新光醫(yī)院感染科敗血癥951005

1、新光醫(yī)院感染科敗血癥標(biāo)準(zhǔn)作業(yè)流程severe sepsis and septic shock,新光醫(yī)院感染科黃建賢,SEPSIS,DEFINITIONSmicrobes involves a rapidly amplifying polyphony of signals and responses that may spread beyond the invaded tissue.,1. 敗血癥的定義,敗血癥的定義1.1宿主因

2、微生物感染大量繁殖並造而造成全身性癥狀，臨床上可表現(xiàn)出發(fā)燒，低體溫，寒顫，呼吸加速，心搏加速，宿主因為微生物的侵犯而表現(xiàn)出”系統(tǒng)性發(fā)炎反應(yīng)癥候群”(systemic inflammatory response syndrome，SIRS)1.2 ”系統(tǒng)性發(fā)炎反應(yīng)癥候群”定義為包函下列或兩者以上1.2.1 體溫38度C以上或36度C以下1.2.2 心跳速度超越每分鐘90下1.2.3 呼吸速率超越每分鐘20下1.2.4 血液中白血

3、球大於每毫升12000或小於每毫升4000或含百分之10以上之不成熟白血球(bands),ETIOLOGY,gram-negative and gram-positive bacteriafungi, mycobacteria, rickettsiae, viruses, or protozoans…Positive blood cultures :30 to 60 % of patients with sepsis

4、60 to 80 % of patients with septic shock,Sepsis,Definitions Used to Describethe Condition of Septic Patients,BacteremiaSystemic inflammatoryresponse syndrome (SIRS)SepsisSevere sepsisSeptic shockMultiple-o

5、rgan dysfunctionsyndrome (MODS),Presence of bacteria in bloodFever, tachypnea, tachycardia,leukocytosis/leukopeniaSIRS has a proven or suspectedmicrobial etiologySepsis with ≥1 signs of organdysfunctionSepsis

6、 with hypotension or needfor vasopressorDysfunction of ≥1 organ,Epidemiology of Sepsis in theUnited States from 1979-2000,N Engl J Med 2003; 348: 1546-54.,EPIDEMIOLOGY,2/3: in hospitalized patients. Risk Factors to

7、 GNB bacteremiadiabetes mellituslymphoproliferative diseasescirrhosis of the liverburnsinvasive procedures or devicesdrugs that cause neutropenia,EPIDEMIOLOGY,Risk factors for GPC bacteremia vascular catheters, i

8、ndwelling mechanical devices, burns, intravenous drug injection.Fungemia : immunosuppressed patients neutropeniabroad-spectrum antimicrobial therapyTPNIntestinal perforation,PATHOPHYSIOLOGYEndotoxin,Gram negati

9、ve bacilliLipopolysaccharide (LPS, also called endotoxin),PATHOPHYSIOLOGYMicrobial signals,Gram positive coccipeptidoglycan and lipoteichoic acids extracellular enzymes,敗血癥的癥狀,Fever or hypothermia (low body temperatu

10、re) Hyperventilation Chills Shaking Warm skin Skin rash Rapid heart beat Confusion or delirium Decreased urine output,CLINICAL MANIFESTATIONS,S/S: fever, chills, tachycardia, tachypnea, altered mental status, an

11、d hypotension.afebrile common in neonates, in elderly patientsand in persons with uremia or alcoholism.,CLINICAL MANIFESTATIONS,Llaboratory finding: C-reactive proteinfibrinogencomplement componentstransferrini

12、nhibits albumin synthesis Leukocytosis, left shift,LABORATORY FINDINGS,Early sepsis leukocytosis with a left shiftRespiratory alkalosisThrombocytopeniaHyperbilirubinemiaproteinuria. neutrophils may contain toxic g

13、ranulations, Dohle bodies, or cytoplasmic vacuoles,LABORATORY FINDINGS,Progressing of sepsis:thrombocytopenia worsens prolongation of the thrombin timedecreased fibrinogenpresence of D-dimers, suggesting DIC)Azotemi

14、a, hyperbilirubinemia become prominentElevated GOT GPT,LABORATORY FINDINGS,Progressing sepsis:hyperventilation induces respiratory alkalosis.accumulation of lactate, metabolic acidosis (with increased anion gap)hype

15、rglycemia, severe infection may precipitate diabetic ketoacidosis(DKA),Multiple organ dysfunction syndrome,MOF: Dysfunction or failure of multiple organsreflecting widespread vascular endothelial injuryassociated with

16、 high fatality rates. Mortality and morbidity correlate with the number of organs affected.,DIAGNOSIS,S/S --Progressing sepsis tachypnea, tachycardia, altered mental status, The septic response can be quite variable

