血管活性药物对脓毒血症微循环障碍的影响

1、会计学1血管活性药物对脓毒血症微循环障碍的血管活性药物对脓毒血症微循环障碍的影响影响 微循环的构成，见下图微循环的构成，见下图H H E E I I 微循环的构成，见下图微循环的构成，见下图H H E E I I【Proc Natl Acad Sci U S A 2000;97:97539758】【Baker CH, Sutton ET. (1993). Arteriolar endothelium-dependent vasodilation occurs during endotoxin. shock. Am J Physiol 264:H1118H1123.】 Aird WC.Blood

2、 2003; 101:376577微循环障碍表现形式：时间微循环障碍表现形式：时间-空间上的异常空间上的异常0.48g/kg/min 0.65g/kg/min 0.74g/kg/min 【Arnaldo Dubin.Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Critical Care 2009, 13:R92 (doi:10.1186/cc7922)】 收缩血管的活性物质收缩血管的活性物质毛细血

3、管流量指数毛细血管流量指数【The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis. Anesthesia and analgesia 2010 110:2 (547-554) 】【The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patient

4、s with septic shock. Critical care medicine 2009 37:6 (1961-1966) 】。SB:125ml/h逐渐增加至逐渐增加至500ml/h【The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis. Anesthesia and analgesia 2010 110:2 (547-554) 】【The effects of vasoact

5、ive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis. Anesthesia and analgesia 2010 110:2 (547-554) 】【Myburgh JA, Higgins A, Jovanovska A, et al., CAT Study investigators. A comparison of epinephrine and norepinephrine in critically ill patie

6、nts. Intensive Care Med 2008; 34:22262234.】 【The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis. Anesthesia and analgesia 2010 110:2 (547-554) 】【Torgersen C, et al. Comparing two different arginine vasopressin doses in

7、 advanced vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med. 2010;36:5765.】 【Torgersen C, et al. Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med. 2010;36:5765.】 【Ertmer

8、C. Current place of vasopressin analogues in the treatment of septic shock. Curr Infect Dis Rep 2008;10:362367.】【Ryckwaert F.Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: consequences on heart perfusion and performance. Crit Care Med 2009;37:876881. 】 缩血管物质的作用缩血管物质的

9、作用 提高提高MAP，储备毛细血管前灌注压力，储备毛细血管前灌注压力 降低体液积聚和逆转毛细血管渗漏降低体液积聚和逆转毛细血管渗漏 恢复毛细血管灌注恢复毛细血管灌注 负性作用负性作用皮肤、内脏阻力血管和微循环过度收缩皮肤、内脏阻力血管和微循环过度收缩心脏负性作用心脏负性作用【Lamontagne F, Meade M, Ondiveeran HK, et al. Nitric oxide donors in sepsis: a systematic review of clinical and in vivo preclinical data. Shock 2008;30:653659.】 【

10、Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: A double-blind randomized placebo controlled trial. Crit Care Med 2010; 38:93100.】 60天存活率也显著降低天存活率也显著降低P=0.08P=0.09NTG ,2mg 持续静推持续静推30分钟，然分钟，然后后23.5h持

11、续持续2mg/h。维持。维持MAP60mmHg【Parker JD, Farrell B, Fenton T, et al: Counter-regulatory responses to continuous and intermittent therapy with nitroglycerin. Circulation 1991; 84:23362345.】【Gori T, Daiber A, Di Stolfo G, et al: Nitroglycerin causes mitochondrial reactive oxygen species production: In vitro

12、 mechanistic insights. Can J Cardiol 2007; 23:990992】Nakajima Y, Baudry N, Duranteau J, et al. Effects of vasopressin, norepinephrine and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 2006; 34:17521757】【De Backer D. L-arginine and vasopressor agents: when antagonists have u

13、nexpected synergistic effects. Crit Care Med 2006; 34:18471849.】 受体兴奋剂受体兴奋剂多培沙明多培沙明 有很强有很强2-受体兴奋作用，受体兴奋作用， 1和和DA1、DA2较弱较弱显著扩张动脉血管，能增加心肌、肾脏、肝脏、骨骼肌的显著扩张动脉血管，能增加心肌、肾脏、肝脏、骨骼肌的血流量，降低心脏后负荷血流量，降低心脏后负荷心肌收缩力加强，心率加快，并有轻微排钠利尿作用；心肌收缩力加强，心率加快，并有轻微排钠利尿作用；0.5ug/kg/min开始应用开始应用Effects of Dopamine, Dobutamine, and Do

14、pexamine on Microcirculatory Blood Flow in the Gastrointestinal Tract during Sepsis and Anesthesia. Anesthesiology 2004; 100:118897【Effects of penehyclidine hydrochloride on the splanchnic perfusion of patients with septic shock. Chinese Critical Care Medicine 2008 20:3 (183-186) 】【Anisodamine count

15、eracts lipopolysaccharide-induced tissue factor and plasminogen activator inhibitor-1 expression in human endothelial cells: Contribution of the NF-B pathway. J Vas Res 2001 38:1 (13-19) 抗氧化剂：抗氧化剂：Vit C恢复依赖内皮的血管节律恢复依赖内皮的血管节律(舒张和收舒张和收缩缩)血管舒张作用血管舒张作用(NO)G抑制抑制iNOS活性增加活性增加eNOS的活性的活性G抑制内皮细胞内的抑制内皮细胞内的NADP

16、H酶活性阻酶活性阻止止NO氧化氧化【Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism. Crit Care Med 2008; 36:23552362】【 Delayed asco

17、rbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle. Crit Care Med 2005; 33:18231828.】同时收缩与扩张血管的活性物质同时收缩与扩张血管的活性物质【Lehr1 HA. Eur J Med Res 2006;11: 516-526】【Nualart FJ. J Biol Chem 2003; 278:10128101331】15例感染性休克病人例感染性休克病人(肺部感染和腹腔感染肺部感染和腹腔感染)去甲肾去甲肾0.

18、3g/kg/min增加氧摄取的活性物质增加氧摄取的活性物质 降低降低PMN与内皮的粘附与内皮的粘附多巴酚丁胺多巴酚丁胺主要兴奋主要兴奋1、对、对2及及受体作用相对弱受体作用相对弱增加心脏指数和全身血流增加心脏指数和全身血流抑制抑制PMN粘附到血管内皮或促进内皮完整性粘附到血管内皮或促进内皮完整性增加微循环血流增加微循环血流 【Secchi A, Ortanderl JM, Schmidt W, et al. Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimenta

19、l endotoxemia: an intravital microscopic study in the rat. Crit Care Med 2001; 29:597600.】 【Birnbaum J, Klotz E, Spies CD, et al. Effects of dopexamine on the intestinal microvascular blood flow and leukocyte activation in a sepsis model in rats. Crit Care 2006; 10:R117.】 Crit Care Med. 2005;33(8):1

20、823-8.Human recombinant activated protein C for severe sepsis.Cochrane database of systematic reviews (Online) 2011; 4 (CD004388) Early intravenous unfractionated heparin and mortality in septic shock. Crit Care Med 2008;36(11):2973-2979Thanks微循环障碍表现形式：时间微循环障碍表现形式：时间-空间上的异常空间上的异常0.48g/kg/min 0.65g/k

21、g/min 0.74g/kg/min 【Arnaldo Dubin.Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Critical Care 2009, 13:R92 (doi:10.1186/cc7922)】 收缩血管的活性物质收缩血管的活性物质【The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis. Anesthesia and analgesia 2010 110:2 (547-554) 】【Torgersen C, et al. Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial. I