Targeted Tissue Perfusion Versus Macrocirculatory-guided Standard Care in Patients With Septic Shock

Study hypothesis: Targeting at clinical tissue perfusion (in the TTP arm) will decrease the use and untoward effects of vasopressors, and result in more days alive in 30-days without vasopressor or inotropic support and without lactatemia, in comparison with standard clinical care with preference of macrocirculatory targets (MCG arm).

Intervention group - Targeted tissue perfusion (TTP) care:

Primary targets /registration period

• capillary refill time (CRT) / <3 sec/ every hour
• skin mottling / absent / every hour
• arterial lactate / <2.0 mmol/l/ per 2hr
• peripheral temperature/ warm /every hour
• urine output/ ≥0.5 mL/kg per hour/ every hour
• mean arterial pressure (MAP) 50-65 mmHg (minimum as a safety limit)/ continuous

• if previous hypertension 65- 70 mmHg
• if oliguria 2-hour trial 75-80 mmHg (If diuresis better, continue 2hr and re-evaluate) Secondary target
• Continuous mixed venous saturation (SvO2) >65%, if available

Control group - Macrocirculatory targets guided (MCG) standard care Primary targets

• Mean arterial pressure (MAP) 65-75 mmHg /continuous

** if previous hypertension 75-80 mmHg

*** if oliguria < 0.3 ml/kg, 2-hour trial 85-90 mmHg (If diuresis better, continue 2hr and re-evaluate)

• Central venous pressure (CVP)/hourly, Adequate fluid therapy is indicated to restore clinical hypovolemia up to the recommended CVP-level of 8-12 mmHg, if needed
• Urine output ≥ 0.5 mL/kg/h/ hourly Secondary target
• Continuous SvO2 >65%, if available

Inclusion criteria

• Septic shock defined as

• Septic infection AND
• systemic mean blood pressure > 65 mmHg requiring any dose of vasopressors (norepinephrine, vasopressin) despite adequate fluid resuscitation (minimum of 20 ml/kg crystalloids) AND
• Elevated lactate ≥ 3.0 mmol/L with suspected hypoperfusion

Exclusion criteria

• aged less than 18 or over 80 years
• any other probable condition than sepsis affecting or expected to affect the central nervous system including post cardiac arrest
• present or suspected myocardial ischemia
• acute pulmonary embolism
• terminal illness and not considered for full intensive care support
• use of extra-corporeal membrane oxygenation (ECMO)
• known liver disease - Child-Pugh -Class B or C
• confirmed chronic kidney disease known on admission
• known to be pregnant or lactating
• more than 4 hours from fulfilled inclusion criteria to randomization
• another probable cause of hyperlactatemia
• patients transferred from another ICU
• patients with active haematological malignancy