Sepsis, Septic Shock
Conditions
Keywords
dexmedetomidine, randomized controlled trial
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.
Interventions
DRUGDexmedetomidine
A highly-selective alpha-2 agonist with sedative, analgesic, and sympatholytic effects.
Sponsors
Mansoura University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
There is no masking
Intervention model description
An open label randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| Initiation of invasive mechanical ventilation (IMV) in non-ventilated patients | Through study completion, an average of 3 months | Categorical variable (as yes/no outcome) |
| 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. |
| 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 |
Countries
Egypt
Outcome results
None listed