolam (Drug)
Normal immune function
The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.
干预措施: Morphine (Drug)
Moderate immunosuppression
The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.
干预措施: blood sample collection (Other)
Moderate immunosuppression
The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.
干预措施: Midazolam (Drug)
Moderate immunosuppression
The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.
干预措施: Morphine (Drug)
Sever immunosuppression
The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.
干预措施: Sedation interruption (Procedure)
Moderate immunosuppression
The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.
干预措施: Sedation interruption (Procedure)
Sever immunosuppression
The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.
干预措施: blood sample collection (Other)
Sever immunosuppression
The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.
干预措施: Midazolam (Drug)
Sever immunosuppression
The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.
干预措施: Morphine (Drug)
Immune paralysis
The value of mHLA-DR is less than 5000 monoclonal antibody.
干预措施: blood sample collection (Other)
Immune paralysis
The value of mHLA-DR is less than 5000 monoclonal antibody.
干预措施: Midazolam (Drug)
Immune paralysis
The value of mHLA-DR is less than 5000 monoclonal antibody.
干预措施: Morphine (Drug)
Immune paralysis
The value of mHLA-DR is less than 5000 monoclonal antibody.
干预措施: Sedation interruption (Procedure)
结局指标
主要结局
T cell subset T Helper 1
时间窗: Change from baseline of T Helper 1 at 3 and 7 days.
T Helper 1(TH1) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.
T cell subset T Helper 2
时间窗: Change from baseline of T Helper 2 at 3 and 7 days.
T Helper 2(TH2) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.
T cell subset Regulatory T Cell
时间窗: Change from baseline of Regulatory T Cell at 3 and 7 days.
Regulatory T Cell are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.
Interleukin-6
时间窗: Change from baseline of Interleukin-6 at 3 and 7 days.
Levels of interleukin-6(IL-6) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Enzyme Linked Immunosorbent Assay（ELISA）.
Interleukin-10
时间窗: Change from baseline of Interleukin-10 at 3 and 7 days.
Levels of interleukin-10(IL-10) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Enzyme Linked Immunosorbent Assay（ELISA）.
Tumo necrosis factor-α(TNF-α)
时间窗: Change from baseline of TNF-α at 3 and 7 days.
Levels of Tumo necrosis factor-α(TNF-α) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Enzyme Linked Immunosorbent Assay（ELISA）.
次要结局
- Index of hepatic function(baseline,the 3rd and 7th day after sedation)
- Index of endocrine function(baseline,the 3rd and 7th day after sedation)
- C-reaction protein(baseline,the 3rd and 7th day after sedation)
- Index of renal function(baseline,the 3rd and 7th day after sedation)
- duration of mechanical ventilation(from the begining of ventilation to weaning, up to 7 days.)
- Number of Participants with Serious and Non-Serious Adverse Events(up to 7 days)
- Mortality(up to 28 days)
- Length of ICU stay(from ICU admmittion to discharge from ICU,up to 28 days.)
- Index of myocardial enzyme(baseline,the 3rd and 7th day after sedation)