Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status

Central South University

Status and phase: Unknown; Phase 4

Conditions: Inflammatory Disorder of Immune System; Sepsis

Treatments: Procedure: Sedation interruption; Drug: Morphine; Drug: Midazolam; Other: blood sample collection

Study type: Interventional

Funder types: Other

Identifiers

NCT02135055

2014021801

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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. -

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 4 patient groups

Normal immune function

Experimental group

Description:

The value of monocyte human leukocyte antigen-DR (mHLA-DR) is equal to or more than 15000 monoclonal antibody.

Treatment:

Drug: Morphine

Drug: Midazolam

Procedure: Sedation interruption

Other: blood sample collection

Moderate immunosuppression

Experimental group

Description:

The value of mHLA-DR is equal to or more than 10000 and less than 15000 monoclonal antibody.

Treatment:

Drug: Morphine

Drug: Midazolam

Procedure: Sedation interruption

Other: blood sample collection

Sever immunosuppression

Experimental group

Description:

The value of mHLA-DR is equal to or more than 5000 and less than 10000 monoclonal antibody.

Treatment:

Drug: Morphine

Drug: Midazolam

Procedure: Sedation interruption

Other: blood sample collection

Immune paralysis

Experimental group

Description:

The value of mHLA-DR is less than 5000 monoclonal antibody.

Treatment:

Drug: Morphine

Drug: Midazolam

Procedure: Sedation interruption

Other: blood sample collection