Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock

Study Overview
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Brief Summary
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in this study the investigators aim to assess the role of using dexmedetomidine as sedative in septic shock patients in comparison with midazolam. The investigators aim to assess the effect on immune response and inflammatory mediators and effect on vasopressors.

Detailed Description
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Sedation protocol All patients will receive analgesia with fentanyl at ﬁxed dose of 0.5 µg.kg.hr-1. Each patient will receive the study drug within 6 hours after ICU admission. Depth of sedation will be assessed using Richmond Agitation and Sedation Scale (RASS) scores (6), which range from -5 (unarousable) to +4 (combative). Study treatments will be infused without loading dose. Group I patients will have dexmedetomidine (4 µg.mL-1) and group II patients will have midazolam (0.33 mg.mL-1). Both drugs will be prepared in 0.9% sodium chloride in 50-mL syringe. Both the agents will be titrated to maintain the RASS in a range of -3 to -1. Dexmedetomidine infusion will be started at 0.1 µg.kg-1.hr-1 and will be adjusted by 0.1 µg.kg-1.h-1 to a maximum of 0.5 µg/kg/h, while midazolam will be started at 1 mg.h-1 (3 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (15 mL.h-1). All infusions will be adjusted by increments of 3 mL/hr-1. Patients in either group not adequately sedated by study drug titration will receive a bolus dose of fentanyl 0.5-1 µg.kg. Assessment of RASS score will be performed every 2 hours and prior to any dose of rescue therapy. The study drugs will be infused for 24 hours and after that the choice of sedation will be determined according to preference of attending physician.

Official Title
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ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial)

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Dexmedetomidine Injection [Precedex]
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age more than 18 years old All mechanically ventilated patients who will be clinically suspected of having septic shock defined by infusion of at least one vasopressor and lactate > 2.0 mmol/l (5) Exclusion Criteria: Age < 18 years old Pregnant patient Source of sepsis not controlled Acute hepatitis or severe liver disease (Child-Pugh class C) Left ventricular ejection fraction less than 30% Heart rate less than 50 beats/min Second or third degree heart block Systolic pressure < 90 mmHg despite of infusion of 2 vasopressors. Psychological illness or severe cognitive dysfunction Patients who are allergic to dexmedetomidine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine Group<br>patients will receive dexmedetomidine as sedative | Drug: Dexmedetomidine Injection [Precedex]<br>* Dexmedetomidine infusion will be started at 0.1 µg.kg-1.hr-1 and will be adjusted by 0.1 µg.kg-1.h-1 to a maximum of 0.5 µg/kg/h,<br>|
| Active Comparator: Midazolam<br>patients will receive midazolam as sedative | Drug: Midazolam<br>* midazolam will be started at 1 mg.h-1 (3 mL.hr-1) and adjusted by 1 mg.h-1 to a maximum of 5 mg.h-1 (15 mL.h-1).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CD42/CD14 | Expression of CD42/CD14 will be measured by flow cytometry | 24 hours after start of study drugs infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect on HLA-DR/CD14 | Expression of HLA-DR/CD14 will be measured by flow cytometry | Baseline before start of drug then 6, 12 and 24 hour after drug | 
| TNFα | Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry | Baseline before start of drug then 6, 12 and 24 hour after drug | 
| IL10 | Interleukin 10 will be measured by flow cytometry | Baseline before start of drug then 6, 12 and 24 hour after drug | 
| KIM-1 level | kidney injury molecule 1 | Baseline before start of drug and 24 hour after drug | 
| number of participants that will die within 28 days | mortality within 28 days | within 28 dyas |