Prolonged inhibition of nitric oxide synthesis in severe septic shock: A clinical study
Prolonged inhibition of nitric oxide synthesis in severe septic shock: A clinical study
复制标题
DOI：
10.1097/00003246-199804000-00012
复制
发表时间：
1998-04-01
影响因子：
8.8
通讯作者：
Bruining, HA
中科院分区：
文献类型：
--
作者：
Avontuur, JAM;Nolthenius, RPT;Bruining, HA
目的：一氧化氮合成抑制剂在脓毒症低血压的治疗中具有重要价值。然而，早期的临床报告仅描述了这些一氧化氮抑制剂的初始作用。本研究的目的是检查长期抑制一氧化氮合成的N-ω-硝基-L-精氨酸甲酯（L-NAME）在严重脓毒性休克患者中的作用。设计：前瞻性，非随机，临床研究。设置：大学医院的内科-外科重症监护室。患者：连续11名患者持续高动力脓毒症棚屋，对液体复苏和血管加压剂治疗无反应。在开始连续静脉输注1 mg/kg/hr的L-NAME（一氧化氮合成抑制剂）12小时之前、期间和之后，对血液动力学、血液学和生化变量进行测量。连续输注L-NAME导致平均动脉压从65 +/- 3（SEM）直接升高至93 +/- 4 mm Hg，全身血管阻力从426 +/- 4 mm Hg升高至426 +/-4 mm Hg。肺动脉压在1小时时从31 +/- 2增加到最大值36 +/- 2 mm Hg，肺血管阻力在3小时时从146 +/- 13增加到最大值210 +/- 23 dyne.sec/cm（5），除了这些变化，心输出量从10.8 +/- 0.8 L/min降至8.7 +/- 0.7 L/min，氧输送从1600 +/- 160 mL/min降至1370 +/- 130 mL/min（所有变化均为p.05）。L-NAME输注可改善动脉氧合，并可减少儿茶酚胺的用量（均P<0.05）。虽然观察到持续的血液动力学效应，但L-NAME在给药的早期阶段最有效，并且L-NAME对血压和血管阻力的影响在L-NAME的连续输注过程中趋于减弱。11例患者中有7例最终死亡，生存时间为2 ~ 34 day.Conclusions：一氧化氮在人脓毒症期间的心血管紊乱中发挥作用。在严重脓毒症休克患者中，在L-NAME长期抑制一氧化氮合成期间，血压和血管阻力升高的值持续存在，尽管血流动力学变化在L-NAME输注的早期阶段最为显着。这些患者的高死亡率可能表明L-NAME对结局的影响有限。
Objectives: Inhibitors of nitric oxide synthesis have been suggested to be of value in the treatment of hypotension during sepsis. However, earlier clinical reports only describe the initial effects of these nitric oxide inhibitors. This study was designed to examine the effects of the prolonged inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine methyl ester (L-NAME) in patients with severe septic shock.Design: Prospective, nonrandomized, clinical study.Setting: Medical-surgical intensive care unit in a university hospital.Patients: Eleven consecutive patients with ongoing hyperdynamic septic shack that was unresponsive to fluid resuscitation and vasopressor therapy.Interventions: Measurements of hemodynamic, hematologic, and biochemical variables were made before, during, and after the start of a continuous intravenous infusion of 1 mg/kg/hr of L-NAME, an inhibitor of nitric oxide synthesis, for a period of 12 hrs.Measurements and Main Results: Continuous infusion of L-NAME resulted in a direct Increase in mean arterial pressure from 65 +/- 3 (SEM) to 93 +/- 4 mm Hg and an increase in systemic vascular resistance from 426 +/- 54 to 700 +/- 75 dyne.sec/cm(5), reaching a maximum at 0.5 hr. Pulmonary arterial pressure was in creased from 31 +/- 2 to a maximum of 36 +/- 2 mm Hg at 1 hr, and pulmonary vascular resistance increased from 146 +/- 13 to a maximum of 210 +/- 23 dyne.sec/cm(5) at 3 hrs, Paralleling these changes, cardiac output decreased from 10.8 +/- 0.8 to 8.7 +/- 0.7 L/min and oxygen delivery decreased from 1600 +/- 160 to 1370 +/- 130 mL/min (for all changes p.05). Arteria[ oxygenation was improved during L-NAME infusion, and the dosage of catecholamines could be reduced (both p< .05). Although sustained hemodynamic effects were seen, L-NAME was most effective during the early stages of administration, and the effect of L-NAME on blood pressure and vascular resistance tended to diminish throughout the continuous infusion of L-NAME. Seven of 11 patients ultimately died, with survival time ranging from 2 to 34 days.Conclusions: Nitric oxide appears to play a role in cardiovascular derangements during human sepsis. The increased blood pressure and vascular resistance Values are sustained during prolonged inhibition of nitric oxide synthesis with L-NAME in patients with severe septic shock, although the hemodynamic changes are most significant in the early stages of L-NAME infusion. The high mortality rate in these patients may suggest that L-NAME has only limited effects on outcome.