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1、严重感染和感染性休克严重感染和感染性休克治疗进展治疗进展邱海波邱海波 东南大学附属中大医院东南大学附属中大医院ICU东南大学急诊与危重病医学研究所东南大学急诊与危重病医学研究所Annual incidence of severe sepsis: 3 cases/ 1,000 Kill: 1,400 people worldwide /d 25 people /hMoreover, No. of sepsis pats is projected to increase by 1.5% per annum 严严重重感感染染的的病病死死人人数数超超过过乳乳腺腺癌癌、直直肠肠癌癌、结结肠肠癌癌、胰腺癌
2、和前列腺癌的总和胰腺癌和前列腺癌的总和严重感染严重感染 vs AMI:发病率相同，病死率明显高发病率相同，病死率明显高Sepsis in worldwide Surviving Sepsis Compaign拯救拯救Sepsis运动运动巴塞罗那宣言巴塞罗那宣言ESICM SCCM ISF 20022002年年1010月月2 2日日, , 西班牙西班牙Commit to a goal of a 25% relative reduction of mortality from sepsis in 5YSurviving Sepsis CampaignPhase : Barcelona Declar
3、ationPhase : Guidelines creationPhase : Clinical outcome evaluationGUIDELINES FOR MANAGEMENGT OF SEVERE SEPSIS AND SEPTIC SHOCKAACCN; American Association of Critical-Care Nurses AACCN; American Association of Critical-Care Nurses ACCP: American College of Chest Physicians ACCP: American College of
4、Chest Physicians ACEP: American College of Emergency PhysiciansACEP: American College of Emergency PhysiciansATS: American Thoracic Society ATS: American Thoracic Society ANZICS: Australian and New Zealand Intensive Care SocietyANZICS: Australian and New Zealand Intensive Care SocietyESCMID: Europea
5、n Society of Clinical Microbiology and Infectious ESCMID: European Society of Clinical Microbiology and Infectious DisDis ERS: European Respiratory Society ERS: European Respiratory Society SIF: Surgical Infection SocietySIF: Surgical Infection SocietyESICM: European Society of Intensive Care Medici
6、neESICM: European Society of Intensive Care Medicine ISF:InternationalISF:International Sepsis Forum Sepsis Forum SCCM: Society of Critical Care MedicineSCCM: Society of Critical Care MedicineGuidelines for sepsis. Intensive Care Med 2004, 30: 536-555循证医学循证医学-推荐级别推荐级别A：至少至少2个个级研究证实级研究证实B： 1个个级研究证实级研
7、究证实C： 级研究证实级研究证实D：至少至少1个个级研究证实级研究证实E：或或级研究证实级研究证实研究级别研究级别I I. Large, randomized trials with . Large, randomized trials with clearcutclearcut results resultsII II. Small, randomized trials with uncertain results. Small, randomized trials with uncertain resultsIIIIII. Nonrandomized, contemporaneous co
8、ntrols. Nonrandomized, contemporaneous controlsIVIV. Nonrandomized, historical controls and expert opinion. Nonrandomized, historical controls and expert opinionV V. Case series, uncontrolled studies, and expert opinion. Case series, uncontrolled studies, and expert opinionA. 早期复苏1. 早期目标性复苏治疗(EGDT)最
9、初6小时应达到的目标 CVP: 8-12 mmHg（MV 12-15mmHg） MAP65 mmHg Urine output0.5mLkg-1h-1 SvO270%Grade BGrade BA. 早期复苏2.若最初6h治疗，CVP达到8-12mmHg，而SvO270%Transfuse packed red blood cells： HCT 30% and/or Dobu iv ( up to max 20 gkg-1min-1)Grade BGrade BB. 病源学诊断1.抗生素治疗前要进行细菌学培养 Appropriate cultures before antimicrobial
