也应及时使用血管活性药物GradeE2去甲肾上腺素和多巴胺是治疗课件

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 /hMoreover, 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 Surviving

2、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 5YSurviving Sepsis CampaignPhase : Barcelona DeclarationPhase : Guidelines creationPhase : Clinical outcome evaluationGUIDELINES FOR MANAGEMENGT OF SEVERE SEPSIS AND

3、SEPTIC SHOCKAACCN; American Association of Critical-Care Nurses ACCP: American College of Chest Physicians ACEP: American College of Emergency PhysiciansATS: American Thoracic Society ANZICS: Australian and New Zealand Intensive Care SocietyESCMID: European Society of Clinical Microbiology and Infec

4、tious Dis ERS: European Respiratory Society SIF: Surgical Infection SocietyESICM: European Society of Intensive Care Medicine ISF:International Sepsis Forum SCCM: Society of Critical Care MedicineGuidelines 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个级研究证实C： 级研究证实D：至少1个级

5、研究证实E：或级研究证实研究级别I. Large, randomized trials with clearcut resultsII. Small, randomized trials with uncertain resultsIII. Nonrandomized, contemporaneous controlsIV. Nonrandomized, historical controls and expert opinionV. Case series, uncontrolled studies, and expert opinionA-Initial resuscitation: ea

6、rly goal-directed therapyB-Diagnosis: appropriate cultureC-Antibiotic therapy: Early broad-spectrum, reassessed 2-3d D-Source control: E-Fluid therapy: colloids=crystalloids,VLTF-Vasopressors: After VLS, NE vs Dopa, Low-dose dopa is not , cath for vaso G-Inotropic therapy: low CO-dobu, high CO is no

7、tH-Steroid: low dose I-rhAPC: APACHE II 25, sepsis-induced ARDS/MOF and no bleeding riskJ-Blood product administration: target Hb 7-9g/dl, EPO only in renal failureK-Mechanical ventilation: Ppla30, Hypercapnia, optimal PEEP, Prone positionL-Sedation, analgesia and NBMs: ProtocolM-Glucose control: 15

8、0mg%N-Renal replacement: O-Bicarbonate: pH 7.15P-DVT: UH/LMWHQ-Stress ulcer prophylaxis: H2blockerR-Consideration of limitation of supportA. 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 mmHg Urine output0.5mLkg-1h-1 SvO270%Grade BA. 早期复苏2.若最初6h治疗，CVP达到8-12mmHg，而SvO270%Transfu

9、se packed red blood cells： HCT 30% and/or Dobu iv ( up to max 20 gkg-1min-1)Grade 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 therapy is initiatedIn order to optimize identification of causative organisms, at least two blood cultures should be obtained with at least one drawn

10、 percutaneously and one drawn through each vascular access device, unless the device was 48h inserted Grade DPeripheral blood(PB) vascular access device(VAD)Same organismThe organism is causing the ssepsisVAD culture is positive 2h earlier than PBVAD is the source of the infectionWeinstein MP. Rev I

11、nfect Dis 1983, 5: 35-53Blot F. J Clin Microbiol 1998, 36: 105-109*p 20 mm HgContinous aspiration of subglottic secretionsContaminated condensate should be emptiedATS. Am J Respir Crit Care Med 2005;171:388-416Modifiable Risk FactorsAspiration, body position, and feedingSemirecumbent position (30-45

12、)Enteral feeding is preferredModulation of colonizationRoutine prophylaxis is not recommendedStress bleeding prophylaxis, transfusion, and hyperglysemiaH2 antogonists or sucralfate is acceptableRestricted transfusion trigger policyIntensive insulin therapyATS. Am J Respir Crit Care Med 2005;171:388-

13、416E. 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 anotherGrade 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

14、 30min and repeated based on response (increase in BP and urine output) and tolerance (evidence of intravascular volume overload)Grade EF. 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 BF. 血管活性药物 4.应用血管

15、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 ENE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CINE通过缩血管效应来提高BP，不改变SV和HRNE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. Chest 1993:1826-1831A large randomized trial and a meta-analysisLow-dose dopamine and place

16、boNo difference inPeak serum Cr, need for RRT,Urine output, timeto recovery of normal renal functionSurvival, ICU stay, Hospital stay, Arrhythmias血管活性药物 Low-dose dopamine should not be used for renal protection as part of the treatment of severe sepsisBellomo R. Lancet 2000, 356: 2139Kellum J. CCM,

17、2003, 29:1526G.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COGrade 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 AH. 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 Ca.

18、对于感染性休克，不需作ACTH应激试验就可应用激素 Grade Eb. 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 rise 9ug/dl)Design: placebo-controlled, randomized,double-blind, parallel-group trialSetting: Multicenter, 19 ICU in

19、 France (95.1099.2)Two groupsHydrocortisone (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减少升压药应用But not in non-AI groupMortality rateAnnane D, et al. JAMA 2002;288:862-871No. (%)VariablePlaceboSteroidsP ValueNo.

20、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. 氢化考地松用量不应大于300mg/day； Grade AH. 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 EI. 重组人活化蛋白C (rhAPC)1. rhAPC is r

21、ecommended in patients at high risk of death APACHE II 25 Sepsis-induced MODS Septic shock Or sepsis-induced-ARDS And no absolute contraindication related to bleeding riskGrade BJ. 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/dlGrade BTransfusion requirements in critical care

22、Multicenter，randomized，controlled6451 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

23、 限制输血组住院生存率高 Exception of AMI and unstable anginaHebert PC,et al. N Engl ed 1999，340：409-417J. 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 BEfficacy of rHuEPOProspective，randomized，double-blind ，placebo- controled，multicenter trial33685 pats assessd, 1302 randomized 650 rHuEPO 652 placebo 40000U ICU d3(

24、1)，continued weekly(7,14,21)Conclusions:Reduce RBC transfusionNo differences in clinical outcomesCorwin HL,et al. JAMA,2002,288:2827-2835J. 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 E4. 重症感染和感染性休克均不推荐应用抗凝血酶Grade B5. 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

25、术或侵入性操作时输pltGrade EK. ALI/ARDS的机械通气1.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)-152.4Grade 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

26、低位转折点选择PEEP (16.4cmH2O), 加以RM( 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 CK. 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 EK. 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

27、半卧位，以防止VAPGrade CK. 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 AEffect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneouslyBackground: ranbomized,controlled trialMethods:in

28、tervention 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. N Engl J Med, 1996,335: 1864-9Ely EW, et al. N Engl J Me

29、d, 1996,335: 1864-9SBT-降低机械通气时间nMV(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-降低MV时间和并发症

30、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 B2. 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 B3. 尽量避免使用肌松剂Grade 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 2001, 345: 1359-1367Base line Convention(n)Intensive(n)N783765Age6263APACHE 99diabetes103101Blood glucose

31、110598557 20010181Reason for ICU Cardiac surgery Neurologic disease Thoracic surgery, respiratory insufficiency Abdominal surgery or peritonitis Multiple trauma or severe burns Transplantation Other 477 33 66 45 33 4635 35Greet VB et al. N Engl J Med 2001, 345: 1359-1367Study design and ResultsP0.00

32、1P0.001P0.001P110 mg/dl 80110 mg/dlMax-dose of insulin: 50 u/hConvention insulin therapy: If 215 mg/dl 180200 mg/dlN.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 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 CProspective, randomized, blinded, crossover study 14 pats with metabolic acidosispH 7.13, bicarbonate 17 mmol / L, BE 15mins Cont