Hemodynamic Phenotype-Based,Capillary Refill Time-Targeted Resuscitation In Early Septic Shock:ANDROMEDA-SHOCK-2

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

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.

Number of days remaining hospitalized (from randomization up to hospital discharge), truncated at day 28.

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.

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

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.

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.

The number of calendar days without vasopressor support from randomization up to day 28. Cessation of vasopressor support implies its complete interruption for at least 24 consecutive hours.

The number of calendar days without mechanical ventilation support from randomization up to day 28. Cessation of mechanical ventilation support implies its complete interruption for at least 48 consecutive hours.

Re-start of mechanical ventilation during follow-up period will be accounted for the original mechanical ventilation-free days only if this occurs within the next week of ICU discharge and by a cause related with the original admission.

The number of calendar days without renal replacement therapy from randomization up to day 28. Cessation of renal replacement therapy implies its complete interruption for at least 72 hours in those receiving continuous replacement modalities and at least 5 days for those receiving intermittent ones.

Re-start of renal replacement therapy during follow-up period will be accounted for the original renal replacement-free days only if this occurs within the next week of ICU discharge and by a cause related with the original admission.

The Sequential Organ Failure Assessment (SOFA) is used to track a patient's status during the stay in the ICU to determine the extent of organ dysfunction. Its values ranges from 0 to 24. Higher SOFA scores associate with a worse outcome.

The SOFA score will be calculated upon the maximum values observed on the day of enrollment and then, at days 2, 3, 4, 5 and 7 (or until patient discharge or death, if this happened before day-7), using clinically available data. If an individual organ dysfunction value is not available (i.e., cardiovascular, respiratory, renal, etc.), it will be assumed to be zero unless previous value was abnormal (in which case it would be considered the same organ score). Neurological score under sedation/invasive mechanical ventilation will be computed as that observed just before sedation/intubation.

Renal function assessed according to "Kidney Disease: Improving Global Outcomes (KDIGO) staging system from randomization through day 7 to assess for "de novo" or "worsening" acute kidney injury. Patients under chronic renal replacement therapy will not meet this end-point

The volume of fluids administered with resuscitative intention up to 72 hours from randomization.

The volume of cumulated fluids during the first 72 hours from randomization.

Evolvement of CRT within the first 72 hours after randomization.

Evolvement of arterial lactate levels within the first 72 hours after randomization.

Evolvement of Central venous pressure within the first 72 hours after randomization.

Evolvement of central venous oxygen saturation within the first 72 hours after randomization

Evolvement of central venous to arterial carbon dioxide difference within the first 72 hours after randomization.

All-cause mortality within 90 days

Number of days remaining hospitalized (from randomization up to hospital discharge), truncated at day 90.

Assess the changes in CRT before and after fluid resuscitation or increase in norepinephrine doses and analyse their correlation with changes in haemodynamic parameters: systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), pulse pressure (PP), cardiac output (CO) when available.