Septic Shock
Conditions
Brief summary
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
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.
Interventions
DRUGDexmedetomidine Injection [Precedex]
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,
DRUGMidazolam
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).
Sponsors
Kasr El Aini Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD42/CD14 | 24 hours after start of study drugs infusion | Expression of CD42/CD14 will be measured by flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| effect on HLA-DR/CD14 | Baseline before start of drug then 6, 12 and 24 hour after drug | Expression of HLA-DR/CD14 will be measured by flow cytometry |
| TNFα | Baseline before start of drug then 6, 12 and 24 hour after drug | Expression of tumor necrosis factor (TNFα) will be measured by flow cytometry |
| IL10 | Baseline before start of drug then 6, 12 and 24 hour after drug | Interleukin 10 will be measured by flow cytometry |
| KIM-1 level | Baseline before start of drug and 24 hour after drug | kidney injury molecule 1 |
| number of participants that will die within 28 days | within 28 dyas | mortality within 28 days |
Countries
Egypt
Outcome results
None listed