10、therapy is initiatedIn order to optimize identification of causative organisms, at least two blood cultures should be obtained with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was 48h inserted Grade DGrade D*p 20 mm HglContinous aspiration o
11、f subglottic secretionslContaminated condensate should be emptiedATS. Am J Respir Crit Care Med 2005;171:388-416Modifiable Risk FactorsAspiration, body position, and feedinglSemirecumbent position (30-45)lEnteral feeding is preferredModulation of colonizationlRoutine prophylaxis is not recommendedSt
12、ress bleeding prophylaxis, transfusion, and hyperglysemialH2 antogonists or sucralfate is acceptablelRestricted transfusion trigger policylIntensive insulin therapyATS. Am J Respir Crit Care Med 2005;171:388-416E. 液体治疗1. Fluid resuscitation may consist of artificial colloids or crystalloids. There i
13、s no evidence-based support of one type of fluid over anotherGrade CGrade CE. 液体治疗2. Fluid challenge in pats with suspected hypovolemia may be given at a rate of 500-1000ml of crystalloids or 300-500ml colloids over 30min and repeated based on response (increase in BP and urine output) and tolerance
14、 (evidence of intravascular volume overload)Grade EGrade EF. 血管活性药物 1. 充充分分液液体体复复苏苏后后血血压压和和器器官官灌灌注注仍仍不不能能维维持持，是是应应用用血血管管活活性性药药物物的的指指征征；对对于于威威胁胁生生命命的的低低血血压压，即即使使低低容容量量状态尚未纠正，也应及时使用血管活性药物状态尚未纠正，也应及时使用血管活性药物Grade E2.去甲肾上腺素和多巴胺是治疗感染性休克的一线药物去甲肾上腺素和多巴胺是治疗感染性休克的一线药物Grade D3.3.小小剂剂量量多多巴巴胺胺对对重重症症感感染染者者无无肾肾保保
15、护护作作用用 Grade BF. 血管活性药物 4.应用血管活性药物时应用血管活性药物时，最好采用动脉置管监测有创血压，最好采用动脉置管监测有创血压Grade E5.充分容量复苏和大剂量传统血管活性药物无效的难治性充分容量复苏和大剂量传统血管活性药物无效的难治性休克，可应用血管加压素（休克，可应用血管加压素（0.010.04Umin） （降低（降低SV）Grade EG.正性肌力药物1.如如果果病病人人经经充充分分容容量量复复苏苏后后,存存在在低低CO，可可应应用用Dobu；对低血压者，应联合应用血管活性药物；对低血压者，应联合应用血管活性药物合适的容量状态和合适的容量状态和MAP时，时，Do
16、bu是低是低CI者首选者首选无无CO监测时，感染性休克监测时，感染性休克CO存在低、正常和高存在低、正常和高3种情况，推荐种情况，推荐NEDopa能够监测血压和能够监测血压和CO时，可目标性应用时，可目标性应用NE提升血提升血压，应用压，应用Dobu提高提高COGrade EGrade EG.正性肌力药物2.应用Dobu以达到超常的氧输送水平对重症感染无效Grade AGrade AH. 糖皮质激素1.经经足足够够液液体体复复苏苏，但但仍仍需需应应用用缩缩血血管管药药物物维维持持血血压压的的感感染染性性休休克克患患者者，推推荐荐应应用用皮皮质质类类固固醇醇激激素素。氢氢化化可可的的松松200-
17、300mg/d，分，分34 次静点，连用次静点，连用7dGrade Ca. 对对于于感感染染性性休休克克，不不需需作作ACTH应应激激试试验就可应用激素验就可应用激素 Grade Eb. 休克改善后，激素应减量休克改善后，激素应减量Grade E肾上腺功能低下的感染性休克肾上腺功能低下的感染性休克低剂量的糖皮质激素可逆转休克、降低病死率低剂量的糖皮质激素可逆转休克、降低病死率IObjective: evaluated low dose GS to survival in septic shock patients and AI (Post-ACTH cortisol rise 9ug/dl)I
