Lemaire Lucienne C, de Kruif Martijn D, Giebelen Ida A, Levi Marcel, van der Poll Tom, Heesen Michael
Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Crit Care Med. 2006 May;34(5):1365-71. doi: 10.1097/01.CCM.0000215514.96888.E3.
Catecholamines have anti-inflammatory and anticoagulant properties. Dobutamine is a synthetic catecholamine frequently used in patients with septic myocardial dysfunction. The objective was to determine whether a continuous infusion of dobutamine exerts immunomodulatory effects in healthy volunteers challenged with endotoxin.
Prospective, open-label study.
Clinical research unit of a university hospital.
Sixteen male healthy volunteers.
Volunteers received a constant infusion with dobutamine (10 microg.kg.min, n = 8) or physiologic saline (n = 8). All participants were challenged with a bolus injection of endotoxin prepared from Escherichia coli (4 ng/kg). Dobutamine infusion was commenced 1 hr before endotoxin challenge and was continued until 3 hrs thereafter.
Dobutamine infusion was associated with an increase in mean arterial blood pressure (peak 122 +/- 5 mm Hg) and heart rate (peak 84 +/- 4 beats/min, both p < .05 vs. saline). Endotoxin injection induced the systemic release of cytokines (tumor necrosis factor-alpha, interleukins-6, -8, and -10) and secretory phospholipase A2, endothelial cell activation (increase in the plasma levels of soluble E-selectin and von Willebrand factor), activation of coagulation (increased plasma levels of soluble tissue factor, F1 + 2 prothrombin fragment, and thrombin-antithrombin complexes), and activation with subsequent inhibition of fibrinolysis (increased plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin-alpha2-antiplasmin complexes). None of these responses were influenced by dobutamine.
Dobutamine, infused in a clinically relevant dose, does not influence inflammatory and coagulant pathways during human endotoxemia.
儿茶酚胺具有抗炎和抗凝特性。多巴酚丁胺是一种合成儿茶酚胺，常用于脓毒症性心肌功能障碍患者。目的是确定持续输注多巴酚丁胺对内毒素攻击的健康志愿者是否具有免疫调节作用。
前瞻性、开放标签研究。
大学医院临床研究单位。
16名男性健康志愿者。
志愿者接受多巴酚丁胺持续输注（10微克·千克·分钟，n = 8）或生理盐水（n = 8）。所有参与者均接受一次由大肠杆菌制备的内毒素静脉推注（4纳克/千克）。多巴酚丁胺输注在内毒素攻击前1小时开始，并持续至攻击后3小时。
多巴酚丁胺输注与平均动脉血压升高（峰值122±5毫米汞柱）和心率加快（峰值84±4次/分钟，与生理盐水组相比，两者p均<0.05）相关。内毒素注射诱导细胞因子（肿瘤坏死因子-α、白细胞介素-6、-8和-10）和分泌型磷脂酶A2的全身释放、内皮细胞活化（可溶性E选择素和血管性血友病因子血浆水平升高）、凝血活化（可溶性组织因子、F1 + 2凝血酶原片段和凝血酶-抗凝血酶复合物血浆水平升高）以及随后纤维蛋白溶解的激活和抑制（组织型纤溶酶原激活物、纤溶酶原激活物抑制剂I型和纤溶酶-α2-抗纤溶酶复合物血浆浓度升高）。这些反应均未受多巴酚丁胺影响。
以临床相关剂量输注的多巴酚丁胺在人类内毒素血症期间不影响炎症和凝血途径。
