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.
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 8
- 主要终点
- Nitric oxide synthesis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
结局指标
主要结局
Nitric oxide synthesis
时间窗: 8 hours
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.
次要结局
- hemodynamics(8 hours)
- blood parameters(8 hours)
- gastric perfusion(8 hours)