http://www.nejm.org/doi/story/10.1056/feature.2013.11.13.18
恩既然ICU裡遍地的ARDS就來稍微看一下吧，前陣子ARDS 50週年ICU晨會系列文連發(只能說呼吸生理實在是各種神之領域)，所以想說就來查一下資料整理一番。先簡單看一下定義，下面主要是從ATS對於呼吸器調整策略的建議該賴衍伸查一些相關的文獻。
古早以前還要漂斯汪槓但這實在是太搞剛，以前還有ALI什麼的..，後來2012年改版的柏林定義如下
JAMA. 2012 Jun 20;307(23):2526-33.
ARDS的治療Lancet整理如上圖，＊字代表目前證據支持有益，†代表目前證據不支持，‡代表仍需更多研究目前無定論。
針對ARDS的呼吸器設定策略，這篇ATS在2017年三月的文章回顧過去的文獻，以問答的方式提出了不同證據強度的建議如下：
Question 1: Should Patients with ARDS Receive Mechanical Ventilation Using LTVs and Inspiratory Pressures?
Recommendation : We recommend that adult patients with ARDS receive mechanical ventilation with strategies that limit tidal volumes (4–8 ml/kg PBW) and inspiratory pressures (plateau pressure , 30 cm H2O)
(strong recommendation, moderate confidence in effect estimates)
Question 2: Should Patients with ARDS Receive Prone Positioning?
Recommendation : We recommend that adult patients with severe ARDS receive prone positioning for more than 12 hours per day.
(strong recommendation, moderate-high confidence in effect estimates)
Question 3: Should Patients with ARDS Receive High-Frequency Oscillatory Ventilation?
We recommend that HFOV not be used routinely in patients with moderate or severe ARDS.
(strong recommendation, moderate-high confidence in effect estimates)
Question 4: Should Patients with ARDS Receive Higher, as Compared with Lower, PEEP?
We suggest that adult patients with moderate or severe ARDS receive higher rather than lower levels of PEEP.
(conditional recommendation, moderate confidence in effect estimates)
Question 5: Should Patients with ARDS Receive recruit maneuvers?
We suggest that adult patients with ARDS receive RMs.
(conditional recommendation, low–moderate confidence in the effect estimates)
Question 6: Should Patients with ARDS Receive Extracorporeal Membrane Oxygenation?
Additional evidence is necessary to make a definitive recommendation for or against the use of ECMO in patients with severe ARDS. In the interim, we recommend ongoing research measuring clinical outcomes among patients with severe ARDS who undergo ECMO.
喔也可以看一下神站Pulmccm的整理
http://pulmccm.org/main/2012/review-articles/mechanical-ventilation-in-ards-2012-update/
對了一個重要的觀念是這些呼吸器設定的策略並不是為了“治療”ARDS，而是為了”減少”因為呼吸器帶來的肺損傷(Ventilator-induced lung injury, VILI)。
ARDS net protocol 如下：
恩那稍微來針對裡面每一項衍伸查點相關文章
＝Lower tidal-volume and lower inspiratory pressures＝
Lower tidal-volume的觀念廣為被接受濫觴為這篇NEJM(雙膝一軟)
後來又一篇NEJM(再跪)探討揪竟Lower TV跟Higher PEEP的策略是如何降低VILI的發生，誒抖，接下來是我的理解可能有錯還請指正。目前LTV的算法是用PBW去算，並不是針對ARDS當下肺部實際的生理狀況去校正。
誒話若要說透支(好老派)，就得來說一下Baby lung的概念，以前以為ARDS的肺部compliance差是因為整個肺部變得很硬(stiff)，後來發現其實是因為能夠行氣體交換的aerated lung/functional lung變得很小，所以其實”the acute respiratory distress syndrome lung is not “stiff” but instead small, with nearly normal intrinsic elasticity”且”what appears dangerous is not the VT/kg ratio but instead the VT/”baby lung” ratio”。
也就是用PBW去校正VT不太能反映當下肺部的狀況，應該要用當時的lower respiratory-system compliance (Crs)校正才合理，所以應該要看的參數是VT /Crs，這個比值即為Driving pressure(ΔP)，其實也就是Pplat-PEEP。
這篇NEJM就是以post hoc observational analysis的方式分析過去的資料，希望能證實ΔP和survival之間的關聯，結果也證實ΔP是個好棒棒的參數。這篇文章也提到單獨改變VT或PEEP和survival並無統計上相關，VT或PEEP的變化一定得要同時伴隨相對應的ΔP，才會有統計上survival相關性。
A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving “protective” plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001).
下面這個圖是神站PulmCCM的解說圖，我們可以控制的參數是VT和PEEP，而其實透過調整這兩個參數我們是在改變ΔP。
Ref: http://pulmccm.org/main/2016/review-articles/icu-physiology-in-1000-words-driving-pressure-stress-index/
Driving Pressure and Survival in the Acute Respiratory Distress Syndrome
＝ Higher PEEP or Lower PEEP? ＝
2010年JAMA上這篇綜合分析了三個RCT得到的結論是對於Moderate to severe ARDS的病人族群，結果是採用Higher PEEP 治療策略的組別得到比較高的存活率.
另一個常被討論的議題是”Optimal PEEP”，下面這篇比較了幾種曾被用於試圖找出optimal PEEP的方法，最後的結論是：‘The best PEEP’ does not exist.
