全身性感染與感染性休克

1、全身性感染與感染性休克全身性感染與感染性休克what is new?嚴(yán)重全身性感染與感染性休克嚴(yán)重全身性感染與感染性休克非特異性損傷引非特異性損傷引起的臨床反應(yīng)起的臨床反應(yīng), 滿足滿足 2條標(biāo)準(zhǔn)條標(biāo)準(zhǔn): t 38 c or 90 bpmrr 20 bpmwcc 12,000/mm3or 10%桿狀核桿狀核sirs = systemic inflammatory response syndrome sirs及可疑或及可疑或明確的感染明確的感染chest 1992;101:1644. 全身性感染全身性感染伴器官衰竭伴器官衰竭頑固性低血壓頑固性低血壓sirssepsissevere sepsisse

2、ptic shock全身性感染全身性感染(sepsis): 流行病學(xué)流行病學(xué)martin gs, mannino dm, stephanie eaton s, et al. the epidemiology of sepsis in the united states from 1979 through 2000. n engl j med 2003; 348: 1546-54.全身性感染發(fā)病率的推算全身性感染發(fā)病率的推算751,000773,875796,750819,625842,500865,375888,250911,125934,000200220032004200520062007

3、200820092010平均每年增加1.5%; 相當(dāng)于年增新發(fā)病例約22,875例angus dc, et al. the epidemiology of severe sepsis in the united states: analysis of incidence, outcome and associated costs of care.全身性感染臨床試驗(yàn)對(duì)照組的病死率全身性感染臨床試驗(yàn)對(duì)照組的病死率全身性感染的醫(yī)療費(fèi)用全身性感染的醫(yī)療費(fèi)用2000年icu醫(yī)療費(fèi)用的40%歐洲每年花費(fèi) 7,600,000,0001美國(guó)每年花費(fèi)$16,700,000,00021.davies a et a

4、l. abstract 581. 14th annual congress of the european society of intensive care medicine, geneva, switzerland, 30 september-3 october 20012.angus dc, linde-zwirble wt, lidicker j, et al. epidemiology of severe sepsis in the united states: analysis of incidence, outcome, and associated costs of care.

5、 crit care med 2001; 29:13031310surviving sepsis campaign: why?過(guò)去5年間陽(yáng)性結(jié)果的干預(yù)措施n嚴(yán)重全身性感染與感染性休克uegdtu激素uapcu小潮氣量通氣策略n危重病患者的一般治療u鎮(zhèn)靜u嚴(yán)格血糖控制u脫機(jī)方案surviving sepsis campaign (ssc) guidelines for management of severe sepsis and septic shockdellinger rp, carlet jm, masur h, gerlach h, calandra t, cohen j, gea-b

6、anacloche j, keh d, marshall jc, parker mm, ramsay g, zimmerman jl, vincent jl, levy mm and the ssc management guidelines committeecrit care med 2004; 32: 858-873intensive care med 2004; 30: 536-555available online the guidelines were published in both critical care medicine and inintensive care med

7、icine, and are available on-linesurviving sepsis campaign guideline最初復(fù)蘇(initial resuscitation)診斷(diagnosis)抗生素治療(antibiotic therapy)感染源控制(source control)液體治療(fluid therapy)升壓藥物(vasopressors)強(qiáng)心藥物(inotropic therapy)激素(steroids)活化蛋白c (recombinant human activated protein c)血液制品(blood product administrat

8、ion)ards機(jī)械通氣(mechanical ventilation of sepsis-induced ali/ards)鎮(zhèn)靜(sedation, analgesia, and nmb in sepsis)血糖控制(glucose control)腎臟替代(renal replacement)碳酸氫鈉(bicarbonate therapy)dvt預(yù)防(dvt prophylaxis)應(yīng)激性潰瘍預(yù)防(stress ulcer prophylaxis)考慮限制支持治療水平(consideration for limitation of support)surviving sepsis cam

9、paign guideline最初復(fù)蘇(initial resuscitation)診斷(diagnosis)抗生素治療(antibiotic therapy)感染源控制(source control)液體治療(fluid therapy)升壓藥物(vasopressors)強(qiáng)心藥物(inotropic therapy)激素(steroids)活化蛋白c (recombinant human activated protein c)血液制品(blood product administration)ards機(jī)械通氣(mechanical ventilation of sepsis-induce