17、systemic inflammatory response syndrome SIRS,DIAGNOSIS,Definitive diagnosis isolation of the microorganism from blood or a local infected site Gram's stain culture of the primary site of infection.,TREATMENT,Seps

18、is may be fatal quickly. Successful managementurgent measures to treat the local site of infection,hemodynamic and respiratory supporteliminate the offending microorganismTherapy of acidosis and DIC, other complica

19、tions,TREATMENT,Outcome influenced by the patient's underlying diseaseaggressively treated.Antimicrobial agents,PROGNOSIS,Mortality: More than 25 %1/3 within the first 48 h mortality can occur 14 or more days l

20、ater. Late deaths poorly controlled infectioncomplications of intensive caremultiple organs failure,2.敗血癥初期之緊急處理,2.1 敗血癥最初七小時之緊急處理措施著眼於恢復(fù)因敗血癥所引起的低血流灌注，恢復(fù)組織功能，應(yīng)包含以下所有之緊急處理2.1.1 中心靜脈壓維持8-12mmHg2.1.2 平均動脈壓維持大於等於65 mmH

21、g2.1.3 小便量維持大於等於每小時每公斤體重0.5毫升2.1.4 中心靜脈氧飽含量維持大於等於70﹪,2.敗血癥初期之緊急處理,2.2 臨床檢驗2.2.1由周邊靜脈至少抽取2至3套血液培養(yǎng)後盡快給予抗生素治療2.2.2盡快找尋可能之感染部位並取得檢體，如導(dǎo)管相關(guān)之感染，呼吸器相關(guān)之肺炎等2.2.3在抗生素使用前須取得可能感染部位之培養(yǎng)檢體，如尿液，腦脊髓液，傷口，呼吸道檢體或其他部位之組織液2.2.4必要時可作血清學(xué)檢查

22、、檢測抗體及抗原或檢測尿液中退伍軍人菌抗體,2.敗血癥初期之緊急處理,2.2 臨床檢驗2.2.5如有液狀檢體，可作染色鏡檢如葛蘭氏染色，抗酸菌染色等2.2.6軟組織感染時，除了做血液培養(yǎng)外，盡可能取得檢體做染色鏡檢2.2.7必要時可在主治醫(yī)師同意下對病灶施行超音波檢查，電腦斷層或核 磁共振檢查以確立病灶及嚴(yán)重程度2.2.8必要時可對病灶做抽吸或切片檢查以取得檢體2.2.9如病灶有明顯積液、必要時可施以抽吸引流或外科治療

23、,3.抗生素療法,3.1抗生素治療必須在取得適當(dāng)檢體後盡快給予3.2當(dāng)病患有嚴(yán)重敗血癥或敗血性休克時，要盡速給予體液補充，除非有相當(dāng)禁忌癥(如急性肺水腫等)3.3抗生素經(jīng)驗療法必須依社區(qū)或院內(nèi)感染，感染部位、菌種、抗生素穿透能力及疾病人實際狀況來給予(參考本院每半年出版之菌種及抗生素敏感試驗表)3.3.1抗生素治療以一種抗生素為原則3.3.2必要時可以合併抗生素使用以治療混合型感染或加強抗生素療效3.3.3抗生素之選擇依病人過

24、去病史，過敏史，合併疾病，合併癥及臨床抗生素敏感性做選擇,3.抗生素療法,3.4抗生素治療必須在使用48小時至72小時後重新評估3.4.1依細菌培養(yǎng)及抗生素敏感性試驗之結(jié)果做調(diào)整3.4.2以窄效性抗生素為原則3.4.3為避免抗藥性產(chǎn)生，抗生素之選擇以低毒性及同類藥中價廉為原則3.4.4治療以7-10天為原則，必要時可延長之3.4.5抗生素之使用及停用以培養(yǎng)結(jié)果及臨床醫(yī)師判定為原則,4 控制病源,4.1臨床上所有敗血癥病患均盡量

25、查出並除去感染源4.1.1必要時以引流、清創(chuàng)或外科手術(shù)行之4.1.2病患有外科手術(shù)需求時，必須在完成初步急救並解釋病情之後、在家屬同意下、盡速施行之,5 輸液治療,5.1輸液治療包括自然血漿，人工血漿及一般輸液5.1.1人工輸液較血漿易出現(xiàn)水份積蓄及水腫5.1.2輸液速度以每30分鐘輸人工輸液300至1000毫升、或血漿以每30分鐘300至500毫升為主5.1.3輸液速度及輸液量以臨床反應(yīng)、血壓及尿液量做調(diào)整5.1.4密切監(jiān)

