This study will describe the change of mitochondrial oxygen tension (mitoPO2) compared to traditional parameters of oxygenation and oxygen balance in the first 24 hours of septic patients admitted to the intensive care unit of an academic hospital. The mitoPO2 will be measured on prespecified measurement moments in the ICU. With each measurement moment, arterial and central venous blood gasses will be taken too.

Evidence is increasing that there is no clear parameter for tissue oxygenation in critically ill septic patients to guide resuscitation. New studies have shown the potential of protoporphyrin IX-triple state lifetime technique to measure mitochondrial oxygenation tension (mitoPO2) in vivo, which possibly is an early indicator of oxygen disbalance in the cell and therefore a physiological trigger for fluid therapy.

Objectives: 1. To describe mitoPO2 measurements in patients with sepsis who are about to receive fluid therapy 2. To describe the effects of fluid therapy and the associated change in mitoPO2 and change in other physiologic measures of tissue oxygenation and oxygen balance 3.To describe the association between mitoPO2 and vital organ (dis)functions and change of SOFA (Sequential organ failure assessment) score after 24hrs 5. To describe the microcirculatory, cellular and mitochondrial function during the first 24 hours of septic patients.

Study population: critically ill patients with sepsis which are admitted to the intensive care unit through the emergency department or hospital ward and in whom fluid therapy (crystalloid, albumin and red cell transfusion) is planned.

Main study endpoints

Primary endpoint: Change in mitoPO2 after fluid therapy. This will be compared to traditional parameters used to measure oxygenation and oxygen balance

Secondary endpoints:

• Association of mitoPO2 trend with separate (ischemic) organ (dis)function. The SOFA score after 24 hours will also be assessed.
• Safety of mitoPO2 measurements in critically ill septic patients.
• Description of the association of sepsis with microcirculatory function, cellular function and mitochondrial function.
• Description of the association between mitoPO2 change and clinical outcomes , like length of stay(both ICU and in-hospital) and mortality (both ICU and in-hospital).

Inclusion Criteria:

• Age of patient is at least 18 years
• Patients diagnosed with sepsis in the emergency department or hospital ward
• Patients are admitted to the ICU via the hospital ward or emergency department
• Informed consent is given either by the patient or if the patient is too ill to give informed consent, by his or her legal representative.
• Patients have an arterial catheter in situ, since blood samples will be taken for the study. Most patients admitted to the ICU have an arterial catheter in place since it is part of standard care.

Exclusion Criteria:

• Patients younger than 18 years
• Patients with sepsis discharged after emergency department visit
• Patients admitted to a hospital ward other than the ICU after emergency department visit
• Patients who cannot give informed consent themselves and without a legal representative will be excluded since no informed consent can be obtained
• Patients known with porphyria and/or photodermatosis will be excluded, since the risk of phototoxicity
• Patients with hypersensitivity to the active substance or to the plaster material of ALA (5-aminolevulinic acid)
• Pregnant or breast feeding women since there is no adequate data form the use of ALA in pregnant or breast feeding women
• Insufficient comprehensibility of the Dutch language

Patients in the emergency department or hospital ward admitted to the Intensive Care Unit of the Leiden University Medical Center with (the suspicion of) sepsis will be the source population of the study. Leiden Univesity Medical Center is an academic hospital.

Septic patients are identified as specified in the Dutch protocol of sepsis identification and management in the emergency department. It consists of having clinical suspicion of sepsis in combination with the at least 2 of the following symptoms: ≥ 20 breaths per minute, heart frequency > 90 beats per minute, leukocytes > 12x109 or leukocytes < 4x10^9, and/or temperature > 38 °C or <36 °C