18、Design: placebo-controlled, randomized,double-blind, parallel-group trialISetting: Multicenter, 19 ICU in France (95.1099.2)ITwo groupsaHydrocortisone (n=151) (50mg,iv bolus Q6h and fludrocortisone 50ug tablet once daily for 7days)aPlacebo(n=149)Annane D,et al. JAMA, 2002,288: 862-871减少升压药应用减少升压药应用B
19、ut not in non-AI groupBut not in non-AI groupMortality rateAnnane D, et al. JAMA 2002;288:862-871No. (%)VariablePlaceboSteroidsP ValueNo. of patients11511428-day mortality73(63)60(53)0.04ICU mortality81(70)66(58)0.02Hospital mortality83(72)70(61)0.041-yr mortality88(77)77(68)0.07 H. 糖皮质激素2. 氢化考地松用量不
20、应大于300mg/day； Grade AH. 糖皮质激素3.不不推推荐荐使使用用于于非非休休克克的的sepsis患患者者，但但对对于于既既往往应应用用皮皮质质类类固固醇醇激激素素或或存存在在肾肾上上腺腺功功能能障障碍碍的的患患者者，不不是是维维持持剂剂量量或或应激剂量激素治疗的禁忌症。应激剂量激素治疗的禁忌症。 Grade EI. 重组人活化蛋白C (rhAPC)1. rhAPC is recommended in patients at high risk of death APACHE II 25 Sepsis-induced MODS Septic shock Or sepsis-in
21、duced-ARDS And no absolute contraindication related to bleeding riskGrade BGrade BJ. 血液制品1.组组织织低低灌灌注注改改善善，而而且且无无严严重重冠冠脉脉疾疾病病、急急 性性 失失 血血 或或 乳乳 酸酸 血血 症症 等等 情情 况况 下下 ，HB7.0g/dl时时，应应该该输输红红细细胞胞，目目标标: 7.09.0 g/dlGrade BGrade BTransfusion requirements in critical careMulticenter，randomized，controlled6451
22、pats assessed，838 consented Hb9 g/dl （72h/ ICU）418 patsrestrictive transfusion strategy Hb 7g/dltransfusion79g/dl420 patsliberal transfusion strategy Hb10g/dltransfusion1012g/dlRestrictive strategy of red-cell transfusion is as effective as and possibly superior 限制输血组住院限制输血组住院生存率高生存率高 Exception of A
23、MI and unstable anginaHebert PC,et al. N Engl ed 1999，340：409-417K. ALI/ARDS的机械通气1.以以较较小小的的VT(如如6ml/kg标标准准体体重重VT)为为调调节起点，以保证节起点，以保证Ppla30cmH2O 标准体重：男标准体重：男=50+0.91身高身高(cm)-152.4 女女=45.5+0.91身高身高(cm)-152.4Grade BGrade BK. ALI/ARDS的机械通气2. 限制限制VT和和Pplt，实施允许性高碳酸血症，实施允许性高碳酸血症相对禁忌：相对禁忌： 已存在代谢性酸中毒的患者已存在代谢性
24、酸中毒的患者禁忌：禁忌： 存在颅内高压的患者存在颅内高压的患者Grade CGrade CK. ALI/ARDS的机械通气3.采用可防止呼气末肺泡采用可防止呼气末肺泡塌陷的最低塌陷的最低PEEPGrade EGrade E4.对对于于需需高高FiO2和和高高Ppla的的ARDS病病人人，若若体体位位改变无严重并发症，可应用俯卧位通气改变无严重并发症，可应用俯卧位通气Grade EGrade EK. ALI/ARDS的机械通气5.若若无无禁禁忌忌症症，机机械械通通气气患患者者应应采采取取头头抬抬高高45。以上的半卧位，以防止以上的半卧位，以防止VAPGrade CGrade CK. ALI/AR
25、DS的机械通气6.患患者者达达到到以以下下条条件件时时，应应进进行行自自主主呼呼吸吸测测试试(SBT)，以指导脱机以指导脱机清醒清醒血流动力学稳定血流动力学稳定无新的患病危险因素无新的患病危险因素较低的通气条件和较低的通气条件和PEEP水平水平所需所需FiO2可通过面罩或鼻导管吸氧实现可通过面罩或鼻导管吸氧实现实施：实施：5cnH2O的的CPAP通气支持或通气支持或T管管Grade AGrade AEffect on the duration of mechanical ventilation of identifying patients capable of breathing spont
26、aneouslyBackground: ranbomized,controlled trialMethods:intervention group149 control group151intervention group:daily screening of respiratory function,followed by two-hour trials of spontaneous breathingControl group: daily screening of respiratory function,but on other interventions.Ely EW, et al.