10、d ali/ards)鎮(zhèn)靜(sedation, analgesia, and nmb in sepsis)血糖控制(glucose control)腎臟替代(renal replacement)碳酸氫鈉(bicarbonate therapy)dvt預(yù)防(dvt prophylaxis)應(yīng)激性潰瘍預(yù)防(stress ulcer prophylaxis)考慮限制支持治療水平(consideration for limitation of support)嚴(yán)重全身性感染與感染性休克的治療嚴(yán)重全身性感染與感染性休克的治療sirssepsissevere sepsisseptic shock血糖控制非

11、常重要:最初病情穩(wěn)定后靜脈輸注胰島素1b目標(biāo)范圍?血糖 215 mg/dl180 200 mg/dl(10.0 11.1 mmol/l)39%應(yīng)用胰島素強(qiáng)化胰島素組 110 mg/dl80 110 mg/dl(4.4 6.1 mmol/l)99%應(yīng)用胰島素van den berghe g, wouters p, weekers f, et al.: intensive insulin therapy in the critically ill patients. n engl j med 2001, 345:1359-1367外科患者的強(qiáng)化胰島素治療外科患者的強(qiáng)化胰島素治療至隨訪第12個(gè)月,

12、強(qiáng)化胰島素治療可以降低病死率3.4% (p 24小時(shí)niss 20n血流動(dòng)力學(xué)穩(wěn)定usbp 100uhr 1 ml/kg/hn乳酸 2.5 mmol/l或其他灌注不足表現(xiàn)blow o, magliore l, claridge j, butler k, young j. the golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma. j trauma 1999; 47(5): 964隱性

13、低灌注與創(chuàng)傷預(yù)后隱性低灌注與創(chuàng)傷預(yù)后blow o, magliore l, claridge j, butler k, young j. the golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma. j trauma 1999; 47(5): 964嚴(yán)重創(chuàng)傷患者兩次嚴(yán)重創(chuàng)傷患者兩次la 2.5輸注液體或血液制品輸注液體或血液制品重復(fù)重復(fù)la 2.5swan-ganz, 動(dòng)脈插管動(dòng)脈插管

14、, 腎臟劑量多巴胺腎臟劑量多巴胺將將pcwp提高到提高到12 15將將hct提高到提高到30%重復(fù)重復(fù)la 2.5升壓藥物升壓藥物(多巴酚丁胺多巴酚丁胺)心臟超聲檢查心臟超聲檢查若若la仍仍 2.5隱性低灌注與創(chuàng)傷預(yù)后隱性低灌注與創(chuàng)傷預(yù)后1001001005700213616943500204060801001200-6 hr7-12 hr13-24 hr 24 hr% of patients存活率存活率呼吸系統(tǒng)并發(fā)癥呼吸系統(tǒng)并發(fā)癥mosfblow o, magliore l, claridge j, butler k, young j. the golden hour and the sil

15、ver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma. j trauma 1999; 47(5): 964全身性感染的診斷全身性感染的診斷適當(dāng)?shù)呐囵B(yǎng)至少留取2個(gè)血培養(yǎng)n1個(gè)外周血培養(yǎng)n每個(gè)留置 48 h的血管通路留取1個(gè)血培養(yǎng)(grade d)抗生素治療前后血培養(yǎng)的陽(yáng)性率抗生素治療前后血培養(yǎng)的陽(yáng)性率139名患者名患者抗生素治療前抗生素治療前抗生素治療過(guò)程中抗生素治療過(guò)程中開(kāi)始抗生素治療開(kāi)始抗生素治療83名患者名患者(60%)血培養(yǎng)陰

16、性或血培養(yǎng)陰性或分離出污染菌分離出污染菌0/83 (0%)分離到致病菌分離到致病菌56名患者名患者(40%)分離到致病菌分離到致病菌26/56 (45%)分離到致病菌分離到致病菌25名患者名患者(45%)分離到致分離到致病的葡萄球菌病的葡萄球菌19/25 (76%)分離到葡萄球菌分離到葡萄球菌14名患者名患者(25%)分離到致分離到致病的鏈球菌病的鏈球菌5/14 (36%)分離到鏈球菌分離到鏈球菌17名患者名患者(30%)分離到革分離到革蘭陰性桿菌蘭陰性桿菌2/17 (12%)分離到革蘭陰性桿菌分離到革蘭陰性桿菌1/139 (0.72%)分離到新的致病菌分離到新的致病菌grace cj, li

