休克及血管活性藥物的使用

休克及血管活性藥物的使用王仟陸,什么是休克-什么時候存在休克,血壓？多少血壓是休克？BP低于90/60mmHg?高血壓病人血壓下降絕對值大于40mmHg或者超過基礎(chǔ)的30-40%？是不是就是以血壓為參考?-夠簡單便捷,血壓僅僅是一方面，休克的綜合評判（生化+臨床）,1、神志改變2、四肢冰涼、末梢發(fā)紺3、少尿、無尿、尿比重增高4、四肢花斑（休克嚴(yán)重程度一致）5、乳酸升高（2mmol/L）6、毛細(xì)血管充盈時間延遲(2s)7、心率快、口渴8、堿剩余消耗-酸中毒9.中心靜脈或者混合靜脈血氧飽和度異常10、動靜脈血二氧化碳分壓差（大于5-6mmHg）,休克核心是-細(xì)胞缺氧,氧輸送不足血色素和氧分壓通常不會影響心輸出量是決定因素（尤其是非分布性休克）-灌注不良細(xì)胞氧利用障礙在分布性休克（高動力狀態(tài)）的重要機制氧供與氧耗之間的平衡,Delivery DO2: DO2 = CO x Hbx1.34xSaO2,休克的定義,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,感染性休克定義,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.,休克的分類-四類,休克到了晚期往往是混合因素休克早期比較單純,休克的分類,休克本質(zhì),組織器官灌注不良決定器官灌注的兩個要素-流量（心輸出量）-基礎(chǔ)-灌注壓（與平均動脈壓相關(guān)最大，心臟是舒張期灌注故舒張壓重要） 心輸出量急劇下降多會引起血壓下降,MAP = CO x SVR,心率,每搏輸出量,心肌收縮力,左心前、后負(fù)荷,平臺期以前可以通過補液增加CO,補液300-500ml后可以使CO提升12-15%即有容量反應(yīng)性-即處于曲線的反應(yīng)期,動靜脈血二氧化碳分壓差正常值小于6mmHg反應(yīng)流量灌注正常-即心輸出量正常-心功能正常或者處于心功能曲線平臺期以前狀態(tài)的病人如果異?？梢匝a液增加CO-心功能異常以及處于心功能曲線平臺期及以后的病人不能補液只能強心或者心臟輔助或者降低氧耗,乳酸,乳酸在休克的診斷及預(yù)后判斷、治療監(jiān)測中意義重要熟悉引起乳酸升高的常見因素對于疾病的分析和把握至關(guān)重要乳酸清除率休克監(jiān)測治療目標(biāo)（2-4h乳酸清除率大于10-20%）,CVP,實際上反應(yīng)右房的壓力受許多因素影響右心功能、胸內(nèi)壓、腹內(nèi)壓、呼吸機PEEP及潮氣量改變、胸水和腹水，心臟瓣膜病，左心功能，心包疾病、血管內(nèi)容量等不論是CVP的絕對值還是變化值均不能反應(yīng)患者的容量反應(yīng)性-對液體復(fù)蘇的反應(yīng),CVP絕對值與容量反應(yīng)性,Osman D, et al. Crit Care Med. 2007;35(1):64-68.,150 volume challenges; sepsis,CVP的變化值與心輸出變化的關(guān)系,CVP的意義何在,不在于它對于容量反應(yīng)性的判斷50%的準(zhǔn)確性（是與不是本來就是各占一半）但臨床上仍有重要的意義維持正常灌注的最低CVP值（靜脈回流量最大同時心臟前負(fù)荷最低-做功最小）,血管活性藥物,分布性休克時什么時候用？先補液還是先血管活性藥物升壓？,休克發(fā)生后的頭6h每延遲1h使用去甲腎死亡率增加5.3%休克發(fā)生后2h內(nèi)使用去甲腎升壓患者28天死亡率顯著低于2h后使用的患者回顧性研究,死亡率最低的患者為休克發(fā)生后1-6h內(nèi)使用去甲腎的病人在休克發(fā)生后1h內(nèi)輸入1L液體的患者死亡率減低提示低血壓的發(fā)生與死亡率相關(guān)回顧性研究Crit Care Med. 2014 Oct;42(10):2158-68.,為什么？,分布性休克時存在高動力狀態(tài)，CO正常甚至增加，主要是血管外周阻力下降，通過補液增加血壓會使心臟做功明顯增加補液會導(dǎo)致灌注壓達標(biāo)時間的延長-與器官功能（尤其是腎衰竭）及死亡率相關(guān)去甲可以增加前負(fù)荷（使靜脈血管床收縮達到自體輸液的作用）,正常時,感染性休克發(fā)生時,擴容補液后,使用去甲后,目標(biāo)血壓多少合適,保證關(guān)鍵器官的灌注壓-腦和腎對灌注壓力依賴程度高 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) 心臟灌注壓為冠脈壓力與室腔內(nèi)壓力差-所以舒張壓絕對心肌供血-心臟是循環(huán)核心，保證心臟灌注重中之重 MAP 65-75mmHg for the Kidneys？ 中心靜脈壓以及腹內(nèi)壓均可影響腎臟灌注壓，MAP大于75mmHg后腎臟灌注并沒有明顯改善,需考慮基礎(chǔ)血壓狀況心臟灌注MAP要求低（30-50mmHg即可），但是有高血壓的病人尤其是左室肥厚的患者需要的血壓要明顯增高達70mmHg腎臟在MAP 65mmHg以上時才有灌注并逐漸增加，大于75mmHg增加不顯著，有高血壓基礎(chǔ)的血壓要求增加,升壓目標(biāo)65-70mmHg與80-85mmHg對比,血管活性藥物-去甲是否可以外周使用,1、置管延遲去甲的使用2、低血壓的發(fā)生時間與腎功能不全及死亡率相關(guān)3、越早使用去甲預(yù)后越好4、限分布性休克尤其感染性休克5、CVP監(jiān)測的無用以及中心靜脈的并發(fā)癥6、目前的研究顯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藥物，67.7%為去甲，最快達0.7ug/kg/min,平均外周輸注時間達49+-22h外滲的發(fā)生只有2%（19例），且不嚴(yán)重可以使用硝酸甘油+酚妥拉明處理最終有13%（95例）病人仍需要中心靜脈置入,J Hosp Med. 2015 Sep;10(9):581-5.,外周靜脈輸入血管活性藥物,盡量短時間（小于72h）低速度（0.7ug/kg/min，休克不嚴(yán)重的患者，作為過度措施）大血管（超聲示靜脈直徑大于4mm，選擇腘窩及肘窩以上血管）輸入側(cè)不能測血壓，有嚴(yán)格的觀察和處置流程不要使用手、足及遠端血管，肘窩盡也量不用如使用小于4h,去甲是否加重腎功能不全及少尿,多巴胺存在多巴能作用導(dǎo)致免疫抑制去甲有輕度beta興奮作用去氧腎上腺素沒有beta興奮作用,去甲腎和多巴胺的對比,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,血管加壓素,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).,去氧腎上腺素,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