1、 全身炎症反应综合症 与脓毒血症（中）XXXX医院六脓毒血症治疗n1。原发病治疗n2。寻找感染源，控制感染n3。器官功能支持n4。针对炎症反应的治疗（酶抑制剂。CRRT清除炎性介质，糖皮质激素等）n5。控制血糖早期液体复苏n早期治疗目标的多中心研究表明，6h内SVO2必须70，通过积极的液体复苏、输血及应用血管活性药物治疗。n采用这种目标治疗的死亡率为30.5%，而传统的治疗方法的死亡率为46.5%。n对脓毒症患者早期积极的容量复苏能显著改善预后。脓毒血症液体复苏 n低血压事件或血乳酸4mmol/Ln 1。晶体液至少20ml/kg补液试验（胶体）等同：B1；n 2。经液体复苏后，血压持续低应给
2、与血管升压药，维持平均动脉血压（MAP）65mmHg：C1 脓毒血症液体复苏 n经液体复苏后持续低血压（脓毒性休克）或血乳酸4mmol/Ln1。建议放置CVP（中心静脉插管）n2。维持CVP 8-12mmHg（在肺顺应性增加或胸腔内压增高可以高于此）n3。达到 ScvO2 70%,SvO265%n ：1C脓毒血症液体复苏 n液体复苏后仍SvO230%。n 2CFluid TherapynCrystalloidsnLactated Ringers solutionnNormal salinenColloidsnHetastarchnAlbuminnGelatinsnPacked red bloo
3、d cellsnInfuse to physiologic endpointsFluid Therapyn Correct hypotension firstnDecrease heart ratenCorrect hypoperfusion abnormalitiesnMonitor for deterioration of oxygenationInotropic/Vasopressor AgentsnDopaminenLow dose(2-3 g/kg/min)mild inotrope plus renal effectnIntermediate dose(4-10 g/kg/min)
4、inotropic effectnHigh dose(10 g/kg/min)vasoconstrictionnChronotropic effectInotropic AgentsnDobutaminen5-20 g/kg/minnInotropic and variable chronotropic effectsnDecrease in systemic vascular resistanceInotropic/Vasopressor AgentsnNorepinephrinen0.05 g/kg/min and titrate to effectnInotropic and vasop
5、ressor effectsnPotent vasopressor at high dosesInotropic/Vasopressor AgentsnEpinephrinenBoth and actions for inotropic and vasopressor effectsn0.1 g/kg/min and titratenIncreases myocardial O2 consumptionTherapeutic Goals in ShocknIncrease O2 deliverynOptimize O2 content of bloodnImprove cardiac outp
6、ut and blood pressurenMatch systemic O2 needs with O2 deliverynReverse/prevent organ hypoperfusion严重脓毒症诊断 n在应用抗生素治疗之前，作各种培养获取病原微生物n对于插管48 小时，应该至少做两个血培养，一个经皮抽取血，另一个经导管取血。n 1C抗生素治疗 n考虑严重感染获取培养标本后，立即静脉抗生素治疗。1Bn开始经验治疗应用抗生素至少1种或几种抗生素，具有广谱抗病源菌的活力（覆盖细菌和真菌）和具有穿透组织能力抗生素。2Bn抗生素方案每日需要评估最优活性，防止耐药菌的形成，降低药物的毒性，及降
7、低医疗费用。1C感染源控制 n控制技术 举例n引流 腹腔脓肿，n 脓胸n清创术 坏死性筋膜炎，n 感染胰腺坏死n拔除管路 感染静脉插管，n 导尿尿管n权威处理 胆囊切除术，n 乙状结肠切除术液体和血管活性药物治疗n液体即可以自然或人工的晶体或胶体1Bn怀疑低血容量时，补液试验1000ml晶体或300-500ml胶体超过30分钟输液。1Dn当心脏充盈压（CVP或PAOP）增加或血液动力学无改善时，输液速度应该降低。1D 血管收缩药物应用n在脓毒血症中纠正低血压建议应用去甲肾上腺素或多巴胺等血管收缩药。1Cn低剂量的多巴胺不用于肾功能保护治疗。1An肾上腺素（2B）或血管加压素（0.03u/min
8、）（2C）可以治疗经液体复苏和高剂量常规血管收缩药无效的难治性休克 SSC Guidelines,Crit Care Med 2008强心药物治疗当心脏充盈压增加和低心输出量时，存在心功能被抑制时，推荐应用多巴酚丁胺。1C避免使用增加心指数以增加超出正常水平状态。1B SSC Guidelines,Crit Care Med 2008皮质醇激素治疗n静脉注射氢化可的松应用于成人伴有脓毒性休克，虽经液体复苏和 血管收缩剂治疗无效者。2Cn如果有氢化可的松时，应该不用地塞米松。2Bn如果应用氢化可的松后，可考虑应用氟氢可的松。1Cn脓毒血症患者氢化可的松 每天剂量不超过300mg。1AnSSC G
9、uidelines,Crit Care Med 2008 重组人活化蛋白-C的应用n推荐成人伴有脓度血症诱导器官功能障碍伴高死亡率（APACHE-25）或多器官功能衰竭并且无出血相关的禁忌症。2Bn成人伴有严重脓度血症和低死亡率（APACHE-20）或一器官功能衰竭者不接受rhAPC。1A脓毒血症诱导ALI/ARDS的机械通气n目标潮气量6ml/kg 1Bn维持平台压 30cmH2O 1Cn允许性高碳酸血症被接受维持最低的平台压和潮气量1CnPEEP设置避免在呼气时广泛的肺塌陷1Cn在严重的ARDS可以腹卧位2Cn降低VAP需要头抬高30-45 2C n建议不常规行PA检测1An建议保守液体疗
10、法减少机械通气时间和在ICU的时间。1C血糖的控制n推荐病人伴有脓毒血症和高血糖者进入ICU应静脉应用胰岛素降低血糖。1Bn应用胰岛素维持血糖 1000 ml of crystalloids or 300-500 ml of colloids over 30 mins.Grade 1DRate of fluid administration should be reduced substantially when cardiac filling pressures(CVP or PAOP)increase without concurrent hemodynamic improvement G
11、rade 1D液体及血管活性药物应用Fluid resuscitation with either natural or artificial colloids or crystalloids.Grade 1BFluid challenge in patients with suspected hypovolemia may start with 1000 ml of crystalloids or 300-500 ml of colloids over 30 mins.Grade 1DRate of fluid administration should be reduced substan
12、tially when cardiac filling pressures(CVP or PAOP)increase without concurrent hemodynamic improvement Grade 1DRCT 7,000 pts in 16 Australian/NZ ICUsExcluded pts after cardiac surgery,liver transplant and burns 4%albumin or NS No significant difference:28-day mortality New organ failure,duration of C
