编译 Josh Farkas：SSC 2016指南试图推销的6个神话

PulmCrit的大神 Josh Farkas最近发表的博文对SSC2016指南打响了第一炮，简直是崩塌式的剿灭! 不过不要紧，黄老司机会在之后的（条件允许的情况下）提供部分解药.........



PulmCrit的大神 Josh Farkas最近发表了一篇博文：Six myths promoted by the new surviving sepsis guidelines（SSC2016指南试图推销的6个神话）

http://emcrit.org/pulmcrit/sepsis-myths/



押题的照片就是一个底盘即将崩塌的高级楼宇的照片，我已经闻到Josh Farkas那上膛的子弹的硝烟味道了。

果然，该博文的的第一自然段的题目就是：

Early Goal-Directed Therapy:  A house collapsing in slow motion 早期目标治疗（EGDT）一座正在缓慢垮塌的house

这个自然段中，作者的观点可以总结为：

1.  SSC,即整个的拯救脓毒症的原始根基就是Rivers当年的那个EGDT研究，这个研究怎么说呢，就是一个和脑卒中溶栓NIND研究类似的研究——NIND研究中只要对照组增加3个患者，整体结局就没有显著性差异了，这个意思，你懂得！
2. 问题是Rivers的研究中有25个已经随机化，但未纳入最终分析的病例；而且Rivers隐瞒了与SCVO2监测的重大的利益冲突！（这已经不是本博客第一次提出，所以就不说了，据说之所以25个患者被曝光出来，是当年参与统计研究的研究生透露出来的，但最终这个研究生也封口了）；当然，Rivers研究的其他诸多不足就不一一陈述了。不好意思——这就是危通社的功能之一，我们只提供给观众基于国际公共信源的最直接的讯息！
3. 随着时间的推移，早期目标导向治疗的几乎每一个组成部分，无论是血红蛋白、ScvO2还是CVP（其价值简直就跟投硬币一样）还是都不成立，唯一证明有效的核心部件只剩下MAP≥65mm！
4. 但这还不是最可怕的，最可怕的是虽然Rivers的每一个部分都被证明不妥，但承认Rivers试验是错误的竟然是亵渎的（怎么感觉不仅是EGDT的组成部分，你要是对SSC指南的任何部分进行责问都是不行的）！ Rivers试验是脓毒症近十余年研究的基础。 如果Rivers试验是无效的，那么基于它的许多研究也是无效的。 承认Rivers是错误的，就像承认我们的房子的基础已腐烂，并即将崩溃。如上所述，整个SSC指南都是基于EGDT思想，2014年SSC对指南的更新中还仍然检查CVP导向。此次SSC指南中与抛弃了EGDT，不为别的-如果不这么做，指南就不可避免的落后于时代了！但是！EGDT的余孽仍然存在，必须对之进行硬性、客观的观察以确定其是否成立，毕竟EGDT已然崩溃...

(这是三个自然段的总结，附上原文，证明老黄翻译的没有添枝加叶或者信口雌黄：Although the components of the Rivers protocol have been disproven, it remains blasphemous to admit that the Rivers trial was wrong.  The Rivers trial is the underpinning of a decade of research in sepsis.  If the Rivers trial isn’t valid, then many studies based on it aren’t valid either.  Admitting Rivers is wrong is like admitting that the foundation of our house has rotted and is about to collapse.The Surviving Sepsis Campaign was founded on the basis of early goal-directed therapy.  As this was disproven, the campaign stubbornly clung to it (for example, continuing to recommend CVP monitoring in 2014).  The current guidelines have finally removed early goal-directed therapy, since to do otherwise would have rendered them irredeemably obsolete.However, many vestiges of early goal-directed therapy remain in the current guidelines (e.g. serial lactate measurement).  We must take a hard, objective look at such therapies to determine if they still stand up, now that early goal-directed therapy has collapsed）.

以下，就是大神 Josh Farkas试图告诉读者SSC2016指南中试图推行的6个（实际上值得商榷的）隐晦的概念，当然都是错误的！！！！

由于翻译很辛苦，只对题目进行翻译。具体解释自己通过链接（http://emcrit.org/pulmcrit/sepsis-myths/）认真研读就行了，黄老司机就不一一翻译了——我一直就是这观点，你TMD连这个都看不明白，还当什么导师，只配改标点符号和引文格式得了）！

Myth #6: Combination therapy is beneficial for gram-negative septic shock.


神话6：“联合治疗”对革兰氏阴性菌引起的感染性休克是有益的！

（注：在新指南中，联合治疗是有特指的——即针对臆测的阴性菌应选择两种在机制上不同且敏感的抗菌药物，例如β-内酰胺类联合氟喹诺酮类与氨基糖甙类；这与β-内酰胺类联合棘白霉素类这样的为了扩大抗菌谱的组合是完全不同的！~）

Myth #5: Norepinephrine is the best vasopressor for all septic patients.

