Sepsis, Septic Shock
Conditions
Brief summary
Rudiger and Singer suggested strategies for refining adrenergic stress (decatecholaminization). They proposed the use of dexmedetomidine and vasopressin to reduce the catecholamine load during sepsis. The investigators will use vasopressin as the primary vasopressor and a heart rate-calibrated dexmedetomidine infusion in septic shock patients. The investigators of the current study will use DEXPRESSIN in septic shock patients to investigate the effects of decatecholaminization on in-hospital mortality.
Detailed description
The investigator will include 260 patients with septic shock. The study will compare the use of vasopressin as the first-line vasopressor in septic shock in addition to the dexmedetomidine infusion as in the DecatSepsis trial versus the standard of care. The standard of care is guided by the Surviving Sepsis campaign in 2021. The main outcomes of the study are in-hospital mortality, norepinephrine equivalent dose, ICU scores, and inflammatory markers.
Interventions
DRUGDEX-PRESSIN
This group will receive vasopressin as the first-line vasopressor. DEX will be started after hemodynamic stabilization if the heart rate is \>90 beats per minute (bpm). NE infusion will be the second-line vasoactive drug.
DRUGStandard of Care
This group will receive conventional treatment according to the SSC 2021 guidelines. This group will receive vasopressin as the second line after NE and will not receive DEX.
Sponsors
Mansoura University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcome assessor will be nurses - not invovled in the study - will be unware about the study drug.
Intervention model description
Randomized controlled superiority trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients who develop septic shock in whom a vasopressor is initiated to maintain a mean arterial blood pressure (MAP) of ≥65 mmHg in the presence 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 g/dL at the time of inclusion * Severe cardiac dysfunction \[i.e., ejection fraction (EF) \<30%\] * History of heart block or patient on pacemaker * Severe valvular heart disease * Chronic liver disease (Child-Pugh classification C) * Pregnancy * Patients with traumatic brain injury
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| in-hospital mortality | throughout the hospitalization period on average 90 days. | All-cause inhospital mortality as a binary outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Norepinephrine Equivalent Dose (NED) | over the first three days after enrolment or death | mean NED over the first three days after enrolment or death, whichever comes first; the NED of epinephrine will be estimated as a 1:1 ratio |
| Duration of vasopressor infusion in survivors | through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days | Duration in hours from the start of the vasopressor (NE or vasopressin) infusion till the time of discontinuation. |
| Initiation of invasive mechanical ventilation (IMV) | through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days | incidence of IMV |
| Duration of IMV | through out the hospitalization period or 28 days after inclusion if discharged from hosptial before 28 days | duratioin in hours |
| Early acute kidney injury (AKI) | within 48 hours | AKI according to the KDIGO guidelines 2012 |
| survival analysis | through out the hospitalization period or 28 days after inclusion if discharged from hosptia; before 28 days | time to die using Kaplan Mier Curve |
| Acute Physiology and Chronic Health Evaluation (APACHE-II) | on the 3rd day after enrollment | As a score on MedCalc |
| Simplified Acute Physiology Score (SAPS) II score | on the 3rd day after enrollment | As a score on MedCalc |
| ICU length of stay | during hospitalization period on average 90 days | duration in days in survivors |
| Hospital length of stay | during hospitlaization period on average 90 days | duration in days in survivors |
| Late acute kidney injury (AKI) | between 48 hours and 7 days | AKI according to the KDIGO guidelines 2012 |
Contacts
Primary ContactMoataz M Emara
Outcome results
None listed