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

NCT ID: NCT02135055

Last Updated: 2014-05-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2015-03-31

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.

Conditions

Inflammatory Disorder of Immune System; Sepsis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normal immune function

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

Group Type: EXPERIMENTAL

blood sample collection

Intervention Type: OTHER

Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Midazolam

Intervention Type: DRUG

The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.

Morphine

Intervention Type: DRUG

Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Sedation interruption

Intervention Type: PROCEDURE

Sedation interruption is performed at 8 am every morning.

Moderate immunosuppression

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

Group Type: EXPERIMENTAL

blood sample collection

Intervention Type: OTHER

Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Midazolam

Intervention Type: DRUG

The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.

Morphine

Intervention Type: DRUG

Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Sedation interruption

Intervention Type: PROCEDURE

Sedation interruption is performed at 8 am every morning.

Sever immunosuppression

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

Group Type: EXPERIMENTAL

blood sample collection

Intervention Type: OTHER

Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Midazolam

Intervention Type: DRUG

The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.

Morphine

Intervention Type: DRUG

Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Sedation interruption

Intervention Type: PROCEDURE

Sedation interruption is performed at 8 am every morning.

Immune paralysis

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

Group Type: EXPERIMENTAL

blood sample collection

Intervention Type: OTHER

Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Midazolam

Intervention Type: DRUG

The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.

Morphine

Intervention Type: DRUG

Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Sedation interruption

Intervention Type: PROCEDURE

Sedation interruption is performed at 8 am every morning.

Interventions

blood sample collection

Patients were included 1 hrs later(before the study drug is administrated), 3 d and 7 d after sedation with midazolam, blood sample is collected. Flow cytometry is performed to test the mHLA-DR and according the value of mHLA-DR, assign the participant to the 4 groups as described in the arm.

Intervention Type: OTHER

Midazolam

The loading dose of midazolam is 0.03-0.3 mg/kg, intravenous injected slowly for 10 minutes, then 0.04-0.2 mg/kg/h for maintenance of sedation.

Intervention Type: DRUG

Morphine

Morphine is the only analgesic drug that permitted to use. 2 mg morphine is given a bolus when the participant feel pain. If the pain is not alleviated, 0.4-1 mg/h morphine is maintained.

Intervention Type: DRUG

Sedation interruption

Sedation interruption is performed at 8 am every morning.

Intervention Type: PROCEDURE

Other Intervention Names

Liyuexi

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. -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yuhang Ai, Doctor.

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Other Identifiers

2014021801

Identifier Type: -

Identifier Source: org_study_id