感染性休克早期目標(biāo)復(fù)蘇治療的幾種觀點(diǎn)

1、EGDT的提出 單中心的急診科(US，Tertiary care hospital) N=263，小樣本 前瞻性隨機(jī)對(duì)照研究 終點(diǎn)目標(biāo)：評(píng)估EGDT對(duì)Sepsis和septic shock患者是 否有益N Engl J Med 2001;345:1368-77補(bǔ)充氧氣管插管和機(jī)械通氣EARLY GOAL-DIRECTED THERAPY, EGDT中心靜脈或者動(dòng)脈穿刺鎮(zhèn)靜，肌松（插管患者）CVPMAPSCVO2達(dá)標(biāo)收住院晶體液膠體液血管活性藥物輸血后紅細(xì)胞壓積30%肌力藥物8mmHg65mmHg90mmHg70%70%70%YESNON Engl J Med 2001;345:1368-77E

2、GDT主要是針對(duì)sepsis或者septic shock血液動(dòng)力學(xué)的優(yōu)化8-12mmHg65或90mmHg70%N Engl J Med 2001;345:1368-77N Engl J Med 2001;345:1368-77EGDT的提出明顯減少患者死亡率（從46.5%到30.5%）迅速的組織缺氧的糾正可改善生存率。住院天數(shù)從18.4天到14.6天，但無統(tǒng)計(jì)學(xué)差異 Early goal-directed therapy (EGDT) provides significant benefits with respect to outcome in patients with severe s

3、epsis and septic shock. (N Engl J Med 2001;345:1368-77.)N Engl J Med 2001;345:1368-77針對(duì)本項(xiàng)研究有較多的疑問？整個(gè)研究未用盲法？穿刺時(shí)必須的嗎？輸血必須嗎？如此多的液體合適嗎？為什么對(duì)照組的死亡率如此之高？為什么本研究是陽性結(jié)果而其他研究是陰性？。SURVIVING SEPSIS CAMPAIGN CARE BUNDLESTO BE COMPLETED WITHIN 3 HOURS Measure lactate level Obtain blood cultures prior to administrat

4、ion of antibiotics Administer broad spectrum antibiotics Administer 30 mL/kg crystalloid for hypotension or lactate 4 mmol/LTO BE COMPLETED WITHIN 6 HOURS Apply vasopressors to maintain a mean arterial pressure (MAP) 65 mm Hg despite volume resuscitation or initial lactate 4 mmol/L - Measure central

5、 venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* Remeasure lactate if initial lactate was elevated* SURVIVING SEPSIS CAMPAIGN CARE BUNDLESEGDT是針對(duì)血液動(dòng)力學(xué)的優(yōu)化有關(guān)SEPSIS 的新的臨床研究ProCESS- Protocolized Care for Early Septic Shock. ARISE- Australasian Resusitation In Sepsis Evaluation

6、ProMISe- Protocolised Management In Sepsis 項(xiàng)目研究地區(qū)起止時(shí)間納入中心數(shù)納入病例場所樣本例數(shù)美國3.2008-12.201331ED1341澳大利亞10.2008-4.201451ED1588英國2.2011-7.201456ED ,ICU1260ProCESS 多中心 N=1341，大樣本 前瞻性隨機(jī)對(duì)照研究 終點(diǎn)目標(biāo)：60天死亡率，90天死亡率，1年死亡率，是否需要器官功能支持The ProCESS Investigations, N England J Med, 2014,370:1683-169312701例患者最終納入1341例研究分三組

7、EGDT組：439例 基于規(guī)范的標(biāo)準(zhǔn)治療組：446例 普通治療組：456例ProCESSThe ProCESS Investigations, N England J Med, 2014,370:1683-1693ProCESSThe ProCESS Investigations, N England J Med, 2014,370:1683-1693ProCESSThe ProCESS Investigations, N England J Med, 2014,370:1683-1693ProCESSThe ProCESS Investigations, N England J Med, 2

8、014,370:1683-1693ARISE 多中心 N=1588，大樣本 前瞻性隨機(jī)對(duì)照研究 終點(diǎn)目標(biāo)：生存時(shí)間，住院期間的病死率，住院時(shí)間，是否需要器官功能支持The ARISE Investigations, N England J Med, 2014,371:1496-1506ARISE3559例患者最終納入1588例研究分組 EGDT組：792例 普通治療組：796例The ARISE Investigations, N England J Med, 2014,371:1496-1506ARISEThe ARISE Investigations, N England J Med, 2

9、014,371:1496-1506ARISEThe ARISE Investigations, N England J Med, 2014,371:1496-1506ARISEARISEThe ARISE Investigations, N England J Med, 2014,371:1496-1506ProMISe 多中心 N=1260，大樣本 前瞻性隨機(jī)對(duì)照研究 終點(diǎn)目標(biāo)：90天死亡率 次要目標(biāo)：靜脈補(bǔ)液量，血管活性藥物，輸血，器官功能支持的評(píng)價(jià)The ProMISe Investigations, N England J Med, 2014,372:1301-1311ProMISe6

10、192例患者最終納入1260名患者研究分組 EGDT組630例 普通治療組630例The ProMISe Investigations, N England J Med, 2014,372:1301-1311The ProMISe Investigations, N England J Med, 2014,372:1301-1311The ProMISe Investigations, N England J Med, 2014,372:1301-1311ProMISeThe ProMISe Investigations, N England J Med, 2014,372:1301-1311

11、ProMISe In conclusion, our results suggest that techniques used in usual resuscitation have evolved over the 15 years since the landmark study by Rivers et al.9 In our study, NHS hospitals achieved levels of in-hospital survival in patients receiving usual care that were similar to those achieved wi

12、th EGDT in the earlier study for patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation. ProMISeThe addition of continuous ScvO2 monitoring and strict protocolization did not improve outcomes in the EGDT group. Our results complete

13、the planned trio of studies of EGDT, all of which showed that EGDT was not superior to usual care.如何看待這三項(xiàng)研究的陰性結(jié)論多中心大樣本隨機(jī)對(duì)照試驗(yàn)前瞻性研究如何看待這三項(xiàng)研究的陰性結(jié)論試驗(yàn)預(yù)計(jì)探查到的組間病死率差異的范圍疾病的基線病死率等因素作者們都明顯高估了基線病死率（28天病死率）和預(yù)計(jì)的組間差異，導(dǎo)致納入病例不足如何看待這三項(xiàng)研究的陰性結(jié)論EGDT，這個(gè)在“Bundle”中擔(dān)當(dāng)核心的主策略終于在強(qiáng)大的證據(jù)面前顯示出裂痕。EGDT，我們還需要嗎？剩下什么？早期識(shí)別SEPSIS關(guān)鍵廣譜抗生素的應(yīng)用降階梯治療進(jìn)行適當(dāng)?shù)娜萘繌?fù)蘇Bundle 帶給我們什么？ 通過對(duì)171個(gè)ICU 101064例患者的回顧性調(diào)查發(fā)現(xiàn)澳大利亞和新西蘭地區(qū)10余年間重癥感染和感染性休克的住院病死率由35.0%下降至18.4%Bundle 帶給我們什么？同樣提示實(shí)施BUNDLE以來，重癥感染和感染性休克的住院病死率在下降，存在統(tǒng)計(jì)學(xué)意義。當(dāng)指南遭遇臨床？總是在評(píng)價(jià)。常常會(huì)疑惑。偶爾很堅(jiān)定。