26、視病患以避免出現(xiàn)肺水腫及其他併發(fā)癥5.2 個人體液需求量依個體及疾病狀況不同依臨床狀況做調(diào)整,6 血管收縮劑,6.1 當(dāng)病患經(jīng)輸液治療後仍無法維持適當(dāng)?shù)难獕杭敖M織灌流時得使用血管收縮劑治療6.2 當(dāng)?shù)脱獕鹤阋晕＜吧鼤r，血管收縮劑得以和輸液治療同時給予6.3 Nor-epinephrine或dopamine須以中心靜脈方式給予6.4 使用血管收縮劑病患得施行動脈血壓監(jiān)測6.5 Nor-epinephrine起始劑量以0.01至

27、0.04 units/分為原則6.6 Cardiac index在2.5 L.min-1.m2以下者不宜使用血管收縮劑,7 升壓劑(Dobutamine),7.1 病患在經(jīng)適當(dāng)輸液治療後仍無法維持正常之輸出量時得以使用升壓劑，必要時得合併血管收縮劑使用,8 類固醇,8.1 休克病患在適當(dāng)補充輸液，使用血管升壓劑後，仍無法維持正常血壓時得以使用類固醇8.2 劑量以每天hydrocortisone200至300毫克，分3至4次給予，使用

28、7天為原則、必要時得延長之8.3 病患在檢測ATCH前得以使用dexamethasone取代hydrocortisone以免影響血中cortisol濃度檢測值8.4 敗血癥病患未合併休克時，不建議使用類固醇,9 人類活性C蛋白使用,9.1 高死亡率之多重器官衰竭、敗血性休克、成人呼吸窘迫癥病患，無出血傾向時、APACHEII score>=25、在主治醫(yī)師同意下得以使用人類活性C蛋白(rhAPC),10 血類製劑,10.1 無

29、特殊禁忌癥之?dāng)⊙Y病患在血色素7.0g/dl以下時得以輸血10.2 輸血目標(biāo)值為血色素7.0至9.0g/dl10.3 病患無明顯出血時、不建議以冷凍新鮮血漿來改善血液中之凝血值10.4不論有無出血現(xiàn)象，嚴(yán)重敗血癥病患得以輸用血小板以維持血小板值在5000/mm3以上(5×10-9/L),11 呼吸器使用,11.1 呼吸器使用依本院呼吸器使用原則，及成人呼吸窘迫癥呼吸器使用原則行之,12 鎮(zhèn)靜劑麻醉藥品及肌肉鬆弛劑使用,1

30、2.1 嚴(yán)重敗血癥病患合併呼吸衰竭及呼吸器使用時、得依本院藥物使用規(guī)範(fàn)使用鎮(zhèn)靜劑麻醉藥物及肌肉鬆弛劑12.2 必要時得以會診麻醉科、以進行藥物調(diào)整及避免藥物副作用,13 血中葡萄糖控制,13.1 敗血癥病患須嚴(yán)密監(jiān)測並控制血糖13.2 血中葡萄糖控制以200 mg/dl以下為原則(有嚴(yán)格監(jiān)測時得控制在140 mg/dl以下)13.3 必要時得以使用胰島素取代口服降血糖藥控制血糖,14 碳酸鹽治療,14.1 碳酸鹽治療得以使用於敗血

31、癥合併血流灌注所引起之酸中毒14.2 碳酸鹽治療酸中毒以pH值7.3以下為原則14.3 嚴(yán)重敗血癥病患得使用低劑量肝素或低分子量肝素預(yù)防深部靜脈血栓形成14.4 病患有出血傾向或其他禁忌癥時應(yīng)避免使用肝素,15 預(yù)防壓力性腸胃道潰瘍,15.1 所有敗血癥病患均應(yīng)預(yù)防壓力性潰瘍之產(chǎn)生15.2 以使用H2 receptor抑制劑為原則，有禁忌癥或不適用者除外,16 褥瘡之預(yù)防,16.1 敗血癥合併活動能力降低之病患、應(yīng)預(yù)防褥瘡之產(chǎn)生

32、16.2 臨床上依預(yù)防褥瘡形成臨床技術(shù)手冊行之16.3 褥瘡之治療、必要時可給予抗生素及施行清創(chuàng)手術(shù),Epidemiology of Sepsis in theUnited States from 1979-2000,N Engl J Med 2003; 348: 1546-54.,Causative OrganismsGram-positive bacteria 52.

