Dose-response Study of Arginine Supplementation in Severe Sepsis

Arginine and Nitric Oxide (NO) Metabolism in Sepsis; Dose-response Study on the Effect of L-arginine Supplementation on NO Metabolism and Gastric Perfusion in Severe Septic Patients.

Pilot data in patients and data from pig studies indicate that arginine-NO metabolism is impaired in sepsis with changes in splanchnic metabolism and function, and reduced survival at low nitrate levels. Prolonged intravenous supplementation of L-arginine proved effective in pigs for increasing NO production, restoring gut function, and inhibiting an increase in pulmonary arterial pressure, without any deleterious systemic side effects. Prolonged intravenous L-arginine supplementation could therefore be useful in septic ICU patients.

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 (see appendix A; in Dutch).
• Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2 h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
• Systemic and pulmonary arterial catheters in place with continuous pressure monitoring.
• Patients in whom the clinician is prepared to provide full life support during the duration of the study, including a life expectance of > 24 h.

Exclusion Criteria:

• Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
• Corticosteroid use (prolonged intake of > 1mg/kg daily or intake of > 70 mg/day for 7 consecutive days within 1 month preceding the study)
• Liver cirrhosis
• Chronic pancreatitis
• Diabetes mellitus type I
• Metastases, haematological malignancies or chemotherapy
• Patients on dialysis (CVVH or other)