Dose-response Study of Arginine Supplementation in Severe Sepsis
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||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.|
- Nitric oxide synthesis [ Time Frame: 8 hours ] [ Designated as safety issue: No ]Nitric oxide synthesis at step-wise increasing doses of L-arginine infusion. Following a 2h baseline measurements, 3 stepwise increasing arginine doses each provided for 2h will be tested for the effect on NO synthesis.
- hemodynamics [ Time Frame: 8 hours ] [ Designated as safety issue: Yes ]Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)
- blood parameters [ Time Frame: 8 hours ] [ Designated as safety issue: No ]Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism
- gastric perfusion [ Time Frame: 8 hours ] [ Designated as safety issue: No ]Regional (gastric) CO2 production measured with tonometry (PrCO2)
|Study Start Date:||October 2003|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2004 (Final data collection date for primary outcome measure)|
Dietary Supplement: L-arginine
Other Name: L-arginine-HCl
Please refer to this study by its ClinicalTrials.gov identifier: NCT01775020
|Principal Investigator:||Nicolaas E Deutz, MD PhD|