休克及血管活性药物的使用

休克及血管活性药物的使用王仟陆,什么是休克-什么时候存在休克,血压？多少血压是休克？BP低于90/60mmHg?高血压病人血压下降绝对值大于40mmHg或者超过基础的30-40%？是不是就是以血压为参考?-够简单便捷,血压仅仅是一方面，休克的综合评判（生化+临床）,1、神志改变2、四肢冰凉、末梢发绀3、少尿、无尿、尿比重增高4、四肢花斑（休克严重程度一致）5、乳酸升高（2mmol/L）6、毛细血管充盈时间延迟(2s)7、心率快、口渴8、碱剩余消耗-酸中毒9.中心静脉或者混合静脉血氧饱和度异常10、动静脉血二氧化碳分压差（大于5-6mmHg）,休克核心是-细胞缺氧,氧输送不足血色素和氧分压通常不会影响心输出量是决定因素（尤其是非分布性休克）-灌注不良细胞氧利用障碍在分布性休克（高动力状态）的重要机制氧供与氧耗之间的平衡,Delivery DO2: DO2 = CO x Hbx1.34xSaO2,休克的定义,A clinical state of acute circulatory failure with inadequate oxygen utilization and/or delivery by the cells resulting in cellular dysoxia/hypoxiaIntensive Care Med 2014;40:1795,感染性休克定义,Severe Sepsis and Septic Shock: A suspected infection With =2 of the SIRS criteria Along with a Lactate =4 mmol/L or hypotension (SBP90, MAP65) after initial fluid resuscitationThis was the definition used in the EGDT Trial PMID 11794169, the ProCESS Trial PMID 24635773, the Arise Trial PMID 25272316, and the ProMISE Trial PMID 25776532.,休克的分类-四类,休克到了晚期往往是混合因素休克早期比较单纯,休克的分类,休克本质,组织器官灌注不良决定器官灌注的两个要素-流量（心输出量）-基础-灌注压（与平均动脉压相关最大，心脏是舒张期灌注故舒张压重要） 心输出量急剧下降多会引起血压下降,MAP = CO x SVR,心率,每搏输出量,心肌收缩力,左心前、后负荷,平台期以前可以通过补液增加CO,补液300-500ml后可以使CO提升12-15%即有容量反应性-即处于曲线的反应期,动静脉血二氧化碳分压差正常值小于6mmHg反应流量灌注正常-即心输出量正常-心功能正常或者处于心功能曲线平台期以前状态的病人如果异常可以补液增加CO-心功能异常以及处于心功能曲线平台期及以后的病人不能补液只能强心或者心脏辅助或者降低氧耗,乳酸,乳酸在休克的诊断及预后判断、治疗监测中意义重要熟悉引起乳酸升高的常见因素对于疾病的分析和把握至关重要乳酸清除率休克监测治疗目标（2-4h乳酸清除率大于10-20%）,CVP,实际上反应右房的压力受许多因素影响右心功能、胸内压、腹内压、呼吸机PEEP及潮气量改变、胸水和腹水，心脏瓣膜病，左心功能，心包疾病、血管内容量等不论是CVP的绝对值还是变化值均不能反应患者的容量反应性-对液体复苏的反应,CVP绝对值与容量反应性,Osman D, et al. Crit Care Med. 2007;35(1):64-68.,150 volume challenges; sepsis,CVP的变化值与心输出变化的关系,CVP的意义何在,不在于它对于容量反应性的判断50%的准确性（是与不是本来就是各占一半）但临床上仍有重要的意义维持正常灌注的最低CVP值（静脉回流量最大同时心脏前负荷最低-做功最小）,血管活性药物,分布性休克时什么时候用？先补液还是先血管活性药物升压？,休克发生后的头6h每延迟1h使用去甲肾死亡率增加5.3%休克发生后2h内使用去甲肾升压患者28天死亡率显著低于2h后使用的患者回顾性研究,死亡率最低的患者为休克发生后1-6h内使用去甲肾的病人在休克发生后1h内输入1L液体的患者死亡率减低提示低血压的发生与死亡率相关回顾性研究Crit Care Med. 2014 Oct;42(10):2158-68.,为什么？,分布性休克时存在高动力状态，CO正常甚至增加，主要是血管外周阻力下降，通过补液增加血压会使心脏做功明显增加补液会导致灌注压达标时间的延长-与器官功能（尤其是肾衰竭）及死亡率相关去甲可以增加前负荷（使静脉血管床收缩达到自体输液的作用）,正常时,感染性休克发生时,扩容补液后,使用去甲后,目标血压多少合适,保证关键器官的灌注压-脑和肾对灌注压力依赖程度高 MAP of 50mmHg in non-vasculopath dogs for the brain? Brain Trauma Foundation (BTF) guidelines support a target CPP of 50-70 mmHg in patients with severe Traumatic Brain Injury MAP of 65 mmHgfor the heart? (Dunser et al. think it is 45-50mmHg for the heart) 心脏灌注压为冠脉压力与室腔内压力差-所以舒张压绝对心肌供血-心脏是循环核心，保证心脏灌注重中之重 MAP 65-75mmHg for the Kidneys？ 