Tailoring PEEP according to the ARDS severity, as defined by the Berlin definition, may be a reasonable approach:
5–10 cmH2O PEEP in mild patients
10–15cmH2O PEEP in moderate patients
15–20 cmH2O PEEP in severe patients
Ref: Selecting the ‘right’ positive end-expiratory pressure level (Current Opinion in Critical Care. 21(1):50–57, FEB 2015)
另一個神站Deranged physiology 整理如下
Optimal PEEP for Open Lung Ventilation in ARDS
方法百百種，我覺得比較親民的是懶人包照著ARDSNet protocol或是用Staircase recruitment/derecruitment 的方法去調。
Should Patients with ARDS Receive RMs?
ATS這篇抓了六篇RCT，結論是RM看起來美賣，ATS推推。但當然要注意hemodymamic compromise，同時這裡也提到
The optimal method, timing, and target population for RMs, as well as the role for concomitant changes in PEEP, remain uncertain and require further study.
- RMs were significantly associated with lower mortality (six studies, 1,423 patients; RR, 0.81; 95% CI, 0.69–0.95; moderate confidence)
- RMs were also associated with higher oxygenation (PaO2/FIO2 ratio) at 24 hours (six studies, 1,400 patients; 52 mm Hg higher; 95% CI, 23–81; low confidence)
- RMs reduced the need for rescue therapy (two studies, 1,003 patients; RR, 0.64; 95% CI, 0.35–0.93; moderate confidence).
” 肺部再擴張術從病生理學的觀點上可以打開塌陷的肺泡、改善氧合、以及降 低呼吸器相關的肺損傷 ，但必須使用在合適的 病人上，如:急性呼吸窘迫症72小時內、肺 外病灶所引起的急性呼吸窘迫症 、肺部順應性 ≧30 ml/cmH2O、和非局部的肺病變。”
Prone position?
在2013這篇NEJM出來之前Prone position雖然已被證實好棒可以增加氧氣交換減低VILI，但就是做不出survival benefit。這篇研究針對severe ARDS的病人主要的結果如下：
The 28-day mortality ： 16.0% in the prone group and 32.8% in the supine group (P<0.001).
The hazard ratio for death ： with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63).
Unadjusted 90-day mortality ： 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67).
Prone Positioning in Severe Acute Respiratory Distress Syndrome
簡單整理就是下面這張圖，我承認我只是想練習一下AI。
High-frequency oscillatory oscillatory ventilation?
小的上個月才剛遇到一台HFOV，後來在摸咪報了一個相關的病例。
Cochrane 2016年的review分析八篇RCT得到的結論是30-day mortality沒有統計上顯著差異。
AJRCCM 2017年2月這篇挑了四篇RCT得到的結論也是30-day mortality沒有統計上顯著差異。
這篇文章中提到PF ratio 和OR間有正相關，PF越低的病人似乎能從HFOV得到survival benefit的勝算越高，不過這個推論沒有達到統計上的差異。
HFOV臨床應用上的時機這篇文章提出了上面投影片(沒錯又是直接拿來用反正都做了XD)的建議。不過我覺得要用到HFOV的病人基本上已經進入專科的神之領域….
Should High-Frequency Ventilation in the Adult Be Abandoned?
Severity of Hypoxemia and Effect of High Frequency Oscillatory Ventilation in ARDS
Extracorporeal Membrane Oxygenation?
ATS這篇是認為目前的文獻證據力不足以給出建議，文內主要提到的文章是這篇09年刊載的RCT(CESAR trial)，ATS這篇提到”no significant difference in mortality for patients transferred for VV ECMO versus not transferred and provided conventional mechanical ventilation”
不過我看原文章其實結果的部分是
63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0·69; 95% CI 0·05–0·97, p=0·03).
不太確定ATS這篇是不是有針對數據做校正。而CESAR這篇雖然是RCT但因為研究本身的限制也招來一些質疑，比如“there was a difference of 23% between treatment groups with respect to the use of a lung protective ventilation strategy at any time.”
2015年Cochrane review有一篇試著分析目前已知的證據，在四篇RCTs共389個病人得到的資料結論如下：
- No statistically significant differences in all-cause mortality at six months (two RCTs) or before six months (during 30 days of randomization in one trial and during hospital stay in another RCT).
- Clinical heterogeneity between studies prevented meta-analyses across outcomes.
- Until these new results become available, data on use of ECMO in patients with acute respiratory failure remain inconclusive
誒我想就是老話一句還需要更多研究(眼神空)。
Inhaled nitric oxide ?
05年NEJM這篇說(這篇各種美圖秀秀)：
On the basis of the evidence, inhaled nitric oxide is not an effective therapeutic intervention in patients with acute lung injury or ARDS, and its routine use to achieve this end is inappropriate.
這篇還提醒
- Ten RCTs involving 1363 participants were included.
整體pooling起來iNO顯著增加AKI(RR, 1.4, 95%CI, 1.06 to 1.83, p = 0.02)
Subgroup analysis發現ARDS組有統計上顯著差異。
整理完的心得是ARDS果然是神的領域啊…..
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各位朋友，請不吝按讚或分享，讓我們一起為美好的二手人生努力(遠目)!
路過看到精采文章~太厲害了我也雙膝一軟XDDD
不過每次遇到ARDS最後還是都會上iNO啊…對於緊急情況拉起O2也都有一定的效果
猜測如果選個FiO2高一點族群的或許可以做出差異?
這不是敬左哥嗎？我都直接先問VS這個病人假如爆炸要選哪個XD。話說我猜幾年後該賴又會改一輪，到時只好交給重症魂的同事們…