The purpose of this study is to study the stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the plasma citrulline concentrations and the Arginine-NO metabolism, the microcirculation, the systemic hemodynamics, vascular permeability, and organ function and disease severity scores.

NO synthesis is compromised during sepsis through lack of arginine de novo synthesis and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-citrulline in septic patients will increase NO production without increased arginase activity and these effects will be studied on arginine-NO metabolism,improved organ function, vascular permeability and microcirculation.

Inclusion Criteria:

• Written informed consent from close relative
• Age > 18 years
• Patient meets the general criteria for severe sepsis or septic shock, diagnosed less than 48 h prior to study inclusion.
• Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
• Systemic arterial catheter in place with continuous pressure monitoring.
• Patients in whom the clinician is prepared to provide full life support during the duration of the study

Exclusion Criteria:

• Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
• Prolonged or high dose corticosteroid use
• Liver cirrhosis
• Chronic pancreatitis
• Insulin-dependent diabetes mellitus
• Metastases, haematological malignancies or chemotherapy
• Patients on dialysis (CVVH or other)
• Pre-existent renal failure (on dialysis)