Kalil Andre C, Sevransky Jonathan E, Myers Daniela E, Esposito Claire, Vandivier R William, Eichacker Peter, Susla Greg M, Solomon Steven B, Csako Gyorgy, Costello Rene, Sittler Kelly J, Banks Steve, Natanson Charles, Danner Robert L
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Crit Care Med. 2006 Nov;34(11):2719-28. doi: 10.1097/01.CCM.0000242757.26245.03.
L-arginine supplementation in sepsis is controversial. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism.
Randomized, placebo-controlled, and double-blinded (investigators, veterinarians, and pharmacists).
Laboratory.
Purpose-bred, 1- to 2-yr-old, 10- to 12-kg beagles.
The effects of parenteral L-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis. Two doses were studied that delivered approximately 1.5-fold (10 mg x kg(-1) x hr(-1)) and 15-fold (100 mg x kg(-1) x hr(-1)) the L-arginine dose typically administered with standard total parenteral nutrition. Animals in the low- and high-dose L-arginine arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg x kg(-1) x hr(-1)) as an antioxidant to prevent peroxynitrite formation.
The main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Both doses of L-arginine similarly increased mortality (p = .02), and worsened shock (p = .001 for reduced mean arterial pressure). These effects were associated with significant increases in plasma arginine (p = .0013) and ornithine (p = .0021). In addition, serum nitrate/nitrite (p = .02), liver enzymes (p = .08), and blood urea nitrogen/creatinine ratios (p = .001) rose, whereas arterial pH (p = .001) and bicarbonate levels (p = .001) fell. N-acetylcysteine did not significantly decrease any of the harmful effects of L-arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals with septic shock.
These findings suggest that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.
脓毒症患者补充L-精氨酸存在争议。脓毒性休克被认为是L-精氨酸缺乏状态，或者是由L-精氨酸代谢终产物一氧化氮过量引起的综合征。
随机、安慰剂对照、双盲（研究者、兽医和药剂师）。
实验室。
专门培育的1至2岁、体重10至12千克的比格犬。
在特征明确的大肠杆菌性腹膜炎犬模型中，比较单独肠外给予L-精氨酸或L-精氨酸与N-乙酰半胱氨酸联合应用与单独给予赋形剂的效果。研究了两个剂量，分别约为标准全肠外营养中通常给予的L-精氨酸剂量的1.5倍（10毫克·千克⁻¹·小时⁻¹）和15倍（100毫克·千克⁻¹·小时⁻¹）。低剂量和高剂量L-精氨酸组的动物进一步随机分组，分别单独接受赋形剂或N-乙酰半胱氨酸（20毫克·千克⁻¹·小时⁻¹）作为抗氧化剂以防止过氧亚硝酸盐形成。
主要测量指标包括血流动力学、血浆精氨酸和鸟氨酸、血清硝酸盐/亚硝酸盐、器官损伤的实验室检查以及生存率。两个剂量的L-精氨酸均同样增加死亡率（p = 0.02），并加重休克（平均动脉压降低，p = 0.001）。这些效应与血浆精氨酸（p = 0.0013）和鸟氨酸（p = 0.0021）显著增加相关。此外，血清硝酸盐/亚硝酸盐（p = 0.02）、肝酶（p = 0.08）以及血尿素氮/肌酐比值（p = 0.001）升高，而动脉pH值（p = 0.001）和碳酸氢盐水平（p = 0.001）降低。N-乙酰半胱氨酸并未显著降低L-精氨酸的任何有害作用。因此，肠外给予L-精氨酸单一疗法对脓毒性休克动物具有明显危害。
这些发现表明，对于患有脓毒性休克的重症患者，应避免给予高于标准饮食剂量的肠外补充L-精氨酸。