13、RRT,or mechanical ventilation ICU and Hospital LOSNEJM 2004;350:2247-2256Either norepinephrine or dopamine is the first choice vasopressor agent to correct hypotension in septic shock.Grade 1CLow-dose dopamine should not be used for renal protection.Grade 1AEpinephrine(2B)or Vasopressin(0.03 U/min)(
14、2C)may be added in pts with refractory shock despite adequate fluids and high-dose conventional vasopressors.SSC Guidelines,Crit Care Med 2008Dobutamine infusion is recommended in the presence of myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output.Grade 1
15、CAvoid use of strategy to increase cardiac index to predetermined supranormal levels.Grade 1BSSC Guidelines,Crit Care Med 2008nIV hydrocortisone should be given only to adult septic shock patients after it has been confirmed that their BP is poorly responsive to fluid resuscitation and vasopressor t
16、herapy.Grade 2CnCrit Care Med 2008 SSC UpdateRelative adrenal insufficiencynFailure to increase cortisol by 9 g/dlat 30-or 60-min following 250 g ACTH stimulation testn nAnnane D,et al.JAMA 2000;283:1038-45nClinical Practice Guidelines for the Diagnosis and Management of Corticosteroid Insufficiency
17、 in Critical Illness:Recommendations from an International Task ForceMarik PE,Pastores SM,Annane D,Meduri GU,Sprung C,et al.Crit Care Med(under review)Consensus StatementAt this time,CIRCI is best diagnosed by a delta cortisol(following 250 g cosyntropin)of 9 g/dl or a random cortisol of 300 mg of h
18、ydrocortisone daily not be used in septic shock(1A)Marik PE,Pastores SM,Annane D,Meduri GU,Sprung C,et al.Crit Care Med 2008(under review);SCC 2008 Update 2008Recombinant Human Activated Protein CnRecommended in adult pts with sepsis-induced organ dysfunction associated with a high risk of death(APA
19、CHE II 25)or multiple organ failure and with no contraindications related to bleeding Grade 2BnAdult patients with severe sepsis and low risk of death(APACHE II 750,000 new cases per year in the U.S.Mortality rates range from 28%to 50%Approximately 500 to 1,000 Americans die daily of severe sepsisAn
20、gus DC,et al.Crit Care Med 2001;29:1303-10Murphy SL.National Center for Health Statistics,2000.DHHS.Angus DC,et al.Crit Care Med 2001;American Cancer SocietyIncidenceCases/100,000MortalityDeaths/YearAngus DC,et al.Crit Care Med 2001.0%5%10%15%20%25%30%35%40%45%01510152025303540455055606570758085AgeM
21、ortalityWithout Co-morbidityWith Co-morbidityOverallPulmonary:50%Abdomen/Pelvis:25%Primary bacteremia:15%Urosepsis:10%Skin:5%Vascular:5%Other:15%Martin GS,et al.NEJM 2003;348:1546 Microbiology of SepsisMartin GS,et al.NEJM 2003;348:1546International effort to increase awareness and improve outcomes
22、in severe sepsisEndorsed by various organizations including SCCM,ACCP,ACEP,SHM,AACCN,and ESICM Crit Care Med 2008;36:296-327 Partial funding by unrestricted educational industry grants from:Edwards Life-SciencesEli Lilly and CompanyPhilips Medical SystemsCoalition for Critical Care Excellence of SCC
23、M No industry funding was used in the guidelines revision processCrit Care Med 2008;36:296-327 Modified GRADE SystemGrading of Evidence1A:Strong recommendation,high quality evidence1B:Strong recommendation,moderate quality of evidence1C:Strong recommendation,low quality or very low quality evidence2
24、A:Weak recommendation,high quality evidence2B:Weak recommendation,moderate quality evidence2C:Weak recommendation,low quality or very low quality of evidenceGuyatt G,et al.Chest 2006;129:174-81Should begin as soon as the syndrome is recognized and should not be delayed pending ICU admission.Elevated
