Clinical trial NCT02135055: Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status
Official title: Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Inflammatory Disorder of Immune System
Sepsis
Keywords: organ function
sedation
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2014-05-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Mechanically ventilated ICU patients, sedation is needed.
2. Sepsis patients.
3. Age 18-80 yrs
4. Anticipated sedation duration is more than 3 days.
5. Agreed to participate the study and assigned the informed consent. -

Exclusion Criteria:

1. Allergic to the Benzodiazepine.
2. Hepatic dysfunction(Child-Pugh is C level).
3. Participated other study.
4. Bad prognosis and possibly become the major reason of patients death, such as sever craniocerebral injury,cardiopulmonary resuscitation,advanced malignant tumor,etc.
5. History of immune system disease, immune treatment (including hormone ) or treatment that could affect immune function (including continuous renal replacement therapy,CRRT).
6. Alcoholic and drug abuse.
7. Tendency for major mental disease or treatment of anti psychotics.
8. Pregnant,lactation woman.
9. Unwilling to assign the informed consent or bad compliance. -

Primary outcomes:
measure: T cell subset T Helper 1
timeFrame: Change from baseline of T Helper 1 at 3 and 7 days.
measure: T cell subset T Helper 2
timeFrame: Change from baseline of T Helper 2 at 3 and 7 days.
measure: T cell subset Regulatory T Cell
timeFrame: Change from baseline of Regulatory T Cell at 3 and 7 days.
measure: Interleukin-6
timeFrame: Change from baseline of Interleukin-6 at 3 and 7 days.
measure: Interleukin-10
timeFrame: Change from baseline of Interleukin-10 at 3 and 7 days.
measure: Tumo necrosis factor-α(TNF-α)
timeFrame: Change from baseline of TNF-α at 3 and 7 days.
Secondary outcomes:
measure: duration of mechanical ventilation
timeFrame: from the begining of ventilation to weaning, up to 7 days.
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: up to 7 days
measure: Mortality
timeFrame: up to 28 days
measure: Length of ICU stay
timeFrame: from ICU admmittion to discharge from ICU,up to 28 days.
measure: Index of renal function
timeFrame: baseline,the 3rd and 7th day after sedation
measure: Index of myocardial enzyme
timeFrame: baseline,the 3rd and 7th day after sedation
measure: Index of hepatic function
timeFrame: baseline,the 3rd and 7th day after sedation
measure: Index of endocrine function
timeFrame: baseline,the 3rd and 7th day after sedation
measure: C-reaction protein
timeFrame: baseline,the 3rd and 7th day after sedation
Other outcomes:
measure: mHLA-DR
timeFrame: baseline,the 3rd and 7th day after sedation
Locations:
Study officials:
affiliation: Xiangya Hospital of Central South University
name: Yuhang Ai, Doctor.
role: PRINCIPAL_INVESTIGATOR
References: