1、严重感染和感染性休克治疗进展,邱海波 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,Annual incidence of severe sepsis: 3 cases/ 1,000 Kill: 1,400 people worldwide /d 25 people /h Moreover, No. of sepsis pats is projected to increase by 1.5% per annum严重感染的病死人数超过乳腺癌、直肠癌、结肠癌、胰腺癌和前列腺癌的总和 严重感染 vs AMI:发病率相同，病死率明显高,Sepsis in worldwide,Survi
2、ving Sepsis Compaign 拯救Sepsis运动,巴塞罗那宣言,ESICM SCCM ISF 2002年10月2日, 西班牙,Commit to a goal of a 25% relative reduction of mortality from sepsis in 5Y,Surviving Sepsis Campaign,Phase : Barcelona DeclarationPhase : Guidelines creationPhase : Clinical outcome evaluation,GUIDELINES FOR MANAGEMENGT OF SEVERE
3、 SEPSIS AND SEPTIC SHOCK,AACCN; American Association of Critical-Care Nurses ACCP: American College of Chest Physicians ACEP: American College of Emergency Physicians ATS: American Thoracic Society ANZICS: Australian and New Zealand Intensive Care Society ESCMID: European Society of Clinical Microbi
4、ology and Infectious Dis ERS: European Respiratory Society SIF: Surgical Infection SocietyESICM: European Society of Intensive Care MedicineISF:International Sepsis Forum SCCM: Society of Critical Care Medicine,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,循证医学-推荐级别,A：至少2个级研究证实 B： 1个级研
5、究证实 C： 级研究证实 D：至少1个级研究证实 E：或级研究证实,研究级别 I. Large, randomized trials with clearcut results II. Small, randomized trials with uncertain results III. Nonrandomized, contemporaneous controls IV. Nonrandomized, historical controls and expert opinion V. Case series, uncontrolled studies, and expert opinion
6、,A-Initial resuscitation: early goal-directed therapy B-Diagnosis: appropriate culture C-Antibiotic therapy: Early broad-spectrum, reassessed 2-3d D-Source control: E-Fluid therapy: colloids=crystalloids,VLT F-Vasopressors: After VLS, NE vs Dopa, Low-dose dopa is not , cath for vaso G-Inotropic ther
7、apy: low CO-dobu, high CO is not H-Steroid: low dose I-rhAPC: APACHE II 25, sepsis-induced ARDS/MOF and no bleeding risk,J-Blood product administration: target Hb 7-9g/dl, EPO only in renal failure K-Mechanical ventilation: Ppla30, Hypercapnia, optimal PEEP, Prone position L-Sedation, analgesia and
8、NBMs: Protocol M-Glucose control: 150mg% N-Renal replacement: O-Bicarbonate: pH 7.15 P-DVT: UH/LMWH Q-Stress ulcer prophylaxis: H2blocker R-Consideration of limitation of support,A. 早期复苏,1. 早期目标性复苏治疗(EGDT)最初6小时应达到的目标CVP: 8-12 mmHg（MV 12-15mmHg）MAP65 mmHgUrine output0.5mLkg-1h-1SvO270%,Grade B,A. 早期复
9、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 B,B. 病源学诊断,1.抗生素治疗前要进行细菌学培养Appropriate cultures before antimicrobial therapy is initiatedIn order to optimize identification of causative organisms, at least two blood cultures
10、should be obtained with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was 48h inserted,Grade D,Peripheral blood(PB),vascular access device(VAD),Same organism,The organism is causing the ssepsis,VAD culture is positive 2h earlier than PB,VAD is
11、 the source of the infection,Weinstein MP. Rev Infect Dis 1983, 5: 35-53 Blot F. J Clin Microbiol 1998, 36: 105-109,*p 0.001,Volume of blood may be important,Mermel LA. Ann Intern Med 1993, 119: 270-272,B. 病源学诊断,2. 尽快确定感染灶和致病菌TO determine the source of infection and the causative organismImaging stu
12、dies Sampling of likely sources of inf Ultrasound,Grade E,C. 抗生素治疗,1.抗生素治疗在病人诊断为重症感染并已取标本后1h内开始2. Initial empiric anti-infective therapy Broad-spectrum Penetrate into the presumed source Guided by the susceptibility patterns of microorganisms in the community and in the hosp,Grade 1E/2D/3E/4E,High m
13、ortality of sepsis, severe sepsis and septic shock,Prospective cohort study ICU of a tertiary hosp 406 pats included At ICU admission: Sepsis 25.9% Ssepsis 28.6% Sshock 45.6%,CCM, 2003, 31: 2742,严重感染的病死率降低23,C. 抗生素治疗,3. The antimicrobial regimen should always be reassessed after 4872h on the microbi
14、ological and clinical data with the aim of using a narrow-spectrum antibiotic (Duration of therapy: 7-10d, guided by clinical response)4. If the clinical syndrome is determined to be due to a non-infectious causeStop antimicrobial therapy promptlyMinimize the resistant and superinfection,Grade 1E/2D
15、/3E/4E,D. 治疗原发病灶,Drainage of an abscess or local focus on infection Debridement of infected necrotic tissue Removal of a potentially infected device,Grade E,D.治疗原发病灶,Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia,This offici
16、al statement American Thoracic Society (ATS) And Infectious Diseases Society of America (ISDA) Approved by the ATS Board of Directors, December 2004 and the IDSA Guideline Committee, October 2004,Am J Respir Crit Care Med 2005, 171. 388416,Modifiable Risk Factors,Intubation & mechanical ventilation
17、Noninvasive positive-pressure ventilation should be preferred Reintubation should be avoided Oral insertion is preferred Cuff pressure 20 mm Hg Continous aspiration of subglottic secretions Contaminated condensate should be emptied,ATS. Am J Respir Crit Care Med 2005;171:388-416,Modifiable Risk Fact
18、ors,Aspiration, body position, and feeding Semirecumbent position (30-45) Enteral feeding is preferred Modulation of colonization Routine prophylaxis is not recommended Stress bleeding prophylaxis, transfusion, and hyperglysemia H2 antogonists or sucralfate is acceptable Restricted transfusion trigg
19、er policy Intensive insulin therapy,ATS. Am J Respir Crit Care Med 2005;171:388-416,E. 液体治疗,1. Fluid resuscitation may consist of artificial colloids or crystalloids. There is no evidence-based support of one type of fluid over another,Grade C,E. 液体治疗,2. Fluid challenge in pats with suspected hypovo
20、lemia 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 (evidence of intravascular volume overload),Grade E,F. 血管活性药物,1. 充分液体复苏后血压和器官灌注仍不能维持，是应用血管活性药物的指征；对于威胁生命的低血压，即使低容量状态尚未纠正，也应及时使用血管
21、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 Grade D3.小剂量多巴胺对重症感染者无肾保护作用 Grade B,F. 血管活性药物,4.应用血管活性药物时，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休克，可应用血管加压素（0.010.04Umin）（降低SV）Grade E,NE和Dopa优于肾上腺素和苯肾上腺素 Dopa通过提高SV和HR来提高动脉BP和CI NE通过缩血管效应来提高BP，不改变SV和HR NE改善低血压状态更有效，Dopa改善心肌收缩力更有效，但易致心律失常,血管活性药物,Martin C
22、. Chest 1993:1826-1831,A large randomized trial and a meta-analysis Low-dose dopamine and placebo No difference in Peak serum Cr, need for RRT,Urine output, timeto recovery of normal renal function Survival, ICU stay, Hospital stay, Arrhythmias,血管活性药物,Low-dose dopamine should not be used for renal p
23、rotection as part of the treatment of severe sepsis,Bellomo R. Lancet 2000, 356: 2139 Kellum J. CCM, 2003, 29:1526,G.正性肌力药物,1.如果病人经充分容量复苏后,存在低CO，可应用Dobu；对低血压者，应联合应用血管活性药物合适的容量状态和MAP时，Dobu是低CI者首选 无CO监测时，感染性休克CO存在低、正常和高3种情况，推荐NEDopa 能够监测血压和CO时，可目标性应用NE提升血压，应用Dobu提高CO,Grade E,G.正性肌力药物,2.应用Dobu以达到超常的氧输送
24、水平对重症感染无效,Grade A,H. 糖皮质激素,1.经足够液体复苏，但仍需应用缩血管药物维持血压的感染性休克患者，推荐应用皮质类固醇激素。氢化可的松200-300mg/d，分34 次静点，连用7dGrade C a. 对于感染性休克，不需作ACTH应激试验就可应用激素Grade E b. 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 低剂量的糖皮质激素可逆转休克、降低病死率,Objective: evaluated low dose GS to survival in septic shock patients and AI (Post-ACTH cortisol
25、rise 9ug/dl) Design: placebo-controlled, randomized,double-blind, parallel-group trial Setting: Multicenter, 19 ICU in France (95.1099.2) Two groups Hydrocortisone (n=151) (50mg,iv bolus Q6h and fludrocortisone 50ug tablet once daily for 7days) Placebo(n=149),Annane D,et al. JAMA, 2002,288: 862-871,
26、减少升压药应用 But not in non-AI group,Mortality rate,Annane D, et al. JAMA 2002;288:862-871,H. 糖皮质激素,2. 氢化考地松用量不应大于300mg/day；Grade A,H. 糖皮质激素,3.不推荐使用于非休克的sepsis患者，但对于既往应用皮质类固醇激素或存在肾上腺功能障碍的患者，不是维持剂量或应激剂量激素治疗的禁忌症。Grade E,I. 重组人活化蛋白C (rhAPC),1. rhAPC is recommended in patients at high risk of death APACHE II
27、 25Sepsis-induced MODSSeptic shockOr sepsis-induced-ARDSAnd no absolute contraindication related to bleeding risk,Grade B,J. 血液制品,1.组织低灌注改善，而且无严重冠脉疾病、急性失血或乳酸血症等情况下，HB7.0g/dl时，应该输红细胞，目标: 7.09.0 g/dl,Grade B,Transfusion requirements in critical care,Multicenter，randomized，controlled 6451 pats assessed
28、，838 consentedHb9 g/dl （72h/ ICU） 418 patsrestrictive transfusion strategyHb 7g/dltransfusion79g/dl 420 patsliberal transfusion strategyHb10g/dltransfusion1012g/dlRestrictive strategy of red-cell transfusion is as effective as and possibly superior 限制输血组住院生存率高 Exception of AMI and unstable angina,He
29、bert PC,et al. N Engl ed 1999，340：409-417,J. 血液制品,2. 不推荐使用EPO，但合并如肾衰影响红细胞生成时可以使用,Grade B,Efficacy of rHuEPO,Prospective，randomized，double-blind ，placebo- controled，multicenter trial 33685 pats assessd, 1302 randomized 650 rHuEPO 652 placebo40000U ICU d3(1)，continued weekly(7,14,21),Conclusions: Redu
30、ce RBC transfusion No differences in clinical outcomes,Corwin HL,et al. JAMA,2002,288:2827-2835,J. 血液制品,3.如无明显出血倾向或计划有创性操作，不推荐常规输注FFP治疗检验性凝血异常Grade E 4. 重症感染和感染性休克均不推荐应用抗凝血酶Grade B 5. 重症感染病人plt输注指征plt5109/L, 无论有无明显出血，必须输plt530 109/L, 有明显出血的危险，可以输plt50109/L, 在外科手术或侵入性操作时输pltGrade E,K. ALI/ARDS的机械通气,1
31、.以较小的VT(如6ml/kg标准体重VT)为调节起点，以保证Ppla30cmH2O标准体重：男=50+0.91身高(cm)-152.4女=45.5+0.91身高(cm)-152.4,Grade B,小潮气量通气研究,结果分析,三个阴性研究结果共288病例 三个阴性研究结果常规机械通气组的Pplat仅略有增高( 26.8, 31.7, 30.6cmH2O) 常规通气组和保护策略组PEEP水平较低 可能影响实验结果 两个阳性结果共914个病例 常规通气组Pplat高于其他实验( 36.8, 34cmH2O) Amato 的研究根据P-V曲线低位转折点选择PEEP (16.4cmH2O), 加以R
32、M( 30-40cmH2O CPAP, 40s), 病死率明显降低(38%) 但常规通气组病死率(72%)高于其他研究,K. ALI/ARDS的机械通气,2. 限制VT和Pplt，实施允许性高碳酸血症相对禁忌： 已存在代谢性酸中毒的患者 禁忌： 存在颅内高压的患者,Grade C,K. ALI/ARDS的机械通气,3.采用可防止呼气末肺泡塌陷的最低PEEPGrade E4.对于需高FiO2和高Ppla的ARDS病人，若体位改变无严重并发症，可应用俯卧位通气Grade E,K. ALI/ARDS的机械通气,5.若无禁忌症，机械通气患者应采取头抬高45。以上的半卧位，以防止VAP Grade C,
33、K. ALI/ARDS的机械通气,6.患者达到以下条件时，应进行自主呼吸测试(SBT)，以指导脱机 清醒 血流动力学稳定 无新的患病危险因素 较低的通气条件和PEEP水平 所需FiO2可通过面罩或鼻导管吸氧实现实施：5cnH2O的CPAP通气支持或T管Grade A,Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously,Background: ranbomized,controlled trial Methods:interventi
34、on group149control group151 intervention group:daily screening of respiratory function,followed by two-hour trials of spontaneous breathing Control group: daily screening of respiratory function,but on other interventions.,Ely EW, et al. N Engl J Med, 1996,335: 1864-9,Ely EW, et al. N Engl J Med, 19
35、96,335: 1864-9,SBT-降低机械通气时间,Ely EW, et al. N Engl J Med, 1996,335: 1864-9,Complications: removal of the brething tube by the patient, reintubation, tracheostomy, MV for more than 21 d,SBT-降低MV时间和并发症,L. 镇静、镇痛和肌松剂应用,1. 应建立镇静的临床应用方案，包括镇静目标和镇静程度评价Grade B 2. 无论是持续镇静还是间断镇静给药，每天均应暂时中断镇静 Grade B 3. 尽量避免使用肌松
36、剂 Grade E,M. 血糖控制,1.严格控制血糖 8.3 mmol/L(150mg/dl) 初期 3060 mins检测血糖一次，血糖值稳定后每4 hrs一次. Grade D 2. 重症感染患者，血糖控制策略应包括营养支持方案，首选肠内营养Grade E,Insulin in critically ill pat,Prospective, randomize, control Surgical ICU（单中心） 12 months 1548 pats with MV Intensive insulin therapy: 80110 mg/dlConvention insulin ther
37、apy: If 215 mg/dl maintain 180200 mg/dl,Greet VB et al. N Engl J Med 2001, 345: 1359-1367,Base line,Greet VB et al. N Engl J Med 2001, 345: 1359-1367,Study design and Results,P0.001,P0.001,P0.001,P0.001,Greet VB et al. N Engl J Med 2001, 345: 1359-1367,Intensive insulin therapy: If 110 mg/dl 80110 m
38、g/dl Max-dose of insulin: 50 u/h,Convention insulin therapy: If 215 mg/dl 180200 mg/dl,N.肾脏替代治疗,1. 合并急性肾衰时，CVVH和或间歇性血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，CRRT更有利于液体管理(Septic shock CRRT: Vasopressor),Grade B,N. 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 C,Prospective, randomized, blinded, crossover study 14
39、 pats with metabolic acidosispH 7.13, bicarbonate 15mins Control: sodium chloride (equal dose, volume, time),Bicarbonate therapy,Cooper DJ. Ann Intern Med 1990, 112:492,P.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 A,Q
40、.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 A,Although these recommendations are written primarily 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 m
41、ay prevent physicians from accomplishing a recommendation.,These recommendations are intended to provide guidance for the clinician caring for 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 approaches,For optimal pat management,谢谢,