神话5：所有感染性休克去甲是最好的升压药物！

Myth #4:  If one vasopressor doesn’t work, additional drugs should be added in a sequential fashion.

神话4：如果任何血管加压药物都无效，联用是合适的方式



Myth #3: Lactate is a measure of tissue perfusion. Normalization of lactate should be used as a resuscitation target.


神话3：乳酸是组织灌注的标志物，乳酸正常化应作为液体复苏的目标

这个部分我认为非常重要，而且有极其重要的启示性，特别全文摘抄如下。

It remains widely believed that lactate is a measurement of perfusion, systemic oxygenation, and anaerobic metabolism.  This is a myth.  Among septic patients, the primary cause of lactate elevation is beta-2 agonist stimulation (from endogenous and exogenous epinephrine).  Beta-2 agonist stimulation causes the liver to secrete lactate via an aerobic mechanism.  Lactate may be used by the heart and brain as a metabolic fuel, suggesting that this is an adaptive mechanism designed to handle physiologic stress.

Once we understand lactate as an index of endogenous epinephrine, using it as a resuscitation target stops making sense:

First, let’s imagine a young woman who is doing great, after receiving some fluids and norepinephrine.  Her blood pressure, urine output, and skin perfusion are excellent.  Her lactate is 6 mM, revealing the presence of endogenous epinephrine.  Giving her additional norepinephrine and dobutamine can overdrive suppress her sympathetic nervous system, shutting down endogenous epinephrine production.  This will reduce lactate, but it probably won’t help her.  It’s basically using exogenous norepinephrine and dobutamine to replace her endogenous epinephrine (which was working perfectly well).

Second, let’s imagine an elderly man who is doing poorly despite receiving fluids and norepinephrine.  His heart rate is in the 70s, his urine output is poor, and his extremities are mottled.  His lactate is 0.5 mM.  This patient is suffering from an inadequate sympathetic response, with a deficiency of endogenous epinephrine.  After an epinephrine infusion is started, he improves dramatically with excellent urine output and skin perfusion.  However, the exogenous epinephrine causes his lactate to increase to 6 mM.  This increase in lactate is actually a positive prognostic sign, indicating that he is likely to improve (Wutrich 2010).  Rising lactate doesn’t mean that he’s getting sicker – it means that the epinephrine is working (2).

There is no persuasive evidence that trying to “normalize” lactate is beneficial.  The new guidelines recommend using lactate to guide resuscitation on the basis of five studies:

Jones 2010:  This showed that chasing lactate was equivalent to chasing svcO2.  However, recent studies suggest that chasing svcO2 isn’t helpful… so chasing lactate and chasing svcO2 may be equally ineffective.

Jansen 2010:  This prospective RCT found no mortality benefit among patients whose lactate levels were measured. However, a post-hoc adjusted analysis did find benefit.

The remaining three studies aren’t available in English (Lyu 2015, Tian 2012, Yu 2013).

Myth #2: All septic patients must receive 30 ml/kg fluid initially.


神话2：所有的脓毒症患者均应来个30ml/Kg的复苏体验

Myth #1: It’s helpful to mandate that specific sepsis therapies be given within a rigid time frame.


神话1：将脓毒症的治疗时间规定以一定的范畴是有益的

作者总结到：

1. We have a history of over-estimating our knowledge of sepsis and the benefit of our interventions.超NB的评论！这也是某些SB的写照！

2. Acknowledging uncertainty is uncomfortable, but it may ultimately make us more thoughtful and flexible clinicians.

3. We need to be honest with ourselves about what is actually known about sepsis therapy (which is surprisingly little).   For example:

• Intentional double-coverage of gram-negative bacilli to achieve synergy has no proven benefit.
• Norepinephrine is a good vasopressor, but it is unclear whether it is the best drug for every patient.  The ideal drug selection and dose is unknown.
• Lactic acid is not a reliable measurement of tissue perfusion.  It is doubtful that using lactate as a resuscitation endpoint is beneficial.
• Nobody knows how much fluid should be given to septic patients or how quickly it should be given.
• The benefit of early therapy is unproven.  Insufficient evidence exists to make any concrete recommendation regarding the timing of interventions.

最后，原文链接不再危通社同名博客，而在：http://emcrit.org/pulmcrit/sepsis-myths/ ，或者点击左下角的“阅读原文”

好了，今天好晚也好累！

难得我今天的感冒终于好转了些，能够下床写点东西了！

其实我每次看 Josh Farkas的文章，都觉得是打脸.......但我不觉得是丑，承认自己不行总比每天扯大旗装虎皮，全世界没谁是绝对不一样的......

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