• Impaired peripheral perfusion is related to worse outcome in critically ill patients. Although this is known, these parameters have never been used as target for hemodynamic therapy.
• We hypothesize that targeting of fluid administration on parameters of peripheral perfusion might prevent excessive fluid administration, leading to less formation of tissue edema, less respiratory dysfunction and shorter duration of mechanical ventilation in critically ill patients.

Rationale: Currently, fluid administration of critically ill patients is aimed at optimizing conventional hemodynamic parameters such as stroke volume and cardiac output. Fluid is infused repeatedly until patients become "non-responsive", i.e. cardiac output does not increase anymore. However, the ultimate goal of hemodynamic therapy should be to improve peripheral (i.e. tissue) perfusion. Recently we have shown that 1) increasing stroke volume does not always have an effect on peripheral perfusion and 2) that peripheral perfusion is not impaired when stroke volume can still be increased with fluid infusion. Furthermore, repeated administration of fluid in order to reach a maximum cardiac output can lead to an enormous accumulation of fluid in the patient. This leads to formation of lung edema and respiratory dysfunction and is associated with prolonged mechanical ventilation and ICU-stay. Recently, techniques have been developed which allow bedside assessment of peripheral perfusion. Although impaired peripheral perfusion was related to worse outcome, these parameters have never been used as target for hemodynamic therapy.

Objective: To study whether peripheral perfusion targeted fluid management (PPTFM) leads to less fluid administration, improved respiratory function and shorter mechanical ventilation.

Study design: The study is a pilot study and is designed as a randomized controlled trial. The study will be conducted as a single-center study at the Intensive Care of the Erasmus Medical Center.

Study population: We aim to include 40 adult patients who are admitted to the Intensive Care with hemodynamic instability (defined as mean arterial pressure < 65 mmHg and an arterial lactate concentration > 3.0 mmol/l) due to severe sepsis and septic shock.

Intervention: In the intervention group fluid management is targeted on peripheral perfusion parameters while in the control group fluid is administered in order to optimize cardiac output.

Main study parameters/endpoints: The main study endpoints are daily fluid balance and duration of mechanical ventilation.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is a possible risk that in the treatment group the patients will remain hypovolemic. To ensure that this will not occur, fluids will be administrated in this group, irrespective of peripheral perfusion parameters, until cardiac index is 2,5 L/min/m2. Assessment of peripheral perfusion is performed with non-invasive optical techniques that impose no burden to the patient.

Inclusion Criteria:

• All adult patients (>18 years) admitted to the intensive care with 1) hemodynamic instability due to severe sepsis, and 2) a mean arterial pressure < 65 mmHg and 3) an arterial lactate concentration > 3.0 mmol/L will be considered for participation

Exclusion Criteria:

• moribund.
• severe coagulation disorder (contraindication for central venous catheter placement).
• severe peripheral vascular disease (interfering with peripheral perfusion measurement).