17、eberman j, pierce k, et al. usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. clin infect dis 2001; 32: 1651-5臨床意義臨床意義應(yīng)用抗生素前進(jìn)行血培養(yǎng)分離到致病菌的可能性增加2.2倍在開(kāi)始抗生素治療最初72小時(shí)內(nèi), 連續(xù)進(jìn)行血培養(yǎng)的結(jié)果, 可以根據(jù)應(yīng)用抗生素前血培養(yǎng)的結(jié)果預(yù)測(cè)極少分離到新的致病菌醫(yī)生可以等待應(yīng)用抗生素前的血培養(yǎng)結(jié)果回報(bào)后, 再進(jìn)行新的血培養(yǎng)grace cj, lieberman j, pi

18、erce k, et al. usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. clin infect dis 2001; 32: 1651-5嚴(yán)重全身性感染與感染性休克的治療嚴(yán)重全身性感染與感染性休克的治療sirssepsissevere sepsisseptic shock抗生素治療與感染灶控制抗生素治療與感染灶控制確診嚴(yán)重全身性感染后1小時(shí)內(nèi)開(kāi)始靜脈抗生素治療1c強(qiáng)化胰島素治療嚴(yán)格控制血糖強(qiáng)化胰島素治療嚴(yán)格控制血糖早期應(yīng)用抗生素與感染患者病死率早期應(yīng)用抗生

19、素與感染患者病死率kumar a, roberts d, wood ke, et al. duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. crit care med 2006; 34: 1589-1596嚴(yán)重全身性感染與感染性休克的治療嚴(yán)重全身性感染與感染性休克的治療sirssepsissevere sepsisseptic shock抗生素治療與感染灶控制抗生素治

20、療與感染灶控制早期目標(biāo)指導(dǎo)治療早期目標(biāo)指導(dǎo)治療持續(xù)低血壓或乳酸持續(xù)低血壓或乳酸 4 mmol/l最初6小時(shí)內(nèi)達(dá)到的目標(biāo)cvp 8 12 mmhgmap 65 mmhguo 0.5 ml/kg/hrscvo2 70%1b強(qiáng)化胰島素治療嚴(yán)格控制血糖強(qiáng)化胰島素治療嚴(yán)格控制血糖全身性感染全身性感染: 早期目標(biāo)指導(dǎo)治療早期目標(biāo)指導(dǎo)治療rivers e, nguyen b, havstad s, et al. early goal-directed therapy in the treatment of severe sepsis and septic shock. n engl j med 2001,

21、345:1368-1377全身性感染全身性感染: 早期目標(biāo)指導(dǎo)治療早期目標(biāo)指導(dǎo)治療rivers e, nguyen b, havstad s, et al. early goal-directed therapy in the treatment of severe sepsis and septic shock. n engl j med 2001, 345:1368-1377egdt組患者輸液更多組患者輸液更多0100020003000400050006000最初6小時(shí)安慰劑egdtrivers e, nguyen b, havstad s, et al. early goal-direc

22、ted therapy in the treatment of severe sepsis and septic shock. n engl j med 2001, 345:1368-1377egdt組輸血及應(yīng)用多巴酚丁胺更多組輸血及應(yīng)用多巴酚丁胺更多0.0%25.0%50.0%75.0%rbcs升壓藥多巴酚丁胺接受治療的患者比例安慰劑egdtrivers e, nguyen b, havstad s, et al. early goal-directed therapy in the treatment of severe sepsis and septic shock. n engl j

23、med 2001, 345:1368-1377egdt與感染性休克的預(yù)后與感染性休克的預(yù)后rivers e, nguyen b, havstad s, et al. early goal-directed therapy in the treatment of severe sepsis and septic shock. n engl j med 2001, 345:1368-1377心血管猝死心血管猝死21% vs. 10%p = 0.02mods22% vs. 16%p = 0.27嚴(yán)重全身性感染與感染性休克的治療嚴(yán)重全身性感染與感染性休克的治療sirssepsissevere seps

24、isseptic shock抗生素治療與感染灶控制抗生素治療與感染灶控制早期目標(biāo)指導(dǎo)治療早期目標(biāo)指導(dǎo)治療死亡高危:apache ii 25感染誘發(fā)的mof感染性休克感染誘發(fā)的ards無(wú)絕對(duì)禁忌癥權(quán)衡相對(duì)禁忌癥b活化蛋白活化蛋白c治療治療強(qiáng)化胰島素治療嚴(yán)格控制血糖強(qiáng)化胰島素治療嚴(yán)格控制血糖全身性感染全身性感染: 活化蛋白活化蛋白c30.8%24.7%0%10%20%30%40%mortality (%)bernard gr, vincent jl, laterre pf, et al. efficacy and safety of recombinant human activated prot