中心静脉压以及腹内压均可影响肾脏灌注压，MAP大于75mmHg后肾脏灌注并没有明显改善,需考虑基础血压状况心脏灌注MAP要求低（30-50mmHg即可），但是有高血压的病人尤其是左室肥厚的患者需要的血压要明显增高达70mmHg肾脏在MAP 65mmHg以上时才有灌注并逐渐增加，大于75mmHg增加不显著，有高血压基础的血压要求增加,升压目标65-70mmHg与80-85mmHg对比,血管活性药物-去甲是否可以外周使用,1、置管延迟去甲的使用2、低血压的发生时间与肾功能不全及死亡率相关3、越早使用去甲预后越好4、限分布性休克尤其感染性休克5、CVP监测的无用以及中心静脉的并发症6、目前的研究显示可以外周短期使用去甲,Safety of peripheral intravenous administration of vasoactive medication,730例病人使用外周血管活性药物，67.7%为去甲，最快达0.7ug/kg/min,平均外周输注时间达49+-22h外渗的发生只有2%（19例），且不严重可以使用硝酸甘油+酚妥拉明处理最终有13%（95例）病人仍需要中心静脉置入,J Hosp Med. 2015 Sep;10(9):581-5.,外周静脉输入血管活性药物,尽量短时间（小于72h）低速度（0.7ug/kg/min，休克不严重的患者，作为过度措施）大血管（超声示静脉直径大于4mm，选择腘窝及肘窝以上血管）输入侧不能测血压，有严格的观察和处置流程不要使用手、足及远端血管，肘窝尽也量不用如使用小于4h,去甲是否加重肾功能不全及少尿,多巴胺存在多巴能作用导致免疫抑制去甲有轻度beta兴奋作用去氧肾上腺素没有beta兴奋作用,去甲肾和多巴胺的对比,Vasopressors should be begun initially to target a mean arterial pressure of 65 mm Hg (Grade 1C).Norepinephrine (Levophed) should be provided as the first-line vasopressor (Grade 1B).Epinephrine is considered the next-line agent for septic shock after norepinephrine in the Surviving Sepsis Guidelines. When norepinephrine is insufficient to maintain MAP 65 mm Hg, epinephrine should be added to or substituted for norepinephrine (Grade 2B).-升高乳酸作用,血管加压素,Vasopressin at 0.03 units/minute is appropriate to use with norephinephrine, either to improve perfusion (increase MAP) or to reduce the required dose of norepinephrine (ungraded recommendation).Vasopressin is not recommended for use as a single vasopressor for septic shock (ungraded recommendation).Vasopressin doses higher than 0.03 - 0.04 units/min are recommended to be reserved only for dire situations of septic shock refractory to standard doses of multiple vasopressors (ungraded recommendation).,多巴胺,Dopamine is suggested to not be used as an alternative to norepinephrine in septic shock, except in highly selected patients such as those with inappropriately low heart rates (absolute or relative bradycardia) who are at low risk for tachyarrhythmias (Grade 2C). Dopamine is recommended to not be used in low doses in a so-called renal-protective strategy (Grade 1A).,去氧肾上腺素,Phenylephrine is recommended to not be used for septic shock, except when 1) septic shock persists despite the use of 2 or more inotrope/vasopressor agents along with low-dose vasopressin; 2) cardiac output is known to be high, or 3) norepinephrine is considered to have already caused serious arrhythmias (Grade 1C).An arterial catheter for hemodynamic monitoring should be placed as soon as practical, if resources are available, for all patients requiring vasopressors (ungraded recommendation).,多巴酚丁胺,Dobutamine should be tried for patients in septic shock who have low cardiac output with high filling pressures while on vasopressors, or who have persistent evidence of hypoperfusion after attaining an adequate mean arterial pressure and intravascular volume (with or without vasopressors) (Grade 1C).,多巴酚丁胺,A dobutamine infusion up to 20 mcg/kg/min can be added to any vasopressor(s) in use. Dobutamine is also an appropriate first-line agent in patient