25、 serum lactate concentration identifies tissue hypoperfusion in patients at risk who are not hypotensive.Goals in the first 6 hours:CVP:8-12 mm HgMAP 65 mm HgUrine output 0.5 ml/kg/hrCentral venous(SVC)or mixed venous oxygen(SvO2)saturation 70%GRADE 1C EGDT for Severe Sepsis and Septic ShockRivers,E
26、 et al.NEJM 2001;345:1368 EGDT in Severe Sepsis and Septic ShockRivers et al,NEJM 2001;345:1368EGDT in the Treatment of Severe Sepsis and Septic Shock Rivers et al,NEJM 2001;345:1368In the event of hypotension and/or lactate 4 mmol/L:Administer a minimum of 20 ml/kg of crystalloid(or colloid equival
27、ent):1BUse vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP 65 mmHg:1CSSC Guidelines-IHIIf persistent arterial hypotension despite volume resuscitation(septic shock)and/or initial lactate 4 mmol/L:Recommend insertion of central venous catheterAchieve CVP of
28、8-12 mmHgHigher with altered ventricular compliance or increased intrathoracic pressureAchieve ScvO2 of 70%or SvO2 65%SSC Guidelines-IHIGrade 1CIf ScvO2 remains 70%after fluid resuscitation goals are metDobutamine up to 20 g/kg/minTransfusion to maintain Hct 30%Grade 2CSSC Guidelines,Crit Care Med 2
29、008 nAppropriate cultures should always be obtained before antimicrobial therapy is initiated.nAt least 2 blood cultures with at least one drawn percutaneously and one drawn through each vascular access device,unless the device was recently(1000 ml of crystalloids or 300-500 ml of colloids over 30 m
30、ins.Grade 1DRate of fluid administration should be reduced substantially when cardiac filling pressures(CVP or PAOP)increase without concurrent hemodynamic improvementGrade 1DSSC Guidelines,Crit Care Med 2008Albumin and Saline for Fluid RCT 7,000 pts in 16 Australian/NZ ICUsExcluded pts after cardia
31、c surgery,liver transplant and burns 4%albumin or NS No significant difference:28-day mortality New organ failure,duration of CRRT,or mechanical ventilation ICU and Hospital LOSNEJM 2004;350:2247-2256Either norepinephrine or dopamine is the first choice vasopressor agent to correct hypotension in se
32、ptic shock.Grade 1CLow-dose dopamine should not be used for renal protection.Grade 1AEpinephrine(2B)or Vasopressin(0.03 U/min)(2C)may be added in pts with refractory shock despite adequate fluids and high-dose conventional vasopressors.SSC Guidelines,Crit Care Med 2008Dobutamine infusion is recommen
33、ded in the presence of myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output.Grade 1CAvoid use of strategy to increase cardiac index to predetermined supranormal levels.Grade 1BSSC Guidelines,Crit Care Med 2008 nIV hydrocortisone should be given only to adu
34、lt septic shock patients after it has been confirmed that their BP is poorly responsive to fluid resuscitation and vasopressor therapy.Grade 2CCrit Care Med 2008 SSC UpdateRelative adrenal insufficiencynFailure to increase cortisol by 9 g/dlat 30-or 60-min following 250 g ACTH stimulation testAnnane
35、 D,et al.JAMA 2000;283:1038-45Onset of shockRandomizationHydrocortisone IV 50-mg every 6 hours x 7 days+Fludrocortisone 50 mcg NGdaily x 7 daysPlaceboX 7 days0EligibilityandACTH testMain Outcome:28-day survivalAnnane,D.JAMA,2002;288(7):863Low Dose Steroids in Septic Shock:28 Day Mortality All Patien
36、tsLow-dose SteroidsPlaceboP=0.0928-day MortalityAnnane,D.JAMA,2002;288(7):868N=150N=14930%40%50%60%70%80%90%100%0481216202428Time(days)Probability of survivalPLACEBOSTEROIDSHazard Ratio:0.67(95%CI,0.47-0.95)p=0.02NON RESPONDER28-Day SurvivalAnnane et al.JAMA 2002;288:86230%40%50%60%70%80%90%100%0481216202428TIME(days)Probability of survivalPLACEBOSTEROIDSRESPONDERSLog-Rank-Test,2=0.56p=0.8128-Day SurvivalAnnane et al.JAMA 2002;288:862