25、ein c for severe sepsis. n engl j med 2001; 344: 699-709.安慰劑安慰劑(n = 840)活化蛋白活化蛋白c(n = 850)絕對(duì)病死率下降6.1%雙尾雙尾p值值校正后的相對(duì)危險(xiǎn)度降低校正后的相對(duì)危險(xiǎn)度降低存活比數(shù)增加存活比數(shù)增加主要分析結(jié)果主要分析結(jié)果0.00519.4%38.1%嚴(yán)重全身性感染與感染性休克的治療嚴(yán)重全身性感染與感染性休克的治療sirssepsissevere sepsisseptic shock抗生素治療與感染灶控制抗生素治療與感染灶控制早期目標(biāo)指導(dǎo)治療早期目標(biāo)指導(dǎo)治療應(yīng)用氫化可的松200 300 mg/d, 分為3 4

26、次給藥或持續(xù)靜脈輸注, 療程7天經(jīng)過(guò)液體復(fù)蘇和升壓藥物治療低血壓持續(xù)1小時(shí)1b充分液體復(fù)蘇后仍需升壓藥物至少1小時(shí)2c活化蛋白活化蛋白c治療治療激素替代治療激素替代治療強(qiáng)化胰島素治療嚴(yán)格控制血糖強(qiáng)化胰島素治療嚴(yán)格控制血糖感染性休克的激素替代治療感染性休克的激素替代治療annane d, sebille v, charpentier c, et al. effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. jama 2

27、002; 288: 862-71.acth test8 hourssepticshockplacebohc 50 mg/6 hours+ fc 50 mcg/day p.o.n = 150n = 14928-daymortality7 days感染性休克的激素替代治療感染性休克的激素替代治療annane d, sebille v, charpentier c, et al. effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic s

28、hock. jama 2002; 288: 862-71.p = 0.04p = 0.96嚴(yán)重全身性感染嚴(yán)重全身性感染 循證醫(yī)學(xué)指南循證醫(yī)學(xué)指南干預(yù)措施nnt小潮氣量通氣策略11早期目標(biāo)指導(dǎo)治療6 8活化蛋白c16 (whole trial)8 (apache ii 25)強(qiáng)化胰島素治療29acth刺激試驗(yàn)無(wú)反應(yīng)者小劑量激素治療7sepsis resuscitation bundle(應(yīng)在最初應(yīng)在最初6小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)1.測(cè)定血清乳酸水平2.應(yīng)用抗生素前留取血培養(yǎng)3.入急診室3小時(shí)或入icu1小時(shí)內(nèi)應(yīng)用抗生素4.低血壓和(或)乳酸 4 mmol/l (36 mg/dl)時(shí):a)最初應(yīng)用晶

29、體液至少20 ml/kg(或等量的膠體液)b)最初液體復(fù)蘇無(wú)效時(shí)應(yīng)用升壓藥物以維持map 65 mmhg5.經(jīng)過(guò)液體復(fù)蘇后仍持續(xù)低血壓(感染性休克)和(或)乳酸 4 mmol/l (36 mg/dl):a)使cvp 8 mmhgb)使scvo2 70%sepsis management bundle(應(yīng)在最初應(yīng)在最初24小時(shí)內(nèi)達(dá)到小時(shí)內(nèi)達(dá)到)1.對(duì)感染性休克患者根據(jù)icu標(biāo)準(zhǔn)化規(guī)定應(yīng)用小劑量激素2.根據(jù)icu標(biāo)準(zhǔn)化規(guī)定應(yīng)用活化蛋白c3.控制血糖水平正常值下限, 且 150 mg/dl (8.3 mmol/l)4.維持機(jī)械通氣患者吸氣平臺(tái)壓力 30 cmh2osurviving sepsis c

30、ampaign initial resultsreporting the gap betweenperception and practicewhat we think we dovs.what we actually doards保護(hù)性通氣策略保護(hù)性通氣策略 ardsnet0%10%20%30%40%50%6 ml/kg12 ml/kgthe acute respiratory distress syndrome network: ventilation with lower tidal volumes as compared with traditional tidal volumes f

