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

NCT02135055 | Unknown Phase 4

• 1 other identifier: 2014021801
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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

Keywords

organ function; sedation

Outcome Measures

Primary Outcomes (6)

• T cell subset T Helper 1

  T Helper 1(TH1) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.

  Change from baseline of T Helper 1 at 3 and 7 days.

• T cell subset T Helper 2

  T Helper 2(TH2) are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.

  Change from baseline of T Helper 2 at 3 and 7 days.

• T cell subset Regulatory T Cell

  Regulatory T Cell are tested before sedation, 3 d and 7 d after sedation with midazolam. The test method is Flow cytometry.

  Change from baseline of Regulatory T Cell at 3 and 7 days.

• Interleukin-6

  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）.

  Change from baseline of Interleukin-6 at 3 and 7 days.

• Interleukin-10

  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）.

  Change from baseline of Interleukin-10 at 3 and 7 days.

• Tumo necrosis factor-α(TNF-α)

  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）.

  Change from baseline of TNF-α at 3 and 7 days.

Secondary Outcomes (9)

• 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 renal function

  baseline,the 3rd and 7th day after sedation

Other Outcomes (1)

• mHLA-DR

  baseline,the 3rd and 7th day after sedation

Study Arms (4)

Normal immune function

EXPERIMENTAL

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

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

Moderate immunosuppression

EXPERIMENTAL

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

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

Sever immunosuppression

EXPERIMENTAL

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

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

Immune paralysis

EXPERIMENTAL

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

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

Interventions

blood sample collection 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.

Immune paralysis; Moderate immunosuppression; Normal immune function; Sever immunosuppression

Midazolam 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.

Also known as: Liyuexi

Immune paralysis; Moderate immunosuppression; Normal immune function; Sever immunosuppression

Morphine 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.

Immune paralysis; Moderate immunosuppression; Normal immune function; Sever immunosuppression

Sedation interruption PROCEDURE

Sedation interruption is performed at 8 am every morning.

Immune paralysis; Moderate immunosuppression; Normal immune function; Sever immunosuppression

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. -

You may not qualify if:

• 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. -

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

MeSH Terms

Conditions

Sepsis

Interventions

Midazolam; Morphine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Yuhang Ai, Doctor.

  Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 9, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 9, 2014

Record last verified: 2014-05