NO synthesis is compromised during sepsis through lack of L-arginine and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-arginine in septic patients can replete L-arginine deficiency and will improve…
ID
Bron
Verkorte titel
Aandoening
Severe sepsis or septic shock ICU patients.
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Microcirculation.
Achtergrond van het onderzoek
Background:
Sepsis is a severe clinical problem with a high mortality rate, which is caused by a severe inflammatory response to an infection. Nitric oxide (NO), which is produced by the body from the amino acid L-arginine, has an important role in the pathophysiology of the disease. NO has an important role as a vasodilator and therefore is important for vascular perfusion. In a previous study we observed that plasma arginine levels were lowered in sepsis. Moreover, L-arginine supplementation approved to be beneficial in a pig model of sepsis. This has led us to the hypothesis that sepsis is an arginine deficiency state (Luiking, CCM 2004;32:2135-45) and that patients could benefit from L-arginine administration in order to enhance NO production and improve organ perfusion and function.
Aim: The aim of our present study is to study the effects of L-arginine administration on NO production and microcirculation in a placebo controlled, double blind randomized study design.
This information adds to our understanding of the mechanism by which L-arginine supplementation may benefit septic patients. This can be a base for larger trials on arginine supplementation in the future.
Doel van het onderzoek
NO synthesis is compromised during sepsis through lack of L-arginine and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-arginine in septic patients can replete L-arginine deficiency and will improve microcirculation, vascular permeability, and organ function.
Onderzoeksopzet
N/A
Onderzoeksproduct en/of interventie
1. 3-days intravenous L-arginine infusion;
2. 3-days intravenous L-alalanine (placebo) infusion.
Publiek
PO Box 7005
Y.C. Luiking
Wageningen 6700 CA
The Netherlands
+31 (0)317 467800
Yvette.Luiking@danone.com
Wetenschappelijk
PO Box 7005
Y.C. Luiking
Wageningen 6700 CA
The Netherlands
+31 (0)317 467800
Yvette.Luiking@danone.com
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Written informed consent from close relative;
2. Age > 18 years;
3. Patient meets the general criteria for severe sepsis or septic shock (International published sepsis definitions), diagnosed less than 48 h prior to study inclusion;
4. 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;
5. Systemic arterial catheter in place with continuous pressure monitoring;
6. Patients in whom the clinician is prepared to provide full life support during the duration of the study.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury, severe blood loss etc.);
2. Prolonged or high dose corticosteroid use;
3. Liver cirrhosis;
4. Chronic pancreatitis;
5. Insulin-dependent diabetes mellitus;
6. Metastases, haematological, malignancies or chemotherapy;
7. Patients on dialysis (CVVH or other);
8. Pre-existent urea cycle disorders or renal failure.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL383 |
| NTR-old | NTR423 |
| Ander register | : MEC 04-136 |
| ISRCTN | ISRCTN56258935 |
Samenvatting resultaten
2. Bruins, M. J., Soeters, P. B., Lamers, W. H. & Deutz, N. E. (2002) L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia. Am J Clin Nutr 75: 1031-1044.<br>
3. Bruins, M. J., Luiking, Y. C., Soeters, P. B., Lamers, W. H., Akkermans, L. M. & Deutz, N. E. (2004) Effects of long-term intravenous and intragastric L-arginine intervention on jejunal motility and visceral nitric oxide production in the hyperdynamic compensated endotoxaemic pig. Neurogastroenterol Motil 16: 819-828.