targeted tissue perfusion versus macrocirculatory-guided standard care in patients with septic shock

Conditions: Shock; Septic; Critical Illness

Summary: background: the recommended monitoring and target levels in septic shock (ssc guidelines 2012) including mean arterial pressure (map) target are not based on robust clinical data. objective: to test, if in patients with septic shock, tissue perfusion guided (tpg) treatment strategy leads to a faster resolution of hypoperfusion than the macrocirculatory target guided standard care. design: a prospective phase ii two-parallel-group open-label randomized controlled trial interventions: 1. intervention group- targeted tissue perfusion guided (ttp) - care. 2. control group - macrocirculatory - guided (mcg) care. randomization: 1:1 stratified according to the site and presence or absence of known hypertension. trial size: 200 randomised patients in 4 icus.

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 1. capillary refill time (crt) / \<3 sec/ every hour 2. skin mottling / absent / every hour 3. arterial lactate / \<2.0 mmol/l/ per 2hr 4. peripheral temperature/ warm /every hour 5. urine output/ ≥0.5 ml/kg per hour/ every hour 6. 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 7. continuous mixed venous saturation (svo2) \>65%, if available control group - macrocirculatory targets guided (mcg) standard care primary targets 1. 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) 2. 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 3. urine output ≥ 0.5 ml/kg/h/ hourly secondary target 4. continuous svo2 \>65%, if available

Eligibility criteria:
inclusion criteria: * septic shock defined as 1. septic infection and 2. systemic mean blood pressure \> 65 mmhg requiring any dose of vasopressors (norepinephrine, vasopressin) despite adequate fluid resuscitation (minimum of 20 ml/kg crystalloids) and 3. 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

Keywords: septic shock tissue perfusion macrocirculatory mean arterial pressure vasopressor use days alive free of organ support