31、or acute lung injury and the acute respiratory distress syndrome. n engl j med 2000; 342:1301-1308p = 0.007研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響研究結(jié)果的發(fā)表對(duì)日常工作并無(wú)影響02.557.51012.515day 1day 3day of ali/ardsali/ards patients receiving lung-protective ventilation (%)prereleasepostreleasepostfeedbackrubenfeld gd, et al. am j re

32、spir crit care med 2001; 163: a295p = 0.11p = 0.02adhere to “best practice”?92%0%20%40%60%80%100%interviewdo you use lung protective strategy in ventilating acute lung injury patients?brunkhorst fm, et al, for the german competence network sepsis sepnet. the gap between perception and practice of se

33、psis therapy. (submitted)adhere to “best practice”?92%4%0%20%40%60%80%100%interviewauditresults of non-scripted care processesbrunkhorst fm, et al, for the german competence network sepsis sepnet. the gap between perception and practice of sepsis therapy. (submitted)supportive and adjunctive therapi

34、esresults of the german “prevalence” study92%67%46%1%79%23%67%45%4%9%18%1%31%0%92%95%0%20%40%60%80%100%low vtventilationglycemiccontrolscvo2apcsteroids forseptic shocksteroids forsevere sepsislow-dosedopaminenon-useat iii non-usebrunkhorst fm, et al, for the german competence network sepsis sepnet.

35、the gap between perception and practice of sepsis therapy. (submitted)為何循證治療在為何循證治療在icu中應(yīng)用并不普遍中應(yīng)用并不普遍缺乏相關(guān)知識(shí)n醫(yī)療費(fèi)用報(bào)銷的限制, 繁忙的工作安排icu醫(yī)生的懷疑n危重病領(lǐng)域眾多的陰性試驗(yàn)結(jié)果對(duì)證據(jù)的主觀選擇臨床惰性不能正確鑒別患者醫(yī)療資源的配置vha 19-icu sepsis bundlesicu los10.07.66.20.02.04.06.08.010.012.0oct - dec2003mar - may2004jul - sept2004daysmortality41.821

36、.913.10.010.020.030.040.050.0oct - dec2003mar - may2004jul - sept2004% %69% reduction (p 0.001)36% reduction (ns)pronovost p, 2005egdt in edmean sdmedianrangecentral line inserted2.1 1.71.51 8cvp goal achieved6.3 3.86.01 14map goal achieved5.6 3.24.02 13scvo2 measured2.4 1.82.01 8scvo2 goal achieved

37、6.4 4.05.02 16trzeciak s, dellinger rp, abate nl, cowan rm, stauss m, kilgannon jh, zanotti s, parrillo je. translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. chest 2006; 129: 225-232egdt in edbef

38、ore egdtegdtp value輸注晶體液ed3509 23125685 30210.02icu第一個(gè)24小時(shí)5548 48782752 17310.03pac應(yīng)用7 (43.8)2 (9.1)0.01icu住院日(d)4.2 (0.5 14.3)1.8 (0.0 34.9)0.12住院病死率7 (43.8)4 (18.2)0.09住院費(fèi)用(usd)135,19982,2330.14trzeciak s, dellinger rp, abate nl, cowan rm, stauss m, kilgannon jh, zanotti s, parrillo je. translatin

39、g research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. chest 2006; 129: 225-232sepsis bundle101名嚴(yán)重全身性感染患者符合6小時(shí)bundle普通病房: 90 (89%)急診科: 11 (11%)71名收入icu符合24小時(shí)bundle: 69 (98%)43 (61%)轉(zhuǎn)出icu28 (39%)死于icu35 (81%)存活8

40、 (19%)死亡65 (64%)存活36 (36%)死亡gao f, melody t, daniels df, giles s, fox s. the impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. critical care 2005, 9:r764-r770 (doi 10.1186/cc3909)sepsis bundle符合6小時(shí)bund

41、le (n = 101)符合24小時(shí)bundle (n = 69)52% (52/101)30% (21/69)依從率gao f, melody t, daniels df, giles s, fox s. the impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. critical care 2005, 9:r764-r770 (doi 10.1186/cc3909)sepsis bundle (6 hour)23%49%0%20%40%60%compliantnon-complianthospital mortalityrr 2.12 (1.20 3.76)p = 0.01nnt =