Decatecholaminisation of Septic Shock With Dexmedetomidine and In-hospital Mortality
- Registration Number
- NCT05283083
- Lead Sponsor
- Mansoura University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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).
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexmedetomidine 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:
- Primary Outcome Measures
Name Time Method In-hospital mortality Through study completion, an average of 3 months The investigators will review the patient status on discharge from the hospital, alive or dead
- Secondary Outcome Measures
Name Time Method Norepinephrine equivalent dose (NED) over the first 3 days after enrolment or death, which comes first reported as the average of the serial measurements; the NED of epinephrine will be estimated as 1:1 ratio, reported as mcg/kg/min (Shruti Goradia et al, 2021)
Need for epinephrine infusion over the first 3 days after enrolment or death, which comes first Categorical variable (as yes/no outcome)
Heart rate (HR) beat per minute over the first 3 days after enrolment or death, which comes first reported as the average of the serial measurements
Mean arterial blood pressure (MAP) mmHg over the first 3 days after enrolment or death, which comes first reported as the average of the serial measurements
Initiation of invasive mechanical ventilation (IMV) in non-ventilated patients Through study completion, an average of 3 months Categorical variable (as yes/no outcome)
Early acute kidney injury 48 hours after ICU admission in previously normal kidney function Categorical variable (as yes/no outcome) - as defined by Khwaja, A., 2012. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice, 120(4), pp.c179-c184.
Late acute kidney injury 7 days after ICU admission in previously normal kidney function Categorical variable (as yes/no outcome) - as defined by the Khwaja, A., 2012. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical Practice, 120(4), pp.c179-c184.
Trial Locations
- Locations (1)
Mansoura University Hospitals
🇪🇬Mansoura, Aldakahlia, Egypt