Over-resuscitation including fluid overload has been associated with increased morbidity (prolonged duration of organ failure) and mortality in septic shock. "One-size-fits-all" resuscitation strategies may increase septic shock mortality. However, clinical studies on individualized resuscitation are lacking. Hemodynamic phenotyping may allow to individualize septic shock resuscitation. The ANDROMEDA-SHOCK trial found that a simple clinical and bedside CRT-targeted resuscitation reduces organ dysfunction and 28-day mortality in septic shock. The current study will examine the hypothesis that a CRT-targeted resuscitation based on hemodynamic phenotyping considering within an decision tree usual bedside clinical parameters such as pulse pressure, diastolic blood pressure, fluid responsiveness and cardiac performance can further decrease mortality in septic shock as compared to usual care.
Consecutive adult patients (≥ 18 years)
Patients with septic shock according to Sepsis-3 consensus conference. In short, septic shock is defined as suspected or confirmed infection, plus hyperlactatemia and NE requirements due to persistent hypotension, after a fluid load of at least 1000mL in 1h
Patient and/or relative informed and having signed the information and consent form for participation in the study
More than 4 hours since septic shock diagnosis,
Anticipated surgery or acute hemodialysis procedure to start during the 6h intervention period
Active bleeding,
Do not resuscitate status,
Parallel
Usual care (UC)
Other intervention\- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP \>65 mmHg, heart rate (HR) \<120 beats per minute (BPM), arterial oxygen saturation (SaO2) \>94%, Hb \> 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.
A composite of all cause 28-days mortality plus time to cessation of vital support and length of hospital stay
A hierarchical composite of all cause mortality within 28 days, time to cessation of vital support (truncated at 28 days) and length of hospital stay (truncated at 28 days).
All-cause mortality within 28 days
All-cause mortality within 28 days
Vital support free days
The number of calendar days between randomization and 28 days that the patient is alive and with no requirement of cardiovascular, respiratory and renal support. Patients who die within 28 days will have zero days counted for this variable, irrespective of vital support status. Resolution of cardiovascular failure implies complete stopping of vasopressor support for at least 24 consecutive hours. Resolution of respiratory failure implies extubation / liberation from mechanical ventilation for at least 48 hours. Resolution of renal failure implies liberation of renal replacement therapy for at least 72 hours in those receiving continuous replacement modalities and at least 5 days for those receiving intermittent ones.
Length of hospital stay
Number of days remaining hospitalized (from randomization up to hospital discharge), truncated at day 28.
Length of ICU stay
Number of days remaining in ICU (from randomization up to ICU discharge). Re-admission to ICU during follow-up period will be accounted for the original ICU length of stay only if occurred within the next week of ICU discharge and by a cause related with the original admission.
Time to cessation of vasopressor support
The number of hours between randomization and complete stopping of vasopressor support (defined as its complete interruption for at least 24 consecutive hours), within 28 days from randomization
Time to cessation of mechanical ventilation
The number of calendar days between intubation / start of mechanical ventilation and extubation / liberation from mechanical ventilation (maintained for at least 48 hours) within 28 days from randomization.
Time to cessation of renal replacement therapy
The number of calendar days between start of renal replacement therapy and complete liberation from renal replacement therapy (at least 48 hours for continuous replacement modalities and 5 days for intermittent ones) within 28 days from randomization.
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