33、1%Gram-negative bacteria 37.6%polymicrobial infections 4.7%anaerobes 1.0%fungi

34、 4.6%Specific organisms causing sepsis were recorded in51% of all discharge records over the 22-year period.,,,,,Antimicrobial Agents in theManagement of Sepsis,Crit Care Med 2004; 32: 858

35、-73.,Two blood culture one percutaneous one from each vascularaccess >48 hrs,,microbial and clinical data narrow-spectrum antibiotics non-infectious cause identified prevent resistance, reduce toxicity and red

36、uce cost,,,one or more drugs active against likely bacterial or fungal pathogens consider microbial susceptibility patterns,,Evaluate patient for afocused infection,Reassess antimicrobialregimen at 48-72 hrs,Begin

37、 IV antibiotics withinthe first hr of recognitionof severe sepsis,Norepinephrine 4 mg/4 ml/amp (diluted by D5W)- 0.03~3.3 μg/kg/min (2~200 μg/kg/hr)Epinephrine 1 mg/1 ml/amp - 0.06~0.47 μg/kg/min (3.6~30 μg/kg/hr)

38、Dopamine 200 mg/5 ml/amp2~55 μg/kg/min (0.12~3.3 mg/kg/hr)Dobutamine 250 mg/20 ml/amp 2~28 μg/kg/min (0.12~1.68 mg/kg/hr)Vasopressin 20 U/1 ml/amp 0.01~0.04 U/min (0.6~2.4 U/hr),Crit Care Med 2004; 32: 1928-48.,

39、Vasopressor and Inotropics,Role of Corticosteroid in theManagement of Septic Shock,Crit Care Med 2004; 32: 858-73.,Treat patients who still require vasopressors despitefluid replacement with hydrocortisone 200-300 mg/d

40、ayfor 7 days divided in 3-4 doses or by continuousinfusion(Grade C)High dose of corticosteroids (> 300 mg/day) shouldNOT be used in severe sepsis or septic shock.(Grade A),Crit Care Med 2004; 32: 858-73.,Role

41、 of Corticosteroid in theManagement of Septic Shock,In the absence of shock, corticosteroids should NOTbe administrated for the treatment of sepsis(Grade E)The use of ACTH stimulation test to identify responders(&

42、gt;9 μg/ml increase in cortisol 30-60 mins post-ACTHadministration) and to continue therapy is optional.Should NOT wait for ACTH stimulation results toadminister corticosteroids(Grade E),Mechanical Ventilation ofS

43、epsis-induced ALI/ARDS,Crit Care Med 2004; 32: 858-73.,High tidal volume that are coupled with high plateaupressures should be avoided in ALI/ARDS. reduce tidal volume over 1-2 hrs to 6 ml/kg predicted body weight

44、maintain inspiratory plateau pressure <30 cmH2O maintain SaO2/SpO2 88-95% anticipated PEEP settings at various FiO2 requirementsFiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0PEEP

45、 5 5 8 8 8 10 10 12 14 14 14 16 18 20-24(Grade B),Intensive Insulin in CriticalIll Patients,Crit Care Med 2004; 32: 858-73.,After initial stabilization of patients with severe sepsis

46、 maintain glucose <150 mg/dl by continuous infusion of insulin monitor blood glucose every 30-60 mins and then q4h(Grade D)In patients with severe sepsis, a strategy of glycemiccontrol should include a nutri

47、tion protocol with thepreferential use of the enteral route.(Grade E),Intensive Insulin in CriticalIll Patients,N Engl J Med 2006; 354: 449-61.,prospective, randomized, controlled trial adults admitted to SICU (N= 1

48、,548) who were receiving MV adults admitted to MICU (N= 1,200) who were considered to need ICU care for at least 3 days 50 IU actrapid HM/ 50 ml NS infused by pump (max. dose 50 IU/hr) intensive insulin (blood

49、glucose ~80-110 mg/dl) conventional treatment (blood sugar ~180-200 mg/dl) primary endpoint: ICU mortality/in-hospital mortality,Intensive Insulin in CriticalIll Patients,N Engl J Med 2001; 345: 1359-67.N Engl J Med

50、 2006; 354: 449-61.,ICU deathIn-hospitaldeathICU deathIn-hospitaldeath,Mortality8.0% vs 4.6%10.9% vs 7.2%26.8% vs 24.2%38.1% vs 31.3%*40.0% vs 37.3%52.5% vs 43.0%*,ARR3.4%3.7%2.6%6.8%2.7%

51、9.5%,NNT2927-14-10,RRR42.5%33.9%9.7%17.8%6.8%18.1%,P value<0.040.010.310.050.330.009,,,* patients who stayed in the ICU ≥3 days,Surgical ICU,Medical ICU,Advances in Therapy forSev

52、ere Sepsis and Septic Shock,Time-sensitive interventionEarly goal-directed therapyDrotrecogin alfa (activated)for high-risk patientsLow-dose steroidsLow tidal volume ventilationTight blood sugar control,Mortal

53、ity reduction (ARR)16% (P= 0.009), NNT= 613% (P= 0.001), NNT= 810% (P= 0.023), NNT= 1010% (P= 0.005), NNT= 103.4% (P= 0.005), NNT= 29,,N Engl J Med. 2001; 345: 1368-77.N Engl J Med. 2001; 344: 699-709.,JAMA 2