Decatecholaminisation With Dexmedetomidine for Reduction of Mortality in Septic Shock: A Randomized Clinical Trial
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Mansoura University
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- In-hospital mortality
Study Overview
Brief Summary
The study aims to determine whether the infusion of DEX in septic shock can reduce in-hospital mortality, norepinephrine infusion, need and duration for mechanical ventilation, and acute kidney injury without significant adverse events.
Detailed Description
During septic shock, acute stress response includes neural and humoral autonomic flaring, which tend to be beneficial in the short term. Once shock occurs, it is a failure of the compensation trial. In addition, chronic autonomic stimulation risks myocardial injury, immunosuppression, insulin resistance, and thrombo-embolic tendency.
The investigators hypothesized that dacatecholaminisation with dexmedetomidine - as calibrated by heart rate control - would reduce the in-hospital mortality in septic shock, whether the patient is mechanically ventilated or not. The study aims to determine whether the infusion of DEX in septic shock can reduce in-hospital mortality, norepinephrine infusion, need and duration for mechanical ventilation, and acute kidney injury without significant adverse events.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
There is no masking
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult (≥ 18 years) patients of either sex who develop septic shock with heart rate (HR) > 90 beats per minute (bpm).
- •We choose the definition of septic shock as the start of norepinephrine (NE) infusion to maintain the mean arterial blood pressure (MAP) of ≥ 65 mmHg in a case of sepsis (≥ 2 SIRS criteria plus suspicion or confirmation of infection).
Exclusion Criteria
- •Patient refusal or inability to obtain consent
- •Failure of hemodynamic stabilization or hemoglobin < 7 gm/dl at time of inclusion
- •Severe cardiac dysfunction (Ejection Fraction (EF) < 30%)
- •History of heart block or patient on pacemaker
- •Chronic liver Disease (Child-Pugh classification C)
- •Severe valvular heart disease
- •Pregnancy
Arms & Interventions
Dexmedetomidine
Patients will receive dexmedetomidine infusion according to the protocol plus the usual care.
We will evaluate patients for inclusion in the study after 6 hours on NE infusion, given stabilization of the MAP > 65 mmHg. In the DEX group, we will commence DEX infusion at the rate of 0.2 mcg.kg-1.h-1 without a loading dose, then titrate DEX infusion to maintain the HR from 60 to 90 bpm.
Titration of the DEX infusion rate will not be more than 0.1 mcg.kg-1.h-1 every 30 minutes at any time. The maximum DEX infusion rate will be 0.7 mcg.kg-1.h-1.
We aim to continue DEX infusion for 48 hours. After 48 hours of DEX infusion, we will taper the DEX infusion over one hour.
According to our protocol, DEX infusion would trigger either STOP events or hemodynamic assessment events:
Intervention: Dexmedetomidine (Drug)
Outcomes
Primary Outcomes
In-hospital mortality
Time Frame: Through study completion, an average of 3 months
The investigators will review the patient status on discharge from the hospital, alive or dead
Secondary Outcomes
- Norepinephrine equivalent dose (NED)(over the first 3 days after enrolment or death, which comes first)
- Need for epinephrine infusion(over the first 3 days after enrolment or death, which comes first)
- Heart rate (HR) beat per minute(over the first 3 days after enrolment or death, which comes first)
- Mean arterial blood pressure (MAP) mmHg(over the first 3 days after enrolment or death, which comes first)
- Initiation of invasive mechanical ventilation (IMV) in non-ventilated patients(Through study completion, an average of 3 months)
- Early acute kidney injury(48 hours after ICU admission in previously normal kidney function)
- Late acute kidney injury(7 days after ICU admission in previously normal kidney function)