27、 N Engl J Med, 1996,335: 1864-9nMV(d)ComplicationsICU CostsHosp CostsSBT1494.520%1574026229Control151641%20890290480.0030.0010.030.3Ely EW, et al. N Engl J Med, 1996,335: 1864-9Complications: removal of the brething tube by the patient, reintubation, tracheostomy, MV for more than 21 dSBT-SBT-降低降低MV
28、MV时间和并发症时间和并发症L. 镇静、镇痛和肌松剂应用镇静、镇痛和肌松剂应用1. 应应建建立立镇镇静静的的临临床床应应用用方方案案，包包括括镇镇静静目目标标和和镇静程度评价镇静程度评价 Grade BGrade B2. 无无论论是是持持续续镇镇静静还还是是间间断断镇镇静静给给药药，每每天天均均应应暂时中断镇静暂时中断镇静 Grade BGrade B3. 尽量避免使用肌松剂尽量避免使用肌松剂Grade EGrade EM. 血糖控制1.严格控制血糖 8.3 mmol/L(215 mg/dl maintain 180200 mg/dlGreet VB et al. N Engl J Med 2
29、001, 345: 1359-1367Base line Convention(n)Intensive(n)N783765Age6263APACHE 99diabetes103101Blood glucose 110598557 20010181Reason for ICU Cardiac surgery Neurologic disease Thoracic surgery, respiratory insufficiency Abdominal surgery or peritonitis Multiple trauma or severe burns Transplantation Ot
30、her493 47730 3356 6658 4535 3344 4635 35Greet VB et al. N Engl J Med 2001, 345: 1359-1367N.肾脏替代治疗1. 合并急性肾衰时，合并急性肾衰时，CVVH和或间歇性血和或间歇性血液透析均可进行肾脏替代治疗，但对于液透析均可进行肾脏替代治疗，但对于血流动力学不稳定者，血流动力学不稳定者，CRRT更有利于液更有利于液体管理体管理(Septic shock CRRT: Vasopressor) Grade BGrade BN. 碱性药物1.pH 7.15时不推荐应用碱性药物以对抗由于低灌注引起的乳酸血症Grade
31、CGrade CP.深静脉血栓预防深静脉血栓预防对于重症感染患者应该应用小剂量肝素或低分子肝素预防DVT对于有肝素禁忌症的全身性感染患者，推荐使用（除非病人有外周血管疾病的禁忌症）机械预防装置。对于极高危者，如有DVT病史的重症感染患者，推荐联合使用抗凝和机械预防装置Grade AGrade AQ.应激性溃疡预防应激性溃疡预防1. 所有重症感染患者都应应用H2受体阻断剂以预防应激性溃疡；H2受体阻断剂比硫糖铝更有效； H2受体阻断剂与PPI缺乏比较性研究，但制酸效果类似Grade AGrade AAlthough these recommendations are written primar
32、ily for the patient in the ICU setting, many recommendations are appropriate targets for the pre-ICU setting.It should also be noted that resource limitations may prevent physicians from accomplishing a recommendation.These recommendations are intended to provide guidance for the clinician caring fo
33、r a pat with severe sepsis and septic shock, but not for all pats.Recommendations from these guidelines cannot replace the clinicians decision-making capability when he or she is provided with pats unique set of clinical variables The challenge is how best to apply these therapie in clinical practice Appropriate patient selection Timing of therapy Combining different approachesFor optimal pat management
